Systemic sclerosis (SSc) is an autoimmune condition affecting several organs. It is identified by thickening of the dermis, connective tissue affected by collagen accumulation, and vascular injuries that induce hypoxia. The present study aimed to determine whether extracellular vesicles (EVs) from adipose-derived stem cells (ADSCs) attenuated bleomycin-induced skin fibrosis and oxidative stress in scleroderma. ADSCs and their EVs were separated and a bleomycin-induced SSc mouse model was constructed. High-throughput sequencing was employed to study abnormal expression of circular RNAs in SSc skin tissues with or without ADSC-EV treatment. The regulatory mechanism and targets were studied using bioinformatics analysis, luciferase reporting analysis, angiogenic differentiation experiments, and RT-qPCR detection analysis. EVs from ADSCs were successfully isolated. The exosome treatment prevented dermal thickening and fibrosis in bleomycin-induced scleroderma. In addition, circ-Zfyve9 was demonstrated to have an important function in ADSC-EV-mediated skin tissue protection. GPX4 and miR-135 were shown to be downstream targets of circ-Zfyve9. Overexpressing miR-135 or downregulating GPX4 reversed the promotion effects of circ-Zfyve9 on angiopoiesis by increasing lipidosome ROS in EPCs under hypoxic conditions. Overexpressing miR-135 or downregulating GPX4 reversed the inhibition effect of circ-Zfyve9 on fibrosis in myofibroblasts under hypoxic conditions. Overexpressing circ-Zfyve9 increased the therapeutic effect of ADSC-EVs. EVs from ADSCs attenuated bleomycin-induced skin fibrosis and oxidative stress in scleroderma via circ-Zfyve9 delivery.

Background/Objectives: Children with juvenile idiopathic arthritis (JIA) frequently develop additional autoimmune conditions during follow-up, yet the clinical and diagnostic profile of this comorbid subgroup is incompletely characterised in single-centre paediatric series. We aimed to describe the prevalence, clinical pattern, and diagnostic features of autoimmune comorbidities in a seven-year cohort of children with JIA monitored at a single tertiary paediatric centre, and to document the diagnostic protocols applied for each comorbidity. Methods: We conducted a retrospective descriptive observational study of 103 consecutive children with JIA classified according to the ILAR 2001 criteria and monitored at the Paediatric Rheumatology Unit of St. Mary Children's Emergency Hospital, Iași, Romania, between 2017 and 2023, with the year 2020 excluded by design owing to the institutional reorganisation during the early COVID-19 pandemic. Autoimmune comorbidities were ascertained from medical records using ICD-10 coding and confirmed by subspecialty evaluation. The diagnostic approach for each comorbidity is reported in detail. Continuous variables are described using mean ± standard deviation, and categorical variables as frequencies (%). No inferential analysis was performed on predictor variables; the study is exploratory and hypothesis-generating. Results: Autoimmune comorbidity was identified in 21 of 103 children (20.4%; 95% confidence interval [CI] 13.1-29.5%), the JIA-AID subgroup. Patients were predominantly female (17 of 21, 81.0%) and aged over 12 years (10 of 21, 47.6%). Autoimmune thyroiditis was the most frequent comorbidity, present in 10 of 21 cases (47.6%) when the euthyroid, hypothyroid, and vitiligo-associated forms were combined, followed by inflammatory bowel disease (4 of 21, 19.0%), alopecia areata (4 of 21, 19.0%), localised scleroderma (2 of 21, 9.5%), and coeliac disease (1 of 21, 4.8%). Three patients (14.3%) had polyautoimmunity, defined as two or more autoimmune diagnoses in addition to JIA. The HLA-B27-positive enthesitis-related arthritis subtype, although small in absolute numbers, was over-represented within the JIA-AID subgroup: 5 of 7 HLA-B27-positive ERA patients (71.4%; 95% CI 29.0-96.3%) carried a coexisting autoimmune diagnosis, compared with 16 of 96 patients in the remainder of the cohort (16.7%; 95% CI 9.8-25.6%); the predominant comorbidity in this subtype was inflammatory bowel disease. Conclusions: Autoimmune comorbidity affected approximately one in five children with JIA in this single-centre cohort, with autoimmune thyroiditis and inflammatory bowel disease as the most frequent associations and a notable concentration of comorbidity within the HLA-B27-positive enthesitis-related arthritis subtype. These descriptive observations are hypothesis-generating and support the case for proactive multidisciplinary screening in selected subgroups. Prospective registry-based studies with explicit exposure classification and standardised functional outcomes will be needed to confirm the patterns reported here.

Eosinophilic fasciitis (EF) is a rare connective tissue disorder characterized by symmetrical or asymmetrical skin induration, fascial inflammation, and peripheral eosinophilia. We report the case of a middle-aged man presenting with left knee pain and swelling, progressive skin induration and pigmentation changes on the thigh and trunk. Blood workup showed peripheral eosinophilia and weakly positive PM-Scl-100 antibodies. MRI demonstrated fascial thickening with subcutaneous edema and fluid tracking along fascial planes, as well as a moderate knee effusion. Muscle biopsy confirmed eosinophilic fasciitis without muscle involvement. He was treated with high-dose prednisolone, methotrexate as a steroid-sparing agent, and adjunctive bone and infection prophylaxis, with marked clinical improvement at follow-up. This case highlights the diagnostic challenges in atypical presentation of eosinophilic fasciitis in the presence of overlap autoantibodies. Careful clinicopathological correlation is critical to exclude other differentials as EF can mimic systemic sclerosis or myositis. Biopsy can improve diagnostic certainty particularly when encountering auto-antibodies that have some association with other diagnoses.

Intracranial aneurysms associated with systemic sclerosis and Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia (CREST) syndrome are rare, and their pathophysiological relationship remains uncertain. We report the case of a 24-year-old male with systemic sclerosis and clinical features suggestive of CREST syndrome who presented with subarachnoid hemorrhage caused by a ruptured right middle cerebral artery bifurcation aneurysm. The aneurysm was treated with microsurgical clipping, followed by stent-assisted coiling for a residual aneurysm neck identified on follow-up angiography. The patient had a favorable neurological outcome with mild persistent cognitive deficits. A review of the literature identified only a small number of reported intracranial aneurysm cases associated with systemic sclerosis or CREST syndrome. This case differs from previously reported CREST-associated cases in patient age, sex, and aneurysm morphology, and highlights the possible contribution of connective tissue disease, smoking, and prior amphetamine exposure to aneurysm formation and rupture.

Anti-topoisomerase I (anti-Scl-70) antibodies are strongly associated with systemic sclerosis and fibrotic organ involvement. However, their significance in ANA-positive individuals without established systemic sclerosis remains unclear. We investigated whether isolated anti-Scl-70 positivity is associated with subclinical cardiac involvement. This retrospective single-center study included 486 ANA-positive individuals identified between 2016 and 2026. Patients were classified as anti-Scl-70-positive (n = 242) or anti-Scl-70-negative (n = 244). Individuals with systemic sclerosis, other rheumatologic diseases, cardiovascular disease (except hypertension), malignancy, or advanced renal/hepatic disease were excluded. All anti-Scl-70-positive patients remained free of systemic sclerosis during at least 12 months of follow-up. Electrocardiographic Diastolic Index-1 (EDI-1) and EDI-2 were calculated from standard 12-lead ECGs. Demographic characteristics, inflammatory markers, ANA titers, and most ENA antibodies were similar between groups. Anti-Ro52 positivity was more frequent in anti-Scl-70-positive individuals (p = 0.004). EDI-1 was significantly lower, whereas EDI-2 was significantly higher in the anti-Scl-70-positive group (both p < 0.001). Among patients with available echocardiographic data, anti-Scl-70-positive individuals demonstrated higher E/e' ratios (p = 0.004) and lower LV-GLS values (p = 0.046). EDI-1 showed a strong correlation with E/e' (rs = -0.898, p < 0.001). In multivariable analysis, anti-Scl-70 positivity was the only independent predictor of electrocardiographic diastolic dysfunction (p < 0.001). Isolated anti-Scl-70 positivity is associated with impaired electrocardiographic markers of diastolic function in ANA-positive individuals without overt systemic sclerosis. These findings suggest that isolated anti-Scl-70 positivity is associated with early subclinical myocardial involvement and support further investigation of ECG-derived diastolic indices as potential screening tools in this population.

Tropical Africa encompasses several biodiversity hotspots, yet knowledge of ectomycorrhizal (EcM) fungi, key organisms for forest ecosystem functioning, remains fragmented. This study provides the first comprehensive synthesis of EcM fungi across the region, aiming to (i) establish a species checklist as a basis for estimating gamma diversity, (ii) analyze spatial turnover across countries, and (iii) assess the functional effects of EcM fungi on tree seedling growth. We conducted a systematic literature search following PRISMA guidelines, retaining 158 publications published between 1927 and 2025. Species occurrence records were extracted from publications and complemented with data from GlobalFungi and GBIF databases. Statistical analyses in R were used to estimate species richness (Chao2, Jackknife 1 and Jackknife 2), analyze spatial turnover (Jaccard dissimilarity, Mantel correlogram, Generalized Dissimilarity Modelling), and assess the overall effect on tree seedling growth (cross-classified random-effects meta-analysis). We recorded 711 EcM fungal species from 59 genera and 20 families. Russula (169 species), Amanita (81), and Lactifluus (71) were the most represented. Estimated richness reached 1,226 species, indicating substantial undocumented diversity. Community composition showed extremely high heterogeneity among countries (95% dissimilarity), and increased turnover over broader geographic distances (r = -0.13, p < 0.05), suggesting dispersal limitation. Meta-analysis revealed that EcM fungi increased tree seedling growth by an average of 6% per month (p < 0.05), with Scleroderma verrucosum showing particularly strong positive effects. These findings indicate that EcM fungi are unevenly distributed across tropical Africa. They refine our understanding of diversity patterns and highlight the need for targeted sampling and integrating native EcM fungi into forest restoration.