Alleviation of adverse effects associated with α-glucosidase inhibitors by Ocimum basilicum L., Matricaria chamomilla L., and Salvia officinalis L. reveals novel selective inhibition of Bacillus α-glucosidase by acarbose.

Hepatoprotective effects of tetrahydropalmatine against NAFLD through autophagy activation and lipid metabolic reprogramming via the AMPK-mTOR-Sirt1 axis.

Imaging alkaline phosphatase activity in alcoholic liver disease via a rational-designed NIR fluorogenic probe.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally. Menopause is associated with increased hepatic fat deposition and thus metabolic dysfunction, contributing to heightened risk of progressive liver and cardiovascular disease. Hormone replacement therapy (HRT), supported by pre-clinical data, may be associated with a lower risk. We performed a retrospective cohort study using the TriNetX global federated research network. Eligible participants were peri-menopausal women (ICD-10 codes N95/Z78.0, AND age 40-65 years) with pre-existing MASLD (based on ICD-10 codes K76.0/K75.81 or positive modified hepatic steatosis index plus ≥ 1 metabolic syndrome, MetS, trait). Patients initiating HRT (oestrogen ± progesterone) were compared with untreated controls using 1:1 propensity score matching for demographics, comorbidities, biochemistry and medications. The primary outcome was a composite of major adverse liver outcomes (MALO: portal hypertension, varices, ascites, spontaneous bacterial peritonitis, encephalopathy, hepatorenal/pulmonary syndromes, cirrhosis, decompensated liver disease, hepatocellular carcinoma, liver transplant). Secondary outcomes were individual MALO components, type 2 diabetes (T2D), major adverse cardiovascular events (MACE), breast and endometrial cancer, and venous thromboembolism (VTE). Cox regression generated hazard ratios (HRs) with 95% CIs over 5 years. Sensitivity analyses adjusted for geography, hormone type, and degree of obesity. After matching, 21 639 patients were included in each treatment arm. HRT was associated with a significantly reduced risk of MALO (HR 0.80; 0.71, 0.9), largely driven by reductions in ascites and SBP (0.78; 0.64, 0.95), and liver cirrhosis (0.75; 0.63, 0.90), and reduced risk of cardiometabolic outcomes: T2D (0.90; 0.84, 0.96), and MACE (0.90; 0.83, 0.98). HRT was not associated with increased risk of breast cancer or VTE, whilst endometrial cancer risk was reduced (0.49; 0.40, 0.61). Oestrogen was linked to greater benefits compared to progesterone, and patients with mild-moderate obesity experienced more significant risk reduction. Treatment of peri-menopausal symptoms with HRT, in patients with pre-existing MASLD, is associated with a lower 5-year risk of major liver and cardiometabolic disease. These findings support early basic science research and should prompt a closer examination through clinical trials.

Emerging importance of ALDH2 in liver diseases and its potential therapeutic role.

Metabolic dysfunction-associated fatty liver disease (MAFLD), recently redefined from non-alcoholic fatty liver disease (NAFLD), highlights the central role of metabolic dysfunction in its pathophysiology. The L-α-lysophosphatidylinositol/G protein-coupled receptor 55 (LPI/GPR55) axis, an element of the endocannabinoidome, has emerged as a key driver behind liver disease progression, leading to the progression of metabolic dysfunction associated steatohepatitis (MASH). Implicated in hepatic lipid accumulation, inflammation and fibrosis, this axis has detrimental effects in hepatocytes, Kupffer cells and hepatic stellate cells. Furthermore, recent evidence suggests that this axis induces de novo lipogenesis, promoting pro-inflammatory cytokine production, leading to fibrosis and the transition toward a steatotic liver. The enzyme membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) modulates this axis by acylation of LPI, exacerbating hepatic steatosis and insulin resistance. Until recently, no pharmacologic treatments were approved for MAFLD. However, resmetirom received FDA approval in March 2024 for the treatment of MASH, and semaglutide (Wegovy) was granted accelerated FDA approval in August 2025 for MASH with moderate-to-advanced fibrosis. Additional agents such as tirzepatide and retatrutide remain in late-stage clinical development. We propose that targeting the endocannabinoidome, specifically the LPI/GPR55 axis, represents a promising therapeutic strategy for liver disease. Previous attempts to target GPR55 therapeutically have involved small-molecule agonists and phytocannabinoids with antagonistic activity. However, progress remains limited due to the context-specific roles of GPR55 across different tissues and signalling pathways. As such, future strategies involving the LPI/GPR55 axis must focus on hepatic-specific GPR55 modulation using selective ligands and advanced delivery systems, mitigating off-target effects. This review elucidates the mechanistic role of the LPI/GPR55 axis, combining the role of MBOAT7 in the pathophysiology of metabolic-associated liver disease.

Dissecting incidence and mortality inequalities of six types of liver diseases in 39 alcohol-dominant countries and 93 virus-dominant countries under the aging context: Insights from the Global Burden of Disease Study 2021.

Non-invasive tests to guide hepatocellular carcinoma surveillance.

Cardiometabolic risk factors (CMRF) are common in alcohol-associated liver disease (ALD), but their impact on clinical outcomes is unclear. We evaluated whether CMRF identifies a higher-risk phenotype among adults with ALD. We performed a multicenter retrospective cohort study within the TriNetX research network, including adults with ALD (ICD-10 K70) from 2010 to 2019. CMRFs were defined by overweight/obesity, dysglycemia, hypertension or dyslipidemia using the steatotic liver disease framework. Individuals with other liver diseases, cancer, prior liver transplantation or pregnancy were excluded. After 1:1 propensity score matching (PSM) on demographics, comorbidities, laboratory indices and medications, we compared ALD with versus without CMRF using Cox models, overall and stratified by cirrhosis. After matching, 2942 adults with ALD were included (ALD with CMRF, n = 1471; without CMRF, n = 1471). Five-year all-cause mortality was similar between groups (Hazard Ratio [HR]: 1.01, 95% CI 0.83-1.23). In contrast, ALD patients with CMRF had higher risks of alcohol-associated hepatitis (HR 2.12, 95% CI 1.62-2.79) and a numerically higher risk of major adverse liver outcomes (HR 1.14, 95% CI 0.98-1.32). Cardiovascular complications were markedly increased, including major adverse cardiovascular events (HR 3.07, 95% CI 2.14-4.39), arrhythmia (12.4% vs. 4.8%, HR 2.24, 95% CI 1.70-2.94) and heart failure (HR 3.70, 95% CI 2.11-6.47). Infectious events were also more frequent among CMRF patients, including sepsis, urinary tract infection and pneumonia. Associations were generally stronger among patients with cirrhosis. Among individuals with ALD, CMRF does not increase short- to intermediate-term mortality but identifies a phenotype with substantially higher liver, cardiovascular and infectious morbidity. Systematic detection and intensive management of CMRF should be integrated into ALD care pathways.

Double Graph Attention Network for predicting non-alcoholic fatty liver disease in patients with type 2 diabetes.

Progress in research on the hepatoprotective effects of C-21 steroidal glycosides from Baishouwu.

An hMAO-B-activatable mitochondrial binding fluorescent probe in live-cell via enzyme-anchored and charge-driven dual targeting.

1-O-acetylbritannilactone alleviates high-fat diet-induced fatty liver by covalently targeting NLRP3.

Ophiopogonis japonicus polysaccharide inhibits oxidative stress in hepatocytes by promoting Runx3 in nonalcoholic fatty liver disease.

Association between plasma trace metals and non-alcoholic fatty liver disease among rural women in Southern China.

FXR overexpression restores NLRP3-mediated mitophagy and improves mitochondrial dysfunction in alcoholic liver disease.

Introduction: Pleural Effusion (PE) results from an imbalance between pleural fluid production and absorption. It may occur due to multiple aetiologies, including heart failure, infections, malignancies, and liver disease. While Light’s criteria remain the gold standard for classification, they misclassify up to 25% of transudates. Additional biochemical markers such as pleural fluid cholesterol, Alkaline Phosphatase (ALP), and D-dimer have shown promise in enhancing diagnostic accuracy. Aim: To compare the diagnostic efficacy of pleural fluid total cholesterol, pleural ALP, and D-dimer levels with Light’s criteria in differentiating exudative from transudative PEs. Materials and Methods: The present hospital-based crosssectional study was conducted jointly in the Departments of Respiratory Medicine and Biochemistry at Adesh Medical College and Hospital, Shahabad (M), Kurukshetra, Haryana, India, from November 2022 to October 2023. A total of 100 adult patients presenting with PE were recruited. Each patient underwent detailed clinical history, physical examination, chest radiography or Computed Tomography (CT) when indicated, and routine laboratory investigations. Pleural fluid samples were analysed for protein, Lactate Dehydrogenase (LDH), cholesterol, ALP, and D-dimer, while corresponding serum levels were also measured. Effusions were classified as transudative or exudative using Light’s criteria. Data were statistically analysed using independent t-test, Chi-square or Fisher’s exact test, binary logistic regression, and Receiver Operating Characteristic (ROC) curve analysis. A p-value <0.05 was considered statistically significant. Results: In the present study, 71% of participants were male, and the mean age was comparable between the exudative and transudative groups. Pleural fluid cholesterol, pleural ALP, pleural/serum ALP ratio, pleural D-dimer, and pleural/serum D-dimer ratio were significantly higher in exudates than in transudates (p <0.001). ROC analysis demonstrated that all parameters had an Area Under the Curve (AUC) of 1.0, with 100% sensitivity and specificity at the identified cut-off values. Logistic regression analysis identified serum ALP as a protective factor and the pleural/serum LDH ratio as an independent predictor of exudative effusion. Conclusion: Pleural fluid cholesterol, ALP, and D-dimer, along with their respective ratios, are highly reliable in differentiating exudative from transudative PEs and may serve as valuable adjuncts to Light’s criteria. These findings warrant validation in larger multicentric studies.

Phytochemicals from Achillea millefolium target NAFLD and NASH: A network pharmacology integrated bioinformatics and molecular docking investigation.

Pedunculoside ameliorates metabolic dysfunction-associated steatotic liver disease by targeting HNRNPA1 and modulating PPARα signaling pathway to enhance Mitochondrial Fatty Acid β-Oxidation.

Solanum americanum, or American black nightshade, is a common weed in Pakistan with a rich history of medicinal applications. Traditionally, its leaves and fruits have been employed to treat various conditions, including skin problems, inflammation, and menstrual irregularities. The plant's therapeutic potential is attributed to its diverse phytochemical composition, encompassing alkaloids, glycosides, and flavonoids. Its traditional use highlights the reliance on folk knowledge for treating liver disease. This study aimed to investigate the pharmacognostic features and evaluate the hepatoprotective activity of the crude fruit extract of S. americanum against ethanol-induced liver toxicity in rats. An aqueous ethanolic extract of S. americanum fruit was administered to rats with ethanol-induced liver toxicity. Silymarin was used as a reference drug for comparison. Hepatoprotective activity was assessed through biochemical analysis of aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and total protein levels. Histopathological examination of liver tissues was also conducted. The ethanol-treated group exhibited intense hepatocellular injuries and necrosis in liver tissues. Treatment with the aqueous ethanolic extract of S. americanum and silymarin resulted in near-normal lobular architecture, with only slight centrilobular degeneration of hepatocytes and minimal necrotic changes. The S. americanum extract demonstrated hepatoprotective activity, as evidenced by the partial normalization of liver biomarkers. However, its effect was less pronounced than that of silymarin. The aqueous ethanolic fruit extract of S. americanum possesses hepatoprotective properties against ethanol-induced liver toxicity in rats. S. americanum mitigates ethanol-induced liver toxicity in rats, partially normalizing liver biomarkers, likely through its antioxidant and nutritional properties, supporting its traditional use in liver disease management.