Malondialdehyde,carbonyl proteins and albumin-disulphide as useful oxidative markers in mild cognitive impairment and Alzheimer's disease

The question arises as to whether oxidative stress has a primary role in neurodegeneration or is a secondary end-stage epiphenomenon. The aim of the present study was to determine oxidative stress parameters like malondialdehyde (MDA), carbonyl proteins (CP) and Albumin-disulphide (Alb-SSR) and relate these parameters to the immune parameter neopterin, folic acid and vitamin B12 as vitamins and homocysteine in patients with neuro-degenerative diseases (NDD), namely mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared to an aged matched control group. MDA, CP and Alb-SSR were significantly increased in the NDD group compared to controls, but not vitamin B12, folic acid and neopterin. Significant correlations were found between CP and Alb-SSR, CP and MDA and between MDA and Alb-SSR including patients with NDD and the control group. These results support the hypothesis that oxidative damage to lipids and proteins is an important early event in the pathogenesis of neurodegenerative diseases.     

Protection of vascular smooth muscle cells by over-expressed methionine sulphoxide reductase A: Role of intracellular localization and substrate availability

Methionine sulphoxide reductase A (MSRA) that reduces methionine-S-sulphoxide back to methionine constitutes a catalytic antioxidant mechanism to prevent oxidative damage at multiple sub-cellular loci. This study examined the relative importance of protection of the cytoplasm and mitochondria by MSRA using A-10 vascular smooth muscle cells, a cell type that requires a low level of reactive oxygen species (ROS) for normal function but is readily damaged by higher concentrations of ROS. Adenoviral over-expression of human MSRA variants, targeted to either mitochondria or the cytoplasm, did not change basal viability of non-stressed cells. Oxidative stress caused by treatment with the methionine-preferring oxidizing reagent chloramine-T decreased cell viability in a concentration-dependent manner. Cytoplasmic MSRA preserved cell viability more effectively than mitochondrial MSRA and co-application of S-methyl-L-cysteine, an amino acid that acts as a substrate for MSRA when oxidized, further increased the extent of protection. This suggests an important role for an MSRA catalytic antioxidant cycle for protection of the cytoplasmic compartment against oxidative damage.     

The signaling pathway of NADPH oxidase and its role in glomerular diseases

Abstract

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), a major source of reactive oxygen species, is a critical mediator of redox signaling. It is well-documented that oxidative stress is associated with the development of glomerular diseases (GN). Hence, the Nox was also thought to be involved in the pathogenesis of GN. However, the expression of Nox in various GN was not consistent, the mechanisms by which the activity of the Nox enzymes in regulating renal cells remains unclear. Signaling pathways might be very important in the pathogenesis of GN. We performed this review to provide a relatively complete signaling pathways flowchart for Nox to the investigators who were interested in the role of Nox in the pathogenesis of GN. Here, we reviewed the signal transduction pathway of Nox and its role in the pathogenesis of GN.     

The signaling pathway of hypoxia inducible factor and its role in renal diseases

Abstract

It is well-documented that hypoxia inducible factor (HIF) is a key mediator of tissue and cellular adaptation to hypoxia. HIF-target genes are also involved in cellular apoptosis and profibrotic mechanisms. The role of HIF in diseases is not consistent. It is a risk factor for tumor progression, whereas it plays a protective role against ischemic hypofusion. For renal diseases, it is not always a risk or protective factor. Many factors are involved in the pathogenesis of renal diseases. It is reported that HIF not only increases hypoxia tolerance, but also regulates a lot of signaling pathways. In the past decades, a number of studies were also conducted to explore the association between HIF and the risk of renal diseases. However, the role of HIF in the development of renal diseases was not entirely clear. In this study, the signal transduction pathways of HIF and its role in the pathogenesis of renal diseases were reviewed.     

Impact of control measures and dynamics of sand flies in southern Brazil

We report the results of control measures introduced to reduce the density of sand flies in domiciles and subsequent monitoring of the effects of these measures on the sand fly populations. The most common species of sand flies were Nyssomyia neivai and Nyssomyia whitmani, which are naturally infected by Leishmania. A total of 268,382 (93.4%) sand flies were collected in ecotypes constructed with the aim of attracting sand flies, and 19,091 (6.6%) sand flies were collected in the ecotypes consisting of residences and other buildings. Human actions determine the growth or reduction of the sand fly population in human‐occupied space. Understanding the dynamics of sand flies in this environment can substantially contribute to the prevention of cutaneous leishmaniasis.     

(Thiazol-2-yl)hydrazone derivatives from acetylpyridines as dual inhibitors of MAO and AChE: synthesis,biological evaluation and molecular modeling studies

Abstract

Several (thiazol-2-yl)hydrazone derivatives from 2-, 3- and 4-acetylpyridine were synthesized and tested against human monoamine oxidase (hMAO) A and B enzymes. Most of them had an inhibitory effect in the low micromolar/high nanomolar range, being derivatives of 4-acetylpyridine selective hMAO-B inhibitors also at low nanomolar concentrations. The structure–activity relationship, as confirmed by molecular modeling studies, proved that the pyridine ring linked to the hydrazonic nitrogen and the substituted aryl moiety at C4 of the thiazole conferred the inhibitory effects on hMAO enzymes. Successively, the strongest hMAO-B inhibitors were tested toward acetylcholinesterase (AChE) and the most interesting compound showed activity in the low micromolar range. Our results suggest that this scaffold could be further investigated for its potential multi-targeted role in the discovery of new drugs against the neurodegenerative diseases.     

Focus: Zoonotic Disease: Bacterial Infections in Humans and Nonhuman Primates from Africa: Expanding the Knowledge

The close phylogenetic relationship between humans and other primates creates exceptionally high potential for pathogen exchange. The surveillance of pathogens in primates plays an important role in anticipating possible outbreaks. In this study, we conducted a molecular investigation of pathogenic bacteria in feces from African nonhuman primates (NHPs). We also investigated the pathogens shared by the human population and gorillas living in the same territory in the Republic of Congo. In total, 93% of NHPs (n=176) and 95% (n=38) of humans were found to carry at least one bacterium. Non-pallidum Treponema spp. (including T. succinifaciens, T. berlinense, and several potential new species) were recovered from stools of 70% of great apes, 88% of monkeys, and 79% of humans. Non-tuberculosis Mycobacterium spp. were also common in almost all NHP species as well as in humans. In addition, Acinetobacter spp., members of the primate gut microbiota, were mainly prevalent in human and gorilla. Pathogenic Leptospira spp. were highly present in humans (82%) and gorillas (66%) stool samples in Congo, but were absent in the other NHPs, therefore suggesting a possible gorillas-humans exchange. Particular attention will be necessary for enteropathogenic bacteria detected in humans such as Helicobacter pylori, Salmonella spp. (including S. typhi/paratyphi), Staphyloccocus aureus, and Tropheryma whipplei, some of which were also present in gorillas in the same territory (S. aureus and T. whipplei). This study enhances our knowledge of pathogenic bacteria that threaten African NHPs and humans by using a non-invasive sampling technique. Contact between humans and NHPs results in an exchange of pathogens. Ongoing surveillance, prevention, and treatment strategies alone will limit the spread of these infectious agents.     

宏基因组学及其在口腔微生物研究中的应用

宏基因组是指环境中所有微生物的遗传物质总和。宏基因组学技术可以最大限度地利用环境中的微生物资源,受到了国内外微生物研究者的重点关注。口腔中寄居着大量的微生物群落,以往对口腔疾病微生物的研究大多局限于单纯的细菌培养技术,然而,由于培养技术的局限性,部分微生物很难或根本不能培养,宏基因组学技术打破了这一局限性,帮助人类发掘更丰富的口腔微生物资源。最近,以宏基因组学测序为基础的研究描绘出了口腔生态系统的图谱,越来越多的实验证明口腔微生物组在各种口腔疾病甚至全身系统性疾病中的重要作用。同时,这也为基于人类微生物组的诊断和治疗开辟了新的途径。本综述旨在说明宏基因组学是研究人类口腔疾病及全身疾病相关微生物的得力工具,而且具有广阔的发展前景,同时也讨论了宏基因组学在应用中有待克服的局限性。     

血液中氧化三甲胺与相关疾病及检测方法

随着代谢组学技术的不断发展及科学研究的不断深入,生物标志物用于预判或诊断机体疾病的价值被更多的科学家所重视。最近几年,大量文献报道了氧化三甲胺与机体疾病之间的相关性。本文通过对近几年血氧化三甲胺与各种疾病之间的关系研究进展及测量方法(如液质联用法、酶联免疫法、磁共振法等)的系统综述,以期为今后的研究提供便捷的参考途径。     

微流控芯片技术在肺部炎性疾病研究和诊断中的进展

微流控芯片技术是指一种将生物、化学等诸多领域的样品从制备、反应到分离检测等多种操作单元高度集成在一块芯片上的技术,由网络状微通道构成,可以通过流体操控整个系统。相比构建模型的传统方法, 具有便携性、高通量、可模拟在体微环境等优势,在研究疾病的诊断、发病机理研究以及药物筛选等方面有着广阔的应用前景。肺部炎性疾病是临床常见的多发病,通常由于细菌、病毒、真菌感染引起。早期肺炎常缺乏明显的呼吸系统症状且症状多不典型,但病情进展快,难以诊断。近年来,微流控芯片技术已经逐渐用于肺部炎性疾病的研究中。尤其是可以再现人肺泡毛细血管界面 (即活肺的基本功能单元) 的关键结构、功能和机械性质的“芯片肺”模型的应用,很好地在体外呈现了肺泡-毛细血管界面模型的生理相关性。相比细胞和动物模型,这种多功能微实验平台具有非常大的优势。文中针对微流控芯片技术在肺部炎性疾病研究和诊断中的进展进行了综述,旨在为肺部炎性疾病的研究和诊断提供新思路。