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.

Connexin mutant embryonic stem cells and human diseases

Intercellular communication via gap junctions allows cells within multicellular organisms to share small molecules. The effect of such interactions has been elucidated using mouse gene knockout strategies. Although several mutations in human gap junction-encoding connexin(Cx) have been described, Cx mutants in mice do not always recapitulate the human disease. Among the 20 mouse Cxs, Cx26, Cx43, and Cx45 play roles in early cardiac or placental development, and disruption of the genes results in lethality that hampers further analyses. Embryonic stem cells(ESCs) that lack Cx43 or Cx45 have made analysis feasible in both in vitro differentiated cell cultures and in vivo chimeric tissues. The success of mouse ESCs studies is leading to the use of induced pluripotent stem cells to learn more about the pathogenesis of human Cx diseases. This review summarizes the current status of mouse Cx disruption models and ESC differentiation studies, and discusses their implication for understanding human Cx diseases.

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.

Oral microbiome in human health and diseases

The oral cavity contains the second-largest microbiota in the human body.The cavity's anatomically and physiologically diverse niches facilitate a wide range of symbiotic bacteria living at distinct oral sites.Consequently,the oral microbiota exhibits site specificity,with diverse species,compositions,and structures influenced by specific aspects of their placement.Variations in oral microbiota structure caused by changes in these influencing factors can impact overall health and lead to the development of diseases-not only in the oral cavity but also in organs distal to the mouth-such as cancer,cardiovascular disease,and respiratory disease.Conversely,diseases can exacerbate the imbalance of the oral microbiota,creating a vicious cycle.Understanding the heterogeneity of both the oral microbiome and individual humans is important for investigating the causal links between the oral microbiome and diseases.Additionally,understanding the intricacies of the oral microbiome's com-position and regulatory factors will help identify the potential causes of related diseases and develop interventions to prevent and treat llnesses in this domain.Therefore,turning to the extant research in this field,we systematically review the relationship between oral microbiome dynamics and human diseases.

AVM:A Manually Curated Database of Aerosol-transmitted Virus Mutations,Human Diseases,and Drugs

Aerosol-transmitted viruses possess strong infectivity and can spread over long distances,earning the difficult-to-control title.They cause various human diseases and pose serious threats to human health.Mutations can increase the transmissibility and virulence of the strains,reducing the protection provided by vaccines and weakening the efficacy of antiviral drugs.In this study,we established a manually curated database(termed AVM)to store information on aerosol-transmitted viral mutations(VMs).The current version of the AVM contains 42,041 VMs(including 2613 immune escape mutations),45 clinical information datasets,and 407 drugs/antibodies/vaccines.Additionally,we recorded 88 human diseases associated with viruses and found that the same virus can target multiple organs in the body,leading to diverse diseases.Furthermore,the AVM database offers a straightforward user interface for browsing,retrieving,and downloading information.This database is a comprehensive resource that can provide timely and valuable information on the transmission,treatment,and diseases caused by aerosol-transmitted viruses(http://www.bio-bigdata.center/AVM).

Exploring the role of N-acetyltransferases in diseases:a focus on N-acetyltransferase 9 in neurodegeneration

Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivotal to basic cellular processes.Close to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and localization.In this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in diseases.Furthermore,we have focused on N-acetyltransferase 9 and its role in microtubule stability.We have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative diseases.We have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.

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.

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.

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.

Exploration of the Relationship between Geographical Environment and Human Diseases in Ancient China

The Yellow Emperor's Classic of Internal Medicine (黄帝内经素问Huangdi Neijing Suwen), created in the Warring States period (475 to 221 BC) described a phenomenon whereby the eastern, western, northern, southern, and central regions were liable to different diseases. It brought forward the principle of treatment in accordance with local conditions. Lv's Spring and Autumn Annals, Huai Nan Tzu (Huainanzi), and the Regiment of Health (Yangshenglun) in the Qin, Han, Wei, Jin, and Southern and Northern Dynasties all describe regional diseases such as goiter (endemic goiter) and yellowish teeth (dental fluorosis) as being caused by geologic and climatic factors. Zhang (miasma), first mentioned in the Han Dynasty, was considered related to the summer heat and dampness particular to the geographical environment of the south. Zhang was further associated with malaria in the Jin Dynasty. General Treatise on the Etiology and Symptomology of Diseases (Zhubingyuanhou Lun), in the Sui Dynasty, held that as a type of poisonous gas, Zhang was the predisposing cause of malaria, seasonal disease, and barbiers, among other conditions. General Guide (Zhinan Zonglun), in the Southern Song Dynasty, regarded Zhang malaria as a separate disease. Healthy Prescription in the Southern Wuling District (Lingnan Weisheng Fang), in the late Song and early Yuan Dynasties, explicitly put forward the concepts of cold Zhang, hot Zhang, and lockjaw Zhang. Guidelines for Treatment of Zhang Malaria (Zhangnue Zhinan), in the Ming Dynasty, maintained that cold Zhang was equivalent to malaria, while hot Zhang and lockjaw Zhang were equivalent to cold damage, the latter of which can be treated by prescriptions for cold damage. Records on Zhang gas and Zhang disease decreased during the Ming and Qing Dynasties.

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.