Matrix metalloproteinases induce extracellular matrix degradation through various pathways to alleviate hepatic fibrosis

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 161, P. 114472 - 114472

Published: March 2, 2023

Liver fibrosis is the common consequence of various chronic liver injuries and mainly characterized by imbalance between production degradation extracellular matrix, which leads to accumulation interstitial collagen other matrix components. Matrix metalloproteinases (MMPs) their specific inhibitors, that is, tissue inhibitors (TIMPs), play a crucial role in synthesis lysis. Previous vivo vitro studies our laboratory found repressing (ECM) restoring balance MMPs TIMPs can alleviate fibrosis. We conducted review articles published PubMed Science Direct last decade until February 1, 2023, were searched for using these words "MMPs/TIMPs" "Hepatic Fibrosis." Through literature review, this article reviews experimental based on MMPs/TIMPs, summarizes components may exert an anti-liver effect affecting expression or activity attempts clarify mechanism MMPs/TIMPs regulating homeostasis, so as provide support development drugs. MMP-TIMP-ECM interaction result better understanding pathogenesis progression hepatic from different angle, targeting be promising therapeutic strategy Additionally, we summarized analyzed drugs have been reduce changing ratio including medicine natural products.

Language: Английский

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Comparative Analysis of Machine Learning Algorithms for Liver Disease Prediction: SVM, Logistic Regression, and Decision Tree

Asian Journal of Research in Computer Science, Journal Year: 2024, Volume and Issue: 17(6), P. 188 - 201

Published: May 14, 2024

This study compares Support Vector Machine (SVM), Logistic Regression, and Decision Tree algorithms for liver disease prediction using a dataset sourced from Kaggle, comprising 20,000 training records approximately 1,000 test records. The research evaluates the based on performance metrics, including accuracy, precision, recall, F1-score. SVM emerged as most effective model with an accuracy of 85%, followed by Regression 82% 79%. findings underscore significance algorithm selection in healthcare applications highlight SVM's potential early detection intervention cases, paving way improved patient outcomes management. Future work will focus refining validating results larger more diverse datasets to enhance predictive robustness further.

Language: Английский

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The role of noninvasive biomarkers for monitoring cell injury in advanced liver fibrosis

Expert Review of Gastroenterology & Hepatology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: Jan. 7, 2025

Introduction Accurate and reliable diagnosis monitoring of hepatic fibrosis is increasingly important given the variable natural history in chronic liver disease (CLD) expanding antifibrotic therapeutic options targeting reversibility early-stage cirrhosis. This highlights need to develop more refined effective noninvasive techniques for dynamic assessment fibrogenesis fibrolysis.

Language: Английский

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Obeticholic acid-loaded exosomes attenuate liver fibrosis through dual targeting of the FXR signaling pathway and ECM remodeling

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115777 - 115777

Published: Oct. 31, 2023

End-stage of liver fibrosis as a precancerous state could lead to cirrhosis and hepatocellular carcinoma which transplantation is the only effective treatment. Previous studies have indicated that farnesoid X receptor (FXR) agonists, such obeticholic acid (OCA) protect against hepatic injuries. However, free OCA administration results in side effects clinical trials be alleviated by applying bio carriers MSC-derived exosomes (Exo) with potential mimic biological regenerative effect their parent cells, proposed this study. Loading into Exo was conducted via water bath sonication. Ex vivo distribution validated Exo-loaded more permanently accumulated liver. Using CCL4-induced fibrosis, we whether isolated from human Warton's Jelly mesenchymal stem cells loaded minimal dosage can facilitate recovery. Notably, exerted additive anti-fibrotic efficacy on histopathological features fibrotic mice. Compared baseline, Exo-mediated delivery marked improvements fibrotic-related indicators well serum aspartate aminotransferase (AST) alanine (ALT) concentrations. Accordingly, synergistic impact promising approach associated inactivation stellate (HSCs), extracellular matrix (ECM) remodeling, Fxr-Cyp7a1 cascade In conclusion, our data confirmed protective mice, suggests valuable therapeutic strategy combat fibrosis. Furthermore, use for accurate drug tissue inspiring.

Language: Английский

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A randomized clinical study to evaluate the possible antifibrotic effect of zinc sulfate in chronic HCV patient receiving direct-acting anti-viral therapy

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Abstract Objective This study aimed to assess the potential antifibrotic impact of zinc sulfate in chronic Hepatitis C Virus (HCV) patients receiving direct-acting antiviral therapy. Methods randomized controlled included 50 HCV-infected with fibrosis stage (F1 & F2). Participants were randomly assigned two groups: Group 1 (Control group, n = 25) received standard therapy for 3 months, while 2 (Zinc mg/day addition same duration. Baseline and 3-month post-intervention assessments evaluating serum levels hyaluronic acid, transforming growth factor beta-1, fibronectin. Furthermore, indices liver fibrosis, such as Fibrosis Index based on 4 factors (FIB-4) Aspartate Transaminase-to-Platelet-Ratio (APRI), calculated during these assessments. Results At baseline, studied groups had no statistical difference demographic laboratory data. After treatment, significantly increased zinc-treated group compared control group. Additionally, fibronectin acid reduced (zinc group) (control group). Moreover, showed lower APRI scores than after a follow-up period, but there was non-significant FIB-4 between treatment. total bilirubin months. Conclusions Administering could potentially serve safe efficient therapeutic strategy management hepatic individuals hepatitis virus. Trial Registration ClinicalTrials.gov identifier: NCT05465434, On 19/7/2022.

Language: Английский

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A Novel Protein‐Polysaccharide Oral Nanoemulsion Targeting Activated Hepatic Stellate Cells to Enhance the Therapeutic Effect of Pirfenidone on Fibrosis After Transarterial Chemoembolization for Liver Cancer

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Abstract Transarterial chemoembolization (TACE) is considered the main treatment for intermediate and advanced liver cancer. Nevertheless, TACE may aggravate fibrosis in these patients, which could affect therapeutic effect after TACE. Pirfenidone (PFD) exhibits significant antifibrotic effects liver, primarily via inhibition of hepatic stellate cells (HSCs) activation. However, owing to high dose required effective treatment, oral administration PFD associated with several side effects. This study introduces an folic acid (FA)‐modified protein‐polysaccharide nanoemulsion designed treat post‐TACE targeting. novel withstands gastrointestinal digestion ensures stability PFD. Furthermore, this improves intestinal permeability efficacy at a lower folate receptors expressed on both epithelial activated HSCs. In conclusion, FA‐modified presents promising approach delivery effectively ameliorate

Language: Английский

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Exposure to Polyethylene Terephthalate Microplastic Induces Mouse Liver Fibrosis Through Oxidative Stress and p38 MAPK/p65 NF‐κB Signaling Pathway

Journal of Applied Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Microplastic (MP) pollution has garnered attention due to its potential impact on living organisms. Among these, polyethylene terephthalate microplastics (PET-MPs) are frequently detected in both environmental samples and human tissues. Despite this, the effects of PET-MPs liver damage fibrosis mammals remain insufficiently understood. This study demonstrated that oral exposure at doses 1 mg/day (with a diameter μm) over 42 days resulted inhibited weight gain altered organ coefficients male mice, suggesting possible damage. Using HE Masson staining revealed pathological changes livers exposed such as hepatocyte swelling, inflammatory cell infiltration, collagen deposition. Liver function tests confirmed elevated serum levels alanine aminotransferase (ALT) aspartate (AST). Further, oxidative stress markers, along with enhanced expression proteins related p38 MAPK/p65 NF-κB signaling pathway by western blot analysis, which strongly associated fibrosis. To further elucidate these mechanisms, experiments involving N-acetylcysteine (NAC) counteract SB203580 inhibit MAPK activation interventions effectively mitigated Exposure may trigger injury mice. During this process, play significant mediating roles.

Language: Английский

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Molecular Changes in Relation to Alcohol Consumption and Hepatocellular Carcinoma

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 9679 - 9679

Published: Aug. 26, 2022

Alcohol is the one of major causes liver diseases and promotes cirrhosis hepatocellular carcinoma (HCC). In hepatocytes, alcohol converted to acetaldehyde, which hepatic steatosis, cellular apoptosis, endoplasmic reticulum stress, peroxidation, production cytokines reduces immune surveillance. Endotoxin lipopolysaccharide produced from intestinal bacteria also enhance cytokines. The development fibrosis occurrence HCC are induced by these metabolites. Several host genetic factors have recently been identified in this process. Here, we reviewed molecular mechanism associated with alcoholic disease.

Language: Английский

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Extracellular matrix turnover: phytochemicals target and modulate the dual role of matrix metalloproteinases (MMPs) in liver fibrosis

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 37(11), P. 4932 - 4962

Published: July 17, 2023

Abstract Extracellular matrix (ECM) resolution by metalloproteinases (MMPs) is a well‐documented mechanism. MMPs play dual and complex role in modulating ECM degradation at different stages of liver fibrosis, depending on the timing levels their expression. Increased MMP‐1 combats disease progression cleaving fibrillar ECM. Activated hepatic stellate cells (HSCs) increase expression MMP‐2, ‐9, ‐13 chemicals‐induced animal models, which may alleviate or worsen based models stage fibrosis. In early stage, elevated certain damage surrounding tissue activate HSCs, promoting fibrosis progression. At later downregulation can facilitate accumulation A number phytochemicals modulate MMP activity turnover, alleviating However, effects are variable depend dosage, duration used each study. Here, we review most recent advances fibrogenesis, indicates that further studies warranted to confirm define potential clinical efficacy these phytochemicals.

Language: Английский

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Extracellular vesicles as advanced therapeutics for the resolution of organ fibrosis: Current progress and future perspectives

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 20, 2022

Organ fibrosis is a serious health challenge worldwide, and its global incidence medical burden are increasing dramatically each year. Fibrosis can occur in nearly all major organs ultimately lead to organ dysfunction. However, current clinical treatments cannot slow or reverse the progression of end-stage failure, thus advanced anti-fibrotic therapeutics urgently needed. As type naturally derived nanovesicle, native extracellular vesicles (EVs) from multiple cell types ( e.g. , stem cells, immune tissue cells) have been shown alleviate many preclinical models through effective mechanisms, such as anti-inflammation, pro-angiogenesis, inactivation myofibroblasts, fibrinolysis ECM components. Moreover, therapeutic potency EVs be further enhanced by engineering strategies, genetic modifications, preconditionings, reagent-loadings, combination with functional biomaterials. In this review, we briefly introduce pathology fibrosis, discuss EV biology production particularly focus on important studies using engineered interventions attenuate fibrosis. This review provides insights into development translation EV-based nanotherapies applications future.

Language: Английский

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