Proteomics approach and techniques in identification of reliable biomarkers for diseases

Biomarkers, also called biological markers, are indicators to identify a biological case or situation as well as detecting any presence of biological activities and processes. Proteins are considered as a type of biomarkers based on their characteristics. Therefore, proteomics approach is one of the most promising approaches in this field. The purpose of this review is to summarize the use of proteomics approach and techniques to identify proteins as biomarkers for different diseases. This review was obtained by searching in a computerized database. So, different researches and studies that used proteomics approach to identify different biomarkers for different diseases were reviewed. Also, techniques of proteomics that are used to identify proteins as biomarkers were collected. Techniques and methods of proteomics approach are used for the identification of proteins' activities and presence as biomarkers for different types of diseases from different types of samples. There are three essential steps of this approach including: extraction and separation of proteins, identification of proteins, and verification of proteins. Finally, clinical trials for new discovered biomarker or undefined biomarker would be on.     

A banana or a syringe: journey to edible vaccines

Constant emergence of diseases, along with the expanding size of world population creates demands for newer vaccines which can meet the challenges that conventional vaccines have not been able to overcome. The application of transgenic plants in the production of pharmaceuticals has led to the new approach of plant-based, orally-delivered vaccines. In recent years a number of recombinant vaccine antigens have been expressed in different plant tissues. The review highlights the generation of edible vaccines, their mode of action and their clinical application in various human diseases. Though the road ahead seems promising, there are several constraints which restrict the success and public acceptability of these vaccines. These include problems of choice of plants, storage, delivery, dosage, safety, public perception, quality control and licensing.     

Stem Cell Therapy: A New Therapeutic Option for Cardiovascular Diseases

Cardiovascular diseases are known as one of major causes of morbidity and mortality worldwide. Despite the many advancement in therapies are associated with cardiovascular diseases, it seems that finding of new therapeutic option is necessary. Cell therapy is one of attractive therapeutic platforms for treatment of a variety of diseases such as cardiovascular diseases. Among of various types of cell therapy, stem cell therapy has been emerged as an effective therapeutic approach in this area. Stem cells divided into multipotent stem cells and pluripotent stem cells. A large number studies indicated that utilization of each of them are associated with a variety of advantages and disadvantages. Multiple lines evidence indicated that stem cell therapy could be used as suitable therapeutic approach for treatment of cardiovascular diseases. Many clinical trials have been performed for assessing efficiency of stem cell therapies in human. However, stem cell therapy are associated with some challenges, but, it seems resolving of them could contribute to using of them as effective therapeutic approach for patients who suffering from cardiovascular diseases. In the current review, we summarized current therapeutic strategies based on stem cells for cardiovascular diseases. J. Cell. Biochem. 119: 95–104, 2018. © 2017 Wiley Periodicals, Inc.     

Personalized health care: from theory to practice

The practice of medicine stands at the threshold of a transformation from its current focus on the treatment of disease events to an emphasis on enhancing health, preventing disease and personalizing care to meet each individual's specific health needs. Personalized health care is a new and strategic approach that is driven by personalized health planning empowered by personalized medicine tools, which are facilitated by advances in science and technology. These tools improve the capability to predict health risks, to determine and quantify the dynamics of disease development, and to target therapeutic approaches to the needs of the individual. Personalized health care can be implemented today using currently available technologies and know-how and thereby provide a market for the rational introduction of new personalized medicine tools. The need for early adoption of personalized health care stems from the necessity to reduce the egregious and wasteful burden of preventable chronic diseases, which is not effectively addressed by our current approach to care.     

Sequence-based prioritization of nonsynonymous single-nucleotide polymorphisms for the study of disease mutations

The increasing demand for the identification of genetic variation responsible for common diseases has translated into a need for sophisticated methods for effectively prioritizing mutations occurring in disease-associated genetic regions. In this article, we prioritize candidate nonsynonymous single-nucleotide polymorphisms (nsSNPs) through a bioinformatics approach that takes advantages of a set of improved numeric features derived from protein-sequence information and a new statistical learning model called "multiple selection rule voting" (MSRV). The sequence-based features can maximize the scope of applications of our approach, and the MSRV model can capture subtle characteristics of individual mutations. Systematic validation of the approach demonstrates that this approach is capable of prioritizing causal mutations for both simple monogenic diseases and complex polygenic diseases. Further studies of familial Alzheimer diseases and diabetes show that the approach can enrich mutations underlying these polygenic diseases among the top of candidate mutations. Application of this approach to unclassified mutations suggests that there are 10 suspicious mutations likely to cause diseases, and there is strong support for this in the literature.     

Plant‐based oral vaccines against zoonotic and non‐zoonotic diseases

The shared diseases between animals and humans are known as zoonotic diseases and spread infectious diseases among humans. Zoonotic diseases are not only a major burden to livestock industry but also threaten humans accounting for >60% cases of human illness. About 75% of emerging infectious diseases in humans have been reported to originate from zoonotic pathogens. Because antibiotics are frequently used to protect livestock from bacterial diseases, the development of antibiotic‐resistant strains of epidemic and zoonotic pathogens is now a major concern. Live attenuated and killed vaccines are the only option to control these infectious diseases and this approach has been used since 1890. However, major problems with this approach include high cost and injectable vaccines is impractical for >20 billion poultry animals or fish in aquaculture. Plants offer an attractive and affordable platform for vaccines against animal diseases because of their low cost, and they are free of attenuated pathogens and cold chain requirement. Therefore, several plant‐based vaccines against human and animals diseases have been developed recently that undergo clinical and regulatory approval. Plant‐based vaccines serve as ideal booster vaccines that could eliminate multiple boosters of attenuated bacteria or viruses, but requirement of injectable priming with adjuvant is a current limitation. So, new approaches like oral vaccines are needed to overcome this challenge. In this review, we discuss the progress made in plant‐based vaccines against zoonotic or other animal diseases and future challenges in advancing this field.     

Multicomponent phytotherapeutic approach gaining momentum: Is the “one drug to fit all” model breaking down?

Natural product based drugs constitute a substantial proportion of the pharmaceutical market particularly in the therapeutic areas of infectious diseases and oncology. The primary focus of any drug development program so far has been to design selective ligands (drugs) that act on single selective disease targets to obtain highly efficacious and safe drugs with minimal side effects. Although this approach has been successful for many diseases, yet there is a significant decline in the number of new drug candidates being introduced into clinical practice over the past few decades. This serious innovation deficit that the pharmaceutical industries are facing is due primarily to the post-marketing failures of blockbuster drugs. Many analysts believe that the current capital-intensive model-“the one drug to fit all” approach will be unsustainable in future and that a new “less investment, more drugs” model is necessary for further scientific growth. It is now well established that many diseases are multi-factorial in nature and that cellular pathways operate more like webs than highways. There are often multiple ways or alternate routes that may be switched on in response to the inhibition of a specific target. This gives rise to the resistant cells or resistant organisms under the specific pressure of a targeted agent, resulting in drug resistance and clinical failure of the drug. Drugs designed to act against individual molecular targets cannot usually combat multifactorial diseases like cancer, or diseases that affect multiple tissues or cell types such as diabetes and immunoinflammatory diseases. Combination drugs that affect multiple targets simultaneously are better at controlling complex disease systems and are less prone to drug resistance. This multicomponent therapy forms the basis of phytotherapy or phytomedicine where the holistic therapeutic effect arises as a result of complex positive (synergistic) or negative (antagonistic) interactions between different components of a cocktail. In this approach, multicomponent therapy is considered to be advantageous for multifactorial diseases, instead of a “magic bullet” the metaphor of a “herbal shotgun” might better explain the state of affairs. The different interactions between various components might involve the protection of an active substance from decomposition by enzymes, modification of transport across membranes of cells or organelles, evasion of multidrug resistance mechanisms among others.     

基于组合药物网络的复杂疾病药物组合模式研究

人体作为一个复杂的功能系统。疾病的发生和发展,尤其是复杂疾病,其病理过程往往涉及多环节、多系统。单一药物难以满足复杂疾病的治疗要求,组合药物成为未来药物发展的新趋势。本文在构建组合药物网络的基础上进行MCODE算法聚类,得到33个独立且内部联系紧密的药物模块。其中26组药物模块用于治疗单一复杂疾病。通过详细分析癌症、疼痛、银屑病、细菌感染、类风湿性关节炎、化疗呕吐这六种复杂疾病,归纳总结出这六种疾病的药物组合模式,从而提出复杂疾病多角度的治疗策略。     

Identifying disease related sub-pathways for analysis of genome-wide association studies

Most methods for genome-wide association studies (GWAS) focus on discovering a single genetic variant, but the pathogenesis of complex diseases is thought to arise from the joint effect of multiple genetic variants. Information about pathway structure, such as the interactions and distances between gene products within pathways, can help us learn more about the functions and joint effect of genes associated with disease risk. We developed a novel sub-pathway based approach to study the joint effect of multiple genetic variants that are modestly associated with disease. The approach prioritized sub-pathways based on the significance values of single nucleotide polymorphisms (SNPs) and the interactions and distances between gene products within pathways. We applied the method to seven complex diseases. The result showed that our method can efficiently identify statistically significant sub-pathways associated with the pathogenesis of complex diseases. The approach identified sub-pathways that may inform the interpretation of GWAS data.     

Polyglutamine-mediated neurodegeneration: Use of chaperones as prevention strategy

Polyglutamine diseases are a class of inherited neurodegenerative disorders caused by the expansion of a polyglutamine tract within the respective proteins. Clinical studies have revealed that the forming of neuronal intranuclear inclusions by the disease protein is a common pathological feature of polyglutamine diseases. Although there has been considerable progress in understanding polyglutamine diseases, many questions regarding their mechanism are still unanswered. The finding that molecular chaperones are associated with ubiquitinated intranuclear inclusions clearly indicates a crucial role of molecular chaperones in the generation of these fatal diseases. Molecular and chemical chaperones have been found to be a good agent for suppressing many polyglutamine diseases in several animal models. In this review, I discuss the roles of the ubiquitin-proteasome pathway and molecular chaperones in the development of polyglutamine diseases and probable approach for the prevention of many of these fatal disorders using molecular chaperones as a therapeutic agent. Newly found chemical chaperones have been demonstrated to be potentially useful and could be used as a therapeutic strategy in preventing many versions of polyglutamine diseases.     

Selecting SNPs for association studies based on population frequencies: a novel interactive tool and its application to polygenic diseases

Common complex polygenic diseases as autoimmune diseases have not been completely understood on a molecular level. While many genes are known to be involved in the pathways responsible for the phenotype, explicit causes for the susceptibility of the disease remain to be elucidated. The susceptibility to disease is thought to be the result of genetic epistatic interactions between common polymorphic genes. This polymorphism is mostly caused by single nucleotide polymorphisms (SNPs). Human subpopulations are known to differ in the susceptibility to the diseases and generally in the distribution of single nucleotide polymorphisms. The here presented approach retrieves SNPs with the most divergent frequencies for selected human subpopulations to help defining properties for the experimental verification of SNPs within defined regions. A web-accessible program implementing this approach was evaluated for multiple sclerosis (MS), a common human polygenic disease. A link to a summary of data from "The SNP Consortium" (TSC) with sex-dependencies of SNPs is available. Associations of SNPs to genes, genetic markers and chromosomal loci are retrieved from the Ensembl project. This tool is recommended to be used in conjunction with microarray analyses or marker association studies that link genes or chromosomal loci to particular diseases.     

复杂疾病基因定位策略与肿瘤易感基因鉴定

对于不存在某单一基因位点经典的孟德尔显性或隐性遗传模式的疾病,称为复杂疾病,肿瘤是最常见的类型之一 . 目前,以连锁和相关分析为基础的功能克隆、功能候选克隆、定位克隆、定位候选克隆、系统生物学等复杂疾病易感基因定位策略逐渐发展起来 . 其中,系统生物学策略由于整合了从 DNA 到蛋白质的各个层面的信息,对复杂疾病基因调控网络做出了良好诠释,使其成为最有潜力的方法之一 . 目前,虽然已有近 100 种肿瘤 / 遗传性癌综合症的易感基因被鉴定出来,但未来的复杂疾病易感基因定位工作仍充满了挑战 .     

Breeding for Improved Disease Resistance in Organic Farming – Possibilities and Constraints

Lowered incidences of disease may be reached in several ways: management and rearing measures, vaccination programmes and preventive medications as well as breeding for improved disease resistance. Here the focus is on breeding for improved resistance to infectious diseases. In comparison to conventional farming, one has to acknowledge that the spectrum of diseases in animals reared under organic conditions is different and that the proportion of the breeding stock of animals in organic farming is considerably smaller. There are at least four different approaches that may be used in breeding towards resistance to infectious diseases. The most obvious is to record disease incidence in the progeny and select those parents that produce the progeny with the lowest incidences of disease. Another approach is to use breeders possessing certain major histo-compatibility complex antigens suggested being associated with resistance to certain infections. A third approach is to analyse the heritability of a set of immune functions or related traits crucial for resistance to infections and then use the traits with high heritability in breeding programmes. Finally, one may genetically select animals for high immune response using an index that combines estimated breeding values for several immunological traits. Examples of these various approaches are given and the feasibility for using these in organic farming are discussed.     

Advancing Drug Innovation for Neglected Diseases—Criteria for Lead Progression

The current drug R&D pipeline for most neglected diseases remains weak, and unlikely to support registration of novel drug classes that meet desired target product profiles in the short term. This calls for sustained investment as well as greater emphasis in the risky upstream drug discovery. Access to technologies, resources, and strong management as well as clear compound progression criteria are factors in the successful implementation of any collaborative drug discovery effort. We discuss how some of these factors have impacted drug discovery for tropical diseases within the past four decades, and highlight new opportunities and challenges through the virtual North–South drug discovery network as well as the rationale for greater participation of institutions in developing countries in product innovation. A set of criteria designed to facilitate compound progression from screening hits to drug candidate selection is presented to guide ongoing efforts.     

Protein network-based Lasso regression model for the construction of disease-miRNA functional interactions

BackgroundThere is a growing body of evidence associating microRNAs (miRNAs) with human diseases. MiRNAs are new key players in the disease paradigm demonstrating roles in several human diseases. The functional association between miRNAs and diseases remains largely unclear and far from complete. With the advent of high-throughput functional genomics techniques that infer genes and biological pathways dysregulted in diseases, it is now possible to infer functional association between diseases and biological molecules by integrating disparate biological information.ResultsHere, we first used Lasso regression model to identify miRNAs associated with disease signature as a proof of concept. Then we proposed an integrated approach that uses disease-gene associations from microarray experiments and text mining, and miRNA-gene association from computational predictions and protein networks to build functional associations network between miRNAs and diseases. The findings of the proposed model were validated against gold standard datasets using ROC analysis and results were promising (AUC=0.81). Our protein network-based approach discovered 19 new functional associations between prostate cancer and miRNAs. The new 19 associations were validated using miRNA expression data and clinical profiles and showed to act as diagnostic and prognostic prostate biomarkers. The proposed integrated approach allowed us to reconstruct functional associations between miRNAs and human diseases and uncovered functional roles of newly discovered miRNAs.ConclusionsLasso regression was used to find associations between diseases and miRNAs using their gene signature. Defining miRNA gene signature by integrating the downstream effect of miRNAs demonstrated better performance than the miRNA signature alone. Integrating biological networks and multiple data to define miRNA and disease gene signature demonstrated high performance to uncover new functional associations between miRNAs and diseases.     

NF2 mutation screening by denaturing high-performance liquid chromatography and high-resolution melting analysis

Neurofibromatosis type 2 (NF2) is an autosomal-dominant disorder caused by mutations in the NF2 gene and predisposing to the development of nervous system. Identification of germline mutations is essential to provide appropriate genetic counseling in NF2 patients, but it represents an extremely challenging task because the vast majority of mutations are unique and spread over the entire coding sequence. Moreover, about 30% of de novo patients are indeed mosaic, and direct sequencing can undetect mutated alleles present in a minority of cells. As most screening techniques do not meet the requirements for efficient NF2 testing, we have developed a semi-automated denaturing high-performance liquid chromatography (DHPLC) method for point mutation detection combined with a multiplex ligation-dependent probe amplification approach to screen for gene rearrangements. In addition, we have evaluated high-resolution melting analysis (HRMA) as an exon scanning procedure to identify point mutations in the NF2 gene. The results obtained in 92 NF2 patients expand the NF2 mutational spectrum and indicate DHPLC and HRMA as good systems to screen for point mutations in diseases with a heterogeneous spectrum of alterations.     

Imino sugar inhibitors for treating the lysosomal glycosphingolipidoses

The inherited metabolic disorders of glycosphingolipid (GSL) metabolism are a relatively rare group of diseases that have diverse and often neurodegenerative phenotypes. Typically, a deficiency in catabolic enzyme activity leads to lysosomal storage of GSL substrates and in many diseases, several other glycoconjugates. A novel generic approach to treating these diseases has been termed substrate reduction therapy (SRT), and the discovery and development of N-alkylated imino sugars as effective and approved drugs is discussed. An understanding of the molecular mechanism for the inhibition of the key enzyme in GSL biosynthesis, ceramide glucosyltransferase (CGT) by N-alkylated imino sugars, has also lead to compound design for improvements to inhibitory potency, bioavailability, enzyme selectivity, and biological safety. Following a successful clinical evaluation of one compound, N-butyl-deoxynojirimycin [(NB-DNJ), miglustat, Zavesca], for treating type I Gaucher disease, issues regarding the significance of side effects and CNS access have been addressed as exposure of drug to patients has increased. An alternative experimental approach to treat specific glycosphingolipid (GSL) lysosomal storage diseases is to use imino sugars as molecular chaperons that assist protein folding and stability of mutant enzymes. The principles of chaperon-mediated therapy (CMT) are described, and the potential efficacy and preclinical status of imino sugars is compared with substrate reduction therapy (SRT). The increasing use of imino sugars for clinical evaluation of a group of storage diseases that are complex and often intractable disorders to treat has considerable benefit. This is particularly so given the ability of small molecules to be orally available, penetrate the central nervous system (CNS), and have well-characterized biological and pharmacological properties.     

A review of wheat diseases—a field perspective

Wheat is one of the primary staple foods throughout the planet. Significant yield gains in wheat production over the past 40 years have resulted in a steady balance of supply versus demand. However, predicted global population growth rates and dietary changes mean that substantial yield gains over the next several decades will be needed to meet this escalating demand. A key component to meeting this challenge is better management of fungal incited diseases, which can be responsible for 15%–20% yield losses per annum. Prominent diseases of wheat that currently contribute to these losses include the rusts, blotches and head blight/scab. Other recently emerged or relatively unnoticed diseases, such as wheat blast and spot blotch, respectively, also threaten grain production. This review seeks to provide an overview of the impact, distribution and management strategies of these diseases. In addition, the biology of the pathogens and the molecular basis of their interaction with wheat are discussed.     

Prospects for gene therapy

Experiments in animal models and human cells in vitro suggest that gene transfer using retroviral vectors may be useful to treat genetic diseases and to gain information that may improve treatment of other common diseases such as cancer. The approach to treatment of genetic diseases by inserting genes into bone marrow cells and experimental models, and a novel application of gene transfer technology to cancer research are discussed herein.     

Co-stimulation agonists as a new immunotherapy for autoimmune diseases

Lymphocytes are important in the pathogenesis of many autoimmune diseases. Blocking co-stimulatory signals for T-cell activation has been widely used as an approach to treating autoimmunity, but it has encountered limited clinical success. Some agonistic monoclonal antibodies to co-stimulatory molecules greatly enhance immune responses mediated by T cells, such as antiviral, anti-tumor and alloresponses. Surprisingly, recent studies have demonstrated that these agonists have profound therapeutic effects on autoimmune diseases by potentially depleting autoreactive lymphocytes or by inhibiting their function. These findings imply that signaling through co-stimulatory molecules can have diametric outcomes in modulating immune responses, thereby providing a novel approach to the treatment of autoimmune diseases.