Velazquezbrooks8706

AIMS To explore the real-world safety and effectiveness of gliclazide modified release (MR) in patients with type 2 diabetes mellitus (T2DM) fasting during Ramadan. METHODS DIA-RAMADAN (NCT04132934) was a prospective, international, observational study conducted in nine countries. Patients >18 years of age with T2DM (N=1,244) were examined at an inclusion visit (V0) occurring 6-8 weeks before the start of Ramadan. Patients received a diary to report treatment changes, hypoglycaemic events (HEs), and other adverse events. Gliclazide MR was taken once daily for 14-18 weeks. A second visit (V1) was conducted 4-6 weeks after the end of Ramadan. The primary endpoint was the proportion of patients reporting ≥1 symptomatic HE. Changes in HbA1c, fasting plasma glucose (FPG), and body weight were secondary endpoints. RESULTS The proportion of patients reporting ≥1 symptomatic HE during Ramadan was low (2.2%) with no reported severe HEs. There was a significant reduction in HbA1c (-0.3%), FPG (-9.7mg/dL), body weight (-0.5 kg) and body mass index (-0.2 kg/m2) between V0 and V1 (p less then 0.001). CONCLUSIONS Patients with T2DM treated with gliclazide MR during Ramadan have a low risk of hypoglycaemia and maintain glycaemic control and weight while fasting. Re-epithelialization of the alveolar surface is a key process of lung alveolar epithelial barrier repair after acute lung injury. The receptor for advanced glycation end-products (RAGE) pathway plays key roles in lung homeostasis, and its involvement in wound repair has been already reported in human bronchial epithelial cells. However, its effects on lung alveolar epithelial repair after injury remain unknown. We investigated whether RAGE stimulation with its ligands high-mobility group box 1 protein (HMGB1) or advanced glycation end-products (AGEs), alone or associated with RAGE inhibition using RAGE antagonist peptide, affects in vitro wound healing in human alveolar epithelial A549 cells. We further asked whether these effects could be associated with changes in cell proliferation and migration. We found that treatment of A549 cells with HMGB1 or AGEs promotes RAGE-dependent wound healing after a scratch assay. In addition, both RAGE ligands increased cell proliferation in a RAGE-dependent manner. Treatment with HMGB1 increased migration of alveolar epithelial cells at 12 h, independently of RAGE, whereas AGEs stimulated migration as measured 48 h after injury in a RAGE-dependent manner. Taken together, these results suggest that RAGE pathway is involved in lung alveolar epithelial wound repair, possibly through enhanced cell migration and proliferation. Renal cell carcinoma (RCC) is one of the most common malignant tumors in the urinary system, whose molecular mechanism is still not clear. ALPK2 is a member of alpha protein kinase family, and its relationship with RCC is never reported. In this study, expression of ALPK2 in tumor tissues or cells of RCC was detected by qPCR, western blotting and immunohistochemical analysis. The effects of ALPK2 knockdown on cell proliferation, colony formation, cell migration and apoptosis were assessed by MTT, colony formation assay, wound-healing assay, Transwell assay and flow cytometry, respectively. The influence of ALPK2 knockdown on tumor growth in vivo was evaluated by mice xenograft models. The results demonstrated that ALPK2 was upregulated in tumor tissues of RCC and its high expression was significantly associated with advanced stage and poor prognosis. Knockdown of ALPK2 could inhibited cell proliferation, colony formation and cell migration of RCC cells, while promoting cell apoptosis. The suppression of tumor growth in vivo by ALPK2 knockdown was also showed by using mice xenograft models. Moreover, the regulation of RCC by ALPK2 may involve Akt, CDK6, Cyclin D1 and PIK3CA signaling. Therefore, our studies suggested that ALPK2 may act as a tumor promotor in the development and progression of RCC, and could be considered as a novel therapeutic target for RCC treatment. This study sought to derive an enhanced understanding of the complex intracellular interactions that drive bone loss in postmenopausal osteoporosis. We applied an in-vitro multicellular niche to recapitulate cell-cell signalling between osteocytes, osteoblasts and osteoclasts to investigate (1) how estrogen-deficient and mechanically loaded osteocytes regulate osteoclastogenesis and (2) whether ROCK-II inhibition affects these mechanobiological responses. We report that mechanically stimulated and estrogen-deficient osteocytes upregulated RANKL/OPG and M-CSF gene expression, when compared to those treated with 10 nM estradiol. Osteoclast precursors (RAW 264.7) cultured within this niche underwent significant reduction in osteoclastogenic gene expression (CTSK), and there was an increasing trend in the area covered by TRAP+ osteoclasts (24% vs. 19.4%, p = 0.06). Most interestingly, upon treatment with the ROCK-II inhibitor, RANKL/OPG and M-CSF gene expression by estrogen-deficient osteocytes were downregulated. Yet, this inhibition of the pro-osteoclastogenic factors by osteocytes did not ultimately reduce the differentiation of osteoclast precursors. Indeed, TRAP and CTSK gene expressions in osteoclast precursors were upregulated, and there was an increased trend for osteoclast area (30.4% vs. 24%, p = 0.07), which may have been influenced by static osteoblasts (MC3T3-E1) that were included in the niche. We conclude that ROCK-II inhibition can attenuate bone loss driven by osteocytes during estrogen deficiency. Nafamostat cell line BACKGROUND AND AIMS Colonoscopy quality indicators such as adenoma detection rate (ADR) are surrogates for the effectiveness of screening-related colonoscopy. It is unclear whether endoscopist feedback on these indicators improves performance. We performed a meta-analysis to determine whether associations exist between endoscopist feedback and colonoscopy performance. METHODS We conducted a search through May 2019 for studies reporting on endoscopist feedback and associations with ADR or other colonoscopy quality indicators. Pooled rate ratios (RR) and weighted mean differences (WMD) were calculated using DerSimonian and Laird random effects models. Subgroup, sensitivity and meta-regression analyses were performed to assess for potential methodological or clinical factors associated with outcomes. RESULTS From 1,326 initial studies, 12 studies were included in the meta-analysis for ADR, representing 33,184 colonoscopies. Endoscopist feedback was associated with an improvement in ADR (RR, 1.21; 95% confidence interval, 1.