Objective: To compare the efficacy of various exercise modalities for Rheumatoid arthritis (RA) employing a network meta-analysis. Methods: A systematic search was conducted across eight databases—PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and SinoMed—up to December 4, 2024, for randomized controlled trials on exercise for RA. The Cochrane Risk of Bias Assessment Tool (RoB 2) assessed study quality. A network meta-analysis was performed utilizing Stata 17.0. Our study measured outcomes through mean differences (MD) accompanied by 95% credible intervals (CIs) to quantify effect sizes, while interventions were ranked using surface under the cumulative ranking curve (SUCRA) probability scores, and the Confidence in Network Meta-Analysis (CINeMA) software to evaluate evidence certainty. Results: A total of 34 trials included 2,435 RA patients and 10 exercise interventions: walking or jogging, relaxation training, resistance exercise, Pilates, aerobic exercise, aerobic exercise + resistance exercise, yoga, traditional Chinese exercise, cycling, and Pilates + walking or jogging. The NMA results indicated that Pilates was the most effective for pain relief (VAS: MD = − 2.17 cm, 95% CI: − 3.77 to − 2.57, SUCRA = 91.8%); aerobic exercise + resistance exercise was most effective for reducing morning stiffness duration (MD = − 8.23 min, 95% CI: − 9.06 to − 7.39, SUCRA = 100.0%); and traditional Chinese exercise was most effective for improving disease activity (DAS28-ESR: MD = − 0.68 scores, 95% CI: − 1.04 to − 0.32, SUCRA = 95.5%). Risk assessment showed 4 studies “low”, 4 “high”, and 26 “some concern” regarding bias. The CINeMA assessment indicated that most comparisons provided low or very low-quality evidence. Conclusion: Exercise interventions are effective supplements for RA treatment, with specific exercises offering distinct benefits: Pilates for pain, aerobic exercise + resistance exercise for morning stiffness, traditional Chinese exercise for disease activity. Further high-quality studies are needed for validation.

The role of HMGB1 in inflammation and autophagy has garnered increasing attention; however, its impact on the activation of dendritic cells (DCs) and autophagy remains unclear. This study aims to explore the effects of HMGB1 on DC activation, autophagy, and its influence on CD4+ T cell responses in a bleomycin-induced pulmonary fibrosis (PF) mouse model. Thirty mice were randomly divided into control and model groups. The model group was established by intratracheal injection of bleomycin to induce PF. Flow cytometry was used to detect DC surface markers, and western blot was employed to assess the expression of autophagy-related protein LC3. Lung DCs and peripheral blood CD14+ monocytes were sorted using magnetic beads and differentiated into M0-DCs, which were then subjected to HMGB1 stimulation experiments to assess activation and cytokine secretion. HMGB1-stimulated or untreated M0-DCs were co-cultured with CFSE-labeled naive CD4+ T cells to evaluate T cell proliferation and differentiation. The effects of HMGB1 on DCs activation, cytokine secretion, and autophagy-related protein expression were assessed after treatment with autophagy regulators. The model group showed significantly elevated levels of HMGB1 in serum and lung tissues, accompanied by upregulated activation markers of DCs and increased expression of autophagy-related protein LC3. HMGB1 stimulation significantly enhanced the activation of M0-DCs and the secretion of pro-inflammatory cytokines, promoting the proliferation of CD4+ T cells and their differentiation into Th1 and Th17 subsets. Rapamycin, which enhances autophagy, potentiated HMGB1-mediated DC activation, while 3-MA, which inhibits autophagy, suppressed the effects of HMGB1, further influencing CD4+ T cell differentiation. HMGB1 modulates DC autophagy, thereby affecting their activation and immune responses of CD4+ T cells in bleomycin-induced PF. Targeting HMGB1 and the autophagy pathway may provide new strategies for the treatment of PF.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a severe complication of systemic lupus erythematosus (SLE). Despite its high morbidity, the exact pathogenesis of NPSLE remains poorly understood, and effective therapeutic options remain unavailable. Here we show gut bacterium Lactobacillus reuteri (L. reuteri) and its metabolite indole-3-acetic acid (IAA) play key roles in the progression of NPSLE. L. reuteri and IAA induce behavioral deficits, microglial activation, pro-inflammatory cytokine secretion, neuronal loss, and blood brain barrier (BBB) disruption in female lupus-prone mice. Mechanistic studies show that IAA activates the aryl hydrocarbon receptor (AHR) and signal transducer and activator of transcription 3 (STAT3) signaling pathways in microglia, thereby upregulating inflammatory responses and exacerbating neuroinflammation. These findings suggest a critical role for gut-microbiota-metabolite-brain axis in NPSLE pathogenesis and provide insights into potential therapeutic targets.