Int J Med Sci
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Interferon gamma (IFNγ) is a cytokine implicated in the pathogenesis of autoimmune diseases. SAM and HD domain-containing protein 1 (SAMHD1) is an IFNγ-inducible protein that modulates cellular dNTP levels. Mutations in the human SAMHD1 gene cause Aicardi-Goutières (AG) syndrome, an autoimmune disease sharing similar clinical features with systemic lupus erythematosus (SLE). ⋯ IFNγ decreased Klotho protein expression in MES-13 cells. Treatment of MES-13 cells with recombinant Klotho protein inhibited SAMHD1 expression by blocking IFNγ-induced NFκB nuclear translocation, but showed no effect on JAK-STAT1 signaling. Collectively, our findings support the protective role of Klotho in attenuating lupus nephritis through the inhibition of IFNγ-induced SAMHD1 expression and IFNγ downstream signaling in MES-13 cells.
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Objective: Studies have revealed the alteration of chemokines in the tumour microenvironment in renal clear cell carcinoma (KIRC), which is closely related with immune infiltration and the prognosis of patients with KIRC. This research aims to comprehensively clarify the signature of chemokines in KIRC and the correlation between chemokines and immune infiltration in the TME of KIRC. Methods: The chemokine expression in KIRC were investigated by using multiple multiomics and bioinformatics tools. ⋯ Using the hub-chemokine CXCL10, multiple immune checkpoints including LAG3, CTLA-4 and PD-1 were identified. Conclusion: Our research sheds light on the chemokines and their important role in promoting the tumor microenvironment of KIRC. The findings could provide more data about the prognosis prediction and treatment targets for KIRC.
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Recurrent miscarriage (RM) is a pregnancy complication associated with dysregulation of the maternal-fetal interface. We aimed to identify dysfunctional interactions between trophoblast cells and decidual immune cells in RM. We downloaded single-cell RNA sequencing (scRNA-seq) datasets (GSE214607) from the Gene Expression Omnibus (GEO) datasets for further analysis using the R software. ⋯ We divided trophoblast cells into three types and analyzed their interactions with decidual immune cells. Additionally, we re-clustered NK&T cells and macrophages, identified differentially expressed genes (DEGs), enriched their functions, and compared the cell interactions with trophoblast cells in each cell type. Our single-cell atlas of the maternal-fetal interface revealed alterations in the cellular organization of the decidua and placenta, cell type-specific transcriptome, and cell communication between immune and non-immune cells in RM, which are critical for illuminating the pathophysiology of RM.
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Type 2 diabetes mellitus (T2DM) is associated with increased incidence and mortality of many cancers and infectious diseases. CD3+CD56+ NKT-like cells play pivotal roles in tumor surveillance and infection control. However, little is known about potential alterations in circulating NKT-like cells in T2DM patients. ⋯ Importantly, we further found that the expression of Tim-3 in NKT-like cells from T2DM patients correlated positively with glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) levels, as well as with diabetes duration. In conclusion, these results indicate that NKT-like cells from T2DM patients display an exhausted phenotype and reduced functionality. Moreover, Tim-3 expression on NKT-like cells likely serves a novel biomarker for duration of T2DM.
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Background: Micro RNAs (miRs) expression is involved in the pathogenesis of type 2 diabetes mellitus (T2DM). This study investigates the expression levels of plasma miR-29a, miR-146a, and miR-147b and their correlations with clinical parameters in patients with T2DM. Methods: 105 patients with T2DM who categorized either as newly diagnosed T2DM (n=52) or treated T2DM (n=53) and 93 healthy individuals were included in this study. ⋯ The expression of studied miRs was correlated with several clinical parameters such as blood glucose levels, HbA1C, microalbuminuria, C-peptide, triglyceride levels as well as the HOMA-β index. The expression levels of miR-29a and miR-147b show a potential diagnostic performance to discriminate newly diagnostic T2DM (AUCs=0.77 and 0.84, respectively) and beta-cell dysfunction (AUCs= 0.62 and 0.75, respectively). Conclusions: The plasma miR-29a and miR-147b expression levels in T2DM patients are significantly associated with T2DM while miR-146a shows poor evidence in relation to T2DM. miR-147b shows potential as a biomarker for the diagnosis of T2DM and pancreatic beta cell dysfunction.