Expression of miR-409-5p in gestational diabetes mellitus and its relationship with insulin resistance.

Expression of miR-409-5p in gestational diabetes mellitus (GDM) and its relationship with insulin resistance were explore. One hundred and forty-nine pregnant women who underwent antenatal examination in Taizhou First People's Hospital were divided into a GDM group and a control group according to whether they had GDM or not. Serum miR-409-5p expression of the two groups was detected, and the levels of glycosylated hemoglobin (HbAlc) and other GDM-related biochemical indicators were measured. Fasting plasma glucose (FPG) was determined by glucose oxidase method, fasting insulin (FINS) was detected by radioimmunoassay, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The relationship between miR-409-5p and other biochemical indicators and insulin resistance was analyzed, and logistic multivariate regression was employed to analyze the risk factors of GDM. miR-409-5p was highly expressed in the serum of GDM patients. HbAlc, FPG, FINS, and HOMA-IR in pregnant women in the GDM group were markedly higher than those in the control group. The serum miR-409-5p in GDM pregnant women showed a positive correlation with HbAlc, FPG, FINS, and HOMA-IR (P<0.05). The insulin resistance group presented remarkably higher serum miR-409-5p level than the non-insulin resistance group. Moreover, it was found that elevated miR-409-5p, FINS, and HOMA-IR were all independent risk factors for the onset of GDM. miR-409-5p is highly expressed in the serum of patients with GDM, and it is positively correlated with insulin resistance index of GDM patients, which may be a potential target for clinical diagnosis and treatment of GDM.

Efficacy and Safety of Denosumab in Postmenopausal Women With Osteoporosis: A Meta-Analysis.

The purpose of this study was to perform a meta-analysis to examine the efficacy and safety of denosumab in postmenopausal women with osteoporosis.Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until October 30, 2014 using combinations of the following search terms: osteoporosis, postmenopause, postmenopausal, women, denosumab. The primary outcome was bone mineral density (BMD) change, and secondary outcomes were change in the bone turnover markers ß-isomerized carboxy-terminal cross-linking telopeptide of type I collagen (CTX) and serum procollagen type I amino-terminal propeptide (P1NP), and adverse events.Patients treated with denosumab had significantly increased BMD of the lumbar spine (7.58%), total hip (4.86%), and distal third of the radius (2.92%) than those treated with placebo (all, P < 0.001). Patients treated with denosumab had a significant decrease of CTX (-66.16%) and P1NP (-64.65%) as compared with those treated with placebo (both, P < 0.001). Adverse events were similar between the 2 groups (pooled odds ratio = 1.04, P = 0.625).Denosumab increases BMD and decreases markers of bone turnover in postmenopausal women with osteoporosis, and is not associated with significant side-effects.

Fasudil inhibits epithelial-myofibroblast transdifferentiation of human renal tubular epithelial HK-2 cells induced by high glucose.

Renal fibrosis is a crucial pathologic process underlying diabetic nephropathy (DN). Central to this process is the epithelial-mesenchymal transformation (EMT) of tubular epithelial cells. Fasudil, a Rho-associated coiled-coil forming protein serine/threonine kimase (ROCK) inhibitor, protects against renal fibrosis in a variety of renal injury models. However, fasudil's effects on renal fibrosis in DN remain unknown. The aim of the present study was to investigate the effects of fasudil on high glucose-induced EMT in human renal tubular epithelial (HK-2) cells. HK-2 cells were exposed to 5.5 or 60 mmol/L D-glucose for 72 h, or to mannitol (osmotic control). RhoA activity was assessed using a RhoA pull-down assay, and ROCK activity was determined by myosin phosphatase target subunit-1 (MYPT1) phosphorylation. Myofibroblast (vimentin and α-smooth muscle actin [α-SMA]) and epithelial (E-cadherin) markers expressions were detected by immunocytochemistry and Western blotting. Transforming growth factor (TGF)-ß1 and fibronectin secretion were detected with enzyme-linked immunosorbent assay (ELISA), and connective tissue growth factor (CTGF) was analyzed by Western blotting. Results showed that high glucose levels induced morphological changes, reduced E-cadherin expression (-73%), increased expression of vimentin (+148%) and α-SMA (+226%), increased TGF-ß1 (from 116.0±5.2 µg/g to 351.0±3.2 µg/g) and CTGF (from 0.26±0.01 to 0.92±0.03) secretion, and increased RhoA and ROCK activation (p<0.05 for all). All these effects of high glucose stimulation were suppressed or abolished by fasudil. In conclusion, fasudil may attenuate EMT through reduced activation of RhoA/ROCK signaling, and decreased expression of TGF-ß1 and CTGF. Thus, fasudil may be a renoprotective agent for the treatment of DN.