Mesenchymal stem cell-derived small extracellular vesicles in the treatment of human diseases:Progress and prospect

Mesenchymal stem cells(MSCs)are self-renewing,multipotent cells that could differentiate into multiple tissues.MSC-based therapy has become an attractive and promising strategy for treating human diseases through immune regulation and tissue repair.However,accumulating data have indicated that MSC-based therapeutic effects are mainly attributed to the properties of the MSC-sourced secretome,especially small extracellular vesicles(sEVs).sEVs are signaling vehicles in intercellular communication in normal or pathological conditions.sEVs contain natural contents,such as proteins,mRNA,and microRNAs,and transfer these functional contents to adjacent cells or distant cells through the circulatory system.MSC-sEVs have drawn much attention as attractive agents for treating multiple diseases.The properties of MSC-sEVs include stability in circulation,good biocompatibility,and low toxicity and immunogenicity.Moreover,emerging evidence has shown that MSC-sEVs have equal or even better treatment efficacies than MSCs in many kinds of disease.This review summarizes the current research efforts on the use of MSC-sEVs in the treatment of human diseases and the existing challenges in their application from lab to clinical practice that need to be considered.

The Olfactory Receptor Pseudo-pseudogene: A Potential Therapeutic Target in Human Diseases

Recently, Prieto-Godino et al.[1] found that the olfactory receptor 75a （Ir75a） gene is a functional pseudo-pseudogene in Drosophila sechellia. For a long time, Ir75a has been regarded as an acetic acid receptor that detects acetic acid and induces obvious olfactory responses in olfactory sensory neurons （OSNs）f2J. Nonetheless, Prieto-Godino et al. confirmed that Ir75a lost its sensitivity to acetic acid in D. sechellia. Thus, the D. sechelfia Ir75a gene is generally recognized as a pseudogene in OSNs.

Black tea in chemo-prevention of cancer and other human diseases

Tea is the most popular functional beverage in the world and has been gaining more and more attention for its health beneficial properties.Among common teas,black tea is consumed more than green tea and oolong tea worldwide.Numerous studies have shown the biological activities of black tea and its polyphenols that include anti-oxidant,anti-tumor,anti-inflammation and metabolic regulation.Tea polyphenols such as theaflavins and catechins are considered to be multifunctional compounds that could be effective in the prevention or treatment of various cancers,cardiovascular disease,chronic inflammation,obesity,metabolic syndrome,and neurodegenerative diseases.In this review,we summarized the up-to-date research and underlying molecular mechanisms of black tea and its polyphenols.©2013 Beijing Academy of Food Sciences.Production and hosting by Elsevier B.V.All rights reserved.

Advances in pig models of human diseases

Animal models of human diseases play a critical role in medical research.Pigs are anatomically and physiologically more like humans than are small rodents such as mice,making pigs an attractive option for modeling human diseases.Advances in recent years in genetic engineering have facilitated the rapid rise of pig models for use in studies of human disease.In the present review,we summarize the current status of pig models for human cardiovascular,metabolic,neurodegenerative,and various genetic diseases.We also discuss areas that need to be improved.Animal models of human diseases play a critical role in medical research.Advances in recent years in genetic engineering have facilitated the rapid rise of pig models for use in studies of human disease.In the present review,we summarize the current status of pig models for human cardiovascular,metabolic,neurodegenerative,various genetic diseases and xenotransplantation.

MicroRNAs in Common Human Diseases

MicroRNAs （miRNAs） are a class of short non-coding RNA molecules that have attracted tremendous attention from the biological and biomedical research communities over the past decade. With over 1900 miRNAs discovered in humans to date, many of them have already been implicated in common human disorders. Facilitated by high-throughput genomics and bioinformatics in conjunction with traditional molecular biology techniques and animal models, miRNA research is now positioned to make the transition from laboratories to clinics to deliver profound benefits to public health. Herein, we overview the progress of miRNA research related to human diseases, as well as the potential for miRNA to becoming the next generation of diagnostics and therapeutics.

JMJD3 in the regulation of human diseases

In recent years,many studies have shown that histone methylation plays an important role in maintaining the active and silent state of gene expression in human diseases.The Jumonji domain-containing protein D3(JMJD3),specifically demethylate di-and trimethyllysine 27 on histone H3(H3K27me2/3),has been widely studied in immune diseases,infectious diseases,cancer,developmental diseases,and aging related diseases.We will focus on the recent advances of JMJD3 function in human diseases,and looks ahead to the future of JMJD3 gene research in this review.

The potential of using blood circular RNA as liquid biopsy biomarker for human diseases

Circular RNA(circRNA)is a novel class of single-stranded RNAs with a closed loop structure.The majority of circRNAs are formed by a back-splicing process in pre-mRNA splicing.Their expression is dynamically regulated and shows spatiotemporal patterns among cell types,tissues and developmental stages.CircRNAs have important biological functions in many physiological processes,and their aberrant expression is implicated in many human diseases.Due to their high stability,circRNAs are becoming promising biomarkers in many human diseases,such as cardiovascular diseases,autoimmune diseases and human cancers.In this review,we focus on the translational potential of using human blood circRNAs as liquid biopsy biomarkers for human diseases.We highlight their abundant expression,essential biological functions and significant correlations to human diseases in various components of peripheral blood,including whole blood,blood cells and extracellular vesicles.In addition,we summarize the current knowledge of blood circRNA biomarkers for disease diagnosis or prognosis.

DNA methylation in human diseases

Even though the importance of epigenetics was first recognized in light of its role in tissue development,an increasing amount of evidence has shown that it also plays an important role in the development and progression of many common diseases.We discuss some recent findings on one representative epigenetic modification,DNA methylation,in some common diseases.While many new risk factors have been identified through the population-based epigenetic epidemiologic studies on the role of epigenetics in common diseases,this relatively new field still faces many unique challenges.Here,we describe those promises and unique challenges of epigenetic epidemiological studies and propose some potential solutions.

LncRNA KCNQ1OT1:Molecular mechanisms and pathogenic roles in human diseases

Long non-coding RNAs(lncRNAs)exhibit a length more than 200 nucleotides and they are characterized by non-coding RNAs(ncRNA)not encoded into proteins.Over the past few years,the role and development of lncRNAs have aroused the rising attention of researchers.To be specific,KCNQ1OT1,the KCNQ1 opposite strand/antisense transcript 1,is clearly classified as a regulatory ncRNA.KCNQ1OT1 is capable of interacting with miRNAs,RNAs and proteins,thereby affecting gene expression and various cell functions(e.g.,cell proliferation,migration,epithelialemesenchymal transition(EMT),apoptosis,viability,autophagy and inflammation).KCNQ1OT1 is dysregulated in a wide range of human diseases(e.g.,cardiovascular disease,cancer,diabetes,osteoarthritis,osteoporosis and cataract),and it is speculated to act as a therapeutic target for treating various human diseases.On the whole,this review aims to explore the biological functions,underlying mechanisms and pathogenic roles of KCNQ1OT1 in human diseases.

CRISPR-mediated genome editing and human diseases

CRISPR(Clustered Regularly Interspaced Short Palindromic Repeats)technology has emerged as a powerful technology for genome editing and is now widely used in basic biomedical research to explore gene function.More recently,this technology has been increasingly applied to the study or treatment of human diseases,including Barth syndrome effects on the heart,Duchenne muscular dystrophy,hemophilia,b-Thalassemia,and cystic fibrosis.CRISPR/Cas9(CRISPR-associated protein 9)genome editing has been used to correct diseasecausing DNA mutations ranging from a single base pair to large deletions in model systems ranging from cells in vitro to animals in vivo.In addition to genetic diseases,CRISPR/Cas9 gene editing has also been applied in immunology-focused applications such as the targeting of C-C chemokine receptor type 5,the programmed death 1 gene,or the creation of chimeric antigen receptors in T cells for purposes such as the treatment of the acquired immune deficiency syndrome(AIDS)or promoting anti-tumor immunotherapy.Furthermore,this technology has been applied to the genetic manipulation of domesticated animals with the goal of producing biologic medical materials,including molecules,cells or organs,on a large scale.Finally,CRISPR/Cas9 has been teamed with induced pluripotent stem(iPS)cells to perform multiple tissue engineering tasks including the creation of disease models or the preparation of donor-specific tissues for transplantation.This review will explore the ways in which the use of CRISPR/Cas9 is opening new doors to the treatment of human diseases.

New glimpses of caveolin-1 functions in embryonic development and human diseases

Caveolin-1(Cav-1)isoforms,including Cav-1αand Cav-1β,were identified as integral membrane proteins and the major components of caveolae.Cav-1 proteins are highly conserved during evolution from Caenorhabditis elegans to human and are capable of interacting with many signaling molecules through their caveolin scaffolding domains to regulate the activities of multiple signaling pathways.Thus,Cav-1 plays crucial roles in the regulation of cellular proliferation,differentiation and apoptosis in a cell-specific and contextual manner.In addition,Cav-1 is essential for embryonic development of vertebrates owing to its regulation of BMP,Wnt,TGF-βand other key signaling molecules.Moreover,Cav-1 is mainly expressed in terminally differentiated cells and its abnormal expression is often associated with human diseases,such as tumor progression,cardiovascular diseases,fibrosis,lung regeneration,and diseases related to virus.In this review,we will further discuss the potential of Cav-1 as a target for disease therapy and multiple drug resistance.

Special Issue on "Biomarkers for Human Diseases and Translational Medicine"

The journal Genomics, Proteomics ＆ Bioinformatics （GPB） is now inviting submissions for a special issue （to be published in the fall of 2016） on the topic of ＂Biomarkers for Human Diseases and Translational Medicine＂. In the personalized medicine era, disease biomarkers have potential application in diagnosis, prognosis, and guidance for treatment, and are important tools in translational medicine. Diagnosis upon biomarkers would aid in early and more efficient intervention, while prognostic biomarkers could lead to right decision of medical treatment.

Special Issue on ‘‘Biomarkers for Human Diseases and Translational Medicine”

The journal Genomics, Proteomics ＆ Bioinformatics （GPB） is now inviting submissions for a special issue （to be published in the fall of 2016） on the topic of ＂Biomarkers for Hunlan Diseases and Translational Medicine＂.

Special Issue on “Biomarkers for Human Diseases and Translational Medicine”

The journal Genomics, Proteomics ＆ Bioinformatics （GPB） is now inviting submissions for a special issue （to be published in the fall of 2016） on the topic of ＂Biomarkers for Human Diseases and Translational Medicine＂. In the personalized medicine era, disease biomarkers have potential application in diagnosis, prognosis, and guidance for treatment, and are important tools in translational medicine. Diagnosis upon biomarkers would aid in early and more efficient intervention, while prognostic biomarkers could lead to right decision of medical treatment.

Sino-UK Symposium on Developmental Biology and Human Diseases Held in Tsinghua

The Sino-UK Symposium on Developmental Biology and Human Diseases opened in Tsinghua May 6, 2006. TheSymposium, which ran through May 8, 2006, was hosted by the Department of Biological Sciences and Biotechnology, Tsinghua University.

Targeting Ageing to Decrease Complex Non-Communicable Human Diseases

During the last two centuries, there have been many spectacular advances in medical science, the main consequence of which has been the dramatically reduced burden of infectious diseases. While in the 1800s many people died before reaching adult- hood, nowadays most people survive. Hence average life ex- pectancy in 1800s was around 30-40, which was barely higher than it had been in Greek and Roman times （Finch, 2010）, but nowadays life expectancy in most modernised economies is around 75 - 80. This demographic shift, which has happened in only 200 years, has created a dramatic change in the causes of mortality. The major killers in the modern world are non- communicable diseases （NCDs）： principally cardiovascular disease, cancer and neurodegenerative disorders such as Alz- heimer＇s disease. A major factor that influences susceptibility to all these diseases is age. As we get older, our risk of developing these NCDs increases enormously. For example, the rate of breast cancer in females at age 15-19 is less than 10 per 100,000 population, but this increases to 100 at age 40-44, 275 at age 55--59 and 450 at age 85 ＋ （http：//www.cancerresearchuk.org/ cancer-info/cancerstats/types/breast/incidence/#age）. Ageing has consequently become a major medical, social and economic burden to many countries.

The human leukocyte antigen and genetic susceptibility in human diseases

The human leukocyte antigen(HLA)complex is involved in immunity,belongs to a highly polymorphic family of genes,and is found in a disease-associated region of the human genome.The HLA region of the genome has been associated with more than hundreds of diseases,including autoimmune diseases,cancer,and infectious diseases.Because of its extensive linkage disequilibrium,HLA represents one of the most attractive and valuable regions that have been discovered in numerous feasibility studies.However,despite its critical role,attempts to apply comprehensive and traditional strategies towards the characterization of the HLA locus have been limited.The recent development of genotyping arrays and sequencing technologies has resulted in the development of technologies that are capable of addressing the extreme polymorphism nature of HLA.In this review,we summarized the current approaches being used to capture,sequence,and analyze HLA genes and loci.In addition,we discussed the new methodologies being used for these applications,including HLA genotyping,population genetics,and disease-association studies.

Genetically Modified Pig Models for Human Diseases

Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies. Although genetically modified mice have been widely used to model human diseases, some of these mouse models do not replicate important disease symptoms or pathology. Pigs are more similar to humans than mice in anatomy, physiology, and genome. Thus, pigs are considered to be better animal models to mimic some human diseases. This review describes genetically modified pigs that have been used to model various diseases including neurological, cardiovascular, and diabetic disorders. We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases,

RT-ABCDE Strategy for Management and Prevention of Human Diseases

In this article, the authors summarized the RT-ABCDE strategy for the management and prevention of human diseases, which includes ReTro-ABCDE （Examination regularity, Disease and risk factor control, Changing lifestyle and reducing pathways of infection and spread, Biochemical and Antagonistic index control and therapeutic treatment as well as RT- Routine and Right Treatment）. The RT-ABCDE strategy, a novel concept and an essential method, should be a routine strategy for disease control and prevention, It should be proposed and applied in both clinical and preventive medicine.

Mechanopathology of red blood cell diseases—Why mechanics matters

During the onset of a disease a cell may experience alterations in both the composition and organization of its cellular and molecular structures.These alterations may eventually lead to changes in its geometrical and mechanical properties such as cell size and shape,deformability and adhesion.As such,knowing how diseased cells respond to mechanical forces can reveal ways by which they differ from healthy ones.Here,we will present biomechanistic insights into red blood cell related diseases that manifest mechanical property changes and how they directly contribute to the pathophysiology of diseases.By conducting cell and molecular mechanics studies,not only can we elucidate changes in the structure-property-function relationship of diseased cells,we can also exploit the new knowledge gained to develop biomechanics based devices that may better detect and diagnose these diseases as well as help identify important biomechanical targets for possible therapeutic interventions.