Effect of dapagliflozin on obstructive sleep apnea in patients with type 2 diabetes: a preliminary study.

OBJECTIVE: The aim of this case-control study was to assess the efficacy of dapagliflozin combined with metformin for type-2 diabetes mellitus (T2DM) with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: A total of 36 patients with newly-diagnosed T2DM and OSAHS were randomized divided into two groups. Eighteen OSAHS patients with T2DM, who were treated with dapagliflozin and metformin, were assigned as the dapagliflozin group. These patients were given dapagliflozin and metformin for 24 weeks between February 2017 and February 2018. Another 18 OSAHS patients with T2DM, who were treated with glimepiride and metformin for 24 weeks, were assigned as the control group. Fasting plasma glucose (FPG) level, postprandial blood glucose (PPG), hemoglobin A1C (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, body mass index (BMI), blood pressure, apnea-hypopnea index (AHI), minimum oxygen saturation (LSpO2), and Epworth Somnolence Scale (ESS) score were measured before and at 24 weeks after the initiation of treatment. RESULTS: In the dapagliflozin group, triglyceride (TG), systolic pressure (SBP) and diastolic pressure (DBP) significantly decreased following treatment, while high-density lipoprotein cholesterol (HDL-C) significantly increased (P < 0.05). Furthermore, a reduction in AHI, an increase in LSpO2 and a decrease in ESS score were observed in the dapagliflozin group (P < 0.05), but not in the control group. Moreover, blood glucose, HbA1c, HOMA-IR, and BMI significantly decreased in these two groups, and the decrease was more significant in the dapagliflozin group. CONCLUSION: These present results indicate that dapagliflozin can significantly reduce glucose, BMI, blood pressure and AHI, and improve hypoxemia during sleep and excessive daytime sleepiness, which thereby has potential as an effective treatment approach for OSAHS.

Microarray Analysis of circRNA Expression Pattern in Corneal Neovascularization.

PURPOSE: To identify differentially expressed circular RNAs (circRNAs) in corneal neovascularization. METHODS: We established an alkali burn-induced corneal neovascularization model and performed circRNA expression profiling to identify differentially expressed circRNAs between avascular corneas and vascularized corneas. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analyses of the host genes of dysregulated circRNAs were performed to determine the related biological modules and pathological pathways. Real-time polymerase chain reactions were performed to detect the expression pattern of circRNAs in the clinical samples. In vitro experiments were performed to determine the role of circRNAs in vascular endothelial angiogenic effects. RESULTS: Two hundred twenty-nine circRNAs were differentially expressed between avascular corneas and vascularized corneas. The host genes of dysregulated circRNAs were targeted to cell cycle (biologic process), cytoplasm (cellular component), and protein binding (molecular function). Rap1 signaling was identified as the most enriched signaling pathway. Clinical studies showed that the human ortholog of cZFP609 and cKifap3 was dysregulated in the vascularized human corneas. cKifap3 silencing facilitated vascular endothelial angiogenic effects by regulating endothelial cell proliferation, migration, and tube formation. CONCLUSIONS: This study suggests that circRNAs are involved in the pathogenesis of corneal neovascularization. cZFP609 and cKifap3 may serve as promising targets for the treatment of corneal neovascularization.

Genome-Wide Identification of Circular RNAs as a Novel Class of Putative Biomarkers for an Ocular Surface Disease.

BACKGROUND/AIMS: Pterygium is a common ocular surface disease with an unknown etiology and threatens vision as it invades into the cornea. Circular RNAs (circRNAs) are a novel class of RNA transcripts that participate in several physiological and pathological processes. However, the role of circRNAs in pathogenesis of pterygium remains largely unknown. METHODS: Genome-wide circRNA expression profiling was performed to identify pterygium -related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was performed to predict the function of differentially expressed circRNAs in pterygium. MTT assays, Ki67 staining, Transwell assay, Hoechst 33342 staining, and Calcein-AM/PI staining were performed to determine the effect of circRNA silencing on pterygium fibroblast and epithelial cell function. RESULTS: Approximately 669 circRNAs were identified to be abnormally expressed in pterygium tissues. GO analysis demonstrated that the host genes of differentially expressed circRNAs were targeted to extracellular matrix organization (ontology: biological process), cytoplasm (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis showed that dysregulated circRNAs-mediated regulatory networks were mostly enriched in focal adhesion signaling pathway. Notably, circ_0085020 (circ-LAPTM4B) was shown as a potential biomarker for pterygium. circ_0085020 (circ-LAPTM4B) silencing affected the viability, proliferation, migration, and apoptosis of pterygium fibroblast and epithelial cells in vitro. CONCLUSIONS: This study provides evidence that circRNAs are involved in the pathogenesis of pterygium and might constitute promising targets for the therapeutic intervention of pterygium.

Long non-coding RNA MEG3 silencing protects against light-induced retinal degeneration.

Excessive light exposure leads to retinal degeneration and accelerates the progression and severity of several ocular diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa. Long non-coding RNAs (LncRNAs) have emerged as important regulators of photoreceptor development and ocular diseases. In this study, we investigated the role of lncRNA-MEG3 in light-induced retinal degeneration. MEG3 expression was significantly up-regulated after light insult in vivo and in vitro. MEG3 silencing protected against light-induced retinal degeneration in vivo and light-induced photoreceptor cell apoptosis in vitro. Mechanistically, MEG3 regulated retinal photoreceptor cell function by acting as p53 decoy. MEG3 silencing decreased caspase 3/7 activity, up-regulated anti-apoptotic protein (Bcl-2) expression, and down-regulated pro-apoptotic protein (Bax) expression. Taken together, this study provides a promising method of MEG3 silencing for treating light-induced retinal degeneration.

HPLC determination of the content and dissolution of isophenylcyclopentylamine hydrochloride capsules / 国际药学研究杂志

Objective To establish a method for the determination of the content and dissolution of isophenylcyclopentyl?amine hydrochloride capsules. Methods The HPLC analysis was performed on a Diamonsil C18 column(150 mm×4.6 mm,5μm). A mixture of 0.02 mol/L KH2PO4 solution containing 0.1%triethylamine with pH adjusted to 3.0 by phosphoric acid-methanol-acetonitrile (30:35:35)was used as the mobile phase with the flow rate at 1.0 ml/min. The detection wavelength was 224 nm. Dissolution was de?termined by the basket method,using the 500 ml of 0.1 mol/L hydrochloric acid solution,pH 4.5 acetic acid buffer,water and pH 6.8 phosphoric acid buffer as dissolution media under the 50,75 and 100 r/min rotation speeds to select the dissolution condition. Re?sults This method had high specificity. The linear range for the quantitative determination was 20.74-155.58 μg/ml(r=1.0000), and the average recovery was 100.1%. The linear range for the determination of dissolution was 2.08-24.90μg/ml(r=0.9998),with the average recovery of 98.9%. The method of dissolution tests was established:0.1 mol/L hydrochloric acid solution was used as disso?lution medium and rotation speed was 50 r/min. The determined content and dissolution of three batches of capsules fulfilled the re?quirements. Conclusion The method is simple,accurate and reproducible for the determination of the content and dissolution of iso?phenylcyclopentylamine hydrochloride capsules.