Inflammation: A New Look at an Old Problem

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 4596 - 4596

Published: April 21, 2022

Pro-inflammatory stress is inherent in any cells that are subject to damage or threat of damage. It defined by a number universal components, including oxidative stress, cellular response DNA damage, unfolded protein mitochondrial and endoplasmic reticulum changes autophagy, inflammasome formation, non-coding RNA response, formation an inducible network signaling pathways, epigenetic changes. The presence receptor secretory phenotype many the cause tissue pro-inflammatory stress. key phenomenon determining occurrence classical inflammatory focus microvascular (exudation, leukocyte migration alteration zone). This same reaction at systemic level leads development life-critical inflammation. From this standpoint, we can characterize common mechanisms pathologies differ their clinical appearance. division inflammation into alternative variants has deep evolutionary roots. Evolutionary aspects also described review. aim review provide theoretical arguments for need up-to-date theory relationship between human pathological processes based on integrative role molecular

Language: Английский

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A Guide to Pathophysiology, Signaling Pathways, and Preclinical Models of Liver Fibrosis

Molecular and Cellular Endocrinology, Journal Year: 2025, Volume and Issue: unknown, P. 112448 - 112448

Published: Jan. 1, 2025

Language: Английский

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An update on animal models of liver fibrosis

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: March 23, 2023

The development of liver fibrosis primarily determines quality life as well prognosis. Animal models are often used to model and understand the underlying mechanisms human disease. Although organoids can be simulate organ disease, technology still faces significant challenges. Therefore animal irreplaceable at this stage. Currently, in vivo classified into five categories based on etiology: chemical, dietary, surgical, transgenic, immune. There is a wide variety with varying efficacy, which have different implications for proper understanding disease effective screening therapeutic agents. no high-quality literature recommending most appropriate models. In paper, we will describe progress commonly terms their mechanisms, applications, advantages disadvantages, recommend research purposes.

Language: Английский

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Mesenchymal stromal cell-derived extracellular vesicles as nanotherapeutics for concanavalin a-induced hepatitis: modulating the gut‒liver axis

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 7, 2025

As cell-free nanotherapeutics, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown potential therapeutic action against liver diseases. However, their effects on autoimmune hepatitis (AIH) are not yet well understood. In this study, we utilized a well-established concanavalin A (Con A)-induced fulminant mouse model to investigate the of MSC-EVs AIH. We found that provide significant protection Con A-induced in C57BL/6 male mice, with effectiveness being critically dependent gut microbiota. modulate composition microbiota, particularly by increasing abundance norank_f__Muribaculaceae, and impact metabolic profiles, leading amelioration injury. The identification Acetyl-DL-Valine as protective metabolite underscores targeting gut‒liver axis interactions Overall, our data demonstrate exhibit nanotherapeutic new insights into treatment hepatitis.

Language: Английский

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Allyl methyl disulfide attenuates liver injury induced by concanavalin A by suppressing M1 polarization of macrophages and NLRP3 inflammasome activation

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 149, P. 114149 - 114149

Published: Feb. 4, 2025

Language: Английский

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MSCs Suppress Macrophage Necroptosis and Foster Liver Regeneration by Modulating SP1/SK1 Axis in Treating Acute Severe Autoimmune Hepatitis

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Abstract Acute severe autoimmune hepatitis (AS‐AIH) is characterized by rapid progression and poor prognosis, with a current lack of effective targeted treatments. Stem cell therapy has demonstrated significant therapeutic promise across various diseases. However, the intricate pathogenesis AS‐AIH hindered widespread utilization mesenchymal stem cells (MSCs) in this domain. Herein, it that necroptosis, as primary mode death AIH, crucial causing AS‐AIH. Inflammatory macrophages are population involved necroptosis. Inhibition specificity protein 1/sphingosine kinase 1/sphingosine‐1‐phosphate (SP1/SK1/S1P) axis responsible for phenomenon, leading to excessive activation intrahepatic immune system aggravating liver damage. Furthermore, S1P/S1PR2/YAP key pathway initiating regeneration during S1P synthesized hepatocytes source, process also regulated SP1/SK1 axis. MSCs promote synthesis through delivery SP1, which inhibits necroptosis synergistically enhances regeneration. In addition, same mechanism, further aiding These findings unveil core provide theoretical foundation using potential modality.

Language: Английский

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Dimethyl fumarate ameliorates autoimmune hepatitis in mice by blocking NLRP3 inflammasome activation

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 108, P. 108867 - 108867

Published: May 20, 2022

Language: Английский

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Corilagin Ameliorates Con A-Induced Hepatic Injury by Restricting M1 Macrophage Polarization

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 13, 2022

Immune-mediated hepatic injury plays a key role in the initiation and pathogenesis of diverse liver diseases. However, treatment choice for immune-mediated remains limited. Corilagin, natural ellagitannin extracted from various traditional Chinese medicines, has been demonstrated to exhibit multiple pharmacological activities, such as anti-inflammatory, anti-tumor, hepatoprotective properties. The present study aimed investigate effects corilagin on using murine model concanavalin A (Con A)-induced hepatitis, which is well-characterized acute hepatitis. Herein, mice were administered (25 mg/kg) intraperitoneally twice at 12 h intervals, 1 later, challenged with Con (20 mg/kg body weight); serum samples collected after h. results showed that significantly increased survival reduced alanine transaminase (ALT) aspartate aminotransferase (AST) levels. In addition, markedly improved histopathological damage, hepatocyte apoptosis, oxidative stress liver. activation M1 macrophages mononuclear cells was also compared control group. expression macrophage-associated proinflammatory cytokines genes, including interleukin (IL)-6, IL-12, inducible nitric oxide synthase (iNOS), decreased treatment. Finally, regulated macrophage polarization by modulating mitogen-activated protein kinases (MAPK), nuclear factor (NF)-κB, interferon regulatory (IRF) signaling pathways. Thus, findings indicate protects A-induced limiting via MAPK, NF-κB, IRF pathways, suggesting possible injury.

Language: Английский

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Research progress on rodent models and its mechanisms of liver injury

Life Sciences, Journal Year: 2023, Volume and Issue: 337, P. 122343 - 122343

Published: Dec. 15, 2023

The liver is the most important organ for biological transformation in body and crucial maintaining body's vital activities. Liver injury a serious pathological condition that commonly found many diseases. It has high incidence rate, difficult to cure, prone recurrence. can cause harm body, ranging from mild severe fatty disease. If continues worsen, it lead fibrosis cirrhosis, ultimately resulting failure or cancer, which seriously endanger human life health. Therefore, establishing an rodent model mimics pathogenesis severity of clinical great significance better understanding patients developing more effective treatment methods. author this article summarizes common chemical models, immune alcoholic drug-induced systematically elaborates on modeling methods, mechanisms action, pathways advantages disadvantages each type model. aim study establish reliable models researchers use exploring anti-liver hepatoprotective drugs. By creating accurate theoretical frameworks, we hope provide new insights into

Language: Английский

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Sophoricoside attenuates autoimmune‑mediated liver injury through the regulation of oxidative stress and the NF‑κB signaling pathway

International Journal of Molecular Medicine, Journal Year: 2023, Volume and Issue: 52(3)

Published: July 17, 2023

The prevalence of autoimmune hepatitis (AIH) is increasing, yet specific pharmacotherapies remain to be explored. present study aimed investigate the effects sophoricoside (SOP), a bioactive component medical herbs, on AIH and elucidate underlying mechanisms. Bioinformatic approaches were used predict potential targets regulatory mechanisms SOP AIH. evaluated by determining expression levels inflammatory cytokines, histological liver injury hepatic fibrosis in an improved chronic cytochrome P450 2D6 (CYP2D6)‑AIH mouse model concanavalin‑A (ConA)‑induced acute immune‑mediated injury. antioxidant activity was detected vivo vitro experiments. selected signal targeted further confirmed using western blot analysis immunofluorescence staining. results bioinformatic revealed that related oxidative stress NF‑κB gene set. transcription factor family key player controls both innate adaptive immunity. activation signaling pathway often associated with disorders. In animal experiments, attenuated CYP2D6/ConA‑induced AIH, as evidenced significant reduction enzymes serum, cytokine lesions liver. response also significantly inhibited SOP, decrease malondialdehyde, elevations total capacity glutathione peroxidase levels. experiments reduced enhanced nuclear translocation phosphorylated p65 livers mice lipopolysaccharide‑stimulated AML12 cells. On whole, demonstrates protective role which may mediated limiting hepatocytes.

Language: Английский

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