SIRT3 regulation of mitochondrial oxidative stress

Mitochondria play a central role in the production of reactive oxygen species as byproducts of metabolism and energy production. In order to protect cellular structures from oxidative stress-induced damage, cells have evolved elegant mechanisms for mitochondrial ROS detoxification. The mitochondrial sirtuin, SIRT3, is emerging as a pivotal regulator of oxidative stress by deacetylation of substrates involved in both ROS production and detoxification. This review will summarize recent findings on the regulation of mitochondrial ROS homeostasis by SIRT3.     

20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol-fortified ginseng extract attenuates the development of atopic dermatitis-like symptoms in NC/Nga mice

Ethnopharmacological relevance

Ginseng and ginsenosides are frequently used in the treatment of chronic inflammatory diseases. Recently, 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol (GPD), the main metabolite of ginsenosides, was reported to have both anti-allergic and anti-pruritic effects. The immunomodulatory effects of GPD-fortified ginseng extract (GFGE) on atopic dermatitis (AD)-like symptoms in mice were investigated. This study was designed to investigate the preventive effect of GFGE on AD-like symptoms.

Materials and methods

The effects of orally administered GFGE on Dermatophagoides farinae body extract (DFE)-induced AD-like symptoms in NC/Nga mice were assessed by analyzing dermatitis score, ear thickness, scratching time, skin histological changes, and serum level of macrophage-derived chemokine (MDC). In addition, splenocytes were isolated from the mice and stimulated with anti-CD3 and anti-CD28 monoclonal antibodies to produce cytokines.

Results

Oral administration of GFGE significantly attenuated DFE-induced increases in dermatitis score, ear thickness, scratching time, and severity of skin lesions in NC/Nga mice. GFGE treatment also reduced level of MDC in serum, infiltration of eosinophils and mast cells in skin, and production of cytokines in splenocytes.

Conclusions

These results suggest that GFGE might ameliorate DFE-induced AD-like symptoms and be an alternative therapeutic agent for the prevention of AD.     

Sequence analysis of the gene coding for glyceraldehyde-3-phosphate dehydrogenase (gpd) of Podospora anserina: use of homologous regulatory sequences to improve transformation efficiency

Summary The glyceraldehyde-3-phosphate dehydrogenase (gpd) gene of Podospora anserina has been isolated from a genomic library by heterologous hybridization with the corresponding gene of Curvularia lunata. The coding region consists of 1014 nucleotides and is interrupted by a single intron. The amino-acid sequence encoded by the gpd gene shows a high degree of sequence identity with the corresponding gene products of various fungi. Multiple alignments of all fungal GPD sequences so far available resulted in the construction of a phylogenetic tree. The evolutionary relationships of the various fungi belonging to different taxa will be discussed on the basis of these data. Sequence analysis of 1.9 kbp of the 5 non-coding region revealed the presence of typical fungal promoter elements. Utilizing different parts of the 5 regulatory sequence of the Podospora gpd gene, expression vectors containing a dominant selectable marker gene (hygromycin B phosphotransferase) have been constructed for the transformation of P. anserina protoplasts. The use of these homologous gpd regulatory sequences resulted in a significant increase in transformation efficiencies compared to those obtained with vectors in which the selectable marker gene is under the control of the corresponding heterologous promoter of Aspergillus nidulans.     

新抑癌基因GPD1在结肠癌细胞HCT-8中的作用及其预后潜力研究

目的 探究新抑癌基因甘油-3-磷酸脱氢酶1（glycerol-3-phosphate dehydrogenase 1,GPD1）在结肠癌发生、发展中的作用及其与临床预后的关系。方法 应用HCT-8结肠癌细胞系,以siRNA干扰GPD1表达后进行细胞功能实验,分别以MTS实验与集落形成实验检测细胞增生活力与集落形成能力,以划痕试验、Transwell实验探究GPD1对HCT-8细胞系迁移能力的影响。对TCGA数据库进行生物信息学分析,探究GPD1表达水平与结直肠癌患者临床预后的关系,并明确GPD1低表达与其编码基因甲基化之间的关系。结果 干扰GPD1基因表达后,HCT-8细胞增生活力明显增强,重复实验差异具有统计学意义（P<0.01）;集落形成实验结果显示,GPD1干扰后的HCT-8细胞集落数目增多且集落直径增大,差异具有统计学意义（P<0.01）。划痕实验与Transwell实验结果显示,敲低GPD1表达的HCT-8细胞迁移能力无显著变化,表明GPD1对结肠癌细胞迁移能力无影响。生物信息学分析结果显示,GPD1低表达的结直肠癌患者总存活率（χ²=4.1,P=0.040）及无病存活率（χ²=13.2,P<0.000 1）均明显低于GPD1高表达患者,且GPD1低表达水平是结直肠癌预后不良的独立风险因素（P<0.05）。甲基化分析结果显示,结直肠癌组织中GPD1低表达与其编码基因高甲基化呈负相关（P<0.05）。结论 GPD1在结肠癌中发挥抑制细胞增生与集落形成的作用,且GPD1低表达是结直肠癌患者不良预后的独立预测因素。     

Inhibition of p-chlorophenoxyisobutyrate by 1-methyl-2-mercaptoimidazole and related compounds

The induction of both rat liver mitochondrial α-glycerophosphate dehydrogenase (GPD) and the soluble malic enzyme by thyroid hormone is enhanced by p-chlorophenoxyisobutyrate (CPIB). CPIB also affects lipid metabolism by a mechanism which is unrelated to the thyroid hormone.The intensification of the T₄ response by CPIB was blocked by the simultaneous administration of the goitrogen, l-methyl-2-mercaptoimidazole (methimazole, MI), and this particular inhibition of CPIB by MI was shared by a number of other compounds containing the ureido or substituted ureido grouping: 1-methylimidazole, imidazole, thiourea, 2-thiouracil, 2-mercaptobenzimidazole, 2-hydroxybenzimidazole and 2- mercaptopyrimidine. However, the effect of CPIB in (a) preventing an orotic acid fatty liver, or (b) intensifying the β-lipoprotein band in serum gel electrophoresis was not inhibited by imidazole.Rat liver malic enzyme activity was increased somewhat by MI and other ureido compounds per se.     

鼻咽癌放射治疗致口腔炎治疗方法探讨

目的探讨鼻咽癌放射性口腔炎临床有效的治疗方法。方法通过40例鼻咽癌Ⅰ～Ⅳ期病人,进行分组,(用药组)20例,(对照组)20例,用GPD混合液口腔含漱治疗。结果口腔炎发生率、口咽疼痛缓解率,用药组与对照组比较,放射剂量≤10GY时放射性口腔炎的发生率分别为25%(5/20)和60%(12/20),X2=5.01,P<0.05。放射剂量在12～36GY时、放射性口腔炎、Ⅲ、Ⅳ级发生率分别为30%(6/20)和70%(14/20),X2=6.4P<0.05。结论鼻咽癌放射治疗的同时,用GPD混合液含漱,能明显减轻放射所致的口咽疼痛及口腔炎发生率。     

非特异性精神发育迟滞相关基因GPD2的研究进展

GPD2基因属于新发现的非特异性神经发育迟滞相关基因之一,编码线粒体甘油磷酸脱氢酶（mGPDH）,最新的分子和功能研究显示GPD2基因的转录物水平和它所翻译的mGPDH蛋白活性在一个轻度非特异性神经发育迟滞患者的淋巴细胞中比正常人减少了约1/2。相关研究显示mGPDH蛋白质的功能缺陷可能与神经发育迟滞（MR）相关,表明GPD2基因在某些方面涉及神经发育迟滞。本文综述了GPD2基因的结构和产物、基因的生物学功能,与精神发育迟滞的相关性的研究现状,并对以后的研究工作进行了展望。     

Persistent generalized periodic discharges: A specific marker of fatal outcome in cerebral hypoxia

Objectives

Electroencephalography (EEG) is one of the methods used in predicting the outcome after cerebral hypoxia. In this study we aim to evaluate the significance of generalized periodic discharges (GPD) as a prognostic marker.

Epileptiform and periodic EEG activities induced by rapid sevoflurane anaesthesia induction

Objectives

The aim of the study was to compare the EEG findings and haemodynamic parameters of adult male patients while undergoing mask induction with sevoflurane anaesthesia with either controlled hyperventilation (CH) or spontaneous breathing (SB).