Possible factors in the etiology of Alzheimer's disease

Inherited cases of Alzheimer's disease (AD) comprise only a very small proportion of the total. The remainder are of unknown etiopathogenesis, but they are very probably multifactorial in origin. This article describes studies on four possible factors: aluminum; viruses—in particular, herpes simplex type I virus (HSV1); defective DNA repair; and head trauma. Specific problems associated with aluminum, such as inadvertent contamination and its insolubility, have led to some controversy over its usage. Nonetheless, the effects of aluminum on animals and neuronal cells in culture have been studied intensively. Changes in protein structure and location in the cell are described, including the finding in this laboratory of a change in τ resembling that in AD neurofibrillary tangles, and also the lack of appreciable binding of aluminum to DNA. As for HSV1, there has previously been uncertainty about whether HSV1 DNA is present in human brain. Work in this laboratory using polymerase chain reaction has shown that HSV1 DNA is present in many normal aged brains and AD brains, but is absent in brains from younger people. Studies on DNA damage and repair in AD and normal cells are described, and finally, the possible involvement of head trauma is discussed.     

Cardioprotective role of extracellular vesicles: A highlight on exosome beneficial effects in cardiovascular diseases

Extracellular vesicles (EVs) are nano-sized vesicles, released from many cell types including cardiac cells, have recently emerged as intercellular communication tools in cell dynamics. EVs are an important mediator of signaling within cells that influencing the functional behavior of the target cells. In heart complex, cardiac cells can easily use EVs to transport bioactive molecules such as proteins, lipids, and RNAs to the regulation of neighboring cell function. Cross-talk between intracardiac cells plays pivotal roles in the heart homeostasis and in adaptive responses of the heart to stress. EVs were released by cardiomyocytes under baseline conditions, but stress condition such as hypoxia intensifies secretome capacity. EVs secreted by cardiac progenitor cells and cardiosphere-derived cells could be pinpointed as important mediators of cardioprotection and cardiogenesis. Furthermore, EVs from many different types of stem cells could potentially exert a therapeutic effect on the damaged heart. Recent evidence shows that cardiac-derived EVs are rich in microRNAs, suggesting a key role in the controlling of cellular processes. EVs harboring exosomes may be clinically useful in cell-free therapy approaches and potentially act as prognosis and diagnosis biomarkers of cardiovascular diseases.     

Carcinoembryonic antigen (CEACAM) family members and Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic intestinal inflammatory condition with increasing incidence worldwide and whose pathogenesis remains largely unknown. The collected evidence indicates that genetic, environmental and microbial factors and a dysregulated immune response are responsible for the disease. IBD has an early onset and long term sufferers present a higher risk of developing colitis associated cancer (CAC). The carcinoembryonic antigen-related adhesion molecules (CEACAM) are a subgroup of the CEA family, found in a range of different cell types and organs including epithelial cells in the intestine. They can act as intercellular adhesions molecules for e.g. bacteria and soluble antigens. CEACAMs are involved in a number of different processes including cell adhesion, proliferation, differentiation and tumour suppression. Some CEACAMs such as CEACAM1, CEACAM5 and CEACAM6 are highly associated with cancer and are even recognised as valid clinical markers for certain cancer forms. However, their role in IBD pathogenesis is less understood. The purpose of this review is to provide a comprehensive summary of published literature on CEACAMs and intestinal inflammation (IBD). The interactions between CEACAMs and bacteria adhesion in relation to IBD pathophysiology will be addressed and potential new therapeutic and diagnostic opportunities will be identified.     

Effects of larval age and prolonged simulated acid rain on the susceptibility of European pine sawfly to virus infection

We studied the effect of simulated acid rain treatment of host trees on the susceptibility of the European pine sawfly larvae to virus, and possible differences when larvae of two different ages were infected. Older larvae were less susceptible to virus. Most larvae treated with virus 2 days after they started feeding on experimental foliage (group A) died rapidly within 10 days after the virus treatment, and survival to the end of the larval period was only 8–25%. Larvae treated with virus 1 week later (group B) were less affected by the virus and 36–49% survived. In group A the larval survival in the pH 3 treatment was higher than in other treatments; at the end of the larval period the difference was twofold. In group B there were no clear effects of acid rain on the susceptibility of larvae to virus. The study yielded the following new information: (1) the effect of prolonged acid rain treatment on reducing the efficacy of virus on young larvae was more distinct than in a previous study with shorter exposure to acid rain, and the difference was maintained to the end of larval period; (2) the susceptibility of older larvae to virus was not affected by acid rain treatments; (3) pH inside the needles did not explain the larval mortality caused by virus.     

τ Self-Association: Stabilization with a Chemical Cross-Linker and Modulation by Phosphorylation and Oxidation State

Abstract: τ is a major component of paired helical filaments found in the neurofibrillary tangles of Alzheimer's diseased brain. However, the mechanism or mechanisms responsible for the association of τ to form these aggregates remains unknown. In this study, the role of intermolecular disulfide bonds in the formation of higher order oligomers of bovine τ and the human recombinant τ isoform T3 was examined using the chemical cross-linking agent disuccinimidylsuberate (DSS). In addition, the role of phosphorylation and oxidation state on the in vitro self-association of τ was studied using this experimental model. Stabilization of τ-τ interactions with DSS indicated that intermolecular disulfide bonds probably play a predominant role in dimer formation, but the formation of higher order oligomers of τ cannot be attributed to these bonds alone. τ-τ interactions were significantly decreased either by blocking Cys residues or by exposing the τ to a reducing (nitrogen and dithiothreitol), instead of an oxidizing, environment. τ self-association was also significantly decreased by prior phosphorylation with calcium/calmodulin-dependent protein kinase II. Phosphorylation by cyclic AMP-dependent protein kinase or dephosphorylation by alkaline phosphatase did not alter τ self-assembly. These data suggest a role for several factors that may modulate τ self-association in vivo.     

细胞重编程和移植技术用于帕金森病治疗的研究进展

帕金森病(Parkinson disease,PD)是一种复杂的中枢神经系统退行性疾病,主要病理特征为黑质致密部多巴胺神经元的进行性丧失.目前PD主要治疗手段包括药物和手术.但药物存在神经保护活性不足、缺乏对因治疗、晚期无药可用等问题,手术治疗风险较大.近年来,细胞重编程技术取得突破性进展,由重编程产生的诱导多能干细胞(induced pluripotent stem cells,iPSCs)、诱导多巴胺神经元(induced dopamine neurons,iDNs)和诱导神经干细胞(induced neural stem cells,i NSCs)可用于治疗PD.移植iPSCs分化而来的多巴胺能神经元、iDNs和iNSCs至相应脑区,可起到神经替代与修复作用,有效治疗PD.本文重点介绍细胞重编程的机制,总结iPSCs、iDNs和iNSCs治疗PD的优缺点,并阐述尚存在的挑战,探讨可能的解决方案.     

Biomechanical rationale of coronary artery bypass grafting of multivessel disease

The biomechanical model of human coronary arteries was modified for improving the quality of diagnosis and surgical treatment for coronary heart disease. The problem of hemodynamics in the left coronary artery with multivessel bed disease – 45% stenosis of the anterior descending branch and 75% stenosis of the circumflex branch – was particularly considered. Numerical simulation of the coronary arterial bypass of the main trunk was carried out to estimate the functional condition of the coronary arteries after restoring myocardial blood supply by surgery.