Search Results (478)

Alcohol-associated hepatitis (AH) is the most severe clinical manifestation of alcohol-associated liver disease. Corticosteroids are the only disease-specific therapy shown to improve short-term survival. Currently, no non-invasive markers are available to predict patient response to corticosteroids or long-term survival in AH. This study investigates whether surface antigens on plasma extracellular vesicles (EVs), key mediators of intercellular communication, can reflect the underlying immune dysregulation in AH and serve as prognostic markers. Patients with AH were prospectively enrolled between 2020 and 2024. Blood samples were collected before corticosteroid initiation during the first 24 h of hospitalization. EVs were characterized using nanoparticle tracking analysis, cryo-electron microscopy, and flow cytometry. Interleukin-6 (IL-6), soluble (s)CD62p, Circulating Vascular Cell Adhesion Molecule-1 (sVCAM), tumor necrosis factor receptor superfamily member 1 (TNRFS1a), and Intercellular Adhesion Molecule 1 (ICAM-1) were quantified by ELISA. Key outcome variables included response to corticosteroids and mortality. A total of 46 patients with AH and 28 healthy donors (HD) were included. EV concentration was significantly higher in AH patients than in HD (9.3 × 10¹¹ [IQR 4–24] versus 2.4 × 10¹¹ [IQR 2–4], p = 0.03). Specific EV antigens were associated with key clinical outcomes: CD20 and CD2 levels differed between patients with or without infections (bacterial, viral, and fungal) developed during hospitalization; CD40 and CD146 were elevated in patients who developed acute kidney injury. EVs enriched in monocyte (CD14) and T-reg (CD25) markers were associated with plasma IL-6 levels, while endothelial markers CD105 and CD146 correlated with sVCAM and sCD62p. EVs enriched in platelet (CD49e) and endothelial (CD31) markers were associated with corticosteroid response, whereas EVs enriched with endothelial (CD105 and CD146) and B lymphocyte (CD19) markers were associated with mortality. Overall, EVs enriched in endothelial and monocyte markers may represent a candidate non-invasive tool for predicting corticosteroid response and mortality in AH, aiding risk stratification and early identification of non-responders for timely transplant evaluation. Full article

Klebsiella pneumoniae is commonly known to cause a vast range of community-acquired or nosocomial infections. The isolation of K. pneumoniae has also been noted in diseased food-producing animals, including swine. The main goals of this study were to document clinical manifestation of a septicaemia outbreak in suckling piglets due to K. pneumoniae ST25 and provide molecular characterisation of the isolates. For the purpose of this investigation, 13 dead suckling piglets with cyanosis were selected. All the isolates obtained from affected lungs were susceptible to apramycin, ceftiofur, gentamycin, neomycin, and spectinomycin, presented intermediate susceptibility to florfenicol, and were resistant to other tested antibiotics. Histopathological examination of lungs, kidneys, and livers revealed lesions typical of septicaemia. MLST analysis of the isolates demonstrated a complex metabolic profile of the bacteria with genes attributable to the hypervirulent phenotype. To the best of our knowledge, we documented the first outbreak of K. pneumoniae septicaemia in suckling piglets reared in Poland. Full article

Diabetic wounds exhibit impaired immune function, delayed neutrophils recruitment, and heightened infection risk which compromises early infection control and delays healing. We have demonstrated that topical CCL3 treatment restores neutrophil influx, reduces bacterial infection by ~99%, and accelerates wound healing in diabetic mice. As per Food and Drug Administration (FDA) Guidelines for Investigational New Drug (IND), we conducted a 14-day acute toxicity study in diabetic mice following a single topical administration of CCL3 at effective low dose (1 µg) and high dose (10 µg) per wound. Mice were monitored for clinical signs, body weight, and food intake throughout the study period. On day 14, serum biochemistry (ALT, AST, BUN, creatinine, metabolic markers) and histopathology of major organs (liver, kidney, heart, lungs, spleen) were assessed. CCL3-treated diabetic mice exhibited no adverse clinical effects. Hematological and biochemical parameters remained within normal limits, and histopathological analyses revealed no additional organ injury in CCL3-treated groups compared to diabetic control mice. Intriguingly, CCL3-treated mice showed improved ALT levels and reduced hepatic pathology, suggesting hepatoprotective effects and reduced serum IgG, indicating reduced systemic inflammation. Overall, our study demonstrates that diabetic mice tolerate topical CCL3 at doses up to 10 times the effective therapeutic concentration without evidence of systemic organ toxicity. These findings provide strong preclinical support for the translational development of CCL3 as a novel therapy for diabetic wound care. Full article

Recombinant baculovirus vectors are recognized as effective gene delivery systems for mammalian cells in vitro. However, their application in vivo has been limited due to inactivation by the host’s complement system. We developed a recombinant baculoviral vector derived from Autographa californica multiple nucleopolyhedrovirus (AcMNPV), incorporating both CMV-IE and polyhedron promoter-driven green fluorescence protein (EGFP) (vAcMBac-CMV-IE-EGFP). We then evaluated the transduction efficiency and safety of vAcMBac-CMV-IE-EGFP at a high multiplicity of infection (MOI) across five distinct cell lines and in Sprague Dawley (SD) rats. In vitro, Sf9, HepG2, and Vero E6 cells showed high transduction rates (95.52 ± 4.86%, 80.53 ± 3.31%, and 80.87 ± 2.50%, respectively), significantly outperforming the other cell types tested, and cell viability remained largely unaffected even at an MOI of 1000. In vivo, EGFP expression was observed in the heart, liver, spleen, lungs, and kidneys of SD rats after tail vein injection. Direct injection of vAcMBac-CMV-IE-EGFP into the rat striatum also resulted in strong EGFP signals in neural tissues. These results demonstrate that a high-MOI baculovirus infection can serve as a remarkably efficient and versatile platform for gene delivery across diverse mammalian cell types as well as in various organs and neural tissues in animal models. This robust method might hold significant promise for future gene therapy applications. Full article

In vertebrates, the interleukin-1β molecule (IL-1β) is among the most important proinflammatory cytokines and plays crucial roles in shaping injury progression, immunological challenges, and local and systemic responses to infection. In the current study, a cDNA encoding the IL-1β gene in Asian seabass (Lates calcarifer) (LcIL-1β) was identified at both the nucleotide and protein levels. Its immune responses were investigated in various tissues from diseased and normal fish. Recombinant rLcIL-1β was produced in Escherichia coli. Furthermore, its ability to control two fish pathogenic bacteria, Flavobacterium covae and Streptococcus iniae, was assessed in vitro. Transcriptional expression was quantified by qRT–PCR, which revealed the highest levels in whole blood, followed by the liver, gills and midgut. Immune response analyses of the head kidney, whole blood, liver, gills, spleen and intestines of fish infected with F. covae and S. iniae at concentrations of 1 × 10³, 1 × 10⁴ and 1 × 10⁵ CFU/fish, respectively, revealed significant upregulation of LcIL-1β (p < 0.05) for 6–24 h (h) after induction. Interestingly, compared with the control treatment, the application of 1, 10 and 100 µg of rLcIL-1β greatly increased the phagocytic activity and phagocytic index of phagocytes (p < 0.05). Antibacterial function analyses of F. covae and S. iniae revealed minimal inhibitory concentrations (MICs) of 29.17 and 85.25 μg/mL, respectively. Finally, injection of S. iniae following rLcIL-1β revealed that 50 and 100 µg of the target protein demonstrated significant functional activity in safeguarding Asian seabass from these pathogenic bacteria (p < 0.05). This information revealed that LcIL-1β in Asian seabass significantly drives immune defense mechanisms against pathogenic bacteria, which is important for the development of effective disease prevention methods for Asian seabass aquaculture. Full article

Background/Objectives: Chronic bone infections require local antimicrobial delivery to achieve high drug concentrations while limiting systemic toxicity. Silver ion-doped calcium phosphate synthetic bone grafts have been proposed as carriers for local antimicrobial release. This study aimed to evaluate the efficacy and safety of a silver ion-doped synthetic bone graft in patients with chronic osteomyelitis, infected nonunion, or implant-related bone infection. Methods: This retrospective cohort included 12 adults who underwent surgery for chronic osteomyelitis or implant-associated infection. All patients received thorough debridement, removal of infected implants when present, and filling of bone defects with a silver ion-doped calcium phosphate graft. The median age was 38 years, and follow-up was 12 months. Clinical and radiographic outcomes, liver and kidney function tests, and blood silver levels were assessed pre- and postoperatively. Results: Infection eradication was achieved in 11 of 12 patients (90%) at 12 months. Functional recovery, defined as return to normal daily activities, occurred within 3–5 months. Bone union was observed in all but one patient within 3–6 months, and no graft resorption was detected at one year. No significant differences in liver or kidney function tests were found compared with the control group (p > 0.05), and blood silver levels remained within normal limits. Conclusions: At 12-month follow-up, silver ion-doped synthetic bone grafts showed encouraging safety and efficacy in the treatment of chronic osteomyelitis. These findings suggest that silver-doped grafts may represent a useful option for one-stage treatment of osteomyelitis. Full article

The infectious diseases have become more frequent with the production of farmed Chinese soft-shelled turtles (Pelodiscus sinensis) increasing. In this study, bacterial strain was isolated, identified, and characterized from the liver of diseased Chinese soft-shelled turtles exhibiting body surface hemorrhages, claws and tail tips necrosis, and bleeding spots in visceral tissues. Based on the analysis results of morphology, biochemistry, and 16S ribosomal RNA (16S rRNA) sequencing, one bacterium Providencia rettgeri (P. rettgeri) was identified. The histopathological examination results revealed varying degrees of tissue damage in the spleen, liver, kidneys, and intestines of individuals with P. rettgeri. Challenge experiments results confirmed that the P. rettgeri caused morbidity and mortality in healthy Chinese soft-shelled turtles, reproducing similar clinical symptoms of naturally infected individuals. And, its mortality rate was up to 91% in the highest concentration group. Screening of eight virulence-associated genes results revealed that this P. rettgeri strain carried virulence factors including invasion protein gene, alpha-hemolysin, and others which were considered to contribute to pathogenicity. Antibiotic susceptibility testing showed that the bacterium was sensitive to amikacin and ciprofloxacin, which may be effective therapeutic options. In conclusion, this bacterium P. rettgeri was the pathogen that caused this disease in Pelodiscus sinensis. These results provide valuable research basis for the disease prevention and control of Pelodiscus sinensis farming. Full article

At the beginning of the COVID-19 pandemic, SARS-CoV-2-positive donors were not considered eligible for organ donation. The Italian National Transplant Centre has gradually introduced measures to prevent donor-to-recipient transmission of SARS-CoV-2 infection through organ transplantation. The current national screening protocol for deceased SARS-CoV-2-positive donors recommends molecular testing of donor lower respiratory tract (LRT) samples, graft biopsies and organ perfusion fluids. The aim of the study is to describe the 3-year experience of protocol application in a northern region of Italy. From 1 January 2022 to 31 January 2025, a total of 132 samples were analyzed (29 liver biopsies, 35 kidney biopsies, 68 perfusion fluids) from 40 organ donors with an active or resolved SARS-CoV-2 infection. SARS-CoV-2 PCR on LRT samples was positive in 26/40 (65%) donors, negative in 11/40 (27.5%) cases and in the remaining 3 (7.5%) the PCR result was unknown. Overall, 65 organs were transplanted into 60 recipients. All processed graft biopsies and organ perfusion fluid samples tested negative for SARS-CoV-2 RNA. Our data suggest that the utilization of non-lung donors with resolved or active SARS-CoV-2 infections who died of other causes appears justified and safe. Full article

Nocardia seriolae infection poses a serious threat to largemouth bass (Micropterus salmoides) aquaculture, owing to the lack of effective control strategies. This study investigated the antibacterial effects and underlying mechanisms of Macleaya cordata alkaloids—sanguinarine (SE) and chelerythrine (CHE)—against N. seriolae through integrated physiological and transcriptomic approaches. Results showed SE and CHE exhibited strong in vitro antibacterial activity, with minimum inhibitory concentrations (MICs) of 62.5 and 7.8 μg/mL, respectively. In vivo trials revealed that dietary supplementation with either alkaloid significantly enhanced the survival of infected fish, yielding relative percent survival (RPS) values of 34.5% for SE and 40.0% for CHE. Concurrently, both treatments reduced bacterial load and alleviated granulomatous pathology in multiple organs, including the liver, spleen, and kidney. Physiological analyses revealed severe damage to the cell envelope, as evidenced by increased membrane permeability and structural disintegration observed under transmission electron microscopy (TEM). Transcriptomic profiling identified 3708 and 5095 differentially expressed genes (DEGs) in the SE- and CHE-treated groups, respectively, with notable downregulation of key genes involved in peptidoglycan biosynthesis, the citrate cycle, oxidative phosphorylation, and the pentose phosphate pathways. These findings demonstrate that SE and CHE inhibit N. seriolae through a multi-target mechanism simultaneously disrupting cell envelope integrity and energy production, laying the groundwork for their development as eco-friendly aquaculture therapeutics. Full article

More than 3 million children are infected with hepatitis C virus (HCV) worldwide. Therapies with direct-acting antivirals (DAAs) are characterized by high efficiency and acceptable tolerability. Rare cases of autoimmune hepatitis (AIH) following HCV elimination have been reported in adults. Here, we present the first pediatric case of AIH after successful treatment with DAAs. A girl, born in 2012, was diagnosed with vertical HCV infection in 2013. In 2023, she was treated with the DAA glecaprevir/pibrentasvir. HCV RNA was undetectable after 4 weeks of treatment and at the end of treatment (EOT). However, at the EOT, the aminotransferase concentration elevated with further increase, despite a confirmed sustained viral response (SVR) 12 weeks after the EOT. Gamma-globulins were elevated, with positive anti-nuclear antibodies (ANA) and anti-liver kidney microsome (LKM) antibodies. Other causes were excluded. Elastography revealed no fibrosis. Aminotransferase levels decreased but did not normalize. A liver biopsy was performed, confirming a diagnosis of AIH. Immunosuppressive therapy with prednisone and azathioprine resulted in normalization of aminotransferase levels, and the titers of both ANA and LKM antibodies decreased. Monitoring aminotransferase levels should not be omitted in patients after successful DAA treatment of HCV infection. Full article

Vibrio harveyi (Vh) and Vibrio vulnificus (Vv) are major bacterial pathogens affecting farmed eels, but their comparative virulence mechanisms remain poorly characterized. This study combined histopathology and transcriptomic profiling to investigate organ-specific damage and host responses in American eels (Anguilla rostrata, 20 g per fish, for a total of 60 fish) following experimental infection with LD₅₀ doses of Vh (strain HA_1, 7.5 × 10⁴ CFU/fish) and Vv (strain FJ_4, 5.0 × 10⁵ CFU/fish). Tissue samples from liver, kidney, and spleen were collected at 0, 36, and 60 h post-infection (hpi). Histopathological analysis revealed distinct injury patterns: Vh induced severe hepatic edema and necrosis, whereas Vv caused vacuolar degeneration and vascular congestion in the liver. In the kidney, Vv triggered acute necrosis and vacuolization by 36 hpi, while Vh-induced renal damage was delayed until 60 hpi. Transcriptomic analysis of spleen tissue identified 4779 and 1215 differentially expressed genes (DEGs) in the Vh_36 vs. Vv_36 and Vh_60 vs. Vv_60 comparisons, respectively. Functional enrichment analysis associated these DEGs with 109 Gene Ontology (GO) terms—mainly catalytic activity, biological regulation, and binding—and 51 KEGG pathways, including “tuberculosis” and “pathways in cancer”. Differential alternative splicing (DAS) analysis further uncovered 1579 and 1214 DAS events originating from 12,482 and 12,316 splicing genes in the two comparisons. These were enriched in GO categories such as “binding”, “cellular process”, and “cell part”, as well as KEGG pathways related to “signal transduction”, “infectious diseases”, and “immune system.” Protein–protein interaction network analysis identified 119 cross-DAS-encoded proteins, including 8 that were predicted as key regulators of virulence differences. In summary, this work presents the first integrative study comparing the pathogenicity and host transcriptional dynamics of Vh and Vv in American eels, providing new molecular insights into their distinct virulence strategies. Full article

Avian haemosporidians are globally distributed protozoan parasites transmitted by hematophagous vectors, yet information on their occurrence in the Stone-curlew (Burhinus oedicnemus), particularly from the Canary Islands, is scarce. Between 2020 and 2024, 47 Stone-curlews were examined for Haemoproteus, Plasmodium, and Leucocytozoon spp. using nested PCR targeting the cytochrome b gene, followed by sequencing and phylogenetic analysis. Histopathological examination was performed on formalin-fixed tissues. Leucocytozoon sp. DNA was detected in one individual (case FS415/23), with identical sequences amplified from multiple organs. Phylogenetic analysis placed this isolate within lineage CIAE02, previously reported in raptors and other avian taxa. Microscopic evaluation revealed megalomeronts in the liver, kidney, and skin, consistent with Leucocytozoon infection. Despite concurrent infection with Avipoxvirus and Aspergillus fumigatus, no prominent inflammatory reaction surrounded the haemosporidian tissue states. The only prior haemosporidian reported in Burhinus is Haemoproteus burhinus, described from B. oedicnemus saharae in Iraq, and no Leucocytozoon infections have previously been recorded in this genus. Therefore, this represents the first evidence of Leucocytozoon infection in the Stone-curlew, extending the known host range of lineage CIAE02. These findings highlight the relevance of integrative diagnostic approaches for detecting latent or cryptic haemosporidian infections in non-passerine avian hosts. Full article

Liver cirrhosis is marked by sodium and water retention, portal hypertension and sharply reduced survival after decompensation. Sodium–glucose cotransporter-2 inhibitors (SGLT2i) induce insulin-independent glycosuria and natriuresis and have proven cardio-renal benefits, prompting interest in their role as adjuncts for ascites. This review synthesizes current evidence on efficacy, safety and mechanistic plausibility of SGLT2i in cirrhosis. Observational cohorts and case series suggest that adding SGLT2i to standard diuretics increases natriuresis, lowers ascites burden and paracentesis requirements, improves weight and aminotransferases and may reduce hepatic decompensation and hepatocellular carcinoma risk. Safety remains paramount: hypotension, acute kidney injury and hepatorenal syndrome-related acute kidney injury, genitourinary infections, electrolyte disturbances and rare euglycemic ketoacidosis necessitate careful patient selection, slow titration and close monitoring, especially in decompensated disease and when combined with loop diuretics or mineralocorticoid receptor antagonists. Overall, the balance of data supports cautious optimism: SGLT2i represent a promising adjunct within protocolized care pathways for selected patients, while definitive trials powered for hepatic outcomes are still required to clarify indications, timing, dosing and long-term impact. Full article

Background/Objectives: Chronic hepatitis C virus (HCV) infection remains a significant comorbidity in patients with end-stage renal disease (ESRD), complicating outcomes after kidney transplantation. The anti-viral treatment of HCV infection including Direct-acting antivirals (DAAs) have transformed HCV treatment, but evidence remains limited. Methods: We conducted a retrospective, real-world cohort study using the TriNetX Analytics Network. Patients were divided into two cohorts: those who received anti-viral treatment of HCV infections before transplant (n = 982) and those who did not (n = 982), following 1:1 propensity score matching. Results: Outcomes assessed one year post-index included mortality, hepatic complications, graft failure, and serum creatinine >6 mg/dL. Anti-HCV infection treated patients had significantly lower risks of graft failure (aHR: 0.656; 95% CI: 0.434, 0.993; p < 0.001) and severe renal dysfunction (aHR: 0.619; 95% CI: 0. 0.390, 0.984; p < 0.001) compared to untreated patients. While mortality (aHR: 0.901; 95% CI: 0.728, 1.114) and liver-related outcomes trended favorably in the treated group, they did not reach statistical significance. Conclusions: Our findings demonstrate that pre-transplant anti-viral treatment of HCV infection in HCV-infected kidney transplant recipients is associated with improved graft survival and renal function. Full article

Hepatorenal syndrome (HRS) is a high-mortality, potentially reversible form of kidney failure that arises from a tight hemodynamic–inflammatory coupling in cirrhosis. Contemporary redefinitions prioritize creatinine kinetics over static thresholds and recognize non-acute kidney injury (AKI) functional phenotypes, enabling earlier recognition but heightening the need for precise etiologic triage. This narrative synthesis integrates current concepts across pathophysiology, diagnosis and management. Portal hypertension, bacterial translocation and inflammatory mediators amplify splanchnic vasodilation and effective arterial underfilling. Compensatory neurohumoral activation precipitates renal vasoconstriction, intrarenal microcirculatory dysfunction and sodium–water retention. The pivotal diagnostic fork remains HRS–AKI versus acute tubular necrosis. A pragmatic, tiered strategy, structured volume assessment, filtration markers and a parsimonious tubular-injury panel offer actionable discrimination, whereas fractional excretion indices serve as adjuncts only. Initial therapy should be bundled and time-sensitive: remove nephrotoxins, treat infection and initiate albumin plus a vasoconstrictor. The transplant strategy should default to isolated liver transplantation unless end-stage renal disease is established. Future priorities include validated biomarker cut-offs, ultrasound-guided volume algorithms and pathway-based trials to reduce diagnostic delay and improve survival. Full article