Suppressor of cytokine signaling 2 modulates regulatory T cell activity to suppress liver hepatocellular carcinoma growth and metastasis

World Journal of Gastroenterology, Год журнала: 2025, Номер 31(13)

Опубликована: Апрель 2, 2025

BACKGROUND Liver hepatocellular carcinoma (LIHC) is a highly aggressive cancer with poor prognosis due to its complex tumor microenvironment (TME) and immune evasion. Regulatory T cells (Tregs) play critical role in progression. Suppressor of cytokine signaling 2 (SOCS2), key regulator, may modulate Treg activity impact LIHC growth metastasis. AIM To explore how the SOCS2 affects on METHODS transcriptome data from The Cancer Genome Atlas database were analyzed using Gene Set Enrichment Analysis, Estimation Stromal Immune Cells Malignant Tumors Using Expression Data, Cell-Type Identification by Estimating Relative Subsets RNA Transcripts evaluate pathways infiltration. Key prognostic genes identified Weighted Co-expression Network Analysis machine learning. In vitro , co-culture experiments, migration assays, apoptosis detection, enzyme-linked immunosorbent assay conducted. vivo growth, metastasis, assessed subcutaneous lung metastasis mouse models hematoxylin eosin staining, Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling, immunohistochemistry analyses. RESULTS overexpression inhibited cell activity, reducing invasion while increasing apoptosis. suppressed confirming therapeutic potential. CONCLUSION modulates CD4+ function TME, contributing Targeting presents potential strategy for treating LIHC.

Язык: Английский

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G0S2 Promotes PD-L1 Expression in Monocytes and Influences the Efficacy of PD-1 Inhibitors in Hepatocellular Carcinoma

Genes, Год журнала: 2025, Номер 16(4), С. 448 - 448

Опубликована: Апрель 13, 2025

Background: Hepatocellular carcinoma (HCC) is a prevalent and highly lethal form of liver cancer, with limited effective treatment options, particularly in the advanced stages. Immunotherapy using PD-1 inhibitors has emerged as promising modality, yet substantial proportion patients exhibit resistance or fail to respond such therapies. This study aimed elucidate role G0/G1 Switch 2 (G0S2) regulating PD-L1 expression monocytes within HCC tumor microenvironment investigate its impact on efficacy inhibitors. Methods: Gene data among treated were obtained from single-cell sequencing database; immunohistochemistry was performed detect G0S2 cancer tissues adjacent non-tumorous patients; flow cytometry utilized analyze G0S2, PD-L1, CD206, CD14 PBMCs CD8+T cell proliferation IFN-γ secretion used evaluate knockdown. Results: Utilizing patients, we identified that significantly elevated non-responders (NR) compared responders (R) inhibitor therapy. The immunohistochemical analysis confirmed higher levels tissues, while revealed increased CD206 peripheral blood mononuclear cells (PBMCs) NR R healthy controls. functional experiments involving knockdown THP-1 monocyte line resulted significant reduction concomitant increase production. Conclusions: These findings indicate facilitates upregulation monocytes, thereby suppressing T activity contributing against HCC. high offers non-invasive easily detectable biomarker for predicting Consequently, targeting may enhance responsiveness immunotherapy providing new avenue optimizing strategies improving patient outcomes.

Язык: Английский

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Mangiferin for the Management of Liver Diseases: A Review

Foods, Год журнала: 2023, Номер 12(13), С. 2469 - 2469

Опубликована: Июнь 23, 2023

The liver is a digestive and metabolic organ, several factors can induce damage, which severe threat to human health. As natural polyphenolic compound, mangiferin belongs xanthone glucoside mainly exists in many plants, such as mango. It notorious that has remarkable pharmacological activities anti-inflammatory, anti-tumor, antioxidative stress, antiviral so on. Emerging evidence indicates the therapeutic benefits of against disease, including injury, nonalcoholic fatty alcoholic fibrosis, hepatocellular carcinoma. This review aims summarize possible underlying signaling mediated by disease treatment available findings mangiferin, be used treat different diseases may contribute agent for humans.

Язык: Английский

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A Review: Cytochrome P450 in Alcoholic and Non-Alcoholic Fatty Liver Disease

Diabetes Metabolic Syndrome and Obesity, Год журнала: 2024, Номер Volume 17, С. 1511 - 1521

Опубликована: Апрель 1, 2024

Alcoholic fatty liver disease (FALD) and non-alcoholic (NAFLD) have similar pathological spectra, both of which are associated with a series symptoms, including steatosis, inflammation, fibrosis.These clinical manifestations caused by hepatic lipid synthesis metabolism dysregulation affect human health.Despite having been studied extensively, targeted therapies remain elusive.The Cytochrome P450 (CYP450) family is the most important drug-metabolising enzyme in body, primarily liver.It responsible for endogenous exogenous compounds, completing biological transformation.This process relevant to occurrence development AFLD NAFLD.In this review, correlation between CYP450 metabolic diseases summarised, providing new insights treatment NAFLD.

Язык: Английский

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RSK1 and RSK2 as therapeutic targets: an up-to-date snapshot of emerging data

Expert Opinion on Therapeutic Targets, Год журнала: 2024, Номер unknown, С. 1 - 13

Опубликована: Дек. 4, 2024

Introduction The four members of the p90 ribosomal S6 kinase (RSK) family are serine/threonine protein kinases, which phosphorylated and activated by ERK1/2. RSK1/2/3 further PDK1. Receiving inputs from two major signaling pathways places RSK as a key node in numerous pathologies. A plethora RSK1/2 substrates have been identified, majority cases causative roles these play pathology unknown.

Язык: Английский

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In vitro digestibility and hepato-protective potential of Lophatherum gracile Brongn. leave extract

Food Chemistry, Год журнала: 2023, Номер 433, С. 137336 - 137336

Опубликована: Авг. 30, 2023

Язык: Английский

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Proteomics and network pharmacology of Ganshu Nuodan capsules in the prevention of alcoholic liver disease

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Сен. 18, 2023

Ganshu Nuodan is a liver-protecting dietary supplement composed of Ganoderma lucidum (G. lucidum) spore powder, Pueraria montana (Lour.) Merr. (P. montana), Salvia miltiorrhiza Bunge (S. miltiorrhiza) and Astragalus membranaceus (Fisch.) Bunge. (A. membranaceus). However, its pharmacodynamic material basis mechanism action remain unknown.A mouse model acute alcohol liver disease (ALD) induced by intragastric administration 50% was used to evaluate the hepatoprotective effect Nuodan. The chemical constituents were comprehensively identified UPLC-QTOF/MS, then potential explored proteomics network pharmacology.Ganshu could ameliorate ALD, which mainly manifested in significant reduction alanine aminotransferase (ALT) aspartate (AST) serum malondialdehyde (MDA) content remarkably increase glutathione (GSH) superoxide dismutase (SOD) activity liver. Totally 76 from including 21 quinones, 18 flavonoids, 11 organic acids, 7 terpenoids, 5 ketones, 4 sterols, 3 coumarins others. Three key signaling pathways via studies, namely Arachidonic acid metabolism, Retinol HIF-1 pathway respectively. Combined with pharmacology molecular docking, six targets subsequently obtained, Ephx2, Lta4h, Map2k1, Stat3, Mtor Dgat1. Finally, these their related components verified explain Nuodan.Ganshu can protect alcohol-induced injury mice inhibiting oxidative stress, lipid accumulation apoptosis. Our study provides scientific for ALD supports traditional application.

Язык: Английский

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FIB‐4 index is associated with mortality in critically ill patients with alcohol use disorder: Analysis from the MIMIC‐IV database

Addiction Biology, Год журнала: 2024, Номер 29(2)

Опубликована: Янв. 23, 2024

Abstract Background The relationship between fibrosis‐4 (FIB‐4) index and all‐cause mortality in critically ill patients with alcohol use disorder (AUD) is unclear. present study aimed to investigate the predictive ability of FIB‐4 for AUD association them. Methods A total 2528 were included using Medical Information Mart Intensive Care IV (MIMIC‐IV) database. was calculated each patient existing formula. equally divided into four groups based on quartiles FIB‐4. Multivariate logistic regression Cox proportional hazard model used evaluate in‐hospital mortality, 28‐day 1‐year mortality. Kaplan–Meier curves analyse incidence among groups. Results positively associated ratio (HR) 1.354 [95% confidence interval (CI) 1.192–1.538]. There similar trends [odds (OR): 1.440, 95% CI (1.239–1.674)] [HR: 1.325, (1.178–1.490)]. Conclusion Increased greater patients.

Язык: Английский

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Modified Buyang Huanwu Decoction alleviates diabetic liver injury via inhibiting oxidative stress in db/db mice

American Journal of Translational Research, Год журнала: 2024, Номер 16(1), С. 39 - 50

Опубликована: Янв. 1, 2024

In diabetes, chronic hyperglycemia increases the overactivation of oxidative phosphorylation mitochondria in liver, resulting stress (OS) damage. The Nrf2 signaling pathway plays a key role preventing hepatic injury and inflammation. This study aims to investigate therapeutic effect mechanism Modified Buyang Huanwu Decoction (mBYHWD) on diabetic liver (DLI) by regulating mediated pathway.

Язык: Английский

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Expansion of effector regulatory T cells in steroid responders of severe alcohol-associated hepatitis

Liver Transplantation, Год журнала: 2024, Номер 30(9), С. 877 - 886

Опубликована: Апрель 16, 2024

While steroid therapy is the preferred treatment for severe alcohol-associated hepatitis, role of effector regulatory T (eTreg) cells and their association with response clinical outcomes in these patients remains to be elucidated. We prospectively enrolled 47 consecutive consisting hepatitis treated steroids (n=18; steroid-treated group) mild (n=29; nontreated group). After isolating peripheral blood mononuclear from at enrollment again 7 days later, frequency eTreg was examined using flow cytometry. Single-cell RNA sequencing analysis conducted paired cells. In vitro experiments were also performed assess phenotype changes suppressive function Treg following treatment. The group exhibited significantly higher Model End-Stage Liver Disease scores than ( p < 0.01). Within group, proportion expanded responders (n=13; = Furthermore, a significant positive correlation observed between decrease score increase 0.05). (pre-steroid post-steroid therapy) responder revealed gene expression monocytes, suggesting enhancement cell function. results showed an elevation after therapy. conclusion, our findings suggest that efficacy mediated by number

Язык: Английский

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