Long-term MNNG exposure promotes gastric carcinogenesis by activating METTL3/m6A/miR1184 axis-mediated epithelial-mesenchymal transition.

As the representative item of environmental chemical carcinogen, MNNG was closely associated with the onset of Gastric cancer (GC), while the underlying mechanisms remain largely unknown. Here, we comprehensively analyzed the potential clinical significance of METTL3 in multiple GC patient cohorts. Additionally, we demonstrated that long-term exposure to MNNG elevated METTL3 and EMT marker expression by in vitro and in vivo models. Furthermore, the depletion of METTL3 impacted the proliferation, migration, invasion, and tumorigenesis of MNNG malignant transformation cells and GC cells. By me-RIP sequencing, we identified a panel of vital miRNAs potentially regulated by METTL3 that aberrantly expressed in MNNG-induced GC cells. Mechanistically, we showed that METTL3 meditated miR-1184/TRPM2 axis by regulating the process of miRNA-118. Our results provide novel insights into critical epigenetic molecular events vital to MNNG-induced gastric carcinogenesis. These findings suggest the potential therapeutic targets of METTL3 for GC treatment.

The influence of hypoglycemia on the specific quality of life in type 2 diabetes mellitus: a comparative cross-sectional study of diabetics with and without hypoglycemia in Xi'an, China.

PURPOSE: This study aims to explore the incidence of hypoglycemia in patients with type 2 diabetes mellitus (T2DM) and the influence of hypoglycemia on the specific quality of life in T2DM patients. METHODS: It was a comparative cross-sectional study consisting of 519 T2DM patients in Xi'an, China and patients were investigated by self-reported hypoglycemia and specific quality of life questionnaires from September 2019 to January 2020. Descriptive analysis, t-test, Chi-square test, hierarchical regression analysis and stepwise multiple regression analysis were applied to assess the influence of hypoglycemia on the specific quality of life. RESULTS: The incidence of hypoglycemia in T2DM patients was 32.18%. The mean score of specific quality of life in diabetes without hypoglycemia was 57.33 ± 15.36 and was 61.56 ± 17.50 in those with hypoglycemia, which indicated that hypoglycemia had a serious impact on the quality of life of diabetics (t = - 5.172, p = 0.000). In the Univariate analysis of specific quality of life, age, education background, marital status, living status, duration of diabetes, monthly income per capita were independent and significant factors associated with specific quality of life of two groups of T2DM patients (p < 0.05). In the hierarchical regression analysis, the duration of the diabetes more than 11 years and the frequency of hypoglycemia more than 6 times in half a year entered the equation of specific quality of life of 519 diabetics respectively (p < 0.001). In multiple linear regression analysis, age, marital status and income all entered the regression equation of quality of life of the two groups (p < 0.05). CONCLUSION: Hypoglycemia will have a serious impact on the quality of life of T2DM patients. In order to improve the living quality in diabetics, effective measurements should be taken to strengthen the management of blood glucose and to avoid hypoglycemia.

BMAL1 Disrupted Intrinsic Diurnal Oscillation in Rat Cerebrovascular Contractility of Simulated Microgravity Rats by Altering Circadian Regulation of miR-103/CaV1.2 Signal Pathway.

The functional and structural adaptations in cerebral arteries could be one of the fundamental causes in the occurrence of orthostatic intolerance after space flight. In addition, emerging studies have found that many cardiovascular functions exhibit circadian rhythm. Several lines of evidence suggest that space flight might increase an astronaut's cardiovascular risks by disrupting circadian rhythm. However, it remains unknown whether microgravity disrupts the diurnal variation in vascular contractility and whether microgravity impacts on circadian clock system. Sprague-Dawley rats were subjected to 28-day hindlimb-unweighting to simulate the effects of microgravity on vasculature. Cerebrovascular contractility was estimated by investigating vasoconstrictor responsiveness and myogenic tone. The circadian regulation of CaV1.2 channel was determined by recording whole-cell currents, evaluating protein and mRNA expressions. Then the candidate miRNA in relation with Ca2+ signal was screened. Lastly, the underlying pathway involved in circadian regulation of cerebrovascular contractility was determined. The major findings of this study are: (1) The clock gene BMAL1 could induce the expression of miR-103, and in turn modulate the circadian regulation of CaV1.2 channel in rat cerebral arteries at post-transcriptional level; and (2) simulated microgravity disrupted intrinsic diurnal oscillation in rat cerebrovascular contractility by altering circadian regulation of BMAL1/miR-103/CaV1.2 signal pathway.