Background Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of many disease progression. However, the role of lncRNA HOX transcript antisense RNA (HOTAIR) in diabetic nephropathy (DN) remains unclear. Methods High glucose (HG)-induced human mesangial cells (HMC) was used to construct DN cell models in vitro. HMC proliferation was evaluated by CCK8 assay and EDU staining. Protein levels of proliferation markers, fibrosis markers, and wingless-type family member 2B (WNT2B) were measured using western blot analysis. HMC oxidative stress was assessed by determining the levels of oxygen species and malondialdehyde, as well as superoxide dismutase activity. Relative expression levels of lncRNA HOTAIR, microRNA (miR)-147a, and WNT2B were examined using quantitative real-time PCR. The interaction between miR-147a and lncRNA HOTAIR or WNT2B was confirmed by dual-luciferase reporter assay and RIP assay. Results Our data showed that lncRNA HOTAIR knockdown could inhibit the proliferation, fibrosis, and oxidative stress in HG-induced HMC. LncRNA HOTAIR could serve as a sponge of miR-147a. The inhibition effect of lncRNA HOTAIR silencing on the biological functions of HG-induced HMC could be reversed by miR-147a inhibitor. WNT2B was targeted by miR-147a, and its overexpression also overturned the suppressive effect of miR-147a on the proliferation, fibrosis, and oxidative stress of HG-induced HMC. Conclusion In total, our research pointed out that lncRNA HOTAIR could mediate miR-147a/WNT2B axis to promote DN progression.
Introduction. As the most malignant type of gliomas, glioblastoma is characterized with disappointing prognosis. Here, we aimed to investigate expression and function of NKD inhibitor of Wnt signaling pathway 1 (NKD1), an antagonist of Wnt-beta-catenin signaling pathways, in glioblastoma. Methods. The mRNA level of NKD1 was firstly retrieved from TCGA glioma dataset to evaluate its correlation with clinical characteristics and its value in prognosis prediction. Then, its protein expression level in glioblastoma was tested by immunohistochemistry staining in a retrospectively cohort collected from our medical center (n = 66). Univariate and multivariate survival analyses were conducted to assess its effect on glioma prognosis. Two glioblastoma cell lines, U87 and U251, were used to further investigate the tumor-related role of NKD1 through overexpression strategy in combination with cell proliferation assays. Immune cell enrichment in glioblastoma and its correlation with NKD1 level was finally assessed using bioinformatics analyses. Results. NKD1 shows a lower expression level in glioblastoma compared to that in the normal brain or other glioma subtypes, which is independently correlated to a worse prognosis in both the TCGA cohort and our retrospective cohort. Overexpressing NKD1 in glioblastoma cell lines can significantly attenuate cell proliferation. In addition, expression of NKD1 in glioblastoma is negatively correlated to the T cell infiltration, indicating it may have crosstalk with the tumor immune microenvironment. Conclusions. NKD1 inhibits glioblastoma progression and its downregulated expression indicates a poor prognosis.
Using rat models of heart failure, we evaluated the effects of rosuvastatin and Huangqi granule alone and in combination on left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole, and left ventricular posterior wall thickness at end-systole. Results showed that left ventricular end-diastolic dimension, left ventricular end-systolic dimension in the rosuvastatin + Huangqi granule group were significantly decreased (P ‹ 0.01), while left ventricular ejection fraction, left ventricular posterior wall thickness at end-diastole and left ventricular posterior wall thickness at end-systole were significantly increased (P ‹ 0.05). The serum IL-2, IFN-β, and TNF-α in rosuvastatin + Huangqi granule group were significantly lower than those in model group (P ‹ 0.05). However, the levels of S-methylglutathione and superoxide dismutase in rosuvastatin + Huangqi granule group were significantly higher, while nitric oxide was significantly lower than that in the model group (P ‹ 0.05). Also, compared to the model group, the apoptosis rate, and the autophagy protein LC3-II in the cardiomyocytes of rosuvastatin + Huangqi granule group was significantly decreased (P ‹ 0.01), while the level of p62 protein was significantly increased (P ‹ 0.01). The levels of AMPK and p-AMPK in cardiomyocytes were significantly lower in rosuvastatin + Huangqi granule group; however, the levels of mTOR and p-mTOR showed an opposite trend (P ‹ 0.05). To sum up, rosuvastatin + Huangqi granule could improve the cardiac function, decrease the level of oxidative stress, and inflammatory cytokines in rats with HF. The possible underlying mechanism might be inhibition of autophagy and reduced apoptosis in cardiomyocytes by regulating AMPK-mTOR signaling pathway.
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