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Zhang Y, Wang J, Yang S, Kou H, Liu P. Tanshinone IIA alleviate atherosclerosis and hepatic steatosis via down-regulation of MAPKs/NF-κB signaling pathway. Int Immunopharmacol 2025; 152:114465. [PMID: 40090083 DOI: 10.1016/j.intimp.2025.114465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 03/09/2025] [Accepted: 03/09/2025] [Indexed: 03/18/2025]
Abstract
OBJECTIVES Tanshinone IIA (Tan IIA) exhibits therapeutic potential for atherosclerosis (AS) and hepatic steatosis (HS). The study aims to explore the mechanisms underlying the anti-atherosclerosis and anti-hepatic steatosis effects of Tan IIA. METHODS The LDLR-/-mice were divided into control, model, low/high Tan IIA and atorvastatin group, which fed with High-fat diet to build NAFLD-associated AS model, then administrated with 0.9 % saline, Tan IIA or atorvastatin. RAW264.7 cells divided into control, LPS, LPS plus low/high Tan IIA and LPS plus Tan IIA plus JNK activator group. The different goups' pathological changes visualized with H&E, Oil Red O and Immunofluorescence staining. The therapeutic effect of Tan IIA was reflected by lipids metabolism changes, hepatic indexes, inflammation levels. ELISA, RT-qPCR and Western blot assay were used to determine the inflammatory factors and upstream proteins. Molecular docking was used to reconfirm the importance of genes studied and locate the specific gene will study. RESULTS Tan IIA alleviated LDLR-/-mice AS and HS by reducing AS plaque area, lowering serum &liver lipid levels (TC, TG), improving liver function (AST, ALT). Tan IIA decreased serum inflammation levels (IL-1β, IL-6, TNF-α) and aorta & liver inflammatory-related cytokines levels (iNOS, VCAM-1, IL-6) and inhibited the phosphorylation of aorta & liver protein ERK1/2, JNK, p38 and NF-κB p65, which were validated in the LPS-stimulated macrophages supernatant and cells. CONCLUSIONS The study indicated that Tan IIA can alleviate atherosclerosis and hepatic steatosis via down-regulating MAPKs/NF-κB signaling pathway. This provides a potential therapeutic strategy for the co-existing situation of atherosclerosis and hepatic steatosis.
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Affiliation(s)
- Yifan Zhang
- Department of Cardiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiarou Wang
- Department of Cardiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Shuo Yang
- Department of Cardiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Haixin Kou
- Department of Cardiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ping Liu
- Department of Cardiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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Wu D, Xiong F, Ran Q, Liu J, Wu Q, Wang L, Lv W. Mendelian randomization of chronic hepatitis B and cardiovascular disease. Front Cardiovasc Med 2024; 11:1332557. [PMID: 38559670 PMCID: PMC10978653 DOI: 10.3389/fcvm.2024.1332557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 03/01/2024] [Indexed: 04/04/2024] Open
Abstract
Background Evidence from observational studies suggests that chronic hepatitis B (CHB) is associated with cardiovascular disease (CVD). However, results have been inconsistent and causality remains to be established. We utilized two-sample Mendelian randomization (MR) to investigate potential causal associations between CHB and CVD, including atherosclerosis, coronary heart disease, hypertension, and ischemic stroke. Methods The analysis was conducted through genome-wide association studies (GWAS), considering chronic hepatitis B as the exposure and cardiovascular disease as the endpoint. The primary method for evaluating causality in this analysis was the inverse-variance weighted (IVW) technique. Additionally, we employed the weighted median, MR-Egger regression, weighted mode, and simple mode methods for supplementary analyses. Finally, heterogeneity tests, sensitivity analyses, and multiple effects analyses were conducted. Results In a random-effects IVW analysis, we found that genetic susceptibility to chronic hepatitis B was associated with an increased risk of atherosclerosis [OR = 1.048, 95% CI (1.022-1.075), P = 3.08E-04], as well as an increased risk of coronary heart disease [OR = 1.039, 95% CI (1.006-1.072), P = 0.020]. However, it was found to be inversely correlated with ischemic stroke risk [OR = 0.972, 95% CI (0.957-0.988), P = 4.13E-04]. There was no evidence that chronic hepatitis B was associated with hypertension [OR = 1.021, 95% CI (0.994-1.049), P = 0.121]. Conclusion Our research indicates that chronic hepatitis B has a correlation with an elevated risk of developing atherosclerosis and coronary heart disease, while it is associated with a decreased risk of experiencing an ischemic stroke.
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Affiliation(s)
- Dongjie Wu
- Department of Infectious Diseases, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China
| | - Feiyang Xiong
- Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Qingzhi Ran
- Department of Cardiovascular Diseases, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China
| | - Jing Liu
- Department of Infectious Diseases, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China
| | - Qingjuan Wu
- Department of Infectious Diseases, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China
| | - Liang Wang
- Beijing Century Forum Hospital, Capital Medical University, Beijing, China
| | - Wenliang Lv
- Department of Infectious Diseases, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China
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Zhang Y, Du M, Wang J, Liu P. Astragaloside IV Relieves Atherosclerosis and Hepatic Steatosis via MAPK/NF-κB Signaling Pathway in LDLR−/− Mice. Front Pharmacol 2022; 13:828161. [PMID: 35264962 PMCID: PMC8899310 DOI: 10.3389/fphar.2022.828161] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 01/31/2022] [Indexed: 01/22/2023] Open
Abstract
Astragaloside IV (AS-IV) is the main active compound of Astragalus membranaceus. In this study, we investigated whether AS-IV could attenuate atherosclerosis and hepatic steatosis in LDLR−/−mice and its potential mechanisms. After 12 weeks of high fat diet, the LDLR−/−mice were randomly divided into four groups. Then, the mice were administrated with 0.9% saline or AS-IV (10 mg/kg) or atorvastatin (1.3 mg/kg) for 12 weeks. Serum lipid profiles and inflammatory cytokines were detected by ELISA, hepatic TC and TG by colorimetric enzymatic kits, gene expression by RT-qPCR, plaque sizes by H&E staining, Oil Red O, liver pathology by H&E staining, collagen content by Masson, α-SMA, caspase-3 and NF-κB p65 production by immunofluorescence staining. MAPK/NF-κB pathway and inflammation related proteins were detected by Western Blot. The results showed that AS-IV decreased the levels of serum lipids, reduced plaque area and increased plaque stability in HFD-induced LDLR−/− mice. AS-IV also decreased the levels of inflammatory cytokines in the serum, aortas and liver tissue, and NF-κB p65 in aortic roots. The phosphorylation of JNK, ERK1/2, p38 and NF-κB, and inflammatory proteins (iNOS, VCAM-1and IL-6) was inhibited in AS-IV-treated group. In summary, AS-IV inhibited inflammation to attenuate atherosclerosis and hepatic steatosis via MAPK/NF-κB signaling pathway in LDLR−/− mice.
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Riveiro-Barciela M, Marcos-Fosch C, Martinez-Valle F, Bronte F, Orozco O, Sanz-Pérez I, Torres D, Salcedo MT, Petta S, Esteban R, Craxi A, Buti M. Naïve hepatitis B e antigen-negative chronic hepatitis B patients are at risk of carotid atherosclerosis: A prospective study. World J Gastroenterol 2021; 27:5112-5125. [PMID: 34497439 PMCID: PMC8384736 DOI: 10.3748/wjg.v27.i30.5112] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 05/13/2021] [Accepted: 07/09/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND There is an increased risk of atherosclerosis in patients with chronic hepatitis C or human immunodeficiency virus, but there is scarce data on hepatitis B virus infection. The hypothesis of this study is that hepatitis B virus infection increases the risk of carotid plaques and subclinical atherosclerosis in naïve hepatitis B e antigen (HBeAg) negative subjects.
AIM To assess the rate of carotid plaques and subclinical atherosclerosis in naïve HBeAg negative subjects in comparison with a cohort of healthy controls.
METHODS Prospective case-control collaborative study conducted in two tertiary hospitals. Four hundred and two subjects prospectively recruited at the outpatient clinic were included from May 2016 to April 2017: 201 naïve HBeAg-negative hepatitis B virus-infected [49 chronic hepatitis B (CHB) and 152 inactive carriers(ICs)] and 201 healthy controls. Anthropomorphic and metabolic measures, liver stiffness and carotid Doppler ultrasound were performed. Subclinical atherosclerosis was established on an intima-media thickness increase of ≥1.2 mm and/or the presence of carotid plaques. Normally distributed quantitative variables were compared with the Student t test and those with a non-normal distribution with the Mann-Whitney U test. Categorical variables were compared between groups using the χ2 or Fisher exact test.
RESULTS Carotid plaques were found more often in CHB (32.7%) than ICs (17.1%) or controls (18.4%) (P = 0.048). Subclinical atherosclerosis was also increased in CHB (40.8%) vsICs (19.1%) or controls (19.4%) (P = 0.003). No differences in the risk of atherosclerosis were observed between controls and ICs. The factors independently associated with the presence of carotid plaques were age [odds ratio(OR) 1.43, P < 0.001] and CHB (OR 1.18, P = 0.004) and for subclinical atherosclerosis, age (OR 1.45, P < 0.001), CHB (OR 1.23, P < 0.001) and diabetes (OR 1.13, P = 0.028). In the subset of young subjects (< 50 years), carotid plaques (12.5% vs 1.1%, P = 0.027) and subclinical atherosclerosis (12.5% vs 2.2%, P = 0.058) were more frequent among CHB than ICs.
CONCLUSION Untreated HBeAg-negative CHB is an independent risk factor for carotid plaques and subclinical atherosclerosis, while ICs present a similar risk to controls.
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Affiliation(s)
- Mar Riveiro-Barciela
- Department of Medicine of the UAB, Hospital Universitari Vall d’Hebron, Barcelona 08035, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Cristina Marcos-Fosch
- Department of Medicine of the UAB, Hospital Universitari Vall d’Hebron, Barcelona 08035, Spain
| | - Fernando Martinez-Valle
- Systemic Autoimmune Diseases Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain
| | - Fabrizio Bronte
- Sezione di Gastroenterologia, Di.Bi.M.I.S, University of Palermo, Palermo 90133, Italy
| | - Olimpia Orozco
- Systemic Autoimmune Diseases Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain
| | - Isidro Sanz-Pérez
- Systemic Autoimmune Diseases Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain
| | - Daniele Torres
- Sezione di Gastroenterologia, Di.Bi.M.I.S, University of Palermo, Palermo 90133, Italy
| | - Maria-Teresa Salcedo
- Pathology Department, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain
| | - Salvatore Petta
- Sezione di Gastroenterologia, Di.Bi.M.I.S, University of Palermo, Palermo 90133, Italy
| | - Rafael Esteban
- Department of Medicine of the UAB, Hospital Universitari Vall d’Hebron, Barcelona 08035, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Antonio Craxi
- Sezione di Gastroenterologia, Di.Bi.M.I.S, University of Palermo, Palermo 90133, Italy
| | - Maria Buti
- Department of Medicine of the UAB, Hospital Universitari Vall d’Hebron, Barcelona 08035, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid 28029, Spain
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Chait A, Wang S, Goodspeed L, Gomes D, Turk KE, Wietecha T, Tang J, Storey C, O'Brien KD, Rubinow KB, Tang C, Vaisar T, Gharib SA, Lusis AJ, Den Hartigh LJ. Sexually Dimorphic Relationships Among Saa3 (Serum Amyloid A3), Inflammation, and Cholesterol Metabolism Modulate Atherosclerosis in Mice. Arterioscler Thromb Vasc Biol 2021; 41:e299-e313. [PMID: 33761762 PMCID: PMC8159856 DOI: 10.1161/atvbaha.121.316066] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
[Figure: see text].
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Affiliation(s)
- Alan Chait
- Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (A.C., S.W., L.G., D.G., K.E.T., J.T., C.S., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
- Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
| | - Shari Wang
- Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (A.C., S.W., L.G., D.G., K.E.T., J.T., C.S., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
- Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
| | - Leela Goodspeed
- Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (A.C., S.W., L.G., D.G., K.E.T., J.T., C.S., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
- Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
| | - Diego Gomes
- Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (A.C., S.W., L.G., D.G., K.E.T., J.T., C.S., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
- Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
| | - Katherine E Turk
- Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (A.C., S.W., L.G., D.G., K.E.T., J.T., C.S., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
- Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
| | - Tomasz Wietecha
- Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
- Department of Medicine, Division of Cardiology (T.W., K.D.O.), University of Washington, Seattle
| | - Jingjing Tang
- Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (A.C., S.W., L.G., D.G., K.E.T., J.T., C.S., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
- Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
| | - Carl Storey
- Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (A.C., S.W., L.G., D.G., K.E.T., J.T., C.S., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
- Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
| | - Kevin D O'Brien
- Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
- Department of Medicine, Division of Cardiology (T.W., K.D.O.), University of Washington, Seattle
| | - Katya B Rubinow
- Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (A.C., S.W., L.G., D.G., K.E.T., J.T., C.S., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
- Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
| | - Chongren Tang
- Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (A.C., S.W., L.G., D.G., K.E.T., J.T., C.S., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
- Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
| | - Tomas Vaisar
- Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (A.C., S.W., L.G., D.G., K.E.T., J.T., C.S., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
- Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
| | - Sina A Gharib
- Division of Pulmonary, Critical Care and Sleep Medicine, Computational Medicine Core, Department of Medicine, Center for Lung Biology (S.A.G.), University of Washington, Seattle
| | - Aldons J Lusis
- Department of Human Genetics, University of California, Los Angeles (A.J.L.)
| | - Laura J Den Hartigh
- Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition (A.C., S.W., L.G., D.G., K.E.T., J.T., C.S., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
- Diabetes Institute (A.C., S.W., L.G., D.G., K.E.T., T.W., J.T., C.S., K.D.O., K.B.R., C.T., T.V., L.J.D.H.), University of Washington, Seattle
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Moheimani HR, Amiriani T, Alizadeh AM, Jand Y, Shakiba D, Ensan PS, Jafarzadeh F, Rajaei M, Enayati A, Pourabouk M, Aliazadeh S, Pourkhani AH, Mazaheri Z, Zeyghami MA, Dehpour A, Khori V. Preconditioning and anti-apoptotic effects of Metformin and Cyclosporine-A in an isolated bile duct-ligated rat heart. Eur J Pharmacol 2021; 893:173807. [PMID: 33359222 DOI: 10.1016/j.ejphar.2020.173807] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 11/18/2020] [Accepted: 12/08/2020] [Indexed: 12/18/2022]
Abstract
Despite all previous studies relating to the mechanism of cirrhotic cardiomyopathy (CCM), the role of cirrhosis on Ischemic Preconditioning (IPC) has not yet been explored. The present study strives to assess the cardioprotective role of IPC in bile duct ligated (BDL) rats as well as the cardioprotective role of Cyclosporin-A (CsA) and Metformin (Met) in CCM. Cirrhosis was induced by bile duct ligation (BDL). Rats' hearts were isolated and attached to a Langendorff Apparatus. The pharmacological preconditioning with Met and CsA was done before the main ischemia. Myocardial infarct size, hemodynamic and electrophysiological parameters, biochemical markers, and apoptotic indices were determined at the end of the experiment. Infarct size, apoptotic indices, arrhythmia score, and incidence of VF decreased significantly in the IPC group in comparison with the I/R group. These significant decreases were abolished in the IPC (BDL) group. Met significantly decreased the infarct size and apoptotic indices compared with I/R (BDL) and normal groups, while CsA led to similar decreases except in the level of caspase-3 and -8. Met and CsA decreased and increased the arrhythmia score and incidence of VF in the BDL groups, respectively. Functional recovery indices decreased in the I/R (BDL) and IPC (BDL) groups. Met improved these parameters. Therefore, the current study depicted that the cardioprotective effect of Met and CsA on BDL rats is mediated through the balance between pAMPK and apoptosis in the mitochondria.
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Key Words
- Bile duct ligation
- Caspase
- Cyclosporin-A
- Cyclosporin-A (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-Ethyl-33-[(E,1R,2R)-1-Hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone, PubChemCID: 5284373
- Ischemic preconditioning
- Metformin
- Metformin 3-(diaminomethylidene)-1,1-dimethylguanidine, PubChem CID:4091
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Affiliation(s)
- Hamid Reza Moheimani
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Taghi Amiriani
- Golestan Research Center of Gastroenterology and Hepatology, Gorgan, Iran
| | - Ali Mohammad Alizadeh
- Cancer Research Center of Institute Cancer, Tehran University of Medical Science, Tehran, Iran
| | - Yahya Jand
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Delaram Shakiba
- Department of Mechanical Engineering and Material Science, Washington University in St. Louis, St. Louis, MO, USA
| | - Parham Sayyah Ensan
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Fatemeh Jafarzadeh
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Maryam Rajaei
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Ayesheh Enayati
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mona Pourabouk
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Shahriar Aliazadeh
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Amir Hoshang Pourkhani
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Zohreh Mazaheri
- Basic Medical Science Research Center, Histogenotech Company, Tehran, Iran
| | - Mohammad Ali Zeyghami
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Ahmadreza Dehpour
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| | - Vahid Khori
- Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
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Magan-Fernandez A, Rizzo M, Montalto G, Marchesini G. Statins in liver disease: not only prevention of cardiovascular events. Expert Rev Gastroenterol Hepatol 2018; 12:743-744. [PMID: 29768950 DOI: 10.1080/17474124.2018.1477588] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Antonio Magan-Fernandez
- a Biomedical Department of Internal Medicine and Medical Specialties , University of Palermo , Palermo , Italy
- b Department of Periodontology, School of Dentistry , University of Granada , Granada , Spain
| | - Manfredi Rizzo
- a Biomedical Department of Internal Medicine and Medical Specialties , University of Palermo , Palermo , Italy
| | - Giuseppe Montalto
- a Biomedical Department of Internal Medicine and Medical Specialties , University of Palermo , Palermo , Italy
| | - Giulio Marchesini
- c Dipartimento di Scienze Mediche e Chirurgiche, 'Alma Mater Studiorum' , University of Bologna , Bologna , Italy
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Morgello S, Murray J, Van Der Elst S, Byrd D. HCV, but not HIV, is a risk factor for cerebral small vessel disease. NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION 2014; 1:e27. [PMID: 25340079 PMCID: PMC4204233 DOI: 10.1212/nxi.0000000000000027] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2014] [Accepted: 07/29/2014] [Indexed: 01/18/2023]
Abstract
OBJECTIVES With the aging of HIV populations, vascular contributions to neuropathogenesis are increasingly important. Indirect analyses of cerebral small vessel disease have been performed, but there have been no direct studies of human brain to elucidate risk factors for arteriolar sclerosis. METHODS Mean arteriolar wall thickness (sclerotic index, SI) was measured in the deep cerebral white matter of 126 brains (96 HIV+, 30 HIV-). Correlations with SI were performed for age, sex, race, hypertension, hyperlipidemia, diabetes, obesity, cirrhosis, hepatitis C virus (HCV) infection, herpes infection, HIV infection, HIV risk, cocaine use, CD4 count, plasma HIV load, and combination antiretroviral therapy (cART) at the time of death. RESULTS Age, hypertension, race, HCV, and cirrhosis were associated with SI; of the HIV variables, only cART at death was associated with SI. To address colinearity, partial correlations were run with HCV and cirrhosis, hypertension and race, and hypertension and age. With HCV controlled, cirrhosis lost significance; with hypertension controlled, age lost significance. For the entire sample, HCV, African American race, and hypertension accounted for 15% of SI variance in multivariate analysis. Each was independently associated with SI, and HCV had the largest effect. For the HIV sample, inclusion of cART in the model increased R (2) to 0.205, with only HCV, hypertension, and cART remaining significant or trend level. CONCLUSIONS This tissue-based analysis of cerebral arteriolar disease demonstrates that HCV constitutes an independent risk, in addition to African American race, hypertension, and cART. Further study is needed to understand what aspects of HCV and cART contribute to cerebrovascular neuropathogenesis.
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Affiliation(s)
- Susan Morgello
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Jacinta Murray
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Sarah Van Der Elst
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Desiree Byrd
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY
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Li Y, Liu L, Wang B, Wang J, Chen D. Simple steatosis is a more relevant source of serum inflammatory markers than omental adipose tissue. Clin Res Hepatol Gastroenterol 2014; 38:46-54. [PMID: 24075193 DOI: 10.1016/j.clinre.2013.08.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2013] [Revised: 07/06/2013] [Accepted: 08/26/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Serum inflammatory biomarkers are closely associated with the risk of cardiovascular disease. However, the major source of these biomarkers is not yet determined. Therefore, we aimed to assess whether simple steatosis or visceral adiposity was a more relevant predictor for serum inflammatory biomarkers. METHODS A double approach was used: i) clinical: 50 patients with biopsy-proven simple steatosis, 50 non-simple steatosis overweight patients, and 50 controls were explored for their serum biomarkers (high-sensitivity C-reactive protein, plasminogen activator inhibitor-1 activity, tumor necrosis factor α, and fibrinogen levels) and for visceral adiposity (measured by computed tomography); ii) experimental: using a rat simple steatosis model the effect of omentectomy on inflammatory biomarkers was investigated. RESULTS Serum inflammatory biomarkers were significantly higher in the simple steatosis group than in the overweight group. Using multivariate analysis, simple steatosis, visceral adiposity index and visceral adiposity were independently associated with inflammatory biomarkers. In particular, serum inflammatory biomarkers increased with the severity of liver histology (p<0.05), but no with visceral adipose tissue increase. In rats with simple steatosis, the omentectomy treatment was not associated with a decrease of serum inflammatory biomarkers in rats with simple steatosis. CONCLUSIONS Clinical and experimental data both indicate that simple steatosis may be more associated with inflammatory biomarkers than omental adipose tissue.
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Affiliation(s)
- Yan Li
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10, Changjiang Zhilu, Da Ping, Chongqing 400042, China
| | - Lei Liu
- Biowave Center and Department of Natural Medicinal Chemistry, College of Pharmacy, Third Military Medical University, Chongqing 400038, China
| | - Bin Wang
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10, Changjiang Zhilu, Da Ping, Chongqing 400042, China
| | - Jun Wang
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10, Changjiang Zhilu, Da Ping, Chongqing 400042, China
| | - Dongfeng Chen
- Department of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10, Changjiang Zhilu, Da Ping, Chongqing 400042, China.
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Liver disease and malnutrition. Best Pract Res Clin Gastroenterol 2013; 27:619-29. [PMID: 24090946 DOI: 10.1016/j.bpg.2013.06.018] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2013] [Revised: 06/01/2013] [Accepted: 06/12/2013] [Indexed: 01/31/2023]
Abstract
Patients with hepatic disorders are exceptionally vulnerable to developing malnutrition because of the key role played by the liver in regulating the nutritional state and the energy balance. Moreover, the presence of chronic liver disorders could reduce the appetite and thus influence the nutrient intake. Poor nutritional status has been shown in various patient groups with hepatic disorders, and particularly in patients with alcoholic cirrhosis who are at high nutritional risk. It is well established that malnourished patients with liver diseases generally have a higher risk of developing adverse clinical outcomes and increased healthcare costs. Nutrition screening with the Subjective Global Assessment and anthropometric measurements are an important first step in the early identification of malnutrition and initiates the whole nutrition care process. It is therefore important for appropriate nutrition policies and protocols to be implemented so that all patients with chronic liver diseases are monitored closely from a nutritional standpoint. Early and evidence-based nutritional interventions are eagerly needed to minimize the nutritional decline associated with chronic liver disorders and ultimately improve the prognosis of such patients. This review includes a comprehensive analysis of methods to identify malnutrition in patients with chronic liver diseases as well as the extent and impact of the malnutrition problem in selected patient populations.
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Purnak T, Olmez S, Torun S, Efe C, Sayilir A, Ozaslan E, Tenlik I, Kalkan IH, Beyazit Y, Yuksel O. Mean platelet volume is increased in chronic hepatitis C patients with advanced fibrosis. Clin Res Hepatol Gastroenterol 2013; 37:41-46. [PMID: 22572524 DOI: 10.1016/j.clinre.2012.03.035] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2012] [Revised: 03/18/2012] [Accepted: 03/28/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Liver biopsy is the gold standard procedure for documenting liver damage in chronic hepatitis C (CHC), as for many other chronic liver diseases. Mean platelet volume (MPV) is a laboratory marker obtained from complete blood count (CBC) analysers in routine clinical practice. The goal of the present study was to evaluate whether MPV would be useful in predicting liver histologic severity in CHC. PATIENTS AND METHODS A total of 59 patients with CHC and 25 control subjects were recruited into the present study. There were 26 men and 33 women in the CHC group and 12 men and 13 women in the control group. MPV was recorded at the time of admission. The clinical characteristics of CHC patients, including demographics, laboratory and liver biopsy findings, were reviewed. RESULTS A statistically significant increase in MPV values was observed in CHC patients (8.54 ± 0.63 fL) compared to healthy controls (7.65 ± 0.42 fL) (P < 0.001). Moreover, MPV values were significantly higher among patients with advanced fibrosis as compared to those with mild fibrosis (8.99 ± 0.57 fL vs. 8.19 ± 0.50 fL P < 0.001). Receiver operator characteristic (ROC) curve analysis suggested that the optimum cut-off point for MPV value in advanced fibrosis was 8.75 fL. (Sensitivity: 80.8%, specificity: 81.8%, positive predictive value [PPV] 77.8%, negative predictive value [NPV] 84.4%, accuracy 81.3%, AUC: 0.98 P < 0.001) CONCLUSION The current study showed that MPV is increased in CHC with advanced fibrosis. Calculation of MPV along with the use of other markers may give further information about liver fibrosis severity in CHC.
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Affiliation(s)
- Tugrul Purnak
- Department of Gastroenterology, Ankara Numune Education and Research Hospital, Ankara, Turkey.
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Abstract
Lysophosphatidic acid (LPA) is a potent bioactive phospholipid. As many other biological active lipids, LPA is an autacoid: it is formed locally on demand, and it acts locally near its site of synthesis. LPA has a plethora of biological activities on blood cells (platelets, monocytes) and cells of the vessel wall (endothelial cells, smooth muscle cells, macrophages) that are all key players in atherosclerotic and atherothrombotic processes. The specific cellular actions of LPA are determined by its multifaceted molecular structures, the expression of multiple G-protein coupled LPA receptors at the cell surface and their diverse coupling to intracellular signalling pathways. Numerous studies have now shown that LPA has thrombogenic and atherogenic actions. Here, we aim to provide a comprehensive, yet concise, thoughtful and critical review of this exciting research area and to pinpoint potential pharmacological targets for inhibiting thrombogenic and atherogenic activities of LPA. We hope that the review will serve to accelerate knowledge of basic and clinical science, and to foster drug development in the field of LPA and atherosclerotic/atherothrombotic diseases.
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Affiliation(s)
- Andreas Schober
- Institute for Molecular Cardiovascular Research, RWTH Aachen University, Aachen, Germany
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