Search Results (1,747)

Porcine rotavirus (PoRV), a major enteric pathogen, causes severe diarrhea, dehydration, high morbidity, and mortality, leading to significant economic losses in the porcine industry. In this study, we established a porcine small intestinal organoid culture system and developed an in vitro model for PoRV infection. Jejunal crypts were isolated from neonatal piglets and subsequently cultured to generate porcine small intestinal organoids in both three-dimensional (3D) and two-dimensional (2D) organoid formats, properties of which were verified via morphological assessment and immunostaining for Lgr5, villin, Ki-67, and lysozyme. Furthermore, a PoRV infection model was established in both 3D and 2D organoid cultures, and growth kinetics demonstrated efficient PoRV replication. PoRV infection also significantly increased the expression of inflammatory cytokines, including IL-6 and IFN-α. Collectively, these results demonstrate that the established porcine small intestinal organoid models support efficient PoRV replication and provide a physiologically relevant platform for studying PoRV pathogenesis and evaluating potential antiviral strategies. Full article

Acute pancreatitis is a common and heterogeneous inflammatory disorder whose clinical course ranges from a self-limited illness to persistent organ failure, infected pancreatic necrosis, and prolonged critical illness. Contemporary management has moved away from protocolised aggressive fluid loading, prolonged fasting, prophylactic antibiotics, and early open necrosectomy. Instead, current care emphasises repeated physiological assessment, moderate goal-directed resuscitation, early enteral or oral nutrition, organ-specific support, antimicrobial stewardship, and delayed minimally invasive intervention within a multidisciplinary step-up strategy. This narrative review examines acute pancreatitis from an intensive care perspective. Particular attention is given to early risk stratification, intensive care unit triage, haemodynamic and respiratory support, acute kidney injury, intra-abdominal hypertension, nutrition, biliary source control, diagnosis and treatment of infected necrosis, and the timing and selection of endoscopic, radiological, and surgical interventions. The implications of obesity, pregnancy, advanced age, and multimorbidity are also discussed. Recent randomised trials have clarified several clinically important questions: aggressive hydration increases fluid overload without improving outcomes; routine urgent endoscopic retrograde cholangiopancreatography is not beneficial in predicted severe biliary pancreatitis without cholangitis; postponed drainage may avoid invasive intervention in a substantial proportion of patients with infected necrosis; and endoscopic or minimally invasive approaches reduce treatment burden compared with primary open surgery. Persistent organ failure remains the principal determinant of mortality, while infected necrosis further increases risk and complexity. Future progress will depend on dynamic prediction models, biomarker-guided antimicrobial decisions, personalised haemodynamic strategies, phenotype-directed immunomodulation, and regionalised multidisciplinary care. Full article

Chronic kidney disease (CKD) is sustained by a network of sterile inflammation, oxidative and metabolic stress, uremic toxin retention, gut barrier dysfunction, and maladaptive immune activation. These processes contribute to kidney fibrosis, cardiovascular injury, wasting, and excess mortality, but inflammatory biomarkers do not by themselves establish therapeutic causality. This narrative review integrates mechanistic and therapeutic evidence using an explicit three-layer translational hierarchy. Renin–angiotensin system inhibitors, sodium–glucose cotransporter-2 inhibitors, finerenone, and glucagon-like peptide-1 receptor agonists improve cardiorenal outcomes and have plausible anti-inflammatory actions, although inflammatory mediation remains unproven. Interleukin-1 blockade provides cardiovascular proof of principle and small dialysis feasibility data. Interleukin-6 ligand inhibition produces marked human target engagement; however, headline results from the completed phase 3 ZEUS trial showed no reduction in three-point major adverse cardiovascular events with ziltivekimab despite biomarker suppression, while serious infections were more frequent. POSIBIL6ESKD continues to test clazakizumab in inflamed dialysis patients. Direct NLRP3 inhibition has entered early human CKD development, whereas senescence-directed and microbiota-based approaches remain less mature. Future progress requires inflammatory endotyping, repeated biomarker assessment, mechanistically aligned outcomes, and rigorous infection surveillance. ZEUS underscores that pathway suppression must deliver clinical benefit beyond contemporary standard therapy. Full article

Chronic hepatitis B virus (CHB) infection remains a major cause of hepatocellular carcinoma (HCC), yet the premalignant microenvironment that links to HBV-associated HCC (HBV-HCC) is still poorly defined. This review synthesizes evidence that HBV-infected hepatocytes function as signaling hubs that, through microRNA (miRNA)-regulated crosstalk with Kupffer cells, liver sinusoidal endothelial cells, hepatic stellate cells and cancer-associated fibroblasts (CAFs), progressively remodel the liver from an antiviral tissue into a premalignant and early tumor microenvironment. Across the HBV-HCC continuum, a core set of dysregulated miRNAs, including miR-21, miR-29a/b, miR-122, miR-146a, miR-155, miR-200a, miR-126, miR-210 and the miR-130/301 family, coordinates transition from innate antiviral responses to HSC activation, extracellular matrix deposition, mechanotransduction, angiogenesis, chronic inflammation and cancer-associated CAF programing. By mapping these stage-specific miRNA networks onto acute infection, CHB, early fibrogenesis, advanced fibrosis and CAF-rich dysplastic states, the review reframes HBV-HCC pathogenesis as a sequence of miRNA-guided hepatocyte–stromal states rather than a purely hepatocyte-intrinsic process. This perspective suggests that composite, cell-type-resolved miRNA signatures in serum or liver tissue could serve as biomarkers for identifying CHB patients who are entering a premalignant microenvironment before conventional surveillance markers become abnormal. It further highlights miRNA hubs that couple antiviral, fibrogenic, angiogenic and CAF-associated signaling as potential therapeutic targets for reprograming the HBV-driven premalignant microenvironment, with the long-term goal of intercepting HBV-HCC development at earlier, microenvironmentally defined stages. Full article

Severe anaemia remains a major public health challenge, disproportionately affecting children and women of reproductive age in sub-Saharan Africa. In high-burden settings, the aetiology of severe anaemia is multifactorial, encompassing nutritional deficiencies, infections, and host genetic factors. Beyond its direct clinical consequences, severe anaemia is also associated with increased susceptibility to invasive bacterial infections, particularly those caused by enteric pathogens such as non-typhoidal Salmonella and Escherichia coli. In this review, we present an integrated framework linking severe anaemia and invasive bacterial infection through three interconnected biological pathways, collectively termed the gut–iron–immune axis: gut microbial dysbiosis and impaired intestinal barrier integrity; disrupted iron homeostasis; and impaired immune function. We examine context-specific modifiers in endemic settings, including iron deficiency, malnutrition, malaria, sickle cell disease, and environmental enteric dysfunction. We also discuss how management of severe anaemia, including blood transfusion and iron supplementation, reshapes the gut microbiome, with direct implications for microbial translocation, invasive bacterial infection, and clinical outcomes. Finally, we identify key knowledge gaps and research priorities to guide safer and more effective prevention and management of severe anaemia in high-burden settings. Full article

Background: Late-onset neutropenia (LON) and hypogammaglobulinemia are recognized sequelae of rituximab therapy in B-cell non-Hodgkin lymphoma, and both may leave patients vulnerable to infection once treatment has ended. Methods: Fifty-three patients with newly diagnosed, unfavorable diffuse large B-cell lymphoma (DLBCL) who entered remission on dose-adjusted (DA) R-EPOCH immunochemotherapy were retrospectively evaluated. Neutropenia (absolute neutrophil count < 1.5 × 10⁹/L, CTCAE-graded), hypogammaglobulinemia and infections were registered at treatment completion and 6 and 12 months later. Results: All laboratory parameters changed significantly over time. Most reached their nadir at the end of treatment, whereas the absolute neutrophil count alone reached its lowest value later, at 6 months. Neutropenia, largely mild to moderate, affected 17.6% of patients at treatment completion, 22.4% at 6 months and 7.9% at 12 months. Neutropenia at 6 months was a new event, with no overlap with end-of-treatment neutropenia, and was mostly transient. Hypogammaglobulinemia (IgG < 5 g/L) occurred in 33.3%, 16.7% and 20.0%, respectively; median IgG declined to a nadir at the end of treatment and recovered thereafter, although the deficit tended to persist in the same patients. Post-treatment infections were recorded in 73.6% of patients (mostly respiratory); neutropenia was not associated with infection at any time point, whereas end-of-treatment hypogammaglobulinemia was associated with respiratory infection (p = 0.040). The independent predictors of 6-month neutropenia were a greater number of dose-escalated cycles, lower baseline leukocyte count and the absence of on-treatment infection, whereas 6-month hypogammaglobulinemia was predicted by autologous transplantation and the absence of B symptoms. In exploratory body composition analyses, lower baseline psoas muscle mass was associated with end-of-treatment neutropenia (p = 0.042) and greater muscle loss with other site (skin and gastrointestinal) infection (p = 0.004). Conclusions: After DA-R-EPOCH, LON is a delayed and largely transient event separate from end-of-treatment neutropenia, whereas hypogammaglobulinemia is more persistent and clinically relevant for respiratory infections. Full article

Among the many concerns surrounding global health, antimicrobial resistance (AMR) is widely recognized as a major threat, especially critical within livestock production, where restrictions on antibiotic use demand effective preventive alternatives. The documented health benefits and structural stability have positioned yeast-derived postbiotics as an attractive alternative, but research has largely focused on Saccharomyces cerevisiae, leaving non-Saccharomyces yeast species underexplored. To this end, in this study nine non-conventional yeast strains were selected and subjected to different thermal and chemical inactivation methods to determine the most suitable conditions for postbiotic obtention. Based on their physicochemical characterization and scalability potential, heat-treated postbiotics were selected for subsequent in vitro evaluation. Immunomodulatory assays demonstrated that heat-inactivated postbiotics from the different yeast strains were internalized by macrophages and induced dose-and-species-dependent expression of maturation markers CD40 and CD86, as well as TNF-α production, eliciting a proinflammatory response in vitro. Moreover, among all the species evaluated in this work, Rhodotorula mucilaginosa and Wickerhamomyces anomalus stood out for their ability to significantly reduce the adhesion of the enteropathogen enterotoxigenic Escherichia coli (ETEC) to intestinal cells in vitro. These results highlight the species-dependent immunomodulatory and anti-infective properties of selected yeast-derived postbiotics. Full article

Sexually transmitted infections (STIs) are common and probably underreported causes of proctitis and colitis. Bacterial (chlamydia, gonorrhoea, syphilis, Mycoplasma genitalium), viral (herpes simplex virus, mpox), and amoebic (Entamoeba histolytica) pathogens can cause inflammatory proctitis or colitis, which, depending on the pathogen, can mimic inflammatory bowel disease both on endoscopy and histopathology. Rectal and colonic masses are uncommon, but important manifestations of these infections, especially with chlamydia, syphilis, and E. histolytica. Testing for HIV is important in this context, since it allows for the inclusion of opportunistic pathogens into the differential diagnosis. Chronic diarrhoea can be a feature of chronic HIV infection. Enteric pathogens, such as Salmonella spp., Shigella spp., or Campylobacter spp., can be transmitted during sex, especially during oral–anal contact (“rimming”). The most common STI, human papillomavirus, is not associated with colitis, but is important because of its causal association with genital warts and anal cancer. Full article

Maraviroc (MVC), a CCR5 antagonist, has been proposed as a potential antiviral agent against SARS-CoV-2; however, its mechanism of action across viral variants remains unclear. Here, we evaluated the antiviral activity of MVC against SARS-CoV-2 wild-type (WT) and Omicron BA.1 variants using single-round infectious particles (SRIPs), virus-like particles (VLPs), and cell-based assays, with a focus on its impact on viral entry and Mpro function. MVC potently inhibited infection of both WT and BA.1 SRIPs in Vero E6 cells, exhibiting EC₅₀ values of 0.0065 μM and 0.016 μM, respectively. Time-of-addition assays revealed that MVC primarily targets the early phase of infection, with the strongest inhibition observed at the viral entry stage, while moderate effects were detected during attachment and post-entry stages. Fluorescence-labeled VLP imaging demonstrated distinct entry pathways, with WT predominantly entering via plasma membrane fusion and BA.1 via endocytosis, independent of cell type. MVC altered WT-VLP trafficking by promoting internalization and lysosomal localization, whereas it had minimal impact on BA.1 internalization. In spike-mediated cell–cell fusion assays, MVC preferentially inhibited WT spike-driven syncytium formation but showed limited effects on BA.1 or BA.4 fusion, while more effectively reducing Omicron spike-mediated binding. At the post-entry stage, MVC inhibited SARS-CoV-2 main protease (Mpro) activity, with BA.1 Mpro (P132H) exhibiting greater sensitivity (IC₅₀ = 0.496 µM) than WT (1.869 µM). Collectively, these findings demonstrate that MVC exerts variant-dependent antiviral effects by targeting viral entry, modulating trafficking pathways, and inhibiting Mpro activity. This study highlights MVC as a multi-stage inhibitor with differential efficacy against SARS-CoV-2 variants, providing insights into its potential therapeutic application. Full article

Background and Objectives: Laboratory parameters associated with nutritional and metabolic status may be substantially influenced by inflammatory activity, complicating their interpretation in patients with advanced neurological diseases. This study aimed to characterize within-patient changes in inflammatory biomarkers and laboratory parameters related to nutritional and metabolic status in multimorbid patients receiving long-term enteral nutrition, with particular emphasis on differences between infectious and clinically non-infectious periods. A secondary objective was to propose a conceptual framework for interpreting these laboratory parameters in the context of inflammatory activity. Materials and Methods: A prospective longitudinal observational case series was conducted in an inpatient palliative care facility. Of 23 patients who entered prospective follow-up, five completed the predefined nine-month observation period and were included in the final longitudinal analysis. Twenty-three predefined assessment time points were evaluated for each participant. Inflammatory parameters, serum proteins, micronutrient-related measurements, and vitamin concentrations were analyzed descriptively in relation to the clinical course of each patient. Results: Patients with recurrent infectious episodes demonstrated pronounced increases in inflammatory biomarkers accompanied by decreases in serum proteins, particularly albumin, transferrin, and total protein, as well as changes in serum iron (Fe) and zinc (Zn). The greatest fluctuations were observed in patients with the highest inflammatory burden, whereas patients without recurrent infections showed comparatively stable laboratory profiles. Vitamin A, vitamin D, and folate concentrations showed relatively limited fluctuations. Importantly, all five patients received continued enteral nutritional support, with daily energy intake ranging from 1450 to 1800 kcal, and body weight increased by 1.0–3.0 kg during follow-up. Based on these case-based observations and current evidence, a conceptual framework for interpreting laboratory parameters in the context of inflammatory activity was proposed. Conclusions: In patients with advanced neurological diseases, laboratory parameters associated with nutritional and metabolic status should be interpreted in the context of inflammatory activity and should not be used independently to determine nutritional status. The proposed conceptual framework is intended as an interpretative aid for laboratory findings rather than as an alternative diagnostic system for malnutrition and requires validation in larger prospective studies. Full article

Background: Salmonellosis is a major global public health concern, commonly caused by serovars such as Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Enteritidis. Rare serovars, however, may represent underrecognized links between environmental reservoirs and human infection. Salmonella enterica serovar Haifa is a sporadic serotype primarily associated with livestock and environmental sources and has previously been reported in Indian poultry but not in human clinical cases to date. Case Presentation: A 70-year-old male with a history of type 2 diabetes, presented with acute watery diarrhea and dehydration. One week prior to symptom onset, the patient reported direct contact with cattle and poultry in a rural setting. Laboratory investigations revealed leucopenia and elevated procalcitonin (3.73 ng/mL). Stool culture yielded non-lactose fermenting colonies on MacConkey agar and H₂S-producing colonies on Hektoen enteric agar. The isolate was identified via VITEK 2 and confirmed as Salmonella enterica serovar Haifa by the National Institute for Research in Bacterial Infections (NIRBI). Antimicrobial susceptibility testing (AST) revealed that the isolate showed resistance to ampicillin, ceftriaxone, and ciprofloxacin. The patient was successfully treated with a three-day course of intravenous Azithromycin (1 g) and achieved rapid clinical recovery. Conclusions: To the best of our knowledge, this case represents the first reported human infection caused by S. Haifa in India. The finding highlights the potential zoonotic risk of rare non-typhoidal Salmonella serovars and emphasizes the importance of surveillance, routine serotyping, and antimicrobial resistance monitoring within a One Health framework. Full article

Increasing antimicrobial resistance and restrictions on antibiotic use in poultry have drawn attention to phytogenic products as a complementary approach for controlling enteric bacterial infections. The aim of this study was to evaluate the effects of a phytogenic product (Herba Top Salmonella, HTS) on selected cultivable intestinal bacterial populations, intestinal histomorphology and tissue distribution of Salmonella Typhimurium in experimentally infected broiler chickens. A total of sixty one-day-old Ross 308 broilers were randomly assigned to six experimental groups (10 birds/group; two pens/group, five birds/pen, with the pen considered the experimental unit. Birds in three groups were experimentally challenged with Salmonella enterica subsp. enterica serovar Typhimurium, and HTS was administered in drinking water for 14 consecutive days at two nominal concentrations (3 mL/L and 6 mL/L). Intestinal microbiological parameters, histomorphometric characteristics, and the presence of Salmonella Typhimurium in tissues by immunohistochemistry were evaluated. The effects of infection status, HTS concentration, and their interaction were analyzed using two-way ANOVA. HTS administration was associated with reduced counts of total aerobic bacteria, Escherichia coli and Enterobacteriaceae counts. In experimentally infected broilers, HTS treatment was also associated with reduced Salmonella Typhimurium in intestinal tissue and significant changes in intestinal histomorphometric parameters, including increased crypt depth and mitotic activity. The observed responses were influenced by both infection status and the HTS nominal concentration. Because of the limited number of independent experimental units and the absence of individual HTS intake measurements, these findings should be considered exploratory preliminary findings, and further studies with larger animal groups under commercial production conditions are required. Full article

The intricate interplay between the gut microbiome and the enteric nervous system remains a paramount focus in understanding the multifactorial pathogenesis of disorders of gut–brain interaction (DGBI), most notably irritable bowel syndrome (IBS). While the clinical entity of post-infectious IBS is well-established, the independent, long-term pathophysiological impact of iatrogenic antibiotic exposure is garnering critical attention within neurogastroenterology. This narrative review provides a comprehensive synthesis of current epidemiological and mechanistic evidence positioning antibiotic-induced microbial depletion as a potential predisposing factor for incident IBS. By evaluating recent literature, we highlight epidemiological trends demonstrating a consistent, dose-dependent relationship between cumulative antibiotic courses, particularly broad-spectrum agents, and an elevated risk of developing IBS, independent of prior acute enteric infections. Furthermore, we explore the mechanistic underpinnings of this association, focusing on how systemic antibiotics induce persistent, detrimental alterations in commensal diversity. This resulting dysbiosis initiates a proposed cascade of downstream consequences, including compromised epithelial barrier integrity, persistent low-grade mucosal inflammation, and altered bile acid metabolism. These localized disruptions serve as established triggers for visceral hypersensitivity and dysregulated gastrointestinal motility communicated via the gut–brain axis. Ultimately, this review underscores that antibiotic exposure may act as a significant, modifiable risk factor for IBS pathogenesis. Recognizing this substantial iatrogenic risk reinforces an urgent clinical imperative for stringent antimicrobial stewardship and emphasizes the necessity for future research directed toward prophylactic, microbiome-sparing strategies to mitigate the escalating global burden of DGBIs. Full article

Background: Donor human milk (DHM) is recommended when the mother’s own milk (MOM) is unavailable for extremely low birth weight (ELBW) infants. However, the impact of DHM implementation on NICUs with already high human milk utilization remains incompletely characterized. Objective: We aimed to evaluate the association between DHM implementation and feeding practices, feeding progression, parenteral nutrition (PN) exposure, and major neonatal morbidities in ELBW infants. Methods: We conducted a retrospective before–after cohort study in a single tertiary NICU including 116 ELBW infants with feeding data through day 28 (58 pre-DHM; 58 post-DHM). Exploratory multivariable models evaluated factors associated with NEC and PN duration. Results: In the post-DHM epoch, enteral feeding was initiated earlier (2 vs. 2.5 days, p < 0.001) and full enteral feeding was achieved sooner (14 vs. 24.5 days, p < 0.001). PN duration was numerically shorter (17.5 vs. 27 days, p = 0.088). Feeding shifted from predominantly exclusive MOM to mixed MOM + DHM regimens, eliminating formula-only feeding. NEC, feeding intolerance, bloodstream infection, and mortality did not differ between epochs. Feeding intolerance was associated with NEC, whereas lower gestational age predicted longer PN duration; epoch was not independently associated with either outcome. Conclusions: In this high-MOM NICU, DHM implementation was associated mainly with earlier feeding progression and reduced formula reliance, without a measurable reduction in NEC. Full article

Background/Objectives: Mpox (formerly monkeypox) is a re-emerging global health threat. While current vaccines are injectable, oral vaccination offers a painless alternative, though the harsh gastrointestinal (GI) environment challenges live viral vaccines. This study evaluated the stability of orthopoxviruses under simulated GI conditions to assess the physicochemical feasibility of oral mpox immunization. Methods: Attenuated and virulent strains of vaccinia, cowpox, and camelpox viruses were exposed to simulated gastric (pH 1.0–2.0 and 3.0–4.0 with pepsin) and intestinal (pH 7.0–7.5) conditions at 37 °C for 180 min. Viral titers were determined via cell culture assays. The physicochemical protective efficacy of enteric-coated capsules was evaluated using standard dissolution testing parameters. Results: All orthopoxviruses were rapidly inactivated under highly acidic fasting conditions (pH 1.0–2.0). However, they exhibited high stability at pH 3.0–4.0 and 7.0–7.5, retaining approximately 20–30% of their initial infectivity after 180 min. Enteric-coated capsules successfully maintained shell integrity in simulated gastric fluids for over 3 h and dissolved completely under intestinal conditions within ~130 min, aligning with small intestine transit times. Conclusions: Orthopoxviruses possess sufficient intestinal stability to support the physicochemical feasibility of oral immunization, provided they are protected from gastric acidity. Enteric-coated capsules represent a highly suitable delivery system for the intestinal release of live orthopoxvirus-based candidates, warranting further in vivo preclinical evaluation. Full article