BackgroundPulmonary complications (PC), including infectious pneumonia (IP) and non-infectious interstitial lung disease (ILD), are major contributors of morbidity and mortality in systemic lupus erythematosus (SLE). As they are fundamentally different with respect to their respective etiologies and pathophysiology, we aimed to comprehensively identify and compare their risk factors.MethodsWe conducted a comprehensive literature search in seven electronic databases from database inception to September 2025. Pooled effect sizes were computed using appropriate model-based methods and thoroughly examined for heterogeneity. Our analytical approach advanced an evidence stratification framework that integrated both univariate associations and multivariate-adjusted results, which classified factors into four strata of findings: robust independent risk factors, preliminary independent risk factors, potential risk factors, and protective factors.ResultsIn total, 16 studies comprising 6,978 participants yielded fundamentally distinct risk architectures. IP was predominantly driven by immunosuppression and systemic inflammation, with robust independent risk factors including advanced age, pulmonary involvement, high CRP/WBC, immunosuppressant use, and antibacterial drug use. In contrast, ILD was strongly driven by autoimmunity and vascular pathology, with preliminary independent risk factors including Raynaud’s phenomenon, anti-Sm antibody positivity, high IgG and C4 levels. Most strikingly, serum IgG emerged as two strongly associated factors: low levels of serum IgG protected against IP, whereas high levels of serum IgG increased ILD risk.ConclusionThis is the first study to systematically stratify PC risk factors in SLE, demonstrating their distinct pathogenesis. The hierarchic framework allows a shift from a uniform management mindset to individualized risk evaluation for the respective complications, supportimg targeted prevention and early detection strategies.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view, identifier CRD420251020965.

Abstract Background Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease involving immune dysregulation, metabolic reprogramming, and multi-organ damage. The Jieduquyuziyin prescription (JP), a contemporary Chinese herbal formula based on the Traditional Chinese Medicine principle of “Jiedu Quyu Ziyin,” has shown clinical efficacy in SLE. This review aims to synthesize clinical and preclinical evidence explaining how JP achieves systemic therapeutic effects by targeting interconnected pathological pathways in SLE. Methods We systematically searched PubMed, Web of Science, and CNKI (January 1999–December 2025) for clinical trials, preclinical studies, and multi-omics analyses investigating JP or its bioactive compounds in SLE. Results Clinical evidence demonstrates that JP-containing regimens significantly reduce SLEDAI scores, alleviate lupus nephritis, lower glucocorticoid requirements, and improve quality of life in SLE patients. Preclinical studies in SLE-prone MRL/lpr mice reveal that JP targets key SLE pathogenic pathways: it restores Th17/Treg balance, suppresses SLE-associated pathogenic B cell proliferation via AKT/mTOR inhibition, and promotes apoptosis of double-negative T cells through UBE2M-mediated Bim upregulation. JP inhibits macrophage IRAK1/ NF-κB signaling, attenuates lupus nephritis by activating renal FXR to suppress TGF-β1/α-SMA-driven fibrosis, and mitigates oxidative damage via Nrf2 activation. Addressing SLE-associated immunometabolic dysfunction, JP reverses pathological glycolytic reprogramming in lymphocytes via AMPK signaling and restores mitochondrial function. Additionally, JP remodels gut microbiota in SLE models, enriching Akkermansia and modulating short-chain fatty acid and bile acid metabolism to reinforce immune homeostasis. Conclusion This review validates JP as a system-level therapeutic strategy targeting immune dysregulation, metabolic reprogramming, and gut dysbiosis in SLE, supporting the TCM principle of “Jiedu Quyu Ziyin” and its integration with modern immunology. Graphical abstract

Humans are concurrently exposed to a variety of environmental endocrine-disrupting chemicals (EDCs), which include such widespread substances like urinary perchlorates, nitrates, thiocyanates, and serum per- and polyfluoroalkyl substances (PFAS). The vast majority of the previous studies were devoted to individual chemicals or certain groups of chemicals, but the impact of co-exposure to mixtures of EDCs was also not thoroughly studied. The objective of this study is to identify the relationship between these EDC mixtures and prevalence of rheumatoid arthritis (RA) based on NHANES database. We used three types of regression models with individual chemical effects, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) in 2005–2012 to analyze results of individuals aged ≥ 20 years. Age and gender subgroup analyses were also done. A total of 4219 patients were analyzed, and 215 (5.10

High relapse rates in lupus nephritis (LN) remain clinically challenging and may contribute to progression toward end-stage renal disease. This study synthesized observational evidence on factors associated with renal relapse after LN remission. PubMed, Embase, Web of Science, the Cochrane Library, CNKI, CBM andWanfang were searched from inception to 10 October 2025. Study quality was assessed using the Newcastle–Ottawa Scale. Remission and relapse definitions were extracted, and unadjusted odds ratios, mean differences, and adjusted hazard ratios were interpreted separately. Thirteen cohort studies involving 2269 patients were included. Definitions of complete remission, partial remission, proteinuric relapse, and nephritic relapse varied across studies. In pooled adjusted analyses, younger age and anti-dsDNA positivity were associated with relapse, although anti-dsDNA was based on two studies. Pooled unadjusted analyses suggested associations for poor adherence, hematuria, elevated serum creatinine, uric acid, reduced albumin, low C3, anti-SSB positivity, and Class IV or mixed Class V + IV pathology. Class V showed a lower observed relapse likelihood, while Class II was borderline and heterogeneous. BUN, ESR, C1q, anti-Sm antibodies, antiphospholipid antibodies, lupus anticoagulant, and SLEDAI were supported mainly by single-study evidence. Several variables were associated with post-remission renal relapse in LN, but evidence strength and outcome definitions differed across studies. These findings should be interpreted as observational associations and candidate monitoring markers rather than validated independent prognostic markers. Prospective studies with standardized remission and relapse definitions and adjustment strategies are needed.

Double-negative (DN) B cells have emerged as pivotal players in autoimmune diseases, transitioning from an overlooked exhausted subpopulation to a lineage with potent pathogenic potential. Based on surface marker expression, DN B cells are subdivided into four distinct subsets: DN1, DN2, DN3, and DN4. This review provides a comprehensive overview of these subsets, focusing on their origins, phenotypes, and developmental trajectories. In disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren’s syndrome (pSS), and multiple sclerosis (MS), expanded DN B cells infiltrate target organs via chemokine receptor-mediated pathways and interact with T cells to drive the pathological remodeling of the local immune microenvironment. Elucidating the regulatory mechanisms of DN B cell differentiation and their functional heterogeneity across disease contexts will provide a critical foundation for the development of targeted precision immunotherapies.

Myricetin (MC) is a natural flavonoid with anti-inflammatory and antioxidant properties that shows protective effects in several renal diseases, yet its specific role in lupus nephritis remains unclear. This study evaluated the therapeutic effect of MC in LN and elucidated its mechanism related to B cell proliferation and differentiation. Using an MRL/lpr mouse model, integrated bioinformatics combining renal transcriptomics, network pharmacology, molecular docking, and machine learning identified the receptor tyrosine kinase AXL as a key target and the PI3K/AKT pathway as the downstream mediator. In vivo, MC treatment significantly reduced lupus activity and kidney damage, as evidenced by decreased proteinuria, autoantibody levels, and immune complex deposition. Mechanistically, MC suppressed renal AXL expression and blocked PI3K/AKT activation, thereby inhibiting abnormal B cell proliferation and plasma cell differentiation. In vitro experiments on primary mouse B cells and Ramos cells confirmed that MC downregulated proliferation markers such as Ki-67 and Ccnd1 as well as differentiation markers including Blimp-1 and Xbp1 via the AXL/PI3K/AKT pathway, demonstrated by CCK-8, EdU, flow cytometry, and Western blot. Collectively, MC alleviates LN by suppressing the AXL/PI3K/AKT axis and restraining pathogenic B cell responses, providing experimental justification for MC as a plant-derived candidate for LN therapy.

Mitochondrial DNA (mtDNA) is increasingly recognized as an active driver of immune dysregulation in systemic lupus erythematosus (SLE), yet most existing reviews treat it as a single damage signal rather than a multifunctional pathological mediator. This review presents an integrated framework examining mtDNA as a central hub linking mitochondrial dysfunction to systemic autoimmunity. We conducted a comprehensive synthesis of published evidence on mtDNA biology, its dysregulation in SLE, organ-specific injury mechanisms, and the clinical landscape of mtDNA-targeted therapeutic strategies. In SLE, intracellular mtDNA depletion coexists paradoxically with markedly elevated circulating cell-free mtDNA, a pattern correlating with disease activity and organ involvement. Sequential cytoplasmic and extracellular release of mtDNA engages cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING), Toll-like receptor 9 (TLR9), and inflammasome platforms, establishing self-amplifying interferon and pro-inflammatory circuits that drive multi-organ pathology. We consolidate emerging evidence for mtDNA-related parameters as clinical biomarkers and propose a provisional patient stratification framework distinguishing two pathological subtypes with distinct therapeutic implications. Among current therapeutic strategies, N-acetylcysteine (NAC) and metformin carry the strongest clinical evidence, while cGAS-STING inhibitors and TLR9 antagonists represent compelling emerging candidates. mtDNA operates as an integrative pathological hub in SLE, and its dysregulation pattern carries both diagnostic and therapeutic significance. Incorporating mtDNA-based biomarkers into clinical monitoring and developing precision strategies targeting mtDNA-driven inflammatory circuits represent important steps toward individualized SLE management.

Background Inflammatory arthritis represents a common and clinically challenging manifestation of systemic lupus erythematosus (SLE), with current therapeutic options often exhibiting limited efficacy. Purpose This study aimed to investigate the anti-arthritic effects and underlying mechanism of gentiopicroside (GPS), a key bioactive constituent of the Jiawei Baihu Jia Guizhi Decoction (JBH), with a specific focus on its interaction with galectin-9-mediated pathways in macrophage activation. Study design The anti-arthritic efficacy of GPS was investigated using a pristane-induced arthritis (PIA) mouse model, which recapitulates key features of SLE-associated arthritis. Integrated transcriptomic and network pharmacology approaches were employed for mechanistic exploration, followed by experimental validation in vitro and in vivo. Methods The PIA mouse model was treated with GPS to evaluate its effects on joint inflammation, synovial pathology, and bone remodeling. Transcriptomic profiling of joint tissues and network pharmacology analysis were conducted to identify potential targets. The interaction between GPS and Galectin-9 (Gal-9) was characterized using molecular docking and biophysical assays (determining a Kd of ∼350 nM). The functional impact of GPS on Gal-9-dependent NF-κB signaling, pro-inflammatory cytokine secretion, and macrophage activation was assessed in cellular models and PIA mice. Results GPS treatment significantly alleviated joint inflammation, synovial hyperplasia, and bone erosion in PIA mice, while also restoring the balance of bone remodeling. Integrative analyses pinpointed Gal-9 as a critical target, and GPS was confirmed to bind Gal-9 with high affinity. Functionally, GPS inhibited Gal-9-triggered NF-κB activation, suppressed the production of pro-inflammatory cytokines, and reduced macrophage infiltration and activation. Furthermore, GPS ameliorated systemic inflammation, lowered autoantibody levels, and improved joint integrity in PIA mice, demonstrating efficacy comparable to methotrexate. Conclusion Gentiopicroside, a key active constituent of the JBH, attenuates lupus arthritis by specifically targeting Galectin-9 and subsequently disrupting galectin-driven macrophage activation. These findings highlight GPS as a promising targeted therapeutic candidate for the management of SLE-related joint damage.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease; hematologic involvement is common and strongly associated with prognosis. Platelets—the second most abundant cellular component of peripheral blood—are anucleate cytoplasmic fragments. Their canonical roles include hemostasis, thrombosis, and vascular repair. More recently, platelets have emerged as regulators of innate and adaptive immunity that amplify inflammatory signaling and may facilitate tumor dissemination, suggesting underappreciated pathogenic roles in the initiation and progression of SLE. This review synthesizes platelet pathobiology in SLE and structures it into four modules: (i) pro-inflammatory actions of activated platelets; (ii) pathogenic effects of platelet-derived microparticles (PMPs); (iii) mechanisms by which platelets exacerbate lupus nephritis; and (iv) pathways linking platelets to SLE-associated cardiovascular disease. We also evaluate platelet-targeted therapeutic strategies and their translational prospects. Our aim is to provide a coherent framework for the platelet–SLE interface that informs mechanistic studies, guides biomarker development, and supports the design of more precise diagnostics and therapies.

BackgroundLupus nephritis (LN) significantly contributes to morbidity and mortality in systemic lupus erythematosus (SLE) patients. Although renal biopsy is the diagnostic “gold standard,” its invasiveness limits ongoing disease monitoring. Recently, research has focused on non-invasive “liquid biopsy” biomarkers, especially in urine. This study uses bibliometric methods to analyze the development and trends in LN biomarker research, highlighting recent advancements and future directions.MethodsWe collected original research articles on LN biomarkers from the Web of Science Core Collection and PubMed databases from 2005 to 2024. We conducted a bibliometric analysis using CiteSpace, VOSviewer, and Bibliometrix, and included 2025 studies on urinary biomarkers, renal pathology, disease activity, and long-term outcomes.ResultsThe analysis encompassed 576 articles, revealing three distinct developmental phases in the field, accompanied by a notable surge in publications since 2016. China and the United States are the top contributors, with the U.S. leading in citation impact and collaboration. The most active journal functions as a crucial repository of knowledge. Keyword and citation analysis reveal a shift from traditional immunological markers to non-invasive urinary biomarkers, such as MCP-1, NGAL, CD163, and complement-related molecules, alongside the adoption of multi-omics approaches and predictive models.ConclusionResearch on LN biomarkers is moving from discovery to clinical application. Advances in single-cell and spatial omics are shifting focus from peripheral biomarkers to renal molecular phenotypes, supporting “liquid biopsy” strategies. Future efforts will emphasize AI-driven multi-omics integration, minimal biomarker panels, and cross-ethnic validation to develop a precise, non-invasive LN monitoring system.

Pulmonary involvement (PI) in ANCA-associated vasculitis (AAV), especially interstitial lung disease (ILD) and diffuse alveolar hemorrhage (DAH), predicts poor outcomes, but a synthesis distinguishing these phenotypes is lacking. We searched seven databases up to April 1, 2026, and included observational studies. Using univariate and multivariate meta-analyses, we calculated pooled odds ratios (OR) or mean differences (MD). Nineteen studies (2,944 patients) were included. For ILD, robust independent risk factors were age > 65 years (OR = 3.60) and male gender (OR = 2.57). MPO-ANCA positivity was more frequent in the ILD group (OR = 2.29). Potential associated factors included smoking, D-dimer, ANA, low C4, and CA199. MPA subtype, cough, and dyspnea were more frequent in the ILD group. Factors associated with lower ILD frequency included GPA subtype, PR3-ANCA positivity, c-ANCA positivity, ENT involvement, gastrointestinal involvement, and a higher BVAS score. For DAH, potential associated factors included proteinuria, high BVAS score, Cr, BUN, PCT, decreased Hb, and low C3. PR3-ANCA positivity and hemoptysis were more frequent in the DAH group. For overall PI, independent risk factors were age (continuous OR = 1.04, > 65 years OR = 4.20), male gender (OR = 3.08), and high BVAS (OR = 3.03). MPO-ANCA positivity (OR = 2.55) was more frequent in the overall PI group, which largely overlapped with those for ILD, suggesting that ILD is the main driver of overall PI. This first meta-analysis combining univariate and multivariate approaches with an evidence-grading framework for ILD demonstrates distinct clinical patterns for ILD versus DAH, offering a clinically actionable tool for risk stratification and personalized management of PI in AAV.

Background Cutaneous involvement is a common manifestation of systemic lupus erythematosus (SLE), and dyslipidemia has emerged as a metabolic factor that aggravates lupus-associated skin injury. Purpose This study investigated the effects of Xijiao Dihuang Decoction derived formula (XJDHD) on dyslipidemia-aggravated lupus skin injury and its underlying immunometabolic mechanisms. Methods A high-fat diet (HFD)-exacerbated lupus-like skin injury model was established in lupus-prone mice. Histopathological, lipid metabolic, inflammatory, and oxidative stress analyses were conducted. Mechanistic exploration integrated molecular docking, network pharmacology, RNA sequencing, and macrophage-based assays. Results XJDHD markedly alleviated HFD-aggravated lupus-like skin lesions, reduced lipid accumulation, and suppressed cutaneous inflammation. Integrated analyses identified PPARγ-associated fatty acid oxidation and mitochondrial regulation as central pathways. XJDHD enhanced fatty acid oxidation, restored mitochondrial homeostasis, reduced oxidative stress, and inhibited pro-inflammatory macrophage polarization. PPARγ, ACADM, and NDUFAB1 were identified as key targets. Conclusion XJDHD attenuates dyslipidemia-associated lupus skin injury by restoring immunometabolic balance through regulation of fatty acid oxidation and mitochondrial homeostasis via the PPARγ-ACADM-NDUFAB1 axis, supporting metabolic-targeted herbal therapy for cutaneous manifestations in SLE.

PurposeModifying iron metabolism to mitigate oxidative stress and rebalance the Th17/Treg cell ratio in systemic lupus erythematosus (SLE) may represent a promising therapeutic target for treating SLE.MethodologyWe used the iron chelator deferoxamine mesylate (DFO) and a low iron diet (LID) to treat imiquimod (IMQ)-induced lupus-like syndrome in mice. We observed the changes in T lymphocytes and iron metabolism in the spleen. Splenic naive CD4+T cells were induced to differentiate into Th17 and Treg cells through magnetic separation and were cultured with DFO solution to observe the effect of DFO on the balance of Th17/Treg cells. Ras-selective lethal3 (RSL3)-induced ferroptosis in Naïve CD4+T cells was treated with DFO.Major FindingsWe found that iron deficiency may promote the expansion of Treg cells and suppress the production of Th17 cells by activating the Nrf2/HO-1/GPX4 signaling pathway, reducing the accumulation of reactive oxygen species (ROS), and thus halting the progression of IMQ-induced lupus-like disease.ConclusionIron deficiency, both in vitro and in vivo, inhibited the inflammatory response, reducing the production of inflammatory cytokines. This could present a possible therapeutic approach for SLE.

OBJECTIVE:Cardiovascular diseases from abnormal lipid metabolism significantly increase mortality in systemic lupus erythematosus (SLE). The causal link between dyslipidemia and SLE is unclear. METHODS:Lipid metabolism in patients with SLE was evaluated based on clinical data from 511 patients with SLE and 706 healthy individuals. Bidirectional Mendelian randomization (MR) was employed to assess causal links between 179 plasma lipid metabolites, lipid-lowering drug targets, and SLE risk. Genetic instruments from GWAS and eQTL data were used to evaluate CETP and APOA4 effects. Peripheral blood CETP and apolipoprotein levels in SLE patients were validated via ELISA. RESULTS:SLE patients exhibited reduced HDL-C (P < 0.0001), APOA1 (P < 0.0001), and APOA4 (P < 0.0001), alongside elevated triglycerides (TG, P < 0.0001), APOC3, APOD, and APOF. MR identified three lipid metabolites-PC(18:2_20:4), TG(56:6), and TG(58:7)-as causal factors for SLE (P < 2.79E-5). CETP inhibition significantly reduced SLE risk via HDL-C modulation (OR = 0.72, P = 3.38E-08) and influenced LDL-C, TG, and apolipoproteins. Clinical validation confirmed elevated CETP and reduced APOA4 in SLE, correlating with disease activity. APOA4 activation showed protective effects, while PCSK9 inhibition lacked relevance. CONCLUSION:Bidirectional Mendelian randomization analyses confirmed dyslipidemia as a causal antecedent to SLE, with no evidence of reverse causation. A variety of MR analyses and clinical validation indicated that targeting HDL-C regulation offers significant advantages for managing dyslipidemia in patients with SLE, with CETP identified as the optimal pharmacological target.

Background:As COVID-19 infection causes a kidney proximal tubule dysfunction with urinary loss of uric acid. Hypouricemia has been found in patients with severe COVID-19 disease. However, gout is a risk factor for COVID-19 incidence and COVID-19-related death. It is not known whether urate-lowering therapy could reduce the risk of infection of COVID-19 in gout patients or not. Methods:Data from collaborative electronic health records were used in this study. A total of 663,729 patients with gout were enrolled between January 1, 2020 and December31, 2022 from 35,528,077 participants in US Collaborative Network with at least two visits. After exclusion and propensity score matching, 5,466 patients with Febuxostat and 5,466 patients with Allopurinol in the comparison group were selected. The hazard ratios (HRs) and 95% confidence intervals of COVID-19 incidence, and mechanical utilization were calculated between Febuxostat and Allopurinol groups. Subgroup analyses on sex, age, levels of serum uric acid, with vaccination group and sensitivity analyses for gout patients due to renal impairment or with tophus, different follow-up durations and considered competing risk were performed. Results:Compared to Allopurinol group, Febuxostat significantly reduced the risk of COVID-19 incidence (HR = 0.878 [0.801-0.963]) and hospitalization (HR = 0.874 [0.772-0.989]). Febuxostat appears to be more effective in male, elder, without record of COVID-19 vaccination, and gout patients with serum uric acid<10 mg/dL in reducing the risk of COVID-19 infection. In addition, Febuxostat markedly reduced the hospitalization (HR = 0.652 [0.485-0.877]) in gout patients due to renal impairment or with tophus and the risks of COVID-19 incidence (HR = 0.878 [0.801-0.963]). Conclusion:In this retrospective cohort study, Febuxostat use was associated with a lower risk of COVID-19 among patients with gout for 3 years follow-up, even with renal impairment or tophus.

OBJECTIVES:To examine the changes in serum levels of endoplasmic reticulum stress (ERS) proteins GRP78/CHOP in patients with lupus nephritis (LN) and analyze their diagnostic value and association with renal pathological features. METHODS:From a sample bank established based on a multicenter cohort study of systemic lupus erythematosus (SLE), 60 LN patients and 35 SLE patients without renal involvement were randomly selected. ELISA was used to detect serum levels of GRP78 and CHOP in the patients to analyze their correlation with clinical features and their diagnostic ability for LN and active LN. MRL/lpr mice were used as an animal model of LN to examine their serum levels of GRP78 and CHOP expression and renal expressions of endoplasmic reticulum apoptosis-related proteins. RESULTS:Serum GRP78 and CHOP levels were significantly higher in LN patients than in SLE patients without renal involvement (P<0.05), and were also higher in active LN patients than in patients in the stable phase (P<0.05). Correlation analysis indicated that serum GRP78 and CHOP levels were positively correlated with SLEDAI scores and 24-h urinary protein. ROC analysis showed that CHOP had a high diagnostic ability for LN (AUC=0.762) and active LN (AUC=0.933). Consistent with the clinical findings, serum GRP78 and CHOP levels were elevated in LN mice, and the expressions of PERK and IRE1α pathway proteins were also increased in the kidneys of the mice. TUNEL staining showed increased renal cell apoptosis and elevated renal expressions of apoptosis-related proteins in LN mice. CONCLUSIONS:Serum levels of GRP78/CHOP are increased in LN patients possibly in association with ERS-induced apoptosis mediated by the PERK/IRE1α dual pathway.

Background:Autoimmune diseases, such as Crohn's disease (CD) and systemic lupus erythematosus (SLE), lead to progressive multi-organ damage due to immune dysregulation and chronic inflammation. Current therapies lack efficacy and safety, often failing to sustain remission. Stem cell therapy has emerged as a promising approach for immune modulation and tissue repair. This study analyzes clinical trial trends and challenges of stem cell therapy in autoimmune diseases. Methods:Clinical trial data (2006-2025) were extracted from Trialtrove. Strict inclusion criteria were applied, restricting the analysis to interventional trials while excluding observational studies, non-autoimmune disease trials, and records with incomplete information. Descriptive statistics were used to analyze trial phases, disease types, geographic distribution, funding sources, therapeutic mechanisms, and stem cell sources, followed by a comparative evaluation of therapeutic efficacy, combination strategies, and safety profiles across autoimmune indications. Results:Of the 1,511 global trials, 244 were included after screening and cross-referencing. Most trials (83.6%) were in Phase I-II. CD (n=85), SLE (n=36), and scleroderma (n=32) were the most studied. The U.S. and China led in trial numbers. Academic institutions funded 49.2% of trials. Key therapeutic strategies included immune modulation, tissue repair via growth factors, and anti-infection/anti-proliferative effects. Disease-specific variations were noted in cell sources and administration routes. Conclusion:Stem cell therapy holds substantial promise for autoimmune disease treatment. Future efforts should prioritize technological innovation, international collaboration, and precision medicine to address current challenges and advance clinical translation.

ETHNOPHARMACOLOGICAL RELEVANCE:Penthorum chinense Pursh (P. chinense), also known as Penthorum sedoides var chinense, is one of homology of medicine and food traditionally used by the Chinese Miao people and has shown beneficial potential effects in the clinical treatment of lupus nephritis (LN) and liver protection. AIM OF THE STUDY:Pinocembrin and gallic acid derivatives-rich fraction from P. chinense (PGF) has shown antioxidant and anti-lipidemic activities, yet its therapeutic potential in LN via macrophage PPARγ pathway modulation remains unexplored. In this study, we treated MRL/lpr mice with PGF to assess its therapeutic effects and verified its regulating signaling pathway through cytological experiments. MATERIALS AND METHODS:Chemical profiling of PGF was performed using UPLC-Q-TOF/MS. LN progression and PGF efficacy were evaluated in MRL/lpr mice via renal function assays and histopathological analysis (immunofluorescence). Integrated transcriptomics, metabolomics, and single-cell RNA sequencing were employed to identify PGF-targeted pathways. PPARγ/NFκB signaling modulation by PGF was validated in LPS-induced Raw264.7 macrophages and HK2 cells using western blotting, dual-luciferase reporter assays, and RT-qPCR. RESULTS:PGF administration significantly attenuated lupus-like symptoms (e.g., proteinuria and anti-dsDNA antibodies) and mitigated renal pathology in MRL/lpr mice. Multi-omics analyses revealed that PGF reshaped macrophage differentiation and activated renal PPARγ signaling. Mechanistically, PGF upregulated PPARγ expression while suppressing NFκB phosphorylation in LPS-stimulated Raw264.7 macrophages, HK2 cells, and kidney tissues. CONCLUSION:PGF ameliorates LN by modulating the PPARγ/NFκB axis in renal macrophages, highlighting its potential as a novel therapeutic strategy for LN through macrophage polarization regulation.

OBJECTIVES:We aimed to evaluate the risk of infectious complications of Belimumab with standard care in systemic lupus erythematosus (SLE). METHODS:We searched PubMed, Web of Science, EMBASE, and Cochrane databases for studies on SLE and Belimumab and evaluated the study quality using the Cochrane Collaboration tool (ROB 2). A random-effect model was employed to analyze the results. To evaluate publication bias, Egger's tests were used. We also performed subgroup analysis based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and British Isles Lupus Assessment Group(BILAG). The study protocol has been registered in PROSPERO (CRD42023421255). RESULTS:Eight studies involving 8545 patients were included, of which four studies had a high attrition bias. The present study suggested that the risks of infectious complications including infection (RR=1.02, 95 %CI=(0.97,1.08), I2=7.7 %) or serious infections (RR=0.94, 95 %CI=(0.77,1.15), I2=0 %), nasopharyngitis(RR=1.02, 95 %CI=(0.79,1.33), I2=36 %), upper respiratory tract infection(RR=0.97, 95 %CI=(0.83,1.14), I2=20.6 %), urinary tract infection(RR=1.09, 95 %CI=(0.91,1.32), I2=0 %), herpes zoster (RR=0.75, 95 %CI=(0.54,1.05), I2=0 %)and influenza(RR=0.98, 95 %CI=(0.69,1.39), I2=0 %) were not significantly increased in patients who received Belimumab with standard care, except for bronchitis (RR=1.51, 95 %CI=(0.98,2.33), I2=23.7 %). Additionally, the subgroup analysis of SLEDAI and the proportion of patients with BILAG 1A/2B did not show any significant impact on infectious complications. CONCLUSION:Meta-analysis results demonstrated that intravenous (IV) Belimumab(≤10 mg/kg), along with standard care, did not significantly increase the risk of infectious complications in SLE patients having mild-to-moderate disease activity, except for bronchitis. Baseline disease activity and organ damage did not impact the risk of infectious complications.