The Role of JAK/STAT Signaling Pathway and Its Downstream Influencing Factors in the Treatment of Atherosclerosis

Journal of Cardiovascular Pharmacology and Therapeutics, Год журнала: 2024, Номер 29

Опубликована: Янв. 1, 2024

Atherosclerosis is now widely considered to be a chronic inflammatory disease, with increasing evidence suggesting that lipid alone not the main factor contributing its development. Rather, atherosclerotic plaques contain significant amount of cells, characterized by accumulation monocytes and lymphocytes on vessel wall. This suggests inflammation may play crucial role in occurrence progression atherosclerosis. As research deepens, other pathological factors have also been found influence development disease. The Janus kinase/signal transducer activator transcription (JAK/STAT) pathway recently discovered target has gained attention recent years. Numerous studies provided for causal this atherosclerosis, downstream signaling process. brief review aims explore JAK/STAT representative It provides new theoretical basis clinically affecting atherosclerosis interfering pathway.

Язык: Английский

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The shared biomarkers and pathways of systemic lupus erythematosus and metabolic syndrome analyzed by bioinformatics combining machine learning algorithm and single-cell sequencing analysis

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Окт. 19, 2022

Background Systemic lupus erythematosus (SLE) is one of the most prevalent systemic autoimmune diseases, and metabolic syndrome (MetS) common disorder that contains hypertension, dyslipidemia, obesity. Despite clinical evidence suggested potential associations between SLE MetS, underlying pathogenesis yet unclear. Methods The microarray data sets MetS were obtained from Gene Expression Omnibus (GEO) database. To identify shared genes Differentially Expressed Genes (DEGs) analysis weighted gene co-expression network (WGCNA) conducted. Then, GO KEGG analyses performed, protein-protein interaction (PPI) was constructed. Next, Random Forest LASSO algorithms used to screen hub genes, a diagnostic model built using machine learning technique XG-Boost. Subsequently, CIBERSORT GSVA estimate correlation immune infiltration as well pathways. Finally, significant verified single-cell RNA sequencing (scRNA-seq) data. Results Using limma WGCNA, we identified 153 feature which enriched in immune- metabolic-related Further, 20 screened successfully build prognostic model. Those associated with immunological processes peripheral blood. scRNA-seq results TNFSF13B OAS1 , possessing highest efficacy, mainly expressed by monocytes. Additionally, they showed positive correlations pathways for metabolism xenobiotics cholesterol, both proven be active this comorbidity, shown concentrated Conclusion This study constructed an effective MetS. had cholesterol xenobiotic metabolism. Both these two biomarkers potentially linked monocytes, provides novel insights into combined therapy comorbidity

Язык: Английский

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The molecular subtypes of autoimmune diseases

Computational and Structural Biotechnology Journal, Год журнала: 2024, Номер 23, С. 1348 - 1363

Опубликована: Март 28, 2024

Autoimmune diseases (ADs) are characterized by their complexity and a wide range of clinical differences. Despite patients presenting with similar symptoms disease patterns, reactions to treatments may vary. The current approach personalized medicine, which relies on molecular data, is seen as an effective method address the variability in these diseases. This review examined pathologic classification ADs, such multiple sclerosis lupus nephritis, over time. Acknowledging limitations inherent classification, focus shifted achieve deeper insight into heterogeneity. study outlined established methods findings from categorizing systemic erythematosus (SLE) four subtypes, inflammatory bowel (IBD) two, rheumatoid arthritis (RA) three, (MS) single subtype. It was observed that high inflammation subtype IBD, RA subtype, MS "inflammation & EGF" share similarities. These subtypes all display consistent pattern primarily driven activation JAK-STAT pathway, drugs being those target this signaling pathway. Additionally, identifying markers uniquely associated various within same disease, able describe differences between detail. expected contribute development treatment plans for establish strong basis tailored approaches treating autoimmune

Язык: Английский

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Shared and distinct peripheral blood immune cell landscape in MCTD, SLE, and pSS

Cell & Bioscience, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 10, 2025

Abstract Background Mixed connective tissue disease (MCTD) is a rare autoimmune disease, and little known about its pathogenesis. Furthermore, MCTD, systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS) share many clinical, laboratory, immunological manifestations. This overlap complicates early diagnosis accurate treatment. Methods The transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) from MCTD patients was performed using both bulk RNA sequencing single-cell (scRNA-seq) for the first time. Additionally, we applied scRNA-seq data, along with datasets SLE (GSE135779) pSS (GSE157278) Gene Expression Omnibus database, to characterize compare similarities heterogeneity among SLE, pSS. Results We resolved changes in immune then revealed shared unique features Analyses showed that percentage CD8 + effector T increased, while mucosal-associated invariant were decreased all three diseases. Genes related ‘interferon (IFN) γ response’ ‘IFN α significantly upregulated. SCENIC analysis activation STAT1 IRF7 states, targeting IFN-related genes. IFN-II signaling network notably elevated Unique also identified. Conclusion dissected landscape at resolution, providing new insights into development novel biomarkers immunotherapies MCTD. offer across different diseases, highlighting prospective therapeutic targets.

Язык: Английский

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Altered kynurenine pathway metabolism and association with disease activity in patients with systemic lupus

Amino Acids, Год журнала: 2023, Номер 55(12), С. 1937 - 1947

Опубликована: Ноя. 5, 2023

Язык: Английский

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Uncoupling interferons and the interferon signature explains clinical and transcriptional subsets in SLE

Cell Reports Medicine, Год журнала: 2024, Номер 5(5), С. 101569 - 101569

Опубликована: Май 1, 2024

Systemic lupus erythematosus (SLE) displays a hallmark interferon (IFN) signature. Yet, clinical trials targeting type I IFN (IFN-I) have shown variable efficacy, and blocking IFN-II failed to treat SLE. Here, we show that levels in SLE vary significantly across transcriptional endotypes. Whereas skin involvement correlated with IFN-I alone, systemic features like nephritis associated co-elevation of IFN-I, IFN-II, IFN-III, indicating additive effects severe Notably, while high IFN-II/-III without had limited effect on disease activity, was linked IFN-I-independent profiles (e.g., OXPHOS CD8+GZMH+ cells), IFN-III enhanced IFN-induced gene expression when co-elevated IFN-I. Moreover, dysregulated IFNs do not explain the signature 64% patients or manifestations including cytopenia, serositis, anti-phospholipid syndrome, implying IFN-independent endotypes This study sheds light mechanisms underlying heterogeneity response IFN-targeted therapies trials.

Язык: Английский

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Allogeneic cord blood regulatory T cells decrease dsDNA antibody and improve albuminuria in systemic lupus erythematosus

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Сен. 5, 2023

Background Lupus nephritis (LN) constitutes the most severe organ manifestations of systemic lupus erythematosus (SLE), where pathogenic T cells have been identified to play an essential role in ‘helping’ B make autoantibodies and produce inflammatory cytokines that drive kidney injury SLE. Regulatory (Tregs), responsible for decreasing inflammation, are defective decreased SLE associated with disease progression. We hypothesize treatment allogeneic, healthy Tregs derived from umbilical cord blood (UCB) may arrest such process protect against damage. Methods UCB-Tregs function was examined by their ability suppress CellTrace Violet-labeled peripheral mononuclear (PBMCs) or donor (HD) conventional (Tcons); inhibiting secretion PBMCs. Humanized model established female Rag2 -/- γc mice were transplanted 3 × 10 6 human SLE-PBMCs intravenous injection on day 0, followed single multiple understand impact development. Mice PB assessed weekly flow cytometry. Phenotypic analysis isolated mouse PB, lung, spleen, liver performed Kidney damage quantifying urinary albumin creatinine secretion. Systemic evaluated anti-dsDNA IgG Ab as well immunohistochemistry organs. inflammation determined measuring cytokine levels. Results In vitro , able HD Tcons a similar extent. decrease several including IFN-γ, IP-10, TNF-α, IL-6, IL-17A, sCD40L PBMCs time-dependent manner, corresponding increase suppressor cytokine, IL-10. vivo doses led CD8 + effector different organs circulating cytokines. Improvement skin loss hair; resolution CD3 CD20 Ki67 SLE-PBMC infiltration observed UCB-Treg recipients plasma anti-double stranded DNA antibody levels improved albuminuria. Conclusions can burden SLE, reduce auto-antibody production resolve end especially, improve function. Adoptive therapy should be explored clinical setting.

Язык: Английский

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cGAS-STING pathway in systemic lupus erythematosus: biological implications and therapeutic opportunities

Immunologic Research, Год журнала: 2024, Номер unknown

Опубликована: Авг. 3, 2024

Язык: Английский

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Levamisole, as a viral vaccine adjuvant, induces robust host defense through the modulation of innate and adaptive immune responses

Frontiers in Microbiology, Год журнала: 2025, Номер 15

Опубликована: Янв. 8, 2025

An effective vaccination policy must be implemented to prevent foot-and-mouth disease (FMD). However, the currently used vaccines for FMD have several limitations, including induction of humoral rather than cellular immune responses. To overcome these shortcomings, we assessed efficacy levamisole, a small-molecule immunomodulator, as an adjuvant vaccine. We conducted in vitro studies using murine peritoneal exudate cells (PECs) and porcine peripheral blood mononuclear (PBMCs) vivo mice (experimental animals) pigs (target animals). evaluated levamisole-mediated modulation innate adaptive responses; early, mid-term, long-term immune-inducing effects; modes action; host defense against viral infection. Levamisole treatment promoted IFNγ secretion PECs PBMCs. Additionally, it induced robust long-lasting responses by eliciting high antibody titers virus-neutralizing titers. By activating downstream signaling pathways various pattern-recognition receptors, levamisole stimulated expression multiple cytokines costimulatory molecules. Owing immunostimulatory effects, elicited infections pigs. Our findings demonstrate potential agent. The results also indicate that animal vaccines, can elicit responses, thereby enhancing infections. This study provides promising approach development improved vaccine strategies future.

Язык: Английский

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Identifying potential mechanism and targets for treatment of tertiary lymphoid structure in lupus nephritis based on bioinformatics analysis

International Immunopharmacology, Год журнала: 2025, Номер 148, С. 114084 - 114084

Опубликована: Янв. 23, 2025

Tertiary lymphoid structure (TLS) is an ectopic that develops in non-lymphoid structures. Some studies have shown the TLS formed autoimmune diseases, such as lupus nephropathy (LN), can cause damage to normal tissues and continuous disease progression. Nevertheless, there still a lack of efficient treatments for LN. Thus, study aims identify potential targets therapy Mice datasets relative were obtained from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) identified mice datasets. Then, Genetic Ontological (GO) Kyoto Encyclopedia Genes Genomes (KEGG) analysis performed. Protein-Protein Interaction (PPI) network was constructed. Additionally, hub selected by Cytoscape verified human databases GEO. relationships between immune cells with explored. Finally, two PSMB9 STAT1 validated kidney LN patients mice. 443 DEGs 178 filtered GSE160488 GSE155405, respectively. enrichment results these mostly focused on inflammatory response, cytokine-cytokine receptor interaction, system process. Six recognized Cytoscape. According validation six databases, (PSMB9 STAT1) also significantly patients. Immune infiltration shows are crucial TLS. may be possible treatment interaction cells, process mediated signature takes part advancement formation

Язык: Английский

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