ABSTRACT Introduction Toxoplasma gondii ( T. gondii ) is an obligate intracellular protozoan parasite that poses a significant threat to both human and animal health worldwide. Despite extensive research efforts, no effective vaccine is currently available for human use. Heat shock protein 90 (Hsp90) is a highly conserved molecular chaperone essential for protein folding, signal transduction, and stress response regulation in T. gondii . Due to its immunological importance and developmental regulation, Hsp90 is a promising target for vaccine development. Material and Methods In the present study, comprehensive immunoinformatics approaches were employed to characterize T. gondii Hsp90. Various bioinformatics tools were used to analyze its physicochemical properties, subcellular localization, post‑translational modifications, structural features, and potential immunogenic epitopes. Results The protein comprised 708 amino acids, had a molecular weight of 81.93 kDa, and was predicted to be unstable, soluble, and nonallergenic. Structural modeling and validation revealed that 50.85% of the residues form α‐helices, and 15.68% β‐strands, with two disulfide bonds contributing to conformational stability. Multiple bioinformatics tools identified several B‐ and T‐cell epitopes with high antigenicity, strong binding affinity to both MHC Class I and II molecules, and favorable immunogenic profiles. The peptide SEDLPLNISRESLQQNKILK obtained the highest predicted B‐cell epitope score using SVMTriP, while ANMERIMKAQALRDN was selected as a promising T‐cell epitope based on MHC‐II binding prediction and VaxiJen antigenicity assessment. The overall antigenicity scores (0.757 for ANTIGENpro and 0.551 for VaxiJen) confirmed Hsp90 as an immunogenic and safe vaccine candidate. Conclusion The findings highlight T. gondii Hsp90 as a promising target for subunit vaccine development, providing a theoretical foundation for future in vitro and in vivo validation studies.
ABSTRACT Background Acupuncture is proposed to operate within the neuro‐endocrine‐immune network. Its therapeutic efficacy is proposed to be partly mediated through the gut microbiota‐macrophage axis. This proposal is based primarily on preclinical findings. This axis may act as a biological transducer that helps sustain systemic homeostasis 1 . This review synthesizes current evidence on how acupuncture may orchestrate a top‐down regulation of the intestinal microenvironment through somato‐vagal circuits, particularly those involving PROKR2‐expressing sensory fibers. Materials and Methods This narrative review examined recent preclinical and clinical literature on acupuncture, gut microbiota, metabolites, and macrophage polarization. Studies were selected by relevance and expert judgment. Evidence was organized around the proposed gut microbiota‐macrophage axis. Results In preclinical rodent models and some human studies, acupuncture has been reported to suppress pathogens such as Proteobacteria . It may also promote symbionts like Akkermansia muciniphila and butyrate‐producing taxa. Butyrate promotes anti‐inflammatory M2 macrophage polarization via histone deacetylase (HDAC) inhibition and G‐protein‐coupled receptor signaling. In rodent models, acupuncture has been shown to strengthen barrier integrity. It may upregulate tight junction proteins. It may also prevent lipopolysaccharide (LPS) translocation and suppress M1‐driven cascades. These effects extend distally via the gut‐lung and gut‐brain axes. Discussion It is important to note that this proposed cascade is primarily derived from preclinical rodent models, and direct evidence in humans that confirms all steps from vagal activation to macrophage reprogramming remains incomplete. Ultimately, acupuncture may serve as a potential eco‐immunological therapy that restores balance between the microbiome and innate immunity. This framework provides a preliminary conceptual basis for the eventual development of personalized, biomarker‐driven protocols for chronic inflammatory diseases, although this hypothesis requires rigorous causal validation.
ABSTRACT Introduction Behçet's disease (BD) is a multisystem inflammatory vasculitis with clinical heterogeneity that may vary across ethnic groups within the same country. This study aimed to evaluate the influence of ethnicity on the clinical manifestations, immunogenic laboratory findings and disease course of BD by comparing Turkic and non‐Turkic patients in a large Iranian referral cohort. Methods In this retrospective cohort study, 2697 patients with BD followed at the BD clinic of Shariati Hospital in Tehran, Iran, from 2007 to 2019 were included. Results Patients were stratified by ethnicity into Turkic ( N = 1037; 38.5%) and non‐Turkic ( N = 1660; 61.5% [with Persian/Fars, N = 980 subgrouping]) groups, and demographic, clinical manifestations, and immunogenic laboratory findings were extracted from medical records. Mean age at BD onset was 25.72 ± 10.02 years in Turkic patients and 24.69 ± 10.23 years in non‐Turkic patients, and males comprised 61.3% and 57.1% of the two groups, respectively. Human leukocyte antigen (HLA)‐B5 positivity was 55.1% in Turkic versus 53.1% in non‐Turkic patients, and HLA‐B51 positivity was 48.7% versus 46.5%, respectively. Most clinical manifestations showed similar prevalence across groups, including oral aphthous ulcers (98.7% vs. 99.0%), genital aphthous ulcers (60.5% vs. 62.0%), uveitis (50.1% vs. 53.2%), and deep vein thrombosis (5.3% vs. 5.1%). Superficial phlebitis was more frequent in Turkic patients ( p = 0.02), and oral aphthous ulcers occurred earlier in Turkic patients ( p = 0.023). A three‐class latent class model demonstrated the best fit (BIC = 14,986.58). In multinomial logistic regression analysis, Turkic patients had slightly higher odds ratio of the ocular‐predominant phenotype (OR = 1.10, 95% CI: 0.91–1.33; p = 0.320) and slightly lower odds ratio of the multisystem phenotype (OR = 0.94, 95% CI: 0.68–1.30; p = 0.692); however, neither association was statistically significant. Female gender was associated with higher odds ratio of the ocular‐predominant phenotype than the mucocutaneous‐predominant phenotype (OR = 1.38, 95% CI: 1.14–1.67; p = 0.001). Conclusion In this large Iranian BD cohort, Turkic and non‐Turkic patients exhibited broadly similar disease phenotypes and comparable HLA‐B51 frequencies, with small but potentially relevant ethnic differences in the timing of oral ulcers and the frequency of superficial phlebitis. These findings suggest that ethnicity may influence BD phenotype through mechanisms beyond HLA‐B51, possibly involving other immune‐related genetic variants such as tumor necrosis factor (TNF)‐α, endoplasmic reticulum aminopeptidase 1(ERAP1), Interleukin (IL)‐10. Of note, the significant differences observed in Turkic versus non‐Turkic comparisons were not present in the Turkic versus Persian (Fars) comparison, indicating that the findings are not driven by a single ethnic subgroup.
ABSTRACT Background Chronic rhinosinusitis (CRS) is a common clinical condition characterized by persistent inflammation of the nasal and sinus mucosa. While inflammatory endotypes are well‐described, the upstream metabolic dysregulations that initiate and perpetuate inflammation remain poorly defined. This review examines how mitochondrial metabolism, biogenesis, and dysfunction contribute to CRS pathogenesis. Methods A comprehensive literature search was performed up to November 2025 using PubMed/MEDLINE, Web of Science, and ScienceDirect. Search terms included “chronic rhinosinusitis,” “mitochondria,” “oxidative stress,” “reactive oxygen species,” “inflammation,” and “epithelial barrier,” together with related keywords and synonyms. Experimental, mechanistic, and translational studies exploring mitochondrial involvement in CRS were included. Results Evidence from multiple experimental studies demonstrates that mitochondrial dysfunction is closely intertwined with key pathological processes in CRS. Mitochondria are damaged by diverse CRS‐related pathogenic factors leading to excessive reactive oxygen species production, impaired biogenesis, and disrupted membrane potential. These mitochondrial abnormalities amplify epithelial inflammation, oxidative stress, and barrier dysfunction, creating a self‐propagating vicious cycle in which mitochondrial injury and inflammation reinforce each other. Mitochondrial dysfunction also contributes to characteristic histopathological changes, including epithelial damage, ciliary impairment, and fibrin deposition. Conclusions Mitochondria play a pivotal role in CRS pathogenesis. Targeting this self‐amplifying cycle of Inflammation–oxidative stress–mitochondrial dysfunction therefore represents a promising therapeutic strategy for breaking the chronicity of CRS.
ABSTRACT Background Miller‐Fisher syndrome (MFS) is characterized by the triad of ataxia, areflexia, and ophthalmoplegia. To our knowledge, the combination of initial dizziness, scanning speech, transient hyperreflexia with a Babinski sign, and persistent anti‐GQ1b seronegativity has not been previously reported. Case Presentation A 27‐year‐old Chinese Han male patient presented with prominent dizziness and scanning speech as the primary symptoms. Physical examination revealed hyperreflexia of all tendon reflexes initially, along with intention tremor and a positive Babinski's sign on the right side. Subsequently, he exhibited the classic triad of MFS, and cerebrospinal fluid analysis showed albuminocytological dissociation. He was ultimately diagnosed with MFS. Electromyography (EMG) revealed significantly abnormal blink reflexes, dysfunction of the brainstem auditory pathway, particularly within the central nervous system, and a descending sensory nerve action potential (SNAP) in the left sural nerve. Cerebral Magnetic Resonance Imaging (MRI) and ganglioside Q1b (GQ1b) antibodies were both negative. After treatment with intravenous immunoglobulin (IVIG) for 5 days, the patient's condition significantly improved. By the 1‐month follow‐up, his neurological function had completely recovered. Conclusion The involvement of dizziness, scanning speech, hyperreflexia, and Babinski's sign in anti‐GQ1b‐negative MFS is quite rare, indicating early central nervous system (CNS) involvement. The pathogenesis of MFS may have a broader immunological basis rather than being solely attributable to a single autoantibody‐mediated response against gangliosides.
