Resveratrol has been suggested to mediate liver fibrosis. The switch from classically M(LPS) to alternatively activated M(IL-4) macrophages shows to protect organs from fibrosis. However, the mechanisms remain unclear. The study aimed to investigate whether resveratrol inhibited liver fibrosis by delivering IL-10 to promote the macrophage polarization in vitro and in vivo. We observed that resveratrol improved CCL₄-induced liver fibrosis, upregulated Kupffer cells, increased the expression of IL-10 and M(IL-4) marks including Mrc1, Mrc2, CD163 and Arg1, whereas it slightly suppressed the level of M(LPS) including iNOS, TNF-α and MCP1. In vitro, resveratrol promoted the M(LPS) switch to M(IL-4) macrophage and elevated the expression of CD206 and iNOS as well. Meanwhile, IL-10 increased in both M(IL-4) and M(LPS). We concluded that resveratrol relieved liver fibrosis by producing more IL-10 to promote the polarization of M(LPS) to M(IL-4)-like macrophages.

Inflammatory bowel disease (IBD) management remains challenging due to limited preventive strategies and the low bioavailability of therapeutic agents like resveratrol (RSV). While RSV exhibits anti-inflammatory properties, its preventive potential via gut microbiome modulation remains unexplored. A murine colitis model was established using 2.5% DSS, with mice randomized into control (CON), DSS, therapeutic RSV treatment (RSV), and preventive RSV treatment (PRE) groups. Clinical outcomes, intestinal barrier integrity, inflammatory cytokines, macrophage polarization, TLR4/NF-κB signaling, and gut microbiota (16S rRNA sequencing) were systematically evaluated. Preventive RSV (PRE) outperformed therapeutic RSV across all metrics. PRE attenuated colitis severity by 51.4% (weight loss, P < 0.001 vs. RSV) and restored mucosal architecture (P = 0.048 vs. DSS). Mechanistically, PRE normalized barrier function via transcriptional (ZO-1: 56.7% of CON; Occludin: 14-fold induction vs. DSS) and protein-level recovery (ZO-1: 96.5% of CON, P = 0.02), suppressed pro-inflammatory cytokines (TNF-α: 80.8%; IL-6: 69.9%; IL-18: >96%, P < 0.001 vs. DSS), and promoted M2 macrophage polarization (CD206: 1.7-fold vs. CON, P = 0.02) through TLR4/NF-κB inhibition (53% TLR4 reduction vs. 15% with RSV, P < 0.001). Despite comparable α-diversity between RSV and PRE, PRE uniquely enriched barrier-protective taxa (Lactococcus, Muribaculum) and restored microbial amino acid biosynthesis. Crucially, PRE’s efficacy despite low systemic bioavailability implicated microbiome-mediated “luminal priming” as its primary mechanism. This study redefines preventive RSV as a microbial ecosystem engineer that preemptively fortifies the gut against inflammation via microbiome-immune-metabolic crosstalk. By prioritizing ecological prevention over symptom suppression, our findings offer a transformative “food as medicine” strategy for IBD, highlighting RSV’s potential as a chronotherapeutic agent to reshape clinical paradigms.

Background: Spontaneous bacterial peritonitis (SBP) is a common complication in patients with cirrhosis. The diagnosis of SBP is still mostly based on ascites cultures and absolute ascites polymorphonuclear (PMN) cell count, which restricts the widely application in clinical settings. This study aimed to identify reliable and easy-to-use biomarkers for both diagnosis and prognosis of cirrhotic patients with SBP. Methods: We conducted a retrospective study including 413 cirrhotic patients from March 2013 to July 2022 in the First Affiliated Hospital of Guangxi Medical University. Patients’ clinical characteristics and laboratory indices were collected and analyzed. Two machine learning methods (Xgboost and LASSO algorithms) and a logistic regression analysis were adopted to screen and validate the indices associated with the risk of SBP. A predictive model was constructed and validated using the estimated area under curve (AUC). The indices related to the survival of cirrhotic patients were also analyzed. Results: A total of 413 cirrhotic patients were enrolled in the study, of whom 329 were decompensated and 84 were compensated. 52 patients complicated and patients with SBP had a poorer Child–Pugh score (P < 0.05). Patients with SBP had a greater proportion of malignancies than those without SBP(P < 0.05). The majority of laboratory test indicators differed significantly between patients with and without SBP (P < 0.05). Albumin, neutrophil-to-lymphocyte ratio (NLR), and ferritin-to-neutrophil ratio (FNR) were found to be independently associated with SBP in decompensated cirrhotic patients using LASSO algorithms, and logistic regression analysis. The model established by the three indices showed a high predictive value with an AUC of 0.808. Furthermore, increased neutrophils, ALP, and C-reactive protein-to-albumin ratio (CAR) were associated with the shorter survival time of patients with decompensated cirrhosis, and the combination of these indices showed a greater predictive value for cirrhotic patients. Conclusions: The present study identified FNR as a novel index in the diagnosis of SBP in decompensated patients with cirrhosis. A model based on neutrophils, ALP and CAR showed high performance in predicting the prognosis of patients with decompensated cirrhosis.

Acute kidney injury (AKI) is a severe complication in patients with decompensated cirrhosis, associated with increased mortality. This study aimed to identify key indicators associated with AKI in patients with decompensated cirrhosis and to develop a predictive model for outcome assessment. A total of 487 patients with cirrhosis were enrolled and divided into decompensated and compensated groups. We found that decompensated cirrhosis patients had significantly higher rates of AKI compared to compensated patients. Patients with AKI exhibited worse clinical outcomes (28-day mortality) and significant differences in multiple laboratory parameters. Three machine learning algorithms identified four common indicators, including activated partial thromboplastin time (APTT), alkaline phosphatase (ALP), total bilirubin (TBil), and maximum creatinine (Cr_max) were associated with AKI outcomes. Logistic regression modeling based on these variables yielded an AUC of 0.811 in the derivation cohort and 0.824 in the external validation cohort with 61 patients, indicating strong predictive accuracy. The nomogram demonstrated good calibration and clinical utility based on decision curve analysis. This study identifies four clinically relevant biomarkers significantly linked to adverse outcomes in patients with decompensated cirrhosis and AKI. A predictive model incorporating these markers demonstrates high accuracy and generalizability, offering a valuable tool for early risk stratification.

Background Spontaneous bacterial peritonitis (SBP) is a common complication in patients with cirrhosis, but the biomarkers for diagnosis have yet to be validated. This study aimed to identify reliable and easy-to-use biomarkers for the diagnosis and prognosis of cirrhotic patients with complicated SBP. Methods Cirrhosis data were collected retrospectively; The clinical features and laboratory test indices were analyzed. The indices related to the SBP of cirrhosis were analyzed. Two machine learning methods (Xgboost and LASSO algorithms) and a logistic regression analysis were adopted to screen and validate the indexed risk associated with SBP risk, then a predictive model was built and validated using the area under curve (AUC) estimated. The indices related to the survival of cirrhotic patients were also analyzed. Results A total of 413 cirrhotic patients were included, of whom 329 were decompensated and 84 were compensated. 52 patients complicated SPB and they were all decompensated patients. Patients with SBP have a poorer Child-Pugh score (P < 0.05) and the proportion of cancers was higher in patients with SBP than in those without SBP (P < 0.05). Most laboratory test indices differed significantly between patients with and without SBP (P < 0.05). Xgboost, LASSO algorithms, and logistic regression analysis identified that albumin, neutrophil-to-lymphocyte ratio (NLR), and ferritin-to-neutrophil ratio (FNR) were independently associated with SBP in uncompensated cirrhotic patients, and that established by the three indices model showed a high predictive value. with the AUC being 0.808. In addition, high neutrophils, ALP and CAR were associated with the shorter survival time of patients with decompensated cirrhosis, and the combination of these indices showed a better prognostic value for cirrhotic patients. Conclusions The present study identified FNR as a new index in the diagnosis of SBP in uncompensated patients with cirrhosis. A model constructed from neutrophils, ALP and CAR showed high performance in predicting the prognosis of patients with uncompensated cirrhosis.

作为慢性肝病研究的新兴概念, 近年来, 肝硬化逆转和再代偿得到了越来越多的证据支持. 增加对肝硬化逆转和再代偿的认识, 有助于进一步划分肝硬化的自然病程, 为肝硬化机制的基础研究和临床管理提供指导. 然而, 对两者的定义、潜在机制和影响因素的研究尚处于早期阶段. 本文强调了肝硬化组织学和功能上的可逆性, 概述了肝硬化逆转和再代偿的可能机制和诊断标准, 总结了现有的相关研究证据, 并提出了该领域亟待解决的挑战.