Search Results (9,558)

Chronic infection with the hepatitis B virus (HBV) results in over 1 million deaths annually. Although currently licensed treatments, including pegylated interferon-α and nucleoside/nucleotide analogs, can inhibit viral replication, they rarely eradicate covalently closed circular DNA (cccDNA) reservoirs. Moreover, vaccination does not offer therapeutic benefit to already infected individuals or non-responders. Consequently, chronic infection is maintained by the persistence of cccDNA in infected hepatocytes. For this reason, novel therapeutic strategies that permanently inactivate cccDNA are a priority. Obligate heterodimeric transcription activator-like effector nucleases (TALENs) provide the precise gene-editing needed to disable cccDNA. To develop this strategy using a therapeutically relevant approach, TALEN-encoding mRNA targeting viral core and surface genes was synthesized using in vitro transcription with co-transcriptional capping. TALENs reduced hepatitis B surface antigen (HBsAg) by 80% in a liver-derived mammalian cell culture model of infection. In a stringent HBV transgenic murine model, a single dose of hepatotropic lipid nanoparticle-encapsulated TALEN mRNA lowered HBsAg by 63% and reduced viral particle equivalents by more than 99%, without evidence of toxicity. A surveyor assay demonstrated mean in vivo HBV DNA mutation rates of approximately 16% and 15% for Core and Surface TALENs, respectively. This study presents the first evidence of the therapeutic potential of TALEN-encoding mRNA to inactivate HBV replication permanently. Full article

Obesity, type 2 diabetes mellitus (T2DM) and steatohepatitis associated with metabolic dysfunction (MASLD) are on the rise and pose serious health challenges worldwide. In recent years, researchers have gained a better understanding of the important role of the gut microbiota in the development and progression of these diseases. Intestinal dysbiosis can contribute to the occurrence of increased intestinal permeability, inflammation and reduced numbers of commensal bacteria. In obesity, these changes contribute to chronic low-grade inflammation and deregulated metabolism. In MASLD, gut microbiota dysbiosis can promote liver fibrosis and impair bile acid metabolism, while in T2DM, they are associated with impaired glycemic control and insulin resistance. Regular physical activity has a positive effect on the composition of the gut microbiota, increasing its diversity, modulating its metabolic functions, strengthening the intestinal barrier and reducing inflammation. These findings suggest that exercise and microbiota-targeted interventions may play an important role in the prevention and treatment of metabolic diseases. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) begins with hepatic lipid accumulation and triggers insulin resistance. Hibiscus leaf extract exhibits antioxidant and anti-atherosclerotic activities, and is rich in (−)-epicatechin gallate (ECG). Despite ECG’s well-known pharmacological activities and its total antioxidant capacity being stronger than that of other catechins, its regulatory effects on MASLD have not been fully described previously. Therefore, this study attempted to evaluate the anti-MASLD potential of ECG isolated from Hibiscus leaves on abnormal lipid and glucose metabolism in hepatocytes. First, oleic acid (OA) was used as an experimental model to induce lipid dysmetabolism in human primary hepatocytes. Treatment with ECG can significantly (p < 0.05) reduce the OA-induced cellular lipid accumulation. Nile red staining revealed, compared to the OA group, the inhibition percentages of 29, 61, and 82% at the tested doses of ECG, respectively. The beneficial effects of ECG were associated with the downregulation of SREBPs/HMGCR and upregulation of PPARα/CPT1 through targeting AMPK. Also, ECG at 0.4 µM produced a significant (p < 0.01) decrease in oxidative stress by 83%, and a marked (p < 0.05) increase in glycogen synthesis by 145% on the OA-exposed hepatocytes with insulin signaling blockade. Mechanistic assays indicated lipid and glucose metabolic homeostasis of ECG might be mediated via regulation of lipogenesis, fatty acid β-oxidation, and insulin resistance, as confirmed by an AMPK inhibitor. These results suggest ECG is a dual modulator of lipid and carbohydrate dysmetabolism in hepatocytes. Full article

Cholangiocarcinoma (CCA) is highly prevalent in the Greater Mekong sub-region, especially northeastern Thailand, where infection with the liver fluke Opisthorchis viverrini is a major etiological factor. Limited therapeutic options and the absence of reliable early diagnosis tools impede effective disease control. Atractylodes lancea (Thunb.) DC.—long used in Thai and East Asian medicine, contains atractylodin (ATD), a potent bioactive compound with anticancer potential. Here, we developed ATD-loaded poly(lactic co-glycolic acid) nanoparticles (ATD PLGA NPs) and evaluated their antitumor efficacy against CCA. The formulated nanoparticles had a mean diameter of 229.8 nm, an encapsulation efficiency of 83%, and exhibited biphasic, sustained release, reaching a cumulative release of 92% within seven days. In vitro, ATD-PLGA NPs selectively reduced the viability of CL-6 and HuCCT-1 CCA cell lines, with selectivity indices (SI) of 3.53 and 2.61, respectively, outperforming free ATD and 5-fluorouracil (5-FU). They suppressed CL-6 cell migration and invasion by up to 90% within 12 h and induced apoptosis in 83% of cells through caspase-3/7 activation. Micronucleus assays showed lower mutagenic potential than the positive control. In vivo, ATD-PLGA NPs dose-dependently inhibited tumor growth and prolonged survival in CCA-xenografted nude mice; the high-dose regimen matched or exceeded the efficacy of 5-FU. Gene expression analysis revealed significant downregulation of pro-tumorigenic factors (VEGF, MMP-9, TGF-β, TNF-α, COX-2, PGE₂, and IL-6) and upregulation of the anti-inflammatory cytokine IL-10. Collectively, these results indicate that ATD-PLGA NPs are a promising nanotherapeutic platform for targeted CCA treatment, offering improved anticancer potency, selectivity, and safety compared to conventional therapies. Full article

Plastic pollution in marine environments poses a new global threat. Microplastics (MPs) can bioaccumulate in marine organisms, leading to oxidative stress (OS). This study investigates MP accumulation and associated OS responses in six invertebrate species (Bivalvia, Gastropoda, and Malacostraca) and three key fish species of the Bulgarian Black Sea ecosystems. The target hydrobionts were collected from nine representative coastal habitats of the northern and southern aquatory. MPs were quantified microscopically, and OS biomarkers (lipid peroxidation, glutathione, and antioxidant enzymes) were analyzed spectrometrically in fish liver and gills and invertebrate soft tissues (STs). The specific OS (SOS) index was calculated as a composite indicator of the ecological impact, incl. MP effects. The results revealed species-specific MP bioaccumulation, with the highest concentrations in Palaemon adspersus, Rathke (1837) (0.99 ± 1.09 particles/g ST) and the least abundance in Bittium reticulatum (da Costa, 1778) (0.0033 ± 0.0025 particles/g ST). In Sprattus sprattus (Linnaeus, 1758), the highest accumulation of MPs was present (2.01 ± 2.56 particles/g muscle). The correlation analyses demonstrated a significant association between MP counts and catalase activity in all examined species. The SOS index varied among species, reflecting different stress responses, and this indicated that OS levels were linked to ecological conditions of the habitat and the species-specific antioxidant defense potential to overcome multiple stressors. These findings confirmed the importance of environmental conditions, including MP pollution and the evolutionarily developed capacity of marine organisms to tolerate and adapt to environmental stress. This study emphasizes the need for novel approaches in monitoring MPs and OS to better assess potential ecological risks. Full article

Selenium (Se) is an essential trace element critical for animal growth and immune function. This study investigated the dietary selenium requirement of juvenile large yellow croaker (Larimichthys crocea) through an 8-week feeding trial. Five experimental diets were formulated by supplementing a basal diet with selenium polysaccharides (Se-PS) at 0, 20, 30, 40, and 50 mg/kg, resulting in analyzed Se concentrations of 0.35, 0.54, 0.71, 0.93, and 1.11 mg/kg, respectively. The results demonstrated that growth performance and feed efficiency improved with increasing dietary selenium, peaking at 0.93 mg/kg before declining at higher levels. Antioxidant enzyme activities—superoxide dismutase (SOD) and catalase (CAT)—in serum and liver tissues exhibited a dose-dependent increase, reaching maximal levels at 1.11 mg/kg. Conversely, malondialdehyde (MDA), a marker of oxidative stress, progressively decreased in both serum and liver, attaining its lowest concentration at 1.11 mg/kg, though this did not differ significantly from the 0.93 mg/kg group (p = 0.056). Tissue selenium accumulation was highest at these optimal dietary levels. Based on the growth performance, oxidative stress response, and tissue selenium retention, the recommended dietary selenium requirement for juvenile large yellow croaker is 0.93 mg/kg. These findings highlight the importance of optimal Se supplementation in aquafeeds to enhance growth and physiological health in farmed fish. Full article

Coffee is one of the most widely consumed beverages globally, with over 60% of Americans drinking it daily. This review examines coffee’s multifaceted impact on health and well-being, drawing on decades of research. Overall, the consensus is that moderate coffee intake is more beneficial than harmful across a wide range of health outcomes. Numerous large-scale, prospective cohort studies from around the world have consistently shown that moderate coffee consumption—typically three to five cups per day—is associated with reduced overall mortality and lower risk of major diseases such as cardiovascular diseases, diabetes, stroke, respiratory conditions, cognitive decline, and potentially several types of cancer, including liver and uterine cancers. Both caffeinated and decaffeinated coffee have shown benefits. The addition of sugar and cream to coffee may attenuate coffee’s positive health effects. Despite historical concerns, coffee consumption is not linked to increased risks of cancer, hypertension, or arrhythmia. However, some concerns remain. For pregnant women, coffee consumption should be limited to lower amounts, such that the daily intake of caffeine does not exceed 200 mg/day. Also, excessive caffeinated coffee intake may cause anxiety or sleep disturbances. Coffee’s health-promoting mechanisms include improved glucose balancing, increased physical activity, increased fat oxidation, improved lung function, and reduced inflammation. Beyond mortality and chronic diseases, coffee consumption affects many aspects of well-being: it supports hydration, boosts mental acuity, enhances physical performance, and may aid bowel recovery after surgery. While the field is well-studied via long-term observational cohorts, future research should focus on randomized controlled trials, Mendelian randomization studies, and granular analyses of coffee types and additives. Full article

Viral outbreaks have caused significant mortality and economic losses in aquaculture, highlighting the urgent need for effective therapies and a deeper understanding of antiviral and immune mechanisms in key species. This study investigates the constitutive and virus-induced antiviral responses in juvenile rainbow trout (Oncorhynchus mykiss) following infection with viral hemorrhagic septicemia virus (VHSV). Trout (30 g) were infected by immersion with VHSV (TCID₅₀ = 10⁵ mL⁻¹) for two hours. Samples were collected at 24, 72, and 120 h post-infection to assess hematology, innate immunity, viral load, and transcriptomic response. At 24 h post-infection, no immune response or increase in viral load was detected, suggesting the host had not yet recognized the virus and was still in the incubation phase. By 72 h, viral replication peaked, with high viral loads observed in mucosal tissues (skin and gills) and immune organs (kidney, spleen, liver), alongside strong up-regulation of antiviral genes, such as viperin. This gene maintained high expression through the final sampling point, indicating its key role in the antiviral response. At this stage, reduced immune competence was observed, marked by elevated nitric oxide and circulating thrombocytes. At 120 h, modest increases in peripheral monocyte, plasma lysozyme, and peroxidase activity were detected; however, these responses were insufficient to reduce viral load, suggesting the resolution phase had not yet begun. In summary, while a limited immune response was observed by the end of the trial, the consistent antiviral activity of viperin from peak infection to 120 h post-infection underscores its importance in the defence against VHSV in rainbow trout. Full article

Background and Objectives: The uric acid to HDL-cholesterol ratio (UHR) has recently emerged as a promising biomarker reflecting systemic inflammation and metabolic disturbances. Elevated liver transaminases are clinical indicators of hepatic injury and underlying metabolic dysfunction. Many Middle Eastern countries face constrained clinical and laboratory resources, where access to comprehensive diagnostic tools may be limited. In such settings, identifying simple and easily accessible markers could offer significant practical value in detecting and monitoring health disorders. This study investigates the potential association between UHR and elevated liver transaminases levels in the Saudi general population. Materials and Methods: This retrospective cross-sectional study included 9618 subjects, and the association between the UHR and elevated liver transaminases, alanine transaminase (ALT), and aspartate transaminase (AST), was comprehensively analysed. In addition, the study assessed risk indicators including the prevalence ratio (PR) and odds ratio (OR) as well as the diagnostic accuracy of UHR and C-reactive protein (CRP) in detecting liver transaminases abnormalities, with analyses stratified by age and gender. Results: UHR was significantly elevated in subjects with increased ALT and AST activities, and this pattern was consistent across all age and gender categories. High UHR was significantly associated with elevated ALT (OR = 2.32, 95% CI: 2.12–2.53, p < 0.001) and AST (OR = 1.38, 95% CI: 1.25–1.52, p < 0.001), with stronger associations observed in males and for ALT activity. In addition, elevated UHR was more prevalent among individuals with increased liver transaminase activities. Receiver operating characteristic (ROC) analysis showed that UHR outperformed CRP in identifying elevated liver transaminases, with better discriminative ability for ALT than AST activity. Conclusions: These findings highlight a significant association between UHR and liver transaminase abnormalities in the general population, underscoring the potential utility of UHR as a simple and accessible indicator for liver function assessment in clinical settings. Full article

Flavonoids constitute a broad class of naturally occurring chemical compounds classified as polyphenols, widely present in various plants, fruits, and vegetables. They share a common flavone backbone, composed of two aromatic rings (A and B) connected by a three-carbon bridge forming a heterocyclic ring (C). One representative flavonoid is chrysin, a compound found in honey, propolis, and passionflower (Passiflora spp.). Chrysin exhibits a range of biological activities, including antioxidant, anti-inflammatory, anticancer, neuroprotective, and anxiolytic effects. Its biological activity is primarily attributed to the presence of hydroxyl groups, which facilitate the neutralization of free radicals and the modulation of intracellular signaling pathways. Cellular uptake of chrysin and other flavonoids occurs mainly through passive diffusion; however, certain forms may be transported via specific membrane-associated carrier proteins. Despite its therapeutic potential, chrysin’s bioavailability is significantly limited due to poor aqueous solubility and rapid metabolism in the gastrointestinal tract and liver, which reduces its systemic efficacy. Ongoing research aims to enhance chrysin’s bioavailability through the development of delivery systems such as lipid-based carriers and nanoparticles. Full article

Early weaning of piglets elicits weaning stress, which in turn induces oxidative stress and consequently impairs growth and development. Hydrogen-rich water (HRW), characterized by selective antioxidant properties, mitigates oxidative stress damage and serves as an ideal intervention. This study aimed to evaluate the effects of HRW on weaned piglets, specifically investigating its impact on growth performance, diarrhea incidence, antioxidant function, intestinal morphology, gut microbiota, and hepatic metabolites. The results demonstrate that HRW significantly increased the average daily feed intake and significantly reduced the diarrhea rate in weaned piglets. Analysis of serum oxidative stress indicators revealed that HRW significantly elevated the activities of total antioxidant capacity and total superoxide dismutase while significantly decreasing malondialdehyde concentration. Assessment of intestinal morphology showed that HRW significantly increased the villus height to crypt depth ratio in the duodenum, jejunum, and ileum. Microbial analysis indicated that HRW significantly increased the abundance of Prevotella in the colon. Furthermore, HRW increased the abundance of beneficial bacteria, such as Akkermansia, in the jejunum and cecum, while concurrently reducing the abundance of harmful bacteria like Escherichia. Hepatic metabolite profiling revealed that HRW significantly altered the metabolite composition in the liver of weaned piglets. Differentially abundant metabolites were enriched in oxidative stress-related KEGG pathways, including ABC transporters; pyruvate metabolism; autophagy; FoxO signaling pathway; glutathione metabolism; ferroptosis; and AMPK signaling pathways. In conclusion, HRW alleviates diarrhea and promotes growth in weaned piglets by enhancing antioxidant capacity. These findings provide a scientific foundation for the application of HRW in swine production and serve as a reference for further exploration into the mechanisms underlying HRW’s effects on animal health and productivity. Full article

Objectives: This study aimed to evaluate the effect of nutritional education on nutritional knowledge, nutritional status, and quality of life in patients with liver cirrhosis. Methods: Thirty patients participated. At baseline, assessments were conducted to collect data on demographics, physical activity, anthropometric and biochemical measures, dietary habits, 24 h food intake, nutritional status, quality of life, and nutritional knowledge. Participants received a 30 min face-to-face nutritional education session by a registered dietitian, repeated after one month. A follow-up phone call was conducted one month later to reinforce the education. Final evaluations were completed one month after the call. Results: A significant upward trend was detected in nutritional knowledge scores after the intervention period (from 7.4 ± 2.76 to 9.2 ± 3.45). The physical component of quality of life improved, while the mental component showed a slight decline. Dietary changes included reduced energy and protein intake among females and increased protein intake in males. In both genders, fat intake increased and carbohydrate intake decreased. Biochemical improvements were observed, including significant reductions in gamma-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and triglycerides in females and alanine aminotransferase and gamma-glutamyl transferase in males. Conclusions: Structured nutritional education may improve nutritional knowledge, dietary behavior, and biochemical markers in cirrhosis patients. Longer follow-up durations may further enhance these improvements. Full article

Maternal undernutrition (MUN) causes severe metabolic disruption in the offspring of mammals. Here we determined the role of histone modification in hepatic gene expression in late-gestation fetuses of nutritionally restricted cows, an established model using low-nutrition (LN) and high-nutrition (HN) conditions. The chromatin immunoprecipitation sequencing results show that genes with an altered trimethylation of histone 3 lysine 4 (H3K4me3) are associated with cortisol synthesis and secretion, the PPAR signaling pathway, and aldosterone synthesis and secretion. Genes with the H3K27me3 alteration were associated with glutamatergic synapse and gastric acid secretion. Compared to HN fetuses, promoter H3K4me3 levels in LN fetuses were higher in GDF15, IRF2BP2, PPP1R3B, and QRFPR but lower in ANGPTL4 and APOA5. Intriguingly, genes with the greatest expression changes (>1.5-fold) exhibited the anticipated up-/downregulation from elevated or reduced H3K4me3 levels; however, a significant relationship was not observed between promoter CpG methylation or H3K27me3 and the gene set with the greatest expression changes. Furthermore, the stress response genes EIF2A, ATF4, DDIT3, and TRIB3 were upregulated in the MUN fetal liver, suggesting involvement of the response in GDF15 activation. Thus, H3K4me3 likely plays a crucial role in MUN-induced physiological adaptation, altering the hepatic gene expression responsible for the integrated stress response and systemic energy metabolism, especially circulating lipoprotein lipase regulation. Full article

Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive liver disorder associated with metabolic risk factors such as obesity, type 2 diabetes, and cardiovascular disease. If left untreated, the accumulation of excess hepatic fat can lead to inflammation, fibrosis, cirrhosis, hepatocellular carcinoma, and ultimately liver failure. Capsaicin (CAP), the primary pungent compound in chili peppers, has previously been shown to prevent weight gain in high-fat diet (HFD)-induced obesity models. In this study, we investigated the potential of dietary CAP to prevent HFD-induced MASLD. Methods: C57BL/6 mice were fed an HFD (60% kcal from fat) with or without 0.01% CAP supplementation for 26 weeks. We evaluated CAP’s effects on hepatic fat accumulation, inflammation, and mitochondrial function to determine its role in preventing MASLD. Results: CAP acts as a potent and selective agonist of the transient receptor potential vanilloid 1 (TRPV1) channel. We confirmed TRPV1 expression in the liver and demonstrated that CAP activates hepatic TRPV1, thereby preventing steatosis, improving insulin sensitivity, reducing inflammation, and enhancing fatty acid oxidation. These beneficial effects were observed in wild-type but not in TRPV1 knockout mice. Mechanistically, CAP-induced TRPV1 activation promotes calcium influx and activates AMPK, which leads to SIRT1-dependent upregulation of PPARα and PGC-1α, enhancing mitochondrial biogenesis and lipid metabolism. Conclusions: Our findings suggest that dietary CAP prevents MASLD through TRPV1 activation. TRPV1 signaling represents a promising therapeutic target for the prevention and management of MASLD in individuals with metabolic disorders. Full article

Background/Objectives: Lysophosphatidylcholine (LPC) is composed of various lipid species, some of which exert pro-inflammatory and others anti-inflammatory activities. However, most of the LPC species analyzed to date are reduced in the serum of patients with inflammatory bowel disease (IBD) compared to healthy controls. To our knowledge, the correlation between serum LPC species levels and measures of inflammation, as well as their potential as markers for monitoring IBD activity, has not yet been investigated. Methods: Thirteen LPC species, varying in acyl chain length and number of double bonds, were measured in the serum of 16 controls and the serum of 57 patients with IBD. Associations with C-reactive protein (CRP) and fecal calprotectin levels as markers of IBD severity were assessed. Results: Serum levels of LPC species did not differ between the healthy controls and the entire patient cohort. In patients with IBD, serum levels of LPC 16:1, 18:0, 18:3, 20:3, and 20:5, as well as total LPC concentrations, showed inverse correlations with both CRP and fecal calprotectin levels, indicating an association with inflammatory activity. Nine LPC species were significantly reduced in patients with high fecal calprotectin compared to those with low values. LPC species with 22 carbon atoms and 4 to 6 double bonds were not related to disease activity. Stool consistency and gastrointestinal symptoms did not influence serum LPC profiles. Corticosteroid treatment was associated with lower serum LPC 20:3 and 22:5 levels, while mesalazine, anti-TNF, and anti-IL-12/23 therapies had no significant impact on LPC concentrations. There was a strong positive correlation between LPC species containing 15 to 18 carbon atoms and serum cholesterol, triglycerides, and phosphatidylcholine levels. However, there was no correlation with markers of liver disease. Conclusions: Shorter-chain LPC species are reduced in patients with active IBD and reflect underlying hypolipidemia. While these lipid alterations provide insight into IBD-associated metabolic changes, they appear unsuitable as diagnostic or disease monitoring biomarkers. Full article