Search Results (16,146)

The present study aimed to investigate the effects of polyvinyl chloride microplastics with different sizes on the growth, intestinal and hepatic health of turbot (Scophthalmus maximus L.) at 3 and 9 weeks of exposure. Three diets were formulated: a control diet with no microplastics, a diet containing 2% micrometer-sized plastics (MPs), and a diet containing 2% nanoplastics (NPs), with four replicates (40 fish/tank, 12 tanks total). The results showed that MPs and NPs had no significant effects on the growth performance of turbot. Analyses of intestinal histology and gene expression (intestinal barrier-related and antioxidant-related genes) indicated that the turbot intestine exhibited a certain degree of tolerance and adaptability to MPs and NPs exposure. Observations of liver histology and analyses of gene expression (inflammatory cytokines, apoptosis-related, and antioxidant-related genes) revealed that the liver damage induced by microplastics in turbot exhibited obvious size-dependent and time-cumulative effects, with NPs exerting a stronger impact. Compared with MPs, long-term exposure to NPs can induce obvious intestinal microbiota dysbiosis in turbot. In summary, particle size and exposure duration are important factors regulating the impacts of PVC microplastics on the intestinal and hepatic health of turbot. Full article

The urea cycle (UC) is usually described as the hepatic metabolic pathway responsible for ammonia detoxification, but its role extends far beyond nitrogen (N) elimination to include cellular biosynthesis and metabolic signalling. In cancer cells, the UC is reconfigured/reorchestrated to support high anabolic demand, often involving the dysregulation of key enzymes such as ASS1, ASL, OTC and CPS1. While these changes support biomass production and stress resistance, they also generate measurable biochemical signatures through kinetic and thermodynamic isotope effects (¹⁴N/¹⁵N). In this review, we summarise UC biochemistry and recall key enzymatic mechanisms. Together, these elements provide a mechanistic framework to interpret changes in ¹⁵N abundance observed in tumour tissues and cells. We discuss how the redirection of N flux toward nucleotide and polyamine synthesis, coupled with partial excretion of ¹⁵N-depleted urea, may shape the isotopic composition of cancer cells. By integrating molecular oncology with stable isotope analysis, this review highlights the potential of natural isotope abundance as a functional readout of tumour metabolism and supports further investigation of its translational relevance in cancer phenotyping and monitoring. Full article

The transjugular intrahepatic portosystemic shunt (TIPS) is a cornerstone intervention for complications of portal hypertension, including variceal bleeding and refractory ascites. As the population with cirrhosis ages, clinicians increasingly face the question of whether and how to perform TIPS safely in older adults. We reviewed observational cohorts, registry analyses, and systematic reviews/meta-analyses. Existing evidence does not support chronological age as an absolute contraindication; however, multiple studies suggest that advanced age is associated with higher rates of post-TIPS hepatic encephalopathy (HE), early mortality, and readmissions. These findings underscore the need to shift from a binary “eligible vs. ineligible” paradigm to a structured, actionable framework that addresses modifiable risks and anticipates age-related vulnerabilities. Recent clinical practice guidance emphasizes comprehensive pre-TIPS assessment and vigilant post-procedure care, with specific attention to HE risk factors (e.g., prior HE, hyponatremia, renal dysfunction, sarcopenia) and cardiopulmonary reserve. In this narrative review, we propose an elderly-focused clinical pathway built around a four-domain assessment (Liver–Brain–Body–Heart/Kidney) and a traffic-light risk tiering system to guide patient selection, procedural strategy, follow-up scheduling, and triggered management of HE, cardiac decompensation, and renal dysfunction. This pathway aims to preserve the benefits of portal decompression while reducing preventable complications and improving outcomes that are meaningful to older patients, including functional status and quality of life. This narrative review emphasizes that outcomes after TIPS in older adults are determined not by chronological age alone but by multidomain physiological reserve. The proposed pathway informs patient selection, procedural planning, and early post-discharge monitoring in older adults. Full article

Background/Objectives: Chemically induced hepatotoxicity is widely used in experimental research to model liver disease pathophysiology and to support preclinical studies. Thioacetamide (TAA) is a well-established hepatotoxic agent in conventional laboratory rodents; however, its effects in synanthropic rats—characterized by genetic heterogeneity and chronic environmental exposure—remain poorly defined. This study aimed to establish and characterize a preclinical model of TAA-induced hepatotoxicity in synanthropic rats and to assess its relevance for experimental liver disease research. Methods: Female synanthropic rats representing four phenotypic variants (albino, mottled, black, and brown; total n = 132) were housed under controlled conditions and assigned to control or TAA-treated groups. TAA was administered intraperitoneally at doses ranging from 200 to 300 mg/kg. Clinical parameters, including body weight and vital signs, were periodically monitored. Hematological profiles and serum biochemical markers of liver function were analyzed. Hepatic injury was evaluated by histopathological examination using hematoxylin–eosin staining. Statistical analyses were performed using R software, with p ≤ 0.05 considered statistically significant. Results: TAA-treated rats developed consistent clinical manifestations of hepatotoxicity, including progressive weight loss and reduced activity. Biochemical analyses revealed significant increases in serum transaminases, gamma-glutamyl transferase, and alkaline phosphatase, accompanied by alterations in hematological parameters. Histological evaluation demonstrated dose-dependent liver injury characterized by centrilobular necrosis, inflammatory infiltration, hepatocellular degeneration, and architectural disruption across all synanthropic rat variants. Conclusions: Synanthropic rats exhibit reproducible biochemical, hematological, and histopathological features of TAA-induced liver injury comparable to those reported in conventional laboratory strains. This model represents a robust preclinical approach for studying chemically induced hepatotoxicity and may provide enhanced translational relevance due to its genetic and environmental heterogeneity. Full article

The present review discusses vitamin A/retinoid metabolism as a cross-organ axis in which hepatic clock-dependent retinoid handling may affect immune clock gene expression through the stimulation of retinoic acid 6–Janus kinase 2–signal transducer and activator of transcription 5 signaling, potentially promoting pro-inflammatory monocyte states. We further highlight mechanosensory signaling as a second convergent layer that integrates hemodynamic forces with tissue microenvironmental cues. Among these pathways, G protein-coupled receptor 68, a proton- and flow-sensitive G protein-coupled receptor, is discussed as a representative druggable node linking mechanical and inflammatory signaling in chronic kidney disease-associated cardiac injury. Finally, we outline potential therapeutic directions, including (i) circadian alignment/chronopharmacology, (ii) modulation of retinoid metabolism and signaling, and (iii) targeted inhibition of primary immune and mechanosensory effectors. Full article

Oxidative stress is characterised by the production of free radicals in higher amounts than the antioxidant scavenging capacity. This may cause damage to several organs especially the main site of detoxification, the liver. In this study, the antioxidant activity of five novel lipophilic fluoroquinolones (FQs) derivatives was evaluated against oxidative stress induced by acetaminophen (APAP) and carbon tetrachloride (CCl₄). Sixty-four male Wistar rats were divided into two oxidative-stress models. FQ compounds (25 mg/kg) were administered six hours after CCl₄ or APAP administration. Serum liver enzymes including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Changes in antioxidant parameters were determined in the serum including measurement of total antioxidant status and reduced-glutathione levels as well as catalase, glutathione peroxidase and superoxide dismutase activities. Additionally, molecular docking analyses were performed against catalase, CYP3A4, and Keap-1 to elucidate the potential molecular interactions underlying the observed biological activities. A significant decrease in ALT and AST levels was seen following FQ compound administration in both models. In addition, FQ compounds exhibited excellent antioxidant activity, leading to increased antioxidant enzyme activity, high total antioxidant status, and elevated reduced-glutathione levels. The docking results revealed that compound 4A exhibited the highest binding affinities toward catalase, CYP3A4, and Keap-1. These interactions suggest a possible enhancement of catalase activity, modulation of CYP3A4, and activation of the Keap-1/Nrf2 signalling pathway. Overall, these findings demonstrate the promising therapeutic potential on hepatic injury and oxidative stress of the novel FQ derivatives. Full article

Bile acids, the primary constituents of mammalian bile, are synthesized in the liver from cholesterol and secreted into the intestine to perform essential physiological functions. Primary bile acid synthesis is the principal pathway for cholesterol catabolism and whole-body cholesterol homeostasis, occurring predominantly via the classical and alternative pathways. To elucidate the effects of altitude on serum bile acid profiles and synthesis pathways in SD rats, this study utilized UPLC-MS/MS to analyze serum bile acid composition in animals housed at high and low altitudes. Additionally, qRT-PCR and Western blotting assessed mRNA transcription and protein expression of key genes involved in primary bile acid synthesis in the liver and intestinal tissues (ileum, duodenum, and colon). Results showed that serum levels of total and primary bile acids significantly decreased with increasing altitude. Furthermore, hepatic mRNA and protein expression of Cyp7a1, Cyp8b1, Cyp27a1, and Cyp7b1 were significantly downregulated. Fxr mRNA expression in the liver, ileum, duodenum, and colon was significantly decreased with increasing altitude. Meanwhile, the protein expression of both FGF15 and SHP showed a downward trend, with a significant decrease for FGF15 and a non-significant decrease for SHP. These findings suggest that primary bile acid synthesis in SD rats is dominated by the classical pathway. As altitude increases, bile acid synthesis in SD rats is significantly inhibited, indicating that high-altitude hypobaric hypoxia is the primary inhibitory factor. This study provides critical data for elucidating the adaptive mechanisms of bile acid metabolism in mammals exposed to high-altitude hypoxia, thereby establishing a theoretical foundation for investigating the regulation of host lipid metabolism influenced by such conditions. Full article

Background: Postoperative hemorrhage is a severe complication after pancreatic surgery. While bleeding related to pancreatic fistula is well characterized, hemorrhage secondary to biliary leakage remains poorly understood. This study investigates the incidence, associated factors, clinical course, and outcomes of hepaticojejunostomy insufficiency-associated arterial hemorrhage (HIAA). Methods: This retrospective single-center study included 1413 patients who underwent pancreatic surgery with hepaticojejunostomy between 2004 and 2014. Demographics, underlying disease, surgical procedures, postoperative complications, management strategies, and outcomes were analyzed. Results: HIAA occurred in 13 patients (0.9%), accounting for one third of all erosion-related hemorrhages. The median onset was 16 days postoperatively, and 77% were preceded by sentinel bleeding. Completion pancreatectomy and sepsis were significantly associated with HIAA. The right hepatic artery was the most frequent bleeding source. Primary interventional angiography achieved hemostasis in 62.5% of patients, while 61.5% required surgical revision. Thirty- and ninety-day mortality rates were 15.4% and 30.8%, respectively, compared with 2.1% and 3.7% in the overall cohort. Conclusions: HIAA is a rare but highly lethal complication after pancreatic surgery. It represents a distinct clinical entity characterized by delayed onset, frequent sentinel bleeding, an association with sepsis and completion pancreatectomy, and markedly increased mortality. Early recognition, prompt imaging, and an interventional-first strategy are essential to improve outcomes. Full article

Background: Astragalus membranaceus Fisch. ex Bunge has long been used in East Asian medicine for gastrointestinal disorders and immune modulation. Astragaloside IV (AS-IV), a major bioactive saponin from its roots, exhibits potent anti-inflammatory and antioxidant activities, yet its protective effects against inflammatory bowel disease (IBD)-associated multi-organ damage via the gut–liver–brain axis remain unclear. Methods: Experimental colitis was induced in C57BL/6N mice by administering 5% dextran sulfate sodium (DSS) in drinking water for seven days. AS-IV (100 mg/kg/day) was orally administered during DSS exposure. Disease severity was evaluated using body weight, colon length, disease activity index, and histopathology. Inflammatory cytokines and oxidative stress markers were measured using ELISA, and NF-κB and MAPK signaling were analyzed through Western blotting and immunohistochemistry in colonic, hepatic, and brain tissues. Results: AS-IV significantly alleviated DSS-induced weight loss, disease activity, and colon shortening, while improving intestinal histopathological damage. AS-IV also reduced systemic pro-inflammatory cytokine levels and oxidative stress. Mechanistically, AS-IV was associated with a reduced expression of phosphorylated NF-κB and MAPK proteins, including p-NF-κB, p-IκBα, p-ERK, p-JNK, and p-p38, across the colon, liver, and brain. Conclusions: AS-IV attenuates DSS-induced multi-organ inflammation via gut–liver–brain axis modulation through NF-κB and MAPK pathway inhibition in experimental colitis models. Full article

Bisphenol A (BPA) is a widely used endocrine-disrupting chemical that has been linked to oxidative stress and inflammation. This study investigated whether carvacrol (CAR), a natural monoterpene with antioxidant potential, mitigates BPA-induced hepatorenal toxicity in rats. Forty-two male Wistar albino rats were allocated into six groups (n = 7/group): control, vehicle (corn oil), BPA (25 mg/kg/day), and BPA co-administered with CAR (12.5, 25, or 50 mg/kg/day) by oral gavage for 30 days. Oxidative status was assessed in liver and kidney homogenates by measuring malondialdehyde (MDA), reduced glutathione (GSH), and the activities of superoxide dismutase (SOD) and catalase (CAT). In addition, histopathological evaluations were performed, and pro-inflammatory gene expression (NF-κB, TNF-α, and IFN-γ) was quantified by RT-qPCR. BPA induced a consistent pro-oxidant pattern, including increased hepatic MDA with depleted antioxidant defenses, and upregulated inflammatory transcripts. Carvacrol attenuated these alterations in a dose-dependent manner, and the CAR50 group was associated with statistically supported improvements across the oxidative stress panel, pro-inflammatory transcript expression, and histopathology scores. Overall, these findings identify carvacrol as a candidate for further preclinical evaluation against BPA-triggered oxidative and inflammatory disturbances in vivo; however, human-relevant extrapolation will require careful attention to dose scaling, bioavailability, and metabolism. Full article

Background: Pemphigus diseases are rare autoimmune blistering disorders mediated by pathogenic autoantibodies directed mainly against desmoglein 1 and desmoglein 3. Although most cases are considered idiopathic, external triggers that can disrupt immune tolerance have been described. Vaccination has been discussed as a potential precipitating factor in autoimmune skin diseases. However, the relationship between vaccination and the induction of pemphigus-related autoantibodies has not been comprehensively summarized. Methods: We conducted a narrative review of all available studies published in the last 25 years identified through medical databases, excluding studies on COVID-19 vaccinations. Reports describing either new-onset pemphigus or exacerbation of preexisting pemphigus with a temporal association to vaccination were included. Clinical characteristics, vaccine type, latency period, direct immunofluorescence findings, and ELISA results for desmoglein autoantibodies were analyzed. In addition, we present our own clinical-laboratory experience illustrating this issue. Results: The current evidence consists predominantly of case reports and small case series. Published cases describe pemphigus vulgaris and pemphigus foliaceus occurring after vaccinations against influenza, hepatitis B, tetanus, diphtheria, pertussis, rabies, and other routinely administered immunizations. The latency period most often ranged from several days to a few weeks. Immunopathological findings were consistent with classical pemphigus diseases, including intercellular IgG deposits in the epidermis and circulating autoantibodies against desmoglein 1 and/or desmoglein 3. Our patient was a 78-year-old woman who developed cutaneous form of pemphigus vulgaris, diagnosed with direct immunofluorescence (DIF) and multiplex ELISA, 10 days after diphtheria–tetanus–pertussis vaccination. The patient had a positive family history of autoimmune blistering disease, namely mucous membrane pemphigoid. Conclusions: Based on the currently available evidence, a direct causal relationship between vaccination and pemphigus diseases cannot be established. Nevertheless, accumulated clinical and serological observations suggest that vaccination may act as a triggering factor in genetically or immunologically predisposed individuals, possibly by amplifying pre-existing subclinical autoreactive immune responses. Further population-based and mechanistic studies are required to clarify this association, while the overall benefits of vaccination remain substantial. Full article

This study aimed to investigate the ameliorative effects of glucuronolactone (GL) as a dietary additive on high-fat diet (HFD)-induced growth suppression and metabolic disorders in turbot. A 10-week feeding trial was conducted using juvenile turbot (16.7 ± 0.03 g). Two diets with different protein (%)/lipid (%) levels were formulated: PC (54/12) and NC (47/17). Based on the NC diet, three experimental diets were prepared by supplementing 200 (G200), 400 (G400), and 600 (G600) mg/kg of GL. The present results show that compared to the PC group, HFDs significantly inhibited the growth performance of turbot and induced severe metabolic disorders, hepatointestinal damage, and gut microbiota dysbiosis. Dietary GL supplementation effectively reversed these adverse effects. Specifically, compared to the NC group, GL supplementation significantly restored growth performance, enhanced non-specific immunity, and systematically improved metabolic health. In the liver, GL notably ameliorated tissue damage and downregulated key lipogenic genes (SREBP1, ACC, FAS, PPARγ), while upregulating genes involved in lipid oxidation and catabolism (PPARα1, CPT1, ACOX1, HSL, LPL) and lipid transport (ApoB100, MTP), thereby alleviating hepatic lipid deposition. Furthermore, GL activated the Nrf2/Keap1 antioxidant pathway, up-regulating the expression of genes such as SOD, CAT, GPX, and HO-1. It also suppressed the NF-κB-mediated inflammatory response (downregulation of IL-1β, IFN-γ and TNF-α2; upregulation of IL-10 and TGF-β2) and the mitochondrial apoptosis pathway (increased Bcl-2/Bax ratio; downregulation of Caspase3/7/9), collectively mitigating oxidative damage and cellular apoptosis. Moreover, GL restored intestinal morphology, enhanced the expression of tight junction proteins (Claudin-3, Claudin-7, ZO-1, Occludin) and MUC2, and inhibited MLCK signaling. These improvements led to a reduction in serum D-LA levels, indicating strengthened intestinal barrier function. Concurrently, GL reshaped the gut microbiota composition by enriching beneficial bacteria such as Akkermansia and suppressing potential pathogens like Listeria. In summary, GL effectively alleviated HFD-induced growth suppression and metabolic damage in turbot by improving lipid metabolism and alleviating hepatic injury, while concurrently restoring intestinal barrier integrity and microbiota homeostasis. Full article

Background: Hepatitis A virus (HAV) infection is a common cause of acute viral hepatitis in children. Severe complications are rare but may occur, particularly in older children or in the presence of concomitant conditions. Case Presentation: We report the case of an 11-year-old girl with acute hepatitis A with severe hepatic derangements who developed life-threatening upper gastrointestinal bleeding due to a previously undiagnosed duodenal ulcer. Emergency endoscopy confirmed active bleeding from a duodenal ulcer, and the patient survived the complications with treatment with a proton pump inhibitor and hemostatic management with blood products. Conclusions: Although hepatitis A is generally benign in children, this case highlights the potential for severe and life-threatening complications. Full article

Chronic hepatitis B (CHB) and Type 2 diabetes (T2DM) are major independent risk factors for Hepatocellular carcinoma (HCC). The bidirectional promotion between T2DM and CHB forms the biological basis for their synergistic carcinogenic effect. T2DM mainly accelerates the progression of CHB through mechanisms such as metabolic disorders, oxidative stress, chronic inflammation, and immunosuppression; CHB promotes the development of T2DM mainly through liver damage leading to dysfunction of the central glucose metabolism, HBx-driven gluconeogenesis, inhibition of the insulin signaling pathway, and potential β-cell damage. In comorbid conditions, these mechanisms intertwine to form a vicious cycle across four key aspects: metabolic and lipid disorders, activation of carcinogenic pathways, oxidative stress, and amplification of chronic inflammation, significantly accelerating the hepatocarcinogenesis. Regarding management strategies, we adopt the concept of three-level prevention, integrate various management plans and combine emerging drug therapies. We thus propose the establishment of a management strategy centered on “liver and glucose co-management” with multi-faceted joint control. This review aims to summarize the latest evidence on the mechanisms and management strategies by which the comorbidity of T2DM and CHB promotes the development of HCC, providing a theoretical basis for research on the mechanisms of this comorbidity and population-level HCC prevention strategies. Full article

A high-fat (HF) diet disrupts metabolic homeostasis and impairs peripheral circadian rhythms in key metabolic tissues. β-Hydroxybutyrate (BHB), a major circulating ketone body, functions not only as an energy substrate but also as a signaling metabolite regulating nutrient-sensing and inflammatory pathways. However, its role in modulating metabolic–circadian interactions under conditions of nutrient excess remains unclear. In this study, we investigated whether BHB supplementation influences metabolic signaling and circadian clock oscillations in liver, skeletal muscle and adipose tissue under chow and HF conditions. Male C57BL/6 mice were fed chow or HF with or without BHB supplementation (500 mg/kg body weight in the diet) for 7 weeks. Metabolic parameters were assessed by indirect calorimetry, and tissues were collected every 4 h across the circadian cycle. HF feeding increased body weight and adiposity (p < 0.01), reduced AMPK activation, enhanced AKT/mTOR signaling, elevated NF-κB levels and dampened clock gene rhythmicity. BHB supplementation significantly decreased food intake in HF-fed mice (p < 0.01) and partially reversed several molecular alterations in a tissue-specific manner. In skeletal muscle and adipose tissue, BHB increased AMPK activation and reduced mTOR and NF-κB signaling (p < 0.05), whereas hepatic effects were more modest. Notably, BHB modulated circadian gene expression, restoring aspects of rhythmic amplitude and/or phase, particularly in adipose tissue. These findings may indicate that BHB supplementation modulates nutrient-sensing pathways and partially restores peripheral circadian rhythms under HF conditions. While some effects may be influenced by reduced energy intake, BHB may serve as a metabolic signal linking nutrient status to circadian regulation. Full article