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Chang CH, Liou HH, Wu CK. Moderate-severe aortic arch calcification and high serum alkaline phosphatase co-modify the risk of cardiovascular events and mortality among chronic hemodialysis patients. Ren Fail 2025; 47:2449572. [PMID: 39801127 PMCID: PMC11731357 DOI: 10.1080/0886022x.2024.2449572] [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: 07/03/2024] [Revised: 12/02/2024] [Accepted: 12/30/2024] [Indexed: 01/16/2025] Open
Abstract
BACKGROUND Patients with end-stage kidney disease undergoing chronic hemodialysis (HD) have an unparalleled risk of vascular calcification (VC) and high alkaline phosphatase (Alk-P) levels. However, whether VC contributed to the cardiovascular risk modified by serum Alk-P levels was not addressed in the population. METHODS A retrospective cohort study was conducted on chronic HD patients, between October 1 and December 31, 2018, with aortic arch calcification (AoAC) scores and serum Alk-P levels. Patients were categorized into four groups: non-to-mild AoAC/low Alk-P, non-to-mild AoAC/high Alk-P, moderate-to-severe AoAC/low Alk-P, and moderate-to-severe AoAC/high Alk-P. The Cox proportional hazard model and Kaplan-Meier analysis were used to evaluate the risks of major adverse cardiovascular effects (MACEs) and cardiovascular and all-cause mortality after multivariate adjustment. RESULTS Among 376 chronic HD patients recruited, 125 (33%) had non-to-mild AoAC/low Alk-P, 76 (20%) had non-to-mild AoAC/high Alk-P, 89 (24%) had moderate-to-severe AoAC/low Alk-P, and 86 (23%) had moderate-to-severe AoAC/high Alk-P. After 3 years of follow-up, patients with coexisting moderate-to-severe AoAC and high Alk-P had a higher risk of MACEs (aHR 1.76; 95% CI 1.06-2.92), and cardiovascular (aHR 2.49; 95% CI 1.21-5.11) and all-cause mortality (aHR 2.67; 95% CI 1.39-5.13) compared to those with non-to-mild AoAC/low Alk-P even after adjustments for significant clinical variables. CONCLUSIONS In chronic HD patients, moderate to severe AoAC co-existed with high Alk-P levels and enhanced the risk of MACEs and cardiovascular and all-cause mortality. Interventions to attenuate these risk factors simultaneously should be emphasized in this population.
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Affiliation(s)
- Cheng-Hao Chang
- Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Hung-Hsiang Liou
- Division of Nephrology, Department of Medicine, Hsin-Jen Hospital, New Taipei County, Taiwan
| | - Chung-Kuan Wu
- Division of Nephrology, Department of Internal Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan
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Zhang R, Liu Z, Liu Y, Peng L. Development and validation of a prediction model of hospital mortality for patients with cardiac arrest survived 24 hours after cardiopulmonary resuscitation. Front Cardiovasc Med 2025; 12:1510710. [PMID: 39931542 PMCID: PMC11808029 DOI: 10.3389/fcvm.2025.1510710] [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: 10/18/2024] [Accepted: 01/14/2025] [Indexed: 02/13/2025] Open
Abstract
Objective Research on predictive models for hospital mortality in patients who have survived 24 h following cardiopulmonary resuscitation (CPR) is limited. We aim to explore the factors associated with hospital mortality in these patients and develop a predictive model to aid clinical decision-making and enhance the survival rates of patients post-resuscitation. Methods We sourced the data from a retrospective study within the Dryad dataset, dividing patients who suffered cardiac arrest following CPR into a training set and a validation set at a 7:3 ratio. We identified variables linked to hospital mortality in the training set using Least Absolute Shrinkage and Selection Operator (LASSO) regression, as well as univariate and multivariate logistic analyses. Utilizing these variables, we developed a prognostic nomogram for predicting mortality post-CPR. Calibration curves, the area under receiver operating curves (ROC), decision curve analysis (DCA), and clinical impact curve were used to assess the discriminability, accuracy, and clinical utility of the nomogram. Results The study population comprised 374 patients, with 262 allocated to the training group and 112 to the validation group. Of these, 213 patients were dead in the hospital. Multivariate logistic analysis revealed age (OR 1.05, 95% CI: 1.03-1.08), witnessed arrest (OR 0.28, 95% CI: 0.11-0.73), time to return of spontaneous circulation (ROSC) (OR 1.05, 95% CI: 1.02-1.08), non-shockable rhythm (OR 3.41, 95% CI: 1.61-7.18), alkaline phosphatase (OR 1.01, 95% CI: 1-1.01), and sequential organ failure assessment (SOFA) (OR 1.27, 95% CI: 1.15-1.4) were independent risk factors for hospital mortality for patients who survived 24 h after CPR. ROC of the nomogram showed the AUC in the training and validation group was 0.827 and 0.817, respectively. Calibration curves, DCA, and clinical impact curve demonstrated the nomogram with good accuracy and clinical utility. Conclusion Our prediction model had accurate predictive value for hospital mortality in patients who survived 24 h after CPR, which will be beneficial for assisting in identifying high-risk patients and intervention. Further confirmation of the model's accuracy required external validation data.
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Affiliation(s)
- Renwei Zhang
- Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Zhenxing Liu
- Department of Neurology, Yiling Hospital of Yichang, Yichang, China
| | - Yumin Liu
- Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Li Peng
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China
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Zhen WC, Sun J, Bai XT, Zhang Q, Li ZH, Zhang YX, Xu RX, Wu W, Yao ZH, Pu CW, Li XF. Trends of alkaline phosphatase to prealbumin ratio in patients with hepatitis B linked to hepatocellular carcinoma development. World J Gastroenterol 2025; 31:99349. [PMID: 39811503 PMCID: PMC11684201 DOI: 10.3748/wjg.v31.i2.99349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Revised: 10/25/2024] [Accepted: 11/18/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND Chronic hepatitis B often progresses silently toward hepatocellular carcinoma (HCC), a leading cause of mortality worldwide. Early detection of HCC is crucial, yet challenging. AIM To investigate the role of dynamic changes in alkaline phosphatase to prealbumin ratio (APR) in hepatitis B progression to HCC. METHODS Data from 4843 patients with hepatitis B (January 2015 to January 2024) were analyzed. HCC incidence rates in males and females were compared using the log-rank test. Data were evaluated using Kaplan-Meier analysis. The Linear Mixed-Effects Model was applied to track the fluctuation of APR levels over time. Furthermore, Joint Modeling of Longitudinal and Survival data was employed to investigate the temporal relationship between APR and HCC risk. RESULTS The incidence of HCC was higher in males. To ensure the model's normality assumption, this study applied a logarithmic transformation to APR, yielding ratio. Ratio levels were higher in females (t = 5.26, P < 0.01). A 1-unit increase in ratio correlated with a 2.005-fold higher risk of HCC in males (95%CI: 1.653-2.431) and a 2.273-fold higher risk in females (95%CI: 1.620-3.190). CONCLUSION Males are more prone to HCC, while females have higher APR levels. Despite no baseline APR link, rising APR indicates a higher HCC risk.
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Affiliation(s)
- Wen-Chong Zhen
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Jing Sun
- Graduate School, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Xue-Ting Bai
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Qian Zhang
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Zi-Han Li
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Yi-Xin Zhang
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Rong-Xuan Xu
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Wei Wu
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Zhi-Han Yao
- School of Public Health, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Chun-Wen Pu
- Dalian Public Health Clinical Center, Dalian Municipal Research Institute for Public Health, Dalian 116001, Liaoning Province, China
| | - Xiao-Feng Li
- Department of Epidemiology and Health Statistics, Dalian Medical University, Dalian 116044, Liaoning Province, China
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4
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Wang J, Xie Z, Xie H, Mo Z, Wang W, Zhu Y. A novel, portable, and cost-effective turbidimetric sensor for sensitive alkaline phosphatase activity assay. Biosens Bioelectron 2025; 267:116857. [PMID: 39426277 DOI: 10.1016/j.bios.2024.116857] [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: 08/09/2024] [Revised: 10/07/2024] [Accepted: 10/14/2024] [Indexed: 10/21/2024]
Abstract
The development of enzyme activity analysis methods is critical for precise and rapid assessments of enzyme activity levels within biological systems, facilitating a more profound comprehension of physiological functions and disease mechanisms. Alkaline phosphatase (ALP) participates in various physiological processes involving phosphate ester hydrolysis. Altered ALP activity levels are often indicative of different diseases, underscoring the necessity for accurate ALP activity determination in medical diagnostics. This study innovatively applies turbidity as a physical variable, proposing a turbidimetric sensor based on an enhanced ammonium molybdate reagent for phosphate analysis. By integrating this with the ALP substrate p-nitrophenyl phosphate, a turbidimetric sensor was devised and employed for ALP activity analysis. The proposed turbidimetric sensor demonstrated high sensitivity both for phosphate (0.18 μmol/L) and ALP activity (0.03 mU/mL) assay. In practical applications, this turbidimetric sensor has been effectively employed to detect ALP activity in mouse feces, showcasing its potential for auxiliary diagnosis of inflammatory bowel disease. Significantly, this novel turbidity-based approach offers not only swift and straightforward procedures but also remarkable portability and cost-efficiency. Requiring solely a handheld turbidimeter and eliminating the need for bulky instruments, this approach holds significant potential for point-of-care testing applications.
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Affiliation(s)
- Jikai Wang
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy & Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China.
| | - Zhulan Xie
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy & Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China
| | - Haitao Xie
- Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China
| | - Ziyi Mo
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy & Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China
| | - Weiguo Wang
- Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy & Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China.
| | - Yanli Zhu
- School of Chemistry and Chemical Engineering, University of South China, Hengyang, Hunan, 421001, PR China.
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Luo W, Sun L. O-Linked N-Acetylglucosamine Transferase Regulates Bone Homeostasis Through Alkaline Phosphatase Pathway in Diabetic Periodontitis. Mol Biotechnol 2024; 66:3475-3484. [PMID: 37951846 DOI: 10.1007/s12033-023-00947-0] [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: 07/26/2023] [Accepted: 10/10/2023] [Indexed: 11/14/2023]
Abstract
Periodontitis is one of the most common complications of diabetes, which seriously affects patients' life quality. It is important to find the key factors and mechanisms to improve the treatment of periodontitis. In our study, high glucose (HG) and lipopolysaccharide (LPS) treated human periodontal ligament cells (hPDLCs) and LPS treated diabetic mice was used to establish the diabetic periodontitis model in vitro and in vivo. O-linked beta-N-acetylglucosamine glycosylation (O-GlcNAcylation) and O-linked N-acetylglucosamine transferase (OGT) protein levels were detected by western blot assay. Cell counting kit-8, alkaline phosphatase (ALP), and alizarin red staining (ARS) assays were used to observe the O-GlcNAcylation and OGT effects on cell viability and osteoblast differentiation. Co-immunoprecipitation (Co-IP) assay was used to detect the relationship between OGT and ALP. The results showed that the levels of OGT and O-GlcNAcylation were significantly increased in both cell and mouse models. ALP and ARS staining results showed that silencing of OGT or inhibition of O-glycosylation notably improved osteogenic differentiation, increased the osteoprotegerin (OPG) protein levels and decreased the receptor activator for nuclear factor-κB Ligand (RANKL) protein levels of the HG and LPS treated hPDLCs. In diabetic periodontitis mice, knockdown of OGT relieved the injury of gingival tissue, increased the ALP and OPG levels and decreased the RANKL levels. Besides, ALP interacted with OGT protein, and OGT protein was found to act on ALP serine 513 glycosylation. In conclusion, our study demonstrated that excessive O-GlcNAcylation could restrain osteoblast differentiation by O-glycosylation in ALP.
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Affiliation(s)
- Wei Luo
- Beijing Hanhe Daguanying Dental Clinic, No. 182 Guang'an Menwai Street, Xicheng District, 100055, Beijing, China.
| | - Lu Sun
- Department of Stomatology, The First Medical Center of Chinese PLA General Hospital, 100853, Beijing, China
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Kuang C, Shang J, Ma M, Huang S, Yan B, Zhong Y, Guan B, Gong J, Liu F, Chen L. Risk factors and clinical prediction models for osteoporosis in pre-dialysis chronic kidney disease patients. Ren Fail 2024; 46:2361802. [PMID: 38874080 PMCID: PMC11182074 DOI: 10.1080/0886022x.2024.2361802] [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: 10/06/2023] [Accepted: 05/24/2024] [Indexed: 06/15/2024] Open
Abstract
BACKGROUND Osteoporosis in pre-dialysis chronic kidney disease (CKD) patients has been overlooked, and the risk factors of osteoporosis in these patients have not been adequately studied. OBJECTIVE To identify risk factors for osteoporosis in pre-dialysis CKD patients and develop predictive models to estimate the likelihood of osteoporosis. METHODS Dual-energy X-ray absorptiometry was used to measure bone mineral density, and clinical examination results were collected from 326 pre-dialysis CKD patients. Binary logistic regression was employed to explore the risk factors associated with osteoporosis and develop predictive models. RESULTS In this cohort, 53.4% (n = 174) were male, 46.6% (n = 152) were female, and 21.8% (n = 71) were diagnosed with osteoporosis. Among those diagnosed with osteoporosis, 67.6% (n = 48) were female and 32.4% (n = 23) were male. Older age and low 25-(OH)-Vitamin D levels were identified as risk factors for osteoporosis in males. For females, older age, being underweight, higher bone alkaline phosphatase (NBAP), and advanced CKD (G5) were significant risk factors, while higher iPTH was protective. Older age, being underweight, and higher NBAP were risk factors for osteoporosis in the G1-4 subgroup. In the G5 subgroup, older age and higher NBAP increased the risk, while high 25-(OH)-Vitamin D or iPTH had protective effects. Nomogram models were developed to assess osteoporosis risk in pre-dialysis patients based on gender and renal function stage. CONCLUSION Risk factors for osteoporosis vary by gender and renal function stages. The nomogram clinical prediction models we constructed may aid in the rapid screening of patients at high risk of osteoporosis.
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Affiliation(s)
- Chaoying Kuang
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Jingjie Shang
- Nuclear Medicine, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Mingming Ma
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Shengling Huang
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Bing Yan
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Yuzhen Zhong
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Baozhang Guan
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Jian Gong
- Nuclear Medicine, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Fanna Liu
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
| | - Liangmei Chen
- Nephrology Department, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China
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Zhang S, Yang Y, Yang D, Yang Y. MOF-mediated cascade reaction system for ultrasensitive detection of alkaline phosphatase activity and organophosphorus pesticides. Mikrochim Acta 2024; 191:673. [PMID: 39404896 DOI: 10.1007/s00604-024-06757-8] [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: 07/15/2024] [Accepted: 10/07/2024] [Indexed: 10/25/2024]
Abstract
A metal-organic-framework (MOF) fluorescent sensor is reported based on NH2-MIL-101(Fe) propelled pesticide and alkaline phosphatase (ALP) catalytic reaction. Different from previous reports, a cascade reaction system combined with MOF structural changes to generate fluorescence was employed. The rationale is that ALP can hydrolyze L-ascorbic acid 2-phosphate (AAP) into L-ascorbic acid (AA), which can reduce Fe3+ to decompose structurally NH2-MIL-101(Fe), resulting in 2-aminoterephthalic acid (NH2-BDC) with intense fluorescence. The fluorescence can be decreased to different degrees due to inhibition of organophosphate pesticides (OPPs) on the activity of ALP. By taking chlorpyrifos (CPY) as the model compound of an OPP pesticide and adding ALP and CPY into the NH2-MIL-101(Fe) framework, the resulting cascade reaction fluorescence sensors exhibit a good sensitivity for CPY and ALP sensing. The working ranges are 0.02-2 μg/L and 0.2-20 mU/mL with detection limits (LOD) of 5.31 ng/L and 0.05 mU/mL, respectively. The proposed sensor has been actually applied to satisfactory detection of CPY and ALP in food and serum samples. This fluorescence-based assay may extend the application of MOF-based biosensors.
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Affiliation(s)
- Shengyuan Zhang
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China
| | - Ying Yang
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China
| | - Dezhi Yang
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
| | - Yaling Yang
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
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Hussain S, Iqbal A, Hamid S, Putra PP, Ashraf M. Identifying alkaline phosphatase inhibitory potential of cyclooxygenase-2 inhibitors: Insights from molecular docking, MD simulations, molecular expression analysis in MCF-7 breast cancer cell line and in vitro investigations. Int J Biol Macromol 2024; 277:132721. [PMID: 38815949 DOI: 10.1016/j.ijbiomac.2024.132721] [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: 02/22/2024] [Revised: 05/10/2024] [Accepted: 05/27/2024] [Indexed: 06/01/2024]
Abstract
Alkaline phosphatases (APs, EC 3.1.3.1) belong to a superfamily of biological macromolecules that dephosphorylate many phosphometabolites and phosphoproteins and their overexpression is intricated in the spread of cancer to liver and bones, neuronal disorders including Alzheimer's disease (AD), inflammation and others. It was hypothesized that cyclooxygenase-2 (COX-2) selective inhibitors may possess anti-APs potential and may be involved in anticancer proceedings. Three COX-2 inhibitors including nimesulide, piroxicam and lornoxicam were evaluated for the inhibition of APs using in silico and in vitro methods. Molecular docking studies against tissue nonspecific alkaline phosphatase (TNAP) offered the best binding affinities for nimesulide (-11.14 kcal/mol) supported with conventional hydrogen bonding and hydrophobic interactions. MD simulations against TNAP for 200 ns and principal component analysis (PCA) reiterated the stability of ligand-receptor complexes. Molecular expression analysis of TNAP enzyme in the breast cancer cell line MCF-7 exhibited 0.24-fold downregulation with 5 μM nimesulide as compared with 0.26-fold standard 10 μM levamisole. In vitro assays against human placental AP (hPAP) displayed potent inhibitions of these drugs with IC50 values of 0.52 ± 0.02 μM to 3.46 ± 0.13 μM and similar results were obtained for bovine intestinal AP (bIAP). The data when generalized collectively emphasizes that the inhibition of APs by COX-2 inhibitors provides another target to work on the development of anticancer drugs.
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Affiliation(s)
- Safdar Hussain
- Institute of Chemistry, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan
| | - Ambar Iqbal
- Institute of Chemistry, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan; Department of Biochemistry, Institute of Biochemistry, Biotechnology, Bioinformatics (IBBB), The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan.
| | - Sujhla Hamid
- Institute of Chemistry, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan
| | - Purnawan Pontana Putra
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Andalas, Padang 256163, Indonesia.
| | - Muhammad Ashraf
- Institute of Chemistry, The Islamia University of Bahawalpur, 63100 Bahawalpur, Pakistan.
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Sheng A, Zhang H, Li Q, Chen S, Wang Q. Application of Intelligent Response Fluorescent Probe in Breast Cancer. Molecules 2024; 29:4294. [PMID: 39339288 PMCID: PMC11434508 DOI: 10.3390/molecules29184294] [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: 08/19/2024] [Revised: 09/08/2024] [Accepted: 09/09/2024] [Indexed: 09/30/2024] Open
Abstract
As one of the leading cancers threatening women's lives and health, breast cancer is challenging to treat and often irreversible in advanced cases, highlighting the critical importance of early detection and intervention. In recent years, fluorescent probe technology, a revolutionary in vivo imaging tool, has gained attention in medical research for its ability to improve tumor visualization significantly. This review focuses on recent advances in intelligent, responsive fluorescent probes, particularly in the field of breast cancer, which are divided into five categories, near-infrared responsive, fluorescein-labeled, pH-responsive, redox-dependent, and enzyme-triggered fluorescent probes, each of which has a different value for application based on its unique biological response mechanism. In addition, this review also covers the strategy of combining fluorescent probes with various anti-tumor drugs, aiming to reveal the possibility of synergistic effects between the two in breast cancer treatment and provide a solid theoretical platform for the clinical translation of fluorescent probe technology, which is expected to promote the expansion of cancer treatment technology.
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Affiliation(s)
- Anqi Sheng
- College of Life Science and Technology, Changchun University of Science and Technology, Changchun 130013, China; (A.S.); (H.Z.)
- Technology Innovation Institute of Jilin Province, Changchun 130012, China; (Q.L.); (S.C.)
| | - Hao Zhang
- College of Life Science and Technology, Changchun University of Science and Technology, Changchun 130013, China; (A.S.); (H.Z.)
| | - Qing Li
- Technology Innovation Institute of Jilin Province, Changchun 130012, China; (Q.L.); (S.C.)
| | - Shu Chen
- Technology Innovation Institute of Jilin Province, Changchun 130012, China; (Q.L.); (S.C.)
| | - Qingshuang Wang
- College of Life Science and Technology, Changchun University of Science and Technology, Changchun 130013, China; (A.S.); (H.Z.)
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Xie Y, Lin L, Sun C, Chen L, Lv W. Association between serum alkaline phosphatase and clinical prognosis in patients with acute liver failure following cardiac arrest: a retrospective cohort study. Eur J Med Res 2024; 29:453. [PMID: 39252119 PMCID: PMC11382480 DOI: 10.1186/s40001-024-02049-2] [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: 06/13/2024] [Accepted: 09/02/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Acute liver failure (ALF) following cardiac arrest (CA) poses a significant healthcare challenge, characterized by high morbidity and mortality rates. This study aims to assess the correlation between serum alkaline phosphatase (ALP) levels and poor outcomes in patients with ALF following CA. METHODS A retrospective analysis was conducted utilizing data from the Dryad digital repository. The primary outcomes examined were intensive care unit (ICU) mortality, hospital mortality, and unfavorable neurological outcome. Multivariable logistic regression analysis was employed to assess the relationship between serum ALP levels and clinical prognosis. The predictive value was evaluated using receiver operator characteristic (ROC) curve analysis. Two prediction models were developed, and model comparison was performed using the likelihood ratio test (LRT) and the Akaike Information Criterion (AIC). RESULTS A total of 194 patients were included in the analysis (72.2% male). Multivariate logistic regression analysis revealed that a one-standard deviation increase of ln-transformed ALP were independently associated with poorer prognosis: ICU mortality (odds ratios (OR) = 2.49, 95% confidence interval (CI) 1.31-4.74, P = 0.005), hospital mortality (OR = 2.21, 95% CI 1.18-4.16, P = 0.014), and unfavorable neurological outcome (OR = 2.40, 95% CI 1.25-4.60, P = 0.009). The area under the ROC curve for clinical prognosis was 0.644, 0.642, and 0.639, respectively. Additionally, LRT analyses indicated that the ALP-combined model exhibited better predictive efficacy than the model without ALP. CONCLUSIONS Elevated serum ALP levels upon admission were significantly associated with poorer prognosis of ALF following CA, suggesting its potential as a valuable marker for predicting prognosis in this patient population.
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Affiliation(s)
- Yuequn Xie
- Department of Emergency, The Third Affiliated to Shanghai University, Wenzhou People's Hospital, No. 299 Guan Road, Louqiao Street, Ouhai District, Wenzhou, 325000, Zhejiang, China
| | - Liangen Lin
- Department of Emergency, The Third Affiliated to Shanghai University, Wenzhou People's Hospital, No. 299 Guan Road, Louqiao Street, Ouhai District, Wenzhou, 325000, Zhejiang, China
| | - Congcong Sun
- Department of Scientific Research Center, The Third Affiliated to Shanghai University, Wenzhou People's Hospital, Wenzhou, 325000, Zhejiang, China
| | - Linglong Chen
- Department of Emergency, The Third Affiliated to Shanghai University, Wenzhou People's Hospital, No. 299 Guan Road, Louqiao Street, Ouhai District, Wenzhou, 325000, Zhejiang, China
| | - Wang Lv
- Department of Emergency, The Third Affiliated to Shanghai University, Wenzhou People's Hospital, No. 299 Guan Road, Louqiao Street, Ouhai District, Wenzhou, 325000, Zhejiang, China.
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Panichi V, Rosati A, Mangione EA, Incognito F, Mattei S, Cupisti A. Serum alkaline phosphatase is a strong predictor of mortality in ESKD patients: analysis of the RISCAVID cohort. J Nephrol 2024; 37:1843-1851. [PMID: 38913269 PMCID: PMC11519089 DOI: 10.1007/s40620-024-01956-1] [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: 01/09/2024] [Accepted: 04/06/2024] [Indexed: 06/25/2024]
Abstract
BACKGROUND Mortality in hemodialysis (HD) patients remains unacceptably high compared with that of the general population and despite the continuous improvement of dialysis techniques. This study aimed to assess the role of alkaline phosphatase serum levels on cardiovascular and overall mortality in the RISCAVID study cohort through a long follow-up period, looking for associations with known risk factors for poor outcome. METHODS In June 2004, a prospective observational study was started focusing on the cardiovascular risk in hemodialysis patients who lived in the north-west area of Tuscany (RISCAVID, "RISchio CArdiovascolare nei pazienti afferenti all'Area Vasta In Dialisi"). The RISCAVID cohort included 572 prevalent patients on maintenance HD for at least three months. Morbid or fatal events were prospectively recorded at 6-month intervals for a follow up time of 216 months. RESULTS In univariable Cox regression analysis, dialysis technique, Geriatric Nutritional Risk Index, peripheral vascular disease, and intact parathyroid hormone and total calcium serum levels were significantly associated with baseline alkaline phosphatase serum levels. Cox multivariable analysis showed that elevated serum alkaline phosphatase levels (the highest quartile), advanced age, dialysis vintage, type of vascular access, Geriatric Nutritional Risk Index, C-reactive protein and calcium serum levels, history of cardiovascular disease and peripheral vascular disease were independent predictors of overall mortality in maintenance HD patients. The fourth quartile of alkaline phosphatase was associated with all-cause 10-year mortality (HR: 1.47; 95% CI: 1.177-1.834) with a 47% increase with respect to the 1st, 2nd, and 3rd quartiles. This was also observed for 18-year all-cause mortality. CONCLUSIONS Adjusted proportional analysis showed the alkaline phosphatase value to be an independent and powerful predictor of overall mortality in the hemodialysis population.
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Affiliation(s)
- Vincenzo Panichi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
- Nephrology, Transplants and Dialysis Unit, AOUP, Pisa, Italy.
| | - Alberto Rosati
- Nephrology and Dialysis Unit, San Giovanni di Dio Hospital, Florence, Italy
| | | | | | - Silvia Mattei
- Nephrology, Transplants and Dialysis Unit, AOUP, Pisa, Italy
| | - Adamasco Cupisti
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
- Nephrology, Transplants and Dialysis Unit, AOUP, Pisa, Italy
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Hou S, Zhang L, Ji H, Zhao T, Hu M, Jiang Y, Sun Q, Zhang M, Dou M. Development and evaluation of the model for acute kidney injury in patients with cardiac arrest after successful resuscitation. BMC Cardiovasc Disord 2024; 24:440. [PMID: 39180000 PMCID: PMC11342716 DOI: 10.1186/s12872-024-04110-8] [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: 02/22/2024] [Accepted: 08/08/2024] [Indexed: 08/26/2024] Open
Abstract
BACKGROUND This study aims to construct a clinical prediction model and create a visual line chart depicting the risk of acute kidney injury (AKI) following resuscitation in cardiac arrest (CA) patients. Additionally, the study aims to validate the clinical predictive accuracy of the developed model. METHODS Data were retrieved from the Dryad database, and publicly shared data were downloaded. This retrospective cohort study included 347 successfully resuscitated patients post-cardiac arrest from the Dryad database. Demographic and clinical data of patients in the database, along with their renal function during hospitalization, were included. Through data analysis, the study aimed to explore the relevant influencing factors of acute kidney injury (AKI) in patients after cardiopulmonary resuscitation. The study constructed a line chart prediction model using multivariate logistic regression analysis with post-resuscitation shock status (Post-resuscitation shock refers to the condition where, following successful cardiopulmonary resuscitation after cardiac arrest, some patients develop cardiogenic shock.), C reactive protein (CRP), Lactate dehydrogenase (LDH), and Alkaline phosphatase (ALP) identified as predictive factors. The predictive efficiency of the fitted model was evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS Multivariate logistic regression analysis showed that post-resuscitation shock status, CRP, LDH, and PAL were the influencing factors of AKI after resuscitation in CA patients. The calibration curve test indicated that the prediction model was well-calibrated, and the results of the Decision Curve Analysis (DCA) demonstrated the clinical utility of the model constructed in this study. CONCLUSION Post-resuscitation shock status, CRP, LDH, and ALPare the influencing factors for AKI after resuscitation in CA patients. The clinical prediction model constructed based on the above indicators has good clinical discriminability and practicality.
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Affiliation(s)
- Shanbing Hou
- Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China
| | - Lixiang Zhang
- Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China
- Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China, Hefei, 230001, Anhui, China
| | - Hongzhi Ji
- Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China
| | - Tingting Zhao
- Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China
| | - Ming Hu
- Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China
| | - Ying Jiang
- Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China
| | - Quanquan Sun
- Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China
| | - Ming Zhang
- School of Innovation and Entrepreneurship, Wannan Medicine College, Wuhu, 241000, Anhui, China
| | - Min Dou
- Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
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Barna M, Dunovska K, Cepova J, Werle J, Prusa R, Bjørklud G, Melichercik P, Kizek R, Klapkova E. Short-term impact of vitamin K2 supplementation on biochemical parameters and lipoprotein fractions. Electrophoresis 2024. [PMID: 39091191 DOI: 10.1002/elps.202400058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 06/29/2024] [Accepted: 07/14/2024] [Indexed: 08/04/2024]
Abstract
This study explored the short-term effects of vitamin K2 (VK2) supplementation on biochemical parameters (vitamin D, vitamin E, vitamin A, alkaline phosphatase, calcium, phosphorus (P), magnesium, metallothionein, triglycerides, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and lipoprotein fractions (albumin, HDL, very low-density lipoprotein (VLDL), LDL, and chylomicrons). A short-term experiment (24 h, six probands) was performed to track changes in VK2 levels after a single-dose intake (360 µg/day). Liquid chromatography-tandem mass spectrometry was used to monitor vitamin K levels (menaquinone-4 (MK-4), menaquinone-7 (MK-7), and vitamin K1 [VK1]) with a limit of detection of 1.9 pg/mL for VK1 and 3.8 pg/mL for the two forms of VK2. Results showed that MK-7 levels significantly increased within 2-6 h post-administration and then gradually declined. MK-4 levels were initially low, showing a slight increase, whereas VK1 levels rose initially and then decreased. Biochemical analyses indicated no significant changes in sodium, chloride, potassium, calcium, magnesium, albumin, or total protein levels. A transient increase in P was observed, peaking at 12 h before returning to baseline. Agarose gel electrophoresis of lipoprotein fractions revealed distinct chylomicron bands and variations in VLDL and HDL mobility, influenced by dietary lipids and VK2 supplementation. These findings suggest effective absorption and metabolism of MK-7 with potential implications for bone metabolism and cardiovascular health.
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Affiliation(s)
- Milos Barna
- Department of Medical Chemistry and Clinical Biochemistry, Second Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czechia
- First Department of Orthopaedics, First Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czechia
| | - Katerina Dunovska
- Department of Medical Chemistry and Clinical Biochemistry, Second Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czechia
| | - Jana Cepova
- Department of Medical Chemistry and Clinical Biochemistry, Second Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czechia
| | - Julia Werle
- Department of Medical Chemistry and Clinical Biochemistry, Second Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czechia
| | - Richard Prusa
- Department of Medical Chemistry and Clinical Biochemistry, Second Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czechia
| | - Geir Bjørklud
- Council for Nutritional and Environmental Medicine, Mo i Rana, Norway
| | - Pavel Melichercik
- First Department of Orthopaedics, First Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czechia
| | - Rene Kizek
- Department of Medical Chemistry and Clinical Biochemistry, Second Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czechia
| | - Eva Klapkova
- Department of Medical Chemistry and Clinical Biochemistry, Second Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czechia
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Cao L, Zhang H, Niu Z, Ma T, Guo W. Aortic mineralization triggers the risk of acute type B aortic dissection. Atherosclerosis 2024; 395:118519. [PMID: 38944894 DOI: 10.1016/j.atherosclerosis.2024.118519] [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: 03/19/2024] [Revised: 06/06/2024] [Accepted: 06/06/2024] [Indexed: 07/02/2024]
Abstract
BACKGROUND AND AIMS The role of aortic mineralization in the pathogenesis of acute type B aortic dissection (TBAD) is unclear. Whether thoracic aortic calcification (TAC) and circulating alkaline phosphatase (ALP) activity are associated with acute TBAD risk remains elusive. METHODS Observational and Mendelian randomization (MR) studies were conducted sequentially. Using propensity score matching (1:1) by age and sex, patients with acute TBAD (n = 125) were compared with control patients (n = 125). Qualitative (score) and quantitative (volume) analyses of the TAC burden on different thoracic aortic segments were conducted using non-enhanced computed tomography. Univariate and multivariate analyses were used to identify significant independent risk factors for TBAD and TAC burden, respectively. MR was finally used to determine the causal relationship between elevated ALP activity and TBAD risk. RESULTS The qualitative and quantitative analyses revealed that TAC burden was significantly higher in the TBAD group, except for in the ascending aortic segment (both p < 0.05). Preoperative circulating ALP was significantly elevated in the TBAD group (p < 0.001). The elevated TAC burden score on the descending thoracic aortic segment (odds ratio [OR] 3.31, 95% confidence interval [CI] 1.31-8.37) and increased ALP activity (OR 1.03, 95% CI 1.01-1.06) was independently associated with TBAD risk. Interestingly, ALP was significantly positively associated with TAC burden, and MR analyses confirmed that ALP genetically predicted TBAD risk. CONCLUSIONS Elevated ALP may trigger TBAD risk via the increased volume of TAC. Aortic mineralization may not protect the aorta itself.
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Affiliation(s)
- Long Cao
- Department of Vascular and Endovascular Surgery, Chinese PLA General Hospital, Beijing, 100853, China; Medical School of Chinese PLA, Beijing, China; Department of General Surgery, The 983rd Hospital of Joint Logistic Support Force of PLA, Tianjin, 300142, China
| | - Hongpeng Zhang
- Department of Vascular and Endovascular Surgery, Chinese PLA General Hospital, Beijing, 100853, China
| | - Zelin Niu
- Department of Vascular and Endovascular Surgery, Chinese PLA General Hospital, Beijing, 100853, China; Medical School of Chinese PLA, Beijing, China
| | - Tianfeng Ma
- Department of Vascular and Endovascular Surgery, Chinese PLA General Hospital, Beijing, 100853, China; Medical School of Chinese PLA, Beijing, China
| | - Wei Guo
- Department of Vascular and Endovascular Surgery, Chinese PLA General Hospital, Beijing, 100853, China.
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Gao Y, Shu S, Zhang D, Wang P, Yu X, Wang Y, Yu Y. Association of Urinary Glyphosate with All-Cause Mortality and Cardiovascular Mortality among Adults in NHANES 2013-2018: Role of Alkaline Phosphatase. TOXICS 2024; 12:559. [PMID: 39195661 PMCID: PMC11360183 DOI: 10.3390/toxics12080559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 07/26/2024] [Accepted: 07/29/2024] [Indexed: 08/29/2024]
Abstract
Glyphosate is the most widely used herbicide in the world. This study aimed to evaluate the relationships among urinary glyphosate, all-cause mortality and cardiovascular diseases (CVD)-related mortality in the general US population of adults, and to determine the role of alkaline phosphatase (ALP), an inflammation marker that is associated with glyphosate exposure, in these relationships. Subjects from the National Health and Nutrition Examination Survey (NHANES) 2013-2018 cycles were included. Survey-weighted Cox regression analysis was applied to estimate the relationship of glyphosate with overall and CVD mortalities. Restricted cubic spline (RCS) analysis was utilized to detect the linearity of associations. The intermediary role of ALP was explored by mediation analysis. Our results found consistent and positive associations of glyphosate with all-cause mortality (HR: 1.29, 95%CI: 1.05-1.59) and CVD mortality (HR: 1.32, 95%CI: 1.02-1.70). RCS curves further validated linear and positive dose-dependent relationships between glyphosate and mortality-related outcomes. Moreover, serum ALP was identified as a mediator in these associations and explained 12.1% and 14.0% of the total associations between glyphosate and all-cause death and CVD death risk, respectively. Our study indicated that glyphosate was associated with increased all-cause and CVD mortality in humans. Increased ALP may play an essential role in these associations.
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Affiliation(s)
- Yongyue Gao
- Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550000, China; (Y.G.); (P.W.)
| | - Shuge Shu
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210000, China; (S.S.); (X.Y.); (Y.W.)
| | - Di Zhang
- Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210000, China;
| | - Pu Wang
- Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550000, China; (Y.G.); (P.W.)
| | - Xiangyu Yu
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210000, China; (S.S.); (X.Y.); (Y.W.)
| | - Yucheng Wang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210000, China; (S.S.); (X.Y.); (Y.W.)
| | - Yongquan Yu
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210000, China; (S.S.); (X.Y.); (Y.W.)
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Sharafat RH, Saeed A. Ectonucleotidase inhibitors: targeting signaling pathways for therapeutic advancement-an in-depth review. Purinergic Signal 2024:10.1007/s11302-024-10031-0. [PMID: 38958821 DOI: 10.1007/s11302-024-10031-0] [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: 12/12/2023] [Accepted: 06/16/2024] [Indexed: 07/04/2024] Open
Abstract
Ectonucleotidase inhibitors are a family of pharmacological drugs that, by selectively targeting ectonucleotidases, are essential in altering purinergic signaling pathways. The hydrolysis of extracellular nucleotides and nucleosides is carried out by these enzymes, which include ectonucleoside triphosphate diphosphohydrolases (NTPDases) and ecto-5'-nucleotidase (CD73). Ectonucleotidase inhibitors can prevent the conversion of ATP and ADP into adenosine by blocking these enzymes and reduce extracellular adenosine. These molecules are essential for purinergic signaling, which is associated with a variability of physiological and pathological processes. By modifying extracellular nucleotide metabolism and improving purinergic signaling regulation, ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) inhibitors have the potential to improve cancer treatment, inflammatory management, and immune response modulation. Purinergic signaling is affected by CD73 inhibitors because they prevent AMP from being converted to adenosine. These inhibitors are useful in cancer therapy and immunotherapy because they may improve chemotherapy effectiveness and alter immune responses. Purinergic signaling is controlled by NTPDase inhibitors, which specifically target enzymes involved in extracellular nucleotide breakdown. These inhibitors show promise in reducing immunological responses, thrombosis, and inflammation, perhaps assisting in the treatment of cardiovascular and autoimmune illnesses. Alkaline phosphatase (ALP) inhibitors alter the function of enzymes involved in dephosphorylation reactions, which has an impact on a variety of biological processes. By altering the body's phosphate levels, these inhibitors may be used to treat diseases including hyperphosphatemia and certain bone problems. This article provides a guide for researchers and clinicians looking to leverage the remedial capability of ectonucleotidase inhibitors in a variety of illness scenarios by illuminating their processes, advantages, and difficulties.
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Affiliation(s)
- R Huzaifa Sharafat
- Department of Chemistry, Quaid-I-Azam University, Islamabad, 45321, Pakistan
| | - Aamer Saeed
- Department of Chemistry, Quaid-I-Azam University, Islamabad, 45321, Pakistan.
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17
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Xiang Y, Ke W, Qin Y, Zhou B, Hu Y. PfAgo-based dual signal amplification biosensor for rapid and highly sensitive detection of alkaline phosphatase activity. Mikrochim Acta 2024; 191:439. [PMID: 38954110 DOI: 10.1007/s00604-024-06516-9] [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: 04/26/2024] [Accepted: 06/18/2024] [Indexed: 07/04/2024]
Abstract
A Pyrococcus furiosus Argonaute (PfAgo)-based biosensor is presented for alkaline phosphatase (ALP) activity detection in which the ALP-catalyzed hydrolysis of 3'-phosphate-modified functional DNA activates the strand displacement amplification, and the amplicon mediates the fluorescent reporter cleavage as a guide sequence of PfAgo. Under the dual amplification mode of PfAgo-catalyzed multiple-turnover cleavage activity and pre-amplification technology, the developed method was successfully applied to ALP activity determination with a detection limit (LOD) of 0.0013 U L-1 (3σ) and a detection range of 0.0025 to 1 U L-1 within 90 min. The PfAgo-based method exhibits satisfactory analytic performance in the presence of potential interferents and in complex human serum samples. The proposed method shows several advantages, such as rapid analysis, high sensitivity, low-cost, and easy operation, and has great potential in disease evolution fundamental studies and clinical diagnosis applications.
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Affiliation(s)
- YuQiang Xiang
- College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, China
| | - Weikang Ke
- National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
- Hubei Hongshan Laboratory, Wuhan, 430070, People's Republic of China
| | - Yuqing Qin
- National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
- Hubei Hongshan Laboratory, Wuhan, 430070, People's Republic of China
| | - Bosheng Zhou
- National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
- Hubei Hongshan Laboratory, Wuhan, 430070, People's Republic of China
| | - Yonggang Hu
- National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
- Hubei Hongshan Laboratory, Wuhan, 430070, People's Republic of China.
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Abedipour F, Mirzaei HH, Ansari H, Ehsanzadeh N, Rashki A, Vahedi MM, Rashki A. Remdesivir-Related Cardiac Adverse Effects in COVID-19 Patients: A Case-Control Study. Drug Res (Stuttg) 2024; 74:290-295. [PMID: 38968952 DOI: 10.1055/a-2332-3253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/07/2024]
Abstract
BACKGROUND There have been reports of serious side effects of Remdesivir, including cardiovascular complications. The present study aimed to determine the adverse cardiovascular effects of Remdesivir and the factors affecting them in COVID-19 patients. METHODS The patients were classified into two groups: those receiving Remdesivir without cardiac complications and those receiving Remdesivir with cardiovascular complications. After reviewing the patient's medical records, the relationship of some factors with the incidence of adverse cardiovascular effects was measured. RESULTS Chi-square test showed that the distribution of complications in men was significantly higher than in women (P=0.001). The independent t-test revealed that the mean age in the group with complications was significantly higher than the group without complications (P=0.013). Fisher's exact test demonstrated a significant relationship between smoking and cardiovascular complications (P=0.05). According to the Mann-Whitney test, a significant difference was found in the mean changes of Bilirubin (P=0.02) and ALKP (P=0.01) before and after treatment in the groups with and without heart complications. CONCLUSION Our findings indicated that most of the COVID-19 patients suffered from sinus bradycardia, and the distribution of complications was more pronounced in men than in women. The mean age in the group with complications was higher than the group without complications. Smoking was found to be associated with the occurrence of cardiovascular complications and the mean changes of Bilirubin and ALKP before and after treatment were significantly different in the groups with and without cardiovascular complications.
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Affiliation(s)
- Fatemah Abedipour
- Department of Infectious Disease, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
- Infectious Diseases and Tropical Medicine Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Hossein Hadavand Mirzaei
- Department of Infectious Disease, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Hossein Ansari
- Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Neda Ehsanzadeh
- Department of Cardiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Amin Rashki
- Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Mohammad Mahdi Vahedi
- Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
- Department of Pharmacology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Asma Rashki
- Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
- Department of Pharmacology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
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Zhao W, Zhang S, Zhao HD. Longitudinal study on the change trend of serum alkaline phosphatase and its possible influencing factors in peritoneal dialysis patients. Sci Rep 2024; 14:13099. [PMID: 38849443 PMCID: PMC11161618 DOI: 10.1038/s41598-024-63721-5] [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: 02/03/2024] [Accepted: 05/31/2024] [Indexed: 06/09/2024] Open
Abstract
The aim of the study was to analyze the change trend of serum ALP over time and identify factors influencing its levels in peritoneal dialysis patients. Then to investigate the impact of serum ALP changes on calcium and phosphorus metabolism in single peritoneal dialysis center utilizing repeated measurement data. A retrospective cohort study was conducted with a total follow-up duration of 30 months. Serum ALP and other biomarkers, including calcium (Ca), phosphorus (P), 25(OH)D, intact parathyroid hormone (iPTH), albumin(ALB), and hemoglobin(Hb) were measured every 3 months. The generalized estimation equation (GEE) was utilized to analyze the change trend of serum ALP over time, and to assess whether there were differences in changes over time between different genders and different primary disease groups. Additionally, factors influencing serum ALP levels were analyzed, and the impact of serum ALP changes on calcium and phosphorus metabolism was also explored. A total of 34 patients were included in the study. Serum ALP and other indicators were measured repeatedly, with a maximum of 8 times and a minimum of 4 times. The median of serum ALP values at all measurement times for all selected patients was 89 U/L. The GEE analysis revealed that serum ALP gradually increased with time, and patients in diabetes group increased faster than those in non-diabetes group. A positive correlation was observed between serum ALP and dialysis duration, also between serum ALP and hemoglobin. However, variations in serum ALP did not significantly affect serum corrected calcium, phosphorus, or iPTH concentrations. The serum ALP levels of peritoneal dialysis patients increase gradually over time, and the concentrations are influenced by dialysis duration. The changes in serum ALP values do not have a significant impact on serum calcium, phosphorus, and iPTH levels.
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Affiliation(s)
- Wei Zhao
- Department of Nephrology, Peking University Shougang Hospital, Shijingshan District, Beijing, 100144, China
| | - Sen Zhang
- Department of Nephrology, Peking University Shougang Hospital, Shijingshan District, Beijing, 100144, China
| | - Hai-Dan Zhao
- Department of Nephrology, Peking University Shougang Hospital, Shijingshan District, Beijing, 100144, China.
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Lederer ED, Sobh MM, Brier ME, Gaweda AE. Application of artificial intelligence to chronic kidney disease mineral bone disorder. Clin Kidney J 2024; 17:sfae143. [PMID: 38899159 PMCID: PMC11184350 DOI: 10.1093/ckj/sfae143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Indexed: 06/21/2024] Open
Abstract
The global derangement of mineral metabolism that accompanies chronic kidney disease (CKD-MBD) is a major driver of the accelerated mortality for individuals with kidney disease. Advances in the delivery of dialysis, in the composition of phosphate binders, and in the therapies directed towards secondary hyperparathyroidism have failed to improve the cardiovascular event profile in this population. Many obstacles have prevented progress in this field including the incomplete understanding of pathophysiology, the lack of clinical targets for early stages of chronic kidney disease, and the remarkably wide diversity in clinical manifestations. We describe in this review a novel approach to CKD-MBD combining mathematical modelling of biologic processes with machine learning artificial intelligence techniques as a tool for the generation of new hypotheses and for the development of innovative therapeutic approaches to this syndrome. Clinicians need alternative targets of therapy, tools for risk profile assessment, and new therapies to address complications early in the course of disease and to personalize therapy to each individual. The complexity of CKD-MBD suggests that incorporating artificial intelligence techniques into the diagnostic, therapeutic, and research armamentarium could accelerate the achievement of these goals.
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Affiliation(s)
- Eleanor D Lederer
- VA North Texas Health Care Services, Dallas TX, USA
- Department of Medicine and Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, UT Southwestern Medical Center, Dallas, TX, USA
- Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY, USA
| | - Mahmoud M Sobh
- Nephrology and Internal Medicine, Mansoura University, Mansoura, Egypt
| | - Michael E Brier
- Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY, USA
- Robley Rex VA Medical Center, Louisville, KY, USA
| | - Adam E Gaweda
- Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY, USA
- Robley Rex VA Medical Center, Louisville, KY, USA
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Vandecruys M, De Smet S, De Beir J, Renier M, Leunis S, Van Criekinge H, Glorieux G, Raes J, Vanden Wyngaert K, Nagler E, Calders P, Monbaliu D, Cornelissen V, Evenepoel P, Van Craenenbroeck AH. Revitalizing the Gut Microbiome in Chronic Kidney Disease: A Comprehensive Exploration of the Therapeutic Potential of Physical Activity. Toxins (Basel) 2024; 16:242. [PMID: 38922137 PMCID: PMC11209503 DOI: 10.3390/toxins16060242] [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: 04/18/2024] [Revised: 05/16/2024] [Accepted: 05/20/2024] [Indexed: 06/27/2024] Open
Abstract
Both physical inactivity and disruptions in the gut microbiome appear to be prevalent in patients with chronic kidney disease (CKD). Engaging in physical activity could present a novel nonpharmacological strategy for enhancing the gut microbiome and mitigating the adverse effects associated with microbial dysbiosis in individuals with CKD. This narrative review explores the underlying mechanisms through which physical activity may favorably modulate microbial health, either through direct impact on the gut or through interorgan crosstalk. Also, the development of microbial dysbiosis and its interplay with physical inactivity in patients with CKD are discussed. Mechanisms and interventions through which physical activity may restore gut homeostasis in individuals with CKD are explored.
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Affiliation(s)
- Marieke Vandecruys
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium; (M.V.); or (P.E.)
| | - Stefan De Smet
- Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, 3000 Leuven, Belgium;
| | - Jasmine De Beir
- Department of Rehabilitation Sciences, Ghent University, 9000 Ghent, Belgium; (J.D.B.); (P.C.)
| | - Marie Renier
- Group Rehabilitation for Internal Disorders, Department of Rehabilitation Sciences, KU Leuven, 3000 Leuven, Belgium; (M.R.); (V.C.)
| | - Sofie Leunis
- Department of Microbiology, Immunology and Transplantation, Abdominal Transplantation, KU Leuven, 3000 Leuven, Belgium; (S.L.); (H.V.C.); (D.M.)
| | - Hanne Van Criekinge
- Department of Microbiology, Immunology and Transplantation, Abdominal Transplantation, KU Leuven, 3000 Leuven, Belgium; (S.L.); (H.V.C.); (D.M.)
| | - Griet Glorieux
- Department of Internal Medicine and Pediatrics, Nephrology Section, Ghent University Hospital, 9000 Ghent, Belgium; (G.G.); (K.V.W.); (E.N.)
| | - Jeroen Raes
- Department of Microbiology and Immunology, Rega Institute for Medical Research, 3000 Leuven, Belgium;
- VIB-KU Leuven Center for Microbiology, 3000 Leuven, Belgium
| | - Karsten Vanden Wyngaert
- Department of Internal Medicine and Pediatrics, Nephrology Section, Ghent University Hospital, 9000 Ghent, Belgium; (G.G.); (K.V.W.); (E.N.)
| | - Evi Nagler
- Department of Internal Medicine and Pediatrics, Nephrology Section, Ghent University Hospital, 9000 Ghent, Belgium; (G.G.); (K.V.W.); (E.N.)
| | - Patrick Calders
- Department of Rehabilitation Sciences, Ghent University, 9000 Ghent, Belgium; (J.D.B.); (P.C.)
| | - Diethard Monbaliu
- Department of Microbiology, Immunology and Transplantation, Abdominal Transplantation, KU Leuven, 3000 Leuven, Belgium; (S.L.); (H.V.C.); (D.M.)
- Transplantoux Foundation, 3000 Leuven, Belgium
| | - Véronique Cornelissen
- Group Rehabilitation for Internal Disorders, Department of Rehabilitation Sciences, KU Leuven, 3000 Leuven, Belgium; (M.R.); (V.C.)
| | - Pieter Evenepoel
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium; (M.V.); or (P.E.)
- Department of Nephrology, University Hospitals Leuven, 3000 Leuven, Belgium
| | - Amaryllis H. Van Craenenbroeck
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium; (M.V.); or (P.E.)
- Department of Nephrology, University Hospitals Leuven, 3000 Leuven, Belgium
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22
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Kim TS, Hong CY, Oh SJ, Choe YH, Hwang TS, Kim J, Lee SL, Yoon H, Bok EY, Cho AR, Do YJ, Kim E. RNA sequencing provides novel insights into the pathogenesis of naturally occurring myxomatous mitral valve disease stage B1 in beagle dogs. PLoS One 2024; 19:e0300813. [PMID: 38753730 PMCID: PMC11098313 DOI: 10.1371/journal.pone.0300813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Accepted: 03/05/2024] [Indexed: 05/18/2024] Open
Abstract
Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disorder in dogs with a high prevalence, accounting for approximately 75% of all canine heart disease cases. MMVD is a complex disease and shows variable progression from mild valve leakage to severe regurgitation, potentially leading to heart failure. However, the molecular mechanisms and age-related changes that govern disease progression, especially at the early stage (B1) before the development of discernable clinical signs, remain poorly understood. In this prospective study, we aimed to compare gene expression differences between blood samples of aged beagle dogs with stage B1 MMVD and those of healthy controls using RNA sequencing. Clinical evaluation was also conducted, which revealed minimal differences in radiographic and echocardiographic measurements despite distinct biomarker variations between the two groups. Comparative transcriptomics revealed differentially expressed genes associated with extracellular matrix remodeling, prostaglandin metabolism, immune modulation, and interferon-related pathways, which bear functional relevance for MMVD. In particular, the top 10 over- and under-expressed genes represent promising candidates for influencing pathogenic changes in MMVD stage B1. Our research findings, which include identified variations in clinical markers and gene expression, enhance our understanding of MMVD. Furthermore, they underscore the need for further research into early diagnosis and treatment strategies, as, to the best of our knowledge, no prior studies have explored the precise molecular mechanisms of stage B1 in MMVD through total RNA sequencing.
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Affiliation(s)
- Tae-Seok Kim
- College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam-do, Republic of Korea
| | - Chae-Yeon Hong
- College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam-do, Republic of Korea
| | - Seong-Ju Oh
- College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam-do, Republic of Korea
| | - Yong-Ho Choe
- College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam-do, Republic of Korea
| | - Tae-Sung Hwang
- College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam-do, Republic of Korea
| | - Jaemin Kim
- Division of Applied Life Science, Gyeongsang National University, Jinju, Gyeongsangnam-do, Republic of Korea
- Institute of Agriculture and Life Sciences, Gyeongsang National University, Jinju, Gyeongsangnam-do, Republic of Korea
| | - Sung-Lim Lee
- College of Veterinary Medicine, Gyeongsang National University, Jinju, Gyeongsangnam-do, Republic of Korea
- Research Institute of Life Sciences, Gyeongsang National University, Jinju, Gyeongsangnam-do, Republic of Korea
| | - Hakyoung Yoon
- College of Veterinary Medicine, Jeonbuk National University, Iksan, Jeollabuk-do, Republic of Korea
| | - Eun-Yeong Bok
- Division of Animal Diseases & Health, National Institute of Animal Science, Rural Development Administration, Wanju, Jeollabuk-do, Republic of Korea
| | - A-ra Cho
- Division of Animal Diseases & Health, National Institute of Animal Science, Rural Development Administration, Wanju, Jeollabuk-do, Republic of Korea
| | - Yoon Jung Do
- Division of Animal Diseases & Health, National Institute of Animal Science, Rural Development Administration, Wanju, Jeollabuk-do, Republic of Korea
| | - Eunju Kim
- Division of Animal Diseases & Health, National Institute of Animal Science, Rural Development Administration, Wanju, Jeollabuk-do, Republic of Korea
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23
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Shi S, Kan A, Lu L, Zhao W, Jiang W. An acid-responsive DNA hydrogel-mediated cascaded enzymatic nucleic acid amplification system for the sensitive imaging of alkaline phosphatase in living cells. Analyst 2024; 149:3026-3033. [PMID: 38618891 DOI: 10.1039/d4an00258j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2024]
Abstract
Alkaline phosphatase (ALP) is a class of hydrolase that catalyzes the dephosphorylation of phosphorylated species in biological tissues, playing an important role in many physiological and pathological processes. Sensitive imaging of ALP activity in living cells is contributory to the research on these processes. Herein, we propose an acid-responsive DNA hydrogel to deliver a cascaded enzymatic nucleic acid amplification system into cells for the sensitive imaging of intracellular ALP activity. The DNA hydrogel is formed by two kinds of Y-shaped DNA monomers and acid-responsive cytosine-rich linkers. The amplification system contained Bst DNA polymerase (Bst DP), Nt.BbvCI endonuclease, a Recognition Probe (RP, containing a DNAzyme sequence, a Nt.BbvCI recognition sequence, and a phosphate group at the 3'-end), and a Signal Probe (SP, containing a cleavage site for DNAzyme, Cy3 and BHQ2 at the two ends). The amplification system was trapped into the DNA hydrogel and taken up by cells, and the cytosine-rich linkers folded into a quadruplex i-motif in the acidic lysosomes, leading to the collapse of the hydrogel and releasing the amplification system. The phosphate groups on RPs were recognized and removed by the target ALP, triggering a polymerization-nicking cycle to produce large numbers of DNAzyme sequences, which then cleaved multiple SPs, restoring Cy3 fluorescence to indicate the ALP activity. This strategy achieved sensitive imaging of ALP in living HeLa, MCF-7, and NCM460 cells, and realized the sensitive detection of ALP in vitro with a detection limit of 2.0 × 10-5 U mL-1, providing a potential tool for the research of ALP-related physiological and pathological processes.
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Affiliation(s)
- Shaochuan Shi
- School of Chemistry and Chemical Engineering, Shandong University, 250100 Jinan, P. R. China.
| | - Ailing Kan
- School of Chemistry and Chemical Engineering, Shandong University, 250100 Jinan, P. R. China.
- Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, P. R. China.
| | - Lu Lu
- Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, P. R. China.
| | - Weichong Zhao
- Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, P. R. China.
| | - Wei Jiang
- School of Chemistry and Chemical Engineering, Shandong University, 250100 Jinan, P. R. China.
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24
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Nayak SPRR, Boopathi S, Chandrasekar M, Yamini B, Chitra V, Almutairi BO, Arokiyaraj S, Guru A, Arockiaraj J. Indole-3 acetic acid induced cardiac hypertrophy in Wistar albino rats. Toxicol Appl Pharmacol 2024; 486:116917. [PMID: 38555004 DOI: 10.1016/j.taap.2024.116917] [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: 01/05/2024] [Revised: 03/25/2024] [Accepted: 03/27/2024] [Indexed: 04/02/2024]
Abstract
Indole-3-acetic acid (IAA) is the most widely utilized plant growth regulator. Despite its extensive usage, IAA is often overlooked as an environmental pollutant. Due to its protein-binding nature, it also functions as a uremic toxin, contributing to its association with chronic kidney disease (CKD). While in vitro and epidemiological research have demonstrated this association, the precise impact of IAA on cardiovascular disease in animal models is unknown. The main objective of this study is to conduct a mechanistic analysis of the cardiotoxic effects caused by IAA using male Wistar albino rats as the experimental model. Three different concentrations of IAA (125, 250, 500 mg/kg) were administered for 28 days. The circulating IAA concentration mimicked previously observed levels in CKD patients. The administration of IAA led to a notable augmentation in heart size and heart-to-body weight ratio, indicating cardiac hypertrophy. Echocardiographic assessments supported these observations, revealing myocardial thickening. Biochemical and gene expression analyses further corroborated the cardiotoxic effects of IAA. Dyslipidemia, increased serum c-Troponin-I levels, decreased SOD and CAT levels, and elevated lipid peroxidation in cardiac tissue were identified. Moreover, increased expression of cardiac inflammatory biomarkers, including ANP, BNP, β-MHC, Col-III, TNF-α, and NF-κB, was also found in the IAA-treated animals. Histopathological analysis confirmed the cardiotoxic nature of IAA, providing additional evidence of its adverse effects on cardiovascular health. These results offer insights into the potential negative impact of IAA on cardiovascular function, and elucidating the underlying mechanisms of its cardiotoxicity.
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Affiliation(s)
- S P Ramya Ranjan Nayak
- Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India
| | - Seenivasan Boopathi
- Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India
| | - Munisamy Chandrasekar
- Resident Veterinary Services Section, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai 600007, Tamil Nadu, India
| | - B Yamini
- International Center for Cardio Thoracic and Vascular Diseases, Dr K M Cherian Heart Foundation, Anna Nagar, Chennai 600040, Tamil Nadu, India
| | - Vellapandian Chitra
- Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India
| | - Bader O Almutairi
- Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Selvaraj Arokiyaraj
- Department of Food Science & Biotechnology, Sejong University, Seoul 05006, Republic of Korea
| | - Ajay Guru
- Department of Cariology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
| | - Jesu Arockiaraj
- Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India.
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25
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Zhang Q, Hu J, Li DL, Qiu JG, Jiang BH, Zhang CY. Construction of single-molecule counting-based biosensors for DNA-modifying enzymes: A review. Anal Chim Acta 2024; 1298:342395. [PMID: 38462345 DOI: 10.1016/j.aca.2024.342395] [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: 12/10/2023] [Revised: 02/18/2024] [Accepted: 02/19/2024] [Indexed: 03/12/2024]
Abstract
DNA-modifying enzymes act as critical regulators in a wide range of genetic functions (e.g., DNA damage & repair, DNA replication), and their aberrant expression may interfere with regular genetic functions and induce various malignant diseases including cancers. DNA-modifying enzymes have emerged as the potential biomarkers in early diagnosis of diseases and new therapeutic targets in genomic research. Consequently, the development of highly specific and sensitive biosensors for the detection of DNA-modifying enzymes is of great importance for basic biomedical research, disease diagnosis, and drug discovery. Single-molecule fluorescence detection has been widely implemented in the field of molecular diagnosis due to its simplicity, high sensitivity, visualization capability, and low sample consumption. In this paper, we summarize the recent advances in single-molecule counting-based biosensors for DNA-modifying enzyme (i.e, alkaline phosphatase, DNA methyltransferase, DNA glycosylase, flap endonuclease 1, and telomerase) assays in the past four years (2019 - 2023). We highlight the principles and applications of these biosensors, and give new insight into the future challenges and perspectives in the development of single-molecule counting-based biosensors.
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Affiliation(s)
- Qian Zhang
- Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan, China; College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan, 250014, China
| | - Juan Hu
- School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China
| | - Dong-Ling Li
- School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China
| | - Jian-Ge Qiu
- Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Bing-Hua Jiang
- Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan, China.
| | - Chun-Yang Zhang
- School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China.
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26
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Koo BS, Jang M, Oh JS, Shin K, Lee S, Joo KB, Kim N, Kim TH. Machine learning models with time-series clinical features to predict radiographic progression in patients with ankylosing spondylitis. JOURNAL OF RHEUMATIC DISEASES 2024; 31:97-107. [PMID: 38559800 PMCID: PMC10973352 DOI: 10.4078/jrd.2023.0056] [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: 09/04/2023] [Revised: 10/15/2023] [Accepted: 10/30/2023] [Indexed: 04/04/2024]
Abstract
Objective Ankylosing spondylitis (AS) is chronic inflammatory arthritis causing structural damage and radiographic progression to the spine due to repeated and continuous inflammation over a long period. This study establishes the application of machine learning models to predict radiographic progression in AS patients using time-series data from electronic medical records (EMRs). Methods EMR data, including baseline characteristics, laboratory findings, drug administration, and modified Stoke AS Spine Score (mSASSS), were collected from 1,123 AS patients between January 2001 and December 2018 at a single center at the time of first (T1), second (T2), and third (T3) visits. The radiographic progression of the (n+1)th visit (Pn+1=(mSASSSn+1-mSASSSn)/(Tn+1-Tn)≥1 unit per year) was predicted using follow-up visit datasets from T1 to Tn. We used three machine learning methods (logistic regression with the least absolute shrinkage and selection operation, random forest, and extreme gradient boosting algorithms) with three-fold cross-validation. Results The random forest model using the T1 EMR dataset best predicted the radiographic progression P2 among the machine learning models tested with a mean accuracy and area under the curves of 73.73% and 0.79, respectively. Among the T1 variables, the most important variables for predicting radiographic progression were in the order of total mSASSS, age, and alkaline phosphatase. Conclusion Prognosis predictive models using time-series data showed reasonable performance with clinical features of the first visit dataset when predicting radiographic progression.
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Affiliation(s)
- Bon San Koo
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Miso Jang
- Department of Biomedical Engineering, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji Seon Oh
- Department of Information Medicine, Big Data Research Center, Asan Medical Center, Seoul, Korea
| | - Keewon Shin
- Department of Biomedical Engineering, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seunghun Lee
- Department of Radiology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
| | - Kyung Bin Joo
- Department of Radiology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
| | - Namkug Kim
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Hwan Kim
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
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27
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Zhu J, Li X. Ratio-fluorescent and naked-eye visualized dual-channel sensing strategy for Cu 2+ and alkaline phosphatase activity assay. ANAL SCI 2024; 40:471-480. [PMID: 38127250 DOI: 10.1007/s44211-023-00479-2] [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: 08/31/2023] [Accepted: 11/20/2023] [Indexed: 12/23/2023]
Abstract
The levels of Cu2+ and alkaline phosphatase (ALP) are the important indicators of the developed stage of the relative diseases. Herein, a binary ratio-fluorescent and smartphone-assisted visual strategy basing on 4'-aminomethyl-4, 5', 8-trimethylpsoralen (AMT) and the oxidation of o-phenylenediamine was developed. Under the action of Cu2+, the fluorescent molecule, 3-diaminophenazine (DAP) formed which can act as a fluorescent acceptor of the ratio-fluorescent sensor. The emission spectrum of AMT overlapped with the excitation spectrum of DAP and, thus, it can act as the fluorescent donor of the ratio-fluorescent sensor. With the increasing concentration of Cu2+ and ALP, the fluorescent intensity of AMT decreased and the fluorescent intensity of DAP increased. The dual-emission reverse change ratio-fluorescent sensor realized the sensitive detection Cu2+ and ALP with the detection limits of 2 nM and 0.03 U/mL, respectively. In addition, the acceptable recoveries were obtained when the Cu2+ and ALP in spiked samples were detected. Furthermore, the relative activity of ALP was assessed by increasing the concentrations of the inhibitor Na3VO4 and IC50 of 25 μM was obtained. Importantly, the target concentration-dependent color change of DAP allowed us to utilize R/B ratio values to design the smartphone-assisting visual detection model of Cu2+ and ALP activity with the detection limits of 0.1 μM and 0.18 U/mL. This simple, flexible, dual-mode sensor strategy has a potential for disease diagnosis and drug screening.
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Affiliation(s)
- Jing Zhu
- College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu Shandong, 273165, People's Republic of China.
| | - Xinyu Li
- College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu Shandong, 273165, People's Republic of China
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28
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Adamidis PS, Florentin M, Liberopoulos E, Koutsogianni AD, Anastasiou G, Liamis G, Milionis H, Barkas F. Association of Alkaline Phosphatase with Cardiovascular Disease in Patients with Dyslipidemia: A 6-Year Retrospective Study. J Cardiovasc Dev Dis 2024; 11:60. [PMID: 38392274 PMCID: PMC10889667 DOI: 10.3390/jcdd11020060] [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: 12/31/2023] [Revised: 02/09/2024] [Accepted: 02/14/2024] [Indexed: 02/24/2024] Open
Abstract
BACKGROUND AND AIM Serum alkaline phosphatase (ALP) activity has been associated with atherosclerotic cardiovascular disease (ASCVD). We aimed to investigate the association of ALP with ASCVD in patients with dyslipidemia. METHODS We conducted a retrospective cohort study including consecutive adults with dyslipidemia followed-up for ≥3 years (from 1999 to 2022) in the outpatient Lipid Clinic of Ioannina University General Hospital, Greece. The primary endpoint was the association between baseline ALP and incident ASCVD after adjusting for traditional risk factors (i.e., sex, age, hypertension, diabetes, smoking, and dyslipidemia), baseline ASCVD, and lipid-lowering treatment. ALP levels were stratified by tertiles as follows: low: <67 U/L, middle: 67-79 U/L, high: ≥79 U/L. RESULTS Overall, 1178 subjects were included; 44% were males, and their median age was 57 years (range: 49-65). During a 6-year median follow-up (interquartile range: IQR: 4-9), 78 new ASCVD events (6.6%) occurred. A statistically significant association between baseline ALP levels and incident ASCVD was demonstrated (Odds Ratio, OR: 6.99; 95% Confidence Interval, CI: 2.29-21.03, p = 0.001). Subjects in the highest ALP tertile had the highest odds for ASCVD when compared with those in the lowest tertile (OR: 2.35; 95% CI: 1.24-4.41, p = 0.008). CONCLUSIONS The present study indicates an association between ALP and the development of ASCVD in patients with dyslipidemia, which underscores the potential of ALP as a predictive tool or a therapeutic target in the realm of ASCVD prevention within this population.
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Affiliation(s)
- Petros Spyridonas Adamidis
- Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
| | - Matilda Florentin
- Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
| | - Evangelos Liberopoulos
- 1st Propedeutic Department of Medicine, School of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Amalia Despoina Koutsogianni
- Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
| | - Georgia Anastasiou
- Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
| | - George Liamis
- Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
| | - Haralampos Milionis
- Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
| | - Fotios Barkas
- Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
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29
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Wang Z, Li J, Jing J, Zhang Z, Xu Q, Liu T, Lin J, Jiang Y, Wang Y, Wang A, Meng X. Impact of alkaline phosphatase on clinical outcomes in patients with ischemic stroke: a nationwide registry analysis. Front Neurol 2024; 15:1336069. [PMID: 38419697 PMCID: PMC10899335 DOI: 10.3389/fneur.2024.1336069] [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: 11/23/2023] [Accepted: 01/18/2024] [Indexed: 03/02/2024] Open
Abstract
Background Data on the association between serum alkaline phosphatase (ALP) levels and clinical outcomes in patients with ischemic stroke (IS) are inconsistent and limited. Therefore, this study aimed to investigate the correlation between ALP and prognosis in patients with IS. Methods Patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) from the Third China National Stroke Registry were divided into four groups according to the quartiles of serum ALP levels on admission. Cox proportional hazards and logistic regression models were used to evaluate the correlation between ALP and the risk of all-cause mortality, disability (modified Rankin Scale (mRS) score 3-5), and poor functional outcomes (mRS score 3-6). Results A total of 11,405 patients were included in the study. Higher levels of ALP were associated with all-cause mortality at 3 months (adjusted hazard ratio [HR] per standard deviation [SD]: 1.16; 95% confidence interval (CI): 1.07-1.27; p = 0.001) and 1 year (adjusted HR: 1.11; 95% CI: 1.03-1.20; p = 0.010). At the 3-month follow-up, each SD increase of ALP was associated with a 12 and 14% higher risk of disability (adjusted odds ratio (OR): 1.12; 95% CI: 1.06-1.18; p < 0.001) and poor functional outcomes (adjusted OR: 1.14; 95% CI: 1.08-1.20; p < 0.001). Similar results were observed at the 1-year follow-up. Higher ALP levels were associated with an increased risk of all-cause mortality, disability, and poor functional outcomes in patients with "others" subtypes (including other determined etiology and undetermined etiology) (p < 0.05). Conclusion Elevated ALP levels were associated with an increased risk of all-cause mortality, disability, and poor function outcomes in patients with IS. Heterogeneity was observed among the subtypes of different etiologies.
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Affiliation(s)
- Zhaobin Wang
- Affiliated Hospital of Hebei University, Baoding, China
- Clinical Medical College, Hebei University, Baoding, China
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Puyang Oilfield General Hospital, Puyang, China
| | - Jing Li
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Jing Jing
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Zhe Zhang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Qin Xu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Tao Liu
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Jinxi Lin
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yong Jiang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yongjun Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Anxin Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Xia Meng
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
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Atanasova D, Mirgorodskaya E, Moparthi L, Koch S, Haarhaus M, Narisawa S, Millán JL, Landberg E, Magnusson P. Glycoproteomic profile of human tissue-nonspecific alkaline phosphatase expressed in osteoblasts. JBMR Plus 2024; 8:ziae006. [PMID: 38505526 PMCID: PMC10945725 DOI: 10.1093/jbmrpl/ziae006] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 01/10/2024] [Accepted: 01/11/2024] [Indexed: 03/21/2024] Open
Abstract
Tissue-nonspecific alkaline phosphatase (TNALP) is a glycoprotein expressed by osteoblasts that promotes bone mineralization. TNALP catalyzes the hydrolysis of the mineralization inhibitor inorganic pyrophosphate and ATP to provide inorganic phosphate, thus controlling the inorganic pyrophosphate/inorganic phosphate ratio to enable the growth of hydroxyapatite crystals. N-linked glycosylation of TNALP is essential for protein stability and enzymatic activity and is responsible for the presence of different bone isoforms of TNALP associated with functional and clinical differences. The site-specific glycosylation profiles of TNALP are, however, elusive. TNALP has 5 potential N-glycosylation sites located at the asparagine (N) residues 140, 230, 271, 303, and 430. The objective of this study was to reveal the presence and structure of site-specific glycosylation in TNALP expressed in osteoblasts. Calvarial osteoblasts derived from Alpl+/- expressing SV40 Large T antigen were transfected with soluble epitope-tagged human TNALP. Purified TNALP was analyzed with a lectin microarray, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and liquid chromatography with tandem mass spectrometry. The results showed that all sites (n = 5) were fully occupied predominantly with complex-type N-glycans. High abundance of galactosylated biantennary N-glycans with various degrees of sialylation was observed on all sites, as well as glycans with no terminal galactose and sialic acid. Furthermore, all sites had core fucosylation except site N271. Modelling of TNALP, with the protein structure prediction software ColabFold, showed possible steric hindrance by the adjacent side chain of W270, which could explain the absence of core fucosylation at N271. These novel findings provide evidence for N-linked glycosylation on all 5 sites of TNALP, as well as core fucosylation on 4 out of 5 sites. We anticipate that this new knowledge can aid in the development of functional and clinical assays specific for the TNALP bone isoforms.
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Affiliation(s)
- Diana Atanasova
- Department of Clinical Chemistry, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping SE-58185, Sweden
| | - Ekaterina Mirgorodskaya
- Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg SE-41346, Sweden
| | - Lavanya Moparthi
- Wallenberg Centre for Molecular Medicine, Linköping University, Linköping SE-58185, Sweden
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping SE-58185, Sweden
| | - Stefan Koch
- Wallenberg Centre for Molecular Medicine, Linköping University, Linköping SE-58185, Sweden
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping SE-58185, Sweden
| | - Mathias Haarhaus
- Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm SE-14186, Sweden
| | - Sonoko Narisawa
- Sanford Children’s Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, United States
| | - José Luis Millán
- Sanford Children’s Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, United States
| | - Eva Landberg
- Department of Clinical Chemistry, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping SE-58185, Sweden
| | - Per Magnusson
- Department of Clinical Chemistry, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping SE-58185, Sweden
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31
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Xu Z, Xu X, Zhu X, Niu K, Dong J, He Z. Attention-Based Deep Learning Model for Prediction of Major Adverse Cardiovascular Events in Peritoneal Dialysis Patients. IEEE J Biomed Health Inform 2024; 28:1101-1109. [PMID: 38048232 DOI: 10.1109/jbhi.2023.3338729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/06/2023]
Abstract
Major adverse cardiovascular events (MACE) encompass pivotal cardiovascular outcomes such as myocardial infarction, unstable angina, and cardiovascular-related mortality. Patients undergoing peritoneal dialysis (PD) exhibit specific cardiovascular risk factors during the treatment, which can escalate the likelihood of cardiovascular events. Hence, the prediction and key factor analysis of MACE have assumed paramount significance for peritoneal dialysis patients. Current pathological methodologies for prognosis prediction are not only costly but also cumbersome in effectively processing electronic health records (EHRs) data with high dimensionality, heterogeneity, and time series. Therefore in this study, we propose the CVEformer, an attention-based neural network designed to predict MACE and analyze risk factors. CVEformer leverages the self-attention mechanism to capture temporal correlations among time series variables, allowing for weighted integration of variables and estimation of the probability of MACE. CVEformer first captures the correlations among heterogeneous variables through attention scores. Then, it analyzes the correlations within the time series data to identify key risk variables and predict the probability of MACE. When trained and evaluated on data from a large cohort of peritoneal dialysis patients across multiple centers, CVEformer outperforms existing models in terms of predictive performance.
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Xu Q, Wang Y, Zhou Y, Zhang L, Xiang X, Xie Y, Lu J, Li L, Zhu Y, Zhang Z, Zhang T, Li L. Phenotypes of a toddler with hereditary sensory and autonomic neuropathy type IV: comparing with normal: A case report. Medicine (Baltimore) 2024; 103:e36955. [PMID: 38241559 PMCID: PMC10798782 DOI: 10.1097/md.0000000000036955] [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: 10/07/2023] [Accepted: 12/21/2023] [Indexed: 01/21/2024] Open
Abstract
RATIONALE Hereditary sensory and autonomic neuropathy type IV (HSAN IV) may be misdiagnosed because of low awareness among clinical professionals and overlap with other subtypes of congenital insensitivity to pain (CIP). PATIENT The patient was a 1-year-and-5-months-old boy whose main symptoms were delayed psychomotor development and recurrent fever. Whole-exome sequencing (WES) revealed a compound heterozygous mutation (c. 1927C > T, c. 851-33T > A) in the NTRK1 gene of the child. Pathological analysis showed decreased autonomic small nerve fibers, sparse hair follicles, and atrophy of the sweat glands. Sweat glands lack innervating nerve fibers. Brain magnetic resonance imaging (MRI) of the patient showed delayed myelination in the brain, slightly enlarged bilateral lateral ventricles, and patchy abnormal signals in the brain. DIAGNOSIS hereditary sensory and autonomic neuropathy type IV (HSAN IV). INTERVENTION Inform parents about the illness and take good care of the child. OUTCOMES The children had less self-harming behavior and no painless fractures during follow-up at 2 years. LESSONS This report describes the pathological and imaging features and clinical manifestations of a child with HSAN IV in early life to provide a reference for the early diagnosis of the disease. Early diagnosis can help avoid self-mutilation and painless injury and reduce wound infection.
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Affiliation(s)
- Qinghua Xu
- Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children’s Major Disease Research, Yunnan Institute of Pediatrics, Kunming Children’s Hospital, Kunming, China
| | - Yanchun Wang
- Department of 2nd Infections, Kunming Children’s Hospital, Kunming, China
| | - Yuantao Zhou
- Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children’s Major Disease Research, Yunnan Institute of Pediatrics, Kunming Children’s Hospital, Kunming, China
| | - Lu Zhang
- Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children’s Major Disease Research, Yunnan Institute of Pediatrics, Kunming Children’s Hospital, Kunming, China
| | - Xiaoyi Xiang
- Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children’s Major Disease Research, Yunnan Institute of Pediatrics, Kunming Children’s Hospital, Kunming, China
| | - Yucheng Xie
- Department of Pathology, Kunming Children’s Hospital, Kunming, China
| | - Jiantian Lu
- Department of Radiology, Kunming Children’s Hospital, Kunming, China
| | - Lei Li
- Department of Electroencephalogram, Kunming Children’s Hospital, Kunming, China
| | - Ying Zhu
- Department of 2nd Infections, Kunming Children’s Hospital, Kunming, China
| | - Zhao Zhang
- Department of Dermatology, Kunming Children’s Hospital, Kunming, China
| | - Tiesong Zhang
- Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children’s Major Disease Research, Yunnan Institute of Pediatrics, Kunming Children’s Hospital, Kunming, China
| | - Li Li
- Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children’s Major Disease Research, Yunnan Institute of Pediatrics, Kunming Children’s Hospital, Kunming, China
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Ortiz MIG, Corrales Ureña YR, Aguiar FHB, Lima DANL, Rischka K. Enzymatically Driven Mineralization of a Calcium-Polyphosphate Bleaching Gel. Bioengineering (Basel) 2024; 11:83. [PMID: 38247960 PMCID: PMC10813067 DOI: 10.3390/bioengineering11010083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 01/09/2024] [Accepted: 01/12/2024] [Indexed: 01/23/2024] Open
Abstract
To examined alkaline phosphatase enzyme (ALP) activity and the effects of incorporating it in the thickener solution of a hydrogen-peroxide-based bleaching gel containing calcium-polyphosphate (CaPP) on the orthophosphate (PO43-) levels, bleaching effectiveness, and enamel microhardness. ALP activity was assessed at different pH levels and H2O2 concentrations, and in H2O- and Tris-based thickeners. Circular dichroism (CD) was used to examine the ALP secondary structure in water-, Tris-, or H2O2-based mediums. The PO43- levels were evaluated in thickeners with and without ALP. Enamel/dentin specimens were allocated into the following groups: control (without bleaching); commercial (Whiteness-HP-Maxx); Exp-H (H2O-based); CaPP-H; ALP-H (CaPP+ALP); Exp-T (Tris-based); CaPP-T; and ALP-T (CaPP+ALP). Color changes (ΔE/ΔE00) and the bleaching index (ΔWID) were calculated, and surface (SMH) and cross-sectional microhardness (CSMH) were assessed. The two-way ANOVA and Tukey's post-hoc tests were used to compare ALP and PO43- levels; generalized linear models were used to examine: ΔE/ΔE00/SMH/CSMH; and Kruskal-Wallis and Dunn's tests were used for ΔWID (α = 5%). The ALP activity was higher at pH 9, lower in H2O2-based mediums, and similar in both thickeners. The CD-spectra indicated denaturation of the enzyme upon contact with H2O2. The PO43- levels were higher after incorporating ALP, and the ΔE/ΔE00/ΔWID were comparable among bleached groups. SMH was lower after bleaching in Exp-H, while CSMH was highest in ALP-T.
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Affiliation(s)
| | - Yendry Regina Corrales Ureña
- Faculty of Production Engineering, University of Bremen, Am Fallturm 1, 28359 Bremen, Germany
- National Laboratory of Nanotechnology LANOTEC—National Center of High Technology CeNAT, 1.3 Km North of the United States Embassy, San José 1174-1200, Costa Rica
| | - Flávio Henrique Baggio Aguiar
- Department of Restorative Dentistry, Piracicaba Dental School, University of Campinas—UNICAMP, Piracicaba 13414-903, Brazil
| | - Débora Alves Nunes Leite Lima
- Department of Restorative Dentistry, Piracicaba Dental School, University of Campinas—UNICAMP, Piracicaba 13414-903, Brazil
| | - Klaus Rischka
- Department of Restorative Dentistry, Piracicaba Dental School, University of Campinas—UNICAMP, Piracicaba 13414-903, Brazil
- Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM, 28359 Bremen, Germany
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Hao QY, Yan J, Wei JT, Zeng YH, Feng LY, Que DD, Li SC, Guo JB, Fan Y, Ding YF, Zhang XL, Yang PZ, Gao JW, Li ZH. Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway. Gut Microbes 2024; 16:2351532. [PMID: 38727248 PMCID: PMC11093026 DOI: 10.1080/19490976.2024.2351532] [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: 10/23/2023] [Accepted: 05/01/2024] [Indexed: 05/16/2024] Open
Abstract
Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.
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MESH Headings
- Animals
- Humans
- Male
- Rats
- Feces/microbiology
- Gastrointestinal Microbiome
- Inflammasomes/metabolism
- Lipopolysaccharides/metabolism
- Muscle, Smooth, Vascular/metabolism
- Muscle, Smooth, Vascular/pathology
- Myocytes, Smooth Muscle/metabolism
- NF-kappa B/metabolism
- NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
- NLR Family, Pyrin Domain-Containing 3 Protein/genetics
- Osteogenesis/drug effects
- Prevotella/metabolism
- Rats, Sprague-Dawley
- Renal Insufficiency, Chronic/complications
- Renal Insufficiency, Chronic/microbiology
- Renal Insufficiency, Chronic/pathology
- Signal Transduction
- Toll-Like Receptor 4/metabolism
- Toll-Like Receptor 4/genetics
- Vascular Calcification/metabolism
- Vascular Calcification/microbiology
- Vascular Calcification/pathology
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Affiliation(s)
- Qing-Yun Hao
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Jing Yan
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Jin-Tao Wei
- Department of Cardiology, Dongguan Hospital of Southern Medical University, Southern Medical University, Dongguan, China
| | - Yu-Hong Zeng
- Medical Apparatus and Equipment Deployment, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Li-Yun Feng
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Dong-Dong Que
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Shi-Chao Li
- Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Jing-Bin Guo
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Ying Fan
- Department of Cardiology, Dongguan Hospital of Southern Medical University, Southern Medical University, Dongguan, China
| | - Yun-Fa Ding
- Department of General Surgery, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiu-Li Zhang
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Ping-Zhen Yang
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Jing-Wei Gao
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ze-Hua Li
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
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Meza K, Biswas S, Talmor C, Baqai K, Samsonov D, Solomon S, Akchurin O. Response to oral iron therapy in children with anemia of chronic kidney disease. Pediatr Nephrol 2024; 39:233-242. [PMID: 37458800 DOI: 10.1007/s00467-023-06048-z] [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: 02/12/2023] [Revised: 05/15/2023] [Accepted: 06/01/2023] [Indexed: 11/25/2023]
Abstract
BACKGROUND Anemia is a common complication of chronic kidney disease (CKD) and oral iron is recommended as initial therapy. However, response to iron therapy in children with non-dialysis CKD has not been formally assessed. METHODS We reviewed medical records of pediatric patients with stages II-IV CKD followed in two New York metropolitan area medical centers between 2010 and 2020 and identified subjects who received oral iron therapy. Response to therapy at follow-up visits was assessed by improvement of hemoglobin, resolution of anemia by the 2012 KDIGO definition, and changes in iron status. Potential predictors of response were examined using regression analyses (adjusted for age, sex, eGFR, and center). RESULTS Study criteria were met by 65 children (median age 12 years, 35 males) with a median time between visits of 81 days. Median eGFR was 44 mL/min/1.73 m2, and 40.7% had glomerular CKD etiology. Following iron therapy, hemoglobin improved from 10.2 to 10.8 g/dL (p < 0.001), hematocrit from 31.3 to 32.8% (p < 0.001), serum iron from 49 to 66 mcg/dL (p < 0.001), and transferrin saturation from 16 to 21.4% (p < 0.001). There was no significant change in serum ferritin (55.0 to 44.9 ng/mL). Anemia (defined according to KDIGO) resolved in 29.3% of children. No improvement in hemoglobin/hematocrit was seen in 35% of children, and no transferrin saturation improvement in 26.9%. There was no correlation between changes in hemoglobin and changes in transferrin saturation/serum iron, but there was an inverse correlation between changes in hemoglobin and changes in ferritin. The severity of anemia and alkaline phosphatase at baseline inversely correlated with treatment response. CONCLUSIONS Anemia was resistant to 3 months of oral iron therapy in ~ 30% of children with CKD. Children with more severe anemia at baseline had better treatment response, calling for additional studies to refine approaches to iron therapy in children with anemia of CKD and to identify additional predictors of treatment response.
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Affiliation(s)
- Kelly Meza
- Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA
| | - Sharmi Biswas
- Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA
| | | | - Kanza Baqai
- Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA
| | | | | | - Oleh Akchurin
- Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA.
- New York-Presbyterian Hospital, New York, NY, USA.
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36
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Chen Y, Yan J, Wang X, Zhang S, Li J, Tang Y, Wang T. Fluorescent assay for alkaline phosphatase by integrating strand displacement amplification with DNAzyme-catalytic recycling cleavage of molecular beacons. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2023; 302:122984. [PMID: 37331255 DOI: 10.1016/j.saa.2023.122984] [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: 01/26/2023] [Revised: 05/14/2023] [Accepted: 06/04/2023] [Indexed: 06/20/2023]
Abstract
A fluorescence sensing method for the quantification of alkaline phosphatase (ALP) was developed by integrating the strand displacement amplification with DNAzyme-catalytic recycling cleavage of molecular beacons. ALP can hydrolyze a 3'-phosphoralated primer into a 3'-hydroxy primer which can initiate the strand displacement amplification to produce the Mg2+-dependent DNAzyme. The DNAzyme can then catalyze the cleavage of the DNA molecular beacon labeled with FAM fluorophore at its 5'-end and BHQ1 quencher at its 3'-end, turning on the fluorescence of FAM fluorophore. The content of ALP in a sample can be deduced from the measured fluorescence intensity. Due to the cascading nature of its amplification strategy, the proposed method achieved sensitive and specific ALP detection in human serum samples. Its results were in good consistent with the corresponding values obtained by a commercial ALP detection kit. The limit of detection of the proposed method for ALP is about 0.015 U/L, lower than some methods recently reported in literature, demonstrating its potential for ALP detection in biomedical research and clinical diagnosis.
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Affiliation(s)
- Yao Chen
- Hunan Key Lab of Biomedical Materials and Devices, College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou 412007, PR China; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China
| | - Jin Yan
- Hunan Key Lab of Biomedical Materials and Devices, College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou 412007, PR China
| | - Xiaozhi Wang
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China
| | - Siwei Zhang
- Hunan Key Lab of Biomedical Materials and Devices, College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou 412007, PR China
| | - Jun Li
- Hunan Key Lab of Biomedical Materials and Devices, College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou 412007, PR China
| | - Ying Tang
- Hunan Key Lab of Biomedical Materials and Devices, College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou 412007, PR China; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China.
| | - Tong Wang
- State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China.
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Priyanka, Maiti S. Co-assembly-mediated biosupramolecular catalysis: thermodynamic insights into nucleobase specific (oligo)nucleotide attachment and cleavage. J Mater Chem B 2023; 11:10383-10394. [PMID: 37874292 DOI: 10.1039/d3tb01747h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2023]
Abstract
Gaining control over the stability and cleavage of phosphoester and phosphodiester remains a matter of interest for their application in biotechnology to oligonucleotide-based therapeutics. Herein, we report an efficient unactivated phosphoester hydrolysis (stable mono/di/tri/cyclic nucleotide to nucleoside conversion) via a biosupramolecular system comprising of a non-covalent complex of enzyme, alkaline phosphatase (ALP), and Zn(II)-metallosurfactant. We also demonstrate the nucleobase selective activation or inhibition of ALP-mediated oligonucleotide digestion process using that complex. The higher binding affinity of Zn(II)-containing headgroup with phosphate-containing substrate enhanced the effective substrate concentration surrounding the enzyme, which, in turn, results in a drastic decrease in the Michaelis constant (KM), along with an increase in the turnover (kcat). The catalytic activation or inhibition of nucleobase-specific oligonucleotide digestion depends on the hydration, localization of the substrates, and viscosity of the resultant co-assembly upon substrate binding with the enzyme-metallosurfactant complex. Additionally, through isothermal titration calorimetry experiment, we demonstrate enthalpy-entropy change during both the supramolecular binding of (oligo)nucleotides and simultaneous activation/inhibition in catalytic cleavage. Overall, it showed the possible modularity of Zn(II)-mediated biosupramolecular interaction, describing intrinsic thermodynamic aspects in developing complex biocatalytic circuits with nucleobase-specific oligonucleotides inputs, which are relevant in designing nucleic acid-based cargo for drug delivery and bioimaging.
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Affiliation(s)
- Priyanka
- Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Manauli 140306, India.
| | - Subhabrata Maiti
- Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Manauli 140306, India.
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Kamei Y, Okumura Y, Adachi Y, Mori Y, Sakai M, Ohnishi K, Ohminami H, Masuda M, Yamanaka-Okumura H, Taketani Y. Humoral and cellular factors inhibit phosphate-induced vascular calcification during the growth period. J Clin Biochem Nutr 2023; 73:198-204. [PMID: 37970550 PMCID: PMC10636584 DOI: 10.3164/jcbn.23-11] [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: 02/07/2023] [Accepted: 02/25/2023] [Indexed: 11/17/2023] Open
Abstract
Hyperphosphatemia is an independent and non-classical risk factor of cardiovascular disease and mortality in patients with chronic kidney disease (CKD). Increased levels of extracellular inorganic phosphate (Pi) are known to directly induce vascular calcification, but the detailed underlying mechanism has not been clarified. Although serum Pi levels during the growth period are as high as those observed in hyperphosphatemia in adult CKD, vascular calcification does not usually occur during growth. Here, we have examined whether the defence system against Pi-induced vascular calcification can exist during the growth period using mice model. We found that calcification propensity of young serum (aged 3 weeks) was significantly lower than that of adult serum (10 months), possibly due to high fetuin-A levels. In addition, when the aorta was cultured in high Pi medium in vitro, obvious calcification was observed in the adult aorta but not in the young aorta. Furthermore, culture in high Pi medium increased the mRNA level of tissue-nonspecific alkaline phosphatase (TNAP), which degrades pyrophosphate, only in the adult aorta. Collectively, our findings indicate that the aorta in growing mouse may be resistant to Pi-induced vascular calcification via a mechanism in which high serum fetuin-A levels and suppressed TNAP expression.
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Affiliation(s)
- Yuki Kamei
- Department of Clinical Nutrition and Food Management, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
- Department of Food and Nutrition, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Yosuke Okumura
- Department of Clinical Nutrition and Food Management, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Yuichiro Adachi
- Department of Clinical Nutrition and Food Management, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Yuki Mori
- Department of Clinical Nutrition and Food Management, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Maiko Sakai
- Department of Clinical Nutrition and Food Management, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Kohta Ohnishi
- Department of Clinical Nutrition and Food Management, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Hirokazu Ohminami
- Department of Clinical Nutrition and Food Management, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Masashi Masuda
- Department of Clinical Nutrition and Food Management, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Hisami Yamanaka-Okumura
- Department of Clinical Nutrition and Food Management, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
- Department of Food Science and Nutrition, Doshisha Women’s College of Liberal Arts, Teramachi Nishi-iru, Imadegawa-dori, Kamigyo-ku, Kyoto 602-0893, Japan
| | - Yutaka Taketani
- Department of Clinical Nutrition and Food Management, Tokushima University Graduate School of Medical Nutrition, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
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Wang C, Liang Q, He S, Zhu J, Lin X, Lin G, Wu D, Zhang W, Wang Z. Role of inflammation and immunity in vascular calcification: a bibliometric and visual analysis, 2000-2022. Front Cardiovasc Med 2023; 10:1258230. [PMID: 37965089 PMCID: PMC10642504 DOI: 10.3389/fcvm.2023.1258230] [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: 07/13/2023] [Accepted: 10/18/2023] [Indexed: 11/16/2023] Open
Abstract
Background In recent years, a great deal of research has been done on vascular calcification (VC), and inflammation and immunity have been displayed to play important roles in the mechanism of VC. However, to date, no comprehensive or systematic bibliometric analyses have been conducted on this topic. Methods Articles and reviews on the roles of inflammation and immunity in VC were obtained from the Web of Science Core Collection on August 5, 2022. Four scientometric software packages-HistCite, CiteSpace, VOSviewer, and R-bibliometrix-were used for the bibliometric and knowledge mapping analyses. Results The obtained 1,868 papers were published in 627 academic journals by 9,595 authors of 2,217 institutions from 69 countries. The annual number of publications showed a clear growth trend. The USA and China were the most productive countries. Karolinska Institutet, Harvard University, and the University of Washington were the most active institutions. Stenvinkel P published the most articles, whereas Demer LL received the most citations. Atherosclerosis published the most papers, while Circulation was the most highly cited journal. The largest cluster among the 22 clusters, based on the analysis of co-citations, was osteo-/chondrogenic transdifferentiation. "Vascular calcification," "inflammation," "chronic kidney disease," and "expression" were the main keywords in the field. The keyword "extracellular vesicle" attracted great attention in recent years with the strongest citation burst. Conclusions Osteo-/chondrogenic transdifferentiation is the primary research topic in this field. Extracellular vesicles are expected to become a new research focus for exploring the inflammatory and immune mechanisms of VC.
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Affiliation(s)
- Chen Wang
- Department of Anesthesiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Qingchun Liang
- Department of Anesthesiology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China
| | - Siyi He
- Department of Anesthesiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Jie Zhu
- Department of Anesthesiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Xiafei Lin
- Department of Anesthesiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Guanwen Lin
- Department of Anesthesiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Duozhi Wu
- Department of Anesthesiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Wenqi Zhang
- Department of Anesthesiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Zhihua Wang
- Department of Anesthesiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
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Deng Y, Jiang T, Li J, Yu P, Mei Y, Li M, Qi X, Liu F. Serum iron fluctuations link ferroptosis process with mortality and prognosis of acute pancreatitis. iScience 2023; 26:107774. [PMID: 37727733 PMCID: PMC10505981 DOI: 10.1016/j.isci.2023.107774] [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: 10/31/2022] [Revised: 04/14/2023] [Accepted: 08/26/2023] [Indexed: 09/21/2023] Open
Abstract
Recently, the existence of ferroptosis has been confirmed in chronic pancreatitis. However, its role in acute pancreatitis (AP) process, especially in critical status, has not yet been mentioned. To verify this hypothesis, we included 873 AP patients (training set) and 1,188 NAFLD patients (internal validation set) selected from MIMIC-III (Medical Information Mark for Intensive Care) database and 218 AP patients (external validation set) in Linshui County People's Hospital ICU data. We analyzed the correlation between mortality and ferroptosis associating factors (such as serum iron, ALP, lactate, etc.) in them through regression analysis. In addition, to test the significance of these factors, the nomogram, AUC, and DCA analysis were applied. The results showed that serum iron, IBC, ALP, and lactate (p < 0.05) were independent factors for the mortality and prognosis of these patients. These correlations suggest ferroptosis and follow-up cell programmed death may own an important clinical interference significance among this population.
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Affiliation(s)
- Yueling Deng
- Health Management Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Tao Jiang
- Health Management Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jinhao Li
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Pingping Yu
- Health Management Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ying Mei
- Health Management Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Maojun Li
- Linshui County People Hospital, Guangan, Sichuan, China
| | - Xiaoya Qi
- Health Management Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Fuyao Liu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Wei J, Li Z, Fan Y, Feng L, Zhong X, Li W, Guo T, Ning X, Li Z, Ou C. Lactobacillus rhamnosus GG aggravates vascular calcification in chronic kidney disease: A potential role for extracellular vesicles. Life Sci 2023; 331:122001. [PMID: 37625519 DOI: 10.1016/j.lfs.2023.122001] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 07/24/2023] [Accepted: 08/01/2023] [Indexed: 08/27/2023]
Abstract
AIMS Lactobacillus rhamnosus GG (LGG) is a probiotic with great promise in future clinical application, which can significantly promote bone formation. However, the effect of LGG on CKD-related vascular calcification is unclear. In this study, we aimed to investigate the effect of LGG on CKD-related vascular calcification. MATERIALS AND METHODS After 2 weeks of 5/6 nephrectomy, CKD rats received a special diet (4 % calcium and 1.8 % phosphate) combined with 1,25-dihydroxyvitamin D3 to induce vascular calcification. Meanwhile, CKD rats in the LGG group were gavaged orally with LGG (1 × 109 CFU bacteria/day). 16S RNA amplicon sequencing was performed to analyze the effect of LGG treatment on gut microbiota composition. Furthermore, differential ultracentrifugation was utilized to extract EVs. The effects of EVs on vascular calcification were evaluated in rat VSMCs, rat aortic rings, and CKD rat calcification models. In this study, vascular calcification was assessed by microcomputed tomography analysis, alizarin red staining, calcium content determination, and the expression of osteogenic transcription factors RUNX2 and BMP2. KEY FINDINGS LGG remarkably aggravated vascular calcification. LGG supplementation significantly altered gut microbiota composition in CKD rats, particularly increasing Lactobacillus. Interestingly, EVs presented a significant promoting effect on the development of calcification. Finally, mechanistic analysis proved that EVs aggravated vascular calcification through PI3K/AKT signaling. SIGNIFICANCE These results do not support the supplementation of LGG in CKD-associated vascular calcification patients. Our study presented a fresh perspective on LGG with potential risks and adverse effects. CKD patients should use specific probiotic strains cautiously.
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Affiliation(s)
- Jintao Wei
- The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Dongguan 523018, PR China
| | - Zehua Li
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Ying Fan
- The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Dongguan 523018, PR China
| | - Liyun Feng
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Xinglong Zhong
- Department of Cardiology, The Fourth Affiliated Hospital of Guangxi Medical University/Liuzhou Workers' Hospital, Liuzhou, PR China
| | - Weirun Li
- The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Dongguan 523018, PR China
| | - Tingting Guo
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China
| | - Xiaodong Ning
- The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Dongguan 523018, PR China
| | - Zhenhua Li
- The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Dongguan 523018, PR China.
| | - Caiwen Ou
- The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Dongguan 523018, PR China.
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Al-Dhalimy AMB, Salim HM, Shather AH, Naser IH, Hizam MM, Alshujery MK. The pathological and therapeutically role of mesenchymal stem cell (MSC)-derived exosome in degenerative diseases; Particular focus on LncRNA and microRNA. Pathol Res Pract 2023; 250:154778. [PMID: 37683391 DOI: 10.1016/j.prp.2023.154778] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 08/17/2023] [Accepted: 08/20/2023] [Indexed: 09/10/2023]
Abstract
By releasing exosomes, which create the ideal milieu for the resolution of inflammation, mesenchymal stem cells (MSCs) enhance tissue healing and have strong immunomodulatory capabilities. MSCs-derived exosome also can affect tumor progress by a myriad of mechanisms. Exosomes function as a cell-cell communication tool to affect cellular activity in recipient cells and include an array of efficient bioactive chemicals. Understanding the fundamental biology of inflammation ablation, tissue homeostasis, and the creation of therapeutic strategies is particularly interested in the horizontal transfer of exosomal long non-coding RNAs (lncRNA) and microRNAs (miRNAs) to recipient cells, where they affect target gene expression. Herein, we propose an exosomal lncRNA and microRNA profile in neurological, renal, cardiac, lung, and liver diseases as well as skin wounds and arthritis.
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Affiliation(s)
| | - Haitham Mukhlif Salim
- Ministry of Health, Directorat of the Public Health, Health Promotion Departments, Baghdad, Iraq
| | - A H Shather
- Department of Computer Engineering Technology, Al Kitab University, Altun Kopru, Kirkuk 00964, Iraq
| | - Israa Habeeb Naser
- Medical Laboratories Techniques Department, AL-Mustaqbal University, 51001 Hillah, Babil, Iraq
| | - Manar Mohammed Hizam
- Collage of Pharmacy, National University of Science and Technology, Dhi Qar, Iraq
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Xue X, Li JX, Wang JW, Lin LM, Cheng H, Deng DF, Xu WC, Zhao Y, Zou XR, Yuan J, Zhang LX, Zhao MH, Wang XQ. Association between alkaline phosphatase/albumin ratio and the prognosis in patients with chronic kidney disease stages 1-4: results from a C-STRIDE prospective cohort study. Front Med (Lausanne) 2023; 10:1215318. [PMID: 37799589 PMCID: PMC10548241 DOI: 10.3389/fmed.2023.1215318] [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: 05/08/2023] [Accepted: 08/11/2023] [Indexed: 10/07/2023] Open
Abstract
Background The alkaline phosphatase-to-albumin ratio (APAR) has been demonstrated to be a promising non-invasive biomarker for predicting prognosis in certain diseases. However, the relationship between APAR and prognosis in non-dialysis chronic kidney disease (CKD) patients remains unclear. This study aims to identify the association between APAR and prognosis among CKD stages 1-4 in China. Methods Patients with CKD stages 1-4 were consecutively recruited from 39 clinical centers in China from 2011 to 2016. New occurrences of end-stage kidney disease (ESKD), major adverse cardiovascular and cerebrovascular events, and all-cause deaths were the outcome events of this study. Subdistribution hazard competing risk and Cox proportional hazards regression models were adopted. Results A total of 2,180 participants with baseline APAR values were included in the analysis. In the primary adjusted analyses, higher APAR level [per 1-standard deviation (SD) increase in natural logarithm transformed (ln-transformed) APAR] was associated with 33.5% higher risk for all-cause deaths [adjusted hazard ratio (HR) 1.335, 95% confidence interval (CI) 1.068-1.670]. In addition, there was evidence for effect modification of the association between APAR and ESKD by baseline estimated glomerular filtration rate (eGFR) (P interaction < 0.001). A higher APAR level (per 1-SD increase in ln-transformed APAR) was associated with a greater risk of ESKD among participants with eGFR ≥ 60 ml/min/1.73 m2 (adjusted SHR 1.880, 95% CI 1.260-2.810) but not in eGFR < 60 ml/min/1.73 m2. Conclusion Higher APAR levels in patients with CKD stages 1-4 seemed to be associated with an increased risk of all-cause death. Thus, APAR appears to be used in risk assessment for all-cause death among patients with CKD stages 1-4.
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Affiliation(s)
- Xue Xue
- The First Clinical Medical School, Hubei University of Chinese Medicine, Wuhan, China
| | - Jia-Xuan Li
- School of Clinical Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
| | - Jin-Wei Wang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, National Health Commission of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - La-Mei Lin
- Department of Nephrology, Affiliated Hospital of Hubei University of Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Hong Cheng
- Department of Nephrology, Affiliated Hospital of Hubei University of Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Dan-Fang Deng
- Department of Nephrology, Affiliated Hospital of Hubei University of Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Wen-Cheng Xu
- Department of Nephrology, Affiliated Hospital of Hubei University of Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Yu Zhao
- Department of Nephrology, Affiliated Hospital of Hubei University of Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Xin-Rong Zou
- Department of Nephrology, Affiliated Hospital of Hubei University of Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Jun Yuan
- Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Lu-Xia Zhang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, National Health Commission of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
- National Institute of Health Data Science at Peking University, Beijing, China
| | - Ming-Hui Zhao
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
- Institute of Nephrology, Peking University, Beijing, China
- Key Laboratory of Renal Disease, National Health Commission of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, China
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiao-Qin Wang
- Department of Nephrology, Affiliated Hospital of Hubei University of Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
- Hubei Key Laboratory of Theory and Application Research of Liver and Kidney in Traditional Chinese Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
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Song Y, Huang C, Li Y. Nanozyme Rich in Oxygen Vacancies Derived from Mn-Based Metal-Organic Gel for the Determination of Alkaline Phosphatase. Inorg Chem 2023; 62:12697-12707. [PMID: 37526919 DOI: 10.1021/acs.inorgchem.3c01020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2023]
Abstract
Vacancy engineering as an effective strategy has been widely employed to regulate the enzyme-mimic activity of nanomaterials by adjusting the surface, electronic structure, and creating more active sites. Herein, we purposed a facile and simple method to acquire transition metal manganese oxide rich in oxygen vacancies (OVs-Mn2O3-400) by pyrolyzing the precursor of the Mn(II)-based metal-organic gel directly. The as-prepared OVs-Mn2O3-400 exhibited superior oxidase-like activity as oxygen vacancies participated in the generation of O2•-. Besides, steady state kinetic constant (Km) and catalytic kinetic constant (Ea) suggested that OVs-Mn2O3-400 had a stronger affinity toward 3,3',5,5'-tetramethylbenzidine and possessed prominent catalytic performance. By taking 2-phospho-l-ascorbic acid as the substrate, which can be converted into reducing substance ascorbic acid in the presence of alkaline phosphatase (ALP), OVs-Mn2O3-400 can be applied as an efficient nanozyme for ALP colorimetric analysis without the help of destructive H2O2. The colorimetric sensor established by OVs-Mn2O3-400 for ALP detection showed a good linearity from 0.1 to 12 U/L and a lower limit of detection of 0.054 U/L. Our work paves the way for designing enhanced enzyme-like activity nanozymes, which is of significance in biosensing.
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Affiliation(s)
- Yunfei Song
- Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, P. R. China
| | - Chengzhi Huang
- Key Laboratory of Luminescent and Real-Time Analytical System (Southwest University), Chongqing Science and Technology Bureau, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, P. R. China
| | - Yuanfang Li
- Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, P. R. China
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Ye T, Deng B, Bai L, Luo X, Yuan M, Cao H, Hao L, Wu X, Yin F, Li Z, Xu F. Butanol accelerated entropy-driven DNA walking machine for rapid and ultrasensitive determination of alkaline phosphatase activity. Talanta 2023; 265:124879. [PMID: 37392708 DOI: 10.1016/j.talanta.2023.124879] [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: 04/16/2023] [Revised: 06/03/2023] [Accepted: 06/22/2023] [Indexed: 07/03/2023]
Abstract
Alkaline phosphatase (ALP) as an important biomarker as well as an index for the pasteurization degree of dairy food. However, there is a dilemma between the sensitivity and time-cost of ALP determination based on nucleic acid amplification approach. Herein, an ultrasensitive and rapid detection method for the ALP assay was developed based on entropy-driven DNA machine. In our design, the ALP catalyzed dephosphorylation of detection probe, which inhibited the digestion effect of lambda exonuclease. The remaining probe as a linker to tether the walking strand proximity to the surface of track strand modified gold nanoparticle, activating entropy-driven DNA machine. Accompany with walking strand moving, a large amount of assembled dye-labelled strand dissociated from gold nanoparticle with fluorescence recovery. More importantly, to further improve the walking efficiency, butanol was introduced to accelerated the signal amplification at interface, which short the incubation time from several hours to 5 min. Under the optimum condition, the change of fluorescence intensity was proportion to the concentration of ALP in the range from 0.05 U L-1 to 5 U L-1 with an ultralow limit of detection of 2.07 × 10-3 U L-1 was achieved, which is superior to other reported methods. Furthermore, the proposed method also successfully applied for the spiked milk sample assay with satisfactory recovery in the range of 98.83%-103.00%. This work proposed a new strategy for the application of entropy-driven DNA machine in the field of rapid and ultrasensitive detection.
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Affiliation(s)
- Tai Ye
- Shanghai Engineering Research Center for Food Rapid Detection, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China
| | - Bitao Deng
- Shanghai Engineering Research Center for Food Rapid Detection, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China
| | - Long Bai
- Shanghai Engineering Research Center for Food Rapid Detection, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China
| | - Xiaorong Luo
- Shanghai Engineering Research Center for Food Rapid Detection, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China
| | - Min Yuan
- Shanghai Engineering Research Center for Food Rapid Detection, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China
| | - Hui Cao
- Shanghai Engineering Research Center for Food Rapid Detection, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China
| | - Liling Hao
- Shanghai Engineering Research Center for Food Rapid Detection, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China
| | - Xiuxiu Wu
- Shanghai Engineering Research Center for Food Rapid Detection, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China
| | - Fengqin Yin
- Shanghai Engineering Research Center for Food Rapid Detection, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China
| | - Zefan Li
- Shanghai Engineering Research Center for Food Rapid Detection, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China
| | - Fei Xu
- Shanghai Engineering Research Center for Food Rapid Detection, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
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Zang X, Qin W, Xiong Y, Xu A, Huang H, Fang T, Zang X, Chen M. Using three statistical methods to analyze the association between aldehyde exposure and markers of inflammation and oxidative stress. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023:10.1007/s11356-023-27717-4. [PMID: 37286832 DOI: 10.1007/s11356-023-27717-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 05/13/2023] [Indexed: 06/09/2023]
Abstract
BACKGROUND Exposure to aldehydes has been linked to adverse health outcomes such as inflammation and oxidative stress, but research on the effects of these compounds is limited. This study is aimed at assessing the association between aldehyde exposure and markers of inflammation and oxidative stress. METHODS The study used data from the NHANES 2013-2014 survey (n = 766) and employed multivariate linear models to investigate the relationship between aldehyde compounds and various markers of inflammation (alkaline phosphatase (ALP) level, absolute neutrophil count (ANC), and lymphocyte count) and oxidative stress (bilirubin, albumin, and iron levels) while controlling for other relevant factors. In addition to generalized linear regression, weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) analyses were applied to examine the single or overall effect of aldehyde compounds on the outcomes. RESULTS In the multivariate linear regression model, each 1 standard deviation (SD) change in propanaldehyde and butyraldehyde was significantly associated with increases in serum iron levels (beta and 95% confidence interval, 3.25 (0.24, 6.27) and 8.40 (0.97, 15.83), respectively) and the lymphocyte count (0.10 (0.04, 0.16) and 0.18 (0.03, 0.34), respectively). In the WQS regression model, a significant association was discovered between the WQS index and both the albumin and iron levels. Furthermore, the results of the BKMR analysis showed that the overall impact of aldehyde compounds was significantly and positively correlated with the lymphocyte count, as well as the levels of albumin and iron, suggesting that these compounds may contribute to increased oxidative stress. CONCLUSIONS This study reveals the close association between single or overall aldehyde compounds and markers of chronic inflammation and oxidative stress, which has essential guiding value for exploring the impact of environmental pollutants on population health.
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Affiliation(s)
- Xiaodong Zang
- Department of Pediatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China
| | - Wengang Qin
- Department of Pediatrics, Provincial Hospital Affiliated to Anhui Medical University, Hefei, 230001, Anhui, China
| | - Yingying Xiong
- Department of Pediatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China
| | - Anlan Xu
- Department of Pediatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China
| | - Hesuyuan Huang
- Orthopedics Department, Peking University Shougang Hospital, Beijing, 100144, China
| | - Tao Fang
- Department of Pediatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China
| | - Xiaowei Zang
- College of Safety Science and Engineering, Nanjing Tech University, Nanjing, 211816, China
| | - Mingwu Chen
- Department of Pediatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
- Department of Pediatrics, Provincial Hospital Affiliated to Anhui Medical University, Hefei, 230001, Anhui, China.
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Kim TH, Park SY, Shin JH, Lee S, Joo KB, Koo BS. Association between changes in serum alkaline phosphatase levels and radiographic progression in ankylosing spondylitis. Sci Rep 2023; 13:9093. [PMID: 37277451 PMCID: PMC10241912 DOI: 10.1038/s41598-023-36340-9] [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: 12/11/2022] [Accepted: 06/01/2023] [Indexed: 06/07/2023] Open
Abstract
This retrospective study evaluated the electronic medical records of patients with ankylosing spondylitis (AS) (January 2001-December 2018) to determine the relationship between serum alkaline phosphatase (ALP) levels and radiographic changes over time. Longitudinal data, including serum ALP levels, were imputed by linear interpolation at 3-month intervals. Among the serum ALP levels calculated for 8 years prior to modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) measurement, those having the highest beta coefficient with the mSASSS were selected in the correlation between ALP and longitudinal mSASSS. Linear mixed models with the selected serum ALP levels, mSASSS, and clinical variables were investigated. We included 1122 patients (mean follow-up, 8.20 [standard deviation: 2.85] years). The serum ALP level from 5 years and 3 months prior showed the highest beta coefficient with the mSASSS. In the linear mixed model, the serum ALP level at 5 years and 3 months before radiographic changes was significantly associated with the mSASSS (β = 0.021, 95% confidence interval: 0.017-0.025, p < 0.001). Serum ALP levels measured approximately 5 years before may be a surrogate marker for predicting spinal radiographic changes. Long-term prospective clinical and experimental studies of > 5 years are required for biomarker discovery or therapeutic research on AS radiographic progression.
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Affiliation(s)
- Tae-Hwan Kim
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea
| | - Seo Young Park
- Department of Statistics and Data Science, Korea National Open University, Seoul, South Korea
| | - Ji Hui Shin
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea
| | - Seunghun Lee
- Department of Radiology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea
| | - Kyung Bin Joo
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea
| | - Bon San Koo
- Division of Rheumatology, Department of Internal Medicine, Inje University Seoul Paik Hospital, Inje University College of Medicine, 9, Mareunnae-ro, Jung-gu, Seoul, 04551, South Korea.
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48
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Torregrosa JV, Bover J, Rodríguez Portillo M, González Parra E, Dolores Arenas M, Caravaca F, González Casaus ML, Martín-Malo A, Navarro-González JF, Lorenzo V, Molina P, Rodríguez M, Cannata Andia J. Recommendations of the Spanish Society of Nephrology for the management of mineral and bone metabolism disorders in patients with chronic kidney disease: 2021 (SEN-MM). Nefrologia 2023; 43 Suppl 1:1-36. [PMID: 37202281 DOI: 10.1016/j.nefroe.2023.03.003] [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: 02/17/2022] [Accepted: 03/26/2022] [Indexed: 05/20/2023] Open
Abstract
As in 2011, when the Spanish Society of Nephrology (SEN) published the Spanish adaptation to the Kidney Disease: Improving Global Outcomes (KDIGO) universal Guideline on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), this document contains an update and an adaptation of the 2017 KDIGO guidelines to our setting. In this field, as in many other areas of nephrology, it has been impossible to irrefutably answer many questions, which remain pending. However, there is no doubt that the close relationship between the CKD-MBD/cardiovascular disease/morbidity and mortality complex and new randomised clinical trials in some areas and the development of new drugs have yielded significant advances in this field and created the need for this update. We would therefore highlight the slight divergences that we propose in the ideal objectives for biochemical abnormalities in the CKD-MBD complex compared to the KDIGO suggestions (for example, in relation to parathyroid hormone or phosphate), the role of native vitamin D and analogues in the control of secondary hyperparathyroidism and the contribution of new phosphate binders and calcimimetics. Attention should also be drawn to the adoption of important new developments in the diagnosis of bone abnormalities in patients with kidney disease and to the need to be more proactive in treating them. In any event, the current speed at which innovations are taking place, while perhaps slower than we might like, globally drives the need for more frequent updates (for example, through Nefrología al día).
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Affiliation(s)
| | - Jordi Bover
- Hospital Germans Trias i Pujol, Badalona, Spain
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Yang YS, Yu SS, Chen MY, Zuo D, Luo Y, Qiang T, Ma H, Yang XF, Ma YB, Wang XH, Zhao ZY, Dong LY. Functionalized pyrite nanozyme probe and imprinted polymer modified with hydrophilic layer for rapid colorimetric analysis of glycoprotein in serum. Talanta 2023; 261:124665. [PMID: 37209585 DOI: 10.1016/j.talanta.2023.124665] [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: 02/23/2023] [Revised: 05/10/2023] [Accepted: 05/11/2023] [Indexed: 05/22/2023]
Abstract
The biological molecules used in the sandwich detection method have problems such as complex extraction processes, high costs, and uneven quality. Therefore we integrated glycoprotein molecularly controllable-oriented surface imprinted magnetic nanoparticles (GMC-OSIMN) and boric acid functionalized pyrite nanozyme probe (BPNP) to replace the traditional antibody and horseradish peroxidase for sensitive detection of glycoproteins through sandwich detection. In this work, a novel nanozyme functionalized with boric acid was used to label glycoproteins that were captured by GMC-OSIMN. The substrate in the working solution catalyzed by the nanozyme labeled on the protein underwent visible color changes to the naked eye, and the generated signal can be quantitatively detected by a spectrophotometer, and the best color development conditions of the novel nanozyme under the influence of many factors were determined through multi-dimensional investigation. The optimum conditions of sandwich are optimized with ovalbumin (OVA), and it was extended to the detection of transferrin (TRF) and alkaline phosphatase (ALP) in the application. The detection range for TRF was 2.0 × 10-1-1.0 × 104 ng mL-1 with a detection limit of 1.32 × 10-1 ng mL-1, The detection range for ALP was 2.0 × 10-3-1.0 × 102 U L-1 with the detection limit of 1.76 × 10-3 U L-1. This method was subsequently used to detect TRF and ALP levels in 16 liver cancer patients, and the standard deviation of the test results of each patient was less than 5.7%.
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Affiliation(s)
- Yuan-Shuo Yang
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China; NHC Key Laboratory of Hormones and Development / Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital / Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300134, China
| | - Shi-Song Yu
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China; NHC Key Laboratory of Hormones and Development / Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital / Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300134, China
| | - Meng-Ying Chen
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China; NHC Key Laboratory of Hormones and Development / Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital / Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300134, China
| | - Duo Zuo
- Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
| | - Yi Luo
- Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China
| | - Titi Qiang
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China
| | - Hui Ma
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China
| | - Xiao-Feng Yang
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China
| | - Yu-Bo Ma
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China
| | - Xian-Hua Wang
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China.
| | - Zhen-Yu Zhao
- NHC Key Laboratory of Hormones and Development / Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital / Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300134, China.
| | - Lin-Yi Dong
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China.
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Cai M, Zhang Y, Cao Z, Lin W, Lu N. DNA-Programmed Tuning of the Growth and Enzyme-Like Activity of a Bimetallic Nanozyme and Its Biosensing Applications. ACS APPLIED MATERIALS & INTERFACES 2023; 15:18620-18629. [PMID: 37017457 DOI: 10.1021/acsami.2c21854] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/19/2023]
Abstract
Nanozymes, which combine the merits of both nanomaterials and natural enzymes, have aroused tremendous attention as new representatives of artificial enzyme mimics. However, it still remains to be a great challenge to rationally engineer the morphologies and surface properties of nanostructures that lead to the desired enzyme-like activities. Here, we report a DNA-programming seed-growth strategy to mediate the growth of platinum nanoparticles (PtNPs) on gold bipyramids (AuBPs) for the synthesis of a bimetallic nanozyme. We find that the preparation of a bimetallic nanozyme is in a sequence-dependent manner, and the encoding of a polyT sequence allows the successful formation of bimetallic nanohybrids with greatly enhanced peroxidase-like activity. We further observe that the morphologies and optical properties of T15-mediated Au/Pt nanostructures (Au/T15/Pt) change over the reaction time, and the nanozymatic activity can be tuned by controlling the experimental conditions. As a concept application, Au/T15/Pt nanozymes are used to establish a simple, sensitive, and selective colorimetric assay for the determination of ascorbic acid (AA), alkaline phosphatase (ALP), and the inhibitor sodium vanadate (Na3VO4), demonstrating excellent analytical performance. This work provides a new avenue for the rational design of bimetallic nanozymes for biosensing applications.
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Affiliation(s)
- Mengchao Cai
- School of Materials Science and Engineering, Shanghai University of Engineering Science, Shanghai 201620, China
| | - Yunqing Zhang
- School of Materials Science and Engineering, Shanghai University of Engineering Science, Shanghai 201620, China
| | - Zhongxu Cao
- School of Materials Science and Engineering, Shanghai University of Engineering Science, Shanghai 201620, China
| | - Wensong Lin
- School of Materials Science and Engineering, Shanghai University of Engineering Science, Shanghai 201620, China
| | - Na Lu
- School of Materials Science and Engineering, Shanghai University of Engineering Science, Shanghai 201620, China
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