“标本配穴”电针对慢性心肌缺血模型大鼠线粒体结构及呼吸酶活性的影响

目的:以心肌线粒体为切入,观察“标本配穴”电针对慢性心肌缺血模型大鼠心肌线粒体结构、GAPDH、CS、CCO的酶活性及心肌组织ATP含量的影响,探讨“标本配穴”电针对慢性心肌缺血模型大鼠心肌线粒体的保护机制。方法:将30只Wistar雄性大鼠随机分为空白组、模型组、标本配穴组,每组10只。模型组、标本配穴组大鼠皮下注射盐酸异丙肾上腺素制备慢性心肌缺血大鼠模型。标本配穴组在造模结束后取“内关”“足三里”“关元”电针干预10 min,疏密波,2~100 Hz,1 mA,连续21天。运用透射电镜观察心肌线粒体结构变化,采用试剂盒检测3-磷酸甘油醛脱氢酶(GAPDH)、柠檬酸合成酶(CS)、细胞色素C氧化酶(CCO)的酶活性及心肌组织ATP含量。结果:与空白组比较,模型组线粒体结构破坏明显,大部分线粒体出现变形空泡化;而与模型组比较,标本配穴组线粒体结构损伤程度明显减轻。与空白组相比,模型组、标本配穴组心肌组织ATP含量、GAPDH、CS、CCO活性均明显降低(P<0.01)。但与模型组相比,标本配穴组4指标均显著增高(P<0.01),且心肌组织ATP含量与GAPDH、CS、CCO活性成线性相关。结论:在慢性心肌缺血状态下,标本配穴电针可提升线粒体呼吸酶活性,增加有氧呼吸产能效率,改善心脏能量代谢,从而减轻心肌细胞的结构破坏,对心肌组织起到保护作用。     

尼罗罗非鱼肉营养成分分析

<正> 尼罗罗非鱼(Tilapia nilotica)是我国从非洲引进的热带鱼类,具有刺少肉味鲜嫩、食性广、生长快、繁殖力强、养殖周期短等特点。已快速地养殖到全国各地。作者对利用地热资源人工喂养条件下的尼罗罗非鱼肉的氨基酸和肉内的粗蛋白、脂肪、维生素等成分进行分析,评估尼罗罗非鱼肉的营养价值,从营养学的角度为人们提供科学依据。     

云南美登木共生放线菌菌株CS产生的新多羟基环己烷衍生物

从云南美登木共生放线菌菌株(Streptomyces sp.)CS的发酵产物中分离得一个新的多羟基环己烷衍生物,并通过波谱学特征鉴定化合物的结构为1-isobutyroxymethyl cyclohex-1(6)-ene-2,3,4,5-tetrol-2-isobutyrate.     

Serum miRNA profiling identifies miR-150/30a as potential biomarker for workers with damaged nerve fibers from carbon disulfide

As crucial small regulatory molecules, serum microRNAs (miRNAs) have been widely identified as potential noninvasive biomarkers. To survey and identify serum miRNAs associated with workers who had experienced injury to their nerve system from carbon disulfide (CS₂), we profiled abnormally expressed miRNAs using the microarray technique and further performed qRT-PCR validation in case and control samples (n=20). Microarray profiling in pooled RNA samples showed that many miRNAs in workers exposed to CS₂ were aberrantly expressed. Based on control samples exposed to CS₂, a great amount of abnormal miRNAs, including some miRNA gene clusters and families, were obtained from microarray datasets. Most of deregulated miRNAs were up-regulated, and almost all miRNAs showed consistent expression patterns between workers with different numbers of damaged nerve fibers. Functional enrichment analysis suggested that these abnormal miRNAs showed versatile roles by contributing to multiple biological processes. Some aberrantly expressed miRNAs were characterized as miRNA gene clusters or families, and they always showed consistent expression patterns. miR-150 and miR-30a were selected to be further validated by qRT-PCR as up-regulated species, and they could discern case samples from control samples. miR-150 and miR-30a may be potential noninvasive biomarkers for a damaged nervous system.     

To which chemical mixtures is the French population exposed? Mixture identification from the second French Total Diet Study

Through their diet, humans are exposed to a wide range of substances with possible adverse effects. Total diet studies (TDS) assess exposure and risk for many single substances or mixtures from the same chemical family.This research aims to identify from 440 substances in the second French TDS, the major mixtures to which the French population is exposed and their associated diet. Firstly, substances with a contamination value over the detection limit were selected. Secondly, consumption systems comprising major consumed foods were identified using non-negative matrix factorisation and combined with concentration levels to form the main mixture. Thirdly, individuals were clustered to identify “diet clusters” with similar consumption patterns and co-exposure profiles.Six main consumption systems and their associated mixtures were identified. For example, a mixture of ten pesticides, six trace elements and bisphenol A was identified. Exposure to this mixture is related to fruit and vegetables consumed by a diet cluster comprising 62% of women with a mean age of 51 years. Six other clusters are described with their associated diets and mixtures. Cluster co-exposures were compared to the whole population.This work helps prioritise mixtures for which it is crucial to investigate possible toxicological effects.     

Next generation histone deacetylase inhibitors: the answer to the search for optimized epigenetic therapies?

Introduction: HDAC inhibitors have demonstrated potent anticancer activities in preclinical and clinical studies. Currently, two drugs (SAHA and romidepsin) have gained the FDA approval for the treatment of cutaneous T-cell lymphoma. Clinical efficacy of HDAC inhibitors has been observed in advanced hematological malignancies, while response in other cancers has been in most cases unpredictable and often rather limited. The search for new molecules with the potential to overcome the limitations of the first HDAC inhibitors has become a primary goal in the field of epigenetic drug discovery as well as drugs acting on other chromatin modifying enzymes.

Areas covered: The article shortlists seven new HDAC inhibitors that have recently entered clinical studies as representative examples of next generation drugs. The most recently published preclinical profile is reviewed, together with the first clinical data for these compounds. The article then focuses on challenges faced during the progress of first generation HDAC inhibitors and analyzes whether these new compounds are likely to provide a solution to the existing issues and needs.

Expert opinion: Next generation HDAC inhibitors have the ‘best-in-class’ potential, particularly regarding potency and in vivo exposure. However, several issues remain unresolved. For example, none of the presented compounds appears to have a significantly different selectivity profile towards various HDAC isoforms and, thus, none of them may provide a further elucidation between the toxicity seen in more advanced HDAC inhibitors and isoform selectivity. Additionally, a need for a continuous effort on target validation is seen as a necessary requirement for further progress in the field.     

Enterotoxigenic Escherichia coli Multilocus Sequence Types in Guatemala and Mexico

The genetic backgrounds of 24 enterotoxigenic Escherichia coli (ETEC) strains from Mexico and Guatemala expressing heat-stable toxin (ST) and coli surface antigen 6 (CS6) were analyzed. US travelers to these countries and resident children in Guatemala were infected by ETEC strains of sequence type 398, expressing STp and carrying genetically identical CS6 sequences.     

三种剖宫产术对再次剖宫产的影响

目的探讨三种不同剖宫产术式对再次剖宫产的影响。方法采用前瞻分析的方法 ,对我院产科2004年4月-2009年3月再次剖宫产279例的术中、术后进行观察,其首次剖宫产I组子宫下段剖宫产65例,Ⅱ组新式剖宫产86例,Ⅲ组改良新式剖宫产128例,比较三组再次剖宫产手术时间、出血量、肛门排气时间、盆腹腔粘连情况及术后情况。结果再次剖宫产时新式剖宫产与子宫下段剖宫产和改良新式剖宫产在腹壁及盆腹腔粘连、切开腹壁至暴露子宫下段的出血量差异有统计学意义(P0.05),而子宫下段剖宫产与改良新式剖宫产差异无统计学意义(P0.05),切开腹壁暴露子宫下段时间、原手术疤痕缺损发生率依次为改良新式剖宫产、子宫下段剖宫产、新式剖宫产,差异有统计学意义(P0.05)。结论改良新式剖宫产吸取了新式剖宫产手术时间短、产妇疼痛轻、术后肛门排气快、恢复快的优点,是值得推广的选择术式。     

SIRT4 inhibits cigarette smoke extracts-induced mononuclear cell adhesion to human pulmonary microvascular endothelial cells via regulating NF-κB activity

Cigarette smoking is an important risk factor for chronic obstructive pulmonary disease (COPD), yet its pathogenic mechanisms are not yet fully understood. Endothelial dysfunction is known to be involved in the pathogenesis of COPD. A detailed understanding of the mechanism involved in its progression would have a substantial impact on the optimization and development of treatment strategies. Here, we report that the expression of SIRT4, a mitochondrial sirtuin, is markedly down-regulated in cigarette smoke extract (CSE)-treated human pulmonary microvascular endothelial cells (HPMECs). Overexpression of SIRT4 significantly inhibits CSE-induced mononuclear cell adhesion to HPMECs. Consistently, we found that overexpression of SIRT4 attenuates the induction of vascular cell adhesion molecule 1 (VCAM-1) and E-selectin. Importantly, SIRT4 was found to negatively regulate CSE-induced NF-κB activation via inhibiting the degradation of IκBα. Moreover, we also found that proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6, the downstream target genes of NF-κB, are also inhibited by overexpression of SIRT4. These results suggest that SIRT4 protects HPMECs exposed to CSE stress via a mechanism that may involve the NF-κB pathway. Strategies based on the enhancement of SIRT4 may prove to be beneficial in the treatment of cigarette smoking caused COPD.     

Structural and biological investigation of chitosan/hyaluronic acid with silanized-hydroxypropyl methylcellulose as an injectable reinforced interpenetrating network hydrogel for cartilage tissue engineering

Cartilage damage continues to pose a threat to humans, but no treatment is currently available to fully restore cartilage function. In this study, a new class of composite hydrogels derived from water-soluble chitosan (CS)/hyaluronic acid (HA) and silanized-hydroxypropyl methylcellulose (Si-HPMC) (CS/HA/Si-HPMC) has been synthesized and tested as injectable hydrogels for cartilage tissue engineering when combined without the addition of a chemical crosslinking agent. Mechanical studies of CS/HA and CS/HA/Si-HPMC hydrogels showed that as Si-HPMC content increased, swelling rate and rheological properties were higher, compressive strength decreased and degradation was faster. Our results demonstrate that the CS and HA-based hydrogel scaffolds, especially the ones with 3.0% (w/v) Si-HPMC and 2.5/4.0% (w/v) CS/HA, have suitable physical performance and bioactive properties, thus provide a potential opportunity to be used for cartilage tissue engineering. In vitro studies of CS/HA and CS/HA/Si-HPMC hydrogels encapsulated in chondrocytes have shown that the proper amount of Si-HPMC increases the proliferation and deposition of the cartilage extracellular matrix. The regeneration rate of the CS/HA/Si-HPMC (3%) hydrogel reached about 79.5% at 21 days for long retention periods, indicating relatively good in vivo bone regeneration. These CS/HA/Si-HPMC hydrogels are promising candidates for tissue compatibility injectable scaffolds. The data provide proof of the principle that the resulting hydrogel has an excellent ability to repair joint cartilage using a tissue-engineered approach.

RESEARCH HIGHLIGHTS

• An injectable hydrogel based on CS/HA/Si-HPMC composites was developed.
• The CS/HA/Si-HPMC hydrogel displays the tunable rheological with mechanical properties.
• The CS/HA/Si-HPMC hydrogel is highly porous with high swelling and degradation ratio.
• Increasing concentration of Si-HPMC promote an organized network in CS/HA/Si-HPMC hydrogels.
• Injectable CS/HA/Si-HPMC hydrogels have a high potential for cartilage tissue engineering.