Salidroside ameliorates insulin resistance through activation of a mitochondria-associated AMPK/PI3K/Akt/GSK3β pathway

Background and Purpose

Recent reports have suggested that salidroside could protect cardiomyocytes from oxidative injury and stimulate glucose uptake in skeletal muscle cells by activating AMP-activated protein kinase (AMPK). The aim of this study was to evaluate the therapeutic effects of salidroside on diabetic mice and to explore the underlying mechanisms.

Experimental Approach

The therapeutic effects of salidroside on type 2 diabetes were investigated. Increasing doses of salidroside (25, 50 and 100 mg·kg⁻¹·day⁻¹) were administered p.o. to db/db mice for 8 weeks. Biochemical analysis and histopathological examinations were conducted to evaluate the therapeutic effects of salidroside. Primary cultured mouse hepatocytes were used to further explore the underlying mechanisms in vitro.

Key Results

Salidroside dramatically reduced blood glucose and serum insulin levels and alleviated insulin resistance. Hypolipidaemic effects and amelioration of liver steatosis were observed after salidroside administration. In vitro, salidroside dose-dependently induced an increase in the phosphorylations of AMPK and PI3K/Akt, as well as glycogen synthase kinase 3β (GSK3β) in hepatocytes. Furthermore, salidroside-stimulated AMPK activation was found to suppress the expression of PEPCK and glucose-6-phosphatase. Salidroside-induced AMPK activation also resulted in phosphorylation of acetyl CoA carboxylase, which can reduce lipid accumulation in peripheral tissues. In isolated mitochondria, salidroside inhibited respiratory chain complex I and disturbed oxidation/phosphorylation coupling and moderately depolarized the mitochondrial membrane potential, resulting in a transient increase in the AMP/ATP ratio.

Conclusions and Implications

Salidroside exerts an antidiabetic effect by improving the cellular metabolic flux through the activation of a mitochondria-related AMPK/PI3K/Akt/GSK3β pathway     

不同方法对食源性致病菌耐药性监测研究

目的了解江苏地区食源性致病菌的常用抗菌药耐药谱,评价不同药敏方法在致病菌耐药性监测中的适用性。方法用Etest和微量肉汤稀释法,对江苏省2012-2014年食源性疾病常规监测检出的金黄色葡萄球菌、副溶血性弧菌、沙门菌菌株进行药敏鉴定。结果金黄色葡萄球菌对红霉素的耐药率最高,其次为复方磺胺甲噁唑和四环素,且有多重耐药;副溶血性弧菌除对四环素和复方磺胺甲噁唑有一定的耐药,对其他6种革兰氏阴性菌抗生素均敏感。沙门菌对萘啶酸的耐药率超过50.0%。两种方法药敏检测结果对不同抗生素符合率有差异,但符合率均80%。结论 Etest和微量肉汤稀释法有较好的一致性,但所需时间及操作要求有差异,可根据实际需要进行选择。     

粮食中微量元素锌与大骨节病的关系

本文就西南大骨节病区粮食中微量元素锌、铁、锰、铜、铬测定作了初步分析。其中较有规律的是锌,并对锌在大骨节病发病过程中的作用进行了试探性讨论。认为锌在发病中占有重要的地位,很可能是硒对大骨节病作用的重要复合因子之一。     

Molecular bases of antithrombin deficiency in French families: identification of seven novel mutations in the antithrombin gene

We have investigated the molecular bases of familial antithrombin deficiency in eight French families. Eight mutations in the antithrombin coding exons were identified, seven of which were novel mutations. In all cases, individuals were heterozygous for the mutation. We found two small frameshift deletions in exon 3a, leading to type I deficiency. Five missense mutations in exons 3b or 5 also caused type I deficiency and their potential consequences on the antithrombin three-dimensional structure were analysed. The last mutation in exon 4 was associated with a type II 'reactive site' deficiency: a dysfunctional antithrombin that is affected in its interaction with thrombin was present in circulation.     

Experimental reconstruction of dog's esophagus with biotype artificial esophagus

OBJECTIVE: At present, there are few materials available for esophagus reconstruction anywhere in the world. The reported survival rate in animals during the perioperative period is comparatively low. The present study assessed the feasibility of using a biotype artificial esophagus in the reconstruction of a dog's esophagus. METHODS: In 30 mongrel dogs, a portion of the thoracic esophagus was resected and an 8 cm section of artificial esophagus was transplanted to reconstruct the organ. The survival rate, food intake and process of healing were observed. RESULTS: Of the 30 dogs, 28 survived the peri­operative period (93.3% survival). Two dogs (6.7%) developed an anastomotic fistula; 19 dogs survived for 1 year, a survival rate of 79.2% (19/24) with the remaining six dogs were killed according to the experimental protocol. Detachment of the artificial esophagus occurred on average 28.8 days after operation and the dogs suffered from varying degrees of dysphagia 23?45 days after operation. Gradual remission occurred after 4 months. The histological study revealed that the regenerated esophagus was composed of fibrous and connective tissues and the luminal surface was covered with squamous epithelium in 3?6 months. CONCLUSION: The transplanted artificial esophagus detached after the surrounding ‘regenerated esophagus’ had formed, and the squamous epithelium gradually covered the luminal surface. Continuous remodeling of the ‘regenerated esophagus’ gradually relieved the stenosis. Whether detachment of the implant and the postoperative stenosis can be solved is the key problem restricting the use of the biotype artificial esophagus in clinical practice.     

The clinical and hemodynamic results of mitral balloon valvuloplasty for patients with mitral stenosis complicated by severe pulmonary hypertension

BACKGROUND: Percutaneous balloon mitral valvuloplasty (PBMV) has become the procedure of choice for isolated, uncomplicated mitral stenosis (MS) with favorable morphology and may be a useful method for surgical high-risk conditions such as advanced age, the presence of severe tricuspid regurgitation, New York Heart Association (NYHA) class IV at presentation, and severe pulmonary hypertension (PH). The development of PH is a common and important sequela in patients with advanced mitral stenosis and is associated with hemodynamic and clinical decompensation. However, the influence of PBMV on patients with severe PH has seldom been evaluated. Our objective was to probe into the immediate and long-term effects of PBMV on patients with MS complicated by severe PH and to predict the factors that determine the prognosis of patients with severe PH. METHODS: We included 44 patients with MS complicated by severe PH (systolic pulmonary pressure >80 mm Hg, group S) and 67 patients with MS complicated by mild PH (systolic pulmonary pressure <50 mm Hg, group M) in this study and we compared their immediate and late results after a follow-up period of 24 months after PBMV. RESULTS: Compared with group M, patients in group S were older, presented more frequently with NYHA III-IV class, valvular echo score >or=8, and more severe tricuspid regurgitation, and had a bigger left atrial diameter before PBMV. The successful rate and the incidence of severe complications from the PBMV procedure were similar in both groups. There were more cases of post-PBMV mitral valve area >or=1.5 cm(2) in group M than in group S, and the average mitral valve area in group M was somewhat larger than that of group S. After PBMV, NYHA class obviously improved in both groups, but there were more patients with NYHA0.05). NYHA class I or II was present for 80.6% in group M and 59.1% in group S (p<0.10). RESULTS: PBMV is a safe and effective procedure for patients with severe PH. It can remarkably improve clinical outcomes, although hemodynamic effects of PBMV on this subgroup are not complete. Pre-existing older age, more severe valvular lesion and tricuspid regurgitation, worse cardiac function, and bigger left atrial size in patients with severe PH may be important risk factors for the poor hemodynamic outcomes of PBMV.     

Dietary Patterns and Chronic Obstructive Pulmonary Disease: A Meta-analysis

Investigation of the relationship between dietary patterns and some chronic noncommunicable diseases has become appealing in nutritional epidemiology. Some studies have reported potential associations between dietary patterns and the risk of chronic obstructive pulmonary disease; however, the results remain conflicting. Thus, we conducted this meta-analysis to pool the results of studies to clarify the associations between dietary patterns and the risk of chronic obstructive pulmonary disease. A literature search of MEDLINE and EBSCO databases was performed to identify relevant studies published from January 1990 up to June 2015. A total of 13 studies met the inclusion criteria and were included in this meta-analysis. The highest category of healthy/prudent dietary patterns when compared with the lowest category was apparently associated with a decreased risk (OR = 0.55; CI: 0.46, 0.66; P < 0.0001). An increase in the risk of chronic obstructive pulmonary disease was shown for the highest compared with the lowest categories of “unhealthy/western-style” dietary patterns (OR = 2.12; CI: 1.64, 2.74; P < (0.0001). The results of this meta-analysis indicate that different dietary pattern may be associated with the risk of chronic obstructive pulmonary disease.     

Paclitaxel-induced stress granules increase LINE-1 mRNA stability to promote drug resistance in breast cancer cells

Abnormal expression of long interspersed element-1 (LINE-1) has been implicated in drug resistance, while our previous study showed that chemotherapy drug paclitaxel (PTX) increased LINE-1 level with unknown mechanism. Bioinformatics analysis suggested the regulation of LINE-1 mRNA by drug-induced stress granules (SGs). This study aimed to explore whether and how SGs are involved in drug-induced LINE-1 increase and thereby promotes drug resistance of triple negative breast cancer (TNBC) cells. We demonstrated that SGs increased LINE-1 expression by recruiting and stabilizing LINE-1 mRNA under drug stress, thereby adapting TNBC cells to chemotherapy drugs. Moreover, LINE-1 inhibitor efavirenz (EFV) could inhibit drug-induced SG to destabilize LINE-1. Our study provides the first evidence of the regulation of LINE-1 by SGs that could be an important survival mechanism for cancer cells exposed to chemotherapy drugs. The findings provide a useful clue for developing new chemotherapeutic strategies against TNBCs.