Search Results (498)

Feline bocavirus (FBoV) is an emerging enteric virus associated with gastrointestinal diseases in cats and has attracted increasing attention in feline health. However, no commercial vaccine is currently available for the prevention and control of FBoV infection. VP2 is the major capsid protein of FBoV and represents a promising target for vaccine development. In this study, the FBoV VP2 protein was expressed using the insect baculovirus expression system. The purified VP2 protein self-assembled into virus-like particles (VLPs), which were formulated with Alum, ISA 206, or GEL 02 adjuvants to prepare VP2 VLP vaccines. The immunogenicity, cellular immune responses, antigen uptake, biodistribution, germinal center responses, and safety of the vaccines were evaluated in BALB/c mice. The results showed that all VP2 VLP vaccine formulations induced VP2-specific IgG antibodies and neutralizing antibodies, promoted B- and T-lymphocyte activation, enhanced dendritic cell maturation, and stimulated germinal center-related immune responses. Among the tested formulations, VP2+GEL 02 induced the strongest immune responses and showed favorable safety in mice. These findings demonstrate that FBoV VP2 exhibits favorable immunogenicity and represents a promising vaccine antigen for further development against feline bocavirus. Full article

Aortopathies in autoimmune rheumatic diseases (ARD) include a spectrum of aortic pathologies—including aortitis, aneurysms, dissections, and insufficiency—primarily caused by systemic inflammation. This comprehensive review investigates the clinical manifestations, pathophysiology, diagnostic modalities, and management strategies across various rheumatic diseases associated with aortopathies such as large vessel vasculitis (e.g., Takayasu arteritis, giant cell arteritis), connective tissue diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, systemic sclerosis) and less common conditions (e.g., relapsing polychondritis, Cogan’s syndrome, Behçet’s disease, IgG4-related disease). Disease-specific pathophysiologic mechanisms of aortic wall inflammation and remodeling, including granulomatous and lymphoplasmacytic patterns and mixed inflammatory infiltrates, are described. Diagnostic imaging modalities—such as CTA, MRI, and PET/CT—are evaluated for their roles in detecting active inflammation, assessing structural complications, and guiding clinical decision-making. Histopathological findings provide insight into disease-specific vascular changes. Management strategies focus on the use of glucocorticoids, disease-modifying antirheumatic drugs (DMARDs), and biologics, including IL-6 and TNF-α inhibitors, with an emphasis on patient-centered approaches, multidisciplinary care, and timely surgical intervention for complications. Evidence gaps include optimal screening intervals and the role of novel biomarkers in risk stratification and in monitoring disease progression, highlighting the need for early recognition, frequent monitoring, and aggressive management of aortic involvement in rheumatic diseases to prevent life-threatening complications. Full article

A 66-year-old man with hypertension, type 2 diabetes mellitus, and a 50-year smoking history was presented with acute chest pain clinically consistent with unstable angina. Coronary computed tomography angiography (CCTA) showed multivessel atherosclerosis and, more strikingly, diffuse sheath-like pericoronary soft-tissue cuffing around the major epicardial arteries—an appearance reported as the “mistletoe sign” and compatible with immunoglobulin G4 (IgG4)-related coronary periarteritis. CT-derived fractional flow reserve (CT-FFR) measured 0.75 in the left anterior descending artery, 0.68 in the left circumflex artery, and 0.94 in the right coronary artery. Invasive angiography identified a 90% proximal left circumflex stenosis as the flow-limiting lesion; drug-eluting stent implantation restored Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow. Serum IgG4 (145 mg/dL) was only marginally above the diagnostic threshold, and troponin was unavailable, so the diagnosis remained clinical. Without histopathology, the findings support possible rather than definite IgG4-related disease, and the contribution of the pericoronary process to the stenosis could not be established. The patient remained stable on conventional medical therapy. CCTA, CT-FFR, and angiography answer complementary questions; diffuse pericoronary change warrants serologic and systemic evaluation for inflammatory coronary involvement, with cautious etiologic attribution. Full article

Objectives: This study aimed to investigate the levels of varicella antibodies in Zhejiang, China, after a decade of implementing the two-dose varicella vaccine (VarV) strategy. Methods: Healthy participants aged 1 to 69 years from Zhejiang, China, were recruited from January to April 2024 using multistage stratified random sampling, and varicella zoster virus (VZV) IgG antibodies were detected by ELISA. We assessed the seroprevalence and geometric mean concentration (GMC) of VZV IgG and analyzed related factors using Logistic and linear regression models. Results: A total of 807 participants were included in the study. The overall seropositivity rate for VZV IgG in the healthy population was 73.08% (95%CI: 69.87–76.11), with a corresponding GMC of 200.97 mIU/mL (95%CI: 182.75 mIU/mL–221.01 mIU/mL). Multivariate analysis identified age group, VarV immunization history, and history of varicella disease as factors significantly associated with both VZV IgG seropositivity and GMC levels (p < 0.05). The seropositivity rate for VZV IgG in children aged 1–14 years was 42.67% (95%CI: 36.22–49.31), with a corresponding GMC of 82.10 mIU/mL (95%CI: 69.14 mIU/mL–97.48 mIU/mL). Furthermore, a significant decline in both seropositivity and GMC was observed over time following vaccination among vaccinated children aged 1–14 years (p < 0.05). Conclusions: Two-dose VarV vaccination may be considered for inclusion in the national immunization program. Full article

Aortitis—inflammation of the aortic wall—presents at the interface of vasculitis, infection, structural aortic disease, and cardiovascular risk. It may occur in giant cell arteritis (GCA), Takayasu arteritis, immunoglobulin G4 (IgG4)-related disease, drug-induced injury, infection, or as an isolated finding after aortic surgery. Modern imaging detects aortic inflammation more frequently, but the main challenge is classification rather than detection: determining whether disease is infectious or immune-mediated, active or dominated by fixed structural damage, systemic or isolated, and whether the dominant threat is aneurysm, dissection, undertreated infection, or avoidable immunosuppression. This review considers aortitis as a high-risk vascular syndrome requiring aetiology-first classification rather than descriptive labelling. Before escalating immunosuppression, infection must be actively excluded and inflammatory activity distinguished from fixed vascular damage. Treatment should be individualised according to phenotype, age, vascular territory, comorbidity, and toxicity risk, with surveillance continuing even after symptoms and inflammatory markers improve. Optimal care depends on multidisciplinary assessment integrating rheumatology, infectious diseases, vascular surgery, radiology, and cardiology expertise. Progress will require standardised imaging definitions, registries linking inflammatory control with structural vascular outcomes, and validation of artificial intelligence (AI) tools before clinical adoption. Full article

Mast cells (MCs) are immune cells that produce numerous immunological mediators involved in inflammatory and allergic responses. Increased numbers of MCs are observed in chronic inflammatory reactions in organs such as the colon. There, MCs seem to participate in deleterious immune responses and tissue damage, but the detailed mechanisms of their activation are not known, mostly because procedures to obtain MC primary cultures from the colonic mucosa are expensive and time-consuming and present low yield. Here we describe a protocol to obtain MCs from the colonic mucosa (cmMCs) of C57BL/6 mice with high yield, viability and purity. Mucosal colon cells were dispersed by enzymatic digestion, and cmMCs were isolated by Percoll continuous-gradient centrifugation. This method allowed for the purification of 1,446,667 ± 112,442 cell/g of mucosal tissue, with 87.22% viability and 95.16% purity. The mucosal-like phenotype was predominant in isolated cmMCs, characterized by weak toluidine blue staining but strong expression of MC protease-1 (Mcpt1). Activation assays showed that freshly isolated cmMCs increased intracellular calcium and showed degranulation in response to ATP or IgE-antigen-dependent FcεRI cross-linking. This highly reproducible technique is cost-effective and requires no specialized equipment. This protocol could be applied in research related to inflammatory bowel disease, colon cancer or food allergies. Full article

Toxocara spp. infection is a neglected zoonotic disease associated with exposure to companion animals and contaminated environments. However, information regarding its seroprevalence and associated risk factors among cat owners in Thailand, particularly in remote island communities, remains limited. This cross-sectional study aimed to determine anti-Toxocara spp. IgG seropositivity and identify associated risk factors among cat owners in Koh Yao District, Phang Nga Province, Thailand. A total of 291 cat owners participated in the study. Sociodemographic characteristics, health-related behaviors, serum anti-Toxocara spp. IgG antibodies, and hematological parameters were collected. Univariate and multivariable logistic regression analyses were performed to identify factors associated with seropositivity. The overall prevalence of anti-Toxocara spp. IgG seropositivity was 34.36%. In the univariate analysis, failure to wash hands after cat contact was significantly associated with higher odds of seropositivity (odds ratio [OR] = 1.96, 95% confidence interval [CI]: 1.16–3.33; p = 0.011). This association remained significant in the multivariable logistic regression model. These findings indicate substantial exposure to Toxocara spp. among cat owners in this island community and highlight the importance of personal hygiene, particularly handwashing after cat contact, in reducing exposure to infective Toxocara eggs. Targeted health education programs and preventive interventions should be strengthened to reduce the risk of Toxocara spp. exposure in endemic communities. Full article

Rett syndrome (RTT, OMIM 312750) is a complex multisystem neurodevelopmental disorder. Evidence suggests that RTT may have an autoimmune component and inflammatory activation. However, the autoimmune manifestations remain poorly described. Pemphigus foliaceus is a debilitating autoimmune blistering condition caused by IgG autoantibodies that target desmoglein-1 (Dsg1), resulting in widespread skin blistering and lesions. We report a case of pemphigus foliaceus in a 20-year-old female with RTT and discuss its clinical implications. Clinical data obtained from electronic health records were extracted and reviewed. Genetic testing was performed to identify the specific methyl-CpG-binding protein 2 (MECP2) mutation and on an expanded panel of 55 genes associated with pemphigus foliaceus and related blistering disorders. The individual had pemphigus foliaceus, which required immunosuppression, intravenous immunoglobulin (IVIg) therapy, and Rituximab. The disease trajectory was complicated by infections, aspiration pneumonia, and hypoxic cardiac arrest. There was progressive functional decline, and disease control was difficult to achieve, with frequent flares. Genetic testing confirmed a heterozygous pathogenic MECP2 variant (NM_001110792.1:c.952C>T; p.(Arg318Cys)). HLA genotyping identified alleles consistent with the HLA-DRB1*04:02–HLA-DQA1*03:01–HLA-DQB1*03:02 (DR4/DQ8) haplotype. Furthermore, genetic analysis identified a heterozygous DSG1 variant rs12967407. This study reports the first case of pemphigus foliaceus in RTT, expanding the clinical spectrum of RTT beyond its neurodevelopmental phenotype. The DR4/DQ8 haplotype, previously associated with pemphigus susceptibility, supports a background of genetic susceptibility in this individual. No causal association between RTT and pemphigus foliaceus can be inferred from this single case. Rather, this case demonstrates that a rare autoimmune disorder such as pemphigus foliaceus can co-occur with a pathogenic MECP2 mutation. The coexistence of a genetic and autoimmune disease can result in a more complex clinical presentation and treatment course. The case further emphasises the need for increased vigilance in identifying new and emerging systemic pathology alongside RTT. Full article

Background: Pediatric idiopathic nephrotic syndrome (INS) is classified primarily by corticosteroid response, delaying identification of steroid-resistant disease and exposing children to unnecessary treatment toxicity. Novel biomarkers could enable earlier biological stratification and treatment guidance. Objectives: The study aimed to map available evidence on candidate biomarkers in pediatric INS published since 2020, with emphasis on anti-nephrin autoantibodies and their potential for clinical translation. Data Sources: PubMed/MEDLINE and Web of Science Core Collection (January 2020–October 2025), with a supplementary verification search in Scopus and Embase and manual reference screening. Eligibility Criteria: Original studies reporting circulating, urinary, or tissue-based biomarkers in children aged 0–18 years with idiopathic NS, with outcomes related to diagnosis, treatment response, relapse prediction, or monitoring. Studies in adults only, secondary NS, or animal models were excluded. Results: After screening, 34 studies met the eligibility criteria and were included, grouped into five categories: autoantibodies, urinary markers, immune cell signatures, cytokines/chemokines, and exploratory markers (metabolomics, extracellular vesicles, lipid profiles, microRNAs). Anti-nephrin IgG emerged as the most mechanistically informative marker, with seroprevalence declining across phenotypes (SSNS 68%, SDNS 28%, non-genetic SRNS 14%, genetic SRNS 2%) and positivity predicting response to intensified immunosuppression. Of the candidates reviewed, urinary NGAL and peripheral B-cell subset monitoring are the most readily implementable with existing laboratory infrastructure. Conclusions: Pediatric INS encompasses a spectrum of immune-mediated podocytopathies that may soon be distinguishable by emerging biomarker profiles. Anti-nephrin autoantibodies provide the strongest mechanistic evidence for an autoimmune podocytopathy. Full article

Background/Objectives: Waning immunity after primary COVID-19 vaccination supports evaluation of additional doses. HXP-GPOVac is an egg-based, inactivated Newcastle disease virus (NDV)-vectored vaccine expressing a prefusion-stabilized SARS-CoV-2 HexaPro spike antigen. We evaluated the safety, tolerability, and immunogenicity of a single additional 10 µg dose of HXP-GPOVac administered to adults previously primed with two doses of either HXP-GPOVac or BNT162b2. Methods: Study GPO NDV-HXP-S 203 was an open-label phase II extension enrolling adults (18–75 years) who previously completed a two-dose primary series in Study 202 with either HXP-GPOVac or BNT162b2 (Pfizer–BioNTech; Comirnaty). All participants received a single additional 10 µg intramuscular dose of HXP-GPOVac ≥ 6 months after their second primary dose. Solicited local/systemic adverse events (AEs) were recorded for 7 days, unsolicited AEs through Day 28, and serious AEs (SAEs) and adverse events of special interest (AESIs) throughout follow-up. Neutralizing antibody titers (pseudovirus 50% neutralization titer, NT₅₀) and anti-spike IgG (BAU/mL) were assessed pre-dose (Day 1) and post-vaccination through 12 months; a predefined subset underwent IFN-γ and IL-5 ELISpot. SARS-CoV-2 infection during follow-up was assessed using anti-nucleocapsid (anti-N) IgG. Symptomatic COVID-19 was identified through symptom-reported, symptom-triggered RT-PCR testing; sequencing was performed when feasible. Results: All 219 participants received HXP-GPOVac (167 primed with HXP-GPOVac and 52 with BNT162b2). Any solicited local reaction occurred in 22.2% (37/167) of HXP-GPOVac-primed and 26.9% (14/52) of BNT162b2-primed participants; any solicited systemic reaction occurred in 10.8% (18/167) and 13.5% (7/52), respectively. No vaccine-related unsolicited AEs or AESIs were reported. Three deaths occurred during the 12-month follow-up; one (a sudden cardiac death in an HXP-GPOVac-primed participant) was assessed by the safety medical team as possibly related to vaccination, and two were assessed as not related. Neutralizing antibody GMTs increased from 46.33 at baseline to 1569.04 at Day 15 in HXP-GPOVac-primed participants and from 77.25 to 841.34 in BNT162b2-primed participants; corresponding SCRs were 78.8% and 76.9%. Anti-spike IgG GMCs increased from 48.79 to 1480.14 BAU/mL and from 194.48 to 1547.88 BAU/mL, respectively. Responses declined over time but remained above baseline through 12 months. In the cellular immunity subset, post-vaccination IFN-γ responses increased, with comparatively modest IL-5 responses and no pattern suggestive of Th2 predominance. Conclusions: A single additional dose of HXP-GPOVac administered ≥6 months after primary vaccination with HXP-GPOVac or BNT162b2 was generally well tolerated and elicited robust recall humoral responses, with supportive findings of cellular immunity. Trial registration: Thai Clinical Trials Registry, TCTR20230213001. Full article

Periodontitis and cardiovascular disease share inflammatory, immune, endothelial, oxidative, and lipid-related pathways. Although sex-related differences are well established for many cardiovascular biomarkers, it remains unclear whether sex modifies biomarker patterns at the intersection of periodontal and cardiovascular disease. PubMed, Scopus, and Web of Science were searched in accordance with PRISMA 2020. Eligible adult human studies evaluated periodontitis or periodontal inflammation together with atherosclerotic or related cardiovascular phenotypes and reported candidate biomarkers in blood or, as supportive evidence, oral fluids. High-throughput omics studies were eligible when available. Data on study design, periodontal and cardiovascular assessment, biological matrix, biomarker findings, sex-stratified analyses, and menopausal status were extracted. Twelve studies were included. Most assessed single biomarkers or small predefined panels rather than discovery-scale omics. Reported markers involved inflammation and immunity (CRP, hs-CRP, IL-6, LPS, and periodontal antibodies), endothelial or vascular injury, lipid and autoimmune pathways (PCSK9 and anti-ApoA-1 IgG), innate-immune and metabolic regulation (MBL and SIRT1), cardiac stress, and oxidative stress. Findings were heterogeneous across cardiovascular phenotypes, and several key associations were null or imprecise. Only two studies performed direct male–female comparisons: one enrolled women only, and none stratified women by menopausal status. No study derived and validated a sex-specific omics signature. The literature identifies overlapping candidate-biomarker pathways but does not establish a causal, clinically validated, sex-specific, or menopause-specific signature of periodontitis-associated cardiovascular disease. The current evidence should be considered hypothesis-generating. Full article

Background: Lymphoepithelial sialadenitis (LESA) is a chronic lymphoid-rich inflammatory disorder of the salivary glands that is strongly associated with Sjögren’s disease and may overlap clinically, radiologically, and histopathologically with IgG4-related sialadenitis, HIV-associated lymphoepithelial lesions, chronic sialadenitis, salivary gland tumors, and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Objective: This scoping review mapped current evidence on diagnostic challenges, differential diagnostic criteria, management strategies, and surveillance considerations for LESA. Eligibility criteria: Sources were selected using the Population–Concept–Context framework and included the literature addressing salivary gland lymphoepithelial lesions, LESA, Sjögren’s disease-associated salivary gland involvement, or related lymphoid-rich salivary gland disorders published from 2010 onward. Sources of evidence and charting methods: Google Scholar was searched, records were screened in sequential stages, and relevant data were charted narratively across clinical, serological, imaging, histopathological, immunophenotypic, molecular, therapeutic, and follow-up domains. Results: Thirty-seven sources were included. The evidence indicates that LESA is usually characterized by chronic lymphoplasmacytic inflammation, acinar atrophy, lymphoepithelial lesions, and preserved lobular architecture; however, these findings may overlap with early or established MALT lymphoma. Immunohistochemistry, assessment of light-chain restriction, clonality testing, serological markers, and imaging are useful adjuncts, but no single test is independently definitive. Conservative management and symptomatic care are appropriate for stable disease, whereas corticosteroids, immunomodulatory therapy, sialendoscopy, surgery, radiotherapy, or systemic lymphoma therapy may be considered according to clinical context. Conclusions: LESA requires integrated clinicopathological interpretation and multidisciplinary follow-up. Key evidence gaps include the absence of standardized LESA-specific diagnostic criteria, limited validation of molecular and flow cytometric approaches in salivary gland specimens, and lack of consensus surveillance protocols. Full article

Porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae (Mhp) are major contributors to the porcine respiratory disease complex. Although PCV2-Mhp bivalent inactivated vaccines are useful for simultaneous disease control, their immunogenicity may be improved by adjuvant optimization. This study evaluated a composite adjuvant consisting of porcine interleukin-2 (IL-2), IL-4, IL-6 and MnJ(beta), a colloidal manganese adjuvant, in an initial murine immunogenicity model. Thirty female Kunming mice were assigned to three groups (n = 10/group): bivalent antigen plus IL-2/IL-4/IL-6/MnJ(beta), bivalent antigen plus MnJ(beta), or phosphate-buffered saline. Body weight, complete blood count, peripheral blood T- and B-cell subsets, PCV2-specific IgG and Mhp-specific indirect hemagglutination titers were monitored after primary and booster immunization. The composite formulation did not suppress body-weight gain or induce sustained abnormalities in erythrocyte- or platelet-related indices. WBC, neutrophil, lymphocyte and monocyte counts were elevated in group A at days 7 and 28 post-primary immunization, indicating transient immune activation. Day-56 flow cytometry indicated increased CD19+IgM-IgD- B-cell and effector/memory T-cell-associated responses. PCV2-specific IgG increased from day 14 onward. At day 56, the OD450 value in group A reached 1.532 ± 0.006, compared with 1.095 ± 0.004 in group C1 and 0.102 ± 0.002 in group C2, corresponding to approximately 1.40-fold and 15.09-fold higher levels than the MnJ(beta)-adjuvanted and PBS control groups, respectively. Mhp-specific IHA titers were also maintained at high levels after booster immunization; at day 56, group A showed a log2 endpoint titer of 13.00 ± 0.00, corresponding to a GMT of 1:8192, whereas group C1 showed a log2 endpoint titer of 12.00 ± 0.00, corresponding to a GMT of 1:4096, and group C2 remained negative. These results indicate that the IL-2/IL-4/IL-6/MnJ(beta) composite adjuvant demonstrates potential for improving antibody and peripheral lymphocyte responses to PCV2-Mhp bivalent antigen, but protective efficacy must be confirmed in target-species challenge studies. Full article

Background/Objectives: Dengue is an emerging arboviral disease in temperate South America, where urban expansion, climate variability, and social vulnerability favor transmission. In Argentina, the endemic circulation of dengue was established in the late 1990s and outbreaks are reported every three or four years. Methods: This cross-sectional study assessed dengue virus (DENV) seropositivity and associated sociodemographic, environmental, and knowledge-attitudes-practices (KAPs) factors in three socioeconomically vulnerable peripheral neighborhoods of Santa Fe, Argentina, between December 2019 and March 2020. Results: A total of 188 adults were surveyed and tested for anti-DENV IgG using ELISA. KAPs questionnaires and direct peridomiciliary observations were used to characterize exposure contexts. Apparent seropositivity was 16.5%, with an adjusted estimate of 10.7% after accounting for test performance, indicating substantial unrecognized DENV circulation. Most seropositive individuals had no previous dengue diagnosis, highlighting underdetection likely related to asymptomatic infections, limited healthcare access, or surveillance gaps. Although dengue awareness was high (98.4%), knowledge was often incomplete and was weakly correlated with preventive practices, suggesting that awareness alone does not translate into effective risk reduction under structural constraints. In multivariate analysis, living farther from vacant lots was associated with higher odds of seropositivity, consistent with transmission concentrated in denser urban settings. Conclusions: Integrating serology with KAPs surveys provides critical insights into hidden transmission and supports targeted surveillance and public health interventions in vulnerable urban settings. Full article

Alcohol-related liver disease (ALD) poses a significant global health burden, driven by complex mechanisms including oxidative stress, inflammation, and gut–liver axis disruption. While the individual roles of gut microbiota dysbiosis and ageing in ALD pathogenesis are increasingly recognized, their synergistic interaction remains poorly understood. This review synthesizes current evidence to argue that there is an interaction between ageing and the gut microbiota that collectively amplifies progression of ALD. Specifically, ageing promotes gut dysbiosis through immunosenescence (e.g., reduced IgA diversification and antimicrobial peptide decline), intestinal barrier failure, and altered microbial metabolite profiles (e.g., decreased short-chain fatty acids and dysregulated bile acid metabolism). Conversely, dysbiosis-derived metabolites and endotoxins modulate ageing-related signaling pathways, including SIRT1, FOXO, and Nrf2, thereby accelerating hepatic cellular senescence, inflammation, and fibrogenesis. Furthermore, we also discussed the typical microbial changes in ALD. These include an increase in the Proteobacteria, a decrease in the Bacteroidetes, as well as imbalances in fungi and viruses. In ageing, similar but distinct shifts occur, such as reduced microbial diversity, decreased short-chain fatty acid producers, and increased intestinal permeability. Therapeutic strategies targeting the gut microbiota (probiotics, fecal microbiota transplantation) or ageing-related pathways (SIRT1 activators) hold promise. Future research priorities include validating ageing-associated microbial signatures as predictors of ALD progression and testing microbiota-targeted interventions in aged preclinical models. Collectively, this review identifies the microbiota–ageing axis as a tractable therapeutic target for ALD and provides a framework for future mechanistic and translational studies. Full article