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Li W, Wang F, Li Z, Feng W, Huang H, Kwan MP, Tse LA. Lipid profile and non-alcoholic fatty liver disease detected by ultrasonography: is systemic inflammation a necessary mediator? Ann Med 2025; 57:2480250. [PMID: 40098359 PMCID: PMC11921154 DOI: 10.1080/07853890.2025.2480250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 02/11/2025] [Accepted: 03/05/2025] [Indexed: 03/19/2025] Open
Abstract
AIMS To examine the relationship between lipid profile and non-alcoholic fatty liver (NAFL), compare the predictive strengths of different lipid indicators to NAFL, and explore the possible mechanisms. METHODS Male workers from a baseline survey of a cohort of workers in southern China were included. Basic information was collected through face-to-face interviews. Plasma concentrations of fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined using a blood biochemical analyzer. Liver sonography was used to identify NAFL cases. Regression models were used to calculate ORs, and examine the association between C-reactive protein (CRP) levels and lipid profiles. Restricted cubic spline regression with four knots was used to examine the dose-response relationship, and mediation analysis was employed to examine the mediation effect. RESULTS h Among the 4016 male workers, 829 (20.64%) were diagnosed with NAFL. Compared with normal lipid profile, individuals with abnormal lipid profile had higher prevalence of NAFL (OR=2.27, 95%CI: 1.85-2.79 for TG; OR=1.45, 95%CI: 1.03-2.04 for TC; OR=1.56, 95%CI: 1.21-2.02 for HDL; OR=1.65, 95%CI: 1.25-2.18 for LDL; OR=2.28, 95%CI: 1.87-2.77 for dyslipidaemia) after adjusting for potential confounders. Dose-response relationships were observed among TG, HDL, and NAFL. In addition, no significant mediation effect of C-reactive protein (CRP) was found in the association between lipid profiles and NAFL. CONCLUSIONS Abnormal TG, TC, HDL, and LDL levels were all positively associated with NAFL, while CRP has no mediating effect, and TG tended to be a better predictor of NAFL.
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Affiliation(s)
- Wenzhen Li
- Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong SAR, China
- CUHK Centre for Public Health and Primary Care (Shenzhen), Shenzhen Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute of the Chinese University of Hong Kong, Shenzhen, China
| | - Feng Wang
- Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong SAR, China
| | - Zhimin Li
- Institute of Occupational Medicine, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, China
| | - Wenting Feng
- Institute of Occupational Medicine, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, China
| | - Hongying Huang
- Institute of Occupational Medicine, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen, China
| | - Mei-Po Kwan
- Department of Geography and Resource Management, The Chinese University of Hong Kong, Hong Kong SAS, China
- Institute of Space and Earth Information Science, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Lap Ah Tse
- Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong SAR, China
- CUHK Centre for Public Health and Primary Care (Shenzhen), Shenzhen Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute of the Chinese University of Hong Kong, Shenzhen, China
- Institute of Space and Earth Information Science, The Chinese University of Hong Kong, Hong Kong SAR, China
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Wu H, Chen J, Guo S, Deng J, Zhou Z, Zhang X, Qi T, Yu F, Yang Q. Advances in the acting mechanism and treatment of gut microbiota in metabolic dysfunction-associated steatotic liver disease. Gut Microbes 2025; 17:2500099. [PMID: 40394806 PMCID: PMC12101596 DOI: 10.1080/19490976.2025.2500099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Revised: 04/17/2025] [Accepted: 04/25/2025] [Indexed: 05/22/2025] Open
Abstract
Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD) is increasing in prevalence worldwide and has become the greatest potential risk for cirrhosis and hepatocellular liver cancer. Currently, the role of gut microbiota in the development of MASLD has become a research hotspot. The development of MASLD can affect the homeostasis of gut microbiota, and significant changes in the composition or abundance of gut microbiota and its metabolite abnormalities can influence disease progression. The regulation of gut microbiota is an important strategy and novel target for the treatment of MASLD with good prospects. In this paper, we summarize the role of gut microbiota and its metabolites in the pathogenesis of MASLD, and describe the potential preventive and therapeutic efficacy of gut microbiota as a noninvasive marker to regulate the pathogenesis of MASLD based on the "gut-hepatic axis", which will provide new therapeutic ideas for the clinic.
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Affiliation(s)
- Huaying Wu
- Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, China
- Department of Clinical Medicine, Shantou University Medical College, Shantou, China
| | - Jingjing Chen
- Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, China
- Department of Clinical Medicine, Shantou University Medical College, Shantou, China
| | - Shuyuan Guo
- Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, China
| | - Jinhao Deng
- Department of Clinical Medicine, Shantou University Medical College, Shantou, China
| | - Zimeng Zhou
- Department of Clinical Medicine, Shantou University Medical College, Shantou, China
| | - Xuan Zhang
- Department of Clinical Medicine, Shantou University Medical College, Shantou, China
| | - TianTian Qi
- Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, China
| | - Fei Yu
- Department of Spine Surgery, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Qi Yang
- Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, China
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Zhang DY, Li D, Chen SJ, Zhang LJ, Zhu XL, Chen FD, Chen C, Wang Q, Du Y, Xiong JX, Huang SM, Zhang XD, Lv YT, Zeng F, Chen RX, Huang X, Mao F, Zhou S, Yao Q, Huang Y, Chen R, Mo Y, Xie Y, Jiang YH, Chen Z, Mo CY, Chen JJ, Bai FH. Bacteroides uniformis-generated hexadecanedioic acid ameliorates metabolic-associated fatty liver disease. Gut Microbes 2025; 17:2508433. [PMID: 40413726 PMCID: PMC12118425 DOI: 10.1080/19490976.2025.2508433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Revised: 04/28/2025] [Accepted: 05/14/2025] [Indexed: 05/27/2025] Open
Abstract
Gut microbiota exerts a pivotal influence on the development of Metabolic Associated Fatty Liver Disease (MAFLD), although the specific contributions of individual bacterial strains and their metabolites remain poorly defined. We conducted stool shotgun metagenomic sequencing and plasma untargeted metabolomics in a large prospective cohort comprising 120 MAFLD patients and 120 matched healthy controls. The mechanisms and microbial-derived metabolites involved in MAFLD were further investigated through multi-omics analyses in vitro and in vivo. Distinct differences were identified in both the microbial community structure and metabolomic profiles between MAFLD patients and healthy controls. Bacteroides uniformis (B. uniformis) was the most significantly depleted species in MAFLD and negatively correlated with hepatic steatosis and BMI. MAFLD was characterized by marked disruptions in fatty acid and amino acid metabolism. Combined analysis of metabolomic and metagenomic data achieved high diagnostic accuracy for MAFLD and hepatic steatosis severity (AUC = 0.93). Transplantation of fecal microbiota from MAFLD subjects into ABX mice led to the onset of MAFLD-like symptoms, whereas B. uniformis administration alleviate disease progression by inhibiting intestinal fat absorption, FFA from eWAT influx into liver via the gut-liver axis, and IRE1α-XBP1s-mediated flipogenesis and ferroptosis, as confirmed by hepatic transcriptomic and proteomic analyses. Hexadecanedioic acid (HDA), potentially identified as a key metabolite produced by B. uniformis, ameliorated MAFLD symptoms. Mechanistically, B. uniformis-derived HDA also inhibited fat absorption and transported, and entered the liver via the portal vein to suppress IRE1α-XBP1s-mediated flipogenesis and ferroptosis. B. uniformis and its potential putative metabolite HDA may contribute to MAFLD progression modulation, through regulation of the IRE1α-XBP1s axis. This study provides new insights into the gut-liver axis in MAFLD and offers promising therapeutic targets based on specific microbes and their metabolites.
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Affiliation(s)
- Da-Ya Zhang
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Da Li
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Shi-Ju Chen
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Li-Jun Zhang
- Health Management Center, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Xu-Li Zhu
- Department of Gastroenterology, Otog Front Banner People’s Hospital, Otog Front Banner, China
| | - Fa-Di Chen
- Wuzhishan Center for Disease Control and Prevention, Wuzhishan, China
| | - Chen Chen
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Qi Wang
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Yiping Du
- Cardiovascular Surgery, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Jian-Xin Xiong
- Department of Gastroenterology, Hainan Second People’s Hospital, Wuzhishan, China
| | - Shi-Mei Huang
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Xiao-Dong Zhang
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Yan-Ting Lv
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Fan Zeng
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Run-Xiang Chen
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Xianfeng Huang
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Fengjiao Mao
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Shuo Zhou
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Qicen Yao
- Department of Rheumatology and Immunology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Yuliang Huang
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Runyu Chen
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Ying Mo
- The Second School of Clinical Medicine, Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Yunqian Xie
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Yue-Hong Jiang
- Department of Gastroenterology, The Second People’s Hospital of Ledong Li Autonomous County, Ledong Li Autonomous County, China
| | - Zhai Chen
- Department of Gastroenterology, Dongfang People’s Hospital, Dongfang, China
| | - Cui-Yi Mo
- Department of Gastroenterology, Qionghai People’s Hospital, Qionghai, China
| | - Jia-Jia Chen
- Department of Gastroenterology, Qionghai People’s Hospital, Qionghai, China
| | - Fei-Hu Bai
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
- Department of Gastroenterology, The Gastroenterology Clinical Medical Center of Hainan Province, Haikou, China
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Wang X, Leng S. Serum uric acid may be a mediator of risk factors in metabolic dysfunction associated steatotic liver disease. Scand J Gastroenterol 2025; 60:581-587. [PMID: 40255082 DOI: 10.1080/00365521.2025.2490994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 04/02/2025] [Accepted: 04/04/2025] [Indexed: 04/22/2025]
Abstract
BACKGROUND In recent years, we have witnessed a sharp growth of metabolic dysfunction associated steatotic liver disease (MASLD). How to achieve early prevention of MASLD is imminent. We aimed to determine the dietary pattern and other factors influencing MASLD, to explore whether it mediated by serum uric acid (SUA) or not. METHODS A total of 4,038 adults attending the Health Management Center of the Second Affiliated Hospital of Dalian Medical University between October 2018 and May 2019 were surveyed using a questionnaire and underwent physical measurements. Structural equation model (SEM) was used to verify the risk factors and determine the path affecting MASLD. RESULTS A total of 3,589 participants were studied. The standardized prevalence of MASLD was 47.8%. Three dietary patterns were identified using factor analysis. The SEM showed that SUA was positively associated with MASLD (standardization coefficient 0.285). In rank order, sex, SUA, dyslipidemia, age, a high-protein diet, and a fast-food diet were risk factors for MASLD. Sex, dyslipidemia, and a fast-food diet had positive and indirect effects on NAFLD through SUA, while age and a high-protein diet had negative and indirect effects on MAFLD through SUA. CONCLUSIONS SUA may be an important mediator of the risk of MASLD. People with abnormal SUA, especially men, should limit their intake of fried and cured foods and desserts; have their blood lipid profiles monitored carefully; appropriately increase their consumption of high-quality protein sources, such as eggs, milk, and beans; and be aware of their MASLD risk.
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Affiliation(s)
- Xueying Wang
- Department of Disease Prevention and Hospital Infection Control, Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Song Leng
- Health Management Center, Second Affiliated Hospital of Dalian Medical University, Dalian, China
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5
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Shu R, Tian S, Qu W, Yang J, Shi W, Li X, Zou T, Jiang C, Zhang Y, Yang Z, Tian H, Yang H, Fu J, She ZG, Li H, Zhang XJ. Hepatoprotective drug screening identifies daclatasvir a promising therapeutic candidate for MASLD by targeting PLIN2. J Lipid Res 2025:100835. [PMID: 40449734 DOI: 10.1016/j.jlr.2025.100835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 05/22/2025] [Accepted: 05/27/2025] [Indexed: 06/03/2025] Open
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) has become global health challenges with limited therapeutic strategy. Here, the present study aims to identify promising drug candidates for MASH and to clarify their pharmacological mechanism. By an extensive screening of FDA-approved hepatoprotective medicines using a PA/OA-stimulated hepatocytes model, we identified daclatasvir showing potent anti-MASH capacity against hepatic steatosis deposition and inflammatory response. The hepatoprotective benefits of daclatasvir was further validated in MASH mouse models, induced by a high-fat high-cholesterol (HFHC) diet for 16 weeks or a methionine-choline-deficient (MCD) diet for 4 weeks, as supported by markedly improved histopathological characteristics, serum biochemical level, and transcriptomic analyses. Using the molecular docking assay followed by isothermal titration calorimetry confirmation, we identified that daclatasvir functions as a new perilipin-2 (PLIN2) inhibitor by interrupting its stability. In specific, PLIN2 subjected to MARCH6-mediated protein degradation in a K11-type ubiquitination. Daclatasvir can directly bind to PLIN2 and enhance its interaction with MARCH6, leading to markedly strengthened PLIN2 ubiquitinational degradation and the subsequent decline in lipid droplet disintegration and lipotoxicity. The specific mutation at the binding amino acid sites of PLIN2 with daclatasvir largely abolished the anti-MASH benefit of daclatasvir. In conclusion, the findings of our present study for the first time identified the anti-HCV drug daclatasvir as a novel and potent PLIN2 protein degradant for MASH protection.
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Affiliation(s)
- Rui Shu
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China
| | - Song Tian
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China; State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute; School of Pharmacy, Gannan Medical University, Ganzhou, China
| | - Weiyi Qu
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jinjie Yang
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China; Qujing Medical College Basic Medical Department, Qujing, China
| | - Wei Shi
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China
| | - Xinyan Li
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China
| | - Toujun Zou
- State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute; School of Pharmacy, Gannan Medical University, Ganzhou, China
| | - Changjin Jiang
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China
| | - Yuxuan Zhang
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China
| | - Zifeng Yang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Han Tian
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Hailong Yang
- State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute; School of Pharmacy, Gannan Medical University, Ganzhou, China
| | - Jiajun Fu
- State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute; School of Pharmacy, Gannan Medical University, Ganzhou, China
| | - Zhi-Gang She
- State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute; School of Pharmacy, Gannan Medical University, Ganzhou, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Hongliang Li
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China; State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute; School of Pharmacy, Gannan Medical University, Ganzhou, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
| | - Xiao-Jing Zhang
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China; State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute; School of Pharmacy, Gannan Medical University, Ganzhou, China.
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Tampaki M, Cholongitas E. Key Points and Future Directions from the 2024 Chinese Guidelines for Fatty Liver Disease. J Clin Transl Hepatol 2025; 13:434-439. [PMID: 40385943 PMCID: PMC12078172 DOI: 10.14218/jcth.2025.00051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 03/10/2025] [Accepted: 03/14/2025] [Indexed: 05/20/2025] Open
Affiliation(s)
- Maria Tampaki
- First Academic Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Cholongitas
- First Academic Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
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Shi X, Tian Z, Wang Y, Cheng X, Zhang Y, Guo X, Zhang Y, Hu B, Liang C, Wang J, Tao F, Yang L. Associations of non‑essential metals and their mixture with non-alcoholic fatty liver disease in Chinese older adults. ENVIRONMENTAL GEOCHEMISTRY AND HEALTH 2025; 47:228. [PMID: 40413681 DOI: 10.1007/s10653-025-02539-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Accepted: 05/04/2025] [Indexed: 05/27/2025]
Abstract
BACKGROUND Research investigating the impact of the non-essential metal (NEM) mixture on non-alcoholic fatty liver disease (NAFLD) among the elderly is presently insufficient. This study investigated the relationships between individual NEMs, their mixtures, and NAFLD in elderly individuals residing in Chinese communities. METHODS The analysis included 2741 participants drawn from the baseline survey of a longitudinal study. Urinary concentrations of aluminum (Al), gallium (Ga), arsenic (As), cesium (Cs), barium (Ba), thallium (Tl), uranium (U), and cadmium (Cd) were quantified using inductively coupled plasma mass spectrometry (ICP-MS). NAFLD diagnosis was determined using abdominal ultrasound imaging. Logistic regression and restricted cubic spline (RCS) models were utilized to evaluate the relationships between individual NEMs and NAFLD. Additionally, Bayesian kernel machine regression (BKMR) and quantile-based computation regression (QGC) models were employed to assess the impact of the NEM mixture on NAFLD. RESULTS After adjusting for covariates, Tl was significantly associated with an increased likelihood of NAFLD (OR 1.26, 95% CI 1.10-1.44). Both RCS and BKMR models confirmed a linear relationship between urine Tl and the risk of NAFLD. Additionally, both BKMR and QGC models highlighted a significant connection between the NEMs mixture and NAFLD, identifying Tl as the primary driver. Significant interactions were observed between Tl and Ba, as well as between Tl and hypertension (Pinteraction = 0.055) and Tl and central obesity (Pinteraction = 0.008), collectively demonstrating synergistic impacts on NAFLD risk. CONCLUSIONS The NEM mixture is associated with a higher risk of NAFLD in Chinese old adults, with Tl as the primary contributor. Additional investigation is required to validate these findings and shed light on underlying biological pathways through which co-exposure to NEMs contribute to NAFLD.
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Affiliation(s)
- Xue Shi
- Department of Epidemiology and Health Statistics, School of Public Health, Center for Big Data and Population Health of IHM, Anhui Medical University, Meishan Road 81, Hefei, 230032, Anhui, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei, 230032, Anhui, China
| | - Ziwei Tian
- Department of Epidemiology and Health Statistics, School of Public Health, Center for Big Data and Population Health of IHM, Anhui Medical University, Meishan Road 81, Hefei, 230032, Anhui, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei, 230032, Anhui, China
| | - Yuan Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Center for Big Data and Population Health of IHM, Anhui Medical University, Meishan Road 81, Hefei, 230032, Anhui, China
- Clinical College of Anhui Medical University, Hefei, 230032, Anhui, China
| | - Xuqiu Cheng
- Department of Epidemiology and Health Statistics, School of Public Health, Center for Big Data and Population Health of IHM, Anhui Medical University, Meishan Road 81, Hefei, 230032, Anhui, China
| | - Yuantao Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, Center for Big Data and Population Health of IHM, Anhui Medical University, Meishan Road 81, Hefei, 230032, Anhui, China
| | - Xianwei Guo
- Department of Epidemiology and Health Statistics, School of Public Health, Center for Big Data and Population Health of IHM, Anhui Medical University, Meishan Road 81, Hefei, 230032, Anhui, China
| | - Yan Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, Center for Big Data and Population Health of IHM, Anhui Medical University, Meishan Road 81, Hefei, 230032, Anhui, China
| | - Bing Hu
- Fuyang Center for Diseases Prevention and Control, Fuyang, 236069, Anhui, China
| | - Changliu Liang
- Fuyang Center for Diseases Prevention and Control, Fuyang, 236069, Anhui, China
| | - Jun Wang
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Fangbiao Tao
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei, 230032, Anhui, China
| | - Linsheng Yang
- Department of Epidemiology and Health Statistics, School of Public Health, Center for Big Data and Population Health of IHM, Anhui Medical University, Meishan Road 81, Hefei, 230032, Anhui, China.
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei, 230032, Anhui, China.
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Jin M, Zhang R, Xin W, Sun L, Fan X, Lu Q, Zhang L, Jiang Z, Yu Q. Fenofibrate promotes erucic acid metabolism by peroxisome enzyme EHHADH activation alleviating high-fat diet-induced steatotic liver disease. Mol Pharmacol 2025; 107:100047. [PMID: 40516250 DOI: 10.1016/j.molpha.2025.100047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 05/05/2025] [Accepted: 05/12/2025] [Indexed: 06/16/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. Fatty-acid metabolism disorders, especially long-chain fatty acids (LCFA) accumulation, is the main pathological feature of high fat diet-induced MASLD. Fenofibrate is mainly used for the treatment of hyperlipidemia and metabolic disorders in clinical settings. In recent years, its therapeutic effect on MASLD has also been reported, but the mechanism is still unclear. Here, we aimed to investigate the effect and mechanism of fenofibrate on hepatic steatosis via fatty-acid metabolism regulation. It was found that fenofibrate strongly reduced hepatic LCFA accumulation, especially decreased the content of erucic acid (EA). In AML-12 cells treated with EA, fenofibrate improved hepatic lipid accumulation by accelerating EA metabolism. In vivo and in vitro experiments have proven that peroxidase enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase is the key enzyme of fenofibrate in promoting LCFA metabolism. This study confirmed that fenofibrate upregulated peroxisome enzyme enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase expression to promote LCFA oxidation, which provided a novel strategy for the treatment of high-fat diet-induced steatotic liver disease in clinical settings. SIGNIFICANCE STATEMENT: We found that long-chain fatty acid overload was a characteristic of high-fat diet-induced fatty liver, and fenofibrate ameliorated high-fat diet-induced fatty liver by upregulating enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase to promote the oxidation of long-chain fatty acids, especially erucic acid. This study may contribute to the use of fenofibrate in the treatment of fatty liver disease.
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Affiliation(s)
- Ming Jin
- New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Rongmi Zhang
- New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Wenwen Xin
- New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Li Sun
- New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Xue Fan
- New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Qian Lu
- New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Luyong Zhang
- New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China; Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, China.
| | - Zhenzhou Jiang
- New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, China.
| | - Qinwei Yu
- New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
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Peng HY, Lu CL, Zhao M, Huang XQ, Huang SX, Zhuo ZW, Liu J, Lu YP, Lv WL. Clinical characteristics of MASLD/MetALD/MAFLD/NAFLD and the relative risk analysis on metabolic disorders. BMC Gastroenterol 2025; 25:372. [PMID: 40369430 PMCID: PMC12079820 DOI: 10.1186/s12876-025-03912-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2025] [Accepted: 04/18/2025] [Indexed: 05/16/2025] Open
Abstract
OBJECTIVES Our objective was to compare the clinical features of Metabolic dysfunction-associated steatotic liver disease (MASLD) /metabolic alcohol-related liver disease (MetALD)/metabolic associated fatty liver disease (MAFLD)/nonalcoholic fatty liver disease (NAFLD) and the relative risk analysis of metabolic disorders. METHODS The National Health and Nutrition Examination Survey for the 2017-2018 cycle was used to screen the participants. Multivariate-adjusted logistic regression models were applied to explore the difference in relative risk analysis between NAFLD/MAFLD/MASLD/MetALD and metabolic disorders. RESULTS Among the 1,862 eligible individuals, 358(44.84%) had MASLD, 213(11.44%) had MetALD, 841(45.17%) had MAFLD, and 1,125(60.42%) had NAFLD. Positive associations with the risk of hypertension were discovered for MASLD (OR = 2.892, 95%CI = 2.226-3.756), MetALD (OR = 1.802, 95% CI = 1.355-2.398), MAFLD (OR = 3.455, 95%CI = 2.741-4.354) and NAFLD (OR = 1.983, 95%CI = 1.584-2.484). Positive associations with the risk of T2DM were discovered for MASLD (OR = 6.360, 95%CI = 4.440-9.109), MAFLD (OR = 7.026, 95%CI = 4.893-10.090) and NAFLD (OR = 3.372, 95%CI = 2.511-4.528). We discovered similar results for hyperlipidemia. Compared to mild steatosis, moderate to severe steatosis in patients with MASLD (OR = 3.924, 95%CI = 2.399-6.419), MAFLD (OR = 3.814, 95%CI = 2.367-6.144), NAFLD (OR = 4.910, 95%CI = 2.983-8.080) has a higher risk for T2DM. CONCLUSION The proposed definitions of MASLD and MetALD are valuable and deserve further exploration. Our findings suggest that MAFLD is a more effective indicator for identifying patients at increased risk for metabolic disorders.
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Affiliation(s)
- Hong-Ye Peng
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Chun-Li Lu
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine (Institute of Traditional Chinese Medicine), Guangdong Pharmaceutical University, 280 Huandong Road, University Town, Guangzhou, Guangdong Province, 510006, China
| | - Mo Zhao
- Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Xiao-Qiang Huang
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine (Institute of Traditional Chinese Medicine), Guangdong Pharmaceutical University, 280 Huandong Road, University Town, Guangzhou, Guangdong Province, 510006, China
| | - Shu-Xia Huang
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Zi-Wen Zhuo
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Jing Liu
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China
| | - Yan-Ping Lu
- Department of Hepatology, Shenzhen Baoan Hospital of Traditional Chinese Medicine, Guangdong, 518100, China.
| | - Wen-Liang Lv
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
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Zhang S, Zhao R, Wang R, Lu Y, Xu M, Lin X, Lan R, Zhang S, Tang H, Fan Q, Yang J, Liu L, Xu J. Weissella viridescens Attenuates Hepatic Injury, Oxidative Stress, and Inflammation in a Rat Model of High-Fat Diet-Induced MASLD. Nutrients 2025; 17:1585. [PMID: 40362894 PMCID: PMC12073722 DOI: 10.3390/nu17091585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2025] [Revised: 05/02/2025] [Accepted: 05/03/2025] [Indexed: 05/15/2025] Open
Abstract
Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder globally. Probiotic supplementation has shown promise in its prevention and treatment. Although Weissella viridescens, a lactic acid bacterium with immunomodulatory effects, has antibacterial and anti-inflammatory activities, there is a lack of direct evidence for its role in alleviating MASLD. This study aimed to investigate the protective effects of W. viridescens strain Wv2365, isolated from healthy human feces, in a high-fat diet (HFD)-induced rat model of MASLD. Methods: Rats were randomly assigned to a normal chow diet (NC), high-fat diet (HFD), and HFD supplemented with W. viridescens Wv2365 (Wv2365) groups. All groups were fed their respective diets for 8 weeks. During this period, the NC and HFD groups received a daily oral gavage of PBS, while the Wv2365 group received a daily oral gavage of Wv2365. Results: Wv2365 supplementation significantly reduced HFD-induced body weight gain, improved NAFLD activity scores, alleviated hepatic injury, and restored lipid metabolism. A liver transcriptomic analysis revealed the downregulation of inflammation-related pathways, along with decreased serum levels of TNF-α, IL-1β, IL-6, MCP-1, and LPS. Wv2365 also activated the Nrf2/HO-1 antioxidant pathway, enhanced hepatic antioxidant enzyme activities and reduced malondialdehyde levels. A gut microbiota analysis showed the enrichment of beneficial genera, including Butyricicoccus, Akkermansia, and Blautia. Serum metabolomic profiling revealed increased levels of metabolites including indole-3-propionic acid, indoleacrylic acid, and glycolithocholic acid. Conclusions: Wv2365 attenuates hepatic injury, oxidative stress, and inflammation in a rat model of high-fat-diet-induced MASLD, supporting its potential as a probiotic candidate for the modulation of MASLD.
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Affiliation(s)
- Shuwei Zhang
- School of Public Health, Nanjing Medical University, Nanjing 211166, China; (S.Z.)
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Ruiqing Zhao
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Ruoshi Wang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Yao Lu
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Mingchao Xu
- Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang 050010, China
| | - Xiaoying Lin
- School of Public Health, Nanjing Medical University, Nanjing 211166, China; (S.Z.)
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Ruiting Lan
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia
| | - Suping Zhang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Huijing Tang
- School of Public Health, Nanjing Medical University, Nanjing 211166, China; (S.Z.)
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Qianhua Fan
- School of Public Health, Nanjing Medical University, Nanjing 211166, China; (S.Z.)
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Jing Yang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
- Research Units of Discovery of Unknown Bacteria and Function, Chinese Academy of Medical Sciences, Beijing 102206, China
- Hebei Key Laboratory of Intractable Pathogens, Shijiazhuang Center for Disease Control and Prevention, Shijiazhuang 050011, China
| | - Liyun Liu
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
- Research Units of Discovery of Unknown Bacteria and Function, Chinese Academy of Medical Sciences, Beijing 102206, China
- Hebei Key Laboratory of Intractable Pathogens, Shijiazhuang Center for Disease Control and Prevention, Shijiazhuang 050011, China
| | - Jianguo Xu
- School of Public Health, Nanjing Medical University, Nanjing 211166, China; (S.Z.)
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
- Research Units of Discovery of Unknown Bacteria and Function, Chinese Academy of Medical Sciences, Beijing 102206, China
- Hebei Key Laboratory of Intractable Pathogens, Shijiazhuang Center for Disease Control and Prevention, Shijiazhuang 050011, China
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Huang C, Gao Z, Huang Z, Xu J. Nonlinear association between body roundness index and metabolic dysfunction associated steatotic liver disease in nondiabetic Japanese adults. Sci Rep 2025; 15:15442. [PMID: 40316694 PMCID: PMC12048529 DOI: 10.1038/s41598-025-99540-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Accepted: 04/21/2025] [Indexed: 05/04/2025] Open
Abstract
The global rise in obesity and diabetes has been paralleled by a rising incidence of metabolic dysfunction-associated steatotic liver disease (MASLD). Although previous studies have explored the association between body roundness index (BRI) and MASLD, the specific relationship in non-diabetic Japanese adults requires further investigation. This study analyzed data from 15,299 participants enrolled in the NAGALA cohort (2004-2015) to explore the association between BRI and MASLD through multivariable logistic regression, stratified analysis, and restricted cubic spline modeling. The prevalence of MASLD was 14.46%, with 13.73% occurring in non-obese individuals (BMI < 30). After adjusting for all confounding factors, BRI demonstrated a significant association with MASLD, yielding an adjusted odds ratio of 1.72 (95% CI 1.48-1.99). The restricted cubic spline model revealed a nonlinear relationship, with an inflection point at 3.06. Stratified analyses revealed stronger associations in individuals with lower BMI (≤ 24 kg/m2).
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Affiliation(s)
- Cheng Huang
- Department of Colorectal Surgery, First People's Hospital of Xiaoshan District, Hangzhou, 311200, Zhejiang, China
| | - Zhichao Gao
- Department of Neurosurgery, First People's Hospital of Xiaoshan District, Hangzhou, 311200, Zhejiang, China
| | - Zhenxia Huang
- Department of Infectious Diseases, First People's Hospital of Xiaoshan District, Hangzhou, 311200, Zhejiang, China
| | - Junfeng Xu
- Department of Colorectal Surgery, First People's Hospital of Xiaoshan District, Hangzhou, 311200, Zhejiang, China.
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Qu X, Sun J, Shen Y, Dong J, Li X, Ma Y, Sun J. Chaihu-Shugan-San for patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis. Medicine (Baltimore) 2025; 104:e42303. [PMID: 40324244 PMCID: PMC12055143 DOI: 10.1097/md.0000000000042303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 12/29/2024] [Accepted: 04/14/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by intrahepatic accumulation and is closely associated with metabolic problems. Some studies have indicated that Chaihu-Shugan-San (CSS) may have a positive effect on NAFLD, but robust evidence-based research to substantiate the application of CSS is scarce. A meta-analysis was conducted to assess the clinical efficacy and safety of CSS in the treatment for NAFLD. METHODS The literature reporting CSS in NAFLD was searched from inception to October 2023 in in 7 Chinese or English databases. Studies were screened and incorporated based on predefined criteria. Data were extracted and quality was assessed independently by 2 researchers according to the Cochrane risk of bias tools. The changes in outcomes were analyzed using the mean difference (MD) and 95% confidence intervals (CIs) with a random- or fixed-effects model to examine the effect of CSS. RevMan5.4 software was used to perform meta-analyses, and the meta package of R 4.0.0 software was used for publication bias analysis. RESULTS A total 17 studies involving 1576 participants were screened for meta-analysis. There was high heterogeneity among studies for all continuous outcomes. Compared with common treatments, CSS could decrease aspartate-aminotransferase (MD = -12.02, 95% CI [-15.97, -8.07]), alanine-aminotransferase (MD = -10.89, 95% CI [-16.35, -5.43]), triglyceride and total cholesterol levels. In addition, CSS may increase the high-density lipoprotein cholesterol levels. And, CSS was associated with a lower incidence of adverse events (RR = 0.79, 95% CI [0.33, 1.91]). CONCLUSION Current evidence shows that single or combined use of CSS is effective for NAFLD liver enzymes and blood lipids. Nevertheless, it is challenging to reach a conclusive determination owing to significant heterogeneity and ambiguous risk of bias in some trials. Therefore, more high-quality evidence is required for the clinical implementation of CSS.
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Affiliation(s)
- Xiangke Qu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Jianrong Sun
- Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
| | - Yue Shen
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Jia Dong
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaofa Li
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yanchun Ma
- Academic Research Department, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China
| | - Jinhui Sun
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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Gu Y, Guo C, Liu Z, Zhang Y, Han X, Zhang X, Zhao S, Wang H, Zhang T. The trend in incidence of non-alcoholic fatty liver disease and its impact on cirrhosis and liver cancer: An analysis from Global Burden of Disease 2021. Public Health 2025; 242:79-86. [PMID: 40037155 DOI: 10.1016/j.puhe.2025.02.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 02/04/2025] [Accepted: 02/20/2025] [Indexed: 03/06/2025]
Abstract
OBJECTIVES We aimed to recognize the burden of NAFLD and support public health policy development for its prevention and management. STUDY DESIGN A cross-sectional analysis of GBD 2021 results was conducted. METHODS We collected incidence data on NAFLD from 1990 to 2021 using Global Burden of Disease Study in 2021. Estimated annual percentage changes (EAPCs) in NAFLD age standardized incidence rate (ASR) were calculated to quantify the temporal trends in NAFLD ASR. Bayesian age-period-cohort models were constructed to project NAFLD incidence rates and cases up to 2050. Additionally, we assessed the percentage of cirrhosis and liver cancer attributable to NAFLD. RESULTS Globally, the newly-occurred cases of NAFLD increased by 94.49 % from 24, 856, 159 in 1990 to 48, 353, 272 in 2021. The case number will further increase to 78,602,984 in 2050, and ASR will increase from 5.93 per 1000 in 2021 to 7.26 per 1000 in 2050. The most pronounced increases were observed in young people and men. In 2021, NAFLD accounted for 82.7 % of cirrhosis and other chronic liver diseases and 8.0 % of liver cancer cases. CONCLUSIONS From 1990 to 2021, the incidence of NAFLD has been continuously increasing and is expected to continue rising until 2050. The increases in young people and men highlight their priority in future schedules. The rising proportions of cirrhosis and liver cancer caused by NAFLD further underscore the serious health risks.
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Affiliation(s)
- Yu Gu
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Chengnan Guo
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China; Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Zhenqiu Liu
- Fudan University Taizhou Institute of Health Sciences, Taizhou, 225300, China; State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, 200032, China
| | - Yujiao Zhang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China; Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Xinyu Han
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Xin Zhang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Shuzhen Zhao
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Haili Wang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China
| | - Tiejun Zhang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200032, China; Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, 200032, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, 225300, China; Yiwu Research Institute, Fudan University, Yiwu, 200032, China.
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Liu J, Deng L, Yao B, Zhang Y, Huang J, Huang S, Liang C, Shen Y, Wang X. Carboxylesterase 2A gene knockout or enzyme inhibition alleviates steatohepatitis in rats by regulating PPARγ and endoplasmic reticulum stress. Free Radic Biol Med 2025; 232:279-291. [PMID: 40089078 DOI: 10.1016/j.freeradbiomed.2025.03.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 03/09/2025] [Accepted: 03/13/2025] [Indexed: 03/17/2025]
Abstract
Metabolic dysfunction associated steatotic liver disease (MASLD) is a widespread liver disease that progresses from simple steatosis to severe steatohepatitis stage. Despite the recognized importance of carboxylesterase 2 (CES2) in hepatic lipid metabolism, the role of CES2 in hepatic inflammation remains unclear. The rat genome encodes six Ces2 genes and Ces2a shows high expression in the liver and intestine. Lipid metabolism, inflammation, fibrosis, and endoplasmic reticulum (ER) stress were investigated in Ces2a knockout (KO) rats. KO rats showed spontaneous liver lipid accumulation due to increased lipogenesis and reduced fatty acid oxidation. Non-targeted lipidomic analysis revealed enhanced lysophosphatidylcholines (LPCs) and phosphatidylcholines (PCs) in KO rats and increased concentrations of ligands, thus activating the expression of PPARγ. Although there was simple lipid accumulation in the liver of KO rats, Ces2a deficiency showed a significant protective effect against LPS and diet-induced hepatic steatohepatitis by inhibiting ER stress regulated by PPARγ activation. In line with this, treatment with tanshinone IIA, a CES2 inhibitor, significantly alleviated the progression of steatohepatitis induced by the MCD diet. In conclusion, the increased PPARγ expression in Ces2a deficiency may counteract liver inflammation and ER stress despite the presence of simple steatosis. Therefore, CES2 inhibition represents a potential therapeutic approach for steatohepatitis.
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Affiliation(s)
- Jie Liu
- Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China
| | - Luyao Deng
- Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China
| | - Bingyi Yao
- Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China
| | - Yuanjin Zhang
- Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China
| | - Junze Huang
- Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China
| | - Shengbo Huang
- Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China
| | - Chenmeizi Liang
- Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China
| | - Yifei Shen
- Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China
| | - Xin Wang
- Changning Maternity and Infant Health Hospital and School of Life Sciences, Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China.
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15
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Tu S, Jing X, Bu X, Zhang Q, Liao S, Zhu X, Guo Y, Sha W. Identification of pyroptosis-associated gene to predict fibrosis and reveal immune characterization in non-alcoholic fatty liver disease. Sci Rep 2025; 15:14944. [PMID: 40301412 PMCID: PMC12041580 DOI: 10.1038/s41598-025-96158-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 03/26/2025] [Indexed: 05/01/2025] Open
Abstract
Despite advances in research, studies on predictive models for Non-Alcoholic Fatty Liver Disease (NAFLD)-related fibrosis remain limited. Identifying new biomarkers to distinguish Non-Alcoholic Steatohepatitis (NASH) from NAFLD would aid in the treatment of NASH. Gene expression and clinical profiles of NAFL and NASH patients were collected from databases. Differentially expressed genes with prognostic value were used to construct predictive model. Validation of fibrosis stage-related pyroptosis-related genes (PRGs) was performed using Sprague-Dawley rats liver fibrosis models induced by CCl4 or PS. Immune cell infiltration assessment demonstrated that stromal score, immune score, and ESTIMATE score were higher in patients with NASH compared to those with NAFL. BAX, BAK1, PYCARD, and NLRP3 were identified as hub genes that exhibit a strong correlation with fibrosis stage. Additionally, the expression of these genes was increased in fibrotic liver tissues induced by CCl4 and PS. The pyroptosis-associated gene signature effectively predicts the degree of liver fibrosis in NASH patients. Our study indicates that BAX, BAK1, PYCARD, and NLRP3 might serve as biomarkers for NASH-associated fibrosis.
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Affiliation(s)
- Sha Tu
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China
| | - Xi Jing
- School of Nursing, Jinan University, Guangzhou, 510632, China
| | - Xiaoling Bu
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China
| | - Qingfang Zhang
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China
| | - Shanying Liao
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China
| | - Xiaobo Zhu
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China
| | - Ying Guo
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China
| | - Weihong Sha
- Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China.
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16
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Li M, Yu B, Zhang X, Pan J, Tang L, Zhang Y, Wang R, Zeng H, Yang S. Association between alcohol consumption and hepatic fibrosis in Chinese adult males with metabolic dysfunction-associated steatotic liver disease. Front Med (Lausanne) 2025; 12:1572853. [PMID: 40357286 PMCID: PMC12066787 DOI: 10.3389/fmed.2025.1572853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Accepted: 04/10/2025] [Indexed: 05/15/2025] Open
Abstract
Background The impact of moderate drinking on the risk of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) remains controversial worldwide. Notably, China, with the fastest-growing incidence of NAFLD and the highest number of alcohol-attributable deaths globally, has relatively few studies addressing this issue. This study aimed to explore the association between alcohol consumption and liver fibrosis in Chinese men with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods We recruited 4,683 male employees diagnosed with MASLD from southwest China, including 4,287 with pure MASLD and 396 with metabolic and alcohol-related liver disease (MetALD) who consumed increased alcohol (30-60 g/d). Advanced fibrosis was defined as a fibrosis-4 index (FIB-4) ≥ 2.67, and FIB-4 ≥ 1.30 indicated an intermediate/high probability of hepatic fibrosis. Logistic regression models were used to assess the association between alcohol consumption and hepatic fibrosis, and analyze the modification effect of body mass index (BMI) and waist-to-hip ratio (WHR) on the association. Propensity score matching method was used to test the robustness of the regression results. Results Compared with non-drinkers, both moderate (OR = 3.02, 95% CI: 1.16-10.31) and increased alcohol consumption (OR = 4.64, 95% CI: 1.60-16.82) were significantly associated with an increased risk of advanced fibrosis in males with MASLD. Additionally, moderate (OR = 1.33, 95% CI: 1.07-1.66) and increased drinking (OR = 1.74, 95% CI: 1.28-2.34) were associated with intermediate/high probability of hepatic fibrosis, with similar results from logistic regression analysis in propensity score-matched cases. Trend analysis revealed the risk of hepatic fibrosis increased with increasing alcohol intake (FIB-4 ≥ 1.30, p for trend < 0.001; FIB-4 ≥ 2.67, p for trend = 0.007). Further subgroup analysis showed that the association between moderate drinking and intermediate/high probability of hepatic fibrosis was predominantly observed in males with BMI ≥ 23 kg/m2 (OR = 1.35, 95% CI: 1.08-1.69) and those with WHR ≥ 0.9 (OR = 1.40, 95% CI: 1.11-1.78). Conclusion In China, moderate alcohol intake may heighten the risk of hepatic fibrosis in males with MASLD who are overweight/obese or have abdominal obesity. Moreover, males with MetALD may have a higher risk of fibrosis compared to those with pure MASLD.
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Affiliation(s)
- Mao Li
- Department of Health Management Centre, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China
| | - Bin Yu
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaoli Zhang
- Department of Health Management Centre, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China
| | - Jia Pan
- Department of Health Management Centre, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China
| | - Lei Tang
- Department of Health Management Centre, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China
| | - Yi Zhang
- Department of Health Management Centre, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China
| | - Ruixin Wang
- North Sichuan Medical College, Nanchong, Sichuan, China
| | - Honglian Zeng
- Department of Health Management Centre, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China
| | - Shujuan Yang
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
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Chen J, Zhang B, Cheng Y, Jia Y, Zhou B. Machine Learning-Based Non-Invasive Prediction of Metabolic Dysfunction-Associated Steatohepatitis in Obese Patients: A Retrospective Study. Diagnostics (Basel) 2025; 15:1096. [PMID: 40361915 PMCID: PMC12072127 DOI: 10.3390/diagnostics15091096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 04/19/2025] [Accepted: 04/22/2025] [Indexed: 05/15/2025] Open
Abstract
Objectives: We aimed to develop and validate machine learning (ML) models that integrate clinical and laboratory data for the non-invasive prediction of metabolic dysfunction-associated steatohepatitis (MASH) in an obese population. Methods: In this retrospective study, clinical and laboratory data were collected from obese patients undergoing bariatric surgery. The cohort was divided using stratified random sampling, and optimal features were selected with SHapley Additive exPlanations (SHAP). Various ML models, including K-nearest neighbors, linear support vector machine, radial basis function support vector machine, Gaussian process, random forest, multilayer perceptron, adaptive boosting, and naïve Bayes, were developed through cross-validation and hyperparameter tuning. Diagnostic performance was assessed via the area under the curve (AUC) in both training and validation sets. Results: A total of 558 patients were analyzed, with 390 in the training set and 168 in the validation set. In the training cohort, the median age was 35 years, the median body mass index (BMI) was 39.8 kg/m2, 39.0% were male, 37.9% had diabetes mellitus, and 62.8% were diagnosed with MASH. The validation cohort had a median age of 34.1 years, a median BMI of 42.5 kg/m2, 41.7% male, 32.7% with diabetes, and 39.9% with MASH. Among the models, the random forest achieved the highest performance among the models with AUC values of 0.94 in the training set and 0.88 in the validation set. The Gaussian process model attained an AUC of 0.97 in the training cohort but 0.79 in the validation cohort, while the other models achieved AUC values ranging from 0.63 to 0.88 in the training cohort and 0.62 to 0.75 in the validation set. Conclusions: ML models, particularly the random forest, effectively predict MASH using readily available data, offering a promising non-invasive alternative to conventional serological scoring. Prospective studies and external validations are needed to further establish clinical utility.
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Affiliation(s)
- Jie Chen
- Department of Ultrasound, China-Japan Friendship Hospital, Beijing 100029, China
| | - Bo Zhang
- Department of Ultrasound, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yong Cheng
- School of Information Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
| | - Yuanchen Jia
- School of Information Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
| | - Biao Zhou
- Department of General Surgery & Obesity and Metabolic Disease Center, China-Japan Friendship Hospital, Beijing 100029, China
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Liu SJ, Duan JH, Chen YY, Gu SL, He YH, Xue MM, Yue JY. Unraveling the triglyceride-glucose index: a key predictor of liver fat content and the amplifying role of BMI: evidence from a large physical examination data. Front Endocrinol (Lausanne) 2025; 16:1555300. [PMID: 40352458 PMCID: PMC12061704 DOI: 10.3389/fendo.2025.1555300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Accepted: 04/07/2025] [Indexed: 05/14/2025] Open
Abstract
Background The triglyceride-glucose (TyG) index is associated with the severity of metabolic-associated fatty liver disease (MASLD), but its link to liver fat content is not fully understood. This study investigates the relationship between the TyG index and liver fat content and explores the role of body mass index (BMI) as a mediator. Methods This cross-sectional study analyzed data from 12,750 participants who underwent health screenings at the first affiliated hospital of Xinxiang Medical University between January 2018 and December 2023. The TyG index, derived as Ln [triglycerides (mg/dl) * fasting plasma glucose (mg/dl)/2], was the independent variable, while liver fat content, measured by quantitative computed tomography (QCT), was the dependent variable. Participants were grouped into tertiles based on their TyG index. Univariate and multivariate analyses, smooth curve fitting (generalized additive models), threshold effect analysis, and subgroup analyses were used to assess the TyG-liver fat content relationship. BMI's mediating effect was also examined. Results Liver fat content increased steadily across TyG index tertiles. After adjusting for confounders, the TyG index remained independently associated with liver fat content [β = 1.42, 95% CI: 1.26-1.57]. Participants in the highest TyG tertile (T3) had a 1.58-fold higher liver fat content compared to those in the lowest tertile (T1) (95% CI: 1.37-1.80, P<0.001). A generalized additive model showed a nonlinear relationship between TyG index and liver fat content. When the TyG index ≤ 7.39, liver fat content increased gradually (β = 0.74, 95% CI: 0.50-0.99, P<0.001). Beyond this threshold, liver fat content rose sharply (β = 2.19, 95% CI: 1.92-2.46, P<0.001). Subgroup analysis indicated that the association between TyG index and liver fat content was stronger at higher BMI levels (P for interaction < 0.001). Mediation analysis revealed that BMI accounted for 26.68% of the observed effect. Conclusion The TyG index is positively associated with liver fat content in a nonlinear manner, with BMI amplifying this effect. These results suggest that the TyG index may be a useful marker for predicting liver fat content, and managing weight could help slow the progression of MASLD.
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Affiliation(s)
| | | | | | | | | | | | - Jun-Yan Yue
- Department of Radiology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
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Mai X, Li M, Jin X, Huang S, Xu M, Yan B, Wei Y, Long X, Wu Y, Mo Z. Identification of a Risk-Prediction Model for Hypertension Patients Concomitant with Nonalcoholic Fatty Liver Disease. Healthcare (Basel) 2025; 13:969. [PMID: 40361747 PMCID: PMC12071756 DOI: 10.3390/healthcare13090969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 04/07/2025] [Accepted: 04/18/2025] [Indexed: 05/15/2025] Open
Abstract
Objective: Our study aims to develop a personalized nomogram model for predicting the risk of nonalcoholic fatty liver disease (NAFLD) in hypertension (HTN) patients and further validate its effectiveness. Methods: A total of 1250 hypertensive (HTN) patients from Guangxi, China, were divided into a training group (875 patients, 70%) and a validation set (375 patients, 30%). LASSO regression, in combination with univariate and multivariate logistic regression analyses, was used to identify predictive factors associated with nonalcoholic fatty liver disease (NAFLD) in HTN patients within the training set. Subsequently, the performance of an NAFLD nomogram prediction model was evaluated in the separate validation group, including assessments of differentiation ability, calibration performance, and clinical applicability. This was carried out using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: The risk-prediction model for the HTN patients concomitant with NAFLD included oral antidiabetic drugs (OADs) (OR = 2.553, 95% CI: 1.368-4.763), antihypertensives (AHs) (OR = 7.303, 95% CI: 4.168-12.794), body mass index (BMI) (OR = 1.145, 95% CI: 1.084-1.209), blood urea nitrogen (BUN) (OR = 0.924, 95% CI: 0.860-0.992), triglycerides (TGs) (OR = 1.474, 95% CI: 1.201-1.809), aspartate aminotransferase (AST) (OR = 1.061, 95% CI: 1.018-1.105), and AST/ALT ratio (AAR) (OR = 0.249, 95% CI: 0.121-0.514) as significant predictors. The AUC of the NAFLD risk-prediction model in the training set and the validation set were 0.816 (95% CI: 0.785-0.847) and 0.794 (95% CI: 0.746-0.842), respectively. The Hosmer-Lemeshow test showed that the model has a good goodness-of-fit (p-values were 0.612 and 0.221). DCA suggested the net benefit of using a nomogram to predict the risk of HTN patients concomitant with NAFLD is higher. These results suggested that the model showed moderate predictive ability and good calibration. Conclusions: BMI, OADs, AHs, BUN, TGs, AST, and AAR were independent influencing factors of HTN combined with NAFLD, and the risk prediction model constructed based on this could help to identify the high-risk group of HTN combined with NAFLD at an early stage and guide the development of interventions. Larger cohorts with multiethnic populations are essential to verify our findings.
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Affiliation(s)
- Xiaoyou Mai
- School of Public Health, Guangxi Medical University, Nanning 530021, China; (X.M.); (Y.W.); (X.L.)
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
| | - Mingli Li
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
| | - Xihui Jin
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
- Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530021, China
| | - Shengzhu Huang
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
| | - Mingjie Xu
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
- Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530021, China
| | - Boteng Yan
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
- Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530021, China
| | - Yushuang Wei
- School of Public Health, Guangxi Medical University, Nanning 530021, China; (X.M.); (Y.W.); (X.L.)
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
| | - Xinyang Long
- School of Public Health, Guangxi Medical University, Nanning 530021, China; (X.M.); (Y.W.); (X.L.)
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
| | - Yongxian Wu
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
- Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530021, China
| | - Zengnan Mo
- Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, China; (M.L.); (X.J.); (S.H.); (M.X.); (B.Y.); (Y.W.)
- Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530021, China
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Li M, Wan Y, Wei Z, Lin W. Comparison of the predictive value of TyG index and METS-IR for OSA combined with NAFLD: a retrospective observational study based on a physical examination population. BMC Gastroenterol 2025; 25:279. [PMID: 40259241 PMCID: PMC12013029 DOI: 10.1186/s12876-025-03856-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 04/04/2025] [Indexed: 04/23/2025] Open
Abstract
BACKGROUND Obstructive sleep apnoea (OSA), Non-alcoholic fatty liver disease (NAFLD) and insulin resistance (IR) are interlinked. The aim of our study was to investigate the predictive value of metabolic score for insulin resistance (METS-IR) and triglyceride-glucose(TyG) index in relation to OSA combined with NAFLD in physical examination population. METHODS This is a retrospective observational study. 329 physical examiners who attended the healthcare centre of the First Affiliated Hospital of Wenzhou Medical University for polysomnography and abdominal ultrasonography (or CT abdominal scanning) from September 2021 to July 2024. Subjects were categorized into two groups according to the presence or absence of combined NAFLD. Logistic regression analysis and restricted cubic spline model (RCS) were used to evaluate the relationship between TyG index and METS-IR and NAFLD. The predictive value of TyG index and METS-IR for NAFLD was determined by receiver operating characteristic curves (ROC curves). RESULTS A total of 329 subjects were analyzed. The prevalence of NAFLD increased with increasing TyG index (P for trend < 0.001), and METS-IR showed an increasing-decreasing-increasing trend with NAFLD risk (P for trend < 0.001). RCS analysis showed a dose-response relationship between NAFLD risk and METS-IR (p = 0.012) and a linear relationship with the TyG index (p = 0.078), with a significant increase in the risk of NAFLD when the METS-IR exceeded a threshold of 47.47 (OR = 1). Compared with TyG index (AUC = 0.775, 95% CI: 0.711-0.828), METS-IR (AUC = 0.778, 95% CI: 0.716-0.836) had a higher predictive value for NAFLD in the OSA physical examination population. CONCLUSIONS In the OSA population, TyG index and METS-IR had predictive value for the development of NAFLD, with METS-IR being superior to TyG index.
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Affiliation(s)
- Min Li
- First Clinical School of Medicine (School of Information and Engineering), Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yujing Wan
- First Clinical School of Medicine (School of Information and Engineering), Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Ziyue Wei
- First Clinical School of Medicine (School of Information and Engineering), Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Weihong Lin
- Department of Healthcare Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
- Wenzhou Key Laboratory of Intelligent Prevention and Active Health for Aging-Related Chronic Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
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Liu H, Yang Z, Li J, Zhang J, Sun C. Expanding the horizons of bicyclol in multiple diseases: Mechanisms, therapeutic implications and challenges. Eur J Pharmacol 2025; 993:177381. [PMID: 39954842 DOI: 10.1016/j.ejphar.2025.177381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 01/25/2025] [Accepted: 02/11/2025] [Indexed: 02/17/2025]
Abstract
Bicyclol, a drug stemmed from the traditional Chinese medicine Schisandra chinensis, has been widely utilized in clinical practice due to its efficacy and safety to manage hepatopathy. Its diverse biological properties-including antiviral, anti-inflammatory, antifibrotic, immunomodulatory, antioxidative, antisteatotic, and antitumor effects-underscore its significant medicinal effects in versatile hepatic disorders, incorporating viral hepatitis, non-alcoholic fatty liver disease, hepatocellular carcinoma, acute hepatic failure, hepatic fibrosis as well as drug-induced liver injury. Furthermore, ongoing researches into the molecular mechanisms, biological activities and mode of actions concerning bicyclol have uncovered its potential therapeutic implications in other multiple diseases/conditions. Studies have indicated promising efficacy pertaining to bicyclol to treat idiopathic pulmonary fibrosis, acute lung injury, cerebral ischemia/reperfusion injury, renal dysfunction, renal cell carcinoma, and cardiovascular diseases. Accordingly, this narrative review article summarizes the current understanding of diverse biological activities and underpinning mechanisms of bicyclol across a range of diseases, as well as its pharmacokinetics, toxicity profile and shed light on future perspectives.
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Affiliation(s)
- Heng Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin, 300308, China
| | - Ziyi Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China
| | - Jia Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China
| | - Jie Zhang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China.
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin, 300308, China.
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Sun Z, Zheng Y. Metabolic diseases in the East Asian populations. Nat Rev Gastroenterol Hepatol 2025:10.1038/s41575-025-01058-8. [PMID: 40200111 DOI: 10.1038/s41575-025-01058-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/05/2025] [Indexed: 04/10/2025]
Abstract
East Asian populations, which account for approximately 20% of the global population, have become central to the worldwide rise of metabolic diseases over the past few decades. The prevalence of metabolic disorders, including type 2 diabetes mellitus, hypertension and metabolic dysfunction-associated steatotic liver disease, has escalated sharply, contributing to a substantial burden of complications such as cardiovascular disease, chronic kidney disease, cancer and increased mortality. This concerning trend is primarily driven by a combination of genetic predisposition, unique fat distribution patterns and rapidly changing lifestyle factors, including urbanization and the adoption of Westernized dietary habits. Current advances in genomics, proteomics, metabolomics and microbiome research have provided new insights into the biological mechanisms that might contribute to the heightened susceptibility of East Asian populations to metabolic diseases. This Review synthesizes epidemiological data, risk factors and biomarkers to provide an overview of how metabolic diseases are reshaping public health in East Asia and offers insights into biological and societal drivers to guide effective, region-specific strategies.
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Affiliation(s)
- Zhonghan Sun
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yan Zheng
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
- Department of Nutrition and Food Hygiene, School of Public Health, Institute of Nutrition, Fudan University, Shanghai, China.
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Zhu X, Sun F, Gao X, Liu H, Luo Z, Sun Y, Fan L, Deng J. Predictive value of triglyceride glucose index in non-obese non-alcoholic fatty liver disease. BMJ Open 2025; 15:e083686. [PMID: 40204316 PMCID: PMC11979504 DOI: 10.1136/bmjopen-2023-083686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 01/21/2025] [Indexed: 04/11/2025] Open
Abstract
OBJECTIVES A large number of patients with non-obese non-alcoholic fatty liver disease (NAFLD) in China remain undiagnosed and untreated due to insufficient awareness and ineffective pharmacotherapy. Therefore, a convenient, predictive marker and diagnostic tools are imperative. This study aimed to investigate the ability of the triglyceride glucose index (TyG) in predicting non-obese NAFLD. DESIGN An observational cross-sectional study. SETTING Department of Health Management, large urban academic medical centre and DRYAD database data. PARTICIPANTS This study included 456 patients with non-obese NAFLD and matched 456 non-fatty liver controls according to age, sex and body mass index (BMI). PRIMARY AND SECONDARY OUTCOME MEASURES The receiver operating characteristic (ROC) curve was used to evaluate the predictive role of the TyG index in non-obese NAFLD. Based on the TyG index, a clinical prediction model for non-obese NAFLD was constructed, then the prediction model was verified by the DRYAD database (n=11 562). RESULTS TyG in non-obese NAFLD was higher than that in controls (9.00 (8.66-9.40) vs 8.46 (8.10-8.83), p<0.001). Logistic regression analysis showed that TyG was an independent risk factor for non-obese NAFLD (OR=9.03, 95% CI: 5.46 to 14.94, p<0.001). ROC analysis showed that the area under the curve (AUC) was 0.78, the sensitivity was 82.5%, the specificity was 60.5%. Based on the TyG index, sex, age and BMI, the AUC of the predictive model for non-obese NAFLD was 0.78 (95% CI: 0.75 to 0.81, p<0.001). Using the DRYAD database to verify the prediction model, the AUC of the verification group was 0.85 (95% CI: 0.84 to 0.86, p<0.001). CONCLUSIONS The high level of the TyG may be an independent risk factor for non-obese NAFLD. The prediction model for non-obese NAFLD based on the TyG index has good clinical prediction value.
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Affiliation(s)
- Xiaopeng Zhu
- Department of Health Management, Daping Hospital, Army Medical University, Chongqing, Chongqing, China
| | - Fang Sun
- Department of Health Management, Daping Hospital, Army Medical University, Chongqing, Chongqing, China
| | - Xia Gao
- Department of Health Management, Daping Hospital, Army Medical University, Chongqing, Chongqing, China
| | - He Liu
- Department of Health Management, Daping Hospital, Army Medical University, Chongqing, Chongqing, China
| | - ZhongYan Luo
- Department of Health Management, Daping Hospital, Army Medical University, Chongqing, Chongqing, China
| | - Yijian Sun
- Department of Health Management, Daping Hospital, Army Medical University, Chongqing, Chongqing, China
| | - Liqi Fan
- Department of Health Management, Daping Hospital, Army Medical University, Chongqing, Chongqing, China
| | - Juan Deng
- Department of Health Management, Daping Hospital, Army Medical University, Chongqing, Chongqing, China
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Xu Y, Wang Y, Yao X, Zhao Q, Chen B, Wang N, Zhang T, Jiang Y, Wu Y, He N, Zhao G, Sun Z, Liu X. Prevalence, Incidence, and Recovery of Metabolic Dysfunction-associated Steatotic Liver Disease and Associations With Weight Loss and Lipid Reduction in a Chinese Community-based Cohort. J Epidemiol 2025; 35:195-205. [PMID: 39401903 PMCID: PMC11882351 DOI: 10.2188/jea.je20240224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 09/23/2024] [Indexed: 03/08/2025] Open
Abstract
BACKGROUND As the most common chronic liver disease worldwide, the natural history of metabolic dysfunction-associated steatotic liver disease (MASLD) in the general population is barely reported. METHODS The Shanghai Suburban Adult Cohort and Biobank study recruited 36,404 adults between 2016 and 2017, and followed up 25,085 participants between 2019 and 2023 in Songjiang District. A questionnaire survey was conducted using face-to-face interview, and physical examination and laboratory tests were conducted. MASLD was diagnosed using liver ultrasound and the cardiometabolic risk factors (CMRF). RESULTS A total of 36,122 and 21,831 participants met the criteria for baseline and follow-up analyses. The prevalence of MASLD at baseline was 36.8% overall, and 73.6% among those with a body mass index (BMI) over 28 kg/m2. After a median follow-up time of 4.26 years, the incidence density for MASLD was 8.4, and the recovery density was 11.4 per 100 person-years overall and was 20.0 and 8.4 per 100 person-years for those with baseline BMI over 28 kg/m2. Per 1 kg/m2 increase in baseline BMI was associated with a 15% increase in incidence (hazard ratio [HR] 1.15; 95% confidence interval [CI], 1.14-1.17) and an 8% decrease in recovery (HR 0.92; 95% CI, 0.90-0.93). From baseline to follow-up visit, participants who remained non-obese or remained normal cardiometabolic status always showed the lowest incidence and the highest recovery rate, followed by those with improved status. CONCLUSION The prevalence and incidence of MASLD were high among Shanghai residents, and active recovery was also observed. Obesity was the most important risk factor, and weight loss and lipid level reduction were beneficial for preventing or reversing MASLD.
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Affiliation(s)
- Yurou Xu
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Youyi Wang
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Xiajing Yao
- Songjiang District Center for Disease Control and Prevention, Shanghai, China
| | - Qi Zhao
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Bo Chen
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Na Wang
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Tiejun Zhang
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Yonggen Jiang
- Songjiang District Center for Disease Control and Prevention, Shanghai, China
| | - Yiling Wu
- Songjiang District Center for Disease Control and Prevention, Shanghai, China
| | - Na He
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Genming Zhao
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Zhongxing Sun
- Songjiang District Center for Disease Control and Prevention, Shanghai, China
| | - Xing Liu
- The Key Laboratory of Public Health Safety of Ministry of Education, Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
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Chen QQ, Yi Y, Ma ZC, Chen QL, Liu YF, Lin CL, Wang HF, Wu QF. Evaluating the adherent perinephric fat risk score in East Asian populations and its correlation with non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis 2025; 35:103806. [PMID: 39732589 DOI: 10.1016/j.numecd.2024.103806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 11/03/2024] [Accepted: 11/15/2024] [Indexed: 12/30/2024]
Abstract
BACKGROUND AND AIMS This study evaluated the predictive value of the APF risk score in East Asian patients undergoing open nephrectomy and its correlation with hypertension and NAFLD. METHODS AND RESULTS A retrospective study used the clinical data of 82 patients who underwent ON between January 2010 and December 2022. Per their APF score, patients were categorized into groups A (0-2 points) and B (3-4 points). Logistic regression analyses were used to compare the overall clinical data between the two groups and identify potential risk factors. Intraoperative APF prevalence was significantly higher in group B compared to group A (P < 0.001). Group B patients were older (63.06 ± 8.88 vs. 53.69 ± 15.21 years) and had higher incidences of hypertension (P < 0.001), diabetes (P = 0.002), and NAFLD (P < 0.001). Preoperative CT scans showed significant differences in posterior (P = 0.009) and lateral perinephric fat thickness (P < 0.001), and perinephric stranding (P < 0.001). Group B also had a higher proportion of malignant tumors (P = 0.039). Multivariate logistic regression revealed that NAFLD (OR = 9.053, P = 0.010) and hypertension (OR = 5.181, P = 0.025) were highly correlated with APF risk scores. CONCLUSIONS In this study, we found that the newly developed APF risk score had significant value in predicting APF in East Asian patients undergoing open nephrectomy. Additionally, NAFLD and hypertension were highly correlated with elevated APF risk scores.
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Affiliation(s)
- Qin-Qi Chen
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, 364000, China
| | - Yi Yi
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, 364000, China.
| | - Ze-Cong Ma
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, 364000, China
| | - Qin-Li Chen
- Department of Radiology, The Hospital of Zhangping City, Zhangping, 364001, China
| | - Yong-Fei Liu
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, 364000, China
| | - Chao-Lu Lin
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, 364000, China
| | - Hai-Feng Wang
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, 364000, China
| | - Qin-Fu Wu
- Department of Urology, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, 364000, China
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Dai JJ, Deng Y, Wang GF, Lin KQ, He JR, Hu XG. Relationship of serum 25(OH)D3 and PTX3 with liver fat content in patients with non-alcoholic fatty liver disease: Diagnostic value for liver fibrosis. Shijie Huaren Xiaohua Zazhi 2025; 33:192-198. [DOI: 10.11569/wcjd.v33.i3.192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Revised: 02/15/2025] [Accepted: 03/16/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in China. Vitamin D and pentraxin 3 (PTX3) participate in the occurrence and development of NAFLD by regulating calcium and phosphorus metabolism and inflammation. This study analyzed the relationship of serum 25-hydroxy vitamin D3 [25(OH)D3] and PTX3 levels with liver fat content and liver fibrosis in patients with NAFLD.
AIM To analyze the relationship of serum 25(OH)D3 and PTX3 with liver fat content in patients with NAFLD, as well as their diagnostic value for liver fibrosis.
METHODS A total of 120 NAFLD patients in our hospital from June 2022 to September 2023 were selected as a study group, and another 120 healthy individuals in the same period were selected as a control group. General information and serum levels of 25(OH)D3 and PTX3 were compared between and two groups, and the levels of 25(OH)D3 and PTX3 were compared in patients with different liver fat contents in the study group. The correlation between serum levels of 25(OH)D3 and PTX3 and liver fat content in NAFLD patients was analyzed. The levels of serum 25(OH)D3, PTX3, liver fibrosis, and liver function indicators [hyaluronic acid (HA), procollagen type Ⅲ (PCⅢ), procollagen type Ⅳ (PCIV), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)] were compared among patients with different degrees of liver fibrosis in the study group. The correlation of serum 25(OH)D3 and PTX3 levels with liver fibrosis and liver function indicators was examined, and their value for diagnosing liver fibrosis was assessed.
RESULTS Serum 25(OH)D3 level in the study group was lower than that of the control group, while PTX3 level was higher than that of the control group (P < 0.05). There was a statistically significant difference in serum 25(OH)D3 and PTX3 levels among patients with different liver fat contents in the study group (P < 0.05). As the liver fat content increased, serum 25(OH)D3 levels significantly decreased, while PTX3 levels significantly increased. Serum 25(OH)D3 levels were negatively correlated with liver fat content in NAFLD patients, while PTX3 levels were positively correlated with liver fat content in NAFLD patients (P < 0.05). Serum 25(OH)D3 levels in patients at risk of liver fibrosis in the study group were lower than those in patients without liver fibrosis, while the levels of PTX3, HA, PC Ⅲ, PC Ⅳ, ALT, and AST were higher than those of patients without liver fibrosis (P < 0.05). Serum 25(OH)D3 levels in NAFLD patients were negatively correlated with HA, PC Ⅲ, PC Ⅳ, ALT, and AST levels, while PTX3 levels were positively correlated with HA, PC Ⅲ, PC Ⅳ, ALT, and AST levels (P < 0.05). The area under the curve (AUC) of serum 25(OH)D3 and PTX3 alone for diagnosing liver fibrosis in patients with NAFLD was 0.713 and 0.781, respectively, while the AUC of their combination was 0.908, which was greater than the AUC of either of them alone (P < 0.05).
CONCLUSION Serum 25(OH)D3 level in NAFLD patients is negatively correlated with liver fat content, while serum PTX3 level is positively correlated with liver fat content. The two have appreciated diagnostic value in liver fibrosis.
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Affiliation(s)
- Jian-Ji Dai
- Department of Oncology and Vascular Intervention, Jinhua Central Hospital, Jinhua 321000, Zhejiang Province, China
| | - Yi Deng
- Department of Oncology and Vascular Intervention, Jinhua Central Hospital, Jinhua 321000, Zhejiang Province, China
| | - Guo-Feng Wang
- Department of Oncology and Vascular Intervention, Jinhua Central Hospital, Jinhua 321000, Zhejiang Province, China
| | - Kai-Qin Lin
- Department of Oncology and Vascular Intervention, Jinhua Central Hospital, Jinhua 321000, Zhejiang Province, China
| | - Jian-Rong He
- Department of Oncology and Vascular Intervention, Jinhua Central Hospital, Jinhua 321000, Zhejiang Province, China
| | - Xiao-Gang Hu
- Department of Oncology and Vascular Intervention, Jinhua Central Hospital, Jinhua 321000, Zhejiang Province, China
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Gui PP, Deng YL, Zhang M, Miao Y, Liu PH, Zeng JY, Wu Y, Li CR, Liu XY, Li YJ, Zhu JQ, Liu AX, Zhou B, Yang F, Zeng Q. Urinary biomarkers of drinking water disinfection byproducts in relation to blood-based liver function parameters among reproductive-aged Chinese women. THE SCIENCE OF THE TOTAL ENVIRONMENT 2025; 970:179016. [PMID: 40037233 DOI: 10.1016/j.scitotenv.2025.179016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 02/25/2025] [Accepted: 02/27/2025] [Indexed: 03/06/2025]
Abstract
BACKGROUND Toxicological studies have documented that disinfection byproducts (DBPs), the ubiquitous drinking water pollutants, induce hepatotoxicity. Yet epidemiological evidence is sparse. OBJECTIVE To assess urinary biomarkers of drinking water DBPs in relation to liver function parameters. METHODS We included 1204 reproductive-aged women from the Tongji Reproductive and Environmental (TREE) study in Wuhan, China between December 2018 and July 2021. Urinary trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) as biomarkers of drinking water DBPs were assessed. Serum liver function parameters such as albumin (ALB), total cholesterol (TC), and alkaline phosphatase (ALP) were determined. Urinary DCAA and TCAA concentrations in relation to liver function parameters were examined by multivariate linear regression or restricted cubic spline (RCS) models. RESULTS There was no evidence of urinary TCAA in relation to serum parameters of liver function. However, monotonic dose-response relationships were estimated between elevated tertiles of urinary DCAA concentrations and increased serum ALP (percent change = 4.25 %; 95 % CI: 0.34 %, 8.32 % for the upper vs. lower tertile) and TC levels (percent change = 3.84 %; 95 % CI: 0.63 %, 7.17 % for the upper vs. lower tertile). These associations remained for urinary DCAA modeled as the continuous exposure variable and were linear in the RCS models. Age, body mass index, and passive smoking status did not modify these associations. CONCLUSION DCAA but not TCAA exposure may contribute to damaged liver function in reproductive-aged women.
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Affiliation(s)
- Ping-Ping Gui
- Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China
| | - Yan-Ling Deng
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Min Zhang
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Department of Environmental Medicine and Climate Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Yu Miao
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Peng-Hui Liu
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jia-Yue Zeng
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yang Wu
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Cheng-Ru Li
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiao-Ying Liu
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yang-Juan Li
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jin-Qin Zhu
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - A-Xue Liu
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Bin Zhou
- Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
| | - Fei Yang
- Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.
| | - Qiang Zeng
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Jiang S, Zhang F, Yang H, Han X, Mao J, Zheng G, Fan Y. Estimated sdLDL-C as a biomarker of hepatic steatosis severity in MASLD: a retrospective study. BMC Gastroenterol 2025; 25:168. [PMID: 40082781 PMCID: PMC11907928 DOI: 10.1186/s12876-025-03759-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 03/04/2025] [Indexed: 03/16/2025] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. However, there is a lack of cost-effective and accurate biomarkers to assess the degree of hepatic steatosis. Estimated small dense low-density lipoprotein cholesterol (EsdLDL-C), a calculated value derived from triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels, has emerged as a potential indicator. This study aimed to explore the relationship between EsdLDL-C and the severity of hepatic steatosis. METHODS This single-center retrospective study estimated and directly measured small dense low-density lipoprotein cholesterol (sdLDL-C) in 1,969 patients who underwent serum lipid testing at Changzhou Third People's Hospital between January and July 2024. Among these, 461 patients diagnosed with MASLD were included in the study. These patients were further classified into mild (Mil) and moderate-to-severe (Mod-Sev) groups based on controlled attenuation parameter (CAP) values to explore the relationship between EsdLDL-C and the severity of hepatic steatosis. RESULTS The correlation coefficient (R) between EsdLDL-C and DsdLDL-C was 0.837, with a bias of 0.223. Both EsdLDL-C (OR 1.095, 95% CI 1.029-1.180) and visceral fat area (VFA) (OR 1.019, 95% CI 1.010-1.028) were identified as independent risk factors for Mod-Sev steatosis compared to the Mil group. After adjusting for all confounders, patients with MASLD had a 1.155-fold increased risk of developing Mod-Sev hepatic steatosis for each unit increase in EsdLDL-C. Furthermore, EsdLDL-C demonstrated good predictive value for Mod-Sev steatosis in MASLD patients, with an area under the curve (AUC) of 0.825 (95% CI 0.784-0.867). CONCLUSIONS EsdLDL-C may serve as a practical and cost-effective biomarker for identifying high-risk MASLD patients. TRIAL REGISTRATION The retrospective study was approved by the Ethics Committee of Changzhou Third People's Hospital (02 A-A20230015), and a waiver of informed consent was agreed to, as the data were obtained from medical records, and a waiver of informed consent would not have affected the participants.
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Affiliation(s)
- Shuo Jiang
- Center of Medical Laboratory, Changzhou Third People's Hospital, Changzhou, Jiangsu, China
| | - Fan Zhang
- Department of Endocrinology, Changzhou Third People's Hospital, Changzhou, Jiangsu, China
| | - Hui Yang
- Center of Medical Laboratory, Changzhou Third People's Hospital, Changzhou, Jiangsu, China
| | - Xue Han
- Center of Medical Laboratory, Changzhou Third People's Hospital, Changzhou, Jiangsu, China
| | - Jieru Mao
- Center of Medical Laboratory, Changzhou Third People's Hospital, Changzhou, Jiangsu, China
| | - Guojun Zheng
- Center of Medical Laboratory, Changzhou Third People's Hospital, Changzhou, Jiangsu, China.
| | - Yan Fan
- Center of Medical Laboratory, Changzhou Third People's Hospital, Changzhou, Jiangsu, China.
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Wang T, Zhao J, Li QY, Yang HQ, Li M, Duan R, Zhang M, Qi Y, Yu J, Yang XX. Poria cocos-Derived Exosome-like Nanovesicles Alleviate Metabolic Dysfunction-Associated Fatty Liver Disease by Promoting Mitophagy and Inhibiting NLRP3 Inflammasome Activation. Int J Mol Sci 2025; 26:2253. [PMID: 40076875 PMCID: PMC11899877 DOI: 10.3390/ijms26052253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Revised: 02/24/2025] [Accepted: 02/25/2025] [Indexed: 03/14/2025] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) affects approximately one-quarter of the world's adult population, and no effective therapeutic drugs are available. Poria cocos is a fungus used as a herb and food nutrient for centuries as well as for MAFLD treatment. Exosome-like nanovesicles have many pharmacological activities; however, studies on the effects of Poria cocos-derived exosome-like nanovesicles (PCELNs) on MAFLD are lacking. Therefore, our study aimed at identifying the effects and mechanism of action of PCELNs on MAFLD. PCELNs were isolated by ultracentrifugation and their morphology was characterized, such as particle size, zeta potential, protein distributions, as well as lipid and miRNA compositions. Then, the absorption and distribution of PCELNs were observed in vivo and in vitro. Finally, L02 cell steatosis model induced by fat emulsion and MAFLD mouse model induced by high-fat diet (HFD) were used to evaluate the effect and mechanism of PCELNs on MAFLD. PCELNs were membrane structured vesicles, with a particle size of 161.4 ± 1.7 nm, a zeta potential of -3.20 ± 0.37 mV, and contained a range of proteins, lipids, and miRNAs. PCELNs were absorbed by L02 cells and targeted the liver and spleen after intraperitoneal injection. PCELNs inhibited body weight gain and improved the index of heart, liver, spleen, and various fats, as well as decreased lipid accumulation and lipid level. They also protected mitochondrial ultrastructure and regulated oxidative stress and energy metabolism disorder. Furthermore, PCELNs increased PTEN induced kinase 1 (PINK1), E3 ubiquitin ligase (Parkin) and microtubule associated protein light chain-3 (LC3) protein expression in the liver, reduced oxidized mitochondrial DNA (Ox-mtDNA) content in mitochondria and cytoplasm of the liver, reduced nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3), pro-cysteinyl aspartate specific proteinase-1 (caspase-1), cleared-caspase-1, and mature-interleukin-1β (IL-1β) protein expression in the liver, and reduced the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and interleukin-18 (IL-18) in serum and liver. In conclusion, we demonstrated that PCELNs may alleviate HFD-induced MAFLD by promoting mitochondrial autophagy and inhibiting NLRP3 inflammasome activation.
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Affiliation(s)
- Tao Wang
- College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China; (T.W.); (J.Z.); (Q.-Y.L.); (H.-Q.Y.); (M.L.); (R.D.); (M.Z.); (Y.Q.)
- Yunnan Key Laboratory of Southern Medicine Utilization, 1076 Yuhua Road, Kunming 650500, China
| | - Jun Zhao
- College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China; (T.W.); (J.Z.); (Q.-Y.L.); (H.-Q.Y.); (M.L.); (R.D.); (M.Z.); (Y.Q.)
- Yunnan Key Laboratory of Southern Medicine Utilization, 1076 Yuhua Road, Kunming 650500, China
| | - Qiu-Yi Li
- College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China; (T.W.); (J.Z.); (Q.-Y.L.); (H.-Q.Y.); (M.L.); (R.D.); (M.Z.); (Y.Q.)
- Yunnan Key Laboratory of Southern Medicine Utilization, 1076 Yuhua Road, Kunming 650500, China
| | - Hui-Qiong Yang
- College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China; (T.W.); (J.Z.); (Q.-Y.L.); (H.-Q.Y.); (M.L.); (R.D.); (M.Z.); (Y.Q.)
- Yunnan Key Laboratory of Southern Medicine Utilization, 1076 Yuhua Road, Kunming 650500, China
| | - Min Li
- College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China; (T.W.); (J.Z.); (Q.-Y.L.); (H.-Q.Y.); (M.L.); (R.D.); (M.Z.); (Y.Q.)
- Yunnan Key Laboratory of Southern Medicine Utilization, 1076 Yuhua Road, Kunming 650500, China
| | - Rong Duan
- College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China; (T.W.); (J.Z.); (Q.-Y.L.); (H.-Q.Y.); (M.L.); (R.D.); (M.Z.); (Y.Q.)
- Yunnan Key Laboratory of Southern Medicine Utilization, 1076 Yuhua Road, Kunming 650500, China
| | - Mei Zhang
- College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China; (T.W.); (J.Z.); (Q.-Y.L.); (H.-Q.Y.); (M.L.); (R.D.); (M.Z.); (Y.Q.)
- Yunnan Key Laboratory of Southern Medicine Utilization, 1076 Yuhua Road, Kunming 650500, China
| | - Yan Qi
- College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China; (T.W.); (J.Z.); (Q.-Y.L.); (H.-Q.Y.); (M.L.); (R.D.); (M.Z.); (Y.Q.)
- Yunnan Key Laboratory of Southern Medicine Utilization, 1076 Yuhua Road, Kunming 650500, China
| | - Jie Yu
- College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China; (T.W.); (J.Z.); (Q.-Y.L.); (H.-Q.Y.); (M.L.); (R.D.); (M.Z.); (Y.Q.)
- Yunnan Key Laboratory of Southern Medicine Utilization, 1076 Yuhua Road, Kunming 650500, China
| | - Xing-Xin Yang
- College of Pharmaceutical Science, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China; (T.W.); (J.Z.); (Q.-Y.L.); (H.-Q.Y.); (M.L.); (R.D.); (M.Z.); (Y.Q.)
- Yunnan Key Laboratory of Southern Medicine Utilization, 1076 Yuhua Road, Kunming 650500, China
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Wang X, You J, Tang J, Li X, Wang R, Li Y, Yin C, Bai Y, Wang M, Zheng S. Is MAFLD better than NAFLD in predicting the risk of major cardiovascular diseases? Evidence from a 7-year prospective cohort study. Nutr Metab Cardiovasc Dis 2025; 35:103799. [PMID: 39674723 DOI: 10.1016/j.numecd.2024.103799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 11/01/2024] [Accepted: 11/15/2024] [Indexed: 12/16/2024]
Abstract
BACKGROUND AND AIMS Whether the new standard of metabolic dysfunction-associated fatty liver disease (MAFLD) has more pronounced clinical and population screening diagnostic value than nonalcoholic fatty liver disease (NAFLD) is unclear. This study evaluated the utility of MAFLD and NAFLD for predicting major cardiovascular disease (CVD) risk. METHODS AND RESULTS A prospective cohort study approach was utilized to collect 19,399 study participants without CVD at baseline who completed follow-up from the Jinchang cohort platform during 2011-2017. According to clinical ultrasonic diagnosis results and disease diagnosis criteria, the baseline population was divided into MAFLD, NAFLD, Both-FLD and No-FLD groups. Based on the multifactorial Cox proportional risk model to analyze the relationship between three kinds of patients and CVD, the score prediction model of CVD was constructed with reference to the Framingham Risk Score (FRS) and the model was evaluated. Compared with No-FLD, the HRs and 95 % CIs for the risk of CVD development in patients with NAFLD, MAFLD, and Both-FLD were 1.54 (1.34-1.76), 1.57 (1.37-1.79), and 1.62 (1.41-1.87), in that order. The scoring model showed a range of 5.90%-84.59 % risk of CVD in the three groups. As the risk score increased, the risk of developing CVD gradually increased. Evaluation metrics of all three models in the training set and validation set showed that the models have good prediction efficacy. CONCLUSION In terms of CVD risk and prognosis, MAFLD had no advantage over NAFLD. However, Both-FLD was found to predict a higher risk of CVD and to have superior predictive efficacy.
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Affiliation(s)
- Xue Wang
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Jinlong You
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Jing Tang
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Xiuqian Li
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Rui Wang
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Yuanyuan Li
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Chun Yin
- Workers' Hospital of Jinchuan Group Co., Ltd., Jinchang, 737100, China
| | - Yana Bai
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Minzhen Wang
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, China.
| | - Shan Zheng
- Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, China.
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Jin M, Lu Q, Xia N, Fan X, Zhang Z, Huang X, Sun L, Zhang L, Jiang Z, Yu Q. LncRNA Gm35585 transcriptionally activates the peroxidase EHHADH against diet-induced fatty liver. Exp Mol Med 2025; 57:652-666. [PMID: 40082671 PMCID: PMC11958773 DOI: 10.1038/s12276-025-01420-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 12/13/2024] [Accepted: 01/01/2025] [Indexed: 03/16/2025] Open
Abstract
Metabolic-dysfunction-associated steatotic liver disease is one of the most common chronic liver diseases worldwide and has no approved treatment thus far. Here we report that the hepatic overexpression of Gm35585, a novel lncRNA downregulated in the livers of mice fed a high-fat diet, is functionally important in alleviating hepatic lipid accumulation pathologies. Gm35585 activates the peroxisome proliferator-activated receptor α (PPARα) signaling pathway and promotes the expression of downstream PPARα-target gene, enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), which is one of the four enzymes of the peroxisomal β-oxidation pathway. Activation of EHHADH promotes the oxidation of long-chain fatty acids (LCFAs), and the increased levels of hepatic LCFAs contribute to metabolic-dysfunction-associated steatotic liver disease. Mechanistically, Gm35585 binds to retinoid X receptor α (RXRα) and then forms a PPARα/RXRα heterodimer with PPARα and guides the heterodimer to recognize the promoter of EHHADH, which is called peroxisome proliferator-activated receptor response element, causing transcriptional activation of EHHADH. Taken together, Gm35585 is a hepatic lipid metabolism regulator that activates EHHADH transcription, promoting peroxisomal β-oxidation of LCFAs and ultimately ameliorating diet-induced fatty liver.
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Affiliation(s)
- Ming Jin
- New Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Qian Lu
- New Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Ninglin Xia
- New Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Xue Fan
- New Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Ziling Zhang
- New Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Xiaofei Huang
- New Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Li Sun
- New Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Luyong Zhang
- New Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
- Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, China.
| | - Zhenzhou Jiang
- New Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
- Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, China.
| | - Qinwei Yu
- New Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
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Alhomaid A, Chauhan S, Katamreddy Y, Sidhu A, Sunkara P, Desai R. Prevalence and association of MASLD in metabolically healthy young Asian Americans with obesity: A nationwide inpatient perspective (2019). OBESITY PILLARS 2025; 13:100168. [PMID: 40104006 PMCID: PMC11919439 DOI: 10.1016/j.obpill.2025.100168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/29/2024] [Accepted: 02/11/2025] [Indexed: 03/20/2025]
Abstract
Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide. Although the epidemiology of MASLD and its association with metabolically healthy obesity (MHO) is well-studied in the United States, data for Asian Americans with MHO is limited. We sought to evaluate the association of MASLD in young Asian American patients with MHO. Methods This was a retrospective, matched cohort, database review of Asian American Individuals. After excluding adult hospitalizations with metabolic risk factors (hypertension, diabetes, or hyperlipidemia), we identified all National Inpatient Sample (2019) admissions with obesity (MHO) and MASLD using relevant ICD-10-CM codes. We matched (1:1) propensity scores for age, sex, household income, hospital location, and teaching status to obtain cohorts with and without obesity (MHO+) vs. (MHO-). Categorical and continuous data were compared using the Chi-square and Mann-Whitney U tests. The primary endpoint was the prevalence and adjusted multivariable odds/predictors of MASLD in (MHO+) vs. (MHO-) cohort. Results In the adjusted multivariate regression for demographics, and comorbidities, the (MHO+) cohort was associated with higher odds of admissions with MASLD (OR 4.07, 95%CI 2.02-8.19, p < 0.001). In addition, among the (MHO+) cohort, higher rates of MASLD-related hospitalizations were observed in males (OR 8.40, p < 0.001), females (OR 2.69, p = 0.025), high-income quartiles (OR 10.51, p < 0.001), no prior bariatric surgery (OR 4.07, p < 0.001), non-tobacco users(OR 4.16, p < 0.001), and non-hypothyroid patients (OR 4.00, p < 0.001) compared to the (MHO-) cohort. There was no statistically significant difference in the groups with low-income quartiles, tobacco use disorder, and hypothyroidism. Conclusion This nationwide analysis demonstrates that (MHO+) is associated with a higher prevalence of MASLD. In the (MHO+) cohort, there was an association of MASLD with sex, high-income quartile, no prior bariatric surgery, non-tobacco use, and non-hypothyroidism. Further prospective multicenter studies are needed to evaluate the association of MASLD in (MHO+) patients with comorbid conditions.
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Affiliation(s)
- Ahmad Alhomaid
- Nazareth Hospital, 2601 Holme Ave, Philadelphia, PA, 19152, USA
| | | | | | - Avideep Sidhu
- Adesh Institute of Health & Medical Sciences, Bathinda, Punjab, 151001, India
| | - Praveena Sunkara
- Passion Health Primary Care, 8195 Custer Rd Ste 110, Frisco, TX, 75035, USA
| | - Rupak Desai
- Independent Researcher, Outcomes Research, Atlanta, GA, USA
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Hu M, Huang H, Jia M, Xu M, Chen M, Wu J, Gu S, Liang H, Zhou H, Gong Y. A panel of miRNAs in the serum extracellular vesicles serve as novel diagnostic biomarkers for MASLD. Biomed J 2025:100838. [PMID: 40024368 DOI: 10.1016/j.bj.2025.100838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 02/01/2025] [Accepted: 02/23/2025] [Indexed: 03/04/2025] Open
Abstract
The increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and its profound implications for global health have sparked extensive research endeavors aimed at developing potential diagnostic methods for this condition. Despite the achievements in defining various environmental factors and genetic predispositions linked to MASLD, diagnosis and clinical staging of the disease remain challenging. Recently, extracellular vesicles (EVs) have garnered considerable attention owing to their roles in metabolic dysfunctions and their potential as biomarkers for various conditions. This study aimed to investigate whether microRNAs (miRNAs) in serum EVs could be utilized for diagnosing and staging MASLD. We applied an innovative and efficient approach that involves capturing and analyzing extracellular vesicles using wheat germ agglutinin (WGA)-coupled magnetic beads, subsequently employing reverse transcription quantitative polymerase chain reaction (RT-qPCR) for analysis. MiR-574-3p, miR-542-3p, and miR-200a-3p in serum extracellular vesicles were significantly elevated in patients with MASLD, indicating their potential as diagnostic markers. This study has established a straightforward assay platform for isolating extracellular vesicles without the need for purification and for quantitatively detecting miR-574-3p, miR-542-3p, and miR-200a-3p in serum extracellular vesicles.
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Affiliation(s)
- Moran Hu
- Department of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Hai Huang
- Department of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China; Department of Emergency, Nanjing Drum Tower Hospital, School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009, China
| | - Meng Jia
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, Jiangsu 210093, China
| | - Min Xu
- Institute of Geriatric Medicine, Jiangsu Province Geriatric Hospital, Nanjing, Jiangsu 210009, China
| | - Malin Chen
- The First Clinical College of Nanjing Medical University, Nanjing, Jiangsu 211166, China
| | - Junxiang Wu
- Department of Emergency, Nanjing Drum Tower Hospital, School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009, China
| | - Shouyong Gu
- Institute of Geriatric Medicine, Jiangsu Province Geriatric Hospital, Nanjing, Jiangsu 210009, China
| | - Hongwei Liang
- Department of Emergency, Nanjing Drum Tower Hospital, School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
| | - Hongwen Zhou
- Department of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
| | - Yingyun Gong
- Department of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
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Yang D, Wuyunsiqin, YanNiu, Hashentuya, Tana, Anna, Ma M, Zhao W, Menggenduxi, Wang M. Traditional Mongolian Medicine Qiqirigan-8 alleviates non-alcoholic fatty liver disease via restoring gut microbiota and metabolism. Front Microbiol 2025; 16:1517082. [PMID: 40083784 PMCID: PMC11905161 DOI: 10.3389/fmicb.2025.1517082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 01/31/2025] [Indexed: 03/16/2025] Open
Abstract
Background Mongolian Medicine Qiqirigan-8 (MMQ-8) is a traditional Mongolian medicine formula used to treat fatty liver disease. However, the material basis and in vivo metabolic process of the therapeutic effect of MMQ-8 on non-alcoholic fatty liver disease (NAFLD) remain unclear. Methods The chemical composition of MMQ-8 was determined using Ultra-high-performance liquid chromatography-quadrupole Exactive Mass spectrometry analysis (UHPLC-QE-MS). C57BL/6J mice were fed a choline-deficient diet for 12 weeks to induce a NAFLD model. Hematoxylin and Eosin (H&E)-staining, combined with serum biochemical indexes, was used to observe liver appearance and characterize the pathological changes and functions of the liver. HE staining and Alcian Blue-Phosphoric Acid Schiff (AB-PAS) staining of the colon, along with ZO-1 immunofluorescence expression in the colon were used to reveal the effect of MMQ-8 on the disruption of the intestinal epithelial mucosal barrier in the NAFLD. The expression of intestinal tight junction genes was analyzed by qRT-PCR to observe the protective effect of MMQ-8 against intestinal epithelial mucosal barrier disruption. Fecal metagenomics and serum non-targeted metabolomics were used to reveal the effects of MMQ-8 on the gut microbiota and metabolism in mice with NAFLD. Finally, we emphasize the interaction between gut microbiota and metabolites through Spearman correlation coefficient analysis. Results Mongolian Medicine Qiqirigan-8 contains 17 active ingredients, which can reduce hepatic steatosis and lobular inflammation in mice with NAFLD, and have protective effects against liver injury. MMQ-8 reduced the infiltration of inflammatory cells in the colon epithelium of model mice while restoring the number of goblet cells. MMQ-8 significantly enhanced ZO-1 protein expression in the colon, as well as the mRNA expression of both ZO-1 and Occludin. Fecal metagenomics results showed that MMQ-8 reduced the Bacillota/Bacteroidota ratio in NAFLD mice. Increased the abundance of beneficial bacteria such as Porphyromonadaceae, Prevotella, and Bacteroidota. and suppressed the abundance of dysfunctional bacteria, such as Bacillota, Acetatifactor, and Erysipelotrichaceae. Furthermore, metabolomics studies revealed that MMQ-8 intervention significantly regulated the expression of metabolites related to glutathione metabolism, butyric acid metabolism, sphingolipid metabolism, and glycerophospholipid metabolism in NAFLD mice compared to the model group. These metabolic pathways play key roles in NAFLD. According to Spearman's correlation coefficient analysis, up-regulation of Porphyromonadaceae, Prevotella, and Bacteroidota after MMQ-8 intervention was negatively correlated with LPC levels in glycerophospholipid metabolic pathways, while positively correlated with PC levels. In contrast, the relationship between Bacillota and Acetatifactor, which were down-regulated after MMQ-8 intervention, was the opposite. In addition, the up-regulation of Porphyromonadaceae, Prevotella, and Bacteroidota after MMQ-8 intervention was positively correlated with fumaric acid, 2-oxoglutaric acid, adenosine, and L-glutathione levels, while those down-regulated after MMQ-8 intervention were positively correlated with the levels of Bacillota, Acetatifactor were negatively correlated with all the above metabolites. Thus, glutathione metabolism, butyric acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism and gut microbial ecosystem are tightly intertwined in this process. Conclusion In summary, these findings indicate that MMQ-8 has a synergistic anti-NAFLD effect through its multi-component, multi-target, gut microbiota-modulating and multi metabolic pathway characteristics. The host's regulation of specific gut microbiota and involvement in multiple metabolic pathways may be one of the important mechanisms by which MMQ-8 exerts its therapeutic effects on NAFLD. It is worth noting that metabolic pathways such as glutathione metabolism, butyric acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and the gut microbiota ecosystem are closely intertwined in this process.
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Affiliation(s)
- Dandan Yang
- School of Traditional Mongolian Medicine, Inner Mongolia Medical University, Hohhot, China
- Key Laboratory of Quality Research and Pharmacodynamic Evaluation of Traditional Chinese Medicine and Mongolia Medicine, Inner Mongolia Medical University, Hohhot, China
| | - Wuyunsiqin
- School of Traditional Mongolian Medicine, Inner Mongolia Medical University, Hohhot, China
- Key Laboratory of Quality Research and Pharmacodynamic Evaluation of Traditional Chinese Medicine and Mongolia Medicine, Inner Mongolia Medical University, Hohhot, China
| | - YanNiu
- School of Basic Medicine, Inner Mongolia Medical University, Hohhot, China
| | - Hashentuya
- School of Traditional Mongolian Medicine, Inner Mongolia Medical University, Hohhot, China
| | - Tana
- School of Traditional Mongolian Medicine, Inner Mongolia Medical University, Hohhot, China
| | - Anna
- School of Traditional Mongolian Medicine, Inner Mongolia Medical University, Hohhot, China
| | - Mingxing Ma
- School of Traditional Mongolian Medicine, Inner Mongolia Medical University, Hohhot, China
| | - Wenhui Zhao
- School of Traditional Mongolian Medicine, Inner Mongolia Medical University, Hohhot, China
| | - Menggenduxi
- School of Traditional Mongolian Medicine, Inner Mongolia Medical University, Hohhot, China
| | - Minjie Wang
- Key Laboratory of Quality Research and Pharmacodynamic Evaluation of Traditional Chinese Medicine and Mongolia Medicine, Inner Mongolia Medical University, Hohhot, China
- School of Basic Medicine, Inner Mongolia Medical University, Hohhot, China
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He Q, Liu X, Ding G, Wang Y, Luo X, Cao W, Xing W. The relationship between serum uric acid level and non-alcoholic fatty liver disease in northern China: a retrospective cohort study. BMC Public Health 2025; 25:718. [PMID: 39984884 PMCID: PMC11843771 DOI: 10.1186/s12889-025-21943-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 02/13/2025] [Indexed: 02/23/2025] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease among adults. High uric acid (UA) increases the incidence of NAFLD in the general population. However, further exploration is warranted to determine the relationship between UA levels and NAFLD in various populations. We conducted a historical cohort study to investigate the causality between UA and NAFLD across different weight categories. METHODS A historical cohort was established from the Jidong community cohort. All participants were enrolled and followed up from July 1st, 2013 to August 1st, 2018. The study participants were retrospectively assigned to four groups according to their UA levels (Q1, 69-210 μmol/L; Q2, 211-255 μmol/L; Q3, 256-310 μmol/L; Q4, 311-593 μmol/L). The NAFLD incidence was investigated in each group. We used the UA level determined by an automatic analyzer. NAFLD was diagnosed with abdominal ultrasonography examination. Demographic information, lifestyle history, clinical anthropometric data, and blood samples of participants were collected. Univariate analysis and multivariable Cox regression were applied to analyze the relationship between UA and NAFLD by stratification of participants' body mass index (BMI) categories (underweight, normal weight, overweight, and obese). RESULTS Two thousand nine hundred eighty four participants were enrolled. 740 (24.8%) were assigned to UA Q1 group, 755 (25.3%) to UA Q2, 743 (24.9%) to UA Q3, and 746 (25.0%) to UA Q4. The global incidence of NAFLD was 26.0% (777/2984). The risk of NAFLD significantly increased with elevated UA levels in underweight and normal-weight participants (HR = 3.498, 95% CI: 2.413-5.072, P < 0.05). In multivariable analysis, UA showed a positive association with NAFLD, independent of other risk factors in underweight and normal-weight participants (UA Q2: 1.152 (0.761-1.743), UA Q3: 2.168 (1.489-3.157), UA Q4: 3.075 (2.103-4.196), P < 0.05). In the absence of other risk factors, high UA levels independently explained 17% of NAFLD risk in underweight and normal-weight participants. CONCLUSIONS High UA levels serve as an independent risk factor for NAFLD in underweight and normal-weight individuals, highlighting the necessity of early NAFLD screening through monitoring liver function and UA levels, and personalized treatment plans for NAFLD patients with higher UA levels, which may include uric acid-lowering therapy and lifestyle modifications. However, the relationship between UA levels and NAFLD in overweight and obese individuals remains inconclusive.
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Affiliation(s)
- Qian He
- School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Xinyue Liu
- Tai'an City Center for Disease Control and Prevention, Taian, China
| | - Guoyong Ding
- School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yiying Wang
- Department of Medical, Rizhao Mental Health Center, Rizhao, China
| | - Xiaoting Luo
- School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Wenyuan Cao
- School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Weijia Xing
- School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
- Shandong First Medical University & Shandong Academy of Medical Sciences, The Second Affiliated Hospital, Taian, 271000, China.
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Huang X, Wu M, Huang B, Zhang Y. Gastrointestinal adverse events associated with GLP-1 receptor agonists in metabolic dysfunction-associated steatotic liver disease (MASLD): a systematic review and meta-analysis. Front Med (Lausanne) 2025; 12:1509947. [PMID: 40051726 PMCID: PMC11882565 DOI: 10.3389/fmed.2025.1509947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 02/10/2025] [Indexed: 03/09/2025] Open
Abstract
Background Metabolic dysfunction-associated steatotic liver disease, a prevalent chronic liver condition, can cause severe complications like hepatitis, cirrhosis, and hepatocellular carcinoma. In recent years, glucagon-like peptide-1 receptor agonists (GLP - 1RA) have shown unique therapeutic advantages and may become a preferred treatment for it. This meta-analysis aims to systematically examine GLP-1RA associated adverse events, providing a basis for guiding patient clinical management. Methods We conducted a search for randomized controlled trials (RCTs) investigating the therapeutic effects of GLP-1RA in the treatment of metabolic dysfunction-associated steatotic liver disease across four databases: PubMed, Embase, Web of Science, and Cochrane Library. The search period extended from the inception of each database until December 2023. Information pertaining to various adverse events was collected as outcome measures. Statistical analysis of the results and assessment of bias risk were conducted utilizing Review Manager (version 5.4.1) software. Results An analysis of 10 studies encompassing 960 participants revealed a significantly higher overall incidence of adverse events in the GLP-1RA group compared to the control group (OR: 2.40 [1.10, 5.26], P = 0.03). Subgroup analysis based on treatment duration demonstrated a higher rate of adverse events in the GLP-1RA group during follow-ups of less than 30 weeks (P = 0.0005, OR: 3.58 [1.75, 7.32]), but no statistical difference was observed between the two groups in follow-ups exceeding 30 weeks. There was no statistically significant difference between the two groups in adverse events leading to discontinuation (P = 0.29, OR: 1.47 [0.72, 2.98]). However, a notable difference was observed in gastrointestinal adverse events (P < 0.00001, OR: 4.83 [3.36, 6.95]). Conclusion GLP-1RA exhibits an overall higher incidence of adverse events in the treatment of metabolic dysfunction-associated steatotic liver disease, particularly in the gastrointestinal domain. Short-term use of GLP-1RA may be associated with a greater occurrence of adverse events, underscoring the importance of educating patients on preventive measures and establishing tolerance. However, there was no statistically significant difference between the two groups in severe adverse events and adverse events leading to discontinuation, confirming the safety profile of GLP-1RA application.
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Affiliation(s)
- Xiaoyan Huang
- Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China
| | - Miaohui Wu
- School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Baoliang Huang
- Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China
| | - Yi Zhang
- Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China
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Zhang H, Liu J, Su D, Bai Z, Wu Y, Ma Y, Miao Q, Wang M, Yang X. Diagnostic of fatty liver using radiomics and deep learning models on non-contrast abdominal CT. PLoS One 2025; 20:e0310938. [PMID: 39946425 PMCID: PMC11825062 DOI: 10.1371/journal.pone.0310938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 12/17/2024] [Indexed: 02/16/2025] Open
Abstract
PURPOSE This study aims to explore the potential of non-contrast abdominal CT radiomics and deep learning models in accurately diagnosing fatty liver. MATERIALS AND METHODS The study retrospectively enrolled 840 individuals who underwent non-contrast abdominal CT and quantitative CT (QCT) examinations at the First Affiliated Hospital of Zhengzhou University from July 2022 to May 2023. Subsequently, these participants were divided into a training set (n = 539) and a testing set (n = 301) in a 9:5 ratio. The liver fat content measured by experienced radiologists using QCT technology served as the reference standard. The liver images from the non-contrast abdominal CT scans were then segmented as regions of interest (ROI) from which radiomics features were extracted. Two-dimensional (2D) and three-dimensional (3D) radiomics models, as well as 2D and 3D deep learning models, were developed, and machine learning models based on clinical data were constructed for the four-category diagnosis of fatty liver. The characteristic curves for each model were plotted, and area under the receiver operating characteristic curve (AUC) were calculated to assess their efficacy in the classification and diagnosis of fatty liver. RESULTS A total of 840 participants were included (mean age 49.1 years ± 11.5 years [SD]; 581 males), of whom 610 (73%) had fatty liver. Among the patients with fatty liver, there were 302 with mild fatty liver (CT fat fraction of 5%-14%), 155 with moderate fatty liver (CT fat fraction of 14%-28%), and 153 with severe fatty liver (CT fat fraction >28%). Among all models used for diagnosing fatty liver, the 2D radiomics model based on the random forest algorithm achieved the highest AUC (0.973), while the 2D radiomics model based on the Bagging decision tree algorithm showed the highest sensitivity (0.873), specificity (0.939), accuracy (0.864), precision (0.880), and F1 score (0.876). CONCLUSION A systematic comparison was conducted on the performance of 2D and 3D radiomics models, as well as deep learning models, in the diagnosis of four-category fatty liver. This comprehensive model comparison provides a broader perspective for determining the optimal model for liver fat diagnosis. It was found that the 2D radiomics models based on the random forest and Bagging decision tree algorithms show high consistency with the QCT-based classification diagnosis of fatty liver used by experienced radiologists.
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Affiliation(s)
- Haoran Zhang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Jinlong Liu
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Danyang Su
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Zhen Bai
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- Department of Medical Equipment, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Yan Wu
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- Department of Medical Equipment, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Yuanbo Ma
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Qiuju Miao
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- Department of Medical Equipment, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Mingyue Wang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Xiaopeng Yang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- Department of Medical Equipment, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
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Khalfallah M, Habib M, Kishk AM, Saeed B, Hemdan S, Eissa A, Aboomar AA, Hagag RY, Elnagar B. Atherosclerotic Cardiovascular Diseases in Middle Delta of Egypt: A Systematic Analysis of Risk Factors Associated with the Rising Burden of the Disease. Glob Heart 2025; 20:11. [PMID: 39925839 PMCID: PMC11804180 DOI: 10.5334/gh.1395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Accepted: 01/15/2025] [Indexed: 02/11/2025] Open
Abstract
Background The popularity of behavioural and metabolic risk factors associated with atherosclerotic cardiovascular diseases (ACVDs) has increased because of social progress, rapid economic development, population aging, and changes in social ideology. We aimed to perform a systematic analysis of risk factors associated with the rising rate of ACVDs in Egypt. Methods This study was carried out on 1,700 participants. The patients were classified into two groups: group 1 included patients with ACVDs, and group 2 (control group) included healthy individuals. All data recorded included patients' anthropometric measurements, and laboratory and clinical examinations were collected. Results The rising burden of ACVDs in Egypt was caused by a variety of risk factors, including diabetes mellitus, smoking, hypertension, dyslipidemia, obesity, and a lack of physical activity. The dominant risk factors recognized through multivariate regression analysis were the existence of metabolic syndrome (OR = 1.463; 95% CI, 1.056-2.026; P = 0.022), increased psychosocial stress among the patients (OR = 1.404; 95% CI, 1.008-1.953; P = 0.044), excessive consumption of high-fat, processed, and fast food (OR = 1.964; 95% CI, 1.489-2.590; P = 0.001), and decreased the income (OR = 1.865; 95% CI, 1.454-2.391; P = 0.001). Conclusions Patients who suffer from uncontrolled diabetes, dyslipidemia, and metabolic syndrome are the most liable to have ACVDs. Psychosocial stress and the excessive intake of processed, high-fat, and fast food are augmenting leading risk features, especially in low-income populations.
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Affiliation(s)
- Mohamed Khalfallah
- Cardiovascular medicine department, faculty of medicine, Tanta University, Egypt
| | - Marwa Habib
- Cardiovascular medicine department, faculty of medicine, Tanta University, Egypt
| | | | - Baraka Saeed
- Family medicine and Community health department, United Arab Emirates
| | - Shreen Hemdan
- Family medicine and Community health department, United Arab Emirates
| | - Ahmad Eissa
- Internal medicine department, faculty of medicine, Tanta University, Egypt
| | - Ahmed A. Aboomar
- Internal medicine department, faculty of medicine, Tanta University, Egypt
| | | | - Basma Elnagar
- Cardiovascular medicine department, faculty of medicine, Tanta University, Egypt
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Zeng Z, Zhao Z, Yuan Q, Yang S, Wang Z, Wang Z, Zeng S, Li A, Chen Q, Zhu G, Xiao X, Luo G, Luo H, Li J, Zu X, Xie H, Liu J. Hepatic Steatosis Aggravates Vascular Calcification via Extracellular Vesicle-Mediated Osteochondrogenic Switch of Vascular Smooth Muscle Cells. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2408660. [PMID: 39680681 PMCID: PMC11791995 DOI: 10.1002/advs.202408660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 10/17/2024] [Indexed: 12/18/2024]
Abstract
The global incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) has risen sharply. This condition is strongly associated with the risk of cardiovascular disease (CVD), but how MAFLD affects the development and progression of CVD, particularly concerning vascular calcification, remains unclear. Herein, extracellular vesicles (EVs) are identified from steatotic hepatocytes as a trigger that accelerated the progression of both vascular intimal and medial calcification. Steatotic hepatocytes are found to release more EVs, which are able to reach the vascular tissue, be taken up by vascular smooth muscle cells (VSMCs), and promote their osteogenic differentiation. Within these toxic vesicles, a protein cargo is identified called lectin galactoside-binding soluble 3 binding protein (Lgals3bp) that acted as a potent inducer of osteochondrogenic transformation in VSMCs. Both the inhibition of EV release and the liver-specific knockdown of Lgals3bp profoundly attenuated vascular calcification. This work partially explains the reason for the high incidence of vascular calcification in MAFLD and unveils a novel mechanism that may be used to prevent or treat cardiovascular complications in patients with MAFLD.
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Affiliation(s)
- Zhao‐Lin Zeng
- Department of Metabolism and EndocrinologyThe First Affiliated Hospital, Hengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
- Department of Cardiovascular MedicineThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016P. R. China
- Diabetes Clinical Medical Research Center of Hunan ProvincialHengyangHunan421001P. R. China
- Department of Clinical Laboratory MedicineThe First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
- Institute of Cardiovascular DiseaseKey Lab for Arteriosclerology of Hunan ProvinceHengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
| | - Zhi‐Bo Zhao
- Department of Metabolism and EndocrinologyThe First Affiliated Hospital, Hengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
- Diabetes Clinical Medical Research Center of Hunan ProvincialHengyangHunan421001P. R. China
- Department of Clinical Laboratory MedicineThe First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
| | - Qing Yuan
- Department of Metabolism and EndocrinologyThe First Affiliated Hospital, Hengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
- Diabetes Clinical Medical Research Center of Hunan ProvincialHengyangHunan421001P. R. China
- Department of Clinical Laboratory MedicineThe First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
| | - Shi‐Qi Yang
- Department of Metabolism and EndocrinologyThe First Affiliated Hospital, Hengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
- Diabetes Clinical Medical Research Center of Hunan ProvincialHengyangHunan421001P. R. China
- Department of Clinical Laboratory MedicineThe First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
| | - Zhen‐Xing Wang
- Department of OrthopedicsMovement System Injury and Repair Research CenterNational Clinical Research Center for Geriatric DisordersHunan Key Laboratory of AngmedicineXiangya HospitalCentral South UniversityChangshaHunan410008P. R. China
| | - Zuo Wang
- Institute of Cardiovascular DiseaseKey Lab for Arteriosclerology of Hunan ProvinceHengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
| | - Shi‐Yu Zeng
- Department of Metabolism and EndocrinologyThe First Affiliated Hospital, Hengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
- Diabetes Clinical Medical Research Center of Hunan ProvincialHengyangHunan421001P. R. China
- Department of Clinical Laboratory MedicineThe First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
| | - An‐Qi Li
- Department of Metabolism and EndocrinologyThe First Affiliated Hospital, Hengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
- Diabetes Clinical Medical Research Center of Hunan ProvincialHengyangHunan421001P. R. China
- Department of Clinical Laboratory MedicineThe First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
| | - Qian Chen
- Department of Metabolism and EndocrinologyThe First Affiliated Hospital, Hengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
- Diabetes Clinical Medical Research Center of Hunan ProvincialHengyangHunan421001P. R. China
- Department of Clinical Laboratory MedicineThe First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
| | - Guo‐Qiang Zhu
- Department of OrthopedicsMovement System Injury and Repair Research CenterNational Clinical Research Center for Geriatric DisordersHunan Key Laboratory of AngmedicineXiangya HospitalCentral South UniversityChangshaHunan410008P. R. China
| | - Xin‐Hua Xiao
- Department of Metabolism and EndocrinologyThe First Affiliated Hospital, Hengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
- Diabetes Clinical Medical Research Center of Hunan ProvincialHengyangHunan421001P. R. China
- Department of Clinical Laboratory MedicineThe First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
| | - Guang‐Hua Luo
- Department of RadiologyThe First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
| | - Hai‐Yan Luo
- Department of GastroenterologyThe First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
| | - Jiao‐Yang Li
- Department of Occupational and Environmental HealthSchool of Public HealthWuhan UniversityWuhan430071P. R. China
| | - Xu‐Yu Zu
- Department of Metabolism and EndocrinologyThe First Affiliated Hospital, Hengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
- Diabetes Clinical Medical Research Center of Hunan ProvincialHengyangHunan421001P. R. China
- Department of Clinical Laboratory MedicineThe First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
| | - Hui Xie
- Department of OrthopedicsMovement System Injury and Repair Research CenterNational Clinical Research Center for Geriatric DisordersHunan Key Laboratory of AngmedicineXiangya HospitalCentral South UniversityChangshaHunan410008P. R. China
| | - Jiang‐Hua Liu
- Department of Metabolism and EndocrinologyThe First Affiliated Hospital, Hengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
- Diabetes Clinical Medical Research Center of Hunan ProvincialHengyangHunan421001P. R. China
- Department of Clinical Laboratory MedicineThe First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan421001P. R. China
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Wang YN, Liu S. The role of ALDHs in lipid peroxidation-related diseases. Int J Biol Macromol 2025; 288:138760. [PMID: 39674477 DOI: 10.1016/j.ijbiomac.2024.138760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 11/26/2024] [Accepted: 12/11/2024] [Indexed: 12/16/2024]
Abstract
Lipid peroxidation presents the oxidative degradation of polyunsaturated fatty acids lincited by reactive species. Excessive accumulation of lipid peroxidation byproducts, including 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA), causes protein dysfunction and various illnesses. Aldehyde dehydrogenases (ALDHs) catalyze the metabolism of both endogenous and exogenous aldehydes. These enzymes participate in detoxification and intermediary metabolism. Contemporary research has affirmed the involvement of both enzymatic and non-enzymatic pathways of ALDHs in modulating the evolution of diseases associated with lipid peroxidation. This review provides an overview of the biological functions and clinical implications concerning the enzymatic and non-enzymatic pathways of ALDHs in diseases related to lipid peroxidation, such as, non-alcoholic fatty liver disease (NAFLD), atherosclerosis, and type 2 diabetes (T2DM). Furthermore, the activators or inhibitors of ALDHs represent a promising therapeutic strategy for lipid peroxidation-related diseases.
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Affiliation(s)
- Ya-Nan Wang
- Department of Implantology & Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong 250012, China; Suzhou Research Institute, Shandong University, Suzhou, Jiangsu 215123, China
| | - Shiyue Liu
- Department of Implantology & Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong 250012, China.
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Li Y, Ma X, Cui S, Jiang G, Jia J, Ge X, Cao L. Association Between Serum Uric Acid and Non-alcoholic Fatty Liver Disease in Non-obese Young Population: A Prospective Cohort Study. Dig Dis Sci 2025; 70:825-834. [PMID: 39719467 DOI: 10.1007/s10620-024-08808-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 12/16/2024] [Indexed: 12/26/2024]
Abstract
OBJECTIVE The prevalence of non-alcoholic fatty liver disease (NAFLD) is gradually increasing among non-obese people and shows a trend of younger age. The objective of this study was to investigate the potential association between serum uric acid (SUA) and NAFLD in a non-obese young population. PATIENTS AND METHODS The study recruited 10,938 participants without NAFLD (18 ≤ age < 45,18.5 ≤ BMI < 25) in 2006. After a median follow-up of 9.95 years, 4835 (44.20%) participants were diagnosed with NAFLD. According to the baseline SUA level, the research subjects were divided into 4 groups by the quartile method. The association between SUA and NAFLD was predicted using the Kaplan -Meier survival curve and Cox hazard regression model. RESULTS After adjusting for all the confounders, the HRs and 95%CI for NAFLD in the quartile 2, quartile 3 and quartile 4 were 1.095(1.004 ~ 1.193), 1.195(1.095 ~ 1.304) and 1.409(1.289 ~ 1.541). The restrictive cubic spline (RCS) functions confirmed the existence of a non-linear association between the initial SUA and NAFLD (non-linearity association P < 0.05). Kaplan-Meier Survival Curve shows that the risk of NAFLD increased with increasing levels of SUA. The cumulative incidences of the four groups were 46.19, 51.99, 56.52 and 65.87%, respectively (log-rank test P < 0.001). CONCLUSION It has been confirmed through a prospective cohort study that in non-obese young population, SUA can serve as an independent predictor of NAFLD. An increase in SUA within the physiological range, even if it doesn't reach the level of hyperuricemia, can impose a significant burden on the occurrence of NAFLD. TRIAL REGISTRATION Trial registration number: ChiCTR-TNC-11001489, registration site: http://www.chictr.org.cn/index.aspx .
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Affiliation(s)
- Yunpeng Li
- Graduate School of North, China University of Science and Technology, Tangshan, China
- Department of Hepatobiliary Surgery, Kailuan General Hospital, Tangshan, 063000, China
| | - Xiangming Ma
- Graduate School of North, China University of Science and Technology, Tangshan, China
- Department of Hepatobiliary Surgery, Kailuan General Hospital, Tangshan, 063000, China
| | - Shuqing Cui
- Graduate School of North, China University of Science and Technology, Tangshan, China
- Department of Hepatobiliary Surgery, Kailuan General Hospital, Tangshan, 063000, China
| | - Guochao Jiang
- Graduate School of North, China University of Science and Technology, Tangshan, China
- Department of Hepatobiliary Surgery, Kailuan General Hospital, Tangshan, 063000, China
| | - Jianguo Jia
- Department of Hepatobiliary Surgery, Kailuan General Hospital, Tangshan, 063000, China
| | - Xinyu Ge
- Graduate School of North, China University of Science and Technology, Tangshan, China
- Department of Hepatobiliary Surgery, Kailuan General Hospital, Tangshan, 063000, China
| | - Liying Cao
- Graduate School of North, China University of Science and Technology, Tangshan, China.
- Department of Hepatobiliary Surgery, Kailuan General Hospital, Tangshan, 063000, China.
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Xiao J, Wang F, Yuan Y, Gao J, Xiao L, Yan C, Guo F, Zhong J, Che Z, Li W, Lan T, Tacke F, Shah VH, Li C, Wang H, Dong E. Epidemiology of liver diseases: global disease burden and forecasted research trends. SCIENCE CHINA. LIFE SCIENCES 2025; 68:541-557. [PMID: 39425834 DOI: 10.1007/s11427-024-2722-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 09/02/2024] [Indexed: 10/21/2024]
Abstract
We assessed the global incidence, mortality, and disability-adjusted life years (DALYs) associated with various liver diseases, including alcohol-related liver disease (ALD), hepatitis B/C virus infections (HBV or HCV), liver cancer, metabolic dysfunction-associated steatotic liver disease (MASLD), and other chronic liver diseases, from the 2019 Global Burden of Disease study. Additionally, we analyzed the global trends in hepatology research and drug development. From 2000 to 2019, prevalence rates increased for ALD, MASLD and other liver diseases, while they decreased for HBV, HCV, and liver cancer. Countries with a high socio-demographic index (SDI) exhibited the lowest mortality rates and DALYs. The burden of liver diseases varied due to factors like sex and region. In nine representative countries, MASLD, along with hepatobiliary cancer, showed highest increase in funding in hepatology research. Globally, the major research categories in hepatology papers from 2000 to 2019 were cancer, pathobiology, and MASLD. The United States (U.S.) was at the forefront of hepatology research, with China gradually increasing its influence over time. Hepatologists worldwide are increasingly focusing on studying the communication between the liver and other organs, while underestimating the research on ALD. Cancer, HCV, and MASLD were the primary diseases targeted for therapeutic development in clinical trials. However, the proportion of new drugs approved for the treatment of liver diseases was relatively low among all newly approved drugs in the U.S., China, Japan, and the European Union. Notably, there were no approved drug for the treatment of ALD in the world.
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Affiliation(s)
- Jia Xiao
- Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266071, China.
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, 510630, China.
| | - Fei Wang
- Division of Gastroenterology, Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China
- School of Biological Sciences, Jinan University, Guangzhou, 519070, China
| | - Yuan Yuan
- Aier Institute of Ophthalmology, Central South University, Changsha, 410015, China
| | - Jinhang Gao
- Lab of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lu Xiao
- Clinical Medicine Research Institute and Department of Metabolic and Bariatric Surgery, the First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
| | - Chao Yan
- Clinical Medicine Research Institute and Department of Metabolic and Bariatric Surgery, the First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
| | - Feifei Guo
- Clinical Medicine Research Institute and Department of Metabolic and Bariatric Surgery, the First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
| | - Jiajun Zhong
- Clinical Medicine Research Institute and Department of Metabolic and Bariatric Surgery, the First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
| | - Zhaodi Che
- Clinical Medicine Research Institute and Department of Metabolic and Bariatric Surgery, the First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
| | - Wei Li
- Faculty of Pharmaceutical Sciences, Toho University, Chiba Tokyo, 143-8540, Japan
| | - Tian Lan
- Lab of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, 610041, China
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, 13353, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, 13353, Germany
| | - Vijay H Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55905, USA
| | - Cui Li
- Department of Health Sciences, National Natural Science Foundation of China, Beijing, 100085, China
| | - Hua Wang
- Department of Oncology, The First Affiliated Hospital, Institute for Liver Diseases of Anhui Medical University, Hefei, 230032, China.
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, 230032, China.
| | - Erdan Dong
- Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, 266071, China.
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, 100191, China.
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Zhao K, Zhang H, Ding W, Yu X, Hou Y, Liu X, Li X, Wang X. Adipokines regulate the development and progression of MASLD through organellar oxidative stress. Hepatol Commun 2025; 9:e0639. [PMID: 39878681 PMCID: PMC11781772 DOI: 10.1097/hc9.0000000000000639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 12/13/2024] [Indexed: 01/31/2025] Open
Abstract
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), which is increasingly being recognized as a leading cause of chronic liver pathology globally, is increasing. The pathophysiological underpinnings of its progression, which is currently under active investigation, involve oxidative stress. Human adipose tissue, an integral endocrine organ, secretes an array of adipokines that are modulated by dietary patterns and lifestyle choices. These adipokines intricately orchestrate regulatory pathways that impact glucose and lipid metabolism, oxidative stress, and mitochondrial function, thereby influencing the evolution of hepatic steatosis and progression to metabolic dysfunction-associated steatohepatitis (MASH). This review examines recent data, underscoring the critical interplay of oxidative stress, reactive oxygen species, and redox signaling in adipokine-mediated mechanisms. The role of various adipokines in regulating the onset and progression of MASLD/MASH through mitochondrial dysfunction and endoplasmic reticulum stress and the underlying mechanisms are discussed. Due to the emerging correlation between adipokines and the development of MASLD positions, these adipokines are potential targets for the development of innovative therapeutic interventions for MASLD management. A comprehensive understanding of the pathogenesis of MASLD/MASH is instrumental for identifying therapies for MASH.
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Affiliation(s)
- Ke Zhao
- Central laboratory, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Central laboratory, Shandong Institute of Endocrine & Metabolic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Central laboratory, Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Jinan, Shandong, China
| | - Heng Zhang
- Central laboratory, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Central laboratory, Shandong Institute of Endocrine & Metabolic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Central laboratory, Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Jinan, Shandong, China
- Central laboratory, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Wenyu Ding
- Central laboratory, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Central laboratory, Shandong Institute of Endocrine & Metabolic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Central laboratory, Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Jinan, Shandong, China
| | - Xiaoshuai Yu
- Central laboratory, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Central laboratory, Shandong Institute of Endocrine & Metabolic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Central laboratory, Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Jinan, Shandong, China
- Central laboratory, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yanli Hou
- Central laboratory, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Central laboratory, Shandong Institute of Endocrine & Metabolic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Central laboratory, Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Jinan, Shandong, China
| | - Xihong Liu
- Department of Pathology, The Fourth People’s Hospital of Jinan, Jinan, Shandong, China
| | - Xinhua Li
- Central laboratory, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Central laboratory, Shandong Institute of Endocrine & Metabolic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Central laboratory, Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Jinan, Shandong, China
| | - Xiaolei Wang
- Central laboratory, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Central laboratory, Shandong Institute of Endocrine & Metabolic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Central laboratory, Jinan Key Laboratory of Translational Medicine on Metabolic Diseases, Jinan, Shandong, China
- First school of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
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Younossi ZM, Kalligeros M, Henry L. Epidemiology of metabolic dysfunction-associated steatotic liver disease. Clin Mol Hepatol 2025; 31:S32-S50. [PMID: 39159948 PMCID: PMC11925440 DOI: 10.3350/cmh.2024.0431] [Citation(s) in RCA: 57] [Impact Index Per Article: 57.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 08/13/2024] [Accepted: 08/15/2024] [Indexed: 08/21/2024] Open
Abstract
As the rates of obesity and type 2 diabetes (T2D) continue to increase globally, so does the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). Currently, 38% of all adults and 7-14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to more than 55%. Although MASLD does not always develop into progressive liver disease, it has become the top indication for liver transplant in the United States for women and those with hepatocellular carcinoma (HCC). Nonetheless, the most common cause of mortality among patients with MASLD remains cardiovascular disease. In addition to liver outcomes (cirrhosis and HCC), MASLD is associated with an increased risk of developing de novo T2D, chronic kidney disease, sarcopenia, and extrahepatic cancers. Furthermore, MASLD is associated with decreased health-related quality of life, decreased work productivity, fatigue, increased healthcare resource utilization, and a substantial economic burden. Similar to other metabolic diseases, lifestyle interventions such as a heathy diet and increased physical activity remain the cornerstone of managing these patients. Although several obesity and T2D drugs are available to treat co-morbid disease, resmetirom is the only MASH-targeted medication for patients with stage 2-3 fibrosis that has approved by the Food and Drug Administration for use in the United States. This review discusses MASLD epidemiology and its related risk factors and outcomes and demonstrates that without further global initiatives, MASLD incidence could continue to increase.
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Affiliation(s)
- Zobair M. Younossi
- The Global NASH Council, Washington DC, USA
- Beatty Liver and Obesity Program, Inova Health System, Falls Church, VA, USA
- Center for Outcomes Research in Liver Disease, Washington DC, USA
| | - Markos Kalligeros
- Beth Israel Deaconess Medical Center, Harvard University, Cambridge, MA, USA
| | - Linda Henry
- The Global NASH Council, Washington DC, USA
- Beatty Liver and Obesity Program, Inova Health System, Falls Church, VA, USA
- Center for Outcomes Research in Liver Disease, Washington DC, USA
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Tian HY, Yu DJ, Xie T, Xu MX, Wang YH, Sun XL, Zhou XM, Han YX, Liao QQ, Zhao YJ, Liao J, El-Kassas M, Sun XD, Zhang YY. Cordycepin alleviates metabolic dysfunction-associated liver disease by restoring mitochondrial homeostasis and reducing oxidative stress via Parkin-mediated mitophagy. Biochem Pharmacol 2025; 232:116750. [PMID: 39793718 DOI: 10.1016/j.bcp.2025.116750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 12/01/2024] [Accepted: 01/07/2025] [Indexed: 01/13/2025]
Abstract
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) keeps rising with only a few drugs available. The present study aims to investigate the effects and mechanisms of cordycepin on MASLD. Male C57BL/6 mice were induced with a 90-day high-fat diet (HFD) and intraperitoneal administration with streptozotocin to establish MASLD murine model. Then they were randomly divided into the HFD and cordycepin groups (15, 30, 45 mg/kg). Cordycepin was orally given for 30 days. Serum total cholesterol (TC), triacylglyceride (TG), and aspartate aminotransferase (AST) levels were measured. L02 cells were induced by oleate acid (OA) or lipopolysaccharides (LPS), and treated with cordycepin or combined with inhibitors including chloroquine, 3-Methyladenine, and compound C. Atg7 and Parkin were knocked down in L02 cells using siRNA. Oil Red O and Nile Red staining for measuring lipid deposition. Mitochondria were visualized by transfection with mCherry-TOMM20-N10. Quantitative real-time PCR, Western blotting, and immunofluorescence staining were used to determine expressions of key molecules in inflammation, lipid metabolism, mitochondria homeostasis, and oxidative stress. Cordycepin significantly mitigated lipid deposition and ballooning in the livers of MASLD mice. Serum TC, TG, and AST levels were decreased by cordycepin. Cordycepin alleviated OA-induced lipid deposition and LPS-induced inflammation in L02 cells, attenuated oxidative stress, promoted autophagy, and maintained the autophagic flux by activating AMP-activated protein kinase (AMPK). Cordycepin reduced the accumulation of impaired mitochondria by enhancing Parkin-dependent mitophagy and promoting mitochondrial biogenesis. Cordycepin alleviates MASLD by restoring mitochondrial homeostasis and reducing oxidative stress via activating the Parkin-mediated mitophagy.
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Affiliation(s)
- Hai-Ying Tian
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Dao-Jiang Yu
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu 610051, China
| | - Teng Xie
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Meng-Xia Xu
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Yu-Hao Wang
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Xi-Lu Sun
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Xin-Meng Zhou
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Ying-Xuan Han
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Qing-Qing Liao
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Yu-Jie Zhao
- Medical College, Tibet University, Lhasa 850000, China
| | - Juan Liao
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt; Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Steatotic Liver Disease Study Foundation in Middle East and North Africa (SLMENA), Cairo, Egypt
| | - Xiao-Dong Sun
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; Medical College, Tibet University, Lhasa 850000, China.
| | - Yuan-Yuan Zhang
- West China School of Pharmacy, West China School of Basic Medical Sciences & Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China; The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu 610051, China.
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La X, Zhang Z, Liang J, Li H, Pang Y, He X, Kang Y, Wu C, Li Z. Isolation and purification of flavonoids from quinoa whole grain and its inhibitory effect on lipid accumulation in nonalcoholic fatty liver disease by inhibiting the expression of CD36 and FASN. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2025; 105:1330-1342. [PMID: 39305086 DOI: 10.1002/jsfa.13923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 09/03/2024] [Accepted: 09/10/2024] [Indexed: 12/12/2024]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD), a chronic metabolic disorder marked by excessive lipid deposition, represents a considerable health burden with no established efficacious treatment strategy. Quinoa (Chenopodium quinoa Willd.), valued for its health benefits, is replete with flavonoid bioactives. The aims of this work are to isolate and purify flavonoids from quinoa whole grain that can intervene in NAFLD and to elucidate some of the underlying mechanisms. RESULTS Chenopodium quinoa Willd. flavonoids (CQWF) were obtained successfully through an optimized ultrasonic extraction methodology, followed by isolation and purification utilizing macroporous resin D101. The study then explored the therapeutic potential of CQWF and its eluted fractions in models emulating NAFLD conditions: an in vitro fatty liver cell model induced by oleic acid (OA) and palmitic acid (PA) in the HepG2 and BEL-7402 cell lines, and an in vivo high-fat diet (HFD)-induced NAFLD model in C57BL/6N mice. The findings revealed a comprehensive mitigating effect of CQWF30 on NAFLD, manifesting in reduced intracellular lipid accumulation in steatotic hepatocytes and a concerted downregulation of key lipid metabolism genes, CD36 and FASN. Administration of CQWF30 reduced triglyceride (TG) levels in both the cellular model and the livers of HFD-fed mice. It also reduced serum concentrations of TG, total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), while increasing high-density lipoprotein cholesterol (HDL-C) in the mice. CONCLUSION These results highlighted the promising therapeutic capacity of CQWF, particularly CQWF30. This research advances the exploration and utilization of flavonoids derived from quinoa whole grain, providing innovative dietary intervention strategies for NAFLD. © 2024 Society of Chemical Industry.
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Affiliation(s)
- Xiaoqin La
- Institutes of Biomedical Sciences, Shanxi University, Taiyuan, China
- Shanxi Provincial Key Laboratory of Medical Molecular Cell Biology, Shanxi University, Taiyuan, China
| | - Zhaoyan Zhang
- Institutes of Biomedical Sciences, Shanxi University, Taiyuan, China
| | - Jingyi Liang
- Institute of Biotechnology, Shanxi University, Taiyuan, China
| | - Hanqing Li
- School of Life Science, Shanxi University, Taiyuan, China
| | - Yan Pang
- School of Life Science, Shanxi University, Taiyuan, China
| | - Xiaoting He
- School of Life Science, Shanxi University, Taiyuan, China
| | - Yurui Kang
- School of Life Science, Shanxi University, Taiyuan, China
| | - Changxin Wu
- Institutes of Biomedical Sciences, Shanxi University, Taiyuan, China
| | - Zhuoyu Li
- Shanxi Provincial Key Laboratory of Medical Molecular Cell Biology, Shanxi University, Taiyuan, China
- Institute of Biotechnology, Shanxi University, Taiyuan, China
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Sun Y, Hu D, Yu M, Liang SB, Zheng Y, Wang X, Tong G. Diagnostic Accuracy of Non-Invasive Diagnostic Tests for Nonalcoholic Fatty Liver Disease: A Systematic Review and Network Meta-Analysis. Clin Epidemiol 2025; 17:53-71. [PMID: 39897720 PMCID: PMC11786599 DOI: 10.2147/clep.s501445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 01/17/2025] [Indexed: 02/04/2025] Open
Abstract
PURPOSE In recent decades, numerous non-invasive tests (NITs) for diagnosing nonalcoholic fatty liver disease (NAFLD) have been developed, however, a comprehensive comparison of their relative diagnostic accuracies is lacking. We aimed to assess and compare the diagnostic accuracy of various NITs for NAFLD using network meta-analysis (NMA). MATERIALS AND METHODS We conducted a systematic search in seven databases up to April 2024 to identify studies evaluating the diagnostic values of NITs, with liver biopsy as the gold standard. The participants included patients with suspected or confirmed NAFLD, irrespective of age, sex, ethnicity. Statistical analysis was conducted using R 4.0.3 for Bayesian NMA and STATA 17.0 for pairwise meta-analysis. Sensitivity, specificity, diagnostic odds ratio (DOR), area under the receiver operating characteristic curve (AUC), and superiority index were calculated. Bayesian calculations were performed using the Rstan package, specifying parameters like MCMC chain count, iteration count, and operational cycles. The methodological quality of included studies was assessed using the QUADAS-2 tool. RESULTS Out of 15,877 studies, 180 were included in the quantitative synthesis, and 102 were used in head-to-head meta-analyses. For diagnosing steatosis stage 1, Hydrogen Magnetic Resonance Spectroscopy (H-MRS, DOR 15,745,657.6, 95% CI 17.2-1,014,063.59) proved to be the most accurate. For significant fibrosis, HRI leading (DOR 80.94, 95% CI 6.46-391.41), For advanced fibrosis, CK-18 showed the highest performance (DOR 102654.16, 95% CI 1.6-134,059.8). For high-risk NASH, Real-Time Elastography showing the highest performance (DOR 18.1, 95% CI 0.7-96.33). Meta-regression analyses suggested that variability in the diagnostic accuracy of NITs for NAFLD may result from differences in study design, thresholds, populations, and performance indicators. CONCLUSION We conducted a network meta-analysis to rank the accuracy of these tests. While some results are promising, not all NITs demonstrate substantial accuracy, highlighting the need for validation with larger datasets. Future research should concentrate on studying the thresholds of NITs and enhancing the clarity of methodological reporting.
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Affiliation(s)
- Yuxin Sun
- Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, People’s Republic of China
| | - Die Hu
- Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, People’s Republic of China
| | - Mingkun Yu
- Department of Oncology, Binzhou Hospital of Traditional Chinese Medicine, Binzhou, People’s Republic of China
| | - Shi-Bing Liang
- Clinical Study Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
- Centre for Evidence-Based Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
- Postdoctoral Research Station, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
| | - Youyou Zheng
- Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
| | - Xin Wang
- Department of Traditional Chinese Medicine, Sanbo Brian Hospital of Capital Medical University, Beijing, People’s Republic of China
| | - Guangdong Tong
- Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, People’s Republic of China
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People’s Republic of China
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Cheng Y, Su J, Wang X, Huang R, Zhao Z, Tian K, Gu T, Wang X, Chen L, Zhao X. Associations between brominated flame retardants exposure and non-alcoholic fatty liver disease: Mediation analysis in the NHANES. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 290:117762. [PMID: 39847885 DOI: 10.1016/j.ecoenv.2025.117762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 12/30/2024] [Accepted: 01/17/2025] [Indexed: 01/25/2025]
Abstract
BACKGROUND Exposure to brominated flame retardants (BFRs) may negatively impact human health. The association of BFRs with nonalcoholic fatty liver disease (NAFLD) in the general population is unclear. Meanwhile, limited studies have investigated the potential role of oxidative stress and inflammation in this link. METHODS We included 4110 adults from the 2009-2014 National Health and Nutrition Examination Survey (NHANES). NAFLD was diagnosed by serum alanine aminotransferase (ALT), hepatic steatosis index (HSI), and United States fatty liver index (USFLI). The link between a single BFR exposure and NAFLD was estimated using weighted logistic regression and restricted cubic splines (RCS). The quantile-based g-computation (QGC), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were applied to evaluate the overall correlation of BFRs mixtures with NAFLD and identify significant compounds. Furthermore, we investigated the potential mediation function of oxidative stress and inflammation. RESULTS Our study demonstrated that specific concentrations of BFRs are related to an increased risk of NAFLD, both individually and when combined. PBB153, PBDE28, PBDE209, and PBDE153 exhibited the highest importance for NAFLD and were potential risk factors worthy of concern. Additionally, mediation analysis showed that absolute neutrophil cell count (ANC) and lymphocyte count (LC) (inflammation markers) have significantly mediated influences on the correlations of PBB153, PBDE85, and PBDE28 with N AFLD risk. Albumin (ALB) (oxidative stress marker) has notably mediated influences on the correlations of PBDE99, PBDE154, and PBDE85 with NAFLD risk. Men had higher serum BFRs concentrations than women, and the association between BFRs and NAFLD was also more prominent in men, which may be related to physiological differences between the sexes. CONCLUSIONS Our findings offer evidence for single and mixed associations of BFRs and NAFLD in ordinary US adults. Furthermore, oxidative stress and chronic inflammation may mediate the effects of BFR exposure on NAFLD development.
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Affiliation(s)
- Yulan Cheng
- Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, China
| | - Jingyi Su
- Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, China
| | - Xiangdong Wang
- Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, China
| | - Ruiyao Huang
- Department of Clinical Medicine, Nantong University Xinglin College, Nantong 226000, China
| | - Zixuan Zhao
- Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, China; Nantong Center for Disease Control and Prevention, Nantong, Jiangsu 226007, China
| | - Kai Tian
- Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, China
| | - Tianxiang Gu
- Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, China
| | - Xiaoke Wang
- Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, China.
| | - Lin Chen
- Nantong Institute of Liver Diseases, Nantong Third People's Hospital Affiliated Nantong Hospital of Nantong University, Nantong, China.
| | - Xinyuan Zhao
- Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, China.
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Zhang X, Zheng Y, Yang J, Yang Y, He Q, Xu M, Long F, Yang Y. Abnormal ac4C modification in metabolic dysfunction associated steatotic liver cells. Sci Rep 2025; 15:1013. [PMID: 39762452 PMCID: PMC11704021 DOI: 10.1038/s41598-024-84564-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 12/24/2024] [Indexed: 01/11/2025] Open
Abstract
The pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear due to the complexity of its etiology. The emerging field of the epitranscriptome has shown significant promise in advancing the understanding of disease pathogenesis and developing new therapeutic approaches. Recent research has demonstrated that N4-acetylcytosine (ac4C), an RNA modification within the epitranscriptome, is implicated in progression of various diseases. However, the role of ac4C modification in MASLD remains unexplored. Herein, we performed acRIP-ac4c-seq and RNA-seq analysis in free fatty acids-induced MASLD model cells, identifying 2128 differentially acetylated ac4C sites, with 1031 hyperacetylated and 1097 hypoacetylated peaks in MASLD model cells. Functional enrichments analysis showed that ac4C differentially modified genes were significantly involved in processes related to MASLD, such as nuclear transport and MAP kinase (MAPK) signaling pathway. We also identified 341 differentially expressed genes (DEGs), including 61 lncRNAs and 280 mRNAs, between control and MASLD model cells. Bioinformatics analysis showed that DEGs were significantly enriched in long-chain fatty acid biosynthetic process. Notably, 118 genes exhibited significant changes in both ac4C modification and expression levels in MASLD model cells. Among these proteins, JUN, caveolin-1 (CAV1), fatty acid synthase (FASN), and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) were identified as core proteins through protein-protein interaction (PPI) network analysis using cytoscape software. Collectively, our findings establish a positive correlation between ac4C modification and the pathogenesis of MASLD and suggest that ac4C modification may serve as a therapeutic target for MASLD.
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Affiliation(s)
- Xiqian Zhang
- Department of Pharmacy, Affiliated Hospital of Southwest Jiao Tong University, The Third People's Hospital of Chengdu, Chengdu, 610014, China
| | - Yaxian Zheng
- Department of Pharmacy, Affiliated Hospital of Southwest Jiao Tong University, The Third People's Hospital of Chengdu, Chengdu, 610014, China
| | - Jing Yang
- Department of Pharmacy, Affiliated Hospital of Southwest Jiao Tong University, The Third People's Hospital of Chengdu, Chengdu, 610014, China
| | - Yan Yang
- Department of Pharmacy, Affiliated Hospital of Southwest Jiao Tong University, The Third People's Hospital of Chengdu, Chengdu, 610014, China
| | - Qin He
- Department of Pharmacy, Affiliated Hospital of Southwest Jiao Tong University, The Third People's Hospital of Chengdu, Chengdu, 610014, China
| | - Min Xu
- Department of Pharmacy, Affiliated Hospital of Southwest Jiao Tong University, The Third People's Hospital of Chengdu, Chengdu, 610014, China
| | - Fangyi Long
- Laboratory Medicine Center, Sichuan Provincial Women's and Children's Hospital, Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu, 610041, China.
| | - Yujie Yang
- Department of Pharmacy, Affiliated Hospital of Southwest Jiao Tong University, The Third People's Hospital of Chengdu, Chengdu, 610014, China.
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Liu D, Yin M, Chen J, Fu C, Schneider M, Nickel D, Yao X. Fatty acid composition evaluation of abdominal adipose tissue using chemical shiftencoded MRI: Association with diabetes. NMR IN BIOMEDICINE 2025; 38:e5290. [PMID: 39511916 DOI: 10.1002/nbm.5290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 09/26/2024] [Accepted: 10/21/2024] [Indexed: 11/15/2024]
Abstract
This study investigated the association between the fatty acid composition of abdominal adipose tissue in NAFLD patients using chemical shift-encoded MRI and the development of insulin resistance and T2DM. We enrolled 231 subjects with NAFLD who underwent both abdominal magnetic resonance spectroscopy and chemical shift-encoded MRI: comprising of 49 T2DM patients and 182 subjects without. MRI- and MRS-based liver fat fraction was measured from a circular region of interest on the right lobe of the liver. The abdominal fatty acid compositions were measured at the umbilical level with chemical shift-encoded MRI. Bland-Altman analysis, Student's t test, Mann-Whitney U test, and Spearman correlation analysis were performed. The logistic regression was applied to identify the independent factors for T2DM. Then, the predictive performance was assessed by Receiver operating characteristic curve analyses. An excellent agreement was found between liver fat fraction measured by MRS and MRI. (slope = 0.8; bias =-0.92%). In, patients with T2DM revealed lower fractions of mono-unsaturated fatty acid (Fmufa) (33.68 ± 10.62 vs 38.62 ± 12.21, P =.0089) and higher fractions of saturated fatty acid (Fsfa) (34.11 ± 9.746 vs 31.25 ± 8.66, P =.0351) of visceral fat tissue compared with patients without. BMI, HDL-c, Fmufa and Fsfa of visceral fat were independent factors for T2DM. Furthermore, Fsfa-S% was positively correlated with liver enzyme levels (P =.003 and 0.04). However, Fmufa-V% was negatively correlated with fasting blood glucose, HbA1c and HOMA-IR (P =.004, P =.001 and P =.03 respectively). Hence, the evaluation of fatty acid compositions of abdominal fat tissue using chemical shift-encoded MRI may have a predictive value for T2DM in patients with NAFLD.
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Affiliation(s)
- Dingxia Liu
- Shanghai Institute of Medical Imaging, Dept. of Radiology, Zhongshan Hospital of Fudan University, Fudan University, Shanghai, China
| | - Minyan Yin
- Shanghai Institute of Medical Imaging, Dept. of Radiology, Zhongshan Hospital of Fudan University, Fudan University, Shanghai, China
| | - Jiejun Chen
- Shanghai Institute of Medical Imaging, Dept. of Radiology, Zhongshan Hospital of Fudan University, Fudan University, Shanghai, China
| | - Caixia Fu
- Application Development, Siemens Shenzhen Magnetic Resonance Ltd, Shenzhen, China
| | - Manuel Schneider
- MR Application Predevelopment, Siemens Healthcare GmbH, Erlangen, Germany
| | - Dominik Nickel
- MR Application Predevelopment, Siemens Healthcare GmbH, Erlangen, Germany
| | - Xiuzhong Yao
- Shanghai Institute of Medical Imaging, Dept. of Radiology, Zhongshan Hospital of Fudan University, Fudan University, Shanghai, China
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