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Clinical Peptidomics: Advances in Instrumentation, Analyses, and Applications

Biomedical Engineering Frontiers 2023年第1期4卷 116-132页

作者： Lin Li Jing Wu Christopher JLyon Li Jiang Tony Y.Hu Center for cellular and Molecular Diagnostics Department of Biochemistry and Molecular BiologySchool of MedicineTulane UniversityNew OrleansLAUSA Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for human Disease Gene Study Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalChengduChina Department of Clinical Laboratory Third Central Hospital of TianjinTianjin Institute of Hepatobiliary DiseaseTianjin Key Laboratory of Artificial CellArtificial Cell Engineering Technology Research Center of Public Health MinistryTianjinChina Department of Biomedical Engineering School of Science and EngineeringTulane UniversityNew OrleansLAUSA

Extensive effort has been devoted to the discovery,development,and validation of biomarkers for early disease diagnosis and prognosis as well as rapid evaluation of the response to therapeutic *** and transcriptomic profiling are well-established means to identify disease-associated ***,analysis of disease-associated peptidomes can also identify novel peptide biomarkers or signatures that provide sensitive and specific diagnostic and prognostic information for specific malignant,chronic,and infectious *** evidence also suggests that peptidomic changes in liquid biopsies may more effectively detect changes in disease pathophysiology than other molecular *** gained from peptide-based diagnostic,therapeutic,and imaging approaches has led to promising new theranostic applications that can increase their bioavailability in target tissues at reduced doses to decrease side effects and improve treatment ***,despite major advances,multiple factors can still affect the utility of peptidomic *** review summarizes several remaining challenges that affect peptide biomarker discovery and their use as diagnostics,with a focus on technological advances that can improve the detection,identification,and monitoring of peptide biomarkers for personalized medicine.

关键词： doses gained devoted

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Injectable collagen scaffold promotes swine myocardial infarction recovery by long-term local retention of transplanted human umbilical cord mesenchymal stem cells

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science China(Life sciences) 2021年第2期64卷 269-281页

作者： Qiang Wangn Xiaojun He Bin Wang Jun Pan Chunying Shi Jie Li Liudi Wang Yannan Zhao Jianwu Dai Dongjin Wang Department of Thoracic and Cardiovascular Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Center for Clinical Stem cell Research the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Department of human anatomy Histology and EmbryologySchool of Basic MedicineQingdao UniversityQingdao 266021China Department of Cardiology the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100190China

Stem cell therapy is an attractive approach for recovery from myocardial infarction(MI)but faces the challenges of rapid diffusion and poor survival after *** we developed an injectable collagen scaffold to promote the long-term retention of transplanted cells in chronic ***-five minipigs underwent left anterior descending artery(LAD)ligation and were equally divided into three groups 2 months later(collagen scaffold loading with human umbilical mesenchymal stem cell(hUMSC)group,hUMSC group,and placebo group(only phosphate-buffered saline(PBS)injection)).Immunofluorescence staining indicated that the retention of transplanted cells was promoted by the collagen *** and cardiac magnetic resonance imaging(CMR)showed much higher left ventricular ejection fraction(LVEF)and lower infarct size percentage in the collagen/hUMSC group than in the hUMSC and placebo groups at 12 months after *** were also higher densities of vWf-,α-sma-,and cTnT-positive cells in the infarct border zone in the collagen/cell group,as revealed by immunohistochemical analysis,suggesting better angiogenesis and more cardiomyocyte survival after ***,the injectable collagen scaffold was safe and effective on a large animal myocardial model,which is beneficial for constructing a favorable microenvironment for applying stem cells in clinical MI.

关键词： injectable collagen scaffold mesenchymal stem cell MI

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Cooperation-based sperm clusters mediate sperm oviduct entry and fertilization

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Protein & cell 2021年第10期12卷 810-817页

作者： Yongcun Qu Qi Chen Shanshan Guo Chiyuan Ma Yonggang Lu Junchao Shi Shichao Liu Tong Zhou Taichi Noda Jingjing Qian Liwen Zhang Xili Zhu Xiaohua Lei Yujing Cao Wei Li Wei Li Nicolas Plachta Martin M.Matzuk Masahito Ikawa Enkui Duan Ying Zhang Hongmei Wang State Key Laboratory of Stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China university of Chinese Academy of sciences Beijing 100049China Division of Biomedical sciences School of MedicineUniversity of CaliforniaRiversideCA 92521USA Research institute for Microbial Diseases Osaka UniversitySuitaOsakaJapan Department of Physiology and cell Biology Reno School of MedicineUniversity of NevadaRenoNVUSA institute of Molecular and cell Biology A*STARSingaporeSin gapore Center for Drug Discovery Department of Pathology and ImmunologyBaylor College of MedicineHoustonTX 77030USA Division of Biology and Biological Engineering California Institute of TechnologyPasadenaCAUSA institute for Stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China The Key Laboratory of cell Proliferation and Regulation Biology Ministry of EducationInstitute of Cell BiologyBeijing Normal UniversityBeijing 100875China

Dear Editor,Sperm cooperation has been observed in multiple species(Pizzari and Foster,2008),yet its existenee and benefit for reproductive success in mammals remains ***,combining tissue-clearing with deep three-dimensional(3D)imagi ng,we dem on strate that postcopulatory mouse sperm congregate into unidirectional sperm cooperative clusters at the utero-tubal junction(UTJ),a key physical barrier for passage into the oviduct.

关键词： passage media Foster

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Apoptotic Effect of Cisplatin and Cordycepin on OC3 human Oral Cancer cells

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Chinese Journal of Integrative Medicine 2014年第8期20卷 624-632页

作者： CHEN Ying-hui HAO Lyh-Jyh HUNG Chih-peng CHEN Jung-wei LEU Sew-fen HUANG Bu-miin Department of Anesthesia Chi-Mei Medical Center Department of Nursing Min-Hwei College of Health Care Management Division of Endocrinology and Metabolism Kaohsiung Veteran General Hospital Tainan Branch Department of Anesthesiology Chang Gung Memorial Hospital and Kaohsiung Medical CenterChang Gung University institute of Hot Spring Industry Chia Nan University of Pharmacy and Science Department of Food science and Technology College of Human EcologyHungKuang University Department of cell Biology and anatomy and College of MedicineNational Cheng Kung University

Objective： To evaluate apoptotic effects of cisplatin and cordycepin as single agent or in combination with cytotoxicity in oral cancer cells. Methods： The influences of cisplatin （2.5 μg/mL） and/or cordycapin treatment （10 or 100 μmol/L） to human OC3 oral cancer cell line were investigated by morphological observation for cell death appearance, methylthiazoletetrazolium （MTT） assay for cell viability, flow cytometry assay for cell apoptosis, and Western blotting for apoptotic protein expressions. Results： Data demonstrated that co-administration of cisplatin （2.5 μg/mL） and cordycepin （10 or 100μmol/L） resulted in the enhancement of OC3 cell apoptosis compared to cisplatin or cordycapin alone treatment （24 h）, respectively （P〈0.05）. In flow cytometry assay, percentage of cells arrested at subG1 phase with co-treatment of cordycepin and cisplatin （30%） was significantly higher than cisplatin （5%） or cordycepin （12%） alone group （P〈0.05）, confirming a synergistically apoptotic effect of cordycepin and cisplatin. In cellular mechanism study, co-treatment of cordycepin and cisplatin induced more stress-activated protein kinase/dun terminal kinase （JNK）, the expressions of caspase-7, and the cleavage of poly ADP-ribose polymerase （PARP） as compared to cisplatin or cordycepin alone treatment （P〈0.05）. Conclusion： Cisplatin and cordycepin possess synergistically apoptotic effect through the activation of JNK/caspase-7/PARP pathway in human OC3 oral cancer cell line.

关键词： cisplatin cordycepin apoptosis OC3 synergistic

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Apoptotic extracellular vesicles are metabolized regulators nurturing the skin and hair

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Bioactive Materials 2023年第1期19卷 626-641页

作者： Lan Ma Chider Chen Dawei Liu Zhiqing Huang Jiaqi Li Haixiang Liu Ryan Tsz Kin Kwok Benzhong Tang Bingdong Sui Xiao Zhang Jianxia Tang Xueli Mao Weiying Huang Songtao Shi Xiaoxing Kou Hospital of Stomatology Guanghua School of StomatologySun Yat-sen UniversitySouth China Center of Craniofacial Stem Cell ResearchGuangdong Provincial Key Laboratory of Stomatology510055GuangzhouChina Department of anatomy and cell Biology University of PennsylvaniaSchool of Dental MedicinePhiladelphiaPA19104USA Department of Orthodontics Peking University School&Hospital of Stomatology#22 Zhongguancun South AvenueBeijing100081China Department of Chemical and Biological Engineering Department of ChemistryThe Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction and Institute for Advanced StudyThe Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Shenzhen institute of Aggregate science and Technology School of Science and EngineeringThe Chinese University of Hong KongShenzhen2001 Longxiang BoulevardLonggang DistrictShenzhen CityGuangdong518172China Key Laboratory of Stem cells and Tissue Engineering(Sun Yat-Sen university) Ministry of EducationGuangzhouGuangdong510055China

Over 300 billion of cells die every day in the human body,producing a large number of endogenous apoptotic extracellular vesicles(apoEVs).Also,allogenic stem cell transplantation,a commonly used therapeutic approach in current clinical practice,generates exogenous *** is well known that phagocytic cells engulf and digest apoEVs to maintain the body’s *** this study,we show that a fraction of exogenous apoEVs is metabolized in the integumentary skin and hair ***,apoEVs activate the Wnt/β-catenin pathway to facilitate their metabolism in a wave-like *** migration of apoEVs is enhanced by treadmill exercise and inhibited by tail suspension,which is associated with the mechanical force-regulated expression of DKK1 in ***,we show that exogenous apoEVs promote wound healing and hair growth via activation of Wnt/β-catenin pathway in skin and hair follicle mesenchymal stem *** study reveals a previously unrecognized metabolic pathway of apoEVs and opens a new avenue for exploring apoEV-based therapy for skin and hair disorders.

关键词： Apoptosis Extracellular vesicle Metabolized regulator Integumentary system Mesenchymal stem cells

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Homozygous deleterious variants in MYCBPAP induce asthenoteratozoospermia involving abnormal acrosome biogenesis,manchette structure and sperm tail assembly in humans and mice

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science China Life sciences 2024年

作者： Yiling Zhou Chaofeng Tu Charles Coutton Jianan Tang Shixiong Tian Shuyan Tang Guillaume Martinez Dapeng Zhou Célia Tebbakh Jiaxiong Wang Raoudha Zouari Xuehai Zhou Selima Fourati Ben Mustapha Xuemei Wang Bangguo Wu Xinyan Geng Shuang Liu Li Jin Huijuan Shi Yue-Qiu Tan Pierre F.Ray Lingbo Wang Xiaoyu Yang Feng Zhang Chunyu Liu Polyclinique les Jasmins Centre d’Aide Médicale à la Procréation Centre Urbain Nord Key Laboratory of Systems health science of Zhejiang Province School of Life Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Soong Ching Ling institute of Maternity and child health International Peace Maternity and Child Health Hospital Shanghai Jiao Tong University School of Medicine CHU Grenoble Alpes UM GI-DPI State Key Laboratory of Reproductive Medicine and offspring health Clinical Center for Reproductive Medicine The First Affiliated Hospital of Nanjing Medical University Shanghai Key Laboratory of Embryo Original Diseases Obstetrics and Gynecology Hospital State Key Laboratory of Genetic Engineering Institute of Medical Genetics and Genomics Fudan University institute of Reproductive and Stem cell Engineering NHC Key Laboratory of Human Stem Cell and Reproductive Engineering School of Basic Medical Science Central South University Clinical Research Center for Reproduction and Genetics in Hunan Province Reproductive and Genetic Hospital of CITIC-XIANGYA Université Grenoble Alpes CNRS UMR 5309 INSERM U1209 Institute for Advanced Biosciences (IAB) Site Santé–Allée des Alpes CHU Grenoble Alpes H?pital Couple-Enfant UM de Génétique Chromosomique Shanghai-MOST Key Laboratory of health and Disease Genomics NHC Key Lab of Reproduction Regulation Shanghai Institute for Biomedical and Pharmaceutical Technologies School of Pharmacy Fudan University Shanghai Key Laboratory of Metabolic Remodeling and health Institute of Metabolism and Integrative Biology Fudan University State Key Laboratory of Reproductive Medicine The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital

Asthenoteratozoospermia is a common cause of male infertility. To further define the genetic causes underlying asthenoteratozoospermia, we performed whole-exome sequencing in a cohort of Han Chinese men with asthenoteratozoospermia. Homozygous deleterious variants of MYCBPAP were first identified in two unrelated Chinese cases. Replication analyses in a French cohort revealed an additional asthenoteratozoospermia-affected case harboring a homozygous nonsense variant in MYCBPAP. All of the identified MYCBPAP variants were absent or extremely rare in the public human genome databases. Further functional assays indicated remarkably reduced abundance of MYCBPAP in the spermatozoa from MYCBPAP-associated cases. Subsequently, we generated a Mycbpap knockout(Mycbpap-/-) mouse model, which also exhibited male infertility with reduced sperm motility and abnormal morphologies in sperm heads and flagella. Further investigations demonstrated that Mycbpap-/-male mice presented disrupted acrosome biogenesis and abnormally elongated manchette during ***, proteomic analyses indicated that the proteins related to spermatogenesis, acrosomal and flagellar functions were significantly down-regulated in the testes from Mycbpap-/-male mice. Endogenous immunoprecipitation combined with mass spectrometry revealed interactions of MYCBPAP with a ribosome elimination related protein ARMC3 and central apparatus proteins including CFAP65 and ***, MYCBPAP-associated male infertility in humans and mice could be partially overcome by using intracytoplasmic sperm injections. Collectively, these findings illustrate the essential role of MYCBPAP in normal spermatogenesis and homozygous deleterious variants in MYCBPAP can be considered as a genetic diagnostic indicator for infertile men with asthenoteratozoospermia. Our study will provide effective guidance for genetic counseling, clinical diagnosis and assisted reproduction treatments of MYCBPAP-associated male

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Overview on signal transduction cascades regulation roles of garlic and its bioactive constituents

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Food science and human Wellness 2024年第5期13卷 2353-2362页

作者： Ammad Ahmad Farooqi Iqra Mobeen Rukset Attar Khalida I.Noel Baojun Xu William C.Cho institute of Biomedical and Genetic Engineering(IBGE) Islamabad 44000Pakistan Khursheed Rasheed Hospital Lahore Lahore 53720Pakistan Department of Obstetrics and Gynecology Yeditepe UniversityAtaşehir 34755Turkey human anatomy Department College of MedicineAl-Mustansiriyah UniversityBaghdad 10036Iraq Food science and Technology Program Department of Life SciencesBNU-HKBU United International CollegeZhuhai 519087China Department of Clinical Oncology Queen Elizabeth HospitalHong Kong G514TFChina

High-throughput technologies in combination with modern exciting advancements in mass spectrometry-based proteomics and data analysis pipelines have empowered comprehensive characterization of disease phenotypes and their mechanistic regulation by dietary agents and bioactive molecules at unprecedented dimensionality and ***-ordinary breakthroughs in the field of nutrigenomics have leveraged our understanding altogether to a new level of *** researchers have extensively analyzed health promoting and pharmacologically significant properties of garlic(Allium sativum).Importantly,garlic and its biologically active chemicals targeted oncogenic signaling *** this mini-review we have attempted to summarize how garlic and its bioactive constituents regulated signal transduction cascades in cell culture studies and tumor-bearing mice.

关键词： Cancer Nutrigenomics Signaling Apoptosis Allium sativum

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The potential of bone morphogenetic protein 2 as a neurotrophic factor for Parkinson’s disease

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Neural Regeneration Research 2020年第8期15卷 1432-1436页

作者： Susan R.Goulding Aideen M.Sullivan Gerard W.O’Keeffe Louise M.Collins Department of Biological sciences Cork Institute of TechnologyCorkIreland Department of anatomy and Neuroscience and Cork Neuroscience Centre University College CorkCorkIreland Department of Physiology University College CorkCorkIreland

Parkinson’s disease is the second most common neurodegenerative disorder;it affects 1%of the population over the age of *** number of people with Parkinson’s disease is set to rapidly increase due to changing demographics and there is an unmet clinical need for disease-modifying *** pathological hallmarks of Parkinson’s disease are the progressive degeneration of dopaminergic neurons in the substantia nigra and their axons which project to the striatum,and the aggregation ofα-synuclein;these result in a range of debilitating motor and non-motor *** application of neurotrophic factors to protect and potentially regenerate the remaining dopaminergic neurons is a major area of research ***,this strategy has had limited success to *** trials of two well-known neurotrophic factors,glial cell line-derived neurotrophic factor and neurturin,have reported limited efficacy in Parkinson’s disease patients,despite these factors showing potent neurotrophic actions in animal *** is therefore a need to identify other neurotrophic factors that can protect againstα-synuclein-induced degeneration of dopaminergic *** bone morphogenetic protein(BMP)family is the largest subgroup of the transforming growth factor-βsuperfamily of *** are naturally secreted proteins that play crucial roles throughout the developing nervous ***,many BMPs have been shown to be potent neurotrophic factors for dopaminergic *** we discuss recent work showing that transcripts for the BMP receptors and BMP2 are co-expressed with several key markers of dopaminergic neurons in the human substantia nigra,and evidence for downregulation of BMP2 expression at distinct stages of Parkinson’s *** also discuss studies that explored the effects of BMP2 treatment,in in vitro and in vivo models of Parkinson’s *** studies found potent effects of BMP2 on dopaminergic neurites,which is important given that axon deg

关键词： axon growth BMP2 dopaminergic neurons neuroprotection neurotrophic factor neuroregeneration Parkinson’s disease α-synuclein

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Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart

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Bioactive Materials 2021年第12期6卷 4415-4429页

作者： Ge Guan Da Huo Yanzhao Li Xiaolin Zhao Yinghao Li Zhongliang Qin Dayu Sun Guanyuan Yang Mingcan Yang Ju Tan Wen Zeng Chuhong Zhu Department of anatomy State Key Laboratory of TraumaBurn and Combined InjuryKey Lab for Biomechanics and Tissue Engineering of ChongqingArmy Medical University(Third Military Medical University)Chongqing400038China Chongqing institute of Zhong Zhi Yi Gu Shapingba DistrictChongqing400030China Department of cell Biology Third Military Army Medical UniversityChongqing400038China

cell therapy has been a promising strategy for cardiac repair after myocardial infarction(MI),but a poor ischemic environment and low cell delivery efficiency remain significant *** spleen serves as a hematopoietic stem cell niche and secretes cardioprotective factors after MI,but it is unclear whether it could be used for human pluripotent stem cell(hiPSC)cultivation and provide a proper microenvironment for cell grafts against the ischemic ***,we developed a splenic extracellular matrix derived thermoresponsive hydrogel(SpGel).Proteomics analysis indicated that SpGel is enriched with proteins known to modulate the Wnt signaling pathway,cell-substrate adhesion,cardiac muscle contraction and oxidation-reduction *** vitro studies demonstrated that hiPSCs could be efficiently induced into endothelial cells(iECs)and cardiomyocytes(iCMs)with enhanced function on *** cytoprotective effect of SpGel on iECs/iCMs against oxidative stress damage was also ***,in vivo studies revealed that iEC/iCM-laden SpGel improved cardiac function and inhibited cardiac fibrosis of infarcted hearts by improving cell survival,revascularization and *** conclusion,we successfully established a novel platform for the efficient generation and delivery of autologous cell grafts,which could be a promising clinical therapeutic strategy for cardiac repair and regeneration after MI.

关键词： Stem cell-laden splenic hydrogel hiPSC differentiation platform Antioxidant stress Myocardial infarction Cardiac repair

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Alpl prevents bone ageing sensitivity by specifically regulating senescence and differentiation in mesenchymal stem cells

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Bone Research 2018年第4期6卷 393-407页

作者： Wenjia Liu Liqiang Zhang Kun Xuan Chenghu Hu Shiyu Liu Li Liao Bei Li Fang Jin Songtao Shi Yan Jin MS-State Key Laboratory & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases Center for Tissue EngineeringSchool of StomatologyFourth Military Medical UniversityXi’anChina Xi’an institute of Tissue Engineering and Regenerative Medicine Xi’anChina Department of anatomy and cell Biology School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA

Mutations in the liver/bone/kidney alkaline phosphatase(Alpl) gene cause hypophosphatasia(HPP) and early-onset bone dysplasia,suggesting that this gene is a key factor in human bone development. However, how and where Alpl acts in bone ageing is largely unknown. Here, we determined that ablation of Alpl induces prototypical premature bone ageing characteristics, including bone mass loss and marrow fat gain coupled with elevated expression of p16INK4A(p16) and p53 due to senescence and impaired differentiation in mesenchymal stem cells(MSCs). Mechanistically, Alpl deficiency in MSCs enhances ATP release and reduces ATP hydrolysis. Then, the excessive extracellular ATP is, in turn, internalized by MSCs and causes an elevation in the intracellular ATP level, which consequently inactivates the AMPKα pathway and contributes to the cell fate switch of MSCs. Reactivating AMPKα by metformin treatment successfully prevents premature bone ageing in Alpl+/-mice by improving the function of endogenous *** results identify a previously unknown role of Alpl in the regulation of ATP-mediated AMPKα alterations that maintain MSC stemness and prevent bone ageing and show that metformin offers a potential therapeutic option.

关键词： Alpl prevents bone ageing sensitivity by specifically regulating senescence and differentiation in mesenchymal stem cells ATP

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