Tau蛋白的翻译后修饰与阿尔茨海默病

阿尔茨海默病（Alzheimer disease,AD）是一种常见的神经退行性疾病,由过度磷酸化Tau蛋白聚集形成的神经纤维缠结是该病主要的病理特征之一,Tau蛋白的异常磷酸化与Tau蛋白的聚集及AD的进程相关.越来越多的证据表明,Tau蛋白的异常聚集与Tau蛋白相关神经退行性疾病的发生和发展及Tau蛋白的其他翻译后修饰有一定的关系,如糖基化、乙酰化、截断、肽脯氨酸异构化、泛素化等.本文重点综述Tau蛋白翻译后修饰与AD相互关系的研究进展.     

Serum Proteomics in Biomedical Research: A Systematic Review

Proteins that are important indicators of physiological or pathological states may contribute to the early diagnosis of disease, which may provide a basis for identifying the underlying mechanism of disease development. Serum, contains an abundance of proteins, offers an easy and inexpensive approach for disease detection and possesses a high potential to revolutionize the diagnostics. These differentially expressed proteins in serum have become an important role to monitoring the state for disease. Availability of emerging proteomic techniques gives optimism that serum can eventually be placed as a biomedium for clinical diagnostics. Advancements have benefited biomarker research to the point where serum is now recognized as an excellent diagnostic medium for the detection of disease. Comprehensive proteome of human serum fluid with high accuracy and availability has the potential to open new doors for disease biomarker discovery and for disease diagnostics, providing insights useful for future study. Thus, this review presents an overview of the value of serum as a credible diagnostic tool, and we aim to summarize the proteomic technologies currently used for global analysis of serum proteins and to elaborate on the application of serum proteomics to the discovery of disease biomarkers, and discuss some of the critical challenges and perspectives for this emerging field.     

Proteomics in molecular medicine: applications in central nervous systems disorders

Bodily fluids such as cerebrospinal fluid (CSF) and serum can be analysed at the time of presentation and throughout the course of the disease. Changes in the protein composition of CSF may be indicative of altered CNS protein expression pattern with a causative or diagnostic disease link. These findings can be strengthened through subsequent proteomic analysis of specific brain areas implicated in the pathology. New isolation strategies of clinically relevant cellular material such as laser capture microdissection, protein enrichment procedures and proteomic approaches to neuropeptide and neurotransmitter analysis give us the opportunity to map out complex cellular interaction at an unprecedented level of detail. In neurological disorders multiple underlying pathogenic mechanisms as well as an acute and a chronic CNS disease components may require a selective repertoire of molecular targets and biomarkers rather than an individual protein to better define a complex disease. The resulting proteome database bypasses many ambiguities of experimental models and may facilitate pre- and clinical development of more specific disease markers and new selective fast acting therapeutics.     

Nano-enabled biosensing systems for intelligent healthcare: towards COVID-19 management

Biosensors are emerging as efficient (sensitive and selective) and affordable analytical diagnostic tools for early-stage disease detection, as required for personalized health wellness management. Low-level detection of a targeted disease biomarker (pM level) has emerged extremely useful to evaluate the progression of disease under therapy. Such collected bioinformatics and its multi-aspects-oriented analytics is in demand to explore the effectiveness of a prescribed treatment, optimize therapy, and correlate biomarker level with disease pathogenesis. Owing to nanotechnology-enabled advancements in sensing unit fabrication, device integration, interfacing, packaging, and sensing performance at point-of-care (POC) has rendered diagnostics according to the requirements of disease management and patient disease profile i.e. in a personalized manner. Efforts are continuously being made to promote the state of art biosensing technology as a next-generation non-invasive disease diagnostics methodology. Keeping this in view, this progressive opinion article describes personalized health care management related analytical tools which can provide access to better health for everyone, with overreaching aim to manage healthy tomorrow timely. Considering accomplishments and predictions, such affordable intelligent diagnostics tools are urgently required to manage COVID-19 pandemic, a life-threatening respiratory infectious disease, where a rapid, selective and sensitive detection of human beta severe acute respiratory system coronavirus (SARS-COoV-2) protein is the key factor.     

维持性血液透析患者血清铁调素水平与心血管疾病的关系研究

目的观察分析维持性血液透析患者血清铁调素水平与心血管疾病的关系。方法选择惠州市第三人民医院2014年12月至2016年12月期间收治的维持性血液透析患者54例作为观察组,包含20例患者出现心血管疾病,另外选择接受体检的健康人25例作为对照组。结果观察组患者的血清铁调素水平、晚期氧化蛋白物及IL-6均显著高于对照组,比较差异具有统计学意义(P0.05);观察组发生心血管疾病患者血清铁调素水平显著高于非心血管疾病患者,数据比较差异具有统计学意义(P0.05)。结论血液透析患者血清铁调素水平与心血管疾病具有相关性,即可作为血透患者发生心血管疾病的新的独立危险因素,但需要进一步验证。     

微量元素与帕金森病

帕金森病是世界公认的第二大神经系统疾病,我国目前的患病人数已超过245万,已成为影响我国人口健康水平的重大社会问题。帕金森病的病因至今不清。该文在分析该病流行状况、危险因素的基础上,探讨了微量元素与帕金森病的相关关系,以及微量元素组学研究用于该病预警和早期诊断的可能性。     

A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha

Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.     

Metabolomic approach to Alzheimer’s disease diagnosis based on mass spectrometry

Alzheimer??s disease is the most common neurodegenerative disease, but there is still no cure and early diagnosis remains very difficult. For this reason, the discovery of new biomarkers is of great importance. The application of metabolomics is emerging in this field, based on the use of mass spectrometry as a technique of analysis. In this work, blood serum samples (from Alzheimer??s disease patients and healthy controls) were analysed by mass spectrometry in order to search for potential metabolomic biomarkers. The application of multivariate statistical tools (PLS-DA) enabled us to discriminate between groups. In addition, some phosphatidylcholine compounds were identified as markers of the disease.     

Electrochemical approaches for the detection of amyloid-β, tau,and α-synuclein

According to the World Health Organization, there are 47 million people worldwide who are afflicted with dementia today, and this is expected to rise to 132 million by 2050. Therefore, it is pertinent to develop efficient analytical methods such as electrochemical biosensors to study these disorders and diagnose them early. This review highlights some of the recent key developments in the use of electrochemical biosensors to study the biomarkers related to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Especially, we focus on the applications of electrochemistry to analyze amyloid-β and tau related to Alzheimer's disease and α-synuclein related to Parkinson's disease.     

Opportunities in multidimensional trace metal imaging: taking copper-associated disease research to the next level

Copper plays an important role in numerous biological processes across all living systems predominantly because of its versatile redox behavior. Cellular copper homeostasis is tightly regulated and disturbances lead to severe disorders such as Wilson disease and Menkes disease. Age-related changes of copper metabolism have been implicated in other neurodegenerative disorders such as Alzheimer disease. The role of copper in these diseases has been a topic of mostly bioinorganic research efforts for more than a decade, metal–protein interactions have been characterized, and cellular copper pathways have been described. Despite these efforts, crucial aspects of how copper is associated with Alzheimer disease, for example, are still only poorly understood. To take metal-related disease research to the next level, emerging multidimensional imaging techniques are now revealing the copper metallome as the basis to better understand disease mechanisms. This review describes how recent advances in X-ray fluorescence microscopy and fluorescent copper probes have started to contribute to this field, specifically in Wilson disease and Alzheimer disease. It furthermore provides an overview of current developments and future applications in X-ray microscopic methods.

Development and application of nano-flavor-drug carriers in neurodegenerative diseases

Nano-drug carriers such as liposomes, polymer micelles, and polymer nanoparticles are used for neurodegenerative diseases, which can help drug pass the blood-brain barrier easily, and improve the therapeutic effect.     

Mammalian plasma membrane proteins as potential biomarkers and drug targets

Defining the plasma membrane proteome is crucial to understand the role of plasma membrane in fundamental biological processes. Change in membrane proteins is one of the first events that take place under pathological conditions, making plasma membrane proteins a likely source of potential disease biomarkers with prognostic or diagnostic potential. Membrane proteins are also potential targets for monoclonal antibodies and other drugs that block receptors or inhibit enzymes essential to the disease progress. Despite several advanced methods recently developed for the analysis of hydrophobic proteins and proteins with posttranslational modifications, integral membrane proteins are still under-represented in plasma membrane proteome. Recent advances in proteomic investigation of plasma membrane proteins, defining their roles as diagnostic and prognostic disease biomarkers and as target molecules in disease treatment, are presented.     

Common Factors of Alzheimer’s Disease and Rheumatoid Arthritis—Pathomechanism and Treatment

The accumulation of amyloid plaques, or misfolded fragments of proteins, leads to the development of a condition known as amyloidosis, which is clinically recognized as a systemic disease. Amyloidosis plays a special role in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease, and rheumatoid arthritis (RA). The occurrence of amyloidosis correlates with the aging process of the organism, and since nowadays, old age is determined by the comfort of functioning and the elimination of unpleasant disease symptoms in the elderly, exposure to this subject is justified. In Alzheimer’s disease, amyloid plaques negatively affect glutaminergic and cholinergic transmission and loss of sympathetic protein, while in RA, amyloids stimulated by the activity of the immune system affect the degradation of the osteoarticular bond. The following monograph draws attention to the over-reactivity of the immune system in AD and RA, describes the functionality of the blood–brain barrier as an intermediary medium between RA and AD, and indicates the direction of research to date, focusing on determining the relationship and the cause–effect link between these disorders. The paper presents possible directions for the treatment of amyloidosis, with particular emphasis on innovative therapies.     

The Structural Basis for Optimal Performance of Oligothiophene‐Based Fluorescent Amyloid Ligands: Conformational Flexibility is Essential for Spectral Assignment of a Diversity of Protein Aggregates

Protein misfolding diseases are characterized by deposition of protein aggregates, and optical ligands for molecular characterization of these disease‐associated structures are important for understanding their potential role in the pathogenesis of the disease. Luminescent conjugated oligothiophenes (LCOs) have proven useful for optical identification of a broader subset of disease‐associated protein aggregates than conventional ligands, such as thioflavin T and Congo red. Herein, the molecular requirements for achieving LCOs able to detect nonthioflavinophilic Aβ aggregates or non‐congophilic prion aggregates, as well as spectrally discriminate Aβ and tau aggregates, were investigated. An anionic pentameric LCO was subjected to chemical engineering by: 1) replacing thiophene units with selenophene or phenylene moieties, or 2) alternating the anionic substituents along the thiophene backbone. In addition, two asymmetric tetrameric ligands were generated. Overall, the results from this study identified conformational freedom and extended conjugation of the conjugated backbone as crucial determinants for obtaining superior thiophene‐based optical ligands for sensitive detection and spectral assignment of disease‐associated protein aggregates.     

Identification of potential inhibitor and enzyme-inhibitor complex on trypanothione reductase to control Chagas disease

Chagas is a parasitic disease with major threat to public health due to its resistance against commonly available drugs. Trypanothione reductase (TryR) is the key enzyme to develop this disease. Though this enzyme is well thought-out as potential drug target, the accurate structure of enzyme-inhibitor complex is required to design a potential inhibitor which is less available for TryR. In this research, we aimed to investigate the advanced drug over the available existing drugs by designing inhibitors as well as to identify a new enzyme-inhibitor complex that may act as a template for drug design. A set of analogues were designed from a known inhibitor Quinacrine Mustard (QUM) to identify the effective inhibitor against this enzyme. Further, the pharmacoinformatics elucidation and structural properties of designed inhibitor proposed effective drug candidates against Chagas disease. Molecular docking study suggests that a designed inhibitor has higher binding affinity in both crystal and modeled TryR and also poses similar interacting residues as of crystal TryR-QUM complex structure. The comparative studies based on in silico prediction proposed an enzyme-inhibitor complex which could be effective to control the disease activity. So our in silico analysis based on TryR built model, Pharmacophore and docking analysis might play an important role for the development of novel therapy for Chagas disease. But both animal model experiments and clinical trials must be done to confirm the efficacy of the therapy.     

铝与人体健康

铝广泛地存在于自然界，由于其具有优良的理化性能，故普遍地用于工业、医药和日常生活中。从铝在体内的吸收、转运、贮存及分布，铝的生理机能，铝的毒性等方面，对铝与人体疾病的关系进行了综述。     

A mathematical model of insulin resistance in Parkinson’s disease

This paper introduces a mathematical model representing the biochemical interactions between insulin signaling and Parkinson’s disease. The model can be used to examine the changes that occur over the course of the disease as well as identify which processes would be the most effective targets for treatment. The model is mathematized using biochemical systems theory (BST). It incorporates a treatment strategy that includes several experimental drugs along with current treatments. In the past, BST models of neurodegeneration have used power law analysis and simulation (PLAS) to model the system. This paper recommends the use of MATLAB instead. MATLAB allows for more flexibility in both the model itself and in data analysis. Previous BST analyses of neurodegeneration began treatment at disease onset. As shown in this model, the outcomes of delayed, realistic treatment and full treatment at disease onset are significantly different. The delayed treatment strategy is an important development in BST modeling of neurodegeneration. It emphasizes the importance of early diagnosis, and allows for a more accurate representation of disease and treatment interactions.     

Application of Mathematical Modeling and Computational Tools in the Modern Drug Design and Development Process

The conventional drug discovery approach is an expensive and time-consuming process, but its limitations have been overcome with the help of mathematical modeling and computational drug design approaches. Previously, finding a small molecular candidate as a drug against a disease was very costly and required a long time to screen a compound against a specific target. The development of novel targets and small molecular candidates against different diseases including emerging and reemerging diseases remains a major concern and necessitates the development of novel therapeutic targets as well as drug candidates as early as possible. In this regard, computational and mathematical modeling approaches for drug development are advantageous due to their fastest predictive ability and cost-effectiveness features. Computer-aided drug design (CADD) techniques utilize different computer programs as well as mathematics formulas to comprehend the interaction of a target and drugs. Traditional methods to determine small-molecule candidates as a drug have several limitations, but CADD utilizes novel methods that require little time and accurately predict a compound against a specific disease with minimal cost. Therefore, this review aims to provide a brief insight into the mathematical modeling and computational approaches for identifying a novel target and small molecular candidates for curing a specific disease. The comprehensive review mainly focuses on biological target prediction, structure-based and ligand-based drug design methods, molecular docking, virtual screening, pharmacophore modeling, quantitative structure–activity relationship (QSAR) models, molecular dynamics simulation, and MM-GBSA/MM-PBSA approaches along with valuable database resources and tools for identifying novel targets and therapeutics against a disease. This review will help researchers in a way that may open the road for the development of effective drugs and preventative measures against a disease in the future as early as possible.     

帕金森氏病与血清中微量元素关系的研究

以人血清为材料，探讨了帕金森氏病与微量元素的关系。采集了６２例患者血清和３３例健康人血清，用电感耦合高频等离子体发射光谱仪进行测定，结果发现，患者组血清锌明显低于对照组、铜、锰低于对照组，还发现患者组轻、中、重分型病人血清铅有明显差异，上述结果提示微量元素可能在帕金森氏病的发生、发展和转归中起着重要的作用。     

线粒体特异性检测与调控

线粒体(mitochondria)是一种由双层膜包被的细胞器,存在于大多数细胞中,能够通过位于线粒体内膜上的呼吸链产生能量,被称为细胞的"能量工厂"。此外,线粒体参与到细胞分化、信息传递和细胞凋亡等过程,并调控细胞周期和细胞生长。线粒体的功能障碍与多种人类疾病相关,如帕金森氏病、阿尔兹海默氏病、心血管疾病和某些癌症等。鉴于其在生物体中的重要作用,线粒体一直是科学家们的研究重点。本文就线粒体特异性检测和调控研究的最新进展进行了综述。