This post hoc analysis of a phase III clinical trial (NCT04333771) was aimed at evaluating the effect of ivarmacitinib (SHR0302) on joint symptoms in small and large joints and imaging changes in patients with moderate-to-severe rheumatoid arthritis (RA). Patients were randomized to receive 24-week ivarmacitinib 4 mg (n = 189), ivarmacitinib 8 mg (n = 189), or placebo (n = 188). At week (W) 24, patients receiving placebo switched to ivarmacitinib 4 mg; others continued initial regimens until W52. Changes in swollen joint count (SJC) and tender joint count (TJC) in small and large joints from baseline, and imaging changes from baseline to W24, were evaluated. Compared with the placebo group, ivarmacitinib 4 mg and 8 mg groups demonstrated greater reductions in SJC and TJC in small and large joints over the initial 24 weeks and showed sustained improvement throughout the treatment. Ivarmacitinib 4 mg and 8 mg groups showed greater reductions in TJC in small joints versus large joints at several time points, with especially pronounced effects in the ivarmacitinib 8 mg group from W20 to W52. From W24 to W52, patients switched to ivarmacitinib 4 mg exhibited sufficient improvement in SJC and TJC of small and large joints, with greater reductions in TJC in small joints versus large joints. Ivarmacitinib 4 mg and 8 mg groups showed greater reductions in bone erosion and synovitis scores under MRI scanning from baseline to W24 versus the placebo group. Ivarmacitinib improves swelling and tenderness in small and large joints in patients with moderate-to-severe RA, with superior effects on tenderness in small joints.

Diabetic eye disease (DED) is a leading cause of vision impairment worldwide, yet the molecular mechanisms underlying its progression remain incompletely understood. In this study, we applied a dual-platform spatial metabolomics strategy integrating air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) and matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) to characterize spatial metabolic alterations in the eyes of diabetic rats. Data-driven segmentation of retinal micro-regions using SCiLS Lab software enabled fine-scale mapping of metabolic heterogeneity. Physiological, biochemical, and histopathological analyses were combined with spatial metabolite mapping to construct a metabolic atlas and evaluate the regulatory effects of ferulic acid. We established a comprehensive spatial metabolome atlas of the rat eye, identifying 135 annotated metabolites and revealing significant region-specific metabolic heterogeneity. Unsupervised k-means clustering was further applied to the high-resolution MALDI-MSI data, successfully delineating distinct functional micro-regions of the retina solely based on endogenous metabolic profiles, demonstrating the power of data-driven tissue segmentation. In diabetic eyes, 39 metabolites were significantly dysregulated, involving amino acid, glucose, lipid, and redox metabolism. Notably, lysine, arginine, carnitine, and glutathione (GSH) were depleted, while glucose-6-phosphate (G6P), glycerol-3-phosphate (G3P), and pro-inflammatory lipids were elevated, highlighting profound metabolic reprogramming across ocular compartments. Ferulic acid treatment restored nine key metabolites, alleviated oxidative stress, normalized lipid and glucose metabolism, and improved retinal structural integrity in a dose-dependent manner. This study shows that integrating mass spectrometry imaging with data-driven tissue segmentation reveals spatial metabolic reprogramming in DED and highlights ferulic acid as a promising therapeutic candidate.

Background:Olanzapine is an atypical antipsychotic used to treat schizophrenia and manic episodes. Its potential thromboembolic risk has been reported, but the evidence remains controversial. This study aimed to comprehensively evaluate the association between olanzapine and pulmonary embolism (PE) and venous thromboembolism (VTE). Methods:This study combined meta-analysis and signal mining from the FDA Adverse Event Reporting System (FAERS) database to assess the association between olanzapine and pulmonary embolism (PE) and venous thromboembolism (VTE). Results:From 55,905 olanzapine-related adverse event reports in the Faers database, 1,233 significant signals were identified, including serious adverse events not fully documented on the drug label, such as pulmonary embolism and venous embolism. A meta-analysis of eight studies showed that olanzapine use significantly increased the risk of VTE and pulmonary embolism (OR = 2.07, 95% CI: 1.37-3.14, P = 0.0006). Conclusion:These findings suggest that olanzapine is associated with an increased risk of thromboembolic events; therefore, enhanced clinical surveillance and further investigation into its safety are necessary. Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD420251003254.

Aristolochic acid I (AAI) is a potent nephrotoxin responsible for aristolochic acid nephropathy (AAN); however, the spatial relationship between toxicant accumulation and region-specific metabolic dysfunction during chronic exposure remains incompletely understood. Here, we established a 12-week chronic AAN rat model using repeated oral administration of AAI (1 and 10 mg/kg/day) and integrated spatial metabolomics, spatial transcriptomics, and regional LC-MS/MS quantification to elucidate the underlying mechanisms. Quantitative analysis revealed dose-dependent accumulation of aristolactam I (ALI), the major Phase I metabolite, predominantly in cortical regions. Airflow-assisted desorption electrospray ionization (AFADESI)-MSI uncovered extensive, region-specific metabolic reprogramming, with the inner cortex exhibiting the greatest perturbation. Integrated analyses demonstrated coordinated disruption of arginine-nitric oxide signaling, mitochondrial oxidative phosphorylation, fatty acid β-oxidation, arachidonic acid-mediated inflammation, purine metabolism, antioxidant defense, and osmolyte homeostasis. Spatial transcriptomics further revealed suppression of redox-regulating enzymes, fatty acid oxidation pathways, and transporters, alongside activation of oxidative stress and inflammatory responses. Mechanistically, chronic AAI exposure induced mitochondrial dysfunction, glutathione depletion, lipid peroxidation, and energy insufficiency, establishing spatially localized redox stress microdomains. The strong spatial concordance between ALI accumulation and metabolic collapse supports a toxicokinetic-toxicodynamic coupling in AAN pathogenesis. Collectively, this study provides a spatially resolved multi-omics framework that advances mechanistic understanding of AAI-induced nephrotoxicity and identifies potential targets for intervention.

BACKGROUND:AllergoOncology has emerged as an interdisciplinary field exploring the interaction between allergic diseases and cancer; however, the lack of stable in vivo models has limited mechanistic investigations. This study aimed to establish an experimental animal model to explore the impact of systemic allergic responses on tumor progression and to provide preliminary insights into the regulatory role of allergy in cancer development. METHODS:An ovalbumin (OVA)-induced systemic allergy tumor-bearing mouse model (OVA-TM) was established by OVA sensitization followed by subcutaneous implantation of CT26 colon cancer cells. Tumor growth, immune responses, and behavioral changes were systematically evaluated. Tumor immune microenvironment alterations were assessed using immunological and histological analyses. Transcriptomic profiling and mass spectrometry imaging (MSI) were integrated to investigate immune-related metabolic alterations. Human tumor survival datasets were used to validate the prognostic relevance of differentially expressed genes (DEGs), and enrichment analyses of allergy- and cancer-associated genes were performed using humanized databases. RESULTS:OVA-induced systemic allergy significantly suppressed tumor growth and promoted immune cell infiltration, particularly CD3+CD8+ T cells. Transcriptomic analysis identified key DEGs, including Aoc1, Apob, Apobec2, and Acta1, whose expression correlated with overall survival in multiple cancer types. Integrated transcriptomics and pathway enrichment analysis revealed extensive functional reprogramming in OVA-TM tumors, including activation of metabolic and immune-related pathways. Consistent with these findings, spatial metabolomics analysis showed synergistic alterations in lipid and amino acid-related metabolic pathways in both tumors and the spleen. CONCLUSION:This study establishes a practical in vivo model for AllergoOncology and demonstrates that systemic allergic responses can modulate tumor progression through immune activation, apoptosis, and inflammation-metabolism axis reprogramming, providing a foundation for future mechanistic and therapeutic studies.

Microplate-based assays are indispensable in life sciences and drug discovery; however, conventional optical readouts provide limited chemical information. Here, we report a microplate-based mass spectrometry imaging (MP-MSI) workflow based on air flow-assisted desorption electrospray ionization (AFADESI) that enables high-throughput molecular analysis of complex biological samples with minimal sample consumption (down to 1 μL). In contrast to existing MSI-based high-throughput strategies that primarily perform single-mode screening, this platform integrates targeted quantitation and untargeted metabolomics from the same sample spot. Using formaldehyde (FA) as a model analyte, we developed a rapid spermidine derivatization method and performed full method validation in blank mouse plasma. The targeted assay achieved an interbatch precision of 6.18% RSD for the analyte-to-internal standard ratio across 0.01-0.8 mmol/L, with a minimum detectable concentration change of 1.12-fold. For untargeted metabolomics, the median within-run RSD evaluated from 180 repeated spottings of blank mouse plasma was 19.1%, corresponding to a minimum detectable fold change of 1.38, at a throughput of 2.2 min per sample. To demonstrate dual-mode integration, we applied the validated FA method to plasma from an Alzheimer's disease mouse model (APP/PS1 and wild-type, 10 and 12 months of age), simultaneously quantifying FA and profiling the global metabolome from the same acquisition. Age- and genotype-dependent metabolic alterations were revealed. The platform was further extended to cell coculture models and to drug quantitation (e.g., irinotecan in plasma), demonstrating versatility across sample types and analytes. This integrated strategy offers a versatile platform for high-content screening in biomedical and pharmacological research.

BACKGROUND:Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by dysregulated T cell responses and metabolic disturbances. Mesenchymal stromal cells (MSCs) have shown therapeutic promise, but their mechanisms, particularly concerning T cell metabolism, remain incompletely defined. This study investigated whether human umbilical cord-derived MSCs (hUC-MSCs) ameliorate collagen-induced arthritis (CIA) by modulating T cell metabolism and differentiation. METHODS:CIA was induced in DBA/1 mice. Animals received PBS or hUC-MSCs on day 28. Arthritis index (AI), joint histology, serum cytokines (TNF-α, IL-6, IL-17, and TGF-β), and metabolites (lactate and pyruvate) were assessed. Splenic T cell transcription factors (FOXP3, RORγt, and PU.1) and glycolytic genes (GLUT1, G6PD, and PFKFB3) were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. In vitro, human CD4+ T cells were cocultured with hUC-MSCs under T-helper 17 (Th17)-polarizing conditions. T cell subsets, glycolytic metabolites, and gene/protein expression were evaluated by flow cytometry, colorimetric assays, RT-qPCR, and western blot. RESULTS:MSC treatment significantly attenuated arthritis severity, joint destruction, and splenomegaly in CIA mice. It reduced serum pro-inflammatory cytokines and normalized elevated lactate and pyruvate levels. In the spleen, MSCs suppressed RORγt and PU.1 while enhancing FOXP3 expression, and downregulated GLUT1 and G6PD mRNA. Positive correlations were found between glycolytic markers (GLUT1 and G6PD) and pro-inflammatory transcription factors (RORγt and PU.1), and between serum lactate and inflammatory cytokines. In vitro, hUC-MSCs directly inhibited Th17 differentiation and promoted Treg generation in human CD4+ T cells. This metabolic reprogramming was functionally coupled to a shift in T cell differentiation: a suppression of pro-inflammatory Th17 cells and a promotion of regulatory T (Treg) generation in human CD4+ T cells. This was accompanied by reduced lactate production and significant downregulation of GLUT1, G6PD, and PFKFB3 at both mRNA and protein levels. CONCLUSIONS:hUC-MSCs ameliorate CIA by restoring the Th17/Treg balance through metabolic reprogramming of T cells, specifically by suppressing glycolysis. This immunometabolic mechanism highlights the therapeutic potential of MSCs in RA.

Evaluating skin sensitization is crucial for the safety of cosmetics and pharmaceuticals. Regulatory bans on animal testing have spurred the development of New Approach Methodologies (NAMs), Integrated Testing Strategies (ITS), and Next Generation Risk Assessment (NGRA). Defined Approaches (DAs) that combine various NAMs have been developed to assess skin sensitization hazards and potency, as recognized by the OECD. However, deriving a quantitative point of departure (PoD) through NAMs in accordance with NGRA remains challenging. This study evaluated the skin sensitization hazard and potency of 5-hydroxymethylfurfural (5-HMF) and 5,5'-oxydimethylenebis(2-furfural) (OBMF), which are by-products of saccharide-containing botanical ingredients in cosmetics and preparations, using an NGRA workflow that integrated ITS DAs and read-across. Within the NGRA framework, NAMs classified 5-HMF and OBMF as weak to moderate skin sensitizers based on the Schiff base formation mechanism. Case studies on hypothetical consumer exposure scenarios (leave-on and rinse-off) for 5-HMF and OBMF derived PoDs and acceptable concentration thresholds raise safety concerns regarding human skin sensitization from topical exposure to 5-HMF and OBMF. The study assessed uncertainties in NGRA and NAMs for exposure-driven risk assessments without animal testing. It advocated for further research to refine tiered NGRA workflows, enhance the protective sufficiency of NAMs, and expand their applicability to botanical ingredients.

Cancer remains a major global health challenge, and although immunotherapy has achieved remarkable breakthroughs, its efficacy is often limited by tumor-induced immunosuppression within the tumor microenvironment (TME). Emerging evidence indicates that metabolic reprogramming plays a pivotal role in shaping the TME and regulating antitumor immune responses. Targeting tumor and immune cell metabolism has therefore become a promising strategy to enhance the effectiveness of cancer immunotherapy. This review first summarizes the metabolic reprogramming that occurs within the TME, including alterations in glucose, lipid, and amino acid metabolism in tumor cells, as well as the metabolic adaptation of immune cells. We then highlight recent advances in natural products that modulate key metabolic pathways and their potential to reshape the immunosuppressive TME. Special emphasis is placed on natural compounds that not only inhibit tumor cell metabolism but also restore the metabolic fitness of immune cells, thereby improving antitumor immunity. In addition, advances in delivery strategies, including nanocarrier-based and stimuli-responsive systems, are reviewed for their roles in improving the bioavailability, stability, and tumor targeting of natural metabolism-regulating agents. Finally, we discuss the current status and challenges of translating natural metabolism-regulating agents into clinical applications, including issues of dose optimization, safety evaluation, and patient selection. Despite these hurdles, precision targeting of metabolic pathways, interdisciplinary collaboration, and the discovery of novel compounds-particularly immune-sensitizing agents derived from traditional medicine-are expected to accelerate progress. Collectively, natural products represent promising adjuvant strategies for cancer immunotherapy, with great potential to overcome current therapeutic limitations and improve clinical outcomes.

ABSTRACT Objective Treatment with human umbilical cord mesenchymal stem cells (hUC‐MSCs) attenuated the clinical manifestations of systemic lupus erythematosus (SLE). We investigated the metabolic mechanism whereby hUC‐MSCs modify CD4 + T cell cytokine secretion in lupus. Methods The study enrolled 30 untreated lupus patients and 20 sex, age, and body mass index matched healthy controls (HCs). CD4 + T cells were isolated by magnetic sorting, and stimulated with anti‐CD3/CD28. The hUC‐MSCs treatment (MSCT) groups were coculturing hUC‐MSCs to CD4 + T cells from moderate and severe SLE (SLE‐MS) groups for 72 h at ratios of 1:25 (T1), 1:10 (T2), and 1:5 (T3). Cytokine concentration and proliferation of the CD4 + T cells were measured by Luminex liquid chip assay and cell counting kit‐8, respectively. Glucose metabolic capacity was measured by Seahorse real‐time metabolic analysis. The role of hUC‐MSCs on cytokine secretion was analyzed by transcriptome sequencing. Glucose enzymes levels and HSP90AA1/PI3K/AKT pathway activity were analyzed by real‐time quantitative PCR and western blot. The CD4 + T cell subsets were detected by flow cytometry. Results Compared with HCs, the enhanced glycolysis and mitochondrial oxygen consumption of SLE‐CD4 + T cells were positively associated with disease activity. Treatment with hUC‐MSCs proportionally decreased glucose metabolism and proliferation of SLE‐CD4 + T cells. The hUC‐MSCs treatment significantly diminished supernatant concentrations of interferon‐γ, tumor necrosis factor‐α, interleukin (IL)‐4, and IL‐17 in SLE‐MS group, as well as inhibited HSP90AA1 in the glucose‐activated PI3K‐AKT pathway. In animal experiment, the systemic administration of hUC‐MSCs and inhibition of HSP90AA1 resulted in a reduction of glucose metabolites, enzymes, pro‐inflammatory factor levels, and HSP90AA1 / PI3K/AKT signaling pathway activity. Conclusions The hUC‐MSCs treatment inhibited overactive glucose metabolism of SLE‐CD4 + T cells. HSP90AA1 in the PI3K‐AKT pathway induced by the glucose metabolism may be involved in the anti‐inflammatory function of hUC‐MSCs treatment.

As a traditional Chinese medicine, the adverse hepatotoxicity effects of Pleuropterus multiflorus (Thunb.) Nakai (PM) have been documented. However, nephrotoxicity has been neglected as studies related to kidney toxicity mechanisms are limited. Our previous research reported that extract D [95% ethanol (EtOH) elution, PM-D] in a 70% EtOH PM extract showed more significant hepatotoxicity than other extracts. In the current study, PM-D was continuously administered to mice for 7 days at a dose of 2 g/kg (equivalent to a human dose of 219.8 mg/kg), which increased renal biochemical indexes and caused pathological kidney injury, suggesting renal toxicity. Therefore, network pharmacology and spatially resolved metabolomics were conducted to explore nephrotoxicity mechanisms underpinning PM-D. Network pharmacology indicated that BCL2, HSP90, ESR1, and CTNNB1 genes were core targets, while the phosphoinositide 3-kinase (PI3K)/protein kinase B(AKT)/signaling pathway was significantly enriched. Spatially resolved metabolomics indicated heterogeneous metabolite distribution in the kidney, further indicating that PM-D nephrotoxic metabolic pathways were enriched for α-linolenic acid and linoleic acid metabolism, pyrimidine metabolism, carnitine synthesis, and branched-chain fatty acid oxidation. Our comprehensive analyses highlighted that nephrotoxicity mechanisms were related to oxidative stress and apoptosis induced by disordered energy metabolism, lipid metabolism issues, and imbalanced nucleotide metabolism, which provide a platform for further research into PM nephrotoxicity mechanisms.

The relationship between allergies and cancer has been a topic of debate for decades. This study conducted a systematic review and meta-analysis of 53 studies to evaluate the association between allergies and cancers. Case-control and cohort studies were analyzed, focusing on cancer incidence. The results showed significant negative correlations between allergies and cancers such as colorectal cancer, lymphoma, pancreatic cancer, leukemia, and brain cancers. For colorectal cancer, the pooled odds ratio (OR) for any allergy was 0.77 (95% CI 0.67-0.87). Asthma was associated with a reduced risk of lymphoma (OR 0.81, 95% CI 0.70-0.94) and gynecological cancers (OR 0.72, 95% CI 0.53-0.97). For Pancreatic cancer, any allergy was associated with an OR of 0.68 (95% CI 0.59-0.77). Hay fever showed a strong inverse association with brain cancer risk (OR 0.66, 95% CI 0.58-0.76). However, atopic allergy was positively linked to an increased risk of lymphoma (OR 2.02, 95%CI 1.10-3.70). The study highlighted significant variations in the effects of different allergy types on cancer risks. These findings suggest that allergies may act as protective factors against certain cancers, while atopic allergy may increase the risk of certain cancers. However, the certainty of evidence, assessed using the GRADE framework, was low to very low, and results should be interpreted with caution. In particular, associations for lung cancer, leukemia, and gastrointestinal cancers were supported by very low-certainty evidence, primarily due to reliance on observational designs, heterogeneity among studies. These findings underscore the complex and heterogeneous relationship between allergies and cancer, and highlight the need for further high-quality research to elucidate the underlying mechanisms and assess clinical implications.

Diabetic liver injury (DLI) is a significant complication of diabetes mellitus, leading to severe liver dysfunction and non-alcoholic fatty liver disease (NAFLD). Understanding the metabolic alterations and reprogramming in DLI is critical for identifying therapeutic targets. Despite the prevalence of DLI, its underlying metabolic mechanisms remain poorly understood, and effective treatments are lacking. In this study, we employed a multimodal mass spectrometry imaging approach, combining air-flow-assisted desorption electrospray ionization (AFADESI-MSI) with matrix-assisted laser desorption ionization (MALDI-MSI) to achieve a comprehensive spatial analysis of metabolic changes in DLI model rats, focusing on the potential therapeutic effects of ferulic acid, a compound known for its antioxidant and anti-inflammatory properties. This approach allowed for the wide-coverage and high-resolution visualization of over 200 metabolites in the liver tissues of DLI model rats. The study involved comparing metabolic profiles between control, DLI, and ferulic acid-treated groups, with ferulic acid administered at a dosage of 50 mg/kg daily for 20 weeks. The analysis revealed significant metabolic reprogramming in DLI, characterized by alterations in glucose, lipid, bile acid, and nucleotide metabolism. Specifically, we identified over 100 metabolites with heterogeneous distributions across liver sections, highlighting region-specific metabolic impairments. Ferulic acid treatment notably reversed many of these metabolic disturbances, particularly in glucose and lipid metabolism, suggesting its potential to restore metabolic homeostasis in DLI. This study provides critical insights into the metabolic underpinnings of DLI and demonstrates the therapeutic potential of ferulic acid in modulating these pathways. The findings underscore the utility of AFADESI- and MALDI-MSI in studying liver diseases and suggest that the metabolites identified could serve as novel biomarkers for DLI diagnosis and treatment.

T cells play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE), with their functions regulated by various metabolic pathways. This study explores SLE pathogenesis and the therapeutic effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) via metabolic reprogramming. Clinical data and peripheral blood samples were collected from 15 SLE patients and matched healthy controls. CD4+ T cells were isolated and activated in vitro with anti-CD3/CD28. Following 72 h of co-culture with hUC-MSCs, CD4+ T cell viability was assessed using the CCK-8 assay. The oxygen consumption rate (OCR) and glycolytic proton efflux rate (glycoPER) were measured with a Seahorse analyzer. Cytokine levels were detected by multiplex assay, and transcriptome sequencing was performed. Western blotting analyzed glucose metabolism-related enzymes and signaling pathways in lupus model mice. Compared to healthy controls, activated CD4+ T cells from SLE patients exhibited significantly increased OCR and glycoPER levels (P < 0.05). Following 72 h of co-culture with hUC-MSCs, OCR, glycoPER, cell viability, and pro-inflammatory factors in SLE-CD4+ T cells decreased markedly (P < 0.01). Upregulation of 434 genes and downregulation of 172 genes was observed, particularly in the JAK-STAT and PI3K-Akt pathways. hUC-MSCs inhibited the expression of glucose metabolism-related enzymes and the JAK-STAT and PI3K-Akt signaling pathways in lupus model mice. hUC-MSCs inhibited the proliferation and function of aberrant CD4+ T cells in SLE patients by modulating glycometabolism and the JAK-STAT and PI3K-Akt signaling pathways, providing new insights into the therapeutic mechanisms of MSCs based on metabolic reprogramming.

The prevalence of herbal medicines has gained widespread, particularly among cancer patients seeking adjunctive therapies. Co-administered with anticancer drugs (ACDs) frequently, herbal medicines result in increasing cases of herb-drug interactions (HDIs), following the serious clinical consequences. While herbal medicines pose negative impacts, such as limiting efficacy and increasing toxicity of ACDs, they also offer potential benefits, including enhancing bioavailability, reducing adverse reactions, and reversing tumor drug resistance. This review is the first to systematically characterize HDI molecular mechanisms at both pharmacodynamic (PD) and pharmacokinetic (PK) levels, elucidating how herbal medicines modulate ACDs efficacy and safety through antagonism/synergy/detoxification target, metabolic enzymes, and transporters. In particular, emerging risk prediction methodologies are proposed to assess the clinical occurrence of potential PD/PK-mediated HDIs. We provide a novel insight for promoting the mechanism study of HDIs, facilitating the safe and effective integration of herbal medicines into cancer treatment.

T cell immuno-metabolic regulation plays a key role in the development of systemic lupus erythematosus (SLE). This study aimed to analyze the role of CD4+ T cell glucose metabolism in SLE development. Clinical data and blood samples were collected from 20 untreated SLE patients and healthy controls (HCs) matched for age, sex, and body mass index. After being isolated by magnetic sorting and cultured with anti-CD3/CD28 for 72 h, CD4+ T cells were subjected to real-time metabolic analysis. CD4+ T cell proliferation and cytokines were measured with cell counting kit-8 and Luminex liquid chip assay, respectively. Compared to HCs, SLE-CD4+ T cells exhibited significantly higher glycolytic capacity and mitochondrial oxidative phosphorylation (OXPHOS) (both p < 0.001). Additionally, SLE-CD4+ T cells demonstrated increased proliferation rates and elevated cytokine levels in both plasma and culture supernatants (both p < 0.05). OXPHOS and glycolysis of SLE-CD4+ T cells were positively correlated with SLE disease activity index-2000 (SLEDAI-2K) and cytokines, and negatively correlated with SLE-CD4+ T cell numbers (all p < 0.05). CD4+ T cells from SLE patients showed higher glucose metabolic activity than those from HCs, and the enhanced glucose metabolism of SLE-CD4+ T cells was strongly correlated with disease activity, suggesting that glucose metabolic reprogramming plays an essential role in the pathogenesis of SLE.