CircTLK1 alleviates oxygen-glucose deprivation/reperfusion induced apoptosis in HK-2 cells through miR-136-5p/Bcl2 signal axis.

The biological functions of circTLK1 in acute kidney injury (AKI), which mainly results from renal ischemia-reperfusion (IR), remain largely unknown. HK-2 cell treatment with oxygen and glucose deprivation, reoxygenation, and glucose (OGD/R) was used to simulate an AKI model that was mainly caused by renal IR. Then, the circTLK1 expression level in HK-2 cells treated with OGD/R was assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Functional experiments were performed with circTLK1 knockdown of HK-2 cells via Cell Counting Kit-8 (CCK8), flow cytometry (FCM), RT-qPCR, and western blotting. The circTLK1-miRNAs-mRNAs network was constructed following the ceRNA mechanism and visualized by Cytoscape software to investigate the mechanism of circTLK1 in AKI. RT-qPCR was performed to verify the relationship between circTLK1, miR-136-5p, and Bcl2. The level of miR-136-5p was knocked down to ensure its function in OGD/R-triggered apoptosis through experiments, including CCK8, FCM, RT-qPCR, and western blotting. CircTLK1 was downregulated in HK-2 cells subjected to OGD/R treatment and in mouse kidney tissues after renal IR, but the expression of miR-136-5p was the opposite. Interference with circTLK1 expression accelerated HK-2 cell apoptosis, which was overturned by miR-136-5p inhibitors. CircTLK1 targets miR-136-5p to upregulate Bcl2 expression and attenuate apoptosis in HK-2 cells. These data revealed the possible role of circTLK1 as a new biomarker for diagnosis as well as a target in AKI through the miR-136-5p/Bcl2 signaling axis.

Association of Choline Intake with Blood Pressure and Effects of Its Microbiota-Dependent Metabolite Trimethylamine-N-Oxide on Hypertension.

Background: The association of total choline (TC) intake and its metabolite trimethylamine-N-oxide (TMAO) with hypertension and blood pressure (BP) has not been elucidated. Methods: For the population study, the association of TC intake with hypertension, as well as blood pressure, was determined through logistic along with multiple linear regression analysis from the National Health and Nutrition Examination Survey 2007 to 2018, respectively. For the animal experimental study, spontaneously hypertensive rats (SHRs) were assigned to the water group or water containing 333 mg/L or 1 g/L TMAO group. After 22 weeks treatment of TMAO, blood pressure measurement, echocardiography, and histopathology of the heart and arteries were evaluated. Results: No significant association of TC with hypertension was observed but the trend for ORs of hypertension was decreased with the increased level of TC. Negative association between TC and BP was significant in quintile 4 and quintile 5 range of TC, and the negative trend was significant. The SHR-TMAO groups showed significant higher urine output levels in contrast with the SHR-water group. No difference of diastolic BP was observed, but there was a trend towards lower systolic BP with the increase doses of TMAO in the SHR group. The SHR 1 g/L TMAO rats had a remarkably lower systolic blood pressure than the SHR-water group. Echocardiography showed a diastolic dysfunction alleviating effect in the 1 g/L TMAO group. Conclusion: High TC intake was not linked to elevated risk of hypertension. An inverse relationship of choline intake with systolic BP was observed. The mechanism for the beneficial effect of TC might be associated with the diuretic effect of its metabolite TMAO.

Functional characterization of TRPM7 in nasopharyngeal carcinoma and its knockdown effects on tumorigenesis.

The aim of this study was to evaluate the association of functional expression of TRPM7 with nasopharyngeal carcinoma (NPC) growth. We examined the correlation of TRPM7 expression with cell growth and proliferation, cell cycle, and apoptosis in vitro in NPC cell lines and NPC tumorigenesis in mice by conducting experiments in mice and by further analyzing the tumor volume and growth. We further explored to see whether there is any positive correlation with the TRPM7 knockdown in NPC cells with their sensitivity to radiation. We found that the functional expression of TRPM7 in nasopharyngeal carcinoma is a critical requirement for physiological processes such as cell cycle, resistance to apoptosis, and cell proliferation. TRPM7 knockdown also enhanced sensitivity to radiotherapy of nasopharyngeal carcinoma. Moreover, we identified TRPM7 as a novel potential regulator of cell proliferation in NPC, through signal transducer and activator of transcription 3 (STAT3)-mediated signaling pathway and other anti-apoptotic factors. TRPM7 and STAT3 activation might be critical for the growth of NPC cells and could be an effective target for treatment of nasopharyngeal carcinoma.