Background: Primary Sjögren's syndrome (pSS) is an autoimmune disease that leads to the destruction of exocrine glands and multisystem lesions. Abnormal proliferation, apoptosis, and differentiation of CD4⁺ T cells are key factors in the pathogenesis of pSS. Autophagy is one of the important mechanisms to maintain immune homeostasis and function of CD4⁺ T cells. Human umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) may simulate the immunoregulation of MSCs while avoiding the risks of MSCs treatment. However, whether UCMSC-Exos can regulate the functions of CD4⁺ T cells in pSS, and whether the effects via the autophagy pathway remains unclear. Methods: The study analyzed retrospectively the peripheral blood lymphocyte subsets in pSS patients, and explored the relationship between lymphocyte subsets and disease activity. Next, peripheral blood CD4⁺ T cells were sorted using immunomagnetic beads. The proliferation, apoptosis, differentiation, and inflammatory factors of CD4⁺ T cells were determined using flow cytometry. Autophagosomes of CD4⁺ T cells were detected using transmission electron microscopy, autophagy-related proteins and genes were detected using western blotting or RT-qPCR. Results: The study demonstrated that the peripheral blood CD4⁺ T cells decreased in pSS patients, and negatively correlated with disease activity. UCMSC-Exos inhibited excessive proliferation and apoptosis of CD4⁺ T cells in pSS patients, blocked them in the G0/G1 phase, inhibited them from entering the S phase, reduced the Th17 cell ratio, elevated the Treg ratio, inhibited IFN-γ, TNF-α, IL-6, IL-17A, and IL-17F secretion, and promoted IL-10 and TGF-β secretion. UCMSC-Exos reduced the elevated autophagy levels in the peripheral blood CD4⁺ T cells of patients with pSS. Furthermore, UCMSC-Exos regulated CD4⁺ T cell proliferation and early apoptosis, inhibited Th17 cell differentiation, promoted Treg cell differentiation, and restored the Th17/Treg balance in pSS patients through the autophagy pathway. Conclusions: The study indicated that UCMSC-Exos exerts an immunomodulatory effect on the CD4⁺ T cells, and maybe as a new treatment for pSS.

DDAH2 inhibits antiviral signaling by promoting mitochondrial fission.

In recent years, an increasing number of observational studies have revealed an association between gut microbiota composition and psoriasis patients. However, whether this association reflects a causal relationship remains unclear. This study aimed to identify the causal relationship between gut microbiota and psoriasis through relevant research. In order to determine whether gut microbiota and psoriasis are causally related, we conducted a Mendelian randomization analysis using summary statistics from genome‐wide association studies (GWAS). As the exposure factor, we used summary statistics data from a GWAS study conducted by the MiBioGen Consortium, including 18,340 individuals with whole‐genome gut microbiota composition, and data from the FinnGen GWAS study on psoriasis, including 9267 patients and 364,071 controls as the disease outcome. Two‐sample Mendelian randomization analysis was subsequently performed with inverse variance weighted, MR‐Egger and weighted median, while sensitivity analyses were conducted to address heterogeneity and horizontal pleiotropy. The IVW results confirmed the causal relationship between certain gut microbiota groups and psoriasis. Specifically, family Veillonellaceae (OR = 1.162, 95% CI: 1.038–1.301, p = 0.009), genus Candidatus Soleaferrea (OR = 1.123, 95% CI: 1.011–1.247, p = 0.030) and genus Eubacterium fissicatena group (OR = 0.831, 95% CI: 0.755–0.915, p = 0.00016) showed significant associations. Sensitivity analysis did not reveal any abnormalities in SNPs. Currently, we have found some causal relationship between the gut microbiota and psoriasis. However, the study needs further RCTs for further validation.

Background: The accelerating process of global aging has made the burden of age‐related diseases increasingly severe, and traditional chronological age fails to reflect individual heterogeneity in aging. The neutrophil percentage‐to‐albumin ratio (NPAR), is a multidimensional health assessment index composed of inflammatory markers (neutrophils) and nutritional markers (albumin) to reflect inflammation and nutritional status, has shown unique potential in rheumatoid arthritis (RA) research. However, its association with biological age (BA; such as Klemera–Doubal method [KDM] age and phenotypic age, PhenoAge) has not yet been systematically validated in RA patients. By evaluating NPAR indicators in patients with RA, this study intends to reveal its value as a potential biomarker for predicting biological aging and its acceleration. Methods: This study was based on the National Health and Nutrition Survey 1999–2018 cycle database, and a cross‐sectional analysis of 1053 adult patients with RA was included. Core variable definitions include: neutrophil–albumin ratio (NPAR) = percentage of neutrophils (%)/albumin (g/dL); BA was calculated by the KDM (including 10 biomarkers) and the PhenoAge algorithm, respectively. Accelerated aging is quantified as the difference between BA and chronological age. The statistical analysis used a multi‐model validation strategy: 1) multivariate linear regression to evaluate the association between NPAR and continuous aging acceleration indicators; 2) the restricted cubic spline (RCS) model explores the nonlinear relationship; 3) stratified subgroup analysis to test for effect heterogeneity. All models were stratified for sociodemographic characteristics (age, sex, and ethnicity), lifestyle factors (smoking, alcohol consumption, and physical activity), and clinical covariates (body mass index [BMI], hypertension, and history of diabetes). Results: In an analysis of 1053 RA patients in the United States, women accounted for 56.48% and men for 43.52%; the group with the highest NPAR (T3) showed more significant aging characteristics (≥65 years old 34.75%, females 62.80%, and diabetes 27.69%) and higher biological aging acceleration rates (KDM acceleration 42.81% vs. low group 25.81%; PhenoAge acceleration 62.13% vs. 37.74%; all p < 0.001). After adjustment for multiple factors, the BA of KDM increased by 0.86 years for every 1 unit increase in NPAR (95% confidence interval [CI]: 0.39–1.32, p < 0.001), and PhenoAge increased by 1.32 years (95% CI: 0.93–1.71, p < 0.001). Taking the lowest NPAR group (T1) as the reference group, the highest NPAR group (T3) had an increased risk of accelerated aging of KDM by 149% (OR = 2.49, 95% CI: 1.44–4.31), and the risk of PhenoAge increased sharply by 259% (OR = 3.59, 95% CI: 2.17–5.95). Nonrestrictive spline curve analysis further revealed that there was a nonlinear positive correlation between the NPAR index and biological aging. When NPAR > 13.128, the growth rate of biological aging was significantly accelerated ( p for nonlinear = 0.05), while when NPAR > 14.512, the risk of phenotypic aging accelerated sharply ( p for nonlinear = 0.002). Area under the curve (AUC) of NPAR in the combined model for predicting biological senescence acceleration was 0.71–0.75. Discussion: Elevated NPAR is significantly associated with accelerated biological aging in RA patients, and the mechanism may involve neutrophil migration dysfunction, oxidative damage caused by albumin deficiency, and chronic inflammatory pathways (such as NF‐ κ B activation). As a low‐cost inflammatory marker, NPAR holds promise for integration into clinical aging risk assessment systems to identify high‐risk RA populations requiring early intervention. The study’s limitations include the inability to infer causality due to the cross‐sectional design and a relatively small sample size, necessitating further validation through cohort studies in the future.

Background: Joint bone destruction in rheumatoid arthritis (RA) leads to poor prognosis, with current treatments mainly targeting inflammation and limited focus on bone damage. Mesenchymal stem cells (MSCs) offer anti-inflammatory and bone repair properties, but their clinical application is hindered by cellular heterogeneity. Induced pluripotent stem cell–derived mesenchymal stem cells (iMSCs) present a promising alternative due to their lower heterogeneity and replicative senescence, although their potential in RA treatment remains underexplored. Methods: iMSCs were injected intraarticularly in a collagen-induced arthritis (CIA) model. Treatment outcomes, including plantar swelling, joint score, histological and immunohistochemical staining, microCT imaging, and bone loss, were assessed. Single-cell RNA sequencing was employed to study iMSCs’ effects on synovial macrophage subsets. Results: In vivo, iMSCs significantly reduced systemic inflammation and joint bone damage. Analysis of macrophage subpopulations revealed that iMSCs shifted macrophages from a pro-inflammatory CD86hiIL1βhi cluster to an anti-inflammatory CD86hiIL1βlo cluster, leading to reduced inflammation and bone resorption. Conclusions: iMSCs effectively alleviate inflammation and bone damage in CIA by modulating macrophage phenotypes, demonstrating potential for RA therapy.