Search Results (2,103)

Porcine circovirus 2 (PCV2) is a DNA virus that is classified in the genus Circovirus of the Circoviridae family, which is a causative agent of Porcine Circovirus-Associated disease (PCVAD). PCVAD continues to cause substantial losses in global pig farming, with PCV2d being the prevalent genotype worldwide, including in Vietnam. In this study, we focused on generating a recombinant PCV2d Cap protein fused to the GCN4pII motif (Cap2d-pII) in a plant-based system and evaluating its immunogenicity. The Cap2d-pII gene was cloned into a plant expression vector and introduced into Agrobacterium tumefaciens for transient expression in Nicotiana benthamiana leaves. Western blot analysis confirmed the high accumulation of the Cap2d-pII protein, which was purified by Immobilized affinity chromatography and used for immunizing mice. ELISA and immunoperoxidase monolayer assay results demonstrated that immunization with the recombinant protein elicited robust humoral and cellular immune responses. At 56 days after immunization, mice vaccinated with the Cap2d-pII protein generated PCV2d-specific IgG titers and IFN-γ responses that were consistent with those in mice receiving the commercial inactivated vaccine. These observations confirm that the plant-expressed Cap2d-pII antigen effectively activates both antibody- and T cell-mediated immune pathways. Collectively, this study identifies the Cap2d-pII protein as a promising plant-derived vaccine candidate for the development of effective and affordable PCV2d subunit vaccines. Full article

Background: Kimura disease (KD) is a rare benign disorder usually presenting in young Asian males as a subcutaneous mass in the head and neck. Common histological findings include lymphoid follicular hyperplasia, eosinophilic infiltrates, and vascular proliferation. Non-endemic presentations, particularly in women, are rare. Methods: We report a case of isolated retroauricular KD in a 28-year-old White woman with a 3-year history of an isolated, enlarging, mildly painful retroauricular mass, accompanied by peripheral eosinophilia and elevated serum immunoglobulin E (IgE) levels. The mass was resected, imaging showed no other sites of concern, and there was no recurrence. Results: Histopathologically, eosinophilic microabscesses, prominent vascular proliferation, and lymphoid follicular hyperplasia with CD20⁺ B cells, CD3⁺ T cells, and preserved CD23⁺ follicular dendritic networks were identified. Conclusions: A diagnosis of angiolymphoid hyperplasia with eosinophilia (ALHE) was excluded, and a final diagnosis of KD was established. Full article

The growing pet economy boosts demand for fiber-enriched functional foods to improve canine gut motility and metabolic health. However, low-bioavailability commercial fibers often falter in high-energy diets. Whole lamb omasum—from grass-fed sheep omasum and gastric contents—repurposes a discarded byproduct for waste reduction and sustainable livestock production. This study evaluated the short-term effects of WLO supplementation on gut health and metabolism in healthy adult Shiba Inu dogs. Twelve dogs were randomly assigned to control or WLO groups in a randomized controlled trial. WLO supplementation significantly reduced fecal scores by 8.91% (p < 0.05), increased apparent crude fat and fiber digestibility by 3.70% and 11.55% (p < 0.05), and elevated serum IgA by 35.79–36.15% and T-AOC by 30.53–35.71% (p < 0.05). Serum metabolome revealed 13 between-group and 8 within-subject differences related to lipid and endocrine modulation. Fecal microbiota analysis indicated enrichment of the Bacillota phylum and Blautia genus (p < 0.05). These findings support WLO as a functional food that enhances gut and metabolic health in small-breed dogs. Full article

Background: A quadrivalent HPV vaccine (BPV) has been developed to prevent diseases caused by HPV types 6, 11, 16, and 18 for the first time in Iran. The BPV is composed of the papillomavirus major capsid protein L1, which serves as the primary target in the design of the prophylactic HPV vaccines. To enhance immunogenicity, BPV was formulated with an amorphous aluminum hydroxy phosphate sulfate adjuvant. Methods: The immunogenicity and safety of BPV were assessed through analyses of both humoral and cell-mediated immunity, single and repeated doses, and reproductive effects using animal models. Results: Acute toxicity assessments showed no abnormalities in ophthalmic examinations, biochemical profiles, hematological parameters, and gross pathology findings. Additionally, no mortality or abnormal clinical signs were observed during a 90-day repeated-dose toxicity study. While some inflammatory reactions were noted at the injection sites and in the liver tissues of BPV-treated groups, these reactions were resolved by day 90 after the initial BPV administration. Furthermore, no signs of toxicity were detected in F1 offspring, and no adverse effects were identified in maternal reproductive performance, fertility, or hematological or biochemical parameters throughout the study duration. The BPV candidate successfully induced T-cell proliferation and increased the proportions of CD₃⁺ CD₄⁺ and CD₃⁺ CD₈⁺ T cells. It also stimulated the secretion of both interferon gamma (IFN-γ) and interleukin-4 (IL-4) cytokines in splenocytes isolated from animal models after the third dose. Moreover, anti-HPV L1 IgG antibody production was confirmed on day 14 after administration of each of the three BPV vaccine doses. Conclusions: The findings suggest that BPV is a vaccine candidate that stimulates both cellular and humoral immunity and demonstrate its safety profile in animal models. Full article

Background/Objectives: The aim of this study was to assess the relationship between the decline in rheumatoid arthritis (RA) disease activity—induced by periodontal treatment—and changes in the microbiology of subgingival plaque and serum antibody levels against the periodontal bacterium Porphyromonas gingivalis. Methods: Twenty-two RA patients with periodontitis underwent non-surgical periodontal treatment and assessment for the disease activity score of 28 joints (DAS28); antibody response to P. gingivalis virulence factors arginine (Rgp) and lysin (Kgp) gingipain; peptidyl arginine deiminase (PAD)2/4-activity; and the presence of P. gingivalis, Tannerella forsythia, and Prevotella intermedia in subgingival plaque through the evaluation of colony-forming units (CFUs) at baseline, two months, and six months post-treatment. Results: Periodontal treatment significantly reduced P. gingivalis CFUs at two and six months, and T. forsythia and P. intermedia CFUs at two months. Anti-RgpB IgG levels decreased at two months (p = 0.020). Higher baseline anti-RgpB IgG levels (r = −0.44, p = 0.039) and P. gingivalis CFU (r = −0.47, p = 0.028) correlated with greater reductions in DAS28. Greater reductions in P. gingivalis CFU were also associated with greater declines in DAS28 (r = 0.426, p = 0.048 and r = 0.467, p = 0.028, at two and six months, respectively). Anti-Kgp IgG and PAD2/PAD4 activity were not significantly affected by periodontal treatment. Conclusions: The impact of periodontal treatment on RA disease activity is more pronounced in patients with higher baseline P. gingivalis load and antibody response to RgpB. Better microbiological responses to periodontal treatment are associated with greater improvements in rheumatological symptoms. Further research is needed to confirm these findings and fully elucidate the underlying mechanisms. Full article

Patients with inflammatory bowel disease (IBD) frequently fail to achieve protective immunity after hepatitis B vaccination, even with intensified vaccination schedules. In this observational real-world study, 18 patients with IBD who were seronegative for hepatitis B virus (HBV) received three standard doses of the Engerix-B^® vaccine (at 0, 1, and 6 months). After immunisation, patients were classified into responders and non-responders according to their serological response. Blood samples were collected before the first dose and after completion of the vaccination schedule. Responders activated pathways that supported durable protection, including conventional dendritic cells type 1 mobilisation, expansion of IgG plasmablasts, and preservation of B- and T-cell memory. In contrast, non-responders displayed a more inflammatory innate profile, characterised by enrichment of CCR2⁺ monocytes. They also showed higher baseline Treg frequencies, which may suppress effective effector responses, together with impaired natural killer (NK) activation and progressive loss of memory potential. This study shows that hepatitis B vaccine failure in inflammatory bowel disease reflects a convergence of excessive immune regulation, inflammatory activation, and loss of memory potential, underscoring that no single pathway can explain the impaired response. Full article

Background: We aimed to investigate the diagnostic performance between the oral glucose tolerance test (OGTT) and HbA1c in diagnosing prediabetes and diabetes among obese individuals, and to evaluate the diagnostic performance of HbA1c for detecting OGTT-defined diabetes in obese individuals referred for evaluation of suspected prediabetes. Methods: Individuals with prediabetes were included between 1 January 2020 and 31 December 2022. Participants were categorized as mildly, moderately, morbidly, or super obese based on body mass index (BMI). According to the 75 g OGTT results, patients were classified into three groups: isolated impaired fasting glucose (IFG), combined IFG + impaired glucose tolerance (IGT), and overt type 2 diabetes mellitus (T2DM). The threshold HbA1c value for T2DM diagnosis in obese patients was determined based on OGTT outcomes. Results: Of the 139 prediabetic obese patients included, 115 (82.7%) were female, with a mean age of 45.18 ± 11.74 years. Based on BMI, 34 patients (24.5%) were mildly obese, 41 (29.5%) moderately obese, 49 (35.3%) morbidly obese, and 15 (10.8%) super obese. According to the 75 g OGTT results, 37.4% (n = 52) had isolated IFG, 45.3% (n = 63) had combined IFG + IGT, and 17.3% (n = 24) had overt T2DM. A weak–moderate positive correlation was observed between HbA1c and fasting blood glucose (Spearman’s rho = 0.263, p = 0.002). ROC–AUC analysis showed that HbA1c had significant discriminatory power in detecting T2DM diagnosed by the 75 g OGTT (AUC = 0.881, 95% CI: 0.816–0.946, p < 0.001). The optimal HbA1c cut-off was 6.15%, with 83.3% sensitivity and 80% specificity. The positive predictive value was 46.1%, and the negative predictive value was 95.8%. Conclusions: An HbA1c threshold of 6.15% demonstrated optimal performance for detecting OGTT-defined diabetes in obese individuals with suspected prediabetes. This value should not be interpreted as a population-wide diagnostic threshold. These findings indicate that HbA1c may serve as a useful screening tool to identify obese individuals who warrant confirmatory OGTT testing, rather than as a stand-alone diagnostic criterion. Further large-scale studies are warranted to confirm these results and support future clinical guidelines. Full article

Background: Emerging immune-evasive viral variants threaten the efficacy of current vaccines, underscoring the need for strategies that elicit broad and durable protection. Heterologous prime–boost regimens combining distinct vaccine platforms can enhance humoral and cellular immunity through complementary mechanisms. Methods: Using an intramuscular immunization scheme aligned with clinical vaccination practice, CD-1 mice received homologous or heterologous prime–boost regimens combining a replication-deficient Orf virus (Parapoxvirus orf, ORFV)-based spike vaccine (ORFV-S) with the licensed adjuvanted recombinant protein vaccine VidPrevtyn Beta. Spike-specific humoral and cellular immune responses were assessed. Results: ORFV-S alone induced potent and broad spike-specific IgG responses and achieved the strongest ACE2-binding inhibition across variants of concern. ORFV-S priming followed by VidPrevtyn Beta boosting markedly enhanced the magnitude and cross-variant breadth of antibody responses compared with homologous protein vaccination. Both homologous ORFV-S and heterologous regimens incorporating ORFV-S elicited strong CD4⁺ and CD8⁺ T-cell responses, whereas VidPrevtyn Beta alone induced only modest T-cell activity, demonstrating that ORFV-S effectively complements protein-based vaccines. Conclusions: The ORFV-S vector represents a potent vaccine platform capable of inducing broad humoral and cellular immunity. Its use in heterologous prime–boost combinations enhances both antibody magnitude and breadth beyond homologous protein vaccination, supporting its application in vaccination strategies against evolving viral pathogens. Full article

The concept of united airway disease (UAD) highlights the bidirectional relationship between inflammatory disorders of the upper airways—such as allergic rhinitis and chronic rhinosinusitis with or without nasal polyps (CRSwNP/CRSsNP)—and lower airway diseases, most notably asthma. This paradigm is supported by epidemiological, embryological, and immunological evidence demonstrating that airway inflammation represents a single, interconnected process rather than isolated compartmental pathology. Central to many UAD phenotypes is type 2 (T2) inflammation, driven by cytokines including IL-4, IL-5, and IL-13, and mediated by effector cells such as eosinophils and group 2 innate lymphoid cells (ILC2s). Epithelial barrier dysfunction often serves as the initiating trigger for this shared inflammatory cascade by production of TSLP, IL-25 and IL-33. Optimal diagnosis and management of UAD require an integrated, multidisciplinary framework. Clinical evaluation remains essential for patient characterization but must be complemented by pheno-endotypic assessment using imaging (CT), allergy testing, biomarker profiling (FeNO, blood eosinophils, IgE), and pulmonary function testing (spirometry, impulse oscillometry). Therapeutic strategies are layered, targeting both symptom control and inflammation across airway compartments. Standard approaches include intranasal and inhaled corticosteroids as well as saline irrigations, while severe T2-high disease increasingly benefits from biologic therapies (anti-IL-5/IL-5R, anti-IL-4R, anti-TSLP), which reduce dependence on systemic corticosteroids and surgical interventions such as endoscopic sinus surgery (ESS). Emerging precision-medicine models, particularly the “treatable traits” approach, further underscore the need to view the airway as a unified system. Collectively, these insights reinforce the clinical imperative of addressing upper and lower airway disease as a continuum, ensuring that inflammation in one district is neither overlooked nor treated in isolation. Full article

Allostatic load is a physiological measure of chronic stress, and stress is implicated in disrupting appetite regulation. Individuals with obesity and type 2 diabetes have higher allostatic load compared to lean counterparts. However, whether allostatic load differs across prediabetes phenotypes and relates to appetite is unknown. Purpose: Test whether prediabetes phenotypes differ in allostatic load in relation to altered appetite regulation. Methods: Individuals with obesity were recruited, and prediabetes was determined using American Diabetes Association (ADA) criteria (75 g OGTT) for this cross-sectional study. After an overnight fast, appetite hormones (ghrelin and PYY), insulin, and glucose were measured every 30 min up to 120 min of the OGTT. Perception of hunger and fullness as well as desire for sweet and fatty foods were assessed using a visual analog scale. Allostatic load was calculated from physiologic markers. Aerobic fitness (VO₂max), body composition (DXA), clinical labs, and quality-of-life questionnaires were also collected. Results: Participants with impaired fasting glucose (IFG) + impaired glucose tolerance (IGT) had a higher allostatic load, obesity, and insulin resistance compared with IFG or IGT (all p < 0.05), independent of fitness. IFG + IGT also had lower fasting ghrelin (p < 0.05) and no difference in fasting PYY. Hunger, fullness, and sweet ratings were comparable across groups, but fatty food ratings tended to be higher in IFG + IGT than NGT. Conclusions: Allostatic load was associated with altered fasting ghrelin levels in individuals with IFG + IGT, along with elevated body weight and insulin resistance. These findings suggest stress is a potential mechanism underlying appetite dysregulation in different forms of prediabetes. Full article

Objective: Idiopathic nephrotic syndrome (INS) is a rare, relapsing kidney disease. Trigger for relapses, among others, may be exposure to gluten in patients with INS and celiac disease (CD). CD is a gluten-sensitive disorder. The prevalence of CD ranges from 1% in the general population to 8% in patients with autoimmune diseases. The aim of the study was to assess the incidence of CD in patients with INS and the influence of a gluten-free diet on the course of INS. Material and Methods: A retrospective cohort study was conducted on 147 patients hospitalized between February 2020 and September 2024 in a single medical center. Patients were categorized into two groups: 98 patients with INS and 49 from the control group. The analysis included age, gender, total dose of glucocorticoids (GCs), duration of INS, serum levels of immunoglobulin class A (IgA) and G (IgG), the presence of antibodies against tissue transglutaminase (tTG) and endomysium (EMA), and urine analysis. A medical questionnaire regarding pathological symptoms during infancy and allergic diseases of patients and family members was conducted. Results: CD was diagnosed in 8% of patients with INS. A total of 66% of patients with INS and CD who followed a gluten-free diet had no or less frequent relapses. Conclusions: CD is more common in patients with INS than in the general population. A gluten-free diet in patients with INS and CD may decrease the frequency of nephrotic proteinuria relapses. CD may be oligosymptomatic, and it is important to search for it in all patients with INS. Owing to the small number of patients with CD among INS in the study, this issue requires further research. Full article

Toxoplasmosis is a parasitic disease associated with significant morbidity and mortality. This cross-sectional study aimed to determine the prevalence, associated risk factors, and ocular health outcomes related to Toxoplasma gondii seropositivity in 161 residents from four Quilombolas communities in the northern region of Tocantins, Brazilian Legal Amazon. Peripheral blood samples were collected and tested by Enzyme-Linked Immunosorbent Assay (ELISA) for Immunoglobulin G (IgG) and/or Immunoglobulin M (IgM) and Polymerase Chain Reaction (PCR), while a standardized form was used to collect sociodemographic, health, and behavioral data. Statistical analysis, conducted using Epi-Info 3.3.2, considered T. gondii seropositivity as the primary outcome, with a significance level less than 5% (p ≤ 0.05). An overall seroprevalence of 62.11% (100/161) was observed. Key risk factors significantly, as measured by the Odds Ratio (OR), associated with T. gondii seropositivity included being elderly (OR: 4.07, CI: 2.05–8.06, p < 0.01), having cats (OR: 5.56, CI: 2.74–22.27, p < 0.01), a low parental education level (OR: 2.97, CI: 1.46–6.02, p < 0.01), children playing on the ground (OR: 2.50, CI: 1.30–4.82, p < 0.01), and having a home vegetable garden (OR: 3.80, CI: 1.94–7.47, p < 0.01). Regarding ocular health, no conclusive direct association was established between T. gondii seropositivity and specific ocular manifestations when analyzed for children and the elderly separately. Observed ocular problems in the grouped population were primarily linked to age-related comorbidities rather than parasitic infection. High rates of T. gondii seropositivity, driven by specific environmental and socioeconomic factors, highlight the vulnerability of these communities, emphasizing the need for targeted preventive strategies. Full article

Background/Objectives: Non-melanoma skin cancer, which includes cutaneous squamous cell carcinoma (cSCC), ranks as the 5th most common cancer globally with high morbidity and more total deaths than melanoma despite having a lower mortality rate. While most cSCC cases can be treated with surgery, locally advanced, metastatic, and high-risk cSCC tumors are associated with a worse prognosis with higher rates of recurrence and require multimodality therapy. However, there is limited data on animal models of cutaneous squamous cell carcinoma for the use of combinatory immunotherapy and radiation. Methods: In this study, spontaneously generated tumors using DMBA/TPA were treated over three weeks with either IgG control, anti-PD1 antibody monotherapy, 8 Gy of localized radiation, or a combination of anti-PD1 and 8 Gy of radiation followed by anti-PD1 therapy. Results: We found that while anti-PD1 therapy showed a trend toward slowed tumor growth compared to controls, this difference was not statistically significant (p = 0.0775), with most mice showing continued tumor progression. Preliminary histological analysis suggested that anti-PD1 treatment increased CD8+ T cell infiltration, and the addition of radiation further enhanced CD8+ responses but added greater variability. A pathologic review revealed that irradiated tumors were associated with fibroblastic spindle-like cell morphology. Conclusions: This animal model represents a potential preclinical model for studying CSCC with limited responses to immunotherapy to understand potential mechanisms of resistance. Full article

Vaccination is a tool to control Lawsonia intracellularis (LI) in pigs. However, pigs may have co-infections that worsen clinical signs and lesions. The aim of this study was to characterize systemic and gut-mediated humoral and cell-mediated immune (CMI) responses in pigs vaccinated with a killed intramuscular LI vaccine and to analyze the impact of co-infection with Brachyspira hyodysenteriae (Bhyo) on the immune response. The study included eighty pigs and five study groups: V-CO (LI-vaccinated and co-infected with LI + Bhyo, n = 21), P-CO (placebo and co-infected with LI + Bhyo, n = 18), V-LI (LI-vaccinated and infected with LI, n = 21), P-LI (placebo and infected with LI, n = 12), and NC (negative control, placebo and non-challenged, n = 8). Parameters analyzed: fecal score and pathogen shedding), gross intestinal lesions, LI intestinal colonization (IHC), serum IgG, LI-specific IFN-γ production (ELISPOT), and immune cell subsets (flow cytometry) in blood, mesenteric lymph nodes, Peyer’s patches, and intestinal epithelium. LI vaccination significantly reduced LI fecal shedding, intestinal colonization, and macroscopic lesions—even under Bhyo co-infection. Vaccinated pigs had earlier and stronger serum IgG and IFN-γ responses. B cells seem to play an important role in the local immune response, and T regulatory cells apparently do not have a significant role in immunomodulation. This study contributes to a better understanding of LI immune response and can provide subtract for further research in the control of LI. Full article

Background/Objectives: In recent years, the recognition that type 2 inflammation plays a leading role in CRSwNP has enabled the more tailored treatment of the disease through improved patient endotyping. We studied 45 patients with severe CRSwNP who were treated with dupilumab or mepolizumab. The aim was to evaluate the efficacy of these treatments on endoscopic, clinical and patient reported parameters, and to assess whether nasal cytology could be useful for identifying responsive patients and monitoring their response to biologic drugs. Methods: Follow-up visits were scheduled at baseline (T0), and at 3 (T3), 6 (T6), 12 (T12), and 24 months (T24). At each visit, patients underwent blood analysis, nasal endoscopy, and nasal scraping for cytology. They also completed the SNOT-22 questionnaire, a visual analog scale (VAS) for nasal obstruction and smell perception, and the Asthma Control Test (ACT) test in cases of concomitant asthma. Results: Biological therapy demonstrated broad efficacy in disease management, based on both clinical and cytological findings. The Nasal Polyp Score, SNOT-22 questionnaire, VAS scores for nasal obstruction and smell, and ACT score showed progressive improvement. Blood eosinophil counts and total IgE levels also decreased over time (T0 vs. T24: p = 0.008 and p < 0.001, respectively). At nasal cytology, a reduction in eosinophil cell count and in the mixed mast cell–eosinophil pattern during treatment with both biologics were observed (T0 vs. T24: p < 0.001). Positive effects were typically recorded within six months of treatment and were sustained after two years. Conclusions: Although the histological evaluation of infiltrated tissues remains the gold standard for assessing mucosal eosinophilia, nasal cytology appears to be a simpler, non-invasive, and repeatable method for evaluating local eosinophilia. Identifying endotypes and assessing the severity of inflammation are crucial for predicting the efficacy of different treatment options. Full article