丹银海绵对糖尿病大鼠皮肤溃疡创面愈合的影响

目的:探讨丹银海绵对糖尿病大鼠皮肤溃疡创面愈合的影响。方法:将雄性Wistar大鼠随机分为8组。除空白对照组外,其余7组大鼠,通过手术在其背部形成一10mm×10mm相同大小,深达肌层的溃疡,分别给予抗生素、生长因子凝胶、纳米银、丹黄散,以及不同浓度的丹银海绵处理溃疡面。给药28d后处死大鼠,取溃疡部位新生肉芽组织,HE染色观察组织形态的变化;WesternBlot检测大鼠创面组织中AGEs、hs-CRP、IL-1、IL-6、bFGF、PDGF、VEGF表达水平。结果:病理切片观察显示适宜浓度的丹银海绵可以促进血管新生并伴扩张,同时生成大量新生成纤维细胞。WesternBlot检测显示高浓度的丹银海绵可以显著上调创面组织中生长因子表达(P<0.05),降低AGEs水平及炎症因子表达(P<0.05)。结论:适宜浓度的丹银海绵对于糖尿病大鼠皮肤溃疡的愈合有明显的促进作用,提高治疗效果。     

艾炷灸命门穴对衰老模型大鼠脑组织中AGEs、RAGE表达影响

目的:观察艾炷灸命门穴对D-半乳糖致衰老大鼠脑组织中AGEs及其受体RAGE表达的影响,探讨艾炷灸命门穴延缓衰老的作用机制。方法:雄性SD大鼠40只,随机分为空白组10只、模型制备组30只,空白组腹腔注射生理盐水,模型制备组进行腹腔注射D-半乳糖500 mg/kg,每日1次,连续60天,模型制备成功后随机选取20只分为模型对照组、命门穴治疗组,艾炷灸治疗4周。酶联免疫吸附测定法(Elisa)观察各组大鼠脑组织匀浆中AGES、RAGE表达水平,RT-PCR观察RAGE mRNA的表达水平。结果:模型对照组大鼠脑组织中AGES、RAGE及RAGE mRNA表达水平比空白组明显增加(P<0.01);命门穴治疗组脑组织中AGES、RAGE及RAGE mRNA表达水平明显低于模型对照组(P<0.01)。结论:艾炷灸命门穴可以延缓衰老,其机制可能是AGEs的水平下调减少了对蛋白的直接修饰及抑制AGEs与特异性配体RAGE结合而引发一系列的生物学效应而达到延缓衰老的目的。     

Simvastatin attenuates the endothelial pro-thrombotic shift in saphenous vein grafts induced by Advanced glycation endproducts

Background

Advanced glycation endproducts (AGEs) and its receptors (RAGEs) are heterogeneous signaling proteins associated to diabetes and responsible of endothelial alterations leading to atherosclerosis progression and graft failure. The aim of this study was to investigate the role of statin in reducing AGEs related endothelial damage.

Methods

Endothelial cell(EC) obtained from leftovers of saphenous vein grafts of non-diabetic patients were incubated with AGEs (2 and 20 μM) and subsequently treated with Simvastatin. Neutrophils (PNM) adherence, ROS production and RAGE and peroxisome proliferator-activated receptors-gamma (PPAR-γ) expression were analyzed. As clinical validation of the in vitro findings, ECs of diabetic patients in optimized glycaemic control administered with a 3 weeks Simvastatin regimen were similarly processed.

Results

Simvastatin blunted the rise in PMN adhesion and ROS generation following stimulation of saphenous vein EC culture with AGEs in vitro. This effect was time dependent and was associated to an increase in PPAR-γ induction paralleled by a decrease in RAGEs expression. Parallely, data from diabetic patients administered with Simvastatin showed a similar significant reduction in PNM adhesion and ROS generation. Simvastatin treatment significantly decreased RAGEs expression in ECs from diabetic patients and determined a slight increase in PPAR-γ expression but the latter failed to reach statistical significance. Interference in the function of these two crucial pathways might be at the root of the statin antinflammatory and antithrombotic effect in the context of AGEs-associated damage.

Conclusions

Despite the recently raised warning on the use of statins in the diabetic population, this study elucidates their cornerstone position in endothelial homeostasis of saphenous grafts in patients with controlled diabetes.     

Antimicrobial activity in medicinal plants of the Scrophulariaceae and Acanthaceae

One hundred and one crude extracts obtained from various plant parts of 59 species representing mostly the plant families Scrophulariaceae and Acanthaceae have been investigated for their antimicrobial activity. Plants were selected using ethnobotanical and chemotaxonomic information. Growth inhibition using agar disk diffusion assays was determined against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans. Growth inhibitory activity against one or more of the microbial species was detected in over 40% of the samples.     

Relationship between advanced glycation end products and gestational diabetes mellitus

Objective: To investigate the levels of and dynamic changes of advanced glycation end products (AGEs) in maternal plasma during pregnancy and explore the association between these levels and gestational diabetes mellitus (GDM).

Methods: This study recruited 90 GDM women and 90 healthy pregnant controls. The women received prenatal care and were hospitalized for delivery in Peking University First Hospital in China between October 2015 and April 2016. The patients were recruited and provided blood samples during gestational weeks 24–29. The levels of AGEs, TNF-α, hs-CRP, plasma glucose, and FINS and lipid profiles were measured, and HOMA-IR was calculated. New blood samples were collected and AGE was measured again in the two groups at 33–41 weeks of gestation to identify its dynamic changes.

Results: The levels of AGEs were significantly higher in the GDM group than in the NGT group at both 24–29 weeks (473.65?±?105.32 versus 324.36?±?57.86?ng/L; p?p?p?p?=?.003), TNF-α (p?=?.005), and hs-CRP (p?AGEs was significantly higher at 33–41 weeks than at 24–29 weeks (p?=?.001). In the NGT group, there was no significant change in the concentration of AGEs between the two gestational periods (p?=?.388).

Conclusions: Plasma levels of AGEs are associated with GDM. During pregnancy, the changes observed in the levels of AGEs were different between GDM and normal pregnancies.     

Threshold serum concentrations of tumour necrosis factor alpha (TNFα) as a potential marker of the presence of microangiopathy in children and adolescents with type 1 diabetes mellitus (T1DM)

The aim of this study was to estimate the threshold serum concentrations of advanced glycation end products (AGEs) and their soluble receptors (sRAGE) as well as tumour necrosis factor alpha (TNFα), vascular endothelial growth factor₁₆₅ (VEGF₁₆₅) and interleukin-12 (IL-12) in predicting the occurrence of microangiopathy in children and adolescents with type 1 diabetes mellitus (T1DM). We studied 88 children and adolescents (age range: 6–20 yrs) with T1DM and 32 control subjects (age range: 7–20 yrs). All study participants had their daily urinary albumin excretion, HbA1c and serum creatinine levels measured, and underwent an eye examination and 24-h blood pressure monitoring. Moreover, serum concentrations of AGEs, sRAGE, TNFα, VEGF₁₆₅ and IL-12 were measured. In order to calculate the threshold values of the studied parameters, the Receiver Operating Characteristic (ROC) curve analysis was used. The results of our study have shown that among all the studied parameters a discriminative ability was found for TNFα, VEGF₁₆₅, duration of the disease, serum AGEs concentrations and daily urinary albumin excretion. However, the highest value of the area under the ROC curve (AUC_ROC) in predicting the occurrence of diabetic microangiopathy was found for serum TNFα concentrations with its threshold value of 1.7 pg/ml [AUC_ROC = 0.88 (95% CI: 0.79–0.97)]. The sensitivity and specificity for this variable was at the level of 85.7% and 94.3%, respectively. In conclusion, according to our results serum TNFα concentrations over 1.7 pg/ml may point to the presence of diabetic microangiopathy in children and adolescents T1DM.     

“赵氏脱疽方”干预AGEs及糖尿病足相关因子的研究

目的:探讨"赵氏脱疽方"治疗糖尿病足,干预血脂、糖基化终末产物(AGEs)及相关因子的作用。方法:将符合纳入标准的糖尿病足患者39例随机分成3组,各组在给予糖尿病常规治疗基础上,给予纯中药组(13例)口服赵氏脱疽汤,并用赵氏脱疽膏外敷;给予中西药结合组(12例)口服赵氏脱疽汤,并用依沙吖啶外敷;给予纯西药对照组(14例)口服已酮可可碱,并用依沙吖啶外敷。观察各组治疗前后糖化血红蛋白、AGEs等。结果:3组治疗前后有明显变化,各组疗效比较,纯中药组疗效优于中西药结合组,纯中药组和中西药结合组疗效均明显优于西药对照组。结论:中医药治疗糖尿病足坏疽有其独特优势,"赵氏脱疽方"对于AGE及相关因子均有不同程度的改善,同时配合中药外治糖尿病足坏疽有明显优势。     

Advanced glycation end products in diabetic and non-diabetic human subjects suffering from cataract

Advanced glycation end products (AGEs) play a pivotal role in loss of lens transparency, i.e., cataract. AGEs formation occurs as a result of sequential glycation and oxidation reaction between reducing sugars and protein. AGEs production takes place throughout the normal aging process but its accumulation is found to be more rapid in diabetic patients. In this study, we quantified AGEs and N-(carboxyethyl) lysine (CEL) in human cataractous lenses from non-diabetic (n = 50) and diabetic patients (n = 50) using ELISA. We observed significantly higher (p < 0.001) levels of lens AGEs and CEL in diabetic patients with cataract as compared with their respective controls. The presence of AGEs and CEL was also determined by western blotting and immuno-histochemical analysis. Furthermore, isolated β-crystallin from cataractous lenses of non-diabetic and diabetic patients was incubated with different sugars to evaluate the extent of glycation in a time dependent manner. Our data indicated more pronounced glycation in patients suffering from diabetes as compared to non-diabetics subjects demonstrating the need to focus on developing normoglycemic approaches. Such studies may provide an insight in developing therapeutic strategies and may have clinical implications.