Int J Med Sci
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Diabetic kidney disease (DKD) is the gradual loss of renal function occurring in patients with diabetes. Stromal cell-derived factor-1 (SDF-1, encoded by SDF-1 gene) is a chemokine that binds to its receptor, CXCR4, to mediate many aspects of renal biology. To test the potential impact of SDF-1/CXCR4 gene variations on the risk for DKD, single-nucleotide polymorphisms (SNPs) of SDF-1/CXCR4 genes were genotyped in 388 DKD patients and 335 DKD-free diabetic controls. ⋯ Instead, another SNP of SDF-1 gene, rs266085, was found in association with the advanced form of DKD (TC vs TT, AOR=2.106, p=0.027; TC+CC vs TT, AOR=2.130, p=0.019), indicating differential impacts of SDF-1 gene polymorphisms on the progressive loss of renal function in diabetic patients. Moreover, preliminary survey of public gene expression datasets showed that rs1801157 and rs266085 modulated SDF-1 expression in many human tissues, and SDF-1/CXCR4 levels were elevated in renal tissues of DKD patients. These data suggest that allele-specific expression of SDF-1 gene may influence DKD progression.
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Background: Frozen shoulder (FS) is characterized by the thickening and fibrosis of the joint capsule, leading to joint contracture and a reduction in joint volume. The precise etiology responsible for these pathological changes remains elusive. Therefore, the primary aim of this study was to explore the potential involvement of pathogenic genes in FS and analyze their underlying roles in the disease progression. ⋯ Notably, a causal relationship between ADAMTS1 and immune cell infiltration in FS was observed. Conclusion: Our study suggested genetic predisposition to higher expression levels of ADAMTS1, NR4A2, PARD6G and SMKR1, was associated with an increased risk of FS. Further investigations elucidating the functional roles of these genes will enhance our understanding of the pathogenesis of FS and may facilitate the development of targeted treatment strategies.
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Purpose: Matrix metalloproteinase-11 (MMP11), which belongs to the stromelysin subgroup, has been reported to play a role in the progression of colorectal cancer (CRC). However, the significance of MMP11 in the tumor microenvironment, immune/stromal cells, and its mechanism in CRC remain unclear. Methods: The impact of MMP11 knockdown using specific short hairpin RNAs (shRNAs) on the metastasis and invasion of colorectal cancer RKO and SW480 cells was investigated using western blot, quantitative real-time polymerase chain reaction (qRT-PCR), transwell assays, and immunohistochemistry. ⋯ Moreover, MMP11 promoted the migration and invasion of CRC cells by elevating the expression of Slug protein. Most importantly, MMP11 was positively associated with M0-macrophages and negatively associated with M1-macrophages, NK cells activated, NK cells resting, T cells CD4 memory activated, and T cells follicular helper, indicating the remarkable interactions of MMP11 with tumor immunology. Conclusions: MMP11 plays an important role in colorectal cancer development, and its mechanism in CRC needs to be further explored in the future.
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Objective: TBC1 domain family member 22A (TBC1D22A) possesses GTPase-activating protein (GAP) activity of Rab family proteins and has not been reported in ovarian serous cystadenocarcinoma (OSC). The research was designed to evaluate the expression and prognostic effect of TBC1D22A in OSC. Methods: TCGA, GTEx, GEO, HPA, and GDSC databases were adopted to explore the oncogenic mechanism of TBC1D22A in OSC, as well as the correlation between TBC1D22A and patient prognosis, IC50, stemness index, immune checkpoint, and immune infiltration. ⋯ IC50 for cisplatin and paclitaxel increased in patients with overexpression of TBC1D22A. Conclusion: TBC1D22A is an independent prognostic risk factor for patients of ovarian cancer. Future research is required to fully understand the carcinogenic mechanism and clinical utility of TBC1D22A in ovarian cancer.
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Pancreatic cancer (PC) is a challenging and heterogeneous disease with a high mortality rate. Despite advancements in treatment, the prognosis for PC patients remains poor, with a high chance of disease recurrence. Biomarkers are crucial for diagnosing cancer, predicting patient prognosis and selecting treatments. ⋯ Furthermore, the infiltration of various immune cells, including B cells, neutrophils, CD8+ T cells, dendritic cells, and macrophages, was positively correlated with KDM1A, KDM5A, and KDM5B expression. Moreover, MetaCore pathway analysis revealed interesting connections between KDM1A and the cell cycle and proliferation, between KDM5A and DNA damage and double-strand break repair through homologous recombination, and between KDM5B and WNT/β-catenin signaling. These findings suggest that KDM1A, KDM5A and KDM5B may serve as promising biomarkers and therapeutic targets for PC, a disease of high importance due to its aggressive nature and urgent need for novel biomarkers to improve diagnosis and treatment.