A network toxicology and molecular docking-based approach revealed shared hepatotoxic mechanisms and targets between the herbicide 2,4-D and its metabolite 2,4-DCP

Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 154086 - 154086

Published: Feb. 1, 2025

Language: Английский

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hAMSCs regulate EMT in the progression of experimental pulmonary fibrosis through delivering miR-181a-5p targeting TGFBR1

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

Published: Jan. 5, 2025

Pulmonary fibrosis (PF) is a common and multidimensional devastating interstitial lung disease. The development of novel more effective interventions for PF an urgent clinical need. A previous study has found that miR-181a-5p plays important role in the PF, human amniotic mesenchymal stem cells (hAMSCs) exert potent therapeutic potential on PF. However, whether hAMSCs act by delivering its detailed mechanism still remain unknown. Thus, this was designed to investigate underlying possible bleomycin (BLM)-induced mouse model, co-culture system A549 epithelial transition (EMT) focusing effects collagen deposition, EMT, cell cycle regulation. with different expression levels were constructed. BLM (4 mg/kg) used create while TGF-β1 induce construct EMT model. Furthermore, deposition during assessed vivo vitro. We exerted anti-fibrotic effect BLM-induced Moreover, also protective TGFβ1-induced ameliorated promoting proliferation, reducing apoptosis, attenuating through paracrine effects. regulated targeting TGFBR1. Our findings reveal first time inhibit EMT. Mechanistically, hMASCs achieved

Language: Английский

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Characterization of rectus femoris lesions in knee osteoarthritis at different stages and the effect of ultrasound-guided acupotomy

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 23, 2025

Introduction Chronic injury to the rectus femoris muscle induces and exacerbates progression of knee osteoarthritis (KOA). However, lesion characteristics in KOA at different stages have not been fully characterized. The aim this study was analyze pattern investigate mechanism by which ultrasound-guided acupotomy operations can prevent control KOA. Methods Early, middle, late-stage rabbit models were constructed using modified Videman method. Ultrasonography used record elastic modulus cross-sectional area muscle, morphology observe ultramicroscopic changes assess degree fibrosis. Additionally, performed on model KOA, alterations key molecular markers fibrosis determined Western Blot qPCR methods. Results As disease progressed, rabbits gradually increased, decreased, increased. In contrast, improved after intervention. Conclusion These findings highlight gradual increase elasticity, decrease area, increased as progressed. Ultrasoundguided shown a protective effect cartilage delay ameliorating pathological muscle. may involve reducing chronic protecting joint homeostasis attenuating

Language: Английский

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Serum CircCSPP1 is Correlated with the Occurrence and Severity of NAFLD in a Chinese Population

Hormone and Metabolic Research, Journal Year: 2025, Volume and Issue: 57(03), P. 208 - 215

Published: March 1, 2025

The relationship between serum circCSPP1, circNIPSNAP3A, or circRFX8 and the occurrence severity of non-alcoholic fatty liver disease (NAFLD) has yet to be fully elucidated. A total 494 participants were divided into NAFLD control groups, clinical data, including demographic, physiological biochemical parameters, collected. Serum levels measured using quantitative real-time PCR, was assessed by ultrasonography computed tomography. group exhibited significantly higher circCSPP1 compared (p=0.04). CircCSPP1 is independently associated with NAFLD. Participants high (>66th percentile) had a greater prevalence mild advanced NAFLD, as well triglyceride levels, those low (<33rd (p<0.05 for all). No significant correlations observed circNIPSNAP3A These findings suggest that potentially mediated hypertriglyceridemia.

Language: Английский

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PI3K/Akt Pathway involvement in hepatic inflammation: In silico evaluation of silybum marianum and a research proposal for homeopathic Carduus marianus

International Journal of Homoeopathic Sciences, Journal Year: 2025, Volume and Issue: 9(1), P. 167 - 183

Published: Jan. 1, 2025

Silybum marianum (SM) (L.) Gaertn is a natural remedy found in Traditional Chinese Medicine (TCM), homeopathy, and the phytotherapy compendium, often prescribed to treat liver ailments. Using silico tools based on TCM research framework, we evaluated SM bioactive compounds within context of hepatic inflammation. Through Cytoscape software STRING platform, confirmed therapeutic relevance several core targets. Via Kyoto Encyclopedia Genes Genomes (KEGG) Gene Ontology (GO) enrichment analyses, characterized pathways involved The PI3K/Akt signaling pathway ranked among top three enriched pathways, with an elevated gene count high statistical significance. Based results, designed study evaluate effects homeopathic Carduus marianus (CM). By transposing "like-cures-like" diagnostic theory, propose strategy for conducting vivo ultradiluted remedies.

Language: Английский

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Comparative Efficacy of β-Carotene and Losartan Against Isoproterenol-Induced Cardiac Fibrosis: An Experimental and Computational Studies

Journal of the American Nutrition Association, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: Feb. 10, 2025

Objective β-carotene, a vitamin A precursor is reported to inhibit molecular pathways cardinal pathogenesis of fibrotic tissue alterations and in this study, the effectiveness 14 days oral administration β-carotene (10, 20, 40 mg/kg/day) cardiac fibrosis (CF) rats was studied explored mechanisms through network pharmacology.

Language: Английский

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Hepatic adverse events associated with anaplastic lymphoma kinase tyrosine kinase inhibitors: a disproportionality analysis based on FAERS Database and analysis of drug-gene interaction network

Expert Opinion on Drug Safety, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Anaplastic lymphoma kinase (ALK) tyrosine inhibitors (TKIs) are vital for treating ALK-positive cancers but have been associated with liver injury, necessitating further safety investigation. This study examines hepatic adverse event (AE) signals related to ALK TKIs using the U.S. FDA Adverse Event Reporting System (FAERS) and explores potential mechanisms of injury. AE reports from FAERS (Q3 2011 Q1 2024) injury were analyzed reporting odds ratio (ROR) multi-item gamma Poisson shrinker (MGPS) methods. Pathway enrichment drug-gene network analyses performed investigate underlying mechanisms. identified 2,132 database linking AEs therapy. Significant detected by ROR MGPS methods, common including aminotransferase abnormalities, hyperbilirubinemia, increased blood alkaline phosphatase, mainly occurring within first 30 days treatment. Gene analysis revealed key nodes in protein-protein interaction (PPI) network, such as PIK3CA, SRC, PTK2. Enriched KEGG pathways included MAPK, PI3K-Akt, Ras signaling. pharmacovigilance identifies significant highlighting providing insights clinical management patient outcomes.

Language: Английский

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1-benzyl-6-nitro-4-phenyl-4-(methoxycarbonyl)-2(1H)-pyridinone, a novel pirfenidone derivative, alleviate hepatic fibrosis through T cells

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 184, P. 117907 - 117907

Published: Feb. 19, 2025

Language: Английский

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Indole-3-propionic acid promotes hepatic stellate cells inactivation

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 1, 2025

Abstract Background & aims We have previously reported that the serum levels of gut-derived tryptophan metabolite indole-3-propionic acid (IPA) are lower in individuals with liver fibrosis. Now, we explored transcriptome and DNA methylome associated IPA human from obese together effects on shifting hepatic stellate cell (HSC) phenotype to inactivation vitro. Methods A total 116 without type 2 diabetes (T2D) (age 46.8 ± 9.3 years; BMI: 42.7 5.0 kg/m ) Kuopio OBesity Surgery (KOBS) study undergoing bariatric surgery were included. Circulating measured using LC–MS, transcriptomics RNA-sequencing methylation Infinium HumanMethylation450 BeadChip. Human cells (LX-2) where used for vitro experiments. Results Serum expression genes enriched apoptosis, mitophagy longevity pathways liver. AKT serine/threonine kinase 1 (AKT1) was shared topmost interactive gene transcript profile. treatment induced reduced mitochondrial respiration as well modified morphology, dynamics by modulating known regulate fibrosis, survival LX-2 cells. Conclusion In conclusion, these data support has a plausible therapeutic effect may induce apoptosis HSC towards state, extending possibilities suppress fibrogenesis interfering activation metabolism. Graphical

Language: Английский

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Fufang-Biejia-Ruangan Tablet targeting both cancer-associated fibroblasts and tumor cells by HIPPO-PI3K/AKT cascades in intrahepatic cholangiocarcinoma treatment

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156690 - 156690

Published: March 1, 2025

Language: Английский

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