Search Results (16,779)

Systemic arterial hypertension (SAH) is a multifaceted condition marked by sustained elevations in arterial blood pressure. Its occurrence is closely related to alterations in target organs, such as the liver. Non-pharmacological treatments have been proposed for these effects. Thus, the aim of this study was to investigate the effects of açaí supplementation and resistance training, applied individually or in combination, on blood pressure and liver structural parameters. An experimental, quantitative, and longitudinal study was conducted using young Wistar rats (~60 days old) and spontaneously hypertensive rat (SHR) strains. Fifty rats were divided into five experimental groups: Wistar Control (C), Hypertensive Control (H), Hypertensive Trained (HT), Hypertensive Açaí-Supplemented (HA), and Hypertensive Trained plus Açaí Supplementation (HAT). Each group consisted of ten animals. Subsequently, analyses were performed for the antioxidant capacity and proximate composition of the açaí pulp, systolic blood pressure assessment, and histological evaluation of the liver. The açaí used exhibited high antioxidant capacity. At the end of the experimental period, the trained groups increased their maximal load carried, along with a reduction in systolic blood pressure in all treated groups. Açaí supplementation resulted in lower relative liver mass compared with the H group. The hypertensive condition promoted extracellular matrix expansion and a reduction in hepatocyte proportion. Both interventions attenuated these effects, and the combined treatment (HAT) produced the greatest improvement, indicating an additive response. Hypertension also elevated hepatic glycogen concentration, and the treatments reduced this alteration. It is concluded that açaí supplementation and resistance training could promote positive adaptations in the liver of hypertensive animals. Full article

Thai shallot (Allium cepa L. var. aggregatum) is rich in quercetin glycosides, which can be enzymatically hydrolyzed into aglycone forms with potentially higher bioavailability. However, whether this structural modification enhances metabolic efficacy in vivo remains unclear. This study aimed to compare the metabolic and histopathological effects of enzymatic (ESE) and non-enzymatic (NES) Thai shallot extracts in a high-fat diet (HFD)-induced obese mouse model. Male C57BL/6 mice were fed HFD for 12 weeks to induce obesity, followed by a 12-week treatment with NES or ESE (1000 and 2000 mg/kg/day). Metabolic parameters, lipid profiles, oxidative stress markers, hepatic enzyme activities, and histopathological changes were evaluated. Enzymatic hydrolysis significantly increased the proportion of quercetin aglycone without altering total quercetin content. Both NES and ESE improved fasting glucose, insulin resistance, lipid profiles, and oxidative stress markers compared with HFD controls. Histological examination showed attenuation of hepatic steatosis and preservation of tissue architecture in treated groups. However, no consistent superiority of ESE over NES was observed across metabolic or histopathological outcomes. Despite substantial modification of flavonoid composition, enzymatic processing did not enhance the measured metabolic efficacy of Thai shallot extract under the conditions tested. Because circulating quercetin and metabolite levels were not assessed, this finding should be interpreted as comparable metabolic efficacy rather than evidence of equivalent bioavailability. These findings suggest that factors beyond aglycone content may play a key role in determining biological activity, with implications for the development and cost-effectiveness of functional food products. Full article

Chronic liver disease (CLD) constitutes a major global health burden, with high morbidity and mortality, limited treatment options for several etiologies, and an urgent need for novel therapeutic targets. Fibroblast growth factor 1 (FGF1) is a unique member of the FGF family capable of binding all four FGFR subtypes, thereby regulating multiple signaling pathways including PI3K/AKT, Ras/MAPK, and PLCγ, which are involved in metabolism, cell survival, proliferation, and tissue repair. Emerging evidence highlights the multifaceted and context-dependent roles of FGF1 in CLD. In drug-induced liver injury (DILI) caused by anti-tuberculosis drugs, acetaminophen, or doxorubicin, FGF1 confers protection by restoring bile acid homeostasis, reducing oxidative stress, inflammation, and apoptosis. In Metabolic dysfunction-associated steatotic liver disease (MASLD), FGF1 ameliorates hepatic steatosis, oxidative injury, and insulin resistance through downregulation of SREBP1, upregulation of PPARα, and activation of Nrf2-mediated antioxidant responses. Conversely, in primary sclerosing cholangitis (PSC), FGF1 aggravates ductular reaction, biliary senescence, and liver fibrosis via upregulation of SASP and TGF-β1, suggesting that inhibition of the FGF1/FGFR axis may be therapeutic. For alcohol-related liver disease (ALD), although direct experimental evidence is lacking, FGF1 is hypothesized to confer protection given its known activities against oxidative stress, lipid dysregulation, and cell death. Despite its promise, the mitogenic potential of FGF1 raises safety concerns; however, N-terminally modified FGF1 analogs (e.g., FGF1Δ) retain metabolic benefits with reduced proliferative activity. Collectively, FGF1 represents a versatile and disease-dependent regulator in CLD, warranting further mechanistic studies, safety evaluations, and development of targeted analogs as a novel therapeutic strategy for difficult-to-treat liver diseases. Full article

Background: Accurate preoperative prediction of length of hospital stay (LOS) after surgery for colorectal liver metastases (CRLMs) could improve patient counselling and resource planning, yet reliable risk tools are lacking. We aimed to develop an interpretable machine learning model predicting LOS following first-time liver-directed surgery for CRLMs. Methods: In this multicenter cohort study, we included patients who underwent first-time liver resection, ablation, or a combination for CRLMs at three Danish hepatobiliary centers between 2016 and 2023. Preoperative features from two national registries were used to train Elastic Net, Random Forest, HistGradientBoosting, and Explainable Boosting Machine (EBM) algorithms. Hyperparameters were optimized using five-fold cross-validation. Performance was evaluated on a 20% hold-out test sample using mean absolute error (MAE) with bootstrapped 95% confidence intervals (CIs). Results: Among 915 patients, median LOS was 4.0 days (interquartile range (IQR) 3.0–6.0). All four algorithms achieved comparable prediction error (MAE 3.0–3.1 days). The EBM (MAE 3.1 days, 95% CI 2.6–4.3) algorithm was selected for its inherent interpretability. Surgical approach was the strongest predictor, where percutaneous and laparoscopic approaches were associated with reductions of 1.9 and 1.2 days, respectively. Tumor burden, including number of lesions and largest lesion diameter, showed progressive non-linear associations with longer stays. Nonetheless, overall explained variance was low (R² ≤ 0.10), and calibration showed systematic underestimation of stays beyond five days. Conclusions: An inherently interpretable machine learning model matched the predictive performance of opaque algorithms for LOS after CRLM surgery, although overall predictive accuracy was modest and longer stays were underestimated. Explainability analysis identified surgical approach and tumor burden as the most influential predictors. External validation in healthcare systems with different discharge practices is warranted. Full article

Background: Portal hypertension can lead to complications such as ascites, hepatic encephalopathy, esophageal varices, and gastrointestinal (GI) bleeding, all of which are associated with significant morbidity and mortality. Variceal bleeding is the most severe complication, with an estimated mortality of up to 30%. In children, evidence-based guidelines for the management of GI bleeding secondary to portal hypertension are lacking. In this con-text, octreotide, a synthetic somatostatin analog approved for other indications, has been increasingly used off-label and represents a paradigmatic example of drug re-purposing in pediatrics. Methods: Following the 2020 PRISMA guidelines, this systematic review evaluated the efficacy and safety of octreotide for the treatment of portal hyperten-sion-related GI bleeding in children. A comprehensive search of six sources, including five bibliographic databases (PubMed, Embase, Web of Science, Cochrane Library, and EBSCOhost) and the ClinicalTrials.gov registry, was conducted to identify studies in-cluding pediatric patients with GI bleeding secondary to portal hypertension. Results: Three non-randomized observational studies were included, assessing bleeding recurrence, packed red blood cell requirements, and adverse events following octreotide admin-istration. Overall, 33 patients were analyzed, with a mean age of 6.3 years. One study reported a reduction in rebleeding episodes and transfusion requirements after oc-treotide treatment. Across all included studies, no serious adverse events were ob-served; mild and reversible hyperglycemia was the only reported drug-related effect. Quantitative synthesis was not feasible due to substantial heterogeneity, missing data, and a serious risk of bias, resulting in very low certainty of evidence. Conclusions: Octreotide may represent a feasible therapeutic option for portal hypertension-related GI bleeding in children; however, further prospective and standardized studies are needed to establish its long-term safety and efficacy. Full article

Hepassocin, also known as fibrinogen-like protein 1 (FGL-1), is a liver-derived secretory protein initially identified as a mitogenic factor involved in hepatocyte proliferation and liver regeneration. Increasing evidence has subsequently suggested that FGL-1 functions as a hepatokine linking hepatic metabolic stress to systemic metabolic regulation. Experimental and clinical studies have demonstrated that circulating FGL-1 levels are associated with obesity, insulin resistance, metabolic dysfunction-associated steatotic liver disease (MASLD), and type 2 diabetes mellitus (T2DM). Mechanistically, FGL-1 appears to contribute to metabolic dysfunction by impairing insulin signaling and promoting hepatic lipid accumulation, although its precise molecular targets remain incompletely defined. In addition to its metabolic roles, FGL-1 has been identified as a major ligand of lymphocyte activation gene-3 (LAG-3), implicating it in immune modulation and tumor progression, particularly in hepatocellular carcinoma (HCC). However, most available human data are observational, and conflicting findings from experimental models suggest that FGL-1 may function as a context-dependent mediator rather than a purely pathogenic factor. Given the expanding but sometimes conflicting evidence, a comprehensive understanding of FGL-1 biology may provide important insights into the complex interactions among hepatic stress responses, metabolic dysfunction, and immune regulation. This review therefore examines the current evidence regarding the physiological and pathological roles of FGL-1 and highlights key unresolved questions that may influence future translational research and therapeutic development. Full article

Background/Objectives: Globally, coverage of the hepatitis B vaccine within 24 h of birth is 45 percent, far below the WHO target of 90 percent by 2030. For newborns delivered in out-of-facility settings, delayed contact with health workers, transportation barriers, and cold chain constraints can impede timely vaccination. This review explores strategies and facilitators for delivering birth dose vaccines to infants born outside of health facilities in low- and middle-income countries. Methods: A rapid scoping review was conducted, searching PubMed and targeted websites for peer-reviewed and gray literature published between 2005 and 2025. Data were charted using a standardized extraction tool. Frequency and thematic analyses were conducted. Results: After screening 315 studies, 26 eligible sources were identified. Delivery strategies consisted of three components: identifying and tracking home births; supporting caregiver uptake through education, reminders, or incentives; and delivering the vaccine through home-based administration or referral to facilities. Sub-components included pregnancy and birth notification systems, postnatal home visits, mobile reminders, incentives, and home-based vaccination by facility or community providers. The feasibility of these strategies was shaped by factors across system levels, such as national policies and financing; health system infrastructure; cold chain capacity; health workforce configuration; caregiver awareness; and community social norms. In several contexts, flexible cold chain approaches and vaccine administration by community-based cadres enabled timely vaccination of infants born at home. Conclusions: Vaccination programs can learn from existing out-of-facility vaccine delivery approaches to strengthen hepatitis B birth dose vaccination programs for timely and equitable coverage. Full article

Background: Normothermic machine perfusion (NMP) is increasingly being used to improve organ utilization in liver transplantation (LT). However, its non-physiological perfusion setting may cause focal hepatic hypoperfusion (FHH), which remains insufficiently characterized in terms of its incidence, risk factors, and clinical impact. Methods: Data on liver grafts that underwent NMP prior to LT at the Department of General, Visceral, and Transplant Surgery, University Hospital Münster, between October 2019 and August 2024 were retrospectively analyzed. Recipients who underwent contrast-enhanced computed tomography within 30 days post-LT were included. The primary outcomes were the Comprehensive Complication Index (CCI) and overall graft survival rate. Ninety-one patients met the inclusion criteria and were stratified according to the presence of FHH in the FHH+ (n = 27) and FHH- (n = 64) groups. Results: FHH was detected in 29.7% of the grafts. Higher graft weight was the only independent predictor of FHH. In addition, graft weight correlated with the extent of FHH (τ = 0.40, p < 0.001). FHH did not affect graft or patient survival but was associated with higher CCI scores (p = 0.001) and prolonged intensive care unit length of stay (p = 0.028). Conclusions: FHH is a common radiological finding after NMP. Although it does not affect graft loss, its association with a higher complication burden warrants further attention. Whether avoiding NMP in very heavy grafts could reduce the incidence of FHH remains to be determined. Full article

The replacement of fishmeal (FM) in aquafeeds for carnivorous fish remains challenging due to reduced palatability and adverse effects on liver health and intestinal microbiota. Marine by-products-based additives containing fish protein hydrolysates and seaweed polysaccharides have shown potential to overcome these limitations. This study evaluated the effects of graded supplementation of Haiweisu (HWS), a multi-marine by-product formulated with squid viscera hydrolysate, small-molecule components from fish protein hydrolysate, seaweed polysaccharides, and seaweed residue as a carrier, in a FM-free diet for juvenile largemouth bass. Four isonitrogenous and isolipidic diets were prepared: a FM-free control diet (CON) and three diets supplemented with 10, 20, or 30 g/kg HWS (designated S10, S20, and S30, respectively). Each diet was fed to triplicate groups of fish (29.26 ± 2.61 g) for 56 days. Results showed that HWS supplementation linearly increased final body weight, weight gain rate, and feed intake, while significantly reducing the feed conversion ratio (p < 0.05). All HWS-supplemented groups exhibited markedly lower hepatic lipid accumulation and plasma total cholesterol levels compared with the CON group, accompanied by alleviated hepatocellular steatosis and inflammatory infiltration as revealed by Oil Red O and H&E staining. Moreover, HWS significantly enhanced intestinal microbiota alpha diversity (Ace, Chao, Sobs, and Shannon indices), decreased the relative abundance of the dominant genus Mesomycoplasma, and enriched potentially beneficial genera including Methylobacterium, Delftia, and Sphingomonas (p < 0.05). In conclusion, dietary HWS supplementation effectively improved growth performance, alleviated hepatic steatosis and inflammation, and beneficially reshaped the intestinal microbiota in juvenile largemouth bass fed a FM-free diet. These findings support HWS as a promising functional additive for sustainable FM-free aquafeeds in carnivorous fish species. Full article

Liver-on-a-chip (LoC) platforms offer promising alternatives to conventional in vitro and animal models for studying hepatic function and drug response; however, wide variability in cell sources, seeding strategies, extracellular matrices (ECMs), and functional assays limits reproducibility. This study reviews reported 2D and 3D LoC systems to identify commonly used liver cell types, seeding densities, ECM materials, and albumin/urea assay methods. Immortalised HepG2-based models dominate current platforms, with optimal seeding densities typically ranging from ~3 × 10⁶ cells/mL in 2D systems and 0.5–5 × 10⁶ cells/mL in 3D constructs. Collagen I, alone or combined with Matrigel, emerged as the most frequently adopted ECM. Functional assessment across studies highlighted albumin and urea as robust markers, with Abcam ELISA and QuantiChrom DIUR assays providing suitable sensitivity for microfluidic sample volumes. Collectively, this work establishes practical benchmarks for hepatic cell selection, seeding parameters, ECM choice, and assay selection, supporting more standardised and reproducible LoC development. Full article

The COVID-19 pandemic highlighted the urgent need to develop effective and broad-spectrum antiviral therapies against coronaviruses. One strategy to address this concern is a combination therapy using repurposed drugs against zoonotic viruses with pandemic potential. We previously demonstrated that the combination of Remdesivir and Ivermectin is highly potent and synergistic in inhibiting the replication of murine hepatitis virus (MHV) in RAW264.7 macrophages. This study investigated the interactions between the drug combination, coronavirus and host by proteomics and RNA sequencing of MHV-infected H2.35 murine liver epithelial cells. Time-of-addition and time-of-removal assays suggested that the drug combination likely affected the synthesis of viral RNA and viral protein. This combination drastically diminished the live virus titer greater than the respective monotherapies in MHV-infected H2.35 cells (by ~4 log₁₀), as well as in SARS-CoV-2-infected VeroE6 cells and human nasal epithelial cells. Proteomic and transcriptomic analyses revealed that viral protein and RNA levels were significantly depressed upon combination treatment. The drug combination exhibited considerable negative effects upon host RNA processes and resulted in the upregulation of host protein processes (e.g., response to unfolded protein; protein insertion into ER membrane). Molecular pathways affected by the combination treatment were markedly distinct from the monotherapies and indicated that Ivermectin enhances Remdesivir by modulating critical host processes to synergistically exert its inhibitory effect on the coronavirus replication cycle. Full article

Background: Hydatid disease, caused by Echinococcus granulosus, remains a significant public health concern in endemic regions. This study aimed to evaluate the role of ultrasound in the diagnosis, staging, and clinical management of liver hydatid cysts in the eastern city of Jalalabad, Afghanistan. Method: A cross-sectional study was conducted between February and November 2024 among 159 patients diagnosed with liver hydatid cysts. Demographic, clinical, laboratory, and imaging data were collected. Cysts were classified according to the WHO Informal Working Group on Echinococcosis (WHO-IWGE) and Gharbi systems. Ultrasound findings were compared with computed tomography (CT), and their association with treatment decisions was assessed. Result: A total of 159 patients with liver hydatid cysts were included in the study. Among them, 91 (57.2%) were female, 80 (50.3%) were aged 20–39 years, and 128 (80.5%) resided in rural areas. Most patients presented with a single cyst (144/159, 90.6%), while multiple cysts were observed in 15 (9.4%). The majority of cysts measured 5–9.9 cm in diameter (43.4%), followed by 1–4.9 cm (42.1%) and ≥10 cm (14.5%). According to the WHO-IWGE classification, CE1 (25.8%) and CE4 (24.5%) were the most common stages, followed by CE2 (17.6%), CE3a (13.8%), CE3b (11.3%), and CE5 (7.0%). Common exposure-related factors included dog ownership, poor hygiene practices, and consumption of raw vegetables. Ultrasound accurately identified cyst stages and demonstrated a significant association between WHO-IWGE staging and treatment modality (χ² = 63.56, p < 0.001). Almost perfect agreement was observed between ultrasound and CT for cyst classification (Cohen’s κ > 0.90), although CT provided additional anatomical information in selected complex cases. Conclusions: Ultrasound is an accessible, accurate, and reliable imaging modality for the diagnosis, staging, and management of liver hydatid cysts. In resource-limited settings, it serves as the primary imaging modality for guiding clinical decision-making, with CT reserved for complex or uncertain cases. Full article

Lead (Pb) induces oxidative stress, inflammation, and hepatorenal injury. We evaluated whether fenugreek (Trigonella foenum-graecum) seed powder (200 mg/kg) protects against subchronic Pb-acetate exposure in male albino mice. Sixty mice were randomized to six groups (n = 10): control (G1), fenugreek-only (G2), Pb 150 mg/kg (G3), and three co-exposure groups receiving fenugreek with Pb at 50, 100, and 150 mg/kg (G4–G6), gavaged daily for 8 weeks. LC–DAD–ESI–MS/MS of the seed batch tentatively identified 32 metabolites, dominated by flavonoid C-glycosides, luteolin dihydrogalloyl-glucosyl-pentosyl glucoside (15.90%), vicenin-3 (14.46%), vicenin-2 (9.66%), vicenin-1 (8.80%), kaempferol 7-O-rhamnosyl-glucoside (8.71%), with additional acylated phenolic conjugates. Pb exposure (G3) significantly reduced growth and intake, elevated serum ALT, AST, ALP, urea, and creatinine, raised blood Pb, and produced hepatic necrosis, vacuolation, and inflammation. Molecularly, Pb upregulated Nrf2, HO-1, SCD-1, TNF-α, and IL-6 and suppressed SOD-3. Fenugreek co-treatment attenuated all these changes across the three Pb doses, with greatest effect at the lowest Pb load (G4). Notably, fenugreek co-treatment reduced rather than further increased Nrf2 and HO-1 expression relative to Pb alone, a pattern most consistent with lowering the upstream oxidative stimulus rather than direct induction of these pathways. The seed’s polyphenolic profile—rich in vicenin-type C-glycosides and luteolin and kaempferol derivatives—offers a plausible chemical basis for the antioxidant, anti-inflammatory, and modest Pb-lowering effects observed; however, because whole seed powder was administered and metabolite identifications are tentative, these structure–activity relationships are presented as hypotheses for future bioactivity-guided fractionation rather than as demonstrated mechanisms. These preclinical findings support further investigation of fenugreek as a candidate dietary adjunct against environmental Pb exposure, contingent on protein-level validation, pharmacokinetic characterization, benchmarking against a standard chelator, and bioactivity-guided fractionation. Full article

Hepatic ischemia–reperfusion injury (HIRI) is a major cause of postoperative liver dysfunction and adverse outcomes in hepatectomy, liver transplantation, and hemorrhagic shock. Among the multiple mechanisms implicated in HIRI, mitochondria are recognized as central organelles that integrate metabolic failure, oxidative stress, inflammation, and cell death. During ischemia, interruption of oxygen and nutrient supply impairs oxidative phosphorylation, depletes ATP, disrupts ionic homeostasis, and renders mitochondria highly vulnerable to subsequent injury. Upon reperfusion, reoxygenation triggers excessive reactive oxygen species production, calcium overload, mitochondrial permeability transition pore opening, and release of damage-associated molecular patterns, thereby amplifying hepatocellular injury and sterile inflammatory responses. As a key component of mitochondrial quality control, mitophagy plays a context-dependent role in HIRI. Appropriate activation of mitophagy facilitates the clearance of damaged mitochondria, limits oxidative stress, restrains inflammasome activation, and preserves hepatocellular homeostasis, whereas insufficient or dysregulated mitophagy contributes to mitochondrial accumulation and aggravates liver injury. This review summarizes mitochondrial alterations during the ischemic and reperfusion phases, outlines the major mitophagy pathways involved in HIRI and discusses recent advances in upstream regulation, disease-specific dysregulation, and mitophagy-targeted interventions. A better understanding of the dynamic and biphasic nature of mitophagy in HIRI may provide a stronger theoretical basis for precision liver-protective strategies and future translational therapies. Full article

The interindividual phenotypic heterogeneity in Alpha-1 Antitrypsin Deficiency (AATD), despite a shared genetic etiology (the Z-allele of SERPINA1), is explained by the interaction of dual pathogenic mechanisms (gain-of-function vs. loss-of-function), additional genetic modifiers, and environmental or metabolic factors. Building on recent evidence suggesting divergent disease trajectories, we investigated whether pulmonary and hepatic impairments represent coupled manifestations or independent clinical dimensions within a large European cohort. Methods: This international multicenter study utilized the European Alpha-1 Research Collaboration (EARCO) registry (n = 1217). Pulmonary and hepatic severities were quantified using concurrent 0.0–10.0 composite indices. Independence was evaluated via partial Spearman correlations, multivariable multinomial regression, and geometric mapping across a continuous phenotypic space. Results: Cross-domain correlations between respiratory metrics and liver stiffness were near zero (r = −0.03), demonstrating statistical independence. Phenotypic dominance classification isolated distinct profiles; the lung-dominant group exhibited a higher age (57.0 vs. 54.0 years; p < 0.001) and tobacco exposure, while the liver-dominant group registered a higher body mass index (25.8 vs. 24.4 kg/m²; p < 0.001). Multivariable models identified age (OR 1.03; 95% CI 1.02–1.05) and smoking as independent predictors of lung dominance, whereas body mass index was independently associated with liver dominance (OR 1.04; 95% CI 1.01–1.07). Geometric mapping revealed advanced disease clusters at orthogonal margins rather than forming a systemic continuum. Conclusions: Hepatic and pulmonary impairments in AATD operate as independent clinical dimensions modulated by distinct metabolic and environmental factors. Risk stratification must transition toward organ-specific prognostic models. Full article