Repression of miR-142–3p alleviates psoriasis-like inflammation by repressing proliferation and promoting apoptosis of keratinocytes via targeting Sema3A

Psoriasis is a multifactorial, recurring, and chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes. Evidence is rapidly accumulating for the role of microRNAs in psoriasis. The object of the study was to explore the functions and precise mechanism of miR-142–3p in human keratinocyte HaCaT cells in the presence of M5. Here, the results showed that miR-142–3p expression was heightened in HaCaT cells induced by M5. In addition, inhibition of miR-142–3p dramatically restricted cell proliferation and enhanced apoptosis in HaCaT cells exposed to M5, as exemplified by a decrease in the antiapoptotic Bcl-2 protein, concomitant with an increase in the proapoptotic proteins Bax. Moreover, depleting miR-142–3p effectively ameliorated M5-induced inflammation response, as reflected by the attenuation of multiple inflammatory factors. Importantly, Sema3A was identified as an authentic target of miR-142–3p, and indeed regulated by miR-142–3p. Mechanistically, silencing of Sema3A effectively abolished the anti-proliferative, apoptosis-promoting, and anti-inflammatory effects of miR-142–3p inhibition in keratinocytes. Taken together, these data elucidated that repression of miR-142–3p protect HaCaT cells against M5-induced hyper-proliferation and inflammatory injury by suppressing its target Sema3A, implying that the miR-142–3p/Sema3A axis may be a new target for preventing keratinocyte injury process. These findings provide a new and better understanding of the mediating role of miR-142–3p in psoriasis.     

某院住院2型糖尿病患者调脂药物应用情况调查

目的 了解我院T2DM患者调脂药物应用情况，促进糖尿病调脂药物的合理应用。方法 从2015年1月至2015年12月在株洲市中心医院代谢内分泌科住院的T2DM患者中抽取资料完整的病例共1148例列入本次分析，评估患者心血管事件的风险因素，统计患者调脂药物使用情况，评估血脂控制达标情况。结果 1148例T2DM患者中极高风险患者884例，较高风险患者256例，低风险患者8例。有990例（86.2%）使用了调脂药物。单用他汀类治疗950例（755例阿托伐他汀20mg qn，194例瑞舒伐他汀钙10mg qn，1例普伐他汀10mg qn），单用贝特类治疗24例（均为非诺贝特200mg qd），联合用药16例（14例联用非诺贝特200mg qd 阿托伐他汀20mg qd，2例联用吉非罗齐300mg bid 阿托伐他汀20mg qd）。血脂异常控制达标者367例，达标率为32.0%。结论 我院T2DM调脂药物使用率低，血脂控制达标率低，调脂药物的选择以他汀类为主，但未根据患者具体情况确定个体化的他汀类药物用药剂量。临床医生需提高T2DM患者心血管风险意识管理，遵循指南个体化给予调脂药物治疗。     

Heterogeneous vestibulocerebellar mossy fiber projections revealed by single axon reconstruction in the mouse

A significant population of neurons in the vestibular nuclei projects to the cerebellum as mossy fibers (MFs) which are involved in the control and adaptation of posture, eye-head movements, and autonomic function. However, little is known about their axonal projection patterns. We studied the morphology of single axons of medial vestibular nucleus (MVN) neurons as well as those originating from primary afferents, by labeling with biotinylated dextran amine (BDA). MVN axons (n = 35) were classified into three types based on their major predominant termination patterns. The Cbm-type terminated only in the cerebellum (15 axons), whereas others terminated in the cerebellum and contralateral vestibular nuclei (cVN/Cbm-type, 13 axons), or in the cerebellum and ipsilateral vestibular nuclei (iVN/Cbm-type, 7 axons). Cbm- and cVN/Cbm-types mostly projected to the nodulus and uvula without any clear relationship with longitudinal stripes in these lobules. They were often bilateral, and sometimes sent branches to the flocculus and to other vermal lobules. Also, the iVN/Cbm-type projected mainly to the ipsilateral nodulus. Neurons of these types of axons showed different distribution within the MVN. The number of MF terminals of some vestibulocerebellar axons, iVN/Cbm-type axons in particular, and primary afferent axons were much smaller than observed in previously studied MF axons originating from major precerebellar nuclei and the spinal cord. The results demonstrated that a heterogeneous population of MVN neurons provided divergent MF inputs to the cerebellum. The cVN/Cbm- and iVN/Cbm-types indicate that some excitatory neuronal circuits within the vestibular nuclei supply their collaterals to the vestibulocerebellum as MFs.     

Interferon-induced Transmembrane Protein 3 Prevents Acute Influenza Pathogenesis in Mice

Objective Interferon-induced transmembrane protein 3(IFITM3) is an important member of the IFITM family. However, the molecular mechanisms underlying its antiviral action have not been completely elucidated. Recent studies on IFITM3, particularly those focused on innate antiviral defense mechanisms, have shown that IFITM3 affects the body's adaptive immune response. The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection in vivo.Methods We performed proteomics, flow cytometry, and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer(NK) cell numbers, their activation, and their immune function in the lungs of Ifitm3-/-and wild-type mice.Results Ifitm3-/-mice developed more severe inflammation and apoptotic responses compared to wild-type mice. Moreover, the NK cell activation was higher in the lungs of Ifitm3-/-mice during acute influenza infection.Conclusions Based on our results, we speculate that the NK cells are more readily activated in the absence of IFITM3, increasing mortality in Ifitm3-/-mice.     

Long-term safety and effectiveness of biosimilar insulin glargine in Japanese patients with diabetes mellitus in routine clinical practice: results of a post-marketing safety study

Abstract

Objective: To evaluate the long-term safety and effectiveness of biosimilar insulin glargine (GLY) in real-world clinical practice.

Methods: This prospective, non-interventional, multicenter, observational, post-marketing safety study (PMSS) enrolled Japanese patients with type 1 or 2 diabetes mellitus (T1DM or T2DM) starting GLY therapy, and was required by Japanese Pharmaceutical Affairs Law mandating post-marketing safety surveillance to acquire safety and effectiveness data of biosimilar products. Data collected from the 12-month observation included patient characteristics, adverse events, and blood glucose control.

Results: The study enrolled 141 patients with T1DM and 1104 patients with T2DM. Pre-study insulin was used by 94.1% of patients with T1DM and 75.0% with T2DM. 65.4% of patients with T1DM and 64.3% with T2DM switched from the reference product (GLY-switched), while 25.0% with T2DM were insulin-naive. Adverse events were reported by 5.7% and 8.5% in T1DM and T2DM, respectively. Similar incidences were reported in GLY-switched. Adverse events were reported by 10.7% in insulin-naive T2DM. Baseline mean hypoglycemic events/month were 1.8 and 0.1 in T1DM and T2DM, respectively: the mean change from baseline (CFB) was –1.2 (p?=?.066) and 0.0 (p?=?.915), respectively. Baseline mean HbA1c was 8.4% and 8.7% in T1DM and T2DM, respectively; the mean CFB was –0.5% (p?<?.001) and –0.9% (p?<?.001), respectively, and –1.5% (p?<?.001) in insulin-naive T2DM.

Conclusions: This first long-term Japanese PMSS of GLY demonstrated adverse events, hypoglycemia, and glycemic control consistent with the known GLY profile for T1DM and T2DM patients, in routine clinical practice.     

Comprehensive profiling of α-glucosidase inhibitors from the leaves of Rubus suavissimus using an off-line hyphenation of HSCCC,ultrafiltration HPLC-UV-MS and prep-HPLC

The leaves of Rubus suavissimus (also called “Chinese sweet tea”) is used not only as a beverage tea and food additive but also as a folk herbal medicine for the treatment of diabetes mellitus. To systematically investigate its material foundation of efficacy for treating diabetes, herein, a hyphenated strategy by off-line coupling high-speed countercurrent chromatography, ultrafiltration HPLC-UV-MS and prep-HPLC was developed. And thus, α-glucosidase inhibitors from Rubus suavissimus leaves was comprehensively profiled, purified and characterized. As a result, twenty-six compounds were identified as potential α-glucosidase inhibitors and favorably isolated by prep-HPLC. Their structures were identified via UV, MS, and ¹H-NMR. Notably, fourteen compounds, including protocatechuic acid (1), myketin (3), epicatechin (4), vanillic acid (6), apigenin (11), catechin (12), ferulic acid (15), luteolin (16), 3, 3′-di-O-methylellagic acid (17), chlorogenic acid (19), 3, 3′-di-O-methylellagic acid-4′-O-β-D-glucoside (20), cinnamic acid (21), syringate (24) and ethylbrevifolin-carboxylate (25), were reported in leaves of Rubus suavissimus for the first time. In addition, α-glucosidase inhibitory activities of compounds 1–26 were evaluated, and eighteen compounds exhibited stronger α-glucosidase inhibitory activities than acarbose (IC₅₀ value at 214.24 ± 3.48 μg/mL, positive control). The results indicated that the proposed method is a highly efficient strategy for comprehensive profiling and purification of bioactive target compounds, including both major and minor components, from natural products.     

超敏C反应蛋白与自发性脑出血患者血肿量及预后的相关性分析

目的探讨超敏C反应蛋白(hs-CRP)与自发性脑出血患者(SICH)血肿量和预后的相关性。方法选取2016-01-2018-10萍乡市人民医院收治的SICH患者162例。将其分为大量血肿组、小量血肿组,选择同时期江西萍乡市人民医院80例门诊体检者为对照组。检测和比较3组入院时hs-CRP水平,比较预后良好和不良患者的hs-CRP水平,评价血清hs-CRP水平与血肿体积、预后的相关性。结果大量及小量血肿组hs-CRP水平显著高于对照组(P<0.01),且大量血肿组hs-CRP水平显著高于小量血肿组(P<0.05)。预后良好组hs-CRP水平显著低于预后不良组(P<0.05)。SICH患者hs-CRP水平与血肿量大小和GOS评分呈正相关(r=0.452,0.433,P<0.05)。结论SICH患者血清hs-CRP水平显著升高,与血肿量大小和预后明显相关。