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

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Protein & Cell 2021年第12期12卷 911-946页

作者： Guoxia Wen Tong Zhou Wanjun Gu State Key Laboratory of Bioelectronics School of Biological Sciences and Medical EngineeringSoutheast UniversityNanjing210096China Department of Physiology and Cell Biology Reno School of MedicineUniversity of NevadaRenoNV89557USA

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.

关键词： peripheral blood circular RNA liquid biopsy human diseases translational biomarkers

DNA methylation in human diseases

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Genes & diseases 2018年第1期5卷 1-8页

作者： Zelin Jin Yun Liu The Ministry of Education Key Laboratory of Metabolism and Molecular Medicine Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesFudan UniversityShanghaiChina

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.

关键词： DNA Methylation Epigenetic epidemiologic studies Epigenetics EWAS human diseases

CRISPR-mediated genome editing and human diseases

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Genes & diseases 2016年第4期3卷 244-251页

作者： Liquan Cai Alfred L.Fisher Haochu Huang Zijian Xie Marshal l Institute for Interdisciplinary Research(MIIR) Marshall UniversityWeisberg Engineering ComplexMarshall University1628 Third AvenueHuntingtonWV 25703USA University of Texas Health Science Center at San Antonio Department of MedicineDivision of GeriatricsGerontologyand Palliative MedicineSan AntonioTX 78229USA GRECC South Texas VA Healthcare SystemSan AntonioTX 78229USA Committee on Immunology Section of RheumatologyDepartment of MedicineKnapp Center for Lupus and Immunology ResearchUniversity of ChicagoChicagoIL 60637USA

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.

关键词： CRISPR DNA double-stranded break Genome editing human diseases iPS cells

MicroRNAs in Common human diseases

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Genomics, Proteomics & Bioinformatics 2012年第5期10卷 246-253页

作者： Yu Li Kris V.Kowdley Benaroya Research Institute and Center for Liver Disease Digestive Disease InstituteVirginia Mason Medical Center

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.

关键词： MicroRNA human diseases Diagnostics Therapeutics Biomarker

The human leukocyte antigen and genetic susceptibility in human diseases

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Journal of Bio-X Research 2019年第3期2卷 112-120页

作者： Jinping Gao Caihong Zhu Zhengwei Zhu Lili Tang Lu Liu Leilei Wen Liangdan Sun Department of Dermatology the First Affiliated Hospital of Anhui Medical UniversityAnhui ProvinceChina Institute of Dermatology Anhui Medical UniversityAnhui ProvinceChina Key Laboratory of Dermatology(Anhui Medical University) Ministry of EducationAnhui ProvinceChina State Key Laboratory Incubation Base of Dermatology Anhui Medical UniversityAnhui ProvinceChina Key Laboratory of Major Autoimmune diseases Anhui ProvinceHefeiAnhui ProvinceChina

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.

关键词： allele genetic susceptibility genome-wide association study human diseases human leukocyte antigen

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

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World Journal of Stem Cells 2021年第1期13卷 49-63页

作者： Jie Shi Yu-Chen Zhao Zhi-Fang Niu Hao-Jun Fan Shi-Ke Hou Xiao-Qin Guo Lu Sang Qi Lv Institute of Disaster Medicine Tianjin UniversityTianjin 300072China Department of Biomaterials and Regenrative Medicine Tianjin Key Laboratory of Disaster Medicine TechnologyTianjin 300072China General Hospital Tianjin Medical UniversityTianjin 300052C

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.

关键词： Mesenchymal stem cells Small extracellular vesicles Exosomes human diseases Therapeutics Prospects

JMJD3 in the regulation of human diseases

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Protein & Cell 2019年第12期10卷 864-882页

作者： Xiangxian Zhang Li Liu Xia Yuan Yuquan Wei Xiawei Laboratory of Aging Research and Nanotoxicology State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China

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.

关键词： histone methylation JMJD3 epigenetics human diseases

Ginseng and Ginsenoside as Soldiers Fight for human diseases

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神经药理学报 2018年第6期 23-24页

作者： GAO Yan Department of Neuroendocrine Pharmacology School of PharmacyChina Medical University

Ginseng has been used as reinforcing drugs or for traditional Chinese medicine for aging,inflammation,stress,diabetes mellitus,liver diseases,and cancer. During these years,numerous animal experiments and human studies have been conducted to investigate the efficacy and safety of various types of ginseng components. Of notes,the anti-human disease effects of ginseng and ginsenosides are already reviewed and summarized.In mammals,the master regulator of antioxidant defense is the Nrf2 pathway. Keap1/Nrf2/ARE is a really important cellular mechanism to control oxidative stress,which can induce many cytoprotective genes like HO-1 and NQO1. Inflammasomes are cytosolic multi-protein complexes that form in response to infectious or injurious challenges. Inflammasomes control the activity of caspase-1,which is essential for the maturation and release of IL-1β family cytokines. The NLRP1,IPAF and AIM2 inflammasomes recognize specific substances,while the NLRP3 inflammasome responds to many structurally and chemically diverse triggers. The role of gut microbiota in health and disease is becoming increasingly recognized. The microbiota,gut,and brain communicate through the microbiota-gut-brain axis in a bidirectional way which involves the autonomic nervous system between brain and gastrointestinal system. Visceral information is continuously fed into subcortical regions of brain including limbic system and the autonomic and neuroendocrine centers. This review critically evaluates the signaling pathways attenuated by ginseng and ginsenosides in various tissues with emphasis on liver diseases,neurodegenerative disorders,and diabetes mellitus.

关键词： ginseng ginsenoside NLRP3/Nrf2 gut microbiota human diseases

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

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Frontiers in Biology 2011年第5期6卷 367-376页

作者： Saijun MO Shengli YANG Zongbin CUI Department of Basic Oncology College of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001China Key Laboratory of Biodiversity and Conservation of Aquatic Organism Institute of HydrobiologyChinese Academy of SciencesWuhan 430072China

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.

关键词： Caveolin-1 signal transduction embryonic development human diseases