Search Results (3,189)

Background: Primary Sclerosing Cholangitis (PSC), Primary Biliary Cholangitis (PBC), and Autoimmune Hepatitis (AIH) are rare immune-mediated liver conditions that significantly affect patients’ quality of life. In Romania, access to specialized information and patient support resources is limited, underscoring the need for tailored educational tools. The aim was to describe the methodology for developing, implementing, and conducting a feasibility study of an online platform for patients with PSC, PBC, and AIH, as a pilot study, providing early insights. Methods: The platform offers educational materials, registration, a discussion forum, and digital tools for quality-of-life assessment. Data on demographics, usage, and quality of life were collected using standardized questionnaires (CLDQ-PSC, PBC-10) and non-standardized questionnaires, and analyzed with Microsoft Office Excel and DATATab. Results: The website was created using an online platform requiring no advanced IT skills. Content was developed in accordance with international guidelines (EASL, AASLD) and translated and adapted for Romanian patients. As of 15 July 2025, 81 patients had been registered (26% PSC, 68% PBC, 6% AIH), with a predominance of urban participants (all patients: 87% female, mean age at diagnosis = 44.5 years). Most participants used mobile devices and reported improved understanding and engagement with their health after using the platform. Conclusions: The first dedicated digital platform has been established in Romania to address the health literacy needs of patients with PSC, PBC, and AIH. The study offers insights into future directions and a replicable model for similar initiatives. The pilot evaluation of the platform faced several limitations, including self-selection bias, non-standardized assessments, and a small sample size. Full article

Liver transplantation (LT) is a curative treatment for hepatocellular carcinoma (HCC). However, lifelong immunosuppressive therapy required to prevent graft rejection inevitably compromises antitumor immunity, thereby increasing the risk of HCC recurrence and metastasis, particularly common in the lungs. This review delves into the complex dynamic equilibrium between immune cell subsets mediating rejection and antitumor immunity, systematically analyzes the impact of current immunosuppressive regimens on this balance, and highlights emerging strategies aimed at minimizing rejection while preserving or enhancing antitumor efficacy. These strategies include immunosuppressive regimen optimization, such as mTOR inhibitor application and calcineurin inhibitor (CNI) minimization, novel immunotherapies, including immune checkpoint inhibitors (ICIs) and adoptive cell therapy (ACT), and immune tolerance induction. This review also summarizes advances in biomarker research guiding immunosuppressant withdrawal, aiming to provide a theoretical basis and clinical insights for personalized immunotherapy strategies and comprehensive tumor management in LT recipients with HCC. Full article

(1) Background: After HBV infection, viral transcripts and host RNA form a multi-layered interwoven regulatory network. However, a comprehensive map encompassing mRNA, miRNA, lncRNA, and circRNA is still lacking. This absence complicates the systematic explanation of the molecular mechanisms driving immune escape and metabolic reprogramming during the persistent infection stage. (2) Methods: In this study, we established a mouse model of chronic HBV infection and analyzed the differential expression of mRNA, miRNA, lncRNA, and circRNA through whole transcriptome sequencing (WTS). We constructed a competing endogenous RNA (ceRNA) network to systematically evaluate the overall impact of HBV on the host’s immune-metabolic pathways. (3) Results: RNA sequencing results indicated that HBV infection significantly up-regulated 194 mRNAs, 18 miRNAs, 184 lncRNAs, and 28 circRNAs, while down-regulating 42, 16, 122, and 31 corresponding transcripts, respectively. The differentially expressed genes were primarily enriched in pathways related to metabolism, immunity/inflammation, and signal transduction-ligand receptor interactions. Furthermore, the competitive endogenous RNA networks of lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA constructed on this basis further identified miR-185-3p as a key core node. (4) Conclusions: In this study, based on whole transcriptome data, the gene expression profiles of rcccDNA/Ad-infected Alb-Cre transgenic mice (chronic HBV infection model) and normal Alb-Cre mice were systematically compared, and the core regulatory factor miR-185-3p of key differentially expressed genes was screened. The microRNA is expected to provide a new target for the precise treatment of chronic hepatitis B by targeted intervention of viral replication and high liver inflammation. Full article

Toll-like receptors (TLRs) are central to pathogen recognition in teleost innate immunity. In this study, we surveyed 41 genomes from four representative teleost orders (i.e., Cypriniformes, Siluriformes, Perciformes, and Pleuronectiformes) for 15 TLR genes (TLR1–9, 12, 13, 18, 20–22) revealed a conserved core (TLR2/3/7 in nearly all examined species) alongside lineage-specific losses (TLR4/9/18/20/21/22), indicating both strong conservation and dynamic diversification of the TLR repertoire. We further identified and characterized 12 TLR genes in economically important darkbarbel catfish (Pelteobagrus vachellii). Corresponding cDNAs span 2089–4456 bp and encode proteins of 789–1,087 aa, with canonical extracellular LRR arrays and C-terminal TIR domains but notable “non-classical” features (such as absence of signal peptides in TLR1/13; no transmembrane segment in TLR7; multiple transmembranes in TLR3/8/13/18/22), suggesting subcellular and functional heterogeneity of various TLR genes. Subsequent gene-structure comparisons uncovered gene-specific exon–intron organizations and variable UTR lengths, implicating differential post-transcriptional regulation. Predicted 3D structures retain the traditional hallmark LRR horseshoe fold with subtle variations potentially tuning ligand specificity. Genomic synteny with Pseudobagrus ussuriensi and Pangasianodon hypophthalmus reveals conserved chromosomal organization, and phylogeny construction resolves each TLR subtype into well-supported monophyletic clades, which underscore evolutionary stability. Functionally, exogenous Aeromonas hydrophila challenge triggered rapid, tissue-dependent TLR up-regulation in the kidney, liver, and especially gill (with some transcripts > 1000-fold), highlighting coordinated mucosal and systemic surveillance in darkbarbel catfish. Taken together, these valuable data provide a comprehensive framework for the structural, evolutionary, and inducible expression landscape of catfish TLRs and establish a foundation for in-depth studies on antibacterial immunity in diverse teleost species. Full article

Introduction and Objectives: Persistent hepatic inflammation serves as a key driver of fibrogenesis in chronic hepatitis B. Fibrosis is a complex molecular and cellular process. Podocalyxin is a type I transmembrane sialomucin, and physiological expression of podocalyxin has been identified in the liver. Pentraxin 3 plays a crucial role in humoral innate immune responses. Isthmin-1 has been associated with metabolic regulation and immune response modulation. We aimed to evaluate the immunoreactivities of podocalyxin, Isthmin-1, and pentraxin-3 in the liver tissue of patients with chronic hepatitis B. Materials and Methods: Power analysis was performed (effect size (f = 0.5), (α) = 0.05 and statistical power of 0.80). Sample size was calculated to be a total of 63 samples, with 21 samples per group. Individuals with negative hepatitis serology and normal liver histopathology, from whom liver tissue was obtained for any reason, were designated as the control group. Liver specimens of chronic hepatitis B were categorized into F0–F2 (no or mild fibrosis) and ≥F3 (advanced fibrosis). Immunohistochemical staining was performed to assess the expression and immunoreactivity of Podocalyxin, Isthmin-1, and Pentraxin-3. A histoscore was created based on the prevalence of staining immunoreactivity (0.1: <25%, 0.4: 26–50%, 0.6: 51–75%, 0.9: 76–100%) and intensity (0: none, +0.5: very low, +1: low, +2: moderate, +3: severe). Results: A statistically significant increase in Podocalyxin, Pentraxin-3, and Isthmin-1 immunoreactivities was found in fibrotic liver tissue compared to normal liver tissue and mild fibrotic groups (p < 0.05). Conclusions: We concluded that our findings suggest these proteins may have an additional role in the progression of liver fibrosis in chronic hepatitis B. Full article

Hemorrhagic septicemia (HS) is a fulminant bovine disease across Asia and Africa, yet Pasteurella multocida (P. multocida) isolated from yak is poorly reported. We isolated strain NQ01 from a fatal HS case in Xizang, China and identified it as P. multocida B:2 by morphology, Gram stain, and PCR (kmt1⁺, bcbD⁺, LPS L2). NQO1 formed smooth, non-hemolytic colonies. After Gram staining, the cells appeared as red rods with bipolar staining. Antimicrobial testing showed broad susceptibility to β-lactams, aminoglycosides, tetracyclines, fluoroquinolones, midecamycin, florfenicol, polymyxin, and vancomycin, with resistance to metronidazole, trimethoprim sulfamethoxazole, and clindamycin. Streptomycin and ofloxacin had intermediate activity. In mice, the intraperitoneal and intranasal LD₅₀ values were 40.64 CFU/mL and 9.53 × 10⁶ CFU/mL, respectively. The intranasal fatal cases were characterized by bacteremia with multifocal disseminated intravascular coagulation involving lung, liver, and spleen. The complete genome comprises a single 2.33 Mb chromosome (40.47% GC, 2115 CDS, no plasmids) with only one resistance gene (Eco_EFTu_PLV) and 28 virulence genes spanning adhesion (tadA, rcpA, ppdD, pilB, tuf/tufA, htpB, PM_RS00430, PM_RS00425, PM_RS08640), immune modulation (lpxB/C/D, msbB, manB, rfaE/F, gmhA/lpcA, kdsA, pgi, wecA, galE, bexD’, ABZJ_RS06285, ABD1_RS00310), and nutritional/metabolic factor (hgbA, hemR, hemN), plus a YadA-like factor. Phylogenetically, NQ01 clusters with regional B:2 bovine/yak isolates. Collectively, these data define NQ01 as a highly virulent, low-resistance yak isolate and a practical model for natural-route HS pathogenesis and targeted control in high-altitude pastoral settings yaks. Full article

Perfluorooctane sulfonate (PFOS) has been widely utilized in products such as cotton textiles, hydraulic oils, coatings, pharmaceuticals, cosmetics, etc. Now it is widely distributed in various environmental media, wildlife, and human bodies. Polystyrene (PS) as a kind of plastics, their products under the physical, chemical, and biological decomposition in the environment are widely distributed in the air, soil, oceans, surface water, and sediments. However, PS and PFOS often coexist in the environment, making the study of their combined exposure mechanisms more aligned with actual conditions. This research integrates network toxicology and molecular biology techniques to predict the toxicity and common differentially expressed gene enrichment pathways of PFOS and PS. This study investigates the toxic effects of combined exposure to PFOS and PS on the mouse growth and development, immune functions, and other aspects. Additionally, it delves into the expression differences in various genes in mice after stimulation by PFOS and PS, the pathological changes in multiple organs, and the toxic effects on organs such as the liver, kidneys, and intestines. The results reveal that combined exposure to PFOS and PS does not significantly damage the kidney but leads to morphological damage in the liver and intestinal tissues, reduced antioxidant capacity, and the occurrence of inflammation. Based on the network toxicology findings, it is hypothesized that during combined exposure to PFOS and PS, the exacerbation of inflammatory responses further mediates the reduction in antioxidant capacity and the intensification of oxidative stress, ultimately resulting in tissue damage. This study provides innovative theoretical and research directions for the detection and prevention of combined exposure to PFOS and PS, offering a new paradigm for toxicological research, with significant theoretical and practical implications. Full article

Food enrichment represents a novel feeding strategy for aquaculture. In the current study, juvenile Nibea albiflora (average weight 29.65 ± 0.13 g) were used and three feeding regimes (A—commercial diet; B—a diet comprising 90% commercial feed and 10% ice-fresh Palaemon gravieri; C—a diet consisting of 90% commercial diet, 5% ice-fresh Palaemon gravieri and 5% live Perinereis nuntia; named control group, Group 1, and Group 2) with comparable nutrient compositions: were designed to establish the food enrichment model and explore the effects of such feeding strategies on the fish. The cultivation period was 60 days, and the physiological, pathological, and RNA-seq analyses were performed to evaluate the effects. The results showed that the food enrichment feeding strategy significantly enhanced fish growth performance, immunity, and stress resistance without increasing the unit production cost (UPC). Furthermore, the tri-combined food feeding (C) was better than the two-combined food feeding (B). Liver transcriptomic analysis revealed that, in the comparison between the control group and Group 1, the up-regulated genes (alox15b, gng7, hif1a, ppara, and pla2g) and down-regulated genes (ins, gck, il4i1) influenced fish physiology and further improved growth. Similar to the comparison between the control group and Group 2, the major functional genes included ugt, nlrp3, mx1, col1a, gst (up-regulated), and map2k1, myc, mmp9, wnt7, socs3 (down-regulated) that participated in regulating the body growth, immunity, and stress resistance. The up-regulated genes (ins, mhc2, foxo3, ppara, and mx1) alongside the down-regulated genes (egfr, fos, cyc, myc, and mmp9) probably contributed to the enhanced efficacy of the tri-combined food feeding compared to the two-combined food feeding. In summary, this study demonstrates the beneficial effects of such a food enrichment model on the fish and provides empirical evidence supporting the implementation of the feeding strategies in the healthy culturing of the fish. Full article

Quail farming necessitates the provision of balanced diets to promote avian health and performance, with dietary fiber and feed additives exerting significant influence on immune and physiological responses. This study aimed to evaluate the effects of stimbiotic inclusion in diets characterized by varying fiber profiles on hematological and biochemical parameters in European quails (Coturnix coturnix coturnix). A total of six hundred quails, aged from 1 to 35 days, were assigned to 12 distinct treatments, each comprising 5 replicates of 10 birds. The dietary treatments included a corn–soy control, two basal diets featuring corn (low soluble fiber) and wheat (high soluble fiber), and three mixed diets that combined corn and wheat in varying proportions, with each diet supplemented with or without 0.01% stimbiotic. Blood samples were collected at 14 and 35 days of age. In the initial phase (1–14 days), the addition of stimbiotic resulted in increased hemoglobin levels and a reduction in total white blood cells, heterophils, and lymphocytes, indicative of an enhanced immune status. In contrast, dietary fiber was found to influence liver enzyme activity and triglyceride levels. During the growth phase (15–35 days), stimbiotic continued to exert positive effects on hemoglobin and packed cell volume, while dietary fiber increased eosinophil counts, modulating the immune response without affecting other parameters. In conclusion, dietary fiber plays a functional role, particularly during the growth phase, while stimbiotic inclusion enhances immune function in both developmental stages, demonstrating that both strategies contribute positively to the health and performance of European quails. Full article

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive destruction of intrahepatic bile ducts. PBC encompasses several clinical subtypes, including classical AMA-positive PBC (90–95% of cases), AMA-negative PBC (5–10%), and overlap syndromes such as AIH-PBC. These subtypes exhibit distinct serological profiles, with AMA-negative cases often presenting PBC-specific antinuclear antibodies (anti-gp210, anti-sp100) and overlap syndromes demonstrating combined autoantibody patterns characteristic of both conditions. Autoantibodies serve as central biomarkers for diagnosis, prognosis, and understanding disease pathogenesis. This review provides a comprehensive overview of classical and emerging autoantibodies associated with PBC, including AMA-M2, anti-gp210, anti-sp100, anti-KLHL12, and anti-RPL30. We discuss their diagnostic significance across PBC subtypes, pathogenic implications, and potential utility in patient stratification and therapeutic monitoring. Recent evidence suggests that bile acid-induced neoantigen formation, rather than classical loss of immune tolerance, may drive AMA production. Advances in autoantibody profiling, including subclass-specific analysis and multi-marker panels, may pave the way for personalized medicine and improved outcomes in PBC. Full article

Newborn immaturity transcends their bodies, immune systems, and communication and perception capabilities, making them vulnerable to the environment. Neonatal jaundice is a common condition, with higher levels of unconjugated bilirubin concentration having neurotoxic effects. Newborns are routinely monitored visually or non-invasively with transcutaneous bilirubinometry (TcB) due to their biological immaturity to conjugate bilirubin. Higher levels of bilirubin are a sign that there is either an unusual rate of red blood cells breaking down or that the liver is not able to eliminate bilirubin through bile into the gastrointestinal tract. Actual devices used in bilirubin screening are hand-held and do not allow operation outside the hospital. Based on these factors, a continuous bilirubin monitoring device for newborns was developed, which enables the evaluation of neonatal jaundice inside or outside the hospital. This non-invasive device operates through a mini-spectrometer in the visible range. It was calibrated with phantoms, and its operation was compared with a gold-standard bilirubinometer through in vitro experiments, exploring the practical range of bilirubin variation in newborns and presenting a clinically acceptable deviation of 1 mg/dL. These experiments showed that the continuous bilirubin monitoring device developed has the potential to be used for remote monitoring of jaundice in newborns. Full article

Background/Objectives: Sepsis-associated liver injury (SALI) is a critical and often early complication of sepsis, defined by distinct hyper-inflammatory and immunosuppressive phases that shape patient phenotypes. Methods: Characterizing these phases establishes a foundation for immunomodulation strategies tailored to individual immune responses, as discussed subsequently. Results: The initial inflammatory response activates pathways such as NF-κB and the NLRP3 inflammasome, leading to a cytokine storm that damages hepatocytes and is frequently associated with higher SOFA scores and a higher risk of 28-day mortality. Kupffer cells and infiltrating neutrophils exacerbate hepatic injury by releasing proinflammatory cytokines and reactive oxygen species, thereby causing cellular damage and prolonging ICU stays. During the subsequent immunosuppressive phase, impaired infection control and tissue repair can result in recurrent hospital-acquired infections and a poorer prognosis. Concurrently, hepatocytes undergo significant metabolic disturbances, notably impaired fatty acid oxidation due to downregulation of transcription factors such as PPARα and HNF4α. This metabolic alteration corresponds with worsening liver function tests, which may reflect the severity of liver failure in clinical practice. Mitochondrial dysfunction, driven by oxidative stress and defective autophagic quality control, impairs cellular energy production and induces hepatocyte death, which is closely linked to declining liver function and increased mortality. The gut-liver axis plays a central role in SALI pathogenesis, as sepsis-induced gut dysbiosis and increased intestinal permeability allow bacterial products, including lipopolysaccharides, to enter the portal circulation and further inflame the liver. This process is associated with sepsis-related liver failure and greater reliance on vasopressor support. Protective microbial metabolites, such as indole-3-propionic acid (IPA), decrease significantly during sepsis, removing key anti-inflammatory signals and potentially prolonging recovery. Clinically, SALI most commonly presents as septic cholestasis with elevated bilirubin and mild transaminase changes, although conventional liver function tests are insufficiently sensitive for early detection. Novel biomarkers, including protein panels and non-coding RNAs, as well as dynamic liver function tests such as LiMAx (currently in phase II diagnostics) and ICG-PDR, offer promise for improved diagnosis and prognostication. Specifying the developmental stage of these biomarkers, such as identifying LiMAx as phase II, informs investment priorities and translational readiness. Current management is primarily supportive, emphasizing infection control and organ support. Investigational therapies include immunomodulation tailored to immune phenotypes, metabolic and mitochondrial-targeted agents such as pemafibrate and dichloroacetate, and interventions to restore gut microbiota balance, including probiotics and fecal microbiota transplantation. However, translational challenges remain due to limitations of animal models and patient heterogeneity. Conclusion: Future research should focus on developing representative models, validating biomarkers, and conducting clinical trials to enable personalized therapies that modulate inflammation, restore metabolism, and repair the gut-liver axis, with the goal of improving outcomes in SALI. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced malignancies, but they may cause a wide range of immune-related adverse events (irAEs). Hepatic toxicity occurs in approximately 1–6% of patients treated with nivolumab and usually presents with a hepatocellular pattern responsive to corticosteroids. The cholestatic-predominant immune-mediated hepatitis seems to respond poorly to immunosuppression. We describe an 87-year-old man with metastatic melanoma treated with nivolumab who developed steroid-refractory, cholestatic-predominant immune-mediated hepatitis after 18 cycles of therapy. Laboratory tests revealed a mixed but predominantly cholestatic pattern (ALT 585 U/L, GGT 2261 U/L, total bilirubin 2.0 mg/dL). Imaging excluded biliary obstruction or hepatic metastases. Liver biopsy showed acute lobular hepatitis with intracanalicular cholestasis and mild bile duct injury, consistent with immune-mediated, drug-induced injury (Ishak score 5). Mycophenolate mofetil produced only partial biochemical improvement. The patient died one month later from influenza A pneumonia in the context of combined immunosuppressive therapy. This case illustrates a cholestatic-predominant phenotype of nivolumab-induced hepatitis, characterized by poor corticosteroid response and incomplete recovery despite second-line immunosuppression. Recognition of this entity is essential, as early introduction of agents such as mycophenolate may improve outcomes. In elderly and frail patients, however, the risks of intensified immunosuppression must be carefully balanced against infection risk, highlighting the need for individualized management and vigilant monitoring. Full article

This study aimed to investigate the effects of rumen-protected methionine (RPM) on the production performance of lactating dairy goats. Thirty first-time lactating Guanzhong dairy goats with identical kidding dates and comparable body weights (41.17 ± 3.05 kg) were randomly assigned to two groups: (1) CON: basal diet and (2) RPM: basal diet + 7.5 g/day RPM. The duration of the experiment was 21 days. Compared with the CON group, the RPM group presented a significant increase in milk yield, 4% fat-corrected milk (FCM), and feed efficiency; however, no significant difference was observed in dry feed intake (DMI). Moreover, milk fat, protein, lactose, and SNF production was greater in the PRM group than in the CON group. Compared with the CON group, the RPM group presented higher nonesterified fatty acid (NEFA) and very-low-density lipoprotein (VLDL) levels, and no significant differences in the other metabolites were detected. The concentrations of acetate, propionate, and total volatile fatty acids (TVFAs) in the feces of the RPM group were significantly greater than those in the CON group; however, no significant differences were detected in the concentrations of isobutyrate, butyrate, and valerate. Furthermore, genera such as Muribaculaceae, Bifidobacterium, and Christensenellaceae were significantly enriched in the feces of the RPM group. Concurrently, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the RPM group was significantly enriched in pathways associated with amino acid synthesis, the immune system, and energy metabolism. In summary, dietary supplementation with RPM improved the lipid metabolism function of the liver, increased the abundance of beneficial bacteria such as Muribaculaceae and Bifidobacterium in the colon, and enriched microbial functions related to energy and amino acid metabolism, thereby enhancing colon fermentation and host metabolic status, ultimately improving the production performance of lactating dairy goats. These findings elucidate the positive effects of RPM on the production performance and metabolic health of dairy goats, potentially offering new perspectives and strategies for optimizing dairy production. Full article

This study evaluated whether iron supplementation in the form of chelated minerals in cows in the final third of lactation has a positive effect on iron bioavailability, immunity, oxidative status, milk quality, and biochemical and hematological parameters, as well as production efficiency and fecal microbiota. Twenty-four multiparous Jersey cows, with 210 ± 18 days in milk (DIM), an average production of 25 kg, and 4 ± 0.6 months of gestation, were divided into two groups: Control (n = 12, without supplementation) and Iron (n = 12, supplemented with 30 mg of iron/kg of dry matter (600 mg/animal/day)). Blood and milk samples were collected on days 1, 16, 29, and 42 of the experiment. Supplemented animals had higher serum iron concentrations and a higher unsaturated iron-binding capacity, especially on day 42. Higher iron content in milk was also observed. A higher granulocyte count was observed in the iron group, as well as a lower number of lymphocytes compared to the control, which may indicate immunosuppression associated with iron supplementation. Fructosamine levels were significantly lower in the iron group animals on days 14 and 28, suggesting a possible alteration in glucose metabolism. In contrast, levels of the liver enzymes AST and ALT increased significantly in the group supplemented with iron on days 28 and 42, indicating potential liver overload or injury. Iron supplementation significantly increased levels of reactive oxygen species and thiobarbituric acid-reactive substances, as well as superoxide dismutase activity in the blood. Iron supplementation altered gut microbial diversity, promoting dysbiosis characterized by increased alpha diversity and enrichment of transient colonization by Nitratireductor, Brevundimonas, Flavobacterium and Sporosarcina. Lower milk production was observed in the iron-supplemented cows in the last 10 days of the experiment, which is related to the occurrence of disease in nine cows in this group: seven with mastitis and two with intestinal peristalsis paralysis. Based on these results, we conclude that chelated iron supplementation at a dose of 600 mg/animal/day should not be used because it harms cow health and productivity. Full article