Malaria is still a pressing global health challenge, especially in sub-Saharan Africa, where behavioural factors such as alcohol consumption may exacerbate its impact. The present study is aimed at investigating the pathogenesis of alcohol-exacerbated malaria in Plasmodium berghei-infected an animal model (mice). Mice were separated into four treatment groups: control, alcohol control, P. berghei and P. berghei plus acute alcohol treatment groups. Animals were infected with malaria through intraperitoneal injection of P. berghei and an acute dose of ethanol (20% v/v, oral) was introduced 48 h post-infection. Parasitaemia was monitored using the Giemsa-stained thin blood smears. Haematological parameters were assessed using an automated blood analyser. Liver function was evaluated by measuring serum levels of AST and ALT; oxidative stress biomarkers (MDA, SOD, CAT, GSH) were evaluated, and cytokine profiles (TNF-α, IFN-γ, IL-6, IL-1β) were quantified using ELISA kits. Results show that acute alcohol intake led to a significant increase in parasitaemia in the P. berghei group (p < 0.01). Haematological analysis revealed a significant (p < 0.001) reduction in RBC count, haemoglobin levels, haematocrit percentage, platelet count and others in the P. berghei plus acute alcohol treatment group. Liver enzyme assays revealed elevated AST and ALT levels (p < 0.001) in the P. berghei group, due to acute alcohol. Cytokine analysis revealed a significant (p < 0.01) upregulation of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β and IL-6), due to acute alcohol. Oxidative stress was significantly (p < 0.001) increased, evidenced by significant elevation of MDA and significant depletions in GSH, SOD and CAT, due to acute alcohol. These results suggest that alcohol exacerbates malaria pathogenesis by increasing parasitaemia, promoting immune dysregulation, liver injury and oxidative stress, in a murine model.

Genipin (GP) is the key metabolite of geniposide (GE), the primary active component of the traditional Chinese medicine Gardeniae Fructus. Its hepatotoxicity poses a potential risk to safe clinical administration, while its core pathophysiological mechanism remains unclear. This study systematically elucidated the molecular mechanisms of GP-induced hepatotoxicity through integrated multi-omics and functional validation. GP treatment induced significant liver damage and oxidative stress in rats, characterized by elevated serum transaminases (alanine aminotransferase (ALT) increased by approximately 63.5-fold; aspartate aminotransferase (AST) by 18.6-fold), an approximately 1.8-fold decrease in superoxide dismutase (SOD) activity, and an approximately 10-fold accumulation of malondialdehyde (MDA) (all P < 0.001). Metabolomic and proteomic analyses revealed that GP binds to carbamoyl phosphate synthetase 1 (CPS1), triggering urea cycle dysfunction marked by citrulline depletion and significant downregulation of its downstream product fumarate. In vitro experiments confirmed that disrupting CPS1 impairs the urea cycle and induces oxidative stress, while CPS1 overexpression or exogenous fumarate supplementation significantly reversed oxidative stress. Clinical sample analysis revealed similar urea cycle metabolic disturbances, characterized by citrulline depletion and reduced fumarate levels, in plasma from patients with liver injury due to inappropriate use of Gardeniae Fructus-containing formulas, confirming clinical relevance. This study reveals a novel hepatotoxic mechanism whereby GP targets CPS1 to disrupt the urea cycle, reducing fumarate production and impairing nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant defense, thereby inducing oxidative stress. These findings provide a scientific basis for improving the safety evaluation and rational clinical use of Gardeniae Fructus-containing preparations.

Chemical pollution from industrial, agricultural, and urban activities represents a major threat to freshwater ecosystems and aquatic organisms. This study evaluated hepatic biomarker responses in Oreochromis niloticus (Nile tilapia) maintained under chronic environmental exposure to water from the Iguaçu River, one of the most polluted urban rivers in Brazil. Juvenile fish were kept in cages at three sites along the river, and hepatic biomarkers were assessed after 15 and 22 months of environmental exposure. Fish showed severe histopathological liver lesions, activation of antioxidant defenses, and oxidative stress responses accompanied by increased DNA damage. Immunological responses, particularly melanomacrophage proliferation and granuloma formation, were also observed across the monitored exposure scenarios. Alterations in plasma biochemical parameters, including AST, ALT, LDH, albumin, and globulin, were consistent with changes in hepatic function. Overall, the integrated biomarker responses revealed distinct patterns of biological alteration among the monitored exposure scenarios and were consistent with chronic exposure to complex environmental contaminant mixtures. These findings are consistent with alterations in liver integrity in fish maintained under long-term environmental exposure in the Iguaçu River. The study highlights the sensitivity of Nile tilapia as a bioindicator species for aquatic biomonitoring and provides valuable information to support environmental monitoring, risk assessment, and conservation strategies for the Iguaçu River Basin.

Background and aims. Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease associated with cirrhosis, hepatocellular carcinoma, and increased risks of liver-related and cardiovascular mortality. Many patients, however, remain asymptomatic until advanced stages. The gamma-glutamyl transferase to high-density lipoprotein cholesterol (GGT/HDL-C) ratio is a simple, noninvasive marker reflecting hepatic dysfunction and cardiometabolic imbalance. This study assessed its association with NAFLD and determined an optimal cutoff for identifying NAFLD. Methods. We conducted a cross-sectional analysis of 575 adults undergoing routine health examinations at the University of Medicine and Pharmacy Hospital in Ho Chi Minh City between 2021 and 2023. Participants with significant alcohol intake, viral hepatitis, or other chronic liver diseases were excluded. NAFLD was diagnosed by standardized abdominal ultrasonography based on increased hepatic echogenicity relative to the renal cortex or spleen. Associations between GGT/HDL-C and NAFLD were assessed by logistic regression (both as a continuous variable and by quartiles), and diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Statistical significance was defined as a two-tailed p-value < 0.05. Results. Individuals with NAFLD showed significantly higher BMI, prevalence of hypertension and diabetes, and elevated glucose, HbA1c, AST, ALT, GGT, cholesterol, triglycerides, and LDL-C, along with lower HDL-C. Each unit increase in the GGT/HDL-C ratio was associated with a 2% increase in the odds of NAFLD based on univariate logistic regression analysis. However, after adjustment for demographic and metabolic covariates, the GGT/HDL-C ratio was no longer independently associated with NAFLD. The highest quartile had an odds ratio of 7.05 (95% CI: 4.2-11.83) compared to the lowest. The area under the ROC curve for GGT/HDL-C was 0.72, outperforming GGT or HDL-C alone. A cutoff of 32.47 UI/mmol had 72.4% sensitivity and 63.3% specificity. Conclusions. The GGT/HDL-C ratio showed a significant unadjusted association with NAFLD and moderate discriminatory performance. However, because the association was no longer significant after full adjustment, the ratio should currently be considered a simple laboratory-based screening marker that requires further validation before routine clinical application.

Renal stones remain a prevalent renal disorder characterized by high recurrence rates and limited therapeutic options, encouraging continued research into novel agents capable of treating established stone disease. Camelus dromedarius hump fat has long been used in North African alternative medicine to treat various dermal and inflammatory diseases. This study aims to evaluate the antioxidant activity, specifically radical scavenging, and the therapeutic potential of this fat against Calcium oxalate stones induced by Ethylene glycol in a Wistar rat model. Twenty Wistar rats were divided into four groups (n=5). The first group serves as the control. The three other groups received EG in their drinking water until stones formed. Rats were fed a fresh dromedary hump fat diet at 45% w/w daily. Urinary parameters (volume, pH, electrolytes), serum biochemical assessments, and measured creatinine clearance were analyzed. Renal histopathology was performed to evaluate tissue changes. The EG-treated rats showed significant disturbances in all physiological parameters, including decreases in urinary volume, pH, and urinary electrolyte excretion. DHF demonstrated strong antioxidant activities, with DPPH scavenging (69.158%-85.571%), FRAP values (70.785%-83.971%), and ABTS (59.145%-89.195%), indicating potential to reduce oxidative stress. In addition to that, treatments with the DHF diet significantly increase urinary volume from 6.3 ± 0.2 ml to 10.12 ± 0.1 ml (p < 0.001). These alterations extend to serum creatinine and urea levels. A high increase in serum creatinine and urea levels was shown. The DHF-treated group showed a creatinine clearance of 3.46 ± 0.68 ml/min on day 21. Importantly, the DHF diet protected the liver from EG-induced damage, as evidenced by serum levels of gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) that were near control levels. In contrast, the EG-only group exhibited marked elevations in enzyme levels (p < 0.01). These findings suggest that the DHF 45% w/w diet may exert its protective effect by reducing oxidative stress and preserving tubular epithelial integrity, thereby improving urinary electrolyte excretion, decreasing crystal formation, and protecting renal tissue.

High-carbohydrate diet (HCD) is commonly used in aquaculture to reduce feed costs, but its use in carnivorous fish is constrained by the low carbohydrate tolerance of these species. Recent studies in herbivorous grass carp have shown that promoting adipocyte hyperplasia shifts adipose tissue expansion from pathological hypertrophy to healthy hyperplasia, thereby improving carbohydrate tolerance. However, whether this strategy is equally effective in carnivorous fish remains unknown. In this study, we fed largemouth bass (Micropterus salmoides) with a control diet, an HCD, or HCD supplemented with 30, 60, or 90 mg/kg rosiglitazone, a PPARγ agonist that induces adipocyte hyperplasia, for 8 weeks. The results showed that promoting adipocyte hyperplasia enhanced glucose-to-lipid conversion and lipid storage capacity in adipose tissue, and also increased lipid catabolism, thereby reducing abdominal fat accumulation. Consequently, rosiglitazone improved serum metabolic parameters, as reflected by lower levels of glucose, ALT, AST, and pro-inflammatory cytokines Il-8 and Il-1β (P < 0.05). In addition, promoting adipocyte hyperplasia alleviated hepatic steatosis by reducing hepatic glucose-to-lipid conversion, and promoted muscle fiber development and enhanced the metabolic capacity of muscle for glucose and lipids. Ultimately, the improved carbohydrate tolerance restored growth performance and reversed muscle texture deterioration, as evidenced by increased chewiness and gumminess and normalized adhesiveness. These findings demonstrate that promoting adipocyte hyperplasia effectively counteracts HCD-induced growth suppression, hepatic steatosis and flesh quality deterioration in carnivorous largemouth bass, providing a promising strategy to improve carbohydrate utilization in carnivorous fish aquaculture.

Chronic intermittent hypoxia (CIH) is an alternating state of recurrent hypoxia and reoxygenation triggered by disorders such as sleep apnea, leading to systemic oxidative stress and organ damage. In this study, we investigate the protective effect and mechanism of atraric acid (AA), a secondary metabolite produced by lichens, against CIH-induced liver injury. By establishing a CIH mouse model (10 h/d, oxygen cycling 5%-21% for 4 weeks) and an in vitro model of AML-12 cell hypoxia/reoxygenation (H/R), we perform H&E staining, biochemical assays (ALT/AST/MDA/CAT/T-AOC/GSH-Px), qPCR, western blotting, immunofluorescence and flow cytometry (JC-1 detection of the mitochondrial membrane potential) analyses. The results show that AA significantly reduces alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, inhibits the elevation of hepatic malondialdehyde (MDA), restores the activities of catalase (CAT), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) in CIH mice, ameliorates mitochondrial dysfunction, activates autophagy, and reduces the expression levels of inflammatory factors. Mechanistically, AA reduces the release of downstream proinflammatory factors by blocking NF-κB nuclear translocation through the inhibition of IκBα phosphorylation. The activation of autophagic flow by AA is accompanied by a significant increase in LC3BII/I protein expression. Furthermore, autophagy blockade impedes the role of AA in alleviating inflammatory oxidative stress and mitochondrial dysfunction in the CIH-induced injury model, confirming that autophagy activation is necessary for the protective effect of AA. In conclusion, the present study reveals that AA alleviates oxidative stress and mitochondrial dysfunction, as well as NF-κB signaling, through the activation of autophagy, providing a novel therapeutic strategy for CIH-associated liver injury.

Schistosoma japonicum infection causes egg-induced hepatic granulomatous inflammation together with extensive remodelling of host immunity. Although infection is known to progress from early Th1-associated immunity to egg-driven type 2 responses, the temporal relationships among egg-induced pathology, CD4+ T-cell polarization, T follicular helper (Tfh)-like phenotypes and parasite-specific humoral immunity remain incompletely defined. We therefore infected BALB/c mice with S. japonicum and examined them at serial time points after infection, assessing hepatic histopathology, serum ALT and AST activities, T-cell frequencies, cytokine-producing CD4+ T cells, helper-lineage transcription factors, PD-1 and ICOS expression on T cells, PD-L1 and ICOSL expression on B cells, CXCR5+ICOS+ phenotypic Tfh-like cells and serum SEA-specific IgG, with five biologically independent mice at each time point. Egg-associated hepatic granulomas first became apparent at week 5, enlarged during the middle stage of infection and regressed at later time points. Early infection was characterized by increased IFN-γ-producing CD4+ T cells and elevated Tbx21 expression; following egg deposition, IL-4-, IL-17A- and IL-21-producing CD4+ T cells and Gata3, Rorc and Bcl6 expression increased, and PD-1 and ICOS on CD4+ T cells together with PD-L1 and ICOSL on B cells changed dynamically over the course of infection. By week 8, CXCR5+ICOS+ Tfh-like cells were increased in the spleen, mesenteric lymph nodes and peripheral blood, and SEA-specific IgG had risen markedly after egg deposition and correlated positively with the frequency of splenic CXCR5+ICOS+ CD4+ T cells (rs = 0.3979, p < 0.001). Egg deposition thus represents a temporal immunological transition point in S. japonicum infection: the onset of egg-induced hepatic pathology coincides with the shift from early Th1-associated features to Th2-, Th17-, Tfh-like and SEA-specific humoral responses.