Mechanical homeostasis imbalance in hepatic stellate cells activation and hepatic fibrosis

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: April 20, 2023

Chronic liver disease or repeated damage to hepatocytes can give rise hepatic fibrosis. Hepatic fibrosis (HF) is a pathological process of excessive sedimentation extracellular matrix (ECM) proteins such as collagens, glycoproteins, and proteoglycans (PGs) in the parenchyma. Changes composition ECM lead stiffness that destroys its inherent mechanical homeostasis, homeostasis imbalance activates stellate cells (HSCs) into myofibroblasts, which overproliferate secrete large amounts proteins. Excessive are gradually deposited Disse gap, regeneration fails, further leads changes components an increase stiffness, forming vicious cycle. These processes promote occurrence development In this review, dynamic remodeling HF activation HSCs mechanotransduction signaling pathways for myofibroblasts participate discussed. may have potential therapeutic targets repairing reversing

Language: Английский

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Progress in clinical and basic research of fuzheng Huayu formula for the treatment of liver fibrosis

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 327, P. 118018 - 118018

Published: March 5, 2024

Language: Английский

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Progress of mesenchymal stem cells (MSCs) & MSC-Exosomes combined with drugs intervention in liver fibrosis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116848 - 116848

Published: June 3, 2024

Liver fibrosis is an intrahepatic chronic damage repair response caused by various reasons such as alcoholic liver, fatty viral hepatitis, autoimmune diseases, etc., and closely related to the progression of liver disease. Currently, mechanisms its treatment are hot research topics in field disease remedy. Mesenchymal stem cells (MSCs) a class adult with self-renewal multidirectional differentiation potential, which can ameliorate through hepatic-directed differentiation, paracrine effects, immunomodulation. However, low inner-liver colonization rate, survival short duration intervention after cell transplantation have limited their wide clinical application. With intensive on worldwide, it has been found that MSCs MSCs-derived exosomes combined drugs shown better efficiency than utilization alone many animal models fibrosis. In this paper, we review interventional effects mesenchymal alleviate hepatic vivo recent years, will provide new ideas improve efficacy treating clinic.

Language: Английский

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Polystyrene microplastics induce liver fibrosis and lipid deposition in mice through three hub genes revealed by the RNA-seq

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 20, 2025

Language: Английский

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Mechanism of Radix Bupleuri and Hedysarum Multijugum Maxim drug pairs on liver fibrosis based on network pharmacology, bioinformatics and molecular dynamics simulation

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0318336 - e0318336

Published: Jan. 27, 2025

A number of studies demonstrate the therapeutic effectiveness Radix Bupleuri (RB) and Hedysarum Multijugum Maxim (HMM) in treating liver fibrosis, but exact molecular mechanisms remain unclear. This study aims to explore mechanism RB-HMM drug pairs fibrosis by using network pharmacology, bioinformatics, docking, dynamics simulation technology vitro experiments. Totally, 155 intersection targets between were identified. In protein-protein interaction (PPI) network, top 10 hub with highest node connection values TNF, IL-6, AKT1, EGFR, HIF1A, PPARG, CASP3, SRC, MMP9 HSP90AA1. GO functional KEGG pathway enrichment analysis involved 335 biological processes, 39 cellular components, 78 functions, 139 signaling pathways. The bioinformatics indicated that PPARG promising candidate genes can serve as diagnostic prognostic biomarkers for fibrosis. Moreover, docking dynamic 50 ns well complemented binding affinity strong stability three common compounds MOL000098 (quercetin), MOL000354 (isorhamnetin) MOL000422 (kaempferol) four final (TNF, MMP9). Calculation free energy decomposition MM_PBSA MM_GBSA also validated 12 systems. (quercetin) was selected via MTT assay western blot verified treatments remarkably decreased protein levels TNF IL-6 TGFβ stimulated LX2 cells. conclusion, affect progression through multiple pathways, treat possibly anti-inflammatory affecting cell apoptosis.

Language: Английский

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Involvement of SIRT1-mediated aging in liver diseases

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 20, 2025

Liver disease is a significant global health issue, responsible for millions of deaths annually. Aging, characterized by the gradual decline in cellular and physiological functions, impairs tissue regeneration, increases susceptibility to liver diseases, leads health. Silent information regulator 1 (SIRT1), NAD⁺-dependent deacetylase, has emerged as pivotal factor modulating age-related changes liver. SIRT1 preserves function regulating essential aging-related pathways, including telomere maintenance, epigenetic modifications, senescence, intercellular communication, inflammation, mitochondrial function. Notably, levels naturally with age, contributing progression increased vulnerability injury. This review summarizes regulatory role aging its impact on diseases such fibrosis, alcoholic associated (ALD), metabolic dysfunction-associated steatotic (MASLD), steatohepatitis (MASH), hepatocellular carcinoma (HCC). We also discuss emerging therapeutic approaches, activators, gene therapy, nutritional interventions, which are evaluated their potential restore mitigate progression. Finally, we highlight future research directions optimize SIRT1-targeted therapies clinical applications conditions.

Language: Английский

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Autophagy and Senescence: The Molecular Mechanisms and Implications in Liver Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 16880 - 16880

Published: Nov. 28, 2023

The liver is the primary organ accountable for complex physiological functions, including lipid metabolism, toxic chemical degradation, bile acid synthesis, and glucose metabolism. Liver function homeostasis essential stability of bodily functions involved in regulation balance between cell proliferation death. Cell proliferation-halting mechanisms, autophagy senescence, are implicated development several diseases, such as cholestasis, viral hepatitis, nonalcoholic fatty disease, fibrosis, hepatocellular carcinoma. Among various death a highly conserved self-degradative cellular process that recycles damaged organelles, debris, proteins. This also provides substrate further A defect machinery can lead to premature accelerated aging, inflammatory state, tumorigenesis, senescence. Senescence, another type, an active player eliminating premalignant cells. At same time, senescent cells affect neighboring by secreting senescence-associated secretory phenotype induce paracrine Autophagy promote delay senescence under different contexts. review decodes roles multiple diseases achieve better understanding regulatory mechanisms implications diseases.

Language: Английский

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Pharmacotherapeutic options for metabolic dysfunction-associated steatotic liver disease: where are we today?

Expert Opinion on Pharmacotherapy, Journal Year: 2024, Volume and Issue: 25(9), P. 1249 - 1263

Published: June 12, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by hepatic steatosis and cardiometabolic risk factors like obesity, type 2 diabetes, dyslipidemia. Persistent metabolic injury may promote inflammatory processes resulting in steatohepatitis (MASH) fibrosis. Mechanistic insights helped to identify potential drug targets, thereby supporting the development of novel compounds modulating drivers.

Language: Английский

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Can Nutraceuticals Support the Treatment of MASLD/MASH, and thus Affect the Process of Liver Fibrosis?

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5238 - 5238

Published: May 11, 2024

Currently, metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) are considered to be the main causes of fibrosis. In turn, fibrosis may lead development hepatocellular carcinoma or advanced cirrhosis, i.e., potentially life-threatening conditions. It is likely that therapy aimed at reducing risk developing hepatic steatosis inflammation could helpful in minimizing threat/probability organ recent years, increasing attention has been paid influence nutraceuticals prevention treatment diseases. Therefore, aim this review was describe precise role selected ingredients such as vitamin C, beta-carotene, omega-3 fatty acids, curcumin. use these patients with MASLD/MASH, along behavioral pharmacological therapy, have a beneficial effect on combating inflammation, oxidative stress, thereby preventing damage.

Language: Английский

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Blockade of KLF5/LDH—A feedback loop contributes to Curcumol inhibition of sinusoidal endothelial cell glycolysis and mitigation of liver fibrosis

Phytomedicine, Journal Year: 2023, Volume and Issue: 114, P. 154759 - 154759

Published: March 22, 2023

Language: Английский

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