The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery

Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.     

吉林农村寄宿中学生生长发育水平调查分析

目的了解吉林省农村寄宿中学生生长发育状况。方法采取整群随机抽样方法,从吉林省某农村寄宿中学生中抽取13～18岁学生127名,对其生长发育指标（年龄、性别、身高、体重、三头肌部皮褶厚度、上臂围、上臂肌围、胸围、腰围、臀围）进行调查,并计算体重指数、腰臀比。结果在身高、体重、上臂围、胸围、腰围、臀围方面,男女生之间有显著差异（P〈0.05）。被调查对象青春期生长有突增的现象。结论吉林省农村寄宿中学生的生长发育指标随年龄增加呈增长的趋势,符合一般生长发育的规律。     

葡萄糖和胰岛素对内皮细胞激肽释放酶mRNA表达的影响

目的观察葡萄糖、L-葡萄糖和胰岛素对内皮细胞激肽释放酶mRNA(TKA-mRNA)表达的影响.方法利用RT-PCR方法观察上述试剂对体外培养的内皮细胞TKA-mRNA表达的影响.结果葡萄糖浓度为4、8mmol/L时对TKA-mRNA的表达无影响;16、32mmol/L时则有明显抑制作用,浓度越高,抑制作用出现越早;等摩尔L-葡萄糖的抑制作用只在32mmol/L、培养15d时显现;胰岛素对TKA-mRNA表达无影响.结论高浓度葡萄糖是抑制内皮细胞TKA-mRNA表达的主要因素.     

银川地区213名正常人口服葡糖耐量试验结果

作者等在进行银川地区糖尿病患病率调查的同时,对213名正常成人进行口服葡糖耐量试验,发现该地区受试者各时限血糖均值较外地报道的数值为高,变异程度也大。造成这种结果的原因,经推测是由于本组受试者包括了一部分高龄人群,且受试者中66.7％为回民,他们的某些特殊饮食习惯(如嗜饮糖茶等)可能对糖耐量有所影响。     

益气活血中药复方与CVB3对乳鼠心肌细胞葡萄糖转运体2表达的影响

目的研究益气活血中药复方与CVB3对乳鼠心肌细胞葡萄糖转运体2表达的影响,以期从基因水平揭示CVB3心肌炎的发病机制及益气活血中药复方治疗病毒性心肌炎的作用机制,并进一步证实益气活血中药复方是治疗CVB3病毒性心肌炎的有效方剂。方法通过改良的抑制性消减杂交技术（suppressionsubtractivehybridization,SSH）,分离大鼠心肌细胞CVB3感染组和益气活血中药复方给药组差异表达的基因,并通过荧光RT-PCR对上述结果进行验证。结果 SSH结果显示益气活血中药复方治疗组中葡萄糖转运体2基因的表达比CVB3病毒组中低,这一结果通过荧光RT-PCR得到验证。结论核糖体蛋白S20基因表达上调可能是CVB3致病毒性心肌炎机制之一;益气活血法能够通过下调核糖体蛋白S20基因的表达而实现治疗病毒性心肌炎的目的。     

Mussel oligopeptides ameliorate cognition deficit and attenuate brain senescence in d-galactose-induced aging mice

Dietary supplementation exerts beneficial effects in reducing incidence of chronic neurodegenerative diseases. The purpose of this study was to examine protective effects of mussel (Mytilus edulis) oligopeptides supplementation on brain function in d-galactose induced aging mice. Sixty female 8-month-old mice were randomly divided into five groups: vehicle control, d-galactose, and d-galactose combined with 200, 500, 1000 mg/kg mussel oligopeptides. The results showed that mussel oligopeptides could improve cognitive learning and memory ability and protect the hippocampal neurons. In addition, GSH, SOD and GSH-pX activities were increased and MDA level was significantly decreased in mice fed with mussel oligopeptides. It was also found that mussel oligopeptides supplementation prevented d-galactose-induced elevations of iNOS activity and NO production and lactate acid levels in brain. Moreover, PI3K and Akt genes were up-regulated by mussel oligopeptides supplementation. These findings suggest that mussel oligopeptides are able to enhance exercise capacity and protect against oxidative damage caused by d-galactose in aging model mice through regulating oxidation metabolism and PI3K/Akt/NOS signal pathway. Therefore, mussel oligopeptides are good materials for future development of healthcare products to combat age-related brain dysfunction and to improve healthy life span.     

Lower Education Level Is a Major Risk Factor for Peritonitis Incidence in Chronic Peritoneal Dialysis Patients: A Retrospective Cohort Study with 12-Year Follow-Up

♦ Background: Peritoneal dialysis (PD)-related peritonitis remains an important complication in PD patients, potentially causing technique failure and influencing patient outcome. To date, no comprehensive study in the Taiwanese PD population has used a time-dependent statistical method to analyze the factors associated with PD-related peritonitis.♦ Methods: Our single-center retrospective cohort study, conducted in southern Taiwan between February 1999 and July 2010, used time-dependent statistical methods to analyze the factors associated with PD-related peritonitis.♦ Results: The study recruited 404 PD patients for analysis, 150 of whom experienced at least 1 episode of peritonitis during the follow-up period. The incidence rate of peritonitis was highest during the first 6 months after PD start. A comparison of patients in the two groups (peritonitis vs null-peritonitis) by univariate analysis showed that the peritonitis group included fewer men (p = 0.048) and more patients of older age (≥65 years, p = 0.049). In addition, patients who had never received compulsory education showed a statistically higher incidence of PD-related peritonitis in the univariate analysis (p = 0.04). A proportional hazards model identified education level (less than elementary school vs any higher education level) as having an independent association with PD-related peritonitis [hazard ratio (HR): 1.45; 95% confidence interval (CI): 1.01 to 2.06; p = 0.045). Comorbidities measured using the Charlson comorbidity index (score >2 vs ≤2) showed borderline statistical significance (HR: 1.44; 95% CI: 1.00 to 2.13; p = 0.053).♦ Conclusions: A lower education level is a major risk factor for PD-related peritonitis independent of age, sex, hypoalbuminemia, and comorbidities. Our study emphasizes that a comprehensive PD education program is crucial for PD patients with a lower education level.     

高脂环境对大鼠成肌细胞糖脂代谢的影响

目的: 探讨棕榈酸(PA)形成的高脂环境对大鼠成肌细胞糖代谢的影响,为深入研究2型糖尿病的发生机制提供理论依据。方法: 用0.1、0.3、0.5 mmol/L棕榈酸处理原代培养大鼠成肌细胞6、12、24 h后,用MTT法检测成肌细胞活力;用油红O染色法检测成肌细胞脂肪变性后甘油三酯沉积;用甘油磷酸氧化酶-过氧化物酶(GPO-POD)法测定成肌细胞脂肪变性后甘油三酯含量;用同位素示踪法检测葡萄糖摄取。结果: 随着PA处理浓度(0.1-0.5 mmol/L)的增加,及暴露时间(6~24 h)的增加,成肌细胞活力逐渐降低、甘油三酯沉积及含量不断增高、葡萄糖摄取不断降低,并呈现剂量和时间依赖性的效应关系。与对照组比较,0.3 mmol/L PA(24 h)和0.5 mmol/L PA(12、24 h)造成细胞活力、甘油三酯沉积及含量、葡萄糖摄取的改变最为明显。结论: PA可以作用于大鼠成肌细胞,使其脂肪沉积,甘油三酯含量增加,糖摄取减少,并呈剂量依赖关系。