Int J Med Sci
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Long non-coding RNAs are considered to be key regulatory factors of oncogenesis and tumor progression. It is reported that LINC00460 plays the role of oncogene in some tumors. However, LINC00460's role and mechanism of action in pancreatic cancer have not yet been fully elucidated. ⋯ Furthermore, LINC00460 functioned as an miR-4689 sponge to regulate the downstream target gene UBE2V1, enhancing the stability of mutant p53 in pancreatic cancer cells. LINC00460 also further promotes pancreatic cancer development by sequestering USP10, a cytoplasmic ubiquitin-specific protease that deubiquitinates p53 and enhances its stability. Collectively, our study demonstrated that LINC00460 is a hypoxia-induced lncRNA that plays the role of oncogene in pancreatic cancer by modulating the miR-4689/UBE2V1 axis, sequestering USP10, and ultimately enhancing the stability of mutant p53.
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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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Observational Study
Use of metagenomic next-generation sequencing for diagnosis of peritonitis in end-stage liver disease.
Background: Conventional methods are low in positive rates and time-consuming for ascites pathogen detection in patients with end-stage liver disease (ESLD). With many advantages, metagenomic next-generation sequencing (mNGS) may be a good alternative method. However, the related studies are still lacking. ⋯ Compared to conventional methods, mNGS had higher positivity rates (84% vs. 20%, P<0.001), sensitivity (45.2% vs. 23.8%, P=0.039), broader pathogen spectrum, shorter detection time (24 hours vs. 3-7 days), but lower specificity (25% vs 100%, P = 0.010). Furthermore, compared to conventional methods, mNGS showed similar consistence with final diagnosis (42% vs. 36%, P=0.539). Conclusions: mNGS may be a good supplement for conventional methods and helpful to early etiological diagnosis of peritonitis, and thus improve ESLD patients' survival.
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Acute myeloid leukemia (AML) is a malignancy of the hematological system, for which there remains an urgent need for new therapeutic and diagnostic targets. COMM domain containing 7 (COMMD7) is a recently-identified oncogene linked to poor prognosis in AML. COMMD7 regulates multiple signaling pathways, including nuclear factor-kappa B (NF-κB) signaling. ⋯ In addition, we noticed that knockdown of ZNF460 reduced proliferation and increased apoptosis rate of AML cells and that the cell cycle was blocked in the G2/M phase. In brief, our results revealed a critical effect of the ZNF460-COMMD7-NF-κB axis for the proliferation of AML cells. Therefore, COMMD7 may be a possible therapeutic target for AML.
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Qinggan Huoxue Recipe (QGHXR) is originated from Xiao Chaihu Decotion. Many experimental studies have confirmed that QGHXR can significantly alleviate the symptoms of alcoholic liver disease (ALD), but the detailed mechanism is still unclear. ⋯ Meanwhile, it can also increase PTEN, decrease PI3K and AKT mRNA levels. In this study, we obtained the targets and pathways of QGHXR in the treatment of ALD, and preliminatively verified that QGHXR may improve ALD through PTEN/PI3K/AKT signaling pathway.