Genome-wide association studies (GWASs) have pinpointed genetic loci associated with juvenile dermatomyositis (JDM). Functional genes within the GWAS loci may be cell type-specific, but their identity remains largely unknown. N-methyladenosine (mA) plays a pivotal role in regulating various cellular processes and is linked to autoimmune diseases. This study aimed to underscore the potential functional genes within the GWAS loci through the analysis of mA-associated SNPs (mA-SNPs), specifically within relevant cell types. JDM-associated mA-SNPs were identified from the GWAS summary dataset. The correlation between mA-SNPs and gene expression was assessed through bulk tissue and single-cell eQTL analyses. To further investigate the relationship between gene expression and JDM, Mendelian randomization analysis was employed. Additionally, differential expression analyses were conducted on bulk tissues, as well as single-cell transcriptomic data comprising 6 JDM patients and 11 juvenile controls (99,396 cells). Seven mA-SNPs associated with JDM were identified. Bulk tissue analysis revealed differential expression of , , , , , , , , , , , and influenced by mA-SNPs, all showing associations with JDM in both differential expression and Mendelian randomization analyses. In single-cell analysis, the six mA-SNPs within the HLA locus acted as cell-type-specific eQTLs, correlating with the expression of , , , , , and in myeloid, T or B cells. Notably, these genes displayed abnormal expression in T, B, and myeloid cells of JDM patients. The present study identified mA-SNPs within JDM susceptibility genes, shedding light on the intricate interplay between mA-SNPs, gene expression, and JDM.

This study aimed to identify genes associated with autophagy and potential diagnostic biomarkers by comparing the gene expression profiles of synovial tissues in patients with rheumatoid arthritis (RA) and healthy individuals, aiming to offer new insights for clinical treatment strategies. We used publicly available datasets to analyze differentially expressed genes (DEGs) between the synovial tissue of RA patients and healthy individuals. Then, we intersected these DEGs with autophagy-related genes to identify autophagy genes in the synovial tissue of RA patients. We further analyzed the biological processes and functions of these genes. Furthermore, we used machine learning to identify characteristic autophagy genes in RA synovial tissue. Finally, we examined the differential expression of these characteristic genes in the blood of RA patients using an external dataset. Our study identified as a potential biomarker for diagnosing RA. gene expression was downregulated in both the synovial tissue and blood of RA patients, suggesting its involvement in multiple biological processes such as local inflammation, oxidative stress, metabolic processes, and immune responses. Our findings suggest that may be a novel biomarker for the clinical diagnosis of RA and may play a crucial role in the pathogenesis of RA. The study provides new insights into the molecular mechanisms of RA and potential new therapeutic targets.

Crohn's disease (CD) presents significant diagnostic and therapeutic challenges due to its unclear etiology, frequent relapses, and limited treatment options. Traditional monitoring often relies on invasive and costly gastrointestinal procedures. This study aimed to identify specific diagnostic markers for CD using advanced computational approaches. Four gene expression datasets from the Gene Expression Omnibus (GEO) were analyzed, identifying differentially expressed genes (DEGs) through gene set enrichment analysis in R. Key biomarkers were selected using machine learning algorithms, including LASSO logistic regression, SVM‑RFE, and Random Forest, and their accuracy was assessed using receiver operating characteristic (ROC) curves and nomogram models. Immune cell infiltration was analyzed using the CIBERSORT algorithm, which helped reveal associations between diagnostic markers and immune cell patterns in CD. From a training set of 605 CD samples and 82 normal controls, we identified eight significant biomarkers: LCN2, FOLH1, CXCL1, FPR1, S100P, IGFBP5, CHP2, and AQP9. The diagnostic model showed high predictive power (AUC=0.954) and performed well in external validation (AUC = 1). Immune cell infiltration analysis highlighted various immune cells involved in CD, with all diagnostic markers strongly linked to immune cell interactions. Our findings propose candidate hub genes and present a nomogram for CD diagnosis, providing potential diagnostic biomarkers for clinical applications in CD.

Lupus nephritis (LN) is a highly prevalent complication of systemic lupus erythematosus (SLE). Long non-coding RNAs (lncRNAs) are essential modulators in multiple types of human diseases, including LN. In the current study, we searched on online GEO database to select out lncRNAs that were differentially expressed in blood samples of LN patients. Through further RT-qPCR analysis, we found that lncRNA Highly Accelerated Region 1 A (HAR1A) is most significantly upregulated in blood samples of LN patients. Functionally, we detected that overexpression of HAR1A could aggravate LPS-induced injury and inflammation. According to the results of bioinformatics analysis and mechanism experiments, we determined that HAR1A binds with miR-149-3p to upregulate SMARCD1 through competing endogenous RNA (ceRNA) mechanism. It has been proven that iNOS is an inflammation inducer. Here, we found that HAR1A/miR-149-3p/SMARCD1 upregulates iNOS expression through enhancing H3K27ac level in iNOS promoter. Previously, we proved that CD8CD103 iTreg cells could alleviate glomerular endothelial cell injury. Moreover, we demonstrated that CD8  CD103 iTreg cells-secreted IL-10 downregulated HAR1A expression by impeding NF-κB pathway activation. In conclusion, this study provides evidences revealing a novel molecular pathway blocked by CD8CD103 iTreg cells in LN.

Asthma poses a major threat to human health. The aim of this study was to identify genetic markers of severe asthma and analyze the relationship between key genes and immune infiltration. Differentially expressed genes (DEGs) were first screened by downloading the training set GSE69683 and validation set GSE137268 from the GEO dataset. SVM-RFE analysis and the LASSO regression model were used to screen key genes, and CIBERSORT was used to assess immune infiltration in the samples. A total of 20 DEGs were identified in this study, mainly enriched for lymph node-like receptors, b-cell receptors, and neutrophil extracellular trap pathway. Comparative validation set GSE137268 identified thioredoxin (TXN) and coagulation factor V (F5) were identified as diagnostic markers of severe asthma. CIBERSORT analysis revealed that TXN and F5 are associated with multiple immune cell infiltrates. In addition, we identified miRNA and TF at the transcriptional level that may regulate F5 and TXN, and found that several commonly used drugs may exert therapeutic effects by targeting F5 and TXN. Taken together, TXN and F5 may be key genes in the development of severe asthma and are associated with immune infiltration. Our study can help to better understand the pathogenesis of asthma and provide new ideas for clinical treatment.

Pyroptosis plays an important role in maintenance of intestinal homeostasis, the abnormal activation of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome can promote the event and development of ulcerative colitis (UC). Its protective effects such as inhibiting pyroptosis in various inflammation-related diseases have been demonstrated, but whether resveratrol (RES) can also alleviate the progression of the disease by inhibiting pyroptosis in UC and the mechanism have rarely been studied. In this study, lipopolysaccharide (LPS) combined with adenosine triphosphate (ATP) was used to induce HT29 human colon cancer cells to construct an intestinal epithelial cell pyroptosis and inflammation model to investigate the anti-inflammatory effect of RES, reveal the regulatory mechanism of RES on pyroptosis, and provide a new theoretical basis for the treatment of UC. experiences, HT29 cells were dividing into control group, LPS/ATP group, RES low-dose group, RES high-dose group, NF-κB inhibitor pyrrolidine dithiocarbamate group (PDTC group), and LPS/ATP+PDTC group. The mRNA expressions of pyroptosis-related indicators such as NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), Caspase-1(CASP1), IL-18, IL-1β, and inflammatory factors such as TNF-α and IL-6 were detected by qRT-PCR. The protein expressions of pyroptosis-related indicators NLRP3, ASC, CASP1, IL-18, IL-1β, NF-κB-p65 in the nucleus, and IκBα and p-IκBα in the cytoplasm were detected by Western blot. Immunofluorescence saw the distribution and expression of NLRP3, ASC and NF-κB-p65 protein in each group. The morphology and degree of pyroptosis in each group were observed by transmission electron microscope. The results showed that compared with the control group, the pyroptosis-related proteins including NLRP3, ASC, CASP1, IL-18, IL-1β, and inflammatory factors including TNF-α and IL-6 in the LPS/ATP group were increased, and LPS/ATP activated the activity of NF-κB signaling pathway. Compared with the LPS/ATP group, RES downregulated the expression of pyroptosis-related proteins and inflammatory factors in HT29 cells, and inhibited the activation of the NF-κB signaling pathway in HT29 cells pyroptosis. RES down-regulates the pyroptosis of HT29 cells induced by LPS/ATP and the expression of pyroptosis-related indicators NLRP3, ASC, CASP1, IL-18, IL-1β and inflammatory factors TNF-α and IL-6 in the inflammatory response and inhibits the occurrence of pyroptosis. The mechanism is related to the inhibition of NF-κB pathway activity.

The study focuses on lung adenocarcinoma (LUAD), a predominant type of lung cancer. Despite advancements in diagnostics and molecular therapies, treatment remains challenging due to its low five-year survival rate. This study aims to investigate the role of the transmembrane protein TMEM164 in ferroptosis and anti-tumor immunity in LUAD, and to evaluate its potential as a therapeutic target. Through cellular experiments (such as QPCR, WB, CCK-8, EdU, Transwell, flow cytometry, CO-IP) and animal model experiments (including HE staining and IHC analysis), the relationship between TMEM164 expression and LUAD progression was explored, with particular attention to its mechanisms in ferroptosis and autophagy. The results show that TMEM164 expression is downregulated in LUAD and is associated with poor prognosis. Increasing TMEM164 expression significantly inhibits cell proliferation, migration, and invasion, while promoting an autophagy process dependent on ATG5 for autophagosome formation, thus facilitating ferroptosis. In mouse models, high TMEM164 expression combined with anti-PD-1 antibodies demonstrated synergistic anti-tumor effects. These findings highlight the critical role of TMEM164 in LUAD, suggesting that modulating TMEM164 expression could open new avenues for LUAD treatment.

It is known that certain human leukocyte antigen (HLA) genes are associated with autoimmune central nervous system (CNS) diseases, such as multiple sclerosis (MS), but their exact role in disease susceptibility and etiopathogenesis remains unclear. The best studied HLA-associated autoimmune CNS disease is MS, and thus will be the primary focus of this review. Other HLA-associated autoimmune CNS diseases, such as autoimmune encephalitis and neuromyelitis optica will be discussed. The lack of animal models to accurately capture the complex human autoimmune response remains a major challenge. HLA transgenic () mice provide researchers with powerful tools to investigate the underlying mechanisms promoting susceptibility and progression of HLA-associated autoimmune CNS diseases, as well as for elucidating the myelin epitopes potentially targeted by T cells in autoimmune disease patients. We will discuss the potential role(s) of autoimmune disease-associated alleles in autoimmune CNS diseases and highlight information provided by studies using HLA mice to investigate the underlying pathological mechanisms and opportunities to use these models for development of novel therapies.

Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA.

Animal models are an important tool in the research of chronic autoimmune diseases, like systemic lupus erythematosus (SLE). MRL-Fas mice are one of different lupus models that develop spontaneously an SLE-like disease with autoantibodies and immune complex deposition that leads into damage of different organs. In contrast to human SLE, both sexes of MRL-Fas mice develop a similar autoimmune disease. Due to the sex bias in human and the delayed disease progression in male MRL-Fas mice, the majority of studies have been performed in female mice. To determine the suitability of male MRL-Fas mice for SLE research, especially with regard to the 3 R-principle and animal welfare, analyses of phenotype, inflammation and damage with focus on kidney and spleen were performed in mice of both sexes. Female mice developed lymphadenopathy and skin lesions earlier as males. At an age of 3.5 month, more immune cells infiltrated kidney and spleen in females compared to males. At the age of 5 months, however, substantially less sex-specific differences were detected. Since other studies have shown differences between both sexes on other manifestations like autoimmune pancreatitis and Sjögren syndrome in MRL-Fas mice, the use of male mice as part of 3 R-principle and animal welfare must be carefully considered.

Lupus, a systemic autoimmune disease shaped by gene-environment interplay, often progresses to endstage renal failure. While subchronic systemic exposure to bacterial lipopolysaccharide (LPS) triggers autoimmunity and glomerulonephritis in lupus-prone mice, it is unknown if inhaling LPS, which is common in certain occupations, can similarly trigger lupus. Here we determined how subchronic intranasal (IN) LPS instillation influences autoimmunity and glomerulonephritis development in lupusprone NZBWF1 female mice. Briefly, mice were IN-instilled with vehicle or E. coli LPS (0.8 μg/g) twice weekly for 5 wk, followed by necropsy. For systemic comparison, additional cohorts of mice were injected with LPS intraperitoneally (IP) using identical doses/timing. Lungs were assessed for inflammatory and autoimmune responses and then related to systemic autoimmunity and glomerulonephritis. IN/LPS exposure induced in the lung: i) leukocyte infiltration, ii)mRNA signatures for cytokines, chemokines, IFN-regulated, and cell death-related genes, iii) ectopic lymphoid tissue formation, and iv)diverse IgM and IgG autoantibodies (AAbs). Pulmonary effects coincided with enlarged spleens, elevated plasma IgG AAbs, and inflamed IgG-containing kidney glomeruli. In contrast, IP/LPS treatment induced systemic autoimmunity and glomerulonephritis without pulmonary manifestations. Taken together, these preclinical findings suggest the lung could serve as a critical nexus for triggering autoimmunity by respirable LPS in genetically predisposed individuals.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune system dysfunction that can lead to serious health issues and mortality. Recent investigations highlight the role of gut microbiota alterations in modulating inflammation and disease severity in SLE. This review specifically summaries the variations in gut microbiota composition across various murine models of lupus. By focusing on these differences, we aim to elucidate the intricate relationship between gut microbiota dysbiosis and the development and progression of SLE in preclinical settings.

Dysregulated circular RNAs (circRNAs) are involved in osteoarthritis (OA) progression.

Keratinocytes in mucosal and skin tissues maintain tissue integrity desmosomes and desmoglein-3 (Dsg3). Pemphigus Vulgaris (PV) is a life-threatening autoimmune blistering disease characterized by autoantibodies against Dsg3, disrupting desmosomes. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates oxidative stress responses crucial for skin tissue protection. Although the pathogenesis of PV is known, the detailed molecular events remain unclear. This study investigates changes in Nrf2 expression in keratinocytes following pathogenic anti-Dsg3 antibody AK23 exposure, using dose- and time-dependent studies employing immunofluorescence analysis. N/TERT keratinocytes were cultured in keratinocytes serum-free medium and treated with AK23 at varying doses (5 µg/mL,40µg/mL,75µg/mL) and durations (2, 6, 24 h). Immunofluorescence staining was performed to assess the expression of Nrf2 and Dsg3. All fluorescent images were analyzed using ImageJ software. A dose-dependent increase in Dsg3 was noted following AK23 treatment, while Nrf2 expression and subcellular localization varied. Time-course analyses showed decreased Nrf2 at 24 h and increased Dsg3 levels. Early time-point (2 and 6 h) variations were evident in Nrf2 levels. This study highlights the impact of AK23 on Nrf2 expression, potentially disrupting Nrf2-mediated cytoprotection and implicating oxidative stress (ROS generation) in PV pathogenesis. Further investigation is necessary to validate the findings.

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that causes a breakdown of immune tolerance. Current treatments mainly involve general immunosuppression, increasing the risk of infections. On the other hand, Bacillus Calmette-Guérin (BCG) has been investigated as a potential therapy for autoimmune diseases in recent years, prompting an ongoing investigation. This study aimed to evaluate the effect of BCG vaccination on early and late clinical presentation of SLE in a murine disease model. MRL/MPJ-Fas mice were immunized with BCG or treated with PBS as a control. The progress of the disease was evaluated at 27 days post-immunization (dpi) (early) and 56 dpi (late). Clinical parameters and proteinuria were monitored. Blood samples were collected for measurement of antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), and cytokine determination was performed using ELISA. Samples collected from mice were analyzed by flow cytometry and histopathology. We observed a clinical improvement in BCG-treated mice, reduced proteinuria in the latter stages of the disease, and decreased TNF-α. However, BCG did not elicit significant changes in ANAs, anti-dsDNA, histopathological scores, or immune cell infiltration. BCG was only partially beneficial in an SLE mouse model, and further research is needed to determine whether the immunity induced by this vaccine can counteract lupus's autoimmune response.

Osteoarthritis (OA) is a worldwide joint disease, leading to the physical pain, stiffness, and even disability. Lactate dehydrogenase A (LDHA) is known as a lactylation mediator that can regulate histone lactylation of its target genes. However, the role of LDHA-mediated histone H3 lysine 18 lactylation (H3K18la) in OA progression is yet to be clarified. Our study aims at revealing the role and mechanism of LDHA-mediated histone lactylation in the glycolysis of chondrocytes. In this study, we determined at first that the H3K18la level was enhanced in OA. Energy metabolism such as glycolysis is often altered in OA progress. Therefore, we further explored the mechanism mediating glycolysis and thus promoting OA progress. Moreover, glycolysis was enhanced in LPS-induced OA cell model, as evidenced by the increased glucose consumption and lactate production. Furthermore, we silenced LDHA for loss-of-function assays. The results showed that knockdown of LDHA suppressed glycolysis of LPS-induced chondrocytes. animal study demonstrated that knockout of LDHA recovered cartilage injury of OA mice. Mechanistically, we uncovered that LDHA-mediated H3K18la in TPI1 promoter enhanced the transcription activity of TPI1. Mutation of K69 site was found to ameliorate LPS-induced glycolysis in OA cell model. In conclusion, our study reveals the role of LDHA-mediated H3K18la of TPI1 promoter in OA progress.

Childhood asthma, a common chronic childhood disease, leads to high mortality and morbidity in the world. Airway smooth muscle cells (ASMCs) is a group of multifunctional cells that has been found to be correlated with the pathogenesis of asthma. Astragaloside IV (AS-IV) is a compound extracted from , which has the anti-asthmatic effect. However, the role of molecular mechanisms regulated by AS-IV in the biological processes of ASMCs in asthma remains unclear. Our current study aims to investigate the downstream molecular mechanism of AS-IV in modulating the aberrant proliferation and pyroptosis of ASMCs in asthma. At first, we determined that the viability of ASMCs could be efficiently suppressed by AS-IV treatment (200 μM). Moreover, AS-IV promoted the pyroptosis and suppressed PDGF-BB-induced aberrant proliferation. Through mechanism investigation, we confirmed that AS-IV could suppress high mobility group box 1 (HMGB1) expression and prevent it from entering the cytoplasm. Subsequently, AS-IV blocked the interaction between HMGB1 and advanced glycosylation end product-specific receptor (RAGE) to inactivate NF-κB pathway. Finally, experiments demonstrated that AS-IV treatment can alleviate the lung inflammation in asthma mice. Collectively, AS-IV alleviates asthma and suppresses the pyroptosis of AMSCs through blocking HMGB1/RAGE axis to inactivate NF-κB pathway.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent arteriovenous thrombosis and pathological pregnancy, accompanied by persistent antiphospholipid antibodies, (aPL). The incidence of APS is increasing year by year, clinicians lack of understanding of this type of disease, easy to misdiagnose and miss the diagnosis. Therefore, it is extremely important to establish a suitable animal model to reduce the process of disease development as much as possible and improve clinicians' understanding and understanding. This review will summarize the animal models of APS from the aspects of modeling methods, modeling mechanism, evaluation indicators and advantages and disadvantages of methods, providing a reference for finding an animal model highly similar to human APS, helping researchers to further clarify the pathogenesis of APS and find potential therapeutic targets, so as to achieve early diagnosis, early intervention, and ultimately improve the prognosis of patients.

Anti-Ro/SS-A antibodies are prevalent across systemic autoimmune rheumatic diseases (SARDs) and may signify a distinctive phenotype. This study aimed to identify protein biomarkers associated with symptom burden and health-related quality of life (HR-QoL), and use protein-based stratification to identify clinically meaningful clusters and inflammatory pathways implicated. Anti-Ro positive SARD patients were enrolled in a 6-month pilot study. HR-QoL was determined using a patient-reported visual analogue scale, and symptom burden was assessed with the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI). Proximity extension immunoassays measured normalized protein expression (NPX) across 92 inflammatory proteins. Linear regression identified proteins linked to patient outcomes. Unsupervised hierarchical clustering of baseline NPX identified patient clusters. Functional protein association networks were visualized using String V.12.0. Diagnostic groups showed no differences in HR-QoL or physician global assessment (PhGA). Poor HR-QoL and high symptom burden correlated with downregulated inflammatory proteins, while PhGA correlated with upregulated proteins. Two distinct clusters were identified; Cluster 1, 'low expression cluster' exhibited higher symptom burden and more impaired HR-QoL, while Cluster 2, 'high expression cluster' correlated with a higher physician global assessment (PhGA). Key hub proteins included TGF-β1, CXCL-8, and CCL-2. This study identified patient clusters across the Ro-positive SARD, linking symptom burden to specific proteomic profiles. Unraveling novel protein networks associated with symptom burden and poor HR-QoL may identify therapeutic targets, which address patient-reported outcome measures (PROMs) across several disease indications.

This study aims to explore the effect of NONHSAT042241 on the function of rheumatoid arthritis -fibroblast-like synoviocyte (RA-FLS) and the underlying mechanisms.