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

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the paraffin‑embedded glioma tissue sections shown in Fig. 2A on p. 494, the Ki‑67/Grade III and DTX3L/Grade IV data panels contained an overlapping section, suggesting that these data panels were derived from the same original source where different experimental groups were reported. In addition, GAPDH control western blots featured in Figs. 1C and 4E were found to be strikingly similar, even though the experimental conditions reported for these figure parts were different. The authors have been contacted by the Editorial Office to offer an explanation for these apparent anomalies in the presentation of the data in their paper, and we are awaiting their response. Due to the fact that we have been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of these potential problems while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 40: 491‑498, 2017; DOI: 10.3892/ijmm.2017.3023].

BACKGROUND:Systemic lupus erythematosus (SLE) is an autoimmune disease with marked female predominance. Lupus nephritis (LN), one of its most severe manifestations, is strongly associated with aberrant activation of signal transducer and activator of transcription 3 (STAT3). Estrogen receptor β (ERβ) has been reported to exert immunoregulatory effects, but its role in restraining STAT3 signaling in LN remains unclear. PURPOSE:This study aimed to investigate whether genistein, a phytoestrogen with selective affinity for ERβ, can modulate the ERβ-STAT3 axis to attenuate lupus nephritis. METHODS:The therapeutic effects of genistein were evaluated in MRL/lpr and pristane-induced lupus mouse models and in LPS-stimulated macrophages. Macrophage polarization, oxidative stress, mitochondrial function, and ERβ-STAT3 signaling were assessed using flow cytometry, biochemical assays, immunoblotting, and bioinformatic analyses. RESULTS:Genistein significantly ameliorated renal injury, reduced proteinuria, and decreased serum autoantibody and IL-6 levels in lupus models. Mechanistically, genistein suppressed M1 macrophage polarization by activating ERβ and inhibiting STAT3 and NF-κB signaling. Genistein also attenuated oxidative stress by preserving mitochondrial membrane potential, reducing reactive oxygen species production, and restoring antioxidant capacity. Pharmacological blockade of ERβ markedly attenuated the anti-inflammatory effects of genistein, confirming ERβ-dependent regulation of STAT3 signaling. CONCLUSION:This study identifies ERβ as a negative regulator of STAT3-driven inflammation and demonstrates that genistein therapeutically engages this axis to suppress macrophage-mediated renal injury, offering a promising therapeutic strategy for lupus nephritis.

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.

Background Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease involving inflammatory macrophage polarization and hepatic acute-phase responses. Serum amyloid A3 (SAA3) is elevated in lupus-prone mice and may participate in the immune link between liver inflammation and macrophage responses. Jieduquyuziyin Prescription (JP) is a traditional formula used clinically for SLE, but its chemical basis and SAA3-related immunomodulatory mechanisms remain incompletely defined. Purpose This study investigated the effects of JP on SLE-related inflammatory phenotypes, hepatocyte SAA3 expression, and macrophage MAPK14/p38-related M1 polarization responses, and examined the interaction between representative JP constituents and MAPK14. Methods MRL/Lpr mice were used to evaluate the in vivo effects of JP. LC-MS and HPLC were used for chemical characterization. Network pharmacology, primary splenic macrophages, primary hepatocytes, and macrophage-naive CD4⁺ T cell co-culture systems were used to characterize JP-associated immune responses. Western blotting, flow cytometry, ELISA, and immunofluorescence were performed to assess p38 phosphorylation, macrophage polarization, cytokines, and SAA3. Molecular docking, SPR, molecular dynamics simulations, and ADP-Glo™ kinase assay were used to evaluate MAPK14 binding and kinase activity modulation by representative constituents. Results JP treatment improved survival and renal-related indices in MRL/Lpr mice, accompanied by lower serum SAA3 levels, reduced splenic F4/80⁺ CD86⁺ macrophages, and decreased F4/80/iNOS signals. JP-medicated serum reduced SAA3-induced p38 phosphorylation, iNOS expression, and IL-6 and IL-1β release, while increasing Arg-1 expression and F4/80⁺ CD206⁺ cells. JP-medicated serum also reduced IL-6-induced SAA3 expression in hepatocytes. In co-culture, systems containing SAA3-treated macrophages showed increased CD4⁺ IL-17A⁺ cells and IL-17 levels, whereas JP treatment reduced these readouts. Hesperidin, glycyrrhizic acid, and paeoniflorin were detected in JP decoction and JP-medicated serum and generated measurable binding responses to MAPK14. The three-compound mixture and individual constituents reduced recombinant MAPK14 kinase activity, with stronger activity observed for the mixture. Conclusion JP treatment was associated with reduced hepatocyte SAA3 expression, attenuated macrophage MAPK14/p38-related M1 inflammatory responses, and decreased Th17-associated inflammatory indices. MAPK14 may serve as a mechanistically relevant molecular node engaged by representative JP constituents, providing experimental support for JP-mediated regulation of SLE-related inflammatory networks.

Pomegranate peel is a food industry waste rich in polyphenols. To date, its effect in alleviating fatigue remains unclear. This study aimed to characterize the chemical composition of pomegranate peel polyphenols (PPPs), evaluate its antioxidant and anti-fatigue capacities, and investigate the underlying mechanism. In the current study, twenty main compounds, primarily flavonoids, phenolic acids, and anthocyanins, were identified from PPPs using LC-MS/MS. In H2O2-induced HepG2 cells, PPPs promoted cellular repair and reduced the production of intracellular malondialdehyde (MDA) and reactive oxygen species (ROS) via enhancing the activity of antioxidant enzymes (SOD, CAT, and GSH-Px). In the endurance swimming-induced fatigue mice model, PPPs prolonged mice exhaustion times, reduced accumulation of fatigue-related metabolites (BUN, LA, BA, LDH and CK), and alleviated liver and muscle tissue damage. Mechanistically, PPPs mitigated oxidative stress via activation of the Keap1/Nrf2 pathway, leading to increased expression of hemeoxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Furthermore, PPPs stimulated energy metabolism by activating the AMPK/PGC-1α/PPAR-α pathway, promoting mitochondrial biogenesis, enhancing glycogen storage, increasing ATPase activity (Na+-K+-ATPase, Ca2+-Mg2+-ATPase, and T-ATPase) and accelerating lipid β-oxidation. These findings suggest that PPPs is a promising anti-fatigue supplement and could be further utilized in the nutritional industry.

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.

Gingival fibroblasts play a pivotal role in the progression of periodontitis, and targeted inhibition of calcium ion influx in gingival fibroblasts represents a potential therapeutic strategy for ameliorating periodontal inflammation. The N-terminal 20-amino-acid peptide derived from cementum protein 1 (N20) possesses calcium-chelating capacity, whereas the glycine-proline-hydroxyproline (GPH) tripeptide confers collagen-targeting binding ability. In this study, we engineered a GPH-modified N20 peptide (GPH-N20) and systematically investigated its anti-inflammatory effects in vitro. Our results demonstrated that GPH-N20 achieved high-efficiency targeted binding to both normal gingival fibroblasts and lipopolysaccharide (LPS)-stimulated inflammatory macrophages. This specific binding significantly blocked intracellular calcium influx and aberrant calcium signaling activation, and effectively abrogated LPS-induced pro-inflammatory responses in these cells. Mechanistic analyses further revealed that the dual functions of GPH-N20, its collagen-targeting capacity and calcium-chelating activity, synergistically suppressed the activation of the LPS-triggered Ca2+/calmodulin-dependent protein kinase II / nuclear factor-κB (CaMKII/NF-κB) signaling pathway, thereby attenuating the downstream pro-inflammatory cascades. Collectively, these findings validate that GPH-N20 is a promising anti-inflammatory agent with specific efficacy in alleviating gingival tissue inflammation, and thus provides a novel therapeutic candidate for the clinical management of periodontal inflammatory diseases.

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.

Acute lung injury (ALI) is a prevalent critical condition for which effective treatments remain elusive. Ferroptosis plays a significant role in the pathophysiology of ALI. The deubiquitinating enzyme YOD1 is implicated in the regulation of infectious diseases; however, its specific role in ALI and ferroptosis is not yet fully understood. In this study, we observed that YOD1 expression was notably elevated in the lung tissue and primary alveolar type II (ATII) cells of mice subjected to lipopolysaccharide (LPS)-induced ALI. Moreover, YOD1 deficiency significantly mitigated ferroptosis and damage to the alveolar epithelial barrier. Mechanistically, YOD1 interacts directly with NCOA4 through its OTU domain, inhibiting K48-linked ubiquitination at the K343/K353 lysis residue of NCOA4, thus facilitating NCOA4-mediated autophagic degradation of FTH1 and promoting ferroptosis. Overall, our findings indicate that YOD1 regulates NCOA4 via deubiquitination, suggesting it may serve as a potential therapeutic target for ALI. This study reveals that the deubiquitinase YOD1 is upregulated in LPS-induced acute lung injury (ALI) and exacerbates ferroptosis by deubiquitinating and stabilizing NCOA4, thereby promoting NCOA4-mediated ferritinophagy. YOD1 deficiency alleviated lung injury, suggesting YOD1 as a potential therapeutic target for ALI.

ABSTRACT Irreversible renal damage in lupus nephritis (LN) results from critical podocyte injury. Disruption in the actin cytoskeleton initiates mitochondrial fission to exacerbate podocyte injury. While ginsenoside compound K (CK) alleviates podocyte injury in lupus‐prone mice, its mechanism in regulating mitochondrial dynamics underlying remains elusive. Based on the open‐source single‐cell RNA sequencing dataset, this study clarified CK's role in alleviating podocyte injury in MRL/ lpr mice by regulating cytoskeleton‐mediated mitochondrial fission and elucidated the molecular mechanisms underlying the BA receptor–YAP axis. MRL/ lpr mice were administered CK (20 or 40 mg/kg) for 10 weeks. Renal function and pathological changes were evaluated, along with renal metabolite profiles and metabolomics analysis. We analyzed publicly available single‐cell RNA sequencing data to specifically profile gene mapping and enrichment analysis during immune‐mediated renal injury. Furthermore, podocyte‐based in vitro assays were conducted to investigate the impact of the BA receptors–YAP axis on mitochondrial dynamics. CK effectively cleared anti‐dsDNA antibodies, attenuated systemic inflammation, and improved renal function through resolving immune complex deposition. Mechanistically, CK restored actin cytoskeleton integrity via Rho GTPase regulation and reshaped BA metabolism to activate TGR5/FXR receptors in podocytes. This dual action suppressed DRP1 s616 phosphorylation, inhibiting excessive mitochondrial fission, regulating while enhancing TFAM‐mediated mtDNA replication for mitochondrial homeostasis. Concurrently, CK attenuated podocyte apoptosis through Hippo signaling inhibition and YAP activation. In conclusion, CK ameliorates podocyte injury by preventing excessive mitochondrial fission through the BA receptors–YAP axis, thus providing a potential therapy for LN.

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.

Rheumatoid arthritis (RA) is a severe inflammatory autoimmune disease with metabolic changes. RA patients have abnormalities in glycolysis, amino acid metabolism, choline metabolism, and fatty acid synthesis. The differential metabolites in individuals of RA patients and animal models were explored to find the potential biomarkers for the risk prediction, diagnosis, and prognosis of RA in the perspective of metabolism. Moreover, we discussed the changes of related metabolites after treatment with anti-rheumatic drugs, Traditional Chinese Medicine (TCM) and potential metabolites for the treatment of RA to explore promising metabolites. In addition, the immunological mechanism of TCM in the treatment of RA from the perspective of metabolism was also clarified. For the perspectives of research and application of the beneficial metabolites in clinic, relevant technologies and focuses for the future studies in the field have been proposed accordingly.

Immune complex deposition is a critical factor in early renal damage associated with lupus nephritis (LN), and targeting plasma cell aggregation offers a promising therapeutic strategy. Ginsenoside compound K (i.e., 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol) (CK), a derivative of ginsenoside, has indicated significant potential in alleviating renal damage in lupus-prone mice, potentially by modulating B cell dynamics in response to endoplasmic reticulum (ER) stress. In this study, CK (20 or 40 mg/kg) was orally administered to female MRL/lpr mice for 10 weeks. The effects of CK on B cell subpopulations, renal function, and histopathological changes were evaluated. Single-cell ribonucleic acid sequencing was employed to analyze gene expression profile and pseudotime trajectories during B cell-mediated renal injury. Additionally, in vitro B cell assays were conducted to explore the role of the sirtuin-1 (SIRT1)-X-box binding protein 1 (XBP1) axis in ER stress. Our findings demonstrated that CK effectively reduced anti-double stranded DNA (dsDNA) antibody levels, alleviated systemic inflammation, improved renal function, and facilitated the clearance of deposited immune complexes. CK likely suppressed the unfolded protein response (UPR), delaying the differentiation of renal-activated B cells into plasma cells. It promoted B cell-specific SIRT1 activation and inhibited the splicing of XBP1 into its active form, XBP1s. CK also restored ER morphology by interacting with calmodulin (CALM) to maintain ER calcium storage, reinforcing SIRT1 functional integrity and promoting XBP1 deacetylation, thereby limiting plasma cell differentiation. In conclusion, CK mitigates plasma cell accumulation in the renal microenvironment by preventing SIRT1-mediated XBP1 splicing, offering a potential therapeutic approach for LN.

Air pollutants contribute to the occurrence and development of asthma by impairing the airway epithelial barrier. However, underlying molecular mechanisms remain unknown. The present study investigated whether co‑exposure to the air pollutant benzo[a]pyrene (BaP) and ovalbumin (OVA) enhanced OVA‑induced epithelial tight junction disruption and explored the potential mechanisms involved. Asthma mouse and airway epithelial cell models were established and exposed to BaP. Lung pathology, immunoglobulin E (IgE), tight junction proteins zonula occludens‑1 (ZO‑1) and occludin, reactive oxygen species (ROS), NOD‑like receptor protein 3 (NLRP3), apoptosis‑associated speck‑like protein containing a CARD, caspase‑1, interleukin (IL)‑18 and IL‑1β were assessed by hematoxylin‑eosin staining, enzyme‑linked immunosorbent assay, western blotting, immunohistochemistry and immunofluorescence. Inhibitors of ROS and NLRP3 were used to assess their effect on ZO‑1 and occludin and downstream signaling pathways to clarify BaP‑induced damage. Lung tissue damage was exacerbated by BaP, the IgE level increased and the ZO‑1 and occludin expression reduced in both models, thereby disrupting airway epithelial tight junctions. Additionally, BaP increased ROS levels and activated the NLRP3/caspase‑1 signaling pathway. However, reducing ROS and NLRP3 restored the ZO‑1 and occludin expression and improved epithelial integrity. Airway tight junction disruption was promoted by BaP by activating the ROS‑driven NLRP3/caspase‑1 signaling pathway.

The natural oil extracted from Isaria cicadae Miquel (ICSO), a rare mushroom species, has demonstrated efficacy in alleviating intestinal fibrosis associated with Crohn's disease (CD), although its precise mechanisms remain unclear. This study employed an integrated approach combining network pharmacology, molecular docking, and experimental validation to investigate ICSO's therapeutic potential. ICSO obtained through Soxhlet extraction was characterized by GC-MS, revealing 21 components including 16 fatty acids (84.82 % of total composition). In a TNBS-induced Caco-2 cell fibrosis model, ICSO (20-200 mu g/mL) dose-dependently attenuated intestinal fibrosis, significantly reducing hydroxyproline accumulation (P < 0.05) and suppressing type I and II collagen deposition (P < 0.01). Furthermore, Consistent with network pharmacology predictions, ICSO (50, 100, and 200 mu g/mL) markedly inhibited EGFR overexpression, suppressed SRC activation, while downregulating AKT (P < 0.001) and MAPK1 phosphorylation (P < 0.05). These coordinated mechanisms effectively ameliorated epithelial-mesenchymal transition (EMT) and prevented intestinal fibrosis progression in CD.

BACKGROUND:Sepsis is the leading cause of death in critically ill patients, with an in-hospital mortality rate of approximately 25% to 40%. Coagulation activation serves as an initial factor to the progression of sepsis into multiple organ dysfunction syndrome (MODS). Therefore, anticoagulant therapy may be beneficial. Both preclinical experiments and clinical studies have evaluated the protective effect of nafamostat mesilate (NM) in sepsis. However, there is still a lack of randomized controlled trials (RCTs) to further confirm the therapeutic effect and safety of NM in sepsis patients. METHODS:This multicenter, double-blind, RCT was designed to recruit 778 subjects who met Sepsis 3.0 criteria. Participants will be randomly assigned (1:1) to receive either intravenous administration of NM or glucose along with standard treatment. The primary outcome is the all-cause mortality rate in the intensive care unit (ICU), and the secondary outcomes include the improvement in SOFA scores, changes in Japanese Association for Acute Medicine (JAAM)/International Society on Thrombosis and Hemostasis (ISTH) scores, 28-day all-cause mortality rate, and the incidence of adverse events. The allocation will remain concealed from investigators, participants, and statisticians to maintain blinding. DISCUSSION:The EASNMS trial aims to assess the efficacy and safety of NM for treating sepsis across various regions in China. As an additional treatment option, NM may potentially enhance the prognosis of sepsis patients. ETHICS AND DISSEMINATION:Ethical approval has been obtained from all ethics committees of the involved centers. The findings of this study will be shared in peer-reviewed journals and will be presented at conferences. TRIAL REGISTRATION:ClinicalTrials.gov NCT06078839. Registered on September 20, 2023.

Systemic lupus erythematosus (SLE), a multifaceted autoimmune disorder, has lupus nephritis (LN) as one of its grave complications and is strongly associated with dyslipidemia. This investigation sought to delineate renal-specific lipid metabolism-related genes (LMRGs) signatures in lupus nephritis (LN) through integrated bioinformatics analysis and explore the therapeutic effect of Alisol B 23-acetate (ABA). Analysis of LN datasets revealed multiple dysregulated pathways and identified 11 key LMRGs, including CD36, associated with LN. In vitro, ABA suppressed CD36 activity, thereby reducing inflammation and lipid accumulation. In vivo, ABA improved lipid metabolism, attenuated immune cell infiltration, and ameliorated renal pathology. Renal lipid metabolic reprogramming exacerbates LN pathology, and ABA shows potential in treating LN by regulating key LMRGs.

Observational studies have shown that physical activity and sedentary behavior are associated with aging. However, whether these associations underlie causal effects remains unknown. Thus, this study aimed to assess the genetic correlation and causal relationships between genetically predicted physical activity, sedentary behavior, and aging. Using linkage disequilibrium score regression (LDSC) and Mendelian Randomization (MR). Genetic variants associated with leisure screen time (LST, as an indicator of sedentary behavior), moderate-to-vigorous physical activity (MVPA), and four aging-related traits (90th survival percentile, facial aging, telomere length, and frailty index) were obtained from genome-wide association studies (GWAS). The primary MR analyses were performed using the inverse variance weighted (IVW) method, followed by various sensitivity and validation analyses. Univariable MR analysis indicated significant associations of LST with telomere length (β = − 0.04, P = 4.95E−06), and facial aging (β = 0.11, P = 2.28E−09), frailty index (β = 0.17, P = 1.93E−35). MVPA had a significant causality with the frailty index (β = − 0.28, P = 6.46E−09). These associations weakened in Multivariable MR Analysis, but the frailty index remained significantly correlated after adjustment. LDSC further supported the genetic correlations identified in the MR analysis. Additionally, pathway analyses, including the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), highlighted potential mechanisms linking LST and aging outcomes. This study reveals that LST and MVPA may play a causal role in the process of aging. Accordingly, public health efforts to promote increased physical activity and reduce sedentary time can effectively combat accelerated aging.

Objective: To investigate the effects of the Tibetan medicine 15-flavor gentian flower pills combined with budesonide on the expression of inflammatory factors in asthmatic mice. Methods: 50 healthy female BALB/c mice of 6–8 weeks were selected and randomly divided into five groups, including the control group, the asthma group, the budesonide group, the 15-flavor gentian flower pill group, and the combination group. The budesonide group was fed with budesonide suspension, the 15-flavor gentian flower pill group was fed with 15-flavor gentian flower pill suspension, and the combined group was fed with budesonide suspension and 15-flavor gentian flower pill suspension. Asthma symptoms of mice in the five groups were recorded. Serum ovalbumin (OVA)-specific antibody levels, the proportion of eosinophils in bronchoalveolar lavage fluid (BALF), and the relative expression of inflammatory factors were compared among the five groups of mice. Results: Mice in the asthma group, budesonide group, 15-flavor gentian flower pill group, and combination group presented asthma symptoms. The OVA-specific antibody levels, the proportion of eosinophils, and expression of inflammatory factors (IL-4, IL-33, IL-5, and TNF-α) in the budesonide group, the 15-flavor gentian flower pill group, and the combined group were significantly better than those in the asthma group (P < 0.05); the OVA-specific antibody levels, the proportion of eosinophils, and expression of inflammatory factors (IL-4, IL-33, IL-5, and TNF-α) in the combined group were significantly lower than those in the budesonide group and the 15-flavor gentian flower pill group (P < 0.05). Conclusion: The Tibetan medicine 15-flavor gentian flower pills combined with budesonide can effectively inhibit the expression of inflammatory factors in asthmatic mice.