Association between overt hepatic encephalopathy and liver pathology after transjugular intrahepatic portosystemic shunt creation in cirrhotic patients

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 9, 2025

To investigate the association between overt hepatic encephalopathy (OHE) and liver pathology after transjugular intrahepatic portosystemic shunt (TIPS) creation in cirrhotic patients. From July 2015 to April 2024, 73 patients from 4 hospitals China who received TIPS biopsy were retrospectively enrolled this study. Based on whether OHE occurred within 3 months creation, categorized into (n = 29) non-OHE 44) groups. The was assessed by hematoxylin-eosin (H&E), Sirius red staining, immunohistochemistry, immunofluorescence. Liver H&E staining showed typical features of cirrhosis (including disordered structure pseudolobule formation) all No marked difference observed extracellular matrix (ECM) deposition However, group had a higher level systemic inflammation than group. And there strong correction macrophage infiltration serum inflammatory indicators. Additionally, more neovascularization, which consistent with inflammation. emergence is closely associated pathology, especially angiogenesis, but not ECM deposition.

Язык: Английский

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Kanglexin, a New Anthraquinone Compound, Inhibits Hepatic Fibrosis by Regulating Glutathione Metabolism with Pck1-Mediated Gluconeogenesis

Опубликована: Янв. 1, 2025

Язык: Английский

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The Novel Long-Acting Peptide S6-FA Attenuates Liver Fibrosis In Vitro and In Vivo

ACS Omega, Год журнала: 2025, Номер 10(9), С. 9661 - 9674

Опубликована: Фев. 27, 2025

Liver fibrosis can progress to cirrhosis and hepatocellular carcinoma. Currently, there is no effective drug for liver fibrosis. The peptide 6 (T6) an endogenous derived from human intrauterine adhesion tissues has antifibrotic potential. Here, improve the long-term efficacy activity of T6, we conducted rational modified T6 through studying structure–activity, synthesized a series analogues. Among them, S6 S6-FA exhibited optimal antihepatic activity, had stronger long-acting effect than S6. two analogues inhibited expression α-SMA Collagen 1 in TGF-β-induced LX2 cells model CCl4-induced mouse Besides, discovered that remarkably reduced AST ALT serum levels. Mechanistic studies have demonstrated inhibiting Erk, Smad P65 pathways. This study provided novel potential candidate compounds treating

Язык: Английский

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Exploring shared pathogenic mechanisms and biomarkers in hepatic fibrosis and inflammatory bowel disease through bioinformatics and machine learning

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Май 12, 2025

The coexistence of hepatic fibrosis (HF) and inflammatory bowel disease (IBD) represents a significant clinical concern due to their poorly characterized shared pathogenic mechanisms. Current limitations in identifying common biomarkers for comorbid cases impede early dual diagnosis therapeutic interventions. Differentially expressed genes (DEGs) were screened, followed by Weighted Gene Co-expression Network Analysis (WGCNA) identify disease-associated modules. key diagnostic determined via protein-protein interaction (PPI) network combined with two machine learning algorithms. logistic regression model was subsequently developed based on these genes. Immune cell infiltration profiling both diseases assessed the CIBERSORT algorithm. construction genes-miRNAs genes-TFs (Transcription Factors) regulatory networks NetworkAnalyst website. Potential drug-gene interactions predicted utilizing DSigDB database. expression distribution validated through single-cell sequencing analysis. A sum 119 up-regulated 17 down-regulated which enriched categories associated immune chemotaxis, cytokine regulation, metabolic processes, enzymatic activity, extracellular matrix deposition, enrichment WGCNA revealed four gene Four including MMP2, COL1A2, STAT1, CXCL1. ROC curve analysis confirmed robust performance as AUC > 0.7 individual 0.85 model. M1 macrophages significantly increased pathologies diseases. total 462 drugs targeting patterns across diverse subpopulations visualized CXCL1, STAT1 identified IBD HF, providing molecular basis precision medicine approaches. It elucidated similarities between HF terms immunity, metabolism, fibrosis.

Язык: Английский

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Evaluation of Aortic Hemodynamics Using Four‐Dimensional Flow of Magnetic Resonance Imaging in Rabbits with Liver Fibrosis

Journal of Magnetic Resonance Imaging, Год журнала: 2024, Номер 60(6), С. 2604 - 2612

Опубликована: Март 23, 2024

Background Liver fibrosis (LF) precipitates systemic hemodynamic alterations, however, its impact on the aorta remaining undefined. Purpose To assess hemodynamics changes during LF development in a rabbit model. Study Type Prospective, experimental. Animal Model Thirty 7‐month‐old male rabbits underwent bile duct ligation (BDL) to induce LF. Field Strength/Sequence Biweekly four‐dimensional (4D) flow imaging incorporating 3D gradient‐echo at 3.0 T scanner for 14 weeks post‐BDL. Assessment Histopathological exams 2–5 were performed each time point, following MRI scan. was graded using Metavir scale by pathologist. 4D analyzed two radiologists dedicated postprocessing software. They recorded parameters four sections (aortic sinus, before and after bifurcation of aortic arch, descending aorta). Statistical Tests The linear mixed model; Bonferroni correction; Pearson correlation coefficient ( r ); receiver operating characteristic (ROC) curve; Delong test. level significance set P < 0.05. Results Following BDL, wall shear stress (WSS) (0.23–0.32 Pa), energy loss (EL) (0.27–1.55 mW) significantly increased second week plane, peaking sixth (WSS: 0.35–0.49 Pa, EL: 0.57–2.0 mW). So did relative pressure difference (RPD) (second week: 1.67 ± 1.63 mmHg, 2.43 0.63 mmHg) plane 2. Notably, RPD 2 displayed highest area under ROC curve 0.998 (specificity: 1, sensitivity: 0.967). found second, fourth, with grade F2, F3, F4, respectively. most strongly correlated severity = 0.86). Data Conclusions occurrence could increase WSS, EL, as early BDL. Level Evidence 1 Technical Efficacy Stage

Язык: Английский

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Hepcidin inhibits hepatocyte apoptosis through the PERK pathway in acute liver injury and fibrosis

Hepatology Communications, Год журнала: 2024, Номер 9(1)

Опубликована: Дек. 19, 2024

Background: Hepcidin, a peptide hormone primarily produced by the liver, regulates iron metabolism interacting with its receptor, ferroportin. Studies have demonstrated that hepcidin participates in progression of liver fibrosis regulating HSC activation, but regulatory effect on hepatocytes remains largely unknown. Methods: A carbon tetrachloride (CCl 4 )-induced model was established C57BL/6 wild-type (WT) and knockout ( Hamp −/− ) mice. Liver injury inflammation were assessed WT mice at 24 48 hours following acute CCl exposure. In addition, transcriptomic sequencing primary performed to compare gene expression profiles between after injury. The function identified molecule Eif2ak3/PERK (protein kinase R(PKR)-like endoplasmic reticulum kinase), evaluated both vitro vivo. Results: We found serum significantly increased during induced bile duct ligation. -treated developed more severe injury, fibrosis, hepatocyte apoptosis, elevated Bax decreased Bcl-2 expression, compared Transcriptomic analysis revealed PERK upregulated treatment, promoting apoptosis expression. Subsequently, we prevents inhibiting Conclusions: Hepcidin inhibits through suppression pathway, highlighting protective role identifying potential therapeutic target for treatment fibrosis.

Язык: Английский

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Bidirectional Impact of Varying Severity of Acute Kidney Injury on Calcium Oxalate Stone Formation

Kidney & Blood Pressure Research, Год журнала: 2024, Номер 49(1), С. 946 - 960

Опубликована: Окт. 18, 2024

Introduction: Acute kidney injury (AKI) is a prevalent renal disorder. The occurrence of AKI may promote the formation calcium oxalate stones by exerting continuous effects on tubular epithelial cells (TECs). We aimed to delineate molecular interplay between and nephrolithiasis. Methods: A mild (20 min) severe (30 ischemia-reperfusion model was established in mice. Seven days after injury, were induced using glyoxylate (Gly) evaluate impact stones. Transcriptome sequencing performed TECs elucidate relationship severity Key transcription factors (TFs) regulating differential gene levels identified motif analysis, pioglitazone, ginkgetin, fludarabine used for targeted therapy validate key TFs as potential targets stone treatment. Results: Severe led increased deposition crystals renal, impaired function, upregulation stone-related expression. In contrast, associated with decreased crystal deposition, preserved downregulation similar Transcriptomic analysis revealed that genes inflammation cell adhesion pathways significantly upregulated AKI, while related energy metabolism AKI. An integrative bioinformatic uncovered TF regulatory network within TECs, pinpointing PKNOX1 involved inflammation-related inhibiting function pioglitazone could simultaneously reduce increase kidney. On other hand, also protective role STAT1 kidneys enhancing ginkgetin formation, specific inhibitor STAT1, fludarabine, eliminate therapeutic Conclusion: Inadequate repair increases risk regulated playing this process. Inhibiting can formation. Conversely, effective through expression protect TEC activating achieve goal treating

Язык: Английский

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