LncRNA KCNQ1OT1 promotes osteogenic differentiation via miR-205-5p/RICTOR axis.

Osteoporosis is a prevalent degenerative disease that is characterized by decreased bone density and strength, resulting in gradually increasing bone fragility. Osteoporosis is caused by an imbalance between osteoblastic bone formation and osteoclastic bone resorption. Recently, increasing evidence has suggested that long non-coding RNAs (lncRNAs) participate in the occurrence and development of osteoporosis. Herein, we explored the role of lncRNA KCNQ1OT1 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). QPCR results indicated that KCNQ1OT1 and RICTOR were down-regulated, while miR-205-5p was up-regulated in the osteoporotic patients, as compared with non-osteoporotic controls. During the osteogenic differentiation of BMSCs, the expression of KCNQ1OT1 and RICTOR was upregulated, whereas miR-205-5p was downregulated. The interaction among KCNQ1OT1, miR-205-5p and RICTOR was validated by dual luciferase reporter system. KCNQ1OT1 promoted RICTOR expression via inhibiting miR-205-5p, therefore promoting osteogenesis as demonstrated by ALP assay, alizarin red staining and the increased expression of osteogenic markers (OPN, RUNX2 and OCN). Furthermore, KCNQ1OT1 overexpression or miR-205-5p inhibition could promote ALP activity and mineralization of BMSCs, while overexpressed miR-205-5p could reverse the effects of overexpressed KCNQ1OT1, and knockdown of RICTOR could reverse the effects of miR-205-5p inhibition. In conclusion, our study illustrated that KCNQ1OT1 might inhibit miR-205-5p in BMSCs, thus upregulating the expression of RICTOR and promoting osteogenic differentiation.

Hyperglycemia and blood glucose deterioration are risk factors for severe COVID-19 with diabetes: A two-center cohort study.

We aimed to assess whether blood glucose control can be used as predictors for the severity of 2019 coronavirus disease (COVID-19) and to improve the management of diabetic patients with COVID-19. A two-center cohort with a total of 241 confirmed cases of COVID-19 with definite outcomes was studied. After the diagnosis of COVID-19, the clinical data and laboratory results were collected, the fasting blood glucose levels were followed up at initial, middle stage of admission and discharge, the severity of the COVID-19 was assessed at any time from admission to discharge. Hyperglycemia patients with COVID-19 were divided into three groups: good blood glucose control, fair blood glucose control, and blood glucose deterioration. The relationship of blood glucose levels, blood glucose control status, and severe COVID-19 were analyzed by univariate and multivariable regression analysis. In our cohort, 21.16% were severe cases and 78.84% were nonsevere cases. Admission hyperglycemia (adjusted odds ratio [aOR], 1.938; 95% confidence interval [95% CI], 1.387-2.707), mid-term hyperglycemia (aOR, 1.758; 95% CI, 1.325-2.332), and blood glucose deterioration (aOR, 22.783; 95% CI, 2.661-195.071) were identified as the risk factors of severe COVID-19. Receiver operating characteristic (ROC) curve analysis, reaching an area under ROC curve of 0.806, and a sensitivity and specificity of 80.40% and 68.40%, respectively, revealed that hyperglycemia on admission and blood glucose deterioration of diabetic patients are potential predictive factors for severe COVID-19. Our results indicated that admission hyperglycemia and blood glucose deterioration were positively correlated with the risk factor for severe COVID-19, and deterioration of blood glucose may be more likely to the occurrence of severe illness in COVID-19.

Accurate diagnosis and heterogeneity analysis of a 17q12 deletion syndrome family with adulthood diabetes onset and complex clinical phenotypes.

PURPOSE: 17q12 Deletion Syndrome is heterogeneous and the reasons remain unclear. We clarified the clinical characteristics of adulthood diabetes onset 17q12 deletion syndrome and investigated the unclear phenotype-genotype correlation. METHODS: We collected the clinical history and laboratory results of a family with autosomal dominant inheritance diabetes and renopathy. Sanger sequencing of HNF1B and a panel of monogenic diabetic genes were performed to identify the monogenetic diabetes. Semiquantitative PCR and Chromosome 100 K sequence analysis were performed to analyze the copy numbers variation of diabetes related genes. Allelic specific quantitative PCR were used for TBC1D3 and paralogues diagnosis. The reported cases were reviewed and assessed to compare with patients in this study. RESULTS: Differential variants in genomic DNA and clinical presentations among family members were explored to determine the probable phenotype-genotypes correlation. The four patients were diagnosed with 17q12 deletion syndrome with 1.47-1.76 Mb heterogeneous deletion, which led to the haploinsufficiency of HNF1B, ACACA, LHX1, PIGW, miRNA2909 and other genes. The patients had different amount of genes deletion in TBC1D3 and paralogues, which might associate with the heterogeneous clinical phenotypes. CONCLUSIONS: We first reported an adulthood diabetes onset 17q12 deletion syndrome family with the largest number of patients. The heterogeneous clinical phenotypes might be related to the haploinsufficiency of TBC1D3 and its paralogues.