Search Results (1,584)

Background/Objectives: The use of intravenous immunoglobulins enriched with IgA and IgM (eIg) in patients with septic shock remains controversial due to a lack of robust, standardized criteria for patient selection and the timing of treatment. This study introduces the SORRISO Score, which is a novel, evidence-informed scoring system designed to guide clinical decision-making for the administration of eIg. Methods: Based on data from the Italian multicentric SORRISO registry, involving 248 patients across seven ICUs from 2015 to 2022, the score integrates patient-related and therapy-related variables. These were derived through an enhanced version of the TO-PIRO Score and include factors such as immunosuppressive status, infection type, timing of treatment, and adequacy of antibiotic therapy. Results: Statistical analyses, including Kaplan–Meier curves and regression models, identified the key predictors of survival and validated the score’s ability to stratify patients by outcome. A cutoff of 13.7 showed a significant prognostic value (AUC = 0.731), with lower scores correlating with increased mortality. Conclusions: The SORRISO Score thus offers a practical bedside tool for improving patient selection for eIg therapy, potentially optimizing outcomes in septic shock; however, it should be validated in a larger cohort of patients. Full article

Objectives: The aim of the present study was to better understand the antibody concentrations in healthcare workers (HCWs) from a hospital in Mexico City with a high density of COVID-19 patients. Methods: Up to 243 HCWs were recruited in 2020 and 2022 and were sorted into three groups: hybrid immunity (HI, natural infection plus vaccination), vaccine-induced immunity (VI), and unvaccinated but RT-qPCR negative at the beginning of the pandemic (UV). Peripheral blood and nasopharyngeal swab samples were obtained; additionally, saliva samples were obtained from the UV group. The titers of IgG, IgM, and IgA against the SARS-CoV-2 receptor-binding domain (RBD) and nucleocapsid (NCP) proteins were assessed using an in-house ELISA, and positivity to the virus was determined via RT-qPCR. Results: Most HI and VI participants were positive for serum anti-RBD IgG (92.8% and 100%, respectively), while 26.6% (for HI) and 19% (for VI) were positive for anti-NCP IgG. Regarding serum anti-RBD IgA, the VI and HI groups had positive rates of 87.3% and 66%, respectively. In contrast, the UV group showed a rate of 5.7% but the positivity for IgA in saliva was higher (52% for RBD and 35% for NCP). In addition, the highest antibody titers were obtained for anti-RBD IgG and IgA in the HI and VI groups, respectively. In saliva, the IgA antibody titer was higher for the RBD antigen (1:1280). Conclusions: These results strengthen our understanding of antibody concentrations in HCWs during two critical years of the pandemic in a general hospital with many COVID-19 patients. Full article

Identifying effective adjuvants to prevent and alleviate the adverse effects of chemotherapy remains a critical challenge in cancer therapy. This study investigated the protective effects of longan polysaccharide (LP) against cyclophosphamide-induced immunosuppression and oxidative stress in mice. Our findings revealed that LP administration significantly improved systemic immune function, as evidenced by marked increases in serum immunoglobulin levels (IgG2a: 1.82-fold, IgG2b: 1.46-fold, IgM: 1.26-fold, and IgG1: 1.22-fold) and key cytokines (IL-10: 1.53-fold, IL-12: 1.22-fold, and IFN-γ: 1.20-fold), accompanied by substantial reductions in pro-inflammatory mediators (TGF-β1: 28.72% decrease and IL-21: 36.28% decrease). Concurrently, LP restored oxidative balance by increasing SOD, GSH, and NO levels in multiple organs (liver, kidneys, and small intestine) and serum. Mechanistic studies using an in vitro Caco-2/RAW264.7 coculture system revealed that four purified LP fractions (LPIa-LPIVa) effectively suppressed NF-κB pathway activation through downregulation of TLR4 expression, reduction of the p-IκB-α/IκB-α ratio, and inhibition of nuclear NF-κB translocation. These molecular effects correlated with decreased production of inflammatory mediators (TNF-α, IL-6, IL-8, iNOS, and NO). Collectively, these findings provide compelling evidence that LP possesses dual immunomodulatory and antioxidant capabilities, highlighting its potential as a natural adjuvant for alleviating chemotherapy-induced side effects. Full article

Encephalitis is a potentially life-threatening condition with long-term neurological sequelae. However, data on early clinical, demographic, and diagnostic predictors of functional outcomes remain limited. We performed a retrospective monocentric study including 98 patients diagnosed with infectious encephalitis of various etiologies treated in the University Hospital Ulm between January 2014 and December 2024. Ordinal logistic regression models were applied to evaluate associations between admission characteristics and functional outcome at discharge, as measured by the modified Rankin Scale. Three multivariate models incorporating clinical, demographic, and MRI/EEG variables explained up to 53% of the variance in mRS at discharge (p < 0.001), outperforming models based solely on CSF parameters. Key predictors of poor functional outcome included ‘altered consciousness’ (OR 7.08, p < 0.001), higher ‘mRS at admission’ (OR 0.03–0.07 across categories, p < 0.001), ‘focal/generalized EEG slowing’ (OR 9.97, p < 0.001), ‘epileptiform EEG activity’ (OR 17.49, p < 0.001), ‘MRI: myelitis’ (OR 16.44, p = 0.004), and ‘intrathecal IgM synthesis’ (OR 8.93, p = 0.018). Conversely, ‘longer hospitalization’ (OR 0.13–0.17 for different intervals, p < 0.006) and ‘intrathecal IgG synthesis’ (OR 0.05, p = 0.03) were associated with more favorable outcomes. Despite the single-center and retrospective aspects of this study, our findings underscore a multifactorial pattern of outcome determinants in infectious encephalitis, highlighting the prognostic relevance of initial neurological status, electrophysiological abnormalities, and neuroimaging features. Full article

Background: Dengue infection is a spreading vector borne disease with most severe infection-related fatalities occurring in adults. This study was conducted to explore prognostic indicators of dengue infection severity. Methods: This study included patients aged over 15 years who were diagnosed with dengue viral infection. Data were collected from nine hospitals across all regions of Thailand between January 2019 and December 2022. Diagnosis of dengue infection was confirmed by a positive result for the NS-1 antigen via RT–PCR, IgM antibody, or IgG antibody tests. Data including gender, age, BMI, underlying disease, clinical characteristics and laboratory findings were collected. Multivariable logistic regression with backward elimination was used to identify a set of prognostic factors. Results: The prognostic indicators of severe dengue were age < 55 years (OR = 6.13, p = 0.054), severe bleeding (bleeding from the gastrointestinal tract, hematemesis, melena, menorrhagia, or hematuria) (OR = 20.75, p < 0.001), pleural effusion (OR = 10.23, p < 0.001), and platelet ≤ 100,000 (/µL) (OR = 3.62, p = 0.035). These predictors were able to accurately estimate the severity of dengue infection with an area under the receiver operating curve (AuROC) of 0.836. Conclusions: The proposed four prognostic factors can be applied to predict severe dengue infections. These findings may inform the development of a risk scoring system to forecast severe dengue infection, early detection, and appropriate treatment during sickness. Full article

This cross-sectional study evaluated the seroprevalence and clinical impact of West Nile virus (WNV) infection in horses from three ecologically high-risk counties in western Romania (Timiș, Arad, and Bihor) between 2023 and 2025. A total of 306 unvaccinated horses were tested using a commercial ELISA, with 8.17% testing positive for WNV antibodies, indicating prior exposure. Passive surveillance for clinical signs during mosquito seasons identified 16 horses with acute neurological symptoms, four of which were confirmed as clinical cases based on WNV-specific IgM positivity, suggesting probable silent WNV circulation in the region. The overall case fatality rate among confirmed clinical cases was 25.0%. WNV seropositivity was highest in Bihor (8.85%), followed by Arad (8.57%) and Timiș (7.32%). Statistical comparisons using χ² tests and binary logistic regression indicated no significant differences in seroprevalence between counties, sexes, or age groups, consistent with the overlapping 95% confidence intervals. These findings suggest the continued silent circulation of WNV in the region and support the integration of equine surveillance into the One Health framework as a potential tool for early detection and risk mitigation. However, in the absence of molecular confirmation (e.g., RT-PCR or virus isolation), these results should be interpreted as indicative of prior exposure rather than direct evidence of ongoing viral activity. Full article

Background/Objectives: The coronavirus disease 2019 (COVID-19) has more severe symptoms and increased mortality among men than women. To address the prognostic impact of vaccination, comorbidities, and inflammatory biomarkers on classified clinical outcomes in hospitalized COVID-19 patients, we compared common and sex differences. Methods: Besides laboratory and clinical parameters at hospital admission, we performed a common and sex-based comparative analysis for the clinical outcomes, RT-qPCR analyses, and measured severe acute respiratory syndrome coronavirus (SARS-CoV-2)-specific IgM and IgG antibody levels of 702 COVID-19 patients in a single centre from June 2020 to April 2022. Results: Pro-inflammatory biomarkers (C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, lactate dehydrogenase (LDH), D-dimer, ferritin), and liver enzymes (AST, ALT, GGT) were significantly more increased in COVID-19 male patients and generally elevated with the severity of clinical outcome, regardless of the SARS-CoV-2 variant. Cycle threshold (Ct) values of RT-qPCR testing were in negative correlation with IL-6 in COVID-19 male patients, indicating that higher viral load largely increased IL-6 levels in parallel with the severity of clinical outcome and regardless of vaccination. IgG levels were higher in early post-COVID-19 male patients. Comorbidities were more frequent in COVID-19 female patients and generally more common in the severe clinical outcomes. Vaccination was negatively correlated with the severity of clinical outcome, liver enzymes, LDH, and inflammatory parameters in hospitalized COVID-19 patients, while the risk of pneumonia was reduced. Vaccination reduced the need for corticosteroid and anti-inflammatory therapies, but increased the need for antiviral drug treatment. Conclusions: In addition to confirming inflammatory biomarkers and the importance of anti-inflammatory therapy in vaccinated patients, this study showed that vaccination reduces, but does not prevent, mortality in patients with COVID-19. Full article

Aeromonas hydrophila (A. hydrophila) is responsible for causing abdominal dropsy, swimming abnormalities, skin ulcerations, and pale gills in fish. Vaccination is an essential strategy for disease prevention in aquaculture. This study evaluated the efficacy of an oral vaccine against A. hydrophila in Ctenopharyngodon idella (C. idella). The vaccine was formulated as feed-based monovalent pellets, incorporating or spraying formalin-killed A. hydrophila on/into commercial feed with 30% crude protein. Mineral and fish oils were used as adjuvants at 10% of the feed. Prior to the trial, the experimental feed groups were subjected to quality and safety tests. Grass carp fingerlings (20 ± 5 g) were divided into seven groups (n = 20 per group): sprayed vaccinated feed with fish oil (SVFF), incorporated vaccinated feed with fish oil (IVFF), sprayed vaccinated feed with mineral oil (SVFM), incorporated vaccinated feed with mineral oil (IVFM), sprayed vaccinated feed (SVF), incorporated vaccinated feed (IVF), and a control group. Feed was provided at 3% of body weight for 60 days. Immunomodulation was investigated through lysozyme activity, antibody titers, and immunoglobulin M (IgM). The IVFF group showed significantly enhanced immunity and growth performance, with an 87% protection rate, 13% mortality, and the highest relative percentage survival (83%) following intraperitoneal A. hydrophila (6.8 × 10⁹ CFU/mL) challenge. Histological analysis indicated minimal pathological changes in the IVFF group compared to controls. Fish oil as an adjuvant enhanced immunity without adverse health effects. Overall, this study demonstrated that feed-based monovalent vaccines effectively improve immune responses and provide protection against A. hydrophila in C. idella. Full article

This study investigates the effect of walnut green husk extract (WE) on gut microbiota, metabolites, and immune-antioxidant changes in fattening pigs through gut microbiota-metabolite interactions. A total of 60 healthy fattening pigs (Duroc × Landrace × Yorkshire) with an initial body weight of 65.2 ± 3.1 kg were randomly assigned to two groups (n = 30 per group): the control group (NC), which was fed a basal diet, and the WE group, which was fed the basal diet supplemented with 0.1% walnut green husk extract (WE). Dietary supplementation with 0.1% WE significantly increased the relative abundances of beneficial bacteria (e.g., Firmicutes, Lactobacillus) and reduced pathogenic bacteria (e.g., Proteobacteria, Shigella). Untargeted metabolomics identified 170 differentially accumulated metabolites, among which propionic acid—a key short-chain fatty acid with immunomodulatory effects—was significantly upregulated by 1.09-fold (p = 0.03) and showed a positive correlation with beneficial microbial abundances. These metabolites were enriched in glycerophospholipid and α-linolenic acid metabolism pathways, where eicosadienoic acid inhibited the nuclear factor kappa-B (NF-κB) pathway for anti-inflammatory effects, and methyl cinnamate synergistically regulated mitogen-activated protein kinase (MAPK) signaling with Lactobacillus. Serum analyses showed that WE significantly enhanced IgA, IgM, and IgG levels by 3.97-fold, 4.67-fold, and 4.43-fold (p < 0.01), reduced malondialdehyde (MDA) concentration by 82.8% (p < 0.01), and trended to improve antioxidant capacity via glutamine. Mechanistically, WE promoted short-chain fatty acid production by beneficial bacteria, forming a “microbiota–metabolite–immunity” cascade to enhance lipid metabolism and alleviate intestinal inflammation. These findings highlight that WE provides multi-omics evidence for its application as a functional feed additive. Full article

Spent mushroom substrate (SMS) is abundant in nutrients, including polysaccharides, essential amino acids, dietary fiber (DF), and other bioactive compounds. The compound microorganism preparation (CMP), comprising multiple beneficial bacterial groups, is widely used as a feed additive to modulate intestinal microbiota and enhance nutrient absorption in animals. This study investigated the effects of supplementing young sika deer’s concentrated feed with SMS and CMP on total intestinal digestibility, growth performance, serum immune indicators, biochemical parameters, and intestinal microbial composition. Ninety animals were randomly assigned to three dietary treatments: control (basal diet), LE1 (basal diet + 5% SMS), and LE2 (basal diet + 5% SMS + 100 mg CMP/deer/day). Results showed that the LE2 group had significantly higher total weight gain (TWG) and average daily gain (ADG) than both the control group and the LE1 group. Levels of crude protein (CP), total protein (TP), albumin (ALB), blood glucose (GLU), and immunoglobulins (IgG, IgM, IgA) were significantly higher in the LE2 group than in the other groups, with LE1 also showing improvement over the control group. Additionally, ether extract (EE) and high-density lipoprotein (HDL) levels were found to be elevated in both the LE1 and LE2 groups when compared to the control group. In contrast, low-density lipoprotein (LDL) levels as well as urea nitrogen concentrations showed a significant increase in the LE1 group compared to both the control and LE2 groups. Notably, when compared to the control group, there was a significant reduction in the abundance of certain pathogenic bacteria within both the LE1 and LE2 groups; conversely, there was a substantial increase in the relative abundance of beneficial bacterial communities. These results demonstrate that combined SMS and CMP supplementation effectively improves growth performance, nutrient utilization, and intestinal health in young sika deer, suggesting its potential as a functional feed additive. Full article

The present study was conducted to evaluate the individual and combined effects of dietary crude protein levels and magnetic water treatment on the growth performance, water quality, body composition, physiological responses, and immunity of Oreochromis niloticus. Using a 3 × 2 factorial design, three levels of dietary crude protein (25%, 30%, and 35%) and two water types (magnetized and non-magnetized) were tested. A total of 180 juvenile tilapia (average initial weight: 4.13 ± 0.004 g) were randomly assigned to six treatment groups and reared for 10 weeks. Results showed that magnetic water treatment significantly improved dissolved oxygen and pH, while reducing ammonia, nitrite, and nitrate concentrations. Growth performance indicators, including final weight, specific growth rate, feed conversion ratio, and average daily gain, were significantly improved by both magnetic water and increased dietary protein. Carcass crude protein content improved with both the higher dietary protein level and magnetic water, while lipid content decreased. Liver and kidney function indicators (AST, ALT, ALP, and urea) were significantly improved by magnetic treatment and higher protein levels. Blood biochemical markers (TP, ALB, and GLO) were elevated, while glucose, cholesterol, and triglycerides were reduced by magnetic water; significant interactions were observed for globulin, triglycerides, and total protein. Antioxidant enzyme activities (SOD, CAT, and GPx) increased, and MDA decreased in response to magnetic water and high-protein diets. Similarly, digestive enzyme activities (lipase, protease, and amylase) and immune parameters (IgM and lysozyme) were significantly improved, with the best values recorded in the 35% protein + magnetic water group. In conclusion, magnetic water treatment and dietary protein level independently and interactively affect the physiological performance and health of Nile tilapia, with the best outcomes obtained at 35% protein under magnetic water conditions. Full article

Grouper (Epinephelus sp.) is one of the most economically important aquaculture species in China and Southeast Asian countries. Nervous necrosis virus (NNV) infection causes significant mortality in grouper aquaculture. Detection of anti-NNV antibodies using the ELISA method has been reported as effective in preventing vertical transmission of NNV in sea bass and flounder. In this study, IgM antibodies were purified from the serum of groupers and subsequently used to immunize rabbits to obtain a secondary antibody. Additionally, the NNV capsid protein (CP) was cloned, over-expressed, and purified in Escherichia coli. Consequently, an ELISA method was developed to detect NNV-specific antibodies in groupers by utilizing purified recombinant NNV capsid protein (CP) and horseradish peroxidase (HRP)-labeled rabbit anti-grouper antibody. This ELISA system was applied in three asymptomatic grouper hatcheries in China, revealing significant variations in antibody levels. Our ELISA method can effectively detect NNV-specific antibodies and is simpler than other methods, making it suitable for subsequent large-scale applications in grouper. Full article

Danshen polysaccharide (DSPS) is the main natural compound extracted from the traditional Chinese herb Danshen. Although DSPS is well-known for its antioxidant and anti-inflammatory properties, its impact on aflatoxin B1 (AFB1)-induced damage has not been explored. This study aims to investigate the potential protective mechanisms of DSPS against AFB1-induced liver damage and immune disorders. The experiment lasted a total of three weeks, during which 120 rabbits were randomly assigned to six groups (n = 20). AFB1 and DSPS were incorporated into the diets of each group. We found that DSPS significantly inhibited AFB1-induced hepatocyte edema, inflammatory cell infiltration, and increased serum aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) levels (p < 0.05). DSPS alleviated oxidative damage by downregulating CYP1A1/A2 mRNA, enhancing liver total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione (GSH) levels, and reducing the production of reactive oxygen species (ROS) and malondialdehyde (MDA) (p < 0.05). DSPS inhibits the expression of cytochrome c (cyt.c), caspase 9, and caspase 3, significantly reducing the apoptosis rate of hepatocytes (p < 0.05). Additionally, DSPS elevates the levels of immunoglobulins (IgA, IgG, IgM) and interferon-gamma (IFN-γ), while decreasing the concentration of IL-4 (p < 0.05). This study demonstrates that DSPS can alleviate AFB1-induced damage, with the underlying mechanisms likely related to enhanced antioxidant capacity, inhibition of oxidative stress, and intrinsic apoptotic pathways, as well as improved immune responses. Full article

Background: Podocalyxin (PODXL) has been identified as a promising therapeutic target and a potential diagnostic biomarker in various tumors. Despite the therapeutic potential of anti-PODXL monoclonal antibodies (mAbs), their further development has been limited by concerns regarding potential on-target off-tumor toxicities. To minimize adverse effects on normal tissues, developing a cancer-specific mAb (CasMab) against PODXL is essential. Methods: Our group established a cancer-specific anti-PODXL mAb, PcMab-60 (IgM, κ), through the screening of over one hundred hybridoma clones. In this study, PcMab-60 was engineered into a humanized IgG₁-type mAb (humPcMab-60), and its antitumor activity was examined using mouse xenograft models of pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer. Results: HumPcMab-60 retains cancer-specific reactivity; humPcMab-60 reacted to PDAC cell lines (PK-45H and MIA PaCa-2) and the colorectal cancer cell line (Caco-2), but not to a normal lymphatic endothelial cell line in flow cytometry. Furthermore, humPcMab-60 exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against PODXL-expressing cell lines and showed antitumor effects against the tumor xenografts. Conclusions: A humanized anti-PODXL CasMab, humPcMab-60, could be a promising mAb-based tumor therapy. Full article

Childbearing-aged and pregnant women represent a risk group for Toxoplasma gondii infection due to possible transplacental transmission resulting in congenital toxoplasmosis. We analyzed the seroepidemiological trends of toxoplasmosis in Croatia over ten years (2015–2024). A total of 2791 childbearing-aged and pregnant women were included. Toxoplasma gondii-specific IgM/IgG antibodies were detected using an enzyme-linked fluorescence assay. Samples with positive IgM and IgG antibodies were tested for IgG avidity. IgG antibodies were detected in 695 (24.9%) participants, while acute toxoplasmosis (IgM antibodies and low avidity IgG antibodies) was confirmed in 32 (1.2%) of participants. The IgG seroprevalence showed a declining trend over the years. Residents of suburban/rural areas were more often seropositive than those in urban areas (31.4 vs. 22.3%). Logistic regression analysis revealed that year of testing, age, and settlement were associated with the risk of seropositivity. For each later calendar year, the log odds of being IgG-positive decreased, while for each additional year of age, the log odds increased. Residence in an urban area was associated with lower log odds. The region was not a significant predictor in the logistic regression. The differences in seropositivity observed across regions can be mainly attributed to Pannonian Croatia, which showed significantly higher odds of IgG seropositivity. Data about the toxoplasma serological status is useful for planning prevention campaigns. Full article