Search Results (1,538)

A single dose of chitosan-tripolyphosphate (TPP) nanoparticles carrying expression plasmids for fish codon-optimized Caenorhabditis elegans fat-1 and fat-2 was intraperitoneally administered to gilthead seabream (Sparus aurata) to stimulate the biosynthesis of omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and evaluate subsequent short-term effects on liver intermediary metabolism and immunity. Seventy-two hours post-injection, the upregulation of fat-1 elevated eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total n-3 fatty acids in the liver, while fat-2 enhanced DHA and n-3 fatty acids. Co-expression of fat-1 and fat-2 increased EPA, DHA, PUFA, and the total n-6 and n-3 LC-PUFA, while reducing plasma triglycerides. The expression of fat-1 and fat-2 suppressed hepatic lipogenesis by downregulating srebf1 and pparg, and consequently key genes in fatty acid synthesis (acaca, acacb, fasn, scd1, and fads2). In contrast, the co-expression of fat-1 and fat-2 upregulated hnf4a, chrebp, and pfkl, a rate-limiting enzyme in glycolysis. Furthermore, fat-1 and fat-2 reduced hepatic proinflammatory markers such as tnfa and nfkb1. In addition to enhancing EPA and DHA biosynthesis, promoting glycolysis, and suppressing lipogenesis, our findings suggest that the short-term expression of C. elegans fat-1 and fat-2 in the liver may also reduce inflammation and, therefore, could impact the health and growth performance of cultured fish. Full article

Duck viral hepatitis (DVH), a highly contagious disease, is caused primarily by duck hepatitis A virus (DHAV). The viral genotypes exhibit significant diversity, creating a challenge as monovalent vaccines fail to provide cross-genotype protection in ducklings. This study aimed to design a multi-epitope peptide vaccine targeting different genotypes of DHAV. Using immunoinformatics approaches, we systematically identified key antigenic determinants, including linear B-cell epitopes, cytotoxic T-cell epitopes (CTL), and helper T-cell epitopes (HTL). Based on these, a novel vaccine candidate was developed. The vaccine construct was subjected to rigorous computational validation: (1) Molecular docking with Toll-like receptors (TLRs) predicted immune interaction potential. (2) Molecular dynamics simulations assessed complex stability. (3) In silico cloning ensured prokaryotic expression feasibility. Then, we conducted preliminary experimental validation for the actual effect of the vaccine candidate, including recombinant protein expression in E. coli, enzyme-linked immunosorbent assay (ELISA) quantification of humoral responses, and Western blot analysis of cross-reactivity. ELISA results demonstrated that the vaccine candidate could induce high-titer antibodies in immunized animals, with potency reaching up to 1:128,000, and the immune serum showed strong reactivity with recombinant VP proteins. Western blot analysis using duck sera confirmed epitope conservancy across genotypes. Collectively, the multi-epitope vaccine candidate developed in this study represents a highly promising broad-spectrum strategy against DHAV. The robust humoral immunity it elicits, coupled with its demonstrated cross-reactivity, constitutes compelling proof-of-concept, laying a solid foundation for advancing to subsequent challenge trials and translational applications. Full article

This study investigated the effects of vitamin E supplementation on growth performance, antioxidant capacity, and hepatic lipid metabolism in one-year-old juvenile Chinese sturgeon (Acipenser sinensis). A total of 270 fish (initial weight 1.37 ± 0.04 kg) were allocated into 9 fiberglass tanks and fed isonitrogenous and isolipidic diets with graded concentrations of vitamin E (DL-α-tocopherol acetate) including, 0, 1000, and 2000 mg/kg, respectively, for 2 months. Results showed that 1000 mg/kg vitamin E significantly improved growth performance and decreased hepatosomatic index. Dietary vitamin E supplementation significantly reduced the hepatic crude protein and crude lipid levels, withnot significantly affecting moisture and crude ash. Dietary vitamin E led to significant increases in plasma high-density lipoprotein cholesterol and vitamin E levels, while decreasing plasma low-density lipoprotein cholesterol. Additionally, it raised liver vitamin E content and reduced hepatic triglycerides, total cholesterol, crude protein, and crude lipid levels. Vitamin E also significantly downregulated mRNA levels of lipogenesis-related genes (ACC1, acetyl-CoA carboxylase 1; FASN, fatty acid synthase; and PPARγ, peroxisome proliferator activated receptor γ) and inhibited the enzyme activities of ACC1 and FASN, while upregulating lipolysis-related genes (HSL, hormone-sensitive lipase; CPT1, carnitine palmitoyltransferase 1α, and PPARα, peroxisome proliferator activated receptor α) and enhancing the activities of HSL and CPT1α. Furthermore, vitamin E supplementation significantly improved plasma reduced glutathione and superoxide dismutase activities, lowered plasma reactive oxygen species, malondialdehyde levels, and hepatic malondialdehyde contents, and upregulated mRNA levels of hepatic Nrf2 (nuclear factor-erythroid 2 related factor 2), Keap1 (Kelch-like epichlorohydrin associating protein 1), and CuZnSOD (copper/zinc superoxide dismutase). In conclusion, dietary 1000 mg/kg vitamin E supplementation could improve growth performance, enhance antioxidant capacity, and reduce liver fat deposition, indicating its potential as a beneficial dietary additive for promoting health and lipid regulation in juvenile Chinese sturgeon. Full article

Therapeutic peptides have gained significant attention due to their high specificity, potency, and safety profiles in treating various diseases. However, their clinical application via the oral route remains challenging. Peptides are inherently unstable in the gastrointestinal environment, where they are rapidly degraded by proteolytic enzymes and acidic pH, leading to poor bioavailability. Additionally, their large molecular size and hydrophilicity restrict passive diffusion across the epithelial barriers of the gastrointestinal tract. These limitations have traditionally necessitated parenteral administration, which reduces patient compliance and convenience. The oral cavity, comprising the buccal and sublingual mucosa, offers a promising alternative for peptide delivery. Its rich vascularization allows for rapid systemic absorption while bypassing hepatic first-pass metabolism. Furthermore, the mucosal surface provides a relatively permeable and accessible site for drug administration. However, the oral cavities also present significant barriers: the mucosal epithelium limits permeability, the presence of saliva causes rapid clearance, and enzymes in saliva contribute to peptide degradation. Therefore, innovative strategies are essential to enhance peptide stability, retention, and permeation in this environment. Nanoparticle-based delivery systems, including lipid-based carriers such as liposomes and niosomes, as well as polymeric nanoparticles like chitosan and PLGA, offer promising solutions. These nanocarriers protect peptides from enzymatic degradation, enhance mucoadhesion to prolong residence time, and facilitate controlled release. Their size and surface properties can be engineered to improve mucosal penetration, including through receptor-mediated endocytosis or by transiently opening tight junctions. Among these, niosomes have shown high encapsulation efficiency and sustained release potential, making them particularly suitable for oral peptide delivery. Despite advances, challenges remain in translating these technologies clinically, including ensuring biocompatibility, scalable manufacturing, and patient acceptance. Nevertheless, the oral cavity’s accessibility, combined with nanotechnological innovations, offers a compelling platform for personalized, non-invasive peptide therapies that could significantly improve treatment outcomes and patient quality of life. Full article

Striped catfish, Pangasianodon hypophthalmus, has recently emerged as a promising candidate for Egyptian aquaculture owing to its rapid growth; however, under intensive culture, it is vulnerable to Aeromonas hydrophila. The efficacy of dietary supplementation with effective probiotic microorganisms (EPMs) in enhancing growth performance, feed utilization, physiological health, and disease resistance of P. hypophthalmus against A. hydrophila challenge was evaluated. A 90-day feeding trial was conducted with 300 fish randomly distributed into four triplicate groups (25 fish per replicate) reared in 12 indoor fiberglass tanks: a control and three groups receiving EPMs at inclusion levels of 1.5%, 3%, and 4.5%. The results showed significant, dose-dependent improvements across all EPMs-supplemented groups in survival, growth rates, feed utilization, and hematological parameters (RBC, Hb, PCV, WBC, and lymphocytes). Dietary EPMs led to significant improvements (p ≤ 0.001) in digestive efficiency, protein and lipid metabolism, antioxidant enzyme activity, immune performance, and the ability of striped catfish to withstand A. hydrophila infection. Hepatobiliary enzyme activities (ALT, AST, and ALKP), glucose levels, lipid profile markers, and hepatic MDA exhibited a significant linear decrease (p ≤ 0.0001) with increasing EPMs levels. The gut microbial composition showed a dose-dependent increase in beneficial lactic acid bacteria (LAB) and a reduction in TAPC, pathogenic coliforms (TFCC), and Vibrio spp. (TVC). These results demonstrate the dose-dependent effects of EPMs on enhancing aquafeed efficiency, overall health, and innate immunity in striped catfish. Full article

Background: Human cell lines underpin modern biomedical research, offering reproducibility, standardisation, and unrestricted access to biological material. Among the 1206 human lines documented in the Human Protein Atlas, in vitro systems overcome the ethical and technical constraints of primary tissues. The liver is an organ of intricate structure, diverse physiological roles, and limited in vitro viability. Liver-derived cell lines are increasingly used to address the growing burden of liver disease and to accelerate pharmaceutical development, yet their capacity to replicate native hepatic functions remains uncertain. The mutational profiles and expression patterns of hepatocyte-characteristic genes provide critical benchmarks for their suitability for pharmacology and toxicology. Methods: Here, we systematically compare ten widely used hepatic cell lines (HepG2, Huh7, Hep3B, LX-2, HepaRG, HLF, HLE, MHCC97H, SK-Hep1, PLC/PRF/5) with primary hepatocytes and liver tissue, focusing on drug-metabolizing enzyme (DME) gene expression. Beyond literature synthesis, we analysed pre-processed RNA-seq expression data. Results: Overall, among the models examined, the HepaRG cell line shows the greatest similarity to liver and primary hepatocytes, most faithfully reproducing the expression patterns of DME genes. HepG2, Hep3B, and Huh7 form a cluster that retains only a subset of hepatic characteristics. Other models display more pronounced deviations from the reference profile and are generally used for specialized applications. Thus, no universal cell line exists that can fully substitute for the liver. Each model has its own limitations and biases in the expression profile of DME genes, which must be carefully considered when selecting an appropriate system for specific research objectives. Full article

The revalorization of animal by-products, such as porcine blood, is a key strategy for sustainable aquaculture and circular economy practices. This study aimed to fill the existing knowledge gap on the effects of spray-dried porcine blood hydrolysate (PBSH), assessing its potential as a functional feed ingredient for gilthead sea bream. Two practical diets were formulated: a control diet containing 5% blood meal, and a PBSH diet including 5% PBSH previously characterized in vitro. The results indicated that the PBSH diet promoted lower hepatosomatic index, a down-regulation of key hepatic lipogenic enzymes (scd1b, hl, lpl), and a better stress condition with lower circulating levels of glucose and cortisol and a reduction in aggressive attacks. Positive findings were also achieved in energy management, obtaining lower metabolic rates along with an enhanced swimming performance (20% increase in the critical speed) and a quicker weigh recovery after a fasting period. The PBSH diet also shaped the intestinal bacterial composition, determining a redistribution of abundant genera including Aureimonas and Halomonas. Ultimately, this study demonstrated that PBSH would act as a functional ingredient capable of enhancing fish energy management and resilience in the face of stressful events, exhibiting a transient transcriptional modulation, yet persistent physiological and welfare benefits. Full article

In this multicenter, retrospective study involving 62 patients, we investigated whether switching from entecavir (ETV) or tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) represents a superior treatment strategy for patients with chronic hepatitis B (CHB) experiencing low-level viremia (LLV). The study determined that TAF significantly improved both virological and biochemical outcomes. At 48 weeks, the complete virological response (CVR) rate was 77.8% for those who switched from ETV and 81.8% for those who switched from TDF, with Hepatitis B virus deoxyribonucleic acid (HBV DNA) negativity reaching 81% by month 12. Additionally, significant normalization of liver enzymes, albumin, and platelet counts was observed across the cohort. While the switch from TDF was associated with a significant increase in triglycerides and high-density lipoprotein (HDL) and a decrease in estimated glomerular filtration rate (eGFR), no such changes were detected in the ETV group. This evidence suggests that TAF provides robust virological control in LLV patients and is associated with favorable biochemical improvements. However, due to the study’s limitations, the strong assertion that TAF promotes the regression of liver fibrosis and reduces the risk of hepatocellular carcinoma (HCC) must be interpreted with caution. Full article

Low-fishmeal feed is increasingly being adopted across the global aquaculture industry. This study evaluated dietary Clostridium butyricum and alanyl-glutamine (Ala-Gln) supplementation in juvenile triploid rainbow trout (Oncorhynchus mykiss) with a low-fishmeal diet. Four diets were tested: basal diet (SBM, 15% fishmeal and 21.6% soybean meal), SBM + 0.5% C. butyricum (CB), SBM + 1.0% Ala-Gln, and SBM + 0.5% C. butyricum + 1.0% Ala-Gln (CB-AG). Fish were fed in 500 L tanks in recirculating aquaculture systems for 8 weeks (62.52 ± 0.47 g). Each group comprised three tanks, with each tank housing 30 fish. Then 10 fish per tank were challenged with Aeromonas salmonicida. CB-AG showed significantly higher weight gain and specific growth rates than the SBM group (p < 0.05). Mortality was significantly lower in CB-AG and AG than in SBM after A. salmonicida challenge. Histomorphology revealed significant differences (p < 0.05) between CB-AG and SBM in muscularis thickness, villus width, and height. SBM sections showed inflammatory infiltration and border damage were attenuated in supplemented groups. Serum malondialdehyde (MDA) and dioxygenase (DAO) were significantly lower in CB-AG than SBM (p < 0.05), while serum and hepatic lysozyme (LZM) and hepatic superoxide dismutase (SOD) were higher. Digestive enzymes indicated significantly higher trypsin and lipase activities in CB-AG (p < 0.05). CB-AG upregulated intestinal tight junction proteins and PepT1 and downregulated pro-inflammatory mediators. Combined 0.5% C. butyricum and 1.0% Ala-Gln inclusion effectively preserved growth performance, antioxidant capacity, gut microbiome homeostasis, and intestinal health in rainbow trout on low-fishmeal diets. Full article

Permethrin (PERM) is a synthetic pyrethroid insecticide initially regarded as low risk. However, evidence now indicates that misuse and prolonged exposure can damage multiple physiological systems by disrupting enzymatic functions in subcellular structures. In this study, male Wistar rats were administered PERM (75, 150, or 300 mg/kg/day) for 15 days to assess its effect on hematological and biochemical parameters, including oxidative stress markers in the liver, kidney, and heart. Subacute PERM administration induced significant, dose-dependent toxicological alterations in exposed animals. Hematological analysis revealed impaired hematopoiesis, characterized by increased erythrocytes and platelets alongside decreased hemoglobin, hematocrit, mean corpuscular volume, and red cell distribution width. Biochemical analysis revealed elevated liver enzymes and bilirubin, along with reduced albumin levels, indicating hepatic alterations associated with PERM. The assessment of oxidative stress revealed tissue-specific responses following PERM exposure. While GPx, CAT, and SOD levels remained unchanged, GR activity increased in the heart, and GST activity increased in the liver. Additionally, a substantial decrease in MDA was observed in both the liver and heart. These collective alterations found in PERM-subacute exposed rats suggest the potential for cellular damage with the possible development of chronic pathologies, warranting further investigation. Full article

Background/Objectives: Plants and fruits of Physalis philadelphica Lam. Solanacea are commonly used in traditional medicine to improve some illnesses such as diabetes, in North and Central American countries. The aim was to evaluate the effects of aqueous maceration (He-M) and ultrasound-assisted (He-US) extracts of P. philadelphica husk on hyperglycemia, insulin resistance, hepatic steatosis, and oxidative stress in obese rats. Methods: The effects of husk extracts on carbohydrate and lipid absorption were evaluated using oral starch and lipid tolerance tests in healthy male Wistar rats. Obesity was then induced using a high-fructose and saturated fat diet, followed by 16 weeks of extract administration. Results: He-US significantly reduced the postprandial glycemic spike, while both extracts lowered serum triglyceride levels (~50%) following lipid loading, compared with the negative control. In obese rats, both extracts reduced body weight gain (~10%) and lowered fasting glucose levels (22% for He-M and 15% for He-US), compared with the obese control. He-US also reduced insulin levels (~32%), insulin resistance (~53%), and free fatty acids (~52%), while He-M improved hepatic steatosis and reduced liver triglycerides (~26%). Both extracts reduced hepatic nitrite levels, although only He-M significantly decreased lipid peroxidation (~32%). Additionally, both treatments enhanced hepatic antioxidant enzyme activity. Conclusions: Husk extracts exerted beneficial effects on hyperglycemia, insulin resistance, hepatic steatosis, and oxidative stress markers in obese rats. Full article

Previous studies have demonstrated that high-yielding dairy cows experience endoplasmic reticulum (ER) stress in the liver during early lactation. To date, most insights into the role of ER stress in metabolism and disease pathophysiology have been derived from rodent and human models. In dairy cattle, however, the specific impact of ER stress on metabolic pathways and its contribution to disease development remain insufficiently characterized. The objective of this study was therefore to investigate the molecular effects of ER stress using a bovine liver cell model (BFH12 cells). ER stress was induced by incubation with Tunicamycin (TM) and Thapsigargin (TG). Molecular responses to ER stress were assessed via a whole-genome array analysis and PCR targeting genes involved in selected metabolic pathways. Incubation with both ER stress inducers resulted in a marked upregulation of genes associated with the unfolded protein response (UPR) within a 4 to 24-h time frame, indicative of the production of robust ER stress in these cells. Unexpectedly, treatment with TM led to a downregulation of numerous genes involved in lipid biosynthesis, including those related to lipogenesis and cholesterol synthesis. Furthermore, incubation with TM and TG induced upregulation of genes involved in fatty acid oxidation and was accompanied by a reduction in intracellular triglyceride concentrations. Genes associated with inflammatory responses were upregulated by both TM and TG, whereas genes encoding antioxidant enzymes were downregulated. Genes involved in ketogenesis did not exhibit a consistent pattern of regulation. Overall, several effects of ER stress previously described in rodent models could not be replicated in this bovine liver cell system. Extrapolating these findings to dairy cows suggests that while ER stress may contribute to hepatic inflammation, it is unlikely to play a significant role in the development of hepatic lipidosis or ketosis. Full article

Background: The aging of people living with HIV (PLWH) necessitates antiretroviral regimens (ART) with high efficacy, a favorable safety profile, and minimal drug–drug interactions. We evaluated the real-world performance of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in PLWH aged ≥ 50 years, stratified by prior treatment experience. Methods: This retrospective cohort study included ART-naïve and virologically suppressed treatment-experienced PLWH aged ≥ 50 years who started B/F/TAF. Primary endpoints were virological suppression (HIV-1 RNA < 50 copies/mL) at 12 months ± 1 month and 24 months ± 1 month, and safety. Changes in immunological (CD4+ count, CD4+/CD8+ ratio), metabolic, and hepatic parameters were assessed. Results: Among 214 patients (37 naïve, 177 experienced; mean age 60.6 years), high virological suppression rates were observed in both naïve (85.7%) and experienced (93.9%) cohorts at 24 months. Immunologically, naïve patients experienced a robust increase in CD4+ counts (from 176 to 450 cells/μL, p < 0.001). A key finding was a significant increase in the CD4+/CD8+ ratio in the experienced cohort, which normalized from 0.95 at baseline to 1.12 at 24 months (p < 0.001). The regimen demonstrated a favorable safety profile: metabolic parameters remained stable, and hepatic enzymes significantly improved in naïve patients. Transient elastography confirmed no worsening of liver fibrosis or steatosis in experienced patients. The overall discontinuation rate was 19.2%, driven by different reasons between cohorts (e.g., comorbidities in naïve, strategic simplification in experienced). Conclusions: This real-world study confirms that B/F/TAF is a versatile cornerstone for the management of older PLWH. It demonstrates high efficacy in initiating treatment and is a safe, effective, and durable platform for treatment simplification. Its favorable metabolic and hepatic profile makes it particularly suitable for an aging population with a high burden of comorbidities, ensuring long-term treatment success. Full article

Background/Objectives: Although several studies have been reported on the modulation of Cytochrome P450 by resveratrol, inconsistencies in the results obtained require further investigation. Here, we report the results of in vivo and in vitro experiments investigating the effect of resveratrol on CYP1A2, which participates in the biotransformation of several drugs used for the treatment of human malignancies. Methods: Male Wistar rats were exposed to resveratrol through diet (1%) for 30 days, and the hepatic CYP1A2 activity and protein concentration were assayed at the end of the treatment. Additionally, the capacity of the phytochemical to interfere with the induction of CYP1A2 by benzo[a]pyrene (50 mg/kg body weight) was also studied. The inhibition of CYP1A2 activity in rat liver microsomal and recombinant human enzymes by resveratrol, as well as its inhibitory kinetics and type of inhibition, were compared. Results: No significant increase in the protein concentration of hepatic CYP1A2 was found in resveratrol-treated rats, but it induces CYP1A2 activity and enhances the induction effect of benzo[a]pyrene. In silico and in vitro experiments demonstrated that resveratrol binds to the active site of human CYP1A2 through hydrophobic interactions with PHE125, PHE226, PHE260, and ALA317, and hydrogen bonds with SER122 and ASP313. It inhibits human recombinant CYP1A2 activity as well as that in rat liver microsomes, with IC₅₀ values of 46 µM and 485 µM, respectively. Resveratrol showed a mixed type of inhibition of recombinant human protein and a competitive inhibition of rat liver microsomal CYP1A. Conclusions: We can conclude that resveratrol is an in vitro inhibitor of CYP1A2, but it increases the benzo[a]pyrene CYP induction effect in vivo. Full article

Alcohol-associated liver disease is a global health burden with high morbidity and mortality, and the fungal microbiome is important for its progression. In particular, Candida albicans and C. albicans-reactive T helper 17 (Th17) cells contribute to alcohol-associated liver disease. Specific C. albicans antigens that activate Th17 cells during this disease are unknown. The C. albicans 65 kDa mannoprotein (CaMp65p) is one of the most abundant and immunodominant proteins of C. albicans, and is capable of eliciting robust T cell and interleukin (IL)-17A responses. The aim of this study was to measure levels of CaMp65p in serum of patients with alcohol use disorder and liver disease. Serum CaMp65p levels were measured in the serum of 60 patients with alcohol use disorder using an indirect competitive Enzyme-Linked Immunoabsorbent Assay (ELISA). Serum CaMp65p levels were correlated with liver disease severity. Serum CaMp65p levels positively correlated with several clinical and biochemical markers of liver injury and disease within the patient group with alcohol use disorder, including serum aspartate aminotransferase (AST; R = 0.33, p = 0.0092), alanine aminotransferase (ALT; R = 0.27, p = 0.037), gamma-glutamyl transferase (GGT; R = 0.35, p = 0.0055) and alkaline phosphatase (R = 0.36, p = 0.0052), and with the circulating M65 fragment of cytokeratin 18 (CK18-M65; R = 0.51, p = 0.0012), a marker of hepatocyte death. In addition, patients with alcohol use disorder in the upper quartile had significantly higher liver stiffness (p = 0.0022). Serum CaMp65p was significantly higher in patients with fibrosis stage F2–F4 as compared with patients with no or minimal fibrosis F0–F1 (p = 0.0082). The area under the curve (AUC) for detecting F2–F4 fibrosis was 0.70. Elevated serum CaMp65p levels are associated not only with more severe hepatic injury, but also with liver fibrosis in patients with alcohol use disorder. Therefore, CaMp65p may serve as a non-invasive biomarker for fibrosis assessment in patients with alcohol use disorder. Full article