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Hong S, Wang H, Qiao L. The Role of miR-144 in Inflammatory Diseases: A Review. Immun Inflamm Dis 2025; 13:e70172. [PMID: 40067024 PMCID: PMC11894823 DOI: 10.1002/iid3.70172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 02/08/2025] [Accepted: 02/27/2025] [Indexed: 03/15/2025] Open
Abstract
BACKGROUND Inflammation, often caused by various stimuli, is a common response to tissue homeostasis disruptions and is considered a key driver of many pathological conditions. MicroRNA-144 (miR-144) has emerged as a critical regulator in inflammatory diseases, with its dysregulation implicated in various pathological conditions. Understanding its role and mechanisms is essential for developing therapeutic strategies. OBJECTIVE This article aimed to evaluate the role of miR-144 in inflammatory diseases through a literature review. METHODS Electronic databases including PubMed, Web of Science, Springer Link, China Knowledge Resource Integrated Database, and Wanfang Data were searched for relevant literature. The following keywords were used and combined differently according to the rules of the databases: "miR-144," "inflammation," "inflammatory," and "immune response." Studies investigating miR-144 in the context of inflammation were included. Data were extracted to assess miR-144's expression patterns and its association with disease severity and outcomes. RESULTS miR-144 was found to be differentially expressed in a range of inflammatory diseases, including sepsis, infectious diseases, respiratory diseases, cardiovascular diseases, digestive diseases, neuropsychiatric diseases, arthritis, and pregnancy complications. The expression patterns varied depending on the disease, with both upregulation and downregulation observed. miR-144 was implicated in the modulation of inflammatory responses through direct and indirect targeting of key proteins and pathways. The review also highlighted the potential of miR-144 as a diagnostic and prognostic biomarker. CONCLUSION miR-144 plays a significant role in the pathogenesis of inflammatory diseases and holds promise as a biomarker. Its expression patterns and regulatory mechanisms offer insights into disease processes and may guide future therapeutic strategies. However, further clinical studies are needed to validate miR-144's utility as a biomarker and to explore its therapeutic potential in a clinical setting.
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Affiliation(s)
- Shukun Hong
- Department of Intensive Care UnitShengli Oilfield Central HospitalDongyingShandongChina
- Clinical Research Center of Dongying Critical Care MedicineDongyingShandongChina
| | - Hongye Wang
- Department of Obstetrics and GynecologyShengli Oilfield Central HospitalDongyingShandongChina
| | - Lujun Qiao
- Department of Intensive Care UnitShengli Oilfield Central HospitalDongyingShandongChina
- Clinical Research Center of Dongying Critical Care MedicineDongyingShandongChina
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Zhou S, Hu Y, Liu L, Li L, Deng F, Mo L, Huang H, Liang Q. Extract of Nanhaia speciosa J. Compton & Schrire alleviates LPS-induced acute lung injury via the NF-κB/Nrf2/AQPs pathway. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:118831. [PMID: 39278292 DOI: 10.1016/j.jep.2024.118831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 08/24/2024] [Accepted: 09/13/2024] [Indexed: 09/18/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Nanhaia speciosas J. Compton & Schrire (the name Nanhaia speciosas J. Compton & Schrire has been accepted by the World Checklist of Vascular Plants https://www.worldfloraonline.org/taxon/wfo-0001444004) is a traditional Zhuang medicine that have been widely used for centuries. It has been used in the treatment of lung inflammation, tuberculosis, rheumatic pain, lumbar muscle strain, and various other ailments, such as chronic hepatitis, menoxenia, leukorrhea, and injuries. In addition, N. speciosa has also been used to treat acute lung injury (ALI). AIM OF THE STUDY The objective of this study was to conduct a comparative analysis of the effects of various constituents present in N. speciosas extract (NSE) on ALI and the related mechanisms while also elucidating the potential active monomeric components. MATERIALS AND METHODS NSE was extracted using an AB-8 macroporous resin column, and five fractions (Fr. 0%, 25%, 50%, 75% and 95%) were obtained. The anti-inflammatory and antioxidant capacities of the five fractions were evaluated in an A549 cell-based in vitro model, with the aim of evaluating their potential therapeutic effects. The anti-inflammatory and antioxidant capacities of NSE were assessed in a murine model of ALI induced by intratracheal injection of LPS. We utilized an in vitro model to analyse the critical molecular mechanisms through which NSE ameliorates ALI. The chemical composition of the optimal fraction was analysed and confirmed using UHPLC/MS. RESULTS Different fractions (especially Fr. 75%) significantly reduced inflammation and oxidative stress in A549 cells. Fr.75% abrogated LPS-induced pathological alterations and decreased the lung W/D ratio, total protein concentration in BALF, and the levels of the proinflammatory factors TNF-α, IL-6, and IL-1β. Moreover, Fr.75% reduced MPO and MDA concentrations and elevated SOD and GSH concentrations in pulmonary tissues. Additionally, it decreased the pulmonary tissue inflammation caused by LPS by downregulating the expression of p-NF-κB p65 and upregulating the expression of Nrf2, AQP1 and AQP5. Fr. 75% decreased p-NF-κB p65 protein levels; increased Keap1, Nrf2, HO-1, NQO1, AQP1 and AQP5 protein levels; and promoted the entry of Nrf2 into the nucleus. After UHPLC/MS analysis was conducted, the flavonoid Maackiain was determined to potentially play a pivotal role in this process. CONCLUSION Fr.75% alleviates ALI by regulating the NF-κB/Nrf2/AQPs signalling pathway. The flavonoid Maackiain may also play an important role in this process. Overall, N. speciosas may be a potential therapeutic agent for the prevention and treatment of ALI.
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Affiliation(s)
- Shiyao Zhou
- Guilin Medical University, Guilin, 541199, China
| | - Yuting Hu
- Guilin Medical University, Guilin, 541199, China
| | - Lihua Liu
- Guilin Medical University, Guilin, 541199, China
| | - Lilan Li
- Guilin Medical University, Guilin, 541199, China
| | - Fang Deng
- Guilin Medical University, Guilin, 541199, China
| | - Luhe Mo
- Guilin Medical University, Guilin, 541199, China
| | - Huixue Huang
- Guilin Medical University, Guilin, 541199, China; Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, Guilin, 541199, China; Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Nanning, 530200, China.
| | - Qiuyun Liang
- Guilin Medical University, Guilin, 541199, China; Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation, Guilin, 541199, China.
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Cao L, Du M, Cai M, Feng Y, Miao J, Sun J, Song J, Du B. Neutrophil membrane-coated nanoparticles for targeted delivery of toll-like receptor 4 siRNA ameliorate LPS-induced acute lung injury. Int J Pharm 2025; 668:124960. [PMID: 39551221 DOI: 10.1016/j.ijpharm.2024.124960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 10/29/2024] [Accepted: 11/13/2024] [Indexed: 11/19/2024]
Abstract
Pulmonary delivery of small interfering RNAs (siRNAs) is an effective treatment for acute lung injury (ALI), which can modulate the expression of pro-inflammatory cytokines and alleviate the symptoms of ALI. However, the rapid degradation of siRNA in vivo and its limited ability to target and validate cells are important challenges it faces in clinical practice. In this work, we developed neutrophil membrane-coated Poly (lactic-co-glycolic acid) nanoparticles loaded with TLR4 siRNA (si-TLR4) (Neutrophil-NP-TLR4), which can target both inflammatory and macrophage cells to alleviate the pulmonary inflammation in lipopolysaccharide (LPS)-induced ALI mice. These Neutrophil-NP-TLR4 effectively reduce the TNF-α and IL-1β expressions both in vitro and in vivo. Meanwhile, they also reduced the expression of TLR4, and its downstream genes including TNF receptor-associated factor 6 (TRAF6), X-linked inhibitor of apoptosis protein (XIAP), and Nuclear Factor kappa-B (NF-κB), but elevated the levels of Aquaporin 1 (AQP1) and Aquaporin 5 (AQP5). Moreover, the Neutrophil-NP-TLR4 precisely targets the inflammatory site to attenuate the lung injury without causing toxicity to normal tissue. This system provides a promising approach to effective delivery of siRNA to precisely treat the ALI.
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Affiliation(s)
- Liang Cao
- Department of ICU, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226014, China
| | - Min Du
- Department of Anesthesiology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226014, China
| | - Mengmeng Cai
- Department of Anesthesiology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226014, China
| | - Yan Feng
- Department of Anesthesiology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226014, China
| | - Juanjuan Miao
- Department of Anesthesiology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226014, China
| | - Jiafeng Sun
- Department of Anesthesiology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226014, China
| | - Jie Song
- Department of Anesthesiology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226014, China
| | - Boxiang Du
- Department of Anesthesiology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226014, China.
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Liu L, Zhang Y, Tang XR, Jia GB, Zhou S, Yue GL, He CS. Effect of emodin on acute lung injury: a meta-analysis of preclinical trials. BMC Pulm Med 2024; 24:596. [PMID: 39623403 PMCID: PMC11613585 DOI: 10.1186/s12890-024-03406-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 11/21/2024] [Indexed: 12/06/2024] Open
Abstract
BACKGROUND Emodin has protective effects on acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). This meta-analysis intended to illustrate the efficacy of emodin on ALI/ARDS animal models. METHODS Relevant preclinical studies were searched on PubMed, EMBASE, and Web of Science. Standardized mean differences (SMDs) with corresponding confidence intervals (CIs) were used to compare lung injury scores, lung wet-to-dry weight ratios (W/D), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-18, PaO2, and PaCO2 between the treatment and control groups. The article quality was appraised using the SYRCLE tool. RESULTS Twenty one studies published between 2014 and 2023 were enrolled. Compared with the control group, emodin significantly reduced lung injury scores (SMD: -3.63; 95% CI: -4.36, -2.90; p < 0.00001), W/D ratios (SMD: -3.23; 95% CI: -4.29, -2.16; p < 0.00001), and MPO levels (SMD: -2.96; 95% CI: -3.92, -1.99; p < 0.00001). Furthermore, emodin downregulated TNF-α (SMD: -3.04; 95% CI: -3.62, -2.47; p < 0.00001), IL-1β (SMD: -3.76; 95% CI: -4.65, -2.87; p < 0.00001), IL-6 (SMD: -3.19; 95% CI: -3.95, -2.43; p < 0.00001), and IL-18 levels (SMD: -4.83; 95% CI: -6.10, -3.57; p < 0.00001). Emodin improved gas exchange dysfunction, increased PaO2 (SMD: 3.76; 95% CI: 2.41, 5.11; p < 0.00001), and decreased PaCO2 (SMD: -3.83; 95% CI: -4.90, -2.76; p < 0.00001). Sensitivity analyses and stratified analyses were conducted for outcome measures with heterogeneity. CONCLUSIONS Emodin treatment can effectively reduce the severity of ALI in animal models. Additional animal investigations and clinical trials involving human subjects are imperative.
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Affiliation(s)
- Lei Liu
- Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu Sichuan, 610000, China
- Department of Respiratory and Critical Care Medicine, Chongqing Hospital of Traditional Chinese Medicine, Jiangbei Chongqing, 400000, China
| | - Yu Zhang
- Department of Respiratory Medicine, Traditional Chinese Medicine Hospital of Renshou County, Meishan Sichuan, 620500, China
| | - Xiao-Ren Tang
- Department of Traditional Chinese Medicine, Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical University, Bishan Chongqing, 404000, China
| | - Guo-Bing Jia
- Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu Sichuan, 610000, China
| | - Shan Zhou
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu Sichuan, 610000, China
| | - Guo-Long Yue
- Department of Respiratory and Critical Care Medicine, Chongqing Hospital of Traditional Chinese Medicine, Jiangbei Chongqing, 400000, China
| | - Cheng-Shi He
- Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu Sichuan, 610000, China.
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Qiu Q, Fu F, Wu Y, Han C, Pu W, Wen L, Xia Q, Du D. Rhei Radix et Rhizoma and its anthraquinone derivatives: Potential candidates for pancreatitis treatment. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 129:155708. [PMID: 38733906 DOI: 10.1016/j.phymed.2024.155708] [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: 03/01/2024] [Revised: 04/22/2024] [Accepted: 05/02/2024] [Indexed: 05/13/2024]
Abstract
BACKGROUND Pancreatitis is a common exocrine inflammatory disease of the pancreas and lacks specific medication currently. Rhei Radix et Rhizoma (RR) and its anthraquinone derivatives (AQs) have been successively reported for their pharmacological effects and molecular mechanisms in experimental and clinical pancreatitis. However, an overview of the anti-pancreatitis potential of RR and its AQs is limited. PURPOSE To summarize and analyze the pharmacological effects of RR and its AQs on pancreatitis and the underlying mechanisms, and discuss their drug-like properties and future perspectives. METHODS The articles related to RR and its AQs were collected from the Chinese National Knowledge Infrastructure, Wanfang data, PubMed, and the Web of Science using relevant keywords from the study's inception until April first, 2024. Studies involving RR or its AQs in cell or animal pancreatitis models as well as structure-activity relationship, pharmacokinetics, toxicology, and clinical trials were included. RESULTS Most experimental studies are based on severe acute pancreatitis rat models and a few on chronic pancreatitis. Several bioactive anthraquinone derivatives of Rhei Radix et Rhizoma (RRAQs) exert local protective effects on the pancreas by maintaining pancreatic acinar cell homeostasis, inhibiting inflammatory signaling, and anti-fibrosis, and they improve systemic organ function by alleviating intestinal and lung injury. Pharmacokinetic and toxicity studies have revealed the low bioavailability and wide distribution of RRAQs, as well as hepatotoxicity and nephrotoxicity. However, there is insufficient research on the clinical application of RRAQs in pancreatitis. Furthermore, we propose effective strategies for subsequent improvement in terms of balancing effectiveness and safety. CONCLUSION RRAQs can be developed as either candidate drugs or novel lead structures for pancreatitis treatment. The comprehensive review of RR and its AQs provides references for optimizing drugs, developing therapies, and conducting future studies on pancreatitis.
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Affiliation(s)
- Qi Qiu
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Fei Fu
- Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China
| | - Yaling Wu
- Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China
| | - Chenxia Han
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Weiling Pu
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Li Wen
- State Key Laboratory of Complex, Severe, and Rare Diseases, Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100073, China
| | - Qing Xia
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Dan Du
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China; Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China.
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Zhang J, Ma B. Alpinetin alleviates LPS-induced lung epithelial cell injury by inhibiting p38 and ERK1/2 signaling via aquaporin-1. Tissue Cell 2024; 87:102305. [PMID: 38217934 DOI: 10.1016/j.tice.2024.102305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 01/03/2024] [Accepted: 01/03/2024] [Indexed: 01/15/2024]
Abstract
Alpinetin has been reported to play a protective role in lung diseases, while its special mechanisms remain indistinct. In this study, acute lung injury (ALI) model was constructed by inducing MLE-12 cells with lipopolysaccharide (LPS). Cell activity together with apoptosis was judged employing cell counting kit-8 (CCK-8), flow cytometry along with western blot. Oxidative stress levels were measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining and corresponding kits. In addition, enzyme-linked immunosorbent assay (ELISA) was to examine the levels of inflammatory factors. The protein expressions of aquaporin-1 (AQP1), p38 and extracellular signal-regulated kinase (ERK) 1/2 pathway were estimated utilizing western blot. The data showed that alpinetin increased the viability, reduced the apoptosis, oxidative stress and inflammation and inactivated p38 and ERK1/2 signaling in LPS-induced MLE-12 cells. Moreover, alpinetin also increased AQP1 expression and AQP1 knockdown reversed the impacts of alpinetin on LPS-induced MLE-12 cells. Additionally, AQP1 agonist AqF026 also exerted anti-apoptotic and anti-inflammatory activities in LPS-treated MLE-12 cells. Evidently, alpinetin may exert its protective role in LPS-induced ALI by inactivation of p38 and ERK1/2 signaling through regulating AQP1.
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Affiliation(s)
- Junjie Zhang
- Cath Lab, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Bin Ma
- Intensive Care Unit, Jinshan Branch of Shanghai Sixth People's Hospital, Shanghai 201599, China.
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Calamita G, Delporte C. Insights into the Function of Aquaporins in Gastrointestinal Fluid Absorption and Secretion in Health and Disease. Cells 2023; 12:2170. [PMID: 37681902 PMCID: PMC10486417 DOI: 10.3390/cells12172170] [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: 07/01/2023] [Revised: 08/16/2023] [Accepted: 08/17/2023] [Indexed: 09/09/2023] Open
Abstract
Aquaporins (AQPs), transmembrane proteins permeable to water, are involved in gastrointestinal secretion. The secretory products of the glands are delivered either to some organ cavities for exocrine glands or to the bloodstream for endocrine glands. The main secretory glands being part of the gastrointestinal system are salivary glands, gastric glands, duodenal Brunner's gland, liver, bile ducts, gallbladder, intestinal goblet cells, exocrine and endocrine pancreas. Due to their expression in gastrointestinal exocrine and endocrine glands, AQPs fulfill important roles in the secretion of various fluids involved in food handling. This review summarizes the contribution of AQPs in physiological and pathophysiological stages related to gastrointestinal secretion.
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Affiliation(s)
- Giuseppe Calamita
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy;
| | - Christine Delporte
- Laboratory of Pathophysiological and Nutritional Biochemistry, Faculty of Medicine, Université Libre de Bruxelles, 1070 Brussels, Belgium
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Evaluation of the Content of Aquaporin-5 and Epithelial Sodium Channel in the Lungs of Rats during the Development of Toxic Pulmonary Edema Caused by Intoxication with Acylating Pulmonotoxicants. Bull Exp Biol Med 2022; 173:623-627. [DOI: 10.1007/s10517-022-05600-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Indexed: 11/06/2022]
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Wu X, Yao J, Hu Q, Kang H, Miao Y, Zhu L, Li C, Zhao X, Li J, Wan M, Tang W. Emodin Ameliorates Acute Pancreatitis-Associated Lung Injury Through Inhibiting the Alveolar Macrophages Pyroptosis. Front Pharmacol 2022; 13:873053. [PMID: 35721108 PMCID: PMC9201345 DOI: 10.3389/fphar.2022.873053] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 05/13/2022] [Indexed: 02/05/2023] Open
Abstract
Objective: To investigate the protective effect of emodin in acute pancreatitis (AP)-associated lung injury and the underlying mechanisms. Methods: NaT-AP model in rats was constructed using 3.5% sodium taurocholate, and CER+LPS-AP model in mice was constructed using caerulein combined with Lipopolysaccharide. Animals were divided randomly into four groups: sham, AP, Ac-YVAD-CMK (caspase-1 specific inhibitor, AYC), and emodin groups. AP-associated lung injury was assessed with H&E staining, inflammatory cytokine levels, and myeloperoxidase activity. Alveolar macrophages (AMs) pyroptosis was evaluated by flow cytometry. In bronchoalveolar lavage fluid, the levels of lactate dehydrogenase and inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Pyroptosis-related protein expressions were detected by Western Blot. Results: Emodin, similar to the positive control AYC, significantly alleviated pancreas and lung damage in rats and mice. Additionally, emodin mitigated the pyroptotic process of AMs by decreasing the level of inflammatory cytokines and lactate dehydrogenase. More importantly, the protein expressions of NLRP3, ASC, Caspase1 p10, GSDMD, and GSDMD-NT in AMs were significantly downregulated after emodin intervention. Conclusion: Emodin has a therapeutic effect on AP-associated lung injury, which may result from the inhibition of NLRP3/Caspase1/GSDMD-mediated AMs pyroptosis signaling pathways.
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Affiliation(s)
- Xiajia Wu
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Jiaqi Yao
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Qian Hu
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Hongxin Kang
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Yifan Miao
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Lv Zhu
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Cong Li
- Research Core Facility, West China Hospital, Sichuan University, Chengdu, China
| | - Xianlin Zhao
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Juan Li
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Meihua Wan
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Wenfu Tang
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
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Xie P, Yan LJ, Zhou HL, Cao HH, Zheng YR, Lu ZB, Yang HY, Ma JM, Chen YY, Huo C, Tian C, Liu JS, Yu LZ. Emodin Protects Against Lipopolysaccharide-Induced Acute Lung Injury via the JNK/Nur77/c-Jun Signaling Pathway. Front Pharmacol 2022; 13:717271. [PMID: 35370650 PMCID: PMC8968870 DOI: 10.3389/fphar.2022.717271] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 02/07/2022] [Indexed: 12/11/2022] Open
Abstract
Background: Acute lung injury (ALI) is a serious inflammatory disease with clinical manifestations of hypoxemia and respiratory failure. Presently, there is no effective treatment of ALI. Although emodin from Rheum palmatum L. exerts anti-ALI properties, the underlying mechanisms have not been fully explored. Purpose: This study aimed to investigate the therapeutic effect and mechanism of emodin on LPS-induced ALI in mice. Methods: RAW264.7 cells and zebrafish larvae were stimulated by LPS to establish inflammatory models. The anti-inflammatory effect of emodin was assessed by ELISA, flow cytometric analysis, and survival analysis. In vitro mechanisms were explored by using Western blotting, luciferase assay, electrophoretic mobility shift assay (EMSA), and small interfering RNA (siRNA) approach. The acute lung injury model in mice was established by the intratracheal administration of LPS, and the underlying mechanisms were assessed by detecting changes in histopathological and inflammatory markers and Western blotting in lung tissues. Results: Emodin inhibited the inflammatory factor production and oxidative stress in RAW264.7 cells, and prolonged the survival of zebrafish larvae after LPS stimulation. Emodin suppressed the expression levels of phosphorylated JNK at Thr183/tyr182 and phosphorylated Nur77 at Ser351 and c-Jun, and increased the expression level of Nur77 in LPS-stimulated RAW264.7 cells, while these regulatory effects of emodin on Nur77/c-Jun were counteracted by JNK activators. The overexpression of JNK dampened the emodin-mediated increase in Nur77 luciferase activity and Nur77 expression. Moreover, the inhibitory effect of emodin on c-Jun can be attenuated by Nur77 siRNA. Furthermore, emodin alleviated LPS-induced ALI in mice through the regulation of the JNK/Nur77/c-Jun pathway. Conclusions: Emodin protects against LPS-induced ALI through regulation on JNK/Nur77/c-Jun signaling. Our results indicate the potential of emodin in the treatment of ALI.
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Affiliation(s)
- Pei Xie
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, China
| | - Li-Jun Yan
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, China
| | - Hong-Ling Zhou
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, China
| | - Hui-Hui Cao
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, China
| | - Yuan-Ru Zheng
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, China
| | - Zi-Bin Lu
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, China
| | - Hua-Yi Yang
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, China
| | - Jia-Mei Ma
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, China
| | - Yu-Yao Chen
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, China
| | - Chuying Huo
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, China
| | - Chunyang Tian
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, China
| | - Jun-Shan Liu
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, China
| | - Lin-Zhong Yu
- Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou, China
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11
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Piccapane F, Gerbino A, Carmosino M, Milano S, Arduini A, Debellis L, Svelto M, Caroppo R, Procino G. Aquaporin-1 Facilitates Transmesothelial Water Permeability: In Vitro and Ex Vivo Evidence and Possible Implications in Peritoneal Dialysis. Int J Mol Sci 2021; 22:12535. [PMID: 34830416 PMCID: PMC8622642 DOI: 10.3390/ijms222212535] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 11/18/2021] [Indexed: 12/18/2022] Open
Abstract
We previously showed that mesothelial cells in human peritoneum express the water channel aquaporin 1 (AQP1) at the plasma membrane, suggesting that, although in a non-physiological context, it may facilitate osmotic water exchange during peritoneal dialysis (PD). According to the three-pore model that predicts the transport of water during PD, the endothelium of peritoneal capillaries is the major limiting barrier to water transport across peritoneum, assuming the functional role of the mesothelium, as a semipermeable barrier, to be negligible. We hypothesized that an intact mesothelial layer is poorly permeable to water unless AQP1 is expressed at the plasma membrane. To demonstrate that, we characterized an immortalized cell line of human mesothelium (HMC) and measured the osmotically-driven transmesothelial water flux in the absence or in the presence of AQP1. The presence of tight junctions between HMC was investigated by immunofluorescence. Bioelectrical parameters of HMC monolayers were studied by Ussing Chambers and transepithelial water transport was investigated by an electrophysiological approach based on measurements of TEA+ dilution in the apical bathing solution, through TEA+-sensitive microelectrodes. HMCs express Zo-1 and occludin at the tight junctions and a transepithelial vectorial Na+ transport. Real-time transmesothelial water flux, in response to an increase of osmolarity in the apical solution, indicated that, in the presence of AQP1, the rate of TEA+ dilution was up to four-fold higher than in its absence. Of note, we confirmed our data in isolated mouse mesentery patches, where we measured an AQP1-dependent transmesothelial osmotic water transport. These results suggest that the mesothelium may represent an additional selective barrier regulating water transport in PD through functional expression of the water channel AQP1.
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Affiliation(s)
- Francesca Piccapane
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy; (F.P.); (A.G.); (S.M.); (L.D.); (M.S.); (R.C.)
| | - Andrea Gerbino
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy; (F.P.); (A.G.); (S.M.); (L.D.); (M.S.); (R.C.)
| | - Monica Carmosino
- Department of Sciences, University of Basilicata, 85100 Potenza, Italy;
| | - Serena Milano
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy; (F.P.); (A.G.); (S.M.); (L.D.); (M.S.); (R.C.)
| | - Arduino Arduini
- Department of Research and Development, CoreQuest Sagl, 6900 Lugano, Switzerland;
| | - Lucantonio Debellis
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy; (F.P.); (A.G.); (S.M.); (L.D.); (M.S.); (R.C.)
| | - Maria Svelto
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy; (F.P.); (A.G.); (S.M.); (L.D.); (M.S.); (R.C.)
| | - Rosa Caroppo
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy; (F.P.); (A.G.); (S.M.); (L.D.); (M.S.); (R.C.)
| | - Giuseppe Procino
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy; (F.P.); (A.G.); (S.M.); (L.D.); (M.S.); (R.C.)
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12
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Jiang N, Li Z, Luo Y, Jiang L, Zhang G, Yang Q, Chen H. Emodin ameliorates acute pancreatitis-induced lung injury by suppressing NLRP3 inflammasome-mediated neutrophil recruitment. Exp Ther Med 2021; 22:857. [PMID: 34178130 PMCID: PMC8220649 DOI: 10.3892/etm.2021.10289] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 03/17/2021] [Indexed: 12/16/2022] Open
Abstract
Severe acute pancreatitis (SAP) activates the systemic inflammatory response and is potentially lethal. The aim of the present study was to determine the effects of emodin on acute lung injury (ALI) in rats with SAP and investigate the role of the Nod-like receptor protein 3 (NLRP3) inflammasome and its association with neutrophil recruitment. Sodium taurocholate (5.0%) was used to establish the SAP model. All animals were randomly assigned into four groups: Sham, SAP, emodin and dexamethasone (positive control drug) groups (n=10 mice per group). Histopathology observation of pancreatic and lung tissues was detected by hematoxylin and eosin staining. The levels of serum amylase, IL-1β and IL-18 were measured by ELISA. Single-cell suspensions were obtained from enzymatically digested lung tissues, followed by flow cytometric analysis for apoptosis. In addition, the expression levels of NLRP3 inflammasome-associated and apoptosis-associated proteins in lung tissues were measured by western blotting. Moreover, lymphocyte antigen 6 complex locus G6D+ (Ly6G+) cell recruitment was detected using immunohistochemical analysis. The results revealed that emodin markedly improved pancreatic histological injury and decreased the levels of serum amylase, IL-1β and IL-18. Pulmonary edema and apoptosis were significantly alleviated by emodin. Additionally, the protein expression levels of intercellular adhesion molecule 1, NLRP3, apoptosis-associated speck-like protein containing a CARD and cleaved caspase-1 were downregulated following emodin treatment. Moreover, emodin inhibited Ly6G+ cell recruitment in lung tissues. The present study demonstrated that emodin may offer protection against ALI induced by SAP via inhibiting and suppressing NLRP3 inflammasome-mediated neutrophil recruitment and may be a novel therapeutic strategy for the clinical treatment of ALI.
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Affiliation(s)
- Nan Jiang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.,Institute (College) of Integrative Medicine and College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.,Department of Obstetrics and Gynecology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Zhaoxia Li
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.,Institute (College) of Integrative Medicine and College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
| | - Yalan Luo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.,Institute (College) of Integrative Medicine and College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
| | - Liu Jiang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.,Institute (College) of Integrative Medicine and College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
| | - Guixin Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.,Institute (College) of Integrative Medicine and College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
| | - Qi Yang
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China
| | - Hailong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
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13
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Xu C, Luo Y, Ntim M, Quan W, Li Z, Xu Q, Jiang L, Zhang J, Shang D, Li L, Zhang G, Chen H. Effect of emodin on long non-coding RNA-mRNA networks in rats with severe acute pancreatitis-induced acute lung injury. J Cell Mol Med 2021; 25:1851-1866. [PMID: 33438315 PMCID: PMC7882958 DOI: 10.1111/jcmm.15525] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 05/11/2020] [Accepted: 05/24/2020] [Indexed: 12/13/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) contribute to disease pathogenesis and drug treatment effects. Both emodin and dexamethasone (DEX) have been used for treating severe acute pancreatitis-associated acute lung injury (SAP-ALI). However, lncRNA regulation networks related to SAP-ALI pathogenesis and drug treatment are unreported. In this study, lncRNAs and mRNAs in the lung tissue of SAP-ALI and control rats, with or without drug treatment (emodin or DEX), were assessed by RNA sequencing. Results showed both emodin and DEX were therapeutic for SAP-ALI and that mRNA and lncRNA levels differed between untreated and treated SAP-ALI rats. Gene expression profile relationships for emodin-treated and control rats were higher than DEX-treated and -untreated animals. By comparison of control and SAP-ALI animals, more up-regulated than down-regulated mRNAs and lncRNAs were observed with emodin treatment. For DEX treatment, more down-regulated than up-regulated mRNAs and lncRNAs were observed. Functional analysis demonstrated both up-regulated mRNA and co-expressed genes with up-regulated lncRNAs were enriched in inflammatory and immune response pathways. Further, emodin-associated lncRNAs and mRNAs co-expressed modules were different from those associated with DEX. Quantitative polymerase chain reaction demonstrates selected lncRNA and mRNA co-expressed modules were different in the lung tissue of emodin- and DEX-treated rats. Also, emodin had different effects compared with DEX on co-expression network of lncRNAs Rn60_7_1164.1 and AABR07062477.2 for the blue lncRNA module and Nrp1 for the green mRNA module. In conclusion, this study provides evidence that emodin may be a suitable alternative or complementary medicine for treating SAP-ALI.
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Affiliation(s)
- Caiming Xu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Yalan Luo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Michael Ntim
- Department of Physiology, Dalian Medical University, Dalian, China
| | - Weili Quan
- Center for Genome Analysis, ABLife Inc, Wuhan, China
| | - Zhaoxia Li
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Qiushi Xu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Liu Jiang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Jingwen Zhang
- Endoscopy Center, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Dong Shang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Lei Li
- Department of Vascular Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Guixin Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Hailong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
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14
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He YQ, Zhou CC, Yu LY, Wang L, Deng JL, Tao YL, Zhang F, Chen WS. Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms. Pharmacol Res 2021; 163:105224. [PMID: 33007416 PMCID: PMC7522693 DOI: 10.1016/j.phrs.2020.105224] [Citation(s) in RCA: 238] [Impact Index Per Article: 59.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 09/15/2020] [Accepted: 09/22/2020] [Indexed: 12/14/2022]
Abstract
Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) as common life-threatening lung diseases with high mortality rates are mostly associated with acute and severe inflammation in lungs. With increasing in-depth studies of ALI/ARDS, significant breakthroughs have been made, however, there are still no effective pharmacological therapies for treatment of ALI/ARDS. Especially, the novel coronavirus pneumonia (COVID-19) is ravaging the globe, and causes severe respiratory distress syndrome. Therefore, developing new drugs for therapy of ALI/ARDS is in great demand, which might also be helpful for treatment of COVID-19. Natural compounds have always inspired drug development, and numerous natural products have shown potential therapeutic effects on ALI/ARDS. Therefore, this review focuses on the potential therapeutic effects of natural compounds on ALI and the underlying mechanisms. Overall, the review discusses 159 compounds and summarizes more than 400 references to present the protective effects of natural compounds against ALI and the underlying mechanism.
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Affiliation(s)
- Yu-Qiong He
- Institute of Chinese Materia Madica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Can-Can Zhou
- Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Lu-Yao Yu
- Institute of Chinese Materia Madica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Liang Wang
- Institute of Chinese Materia Madica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Jiu-Ling Deng
- Institute of Chinese Materia Madica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yu-Long Tao
- Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
| | - Feng Zhang
- Institute of Chinese Materia Madica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
| | - Wan-Sheng Chen
- Institute of Chinese Materia Madica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
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15
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Wang T, Liu C, Pan LH, Liu Z, Li CL, Lin JY, He Y, Xiao JY, Wu S, Qin Y, Li Z, Lin F. Inhibition of p38 MAPK Mitigates Lung Ischemia Reperfusion Injury by Reducing Blood-Air Barrier Hyperpermeability. Front Pharmacol 2020; 11:569251. [PMID: 33362540 PMCID: PMC7759682 DOI: 10.3389/fphar.2020.569251] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 10/29/2020] [Indexed: 01/18/2023] Open
Abstract
Background: Lung ischemia reperfusion injury (LIRI) is a complex pathophysiological process activated by lung transplantation and acute lung injury. The p38 mitogen-activated protein kinase (MAPK) is involved in breakdown of the endothelial barrier during LIRI, but the mechanism is still unclear. Therefore, we investigated the function of p38 MAPK in LIRI in vivo and in vitro. Methods: Sprague–Dawley rats were subjected to ischemia reperfusion with or without pretreatment with a p38 MAPK inhibitor. Lung injury was assessed using hematoxylin and eosin staining, and pulmonary blood–air barrier permeability was evaluated using Evans blue staining. A rat pulmonary microvascular endothelial cell line was infected with lentiviral expressing short hairpin (sh)RNA targeting p38 MAPK and then cells were subjected to oxygen/glucose deprivation and reoxygenation (OGD/R). Markers of endothelial destruction were measured by western blot and immunofluorescence. Results:In vivo LIRI models showed structural changes indicative of lung injury and hyperpermeability of the blood–air barrier. Inhibiting p38 MAPK mitigated these effects. Oxygen/glucose deprivation and reoxygenation promoted hyperpermeability of the endothelial barrier in vitro, but knockdown of p38 MAPK attenuated cell injury; maintained endothelial barrier integrity; and partially reversed injury-induced downregulation of permeability protein AQP1, endothelial protective protein eNOS, and junction proteins ZO-1 and VE-cadherin while downregulating ICAM-1, a protein involved in destroying the endothelial barrier, and ET-1, a protein involved in endothelial dysfunction. Conclusion: Inhibition of p38 MAPK alleviates LIRI by decreasing blood–air hyperpermeability. Blocking p38 MAPK may be an effective treatment against acute lung injury.
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Affiliation(s)
- Tiantian Wang
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Chunxia Liu
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Ling-Hui Pan
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Zhen Liu
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Chang-Long Li
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jin-Yuan Lin
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yi He
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jing-Yuan Xiao
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Siyi Wu
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yi Qin
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Zhao Li
- Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Fei Lin
- Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China
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16
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Hu J, Zhang YM, Miao YF, Zhu L, Yi XL, Chen H, Yang XJ, Wan MH, Tang WF. Effects of Yue-Bi-Tang on water metabolism in severe acute pancreatitis rats with acute lung-kidney injury. World J Gastroenterol 2020; 26:6810-6821. [PMID: 33268963 PMCID: PMC7684462 DOI: 10.3748/wjg.v26.i43.6810] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 08/07/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The complications acute lung injury and acute kidney injury caused by severe inflammation are the main reasons of high mortality of severe acute pancreatitis (SAP). These two complications can both lead to water metabolism and acid-base balance disorders, which could act as additional critical factors affecting the disease trend. Aquaporins (AQPs), which can regulate the transmembrane water transport, have been proved to participate in the pathophysiological process of SAP and the associated complications, such as acute lung injury and acute kidney injury. Thus, exploring herbs that can effectively regulate the expression of AQP in SAP could benefit the prognosis of this disease.
AIM To determine whether Yue-Bi-Tang (YBT) can regulate the water metabolism in rats with severe acute pancreatitis via regulating the expression of aquaporins.
METHODS Sprague-Dawley rats were randomly divided into three groups, sham operation group (SOG), model group (MG), and treatment group (TG). SAP was induced with 3.5% sodium taurocholate in the MG and TG. Rats in the TG were administered with YBT while SOG and MG rats were given the same volume of saline. Blood and tissue samples were harvested to detect serum inflammatory cytokines, histopathological changes, malondialdehyde and superoxide dismutase in the lung, and protein and mRNA expression of kidney injury molecule-1, α-smooth muscle actin, and vimentin in the kidney, and AQP1 and 4 in the lung, pancreas, and kidney.
RESULTS The serum interleukin-10, tumor necrosis factor α, and creatinine levels were higher in the MG than in the SOG. Tumor necrosis factor α level in the TG was lower than that in the MG. Malondialdehyde level in lung tissues was higher than in the SOG. The pathological scores and edema scores of the pancreas, lung, and kidney tissues in the MG were all higher than those in the SOG and TG. The protein expression of AQP4 in lung tissues and AQP1 in kidney tissues in the MG were higher than those in the SOG and TG. The expression of vimentin was significantly higher in the MG than in the SOG. The expression of AQP1 mRNA in the lung and kidney, and AQP4 mRNA in the kidney was up-regulated in the MG compared to the SOG.
CONCLUSION YBT might regulate water metabolism to reduce lung and kidney edema of SAP rats via decreasing AQP expression, and alleviate the tissue inflammatory injury.
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Affiliation(s)
- Jing Hu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yu-Mei Zhang
- Department of Traditional Chinese Medicine, Xiang’an Hospital of Xiamen University, Xiamen 361101, Fujian Province, China
| | - Yi-Fan Miao
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lv Zhu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xiao-Lin Yi
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Huan Chen
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xi-Jing Yang
- Animal Experiment Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Mei-Hua Wan
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Wen-Fu Tang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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17
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Cui Y, Chen LJ, Huang T, Ying JQ, Li J. The pharmacology, toxicology and therapeutic potential of anthraquinone derivative emodin. Chin J Nat Med 2020; 18:425-435. [PMID: 32503734 DOI: 10.1016/s1875-5364(20)30050-9] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Indexed: 02/06/2023]
Abstract
Emodin (1, 3, 8-trihydroxy-6-methylanthraquinone) is a derived anthraquinone compound extracted from roots and barks of pharmaceutical plants, including Rheum palmatum, Aloe vera, Giant knotweed, Polygonum multiflorum and Polygonum cuspidatum. The review aims to provide a scientific summary of emodin in pharmacological activities and toxicity in order to identify the therapeutic potential for its use in human specific organs as a new medicine. Based on the fundamental properties, such as anticancer, anti-inflammatory, antioxidant, antibacterial, antivirs, anti-diabetes, immunosuppressive and osteogenesis promotion, emodin is expected to become an effective preventive and therapeutic drug of cancer, myocardial infarction, atherosclerosis, diabetes, acute pancreatitis, asthma, periodontitis, fatty livers and neurodegenerative diseases. This article intends to provide a novel insight for further development of emodin, hoping to reveal the potential of emodin and necessity of further studies in this field.
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Affiliation(s)
- Ya Cui
- State Key laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of orthodontics, West China School of Stomatology Sichuan University, Chengdu 610041, China
| | - Liu-Jing Chen
- State Key laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of orthodontics, West China School of Stomatology Sichuan University, Chengdu 610041, China
| | - Tu Huang
- State Key laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of orthodontics, West China School of Stomatology Sichuan University, Chengdu 610041, China
| | - Jian-Qiong Ying
- West China Hospital of Clinical Medicine, Sichuan University, Chengdu 610041, China
| | - Juan Li
- State Key laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China; Department of orthodontics, West China School of Stomatology Sichuan University, Chengdu 610041, China.
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18
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Yadav E, Yadav N, Hus A, Yadav JS. Aquaporins in lung health and disease: Emerging roles, regulation, and clinical implications. Respir Med 2020; 174:106193. [PMID: 33096317 DOI: 10.1016/j.rmed.2020.106193] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 08/17/2020] [Accepted: 10/13/2020] [Indexed: 12/16/2022]
Abstract
Aquaporins (AQPs) aka water channels are a family of conserved transmembrane proteins (~30 kDa monomers) expressed in various organ systems. Of the 13 AQPs (AQP0 through AQP12) in the human body, four (AQPs 1, 3, 4, and 5) are expressed in the respiratory system. These channels are conventionally known for mediating transcellular fluid movements. Certain AQPs (aquaglyceroporins) have the capability to transport glycerol and potentially other solutes. There is an emerging body of literature unveiling the non-conventional roles of AQPs such as in cell proliferation and migration, gas permeation, signal potentiation, etc. Initial gene knock-out studies established a physiological role for lung AQPs, particularly AQP5, in maintaining homeostasis, by mediating fluid secretion from submucosal glands onto the airway surface liquid (ASL) lining. Subsequent studies have highlighted the functional significance of AQPs, particularly AQP1 and AQP5 in lung pathophysiology and diseases, including but not limited to chronic and acute lung injury, chronic obstructive pulmonary disease (COPD), other inflammatory lung conditions, and lung cancer. AQP1 has been suggested as a potential prognostic marker for malignant mesothelioma. Recent efforts are directed toward exploiting AQPs as targets for diagnosis, prevention, intervention, and/or treatment of various lung conditions. Emerging information on regulatory pathways and directed mechanistic research are posited to unravel novel strategies for these clinical implications. Future considerations should focus on development of AQP inhibitors, blockers, and modulators for therapeutic needs, and better understanding the role of lung-specific AQPs in inter-individual susceptibility to chronic lung diseases such as COPD and cancer.
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Affiliation(s)
- Ekta Yadav
- Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
| | - Niket Yadav
- Medical Scientist Training Program, University of Virginia School of Medicine, Charlottesville, VA, 22908-0738, USA
| | - Ariel Hus
- Department of Biology, University of Miami, Coral Gables, Florida, 33146, USA
| | - Jagjit S Yadav
- Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
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19
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Ferrero-Andrés A, Panisello-Roselló A, Roselló-Catafau J, Folch-Puy E. NLRP3 Inflammasome-Mediated Inflammation in Acute Pancreatitis. Int J Mol Sci 2020; 21:5386. [PMID: 32751171 PMCID: PMC7432368 DOI: 10.3390/ijms21155386] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 07/17/2020] [Accepted: 07/28/2020] [Indexed: 12/11/2022] Open
Abstract
The discovery of inflammasomes has enriched our knowledge in the pathogenesis of multiple inflammatory diseases. The NLR pyrin domain-containing protein 3 (NLRP3) has emerged as the most versatile and well-characterized inflammasome, consisting of an intracellular multi-protein complex that acts as a central driver of inflammation. Its activation depends on a tightly regulated two-step process, which includes a wide variety of unrelated stimuli. It is therefore not surprising that the specific regulatory mechanisms of NLRP3 inflammasome activation remain unclear. Inflammasome-mediated inflammation has become increasingly important in acute pancreatitis, an inflammatory disorder of the pancreas that is one of the fatal diseases of the gastrointestinal tract. This review presents an update on the progress of research into the contribution of the NLRP3 inflammasome to acute pancreatic injury, examining the mechanisms of NLRP3 activation by multiple signaling events, the downstream interleukin 1 family of cytokines involved and the current state of the literature on NLRP3 inflammasome-specific inhibitors.
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Affiliation(s)
- Ana Ferrero-Andrés
- Experimental Pathology Department, Institut d’Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones científicas (IIBB-CSIC), Barcelona, 08036 Catalonia, Spain; (A.F.-A.); (A.P.-R.)
| | - Arnau Panisello-Roselló
- Experimental Pathology Department, Institut d’Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones científicas (IIBB-CSIC), Barcelona, 08036 Catalonia, Spain; (A.F.-A.); (A.P.-R.)
| | - Joan Roselló-Catafau
- Experimental Pathology Department, Institut d’Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones científicas (IIBB-CSIC), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, 08036 Catalonia, Spain;
| | - Emma Folch-Puy
- Experimental Pathology Department, Institut d’Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones científicas (IIBB-CSIC), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, 08036 Catalonia, Spain;
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Guo R, Li Y, Han M, Liu J, Sun Y. Emodin attenuates acute lung injury in Cecal-ligation and puncture rats. Int Immunopharmacol 2020; 85:106626. [PMID: 32492627 DOI: 10.1016/j.intimp.2020.106626] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 05/15/2020] [Accepted: 05/19/2020] [Indexed: 12/12/2022]
Abstract
Acute lung injury (ALI) is a major cause of sepsis-induced acute respiratory failure. Emodin has been considered to play a protective role for acute lung edema in cecal ligation and puncture (CLP)-induced sepsis model. In this study we aimed to investigate whether emodin could improve CLP-induced lung sepsis via regulating aquaporin (AQP) and tight junction (TJ), inflammatory factors, and pulmonary apoptosis. The results showed that sepsis-induced pulmonary pathological changes were significantly improved after emodin treatment. Emodin was found to upregulate AQP and TJ expression in the CLP model. Meanwhile, inflammatory cytokine release and pulmonary apoptosis was remarkably reduced after emodin treatment in lung sepsis. Our data demonstrated that emodin could suppresse inflammation, restore pulmonary epithelial barrier and reduce mortality in CLP-induced ALI, suggesting the potential therapeutic application of emodin in sepsis.
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Affiliation(s)
- Ruimin Guo
- Department of Emergency, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Yanjun Li
- Department of Emergency, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Min Han
- Department of Emergency, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Jun Liu
- Department of Emergency, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Yanni Sun
- Department of Emergency, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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21
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Gao Z, Sui J, Fan R, Qu W, Dong X, Sun D. Emodin Protects Against Acute Pancreatitis-Associated Lung Injury by Inhibiting NLPR3 Inflammasome Activation via Nrf2/HO-1 Signaling. DRUG DESIGN DEVELOPMENT AND THERAPY 2020; 14:1971-1982. [PMID: 32546964 PMCID: PMC7247729 DOI: 10.2147/dddt.s247103] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 04/27/2020] [Indexed: 12/12/2022]
Abstract
Aim Lung injury is a common complication of acute pancreatitis (AP), which leads to the development of acute respiratory distress syndrome and causes high mortality. In the present study, we investigated the therapeutic effect of emodin on AP-induced lung injury and explored the molecular mechanisms involved. Materials and Methods Thirty male Sprague-Dawley rats were randomly divided into AP (n=24) and normal (n=6) groups. Rats in the AP group received a retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct and then randomly assigned to untreated, emodin, combined emodin and ML385, and dexamethasone (DEX) groups. Pancreatic and pulmonary injury was assessed using H&E staining. In in vitro study, rat alveolar epithelial cell line L2 cells were exposed to lipopolysaccharide and treated with emodin. Nrf2 siRNA pool was applied for the knockdown of Nrf2. The contents of the pro-inflammatory cytokines in the bronchoalveolar lavage fluid and lung were determined using enzyme-linked immunosorbent assay. The expressions of related mRNAs and proteins in the lung or L2 cells were detected using real-time polymerase chain reaction, Western blot, immunohistochemistry and immunofluorescence. Key Findings Emodin administration alleviated pancreatic and pulmonary injury of rats with AP. Emodin administration suppressed the production of proinflammatory cytokines, downregulated NLRP3, ASC and caspase-1 expressions and inhibited NF-κB nuclear accumulation in the lung. In addition, Emodin increased Nrf2 nuclear translocation and upregulated HO-1 expression. Moreover, the anti-inflammatory effect of emodin was blocked by Nrf2 inhibitor ML385. Conclusion Emodin effectively protects rats against AP-associated lung injury by inhibiting NLRP3 inflammasome activation via Nrf2/HO-1 signaling.
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Affiliation(s)
- Zhenming Gao
- Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, People's Republic of China
| | - Jidong Sui
- Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, People's Republic of China
| | - Rong Fan
- Department of International Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, People's Republic of China
| | - Weikun Qu
- Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, People's Republic of China
| | - Xuepeng Dong
- Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, People's Republic of China
| | - Deguang Sun
- Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, People's Republic of China
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Xu C, Zhang J, Liu J, Li Z, Liu Z, Luo Y, Xu Q, Wang M, Zhang G, Wang F, Chen H. Proteomic analysis reveals the protective effects of emodin on severe acute pancreatitis induced lung injury by inhibiting neutrophil proteases activity. J Proteomics 2020; 220:103760. [PMID: 32244009 DOI: 10.1016/j.jprot.2020.103760] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 03/04/2020] [Accepted: 03/23/2020] [Indexed: 02/08/2023]
Abstract
Acute lung injury (ALI) is the most common remote organ complication induced by severe acute pancreatitis (SAP). Almost 60-70% SAP-induced deaths are caused by ALI. Efficient clinical therapeutic strategy for SAP-induced ALI is still lacking. In this study, we demonstrate that Emodin (EMO) can significantly alleviate SAP-induced ALI. We investigate the therapeutic mechanisms of EMO by proteomic analysis, which indicates that EMO protects lung tissue against SAP-ALI by negative regulation of endopeptidase activity and inhibition of collagen-containing extracellular matrix degradation. Protein-protein interaction analysis showed Lamc2, Serpina1 and Serpinb1 play important roles in the above pathways. This study elucidates the possible mechanism and suggests the candidacy of EMO in the clinical treatment of SAP-ALI. SIGNIFICANCE: ALI is a major leading cause of death in SAP. DEX is the standard of care drug for treatment of SAP-ALI, but often associated with inevitable side effects. In the present study, EMO was demonstrated to greatly alleviate the lung injury induced by SAP. Through proteomic analysis, the recovered protein profiles in response to EMO treatment in SAP-ALI rat models was obtained, among which Lamc2, Serpina1 and Serpinb1 were discovered as crucial regulatory proteins in SAP-ALI disease. Our study provides the underlying mechanisms and novel targets of EMO protective effect against SAP-ALI.
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Affiliation(s)
- Caiming Xu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China; Institute (College) of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, China; Department of Traditional Chinese Medicine, Dalian Obstetrics and Gynecology Hospital, Dalian 116021, China
| | - Jingyu Zhang
- CAS key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R&A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian, Liaoning Province 116023, China
| | - Jing Liu
- Institute (College) of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, China; CAS key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R&A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian, Liaoning Province 116023, China
| | - Zhaoxia Li
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China; Institute (College) of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, China
| | - Zheyi Liu
- CAS key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R&A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian, Liaoning Province 116023, China
| | - Yalan Luo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China; Institute (College) of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, China
| | - Qiushi Xu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China; Institute (College) of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, China
| | - Mengfei Wang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China; Institute (College) of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, China
| | - Guixin Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China; Institute (College) of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, China
| | - Fangjun Wang
- CAS key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R&A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian, Liaoning Province 116023, China.
| | - Hailong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China; Institute (College) of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, China.
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Li LX, Zhang B, Gong RZ. Insights into the role of tumor abnormal protein in early diagnosis of cancer: A prospective cohort study. Medicine (Baltimore) 2020; 99:e19382. [PMID: 32176062 PMCID: PMC7220304 DOI: 10.1097/md.0000000000019382] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The aim of this study was to evaluate the clinical use of tumor abnormal protein (TAP) in the diagnosis of different cancers.Totally 394 patients were divided into 4 groups, namely 100 healthy volunteers, 167 patients with cancer, 20 subjects with precancerous lesions, and 107 subjects with benign lesions. TAP was detected in 4 groups of research subjects using a TAP testing kit and examination system. We correlated TAP levels with a wide variety of clinical indicators as well as established cancer markers, including alpha fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9). Besides, the changes of TAP level in 51 patients with liver cancer before and after surgery, and overall survival of patients with high or low TAP expression in pancreatic, gallbladder, bile duct, and liver cancers were analyzed.Statistically significant difference was observed in the TAP-positive ratio among subjects with cancer (79.6%) and precancerous lesions (45.0%) compared to the healthy volunteers (4.0%). TAP expression in different cancers was characterized by high sensitivity (79.64%), specificity (89.87%), positive and negative predictive value (85.25% and 85.71%), overall compliance rate (85.53%) but low omission and mistake diagnostic rate (20.36% and 10.13%), Youden index (0.6951). In addition, there was no significant difference among patients with different types of cancer (χ = 2.886, P = .410), and TAP expression was shown to be correlated with AFP in liver cancer (P = .034) but not with CA19-9 in pancreatic cancer (P = .241). Moreover, the overall survival of patients with low expression of TAP in pancreatic, gallbladder, bile duct, and liver cancers were significantly higher than of patients with high expression of TAP. Compared with the preoperative patients with cancer, TAP levels decreased dramatically among postoperative subjects (P < .001).In summary, TAP might hold promise in serving as universal indicator for the diagnosis of different cancers.
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Affiliation(s)
- Lu-Xi Li
- Department of Ophthalmology, Xi’an No 3 Hospital, The Affiliated Hospital of Northwest University
| | - Bin Zhang
- Department of Hepatobiliary Surgery, Xijing Hospital, The Air Force Medical University
| | - Rui-Zhi Gong
- Department of Oncology, Xi’an International Medical Center, Xi’an, Shaanxi, China
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Arsenijevic T, Perret J, Van Laethem JL, Delporte C. Aquaporins Involvement in Pancreas Physiology and in Pancreatic Diseases. Int J Mol Sci 2019; 20:E5052. [PMID: 31614661 PMCID: PMC6834120 DOI: 10.3390/ijms20205052] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 10/10/2019] [Accepted: 10/11/2019] [Indexed: 12/14/2022] Open
Abstract
Aquaporins are a family of transmembrane proteins permeable to water. In mammals, they are subdivided into classical aquaporins that are permeable to water; aquaglyceroporins that are permeable to water, glycerol and urea; peroxiporins that facilitate the diffusion of H2O2 through cell membranes; and so called unorthodox aquaporins. Aquaporins ensure important physiological functions in both exocrine and endocrine pancreas. Indeed, they are involved in pancreatic fluid secretion and insulin secretion. Modification of aquaporin expression and/or subcellular localization may be involved in the pathogenesis of pancreatic insufficiencies, diabetes and pancreatic cancer. Aquaporins may represent useful drug targets for the treatment of pathophysiological conditions affecting pancreatic function, and/or diagnostic/predictive biomarker for pancreatic cancer. This review summarizes the current knowledge related to the involvement of aquaporins in the pancreas physiology and physiopathology.
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Affiliation(s)
- Tatjana Arsenijevic
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, 1070 Brussels, Belgium.
- Department of Gastroenterology, Hepatology and Digestive Oncology, Hôpital Erasme, Université Libre de Bruxelles, 808, Route de Lennik, 1070 Brussels, Belgium.
| | - Jason Perret
- Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, 1070 Brussels, Belgium.
| | - Jean-Luc Van Laethem
- Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, 1070 Brussels, Belgium.
- Department of Gastroenterology, Hepatology and Digestive Oncology, Hôpital Erasme, Université Libre de Bruxelles, 808, Route de Lennik, 1070 Brussels, Belgium.
| | - Christine Delporte
- Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, 1070 Brussels, Belgium.
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Wang JJ, Kong H, Xu J, Wang YL, Wang H, Xie WP. Fasudil alleviates LPS-induced lung injury by restoring aquaporin 5 expression and inhibiting inflammation in lungs. J Biomed Res 2019; 33:156-163. [PMID: 28963443 PMCID: PMC6551422 DOI: 10.7555/jbr.31.20170024] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Fasudil, a selective rho kinase (ROCK) inhibitor, has been reported to play a beneficial role in systemic?inflammation?in acute?lung injury, but its mechanism for ameliorating pulmonary edema and inflammation remains unclear. Using hematoxylin-and-eosin (H&E) staining, immunohistochemistry, enzyme-linked immunosorbent assay, quantitative real time PCR and Western blotting, we found that fasudil attenuated LPS-induced lung injury, decreased lung edema, and suppressed inflammatory responses including leukocyte infiltration and IL-6 production. Further, fasudil upregulated LPS-induced aquaporin 5 reduction and inhibited NF-κB activation in the lungs of mice. Our results suggest that fasudil could restore the expression of aquaporin 5 to eliminate LPS-induced lung edema and prevent LPS-induced pulmonary inflammation by blocking the inflammatory pathway. Collectively, blockade of the ROCK pathway by fasudil may be a potential strategy for the treatment of acute lung injury.
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Affiliation(s)
- Jing-Jing Wang
- Department of Respiratory & Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Hui Kong
- Department of Respiratory & Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Jian Xu
- Department of Respiratory & Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Yan-Li Wang
- Department of Respiratory & Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Hong Wang
- Department of Respiratory & Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Wei-Ping Xie
- Department of Respiratory & Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
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Mukherjee R, Wen L, Zhang X, Bhattacharya P, Huang W, Sutton R. A novel digital method to assess air space loss associated with acute lung injury in experimental acute pancreatitis. Pancreatology 2018; 18:513-515. [PMID: 29784598 DOI: 10.1016/j.pan.2018.04.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2018] [Revised: 04/11/2018] [Accepted: 04/30/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND/OBJECTIVES Respiratory dysfunction and/or failure from acute lung injury (ALI) are common in acute pancreatitis (AP), but assessment of ALI in experimental AP has lacked standardisation. METHODS A range of experimental AP models induced in C57BL/6 mice with corresponding controls (n = 6/group). Full double lung or right lung specimens were taken for histopathological assessment and slides analysed by a pre-set pipeline using Aperio Scanner (Leica), ImageJ software and CellProfiler software. Findings were compared to other routinely assessed parameters. RESULTS Overall histopathological changes were similar between both lungs. Mean lung field occupancy was significantly different between moderate and severe CER-AP (21.9% v 27.5%, p < 0.05) and corresponded with lung MPO and local injury severity parameters and was mirrored for all models tested. CONCLUSION We have developed a novel, simple method for assessment of ALI to improve measurement of systemic organ injury in experimental AP and contribute to preclinical drug development.
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Affiliation(s)
- R Mukherjee
- Liverpool Pancreatitis Research Group, Institute of Translational Medicine, University of Liverpool, UK.
| | - L Wen
- Liverpool Pancreatitis Research Group, Institute of Translational Medicine, University of Liverpool, UK; Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre, West China Hospital, Sichuan University, Chengdu, China
| | - X Zhang
- Liverpool Pancreatitis Research Group, Institute of Translational Medicine, University of Liverpool, UK; Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre, West China Hospital, Sichuan University, Chengdu, China
| | - P Bhattacharya
- Liverpool Pancreatitis Research Group, Institute of Translational Medicine, University of Liverpool, UK
| | - W Huang
- Liverpool Pancreatitis Research Group, Institute of Translational Medicine, University of Liverpool, UK; Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre, West China Hospital, Sichuan University, Chengdu, China
| | - R Sutton
- Liverpool Pancreatitis Research Group, Institute of Translational Medicine, University of Liverpool, UK
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Phytoceuticals in Acute Pancreatitis: Targeting the Balance between Apoptosis and Necrosis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:5264592. [PMID: 29686719 PMCID: PMC5857302 DOI: 10.1155/2018/5264592] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Revised: 11/29/2017] [Accepted: 12/20/2017] [Indexed: 12/11/2022]
Abstract
Despite recent advances in understanding the complex pathogenesis of pancreatitis, the management of the disease remains suboptimal. The use of phytoceuticals (plant-derived pleiotropic multitarget molecules) represents a new research trend in pancreatology. The purpose of this review is to discuss the phytoceuticals with pancreatoprotective potential in acute pancreatitis and whose efficacy is based, at least in part, on their capacity to modulate the acinar cell death. The phytochemicals selected, belonging to such diverse classes as polyphenols, flavonoids, lignans, anthraquinones, sesquiterpene lactones, nitriles, and alkaloids, target the balance between apoptosis and necrosis. Activation of apoptosis via various mechanisms (e.g., inhibition of X-linked inhibitor of apoptosis proteins by embelin, upregulation of FasL gene expression by resveratrol) and/or inhibition of necrosis seem to represent the essential key for decreasing the severity of the disease. Apart from targeting the apoptosis/necrosis balance, the phytochemicals displayed other specific protective activities: inhibition of inflammasome (e.g., rutin), suppression of neutrophil infiltration (e.g., ligustrazine, resveratrol), and antioxidant activity. Even though many of the selected phytoceuticals represent a promising therapeutic alternative, there is a shortage of human evidence, and further studies are required to provide solid basis to justify their use in the treatment of pancreatitis.
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Li H, Shi H, Gao M, Ma N, Sun R. Long non-coding RNA CASC2 improved acute lung injury by regulating miR-144-3p/AQP1 axis to reduce lung epithelial cell apoptosis. Cell Biosci 2018; 8:15. [PMID: 29492259 PMCID: PMC5828141 DOI: 10.1186/s13578-018-0205-7] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Accepted: 01/20/2018] [Indexed: 12/20/2022] Open
Abstract
Background and objective Apoptosis of lung epithelial cell is implicated in the pathogenesis of acute lung injury (ALI). To study the protective effect and mechanism of cancer susceptibility candidate 2 (CASC2) on reducing lung epithelial cell apoptosis after LPS inducing acute lung injury in mice. Methods and results The ALI mice model was performed by intratracheally instilling with lipopolysaccharide (LPS). The CASC2 expression detected by quantitative real-time polymerase chain reaction was significantly decreased in LPS-induced A549 cell and ALI mice model. LPS induced A549 cell apoptosis, while transfection with pcDNA-CASC2 reversed the increased cell apoptosis, suggesting overexpression of CASC2 inhibited LPS-induced A549 cell apoptosis. In addition, we found that miR-144-3p expression were opposite to CASC2, while Aquaporin-1 (AQP1) expression was opposite to miR-144-3p in LPS-induced A549 cell and ALI mice model. The RNA immunoprecipitation and RNA pull-down assay demonstrated that CASC2 could function as a miR-144-3p decoy. The luciferase reporter assay revealed that AQP1 was a target of miR-144-3p in A549 cell. And then, further in vitro studied showed that CASC2 controlled AQP1 expression by regulating miR-144-3p, and LPS induced A549 cell apoptosis by regulating CASC2/miR-144-3p/AQP1 axis. At last, after injection with lentivirus-expressing CASC2 or control lentivirus, the mice were intratracheally instilled with LPS. Comparing to the mice injected with pcDNA, the mice injected with pcDNA-CASC2 had a significantly reduced lung wet–dry weight ratio. Conclusions Long non-coding RNA CASC2 improved acute lung injury by regulating miR-144-3p/AQP1 axis to reduce lung epithelial cell apoptosis.
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Affiliation(s)
- Hongbin Li
- Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052 Henan China
| | - Huijuan Shi
- Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052 Henan China
| | - Min Gao
- Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052 Henan China
| | - Ning Ma
- Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052 Henan China
| | - Rongqing Sun
- Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052 Henan China
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29
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Zhao Y, Xiong RP, Chen X, Li P, Ning YL, Yang N, Peng Y, Jiang YL, Zhou YG. Hsp90 regulation affects the treatment of glucocorticoid for pancreatitis-induced lung injury. Mol Cell Biochem 2017; 440:189-197. [PMID: 28828564 DOI: 10.1007/s11010-017-3166-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Accepted: 08/16/2017] [Indexed: 12/19/2022]
Abstract
Glucocorticoids are commonly used for the treatment of pancreatitis and complicated acute lung injury and help to reduce the mortality rates of both. The effect of gene variants in heat shock protein 90 (Hsp90), a key chaperone molecule of the glucocorticoid receptor (GR), on the therapeutic effect of glucocorticoids is unclear. Our study aims to investigate the different susceptibility to glucocorticoid treatment in BALB/c and C57BL/6 mice carrying different Hsp90 genotypes in an animal model of pancreatitis-induced lung injury. Compared with BALB/c mice, C57BL/6 mice have lower mortality rates, decreased water content in their lungs, and a lower level of IL-1 beta in an animal model of acute pancreatitis. C57BL/6 mice show a greater therapeutic effect and increased GR binding activities with glucocorticoid responsive element compared to BALB/c mice after a 0.4 mg/kg dexamethasone (DEX) treatment. Treatment with a higher dose of DEX (4 mg/kg) significantly reduced mortality rates and increased GR-GRE binding activity in both strains of mice, and there was no significant difference between the two strains. DEX did not exert a protective role after geldanamycin, a specific inhibitor of Hsp90, was administered in both strains of mice. Our study revealed that Hsp90 gene variants are responsible for the greater therapeutic effect of DEX in C57BL/6 mice compared to BALB/c mice, which implies that combining DEX treatment with Hsp90 regulation would promote the efficiency of DEX and would be an effective way to alleviate the side effects of hormone therapy.
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Affiliation(s)
- Yan Zhao
- Molecular Biology Center, The State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Chongqing, 400042, China
| | - Ren-Ping Xiong
- Molecular Biology Center, The State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Chongqing, 400042, China
| | - Xing Chen
- Molecular Biology Center, The State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Chongqing, 400042, China
| | - Ping Li
- Molecular Biology Center, The State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Chongqing, 400042, China
| | - Ya-Lei Ning
- Molecular Biology Center, The State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Chongqing, 400042, China
| | - Nan Yang
- Molecular Biology Center, The State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Chongqing, 400042, China
| | - Yan Peng
- Molecular Biology Center, The State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Chongqing, 400042, China
| | - Yu-Lin Jiang
- Molecular Biology Center, The State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Chongqing, 400042, China
| | - Yuan-Guo Zhou
- Molecular Biology Center, The State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, 10 Changjiang Zhilu, Chongqing, 400042, China.
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Cui H, Li S, Xu C, Zhang J, Sun Z, Chen H. Emodin alleviates severe acute pancreatitis-associated acute lung injury by decreasing pre-B-cell colony-enhancing factor expression and promoting polymorphonuclear neutrophil apoptosis. Mol Med Rep 2017; 16:5121-5128. [PMID: 28849044 PMCID: PMC5647045 DOI: 10.3892/mmr.2017.7259] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Accepted: 04/20/2017] [Indexed: 12/16/2022] Open
Abstract
The present study aimed to evaluate the protective effects of emodin on severe acute pancreatitis (SAP)‑associated acute lung injury (ALI), and investigated the possible mechanism involved. SAP was induced in Sprague‑Dawley rats by retrograde infusion of 5% sodium taurocholate (1 ml/kg), after which, rats were divided into various groups and were administered emodin, FK866 [a competitive inhibitor of pre‑B‑cell colony‑enhancing factor (PBEF)] or dexamethasone (DEX). DEX was used as a positive control. Subsequently, PBEF expression was detected in polymorphonuclear neutrophils (PMNs) isolated from rat peripheral blood by reverse transcription‑quantitative polymerase chain reaction and western blotting. In addition, histological alterations, apoptosis in lung/pancreatic tissues, apoptosis of peripheral blood PMNs and alterations in the expression of apoptosis‑associated proteins were examined by hematoxylin and eosin staining, terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assay, Annexin V/propidium iodide (PI) assay and western blotting, respectively. Serum amylase activity and wet/dry (W/D) weight ratios were also measured. An in vitro study was also conducted, in which PMNs were obtained from normal Sprague‑Dawley rats and were incubated with emodin, FK866 or DEX in the presence of lipopolysaccharide (LPS). Apoptosis of PMNs and the expression levels of apoptosis‑associated proteins were examined in cultured PMNs in vitro by Annexin V/PI assay and western blotting, respectively. The results demonstrated that emodin, FK866 and DEX significantly downregulated PBEF expression in peripheral blood PMNs. In addition, emodin, FK866 and DEX reduced serum amylase activity, decreased lung and pancreas W/D weight ratios, alleviated lung and pancreatic injuries, and promoted PMN apoptosis by regulating the expression of apoptosis‑associated proteins: Fas, Fas ligand, B‑cell lymphoma (Bcl)‑2‑associated X protein, cleaved caspase‑3 and Bcl‑extra‑large. In addition, the in vitro study demonstrated that emodin, FK866 and DEX significantly reversed the LPS‑induced decrease of apoptosis in PMNs by regulating the expression of apoptosis‑associated proteins. In conclusion, the present study demonstrated that emodin may protect against SAP‑associated ALI by decreasing PBEF expression, and promoting PMN apoptosis via the mitochondrial and death receptor apoptotic pathways.
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Affiliation(s)
- Hongzhang Cui
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Shu Li
- Department of Chinese Medicine, Dalian Municipal Central Hospital, Dalian, Liaoning 116033, P.R. China
| | - Caiming Xu
- Department of Chinese Medicine, Dalian Obstetrics and Gynecology Hospital, Dalian, Liaoning 116083, P.R. China
| | - Jingwen Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Zhongwei Sun
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Hailong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
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Li J, Zhang S, Zhou R, Zhang J, Li ZF. Perspectives of traditional Chinese medicine in pancreas protection for acute pancreatitis. World J Gastroenterol 2017; 23:3615-3623. [PMID: 28611514 PMCID: PMC5449418 DOI: 10.3748/wjg.v23.i20.3615] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 03/13/2017] [Accepted: 05/04/2017] [Indexed: 02/06/2023] Open
Abstract
Acute pancreatitis (AP) is one of the most common diseases. AP is associated with significant morbidity and mortality, but it lacks specific and effective therapies. Traditional Chinese medicine (TCM) is one of the most popular complementary and alternative medicine modalities worldwide for the treatment of AP. The current evidence from basic research and clinical studies has shown that TCM has good therapeutic effects on AP. This review summarizes the widely used formulas, single herbs and monomers that are used to treat AP and the potential underlying mechanisms of TCM. Because of the abundance, low cost, and safety of TCM as well as its ability to target various aspects of the pathogenesis, TCM provides potential clinical benefits and a new avenue with tremendous potential for the future treatment of AP.
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Xiang H, Zhang Q, Qi B, Tao X, Xia S, Song H, Qu J, Shang D. Chinese Herbal Medicines Attenuate Acute Pancreatitis: Pharmacological Activities and Mechanisms. Front Pharmacol 2017; 8:216. [PMID: 28487653 PMCID: PMC5403892 DOI: 10.3389/fphar.2017.00216] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Accepted: 04/06/2017] [Indexed: 12/12/2022] Open
Abstract
Acute pancreatitis (AP) is a commonly occurring gastrointestinal disorder. An increase in the annual incidence of AP has been observed, and it causes acute hospitalization and high mortality. The diagnosis and treatment guidelines for AP recommend conservative medical treatments focused on reducing pancreatic secretion and secondary injury, as a primary therapeutic approach. Unfortunately, the existing treatment options have limited impact on the incidence and severity of AP due to the complex and multifaceted pathological process of this disease. In recent decades, Chinese herbal medicines (CHMs) have been used as efficient therapeutic agents to attenuate AP in Asian countries. Despite early cell culture, animal models, and clinical trials, CHMs are capable of interacting with numerous molecular targets participating in the pathogenesis of AP; however, comprehensive, up-to-date communication in this field is not yet available. This review focuses on the pharmacological activities of CHMs against AP in vitro and in vivo and the underlying mechanisms. A computational prediction of few selected and promising plant-derived molecules (emodin, baicalin, resveratrol, curcumin, ligustrazine, and honokiol) to target numerous proteins or networks involved in AP was initially established based on a network pharmacology simulation. Moreover, we also summarized some potential toxic natural products for pancreas in order to more safe and reasonable medication. These breakthrough findings may have important implications for innovative drug research and the future development of treatments for AP.
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Affiliation(s)
- Hong Xiang
- College (Institute) of Integrative Medicine, Dalian Medical UniversityDalian, China
| | - Qingkai Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical UniversityDalian, China
| | - Bing Qi
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical UniversityDalian, China
| | - Xufeng Tao
- College of Pharmacy, Dalian Medical UniversityDalian, China
| | - Shilin Xia
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical UniversityDalian, China
| | - Huiyi Song
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical UniversityDalian, China
| | - Jialin Qu
- Clinical Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical UniversityDalian, China
| | - Dong Shang
- College (Institute) of Integrative Medicine, Dalian Medical UniversityDalian, China.,Department of General Surgery, The First Affiliated Hospital of Dalian Medical UniversityDalian, China
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