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Current methods for the maturation of induced pluripotent stem cellderived cardiomyocytes

World Journal of Stem Cells 2019年第1期11卷 33-43页

作者： Pranav Machiraju Steven C Greenway Departments of Pediatrics and Cardiac Sciences Alberta Children’s Hospital Research Institute Libin Cardiovascular Institute of Alberta Cumming School of MedicineUniversity of Calgary Departments of Pediatrics Cardiac Sciences Biochemistry & Molecular Biology Alberta Children’s Hospital Research Institute Libin Cardiovascular Institute of Alberta Cumming School of Medicine University of Calgary

Induced pluripotent stem cells(iPSCs) were first generated by Yamanaka and colleagues over a decade ago. Since then, iPSCs have been successfully differentiated into many distinct cell types, enabling tissue-, disease-, and patientspecific in vitro modelling. Cardiovascular disease is the greatest cause of mortality worldwide but encompasses rarer disorders of conduction and myocardial function for which a cellular model of study is ideal. Although methods to differentiate iPSCs into beating cardiomyocytes(iPSC-CMs) have recently been adequately optimized and commercialized, the resulting cells remain largely immature with regards to their structure and function,demonstrating fetal gene expression, disorganized morphology, reliance on predominantly glycolytic metabolism and contractile characteristics that differ from those of adult cardiomyocytes. As such, disease modelling using iPSC-CMs may be inaccurate and of limited utility. However, this limitation is widely recognized, and numerous groups have made substantial progress in addressing this problem. This review highlights successful methods that have been developed for the maturation of human iPSC-CMs using small molecules,environmental manipulation and 3-dimensional(3 D) growth approaches.

关键词： Induced pluripotent stem cells Induced pluripotent stem cell-derived cardiomyocytes Regenerative medicine Stem cell biology translational research

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Evolution of treatment options for juvenile idiopathic arthritis

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World Journal of Orthopedics 2024年第9期15卷 831-835页

作者： Tao Ren Jia-Hui Guan Yu Li Nan-Nan Li Zheng Li Department of Colorectal Surgery Taihe County People’s Hospital of Anhui ProvinceFuyang 236600Anhui ProvinceChina Department of Pharmacy Taihe County People’s Hospital of Anhui ProvinceFuyang 236600Anhui ProvinceChina University of Science and Technology of China The First Affiliated Hospital of University of Science and Technology of ChinaHefei 230001Anhui ProvinceChina Jiangsu Engineering research Center of Cardiovascular Drugs Targeting Endothelial Cells College of Health SciencesSchool of Life SciencesJiangsu Normal UniversityXuzhou 221116Jiangsu ProvinceChina

A recent study published in World J Clin Cases addressed the optimal non-steroidal anti-inflammatory drugs(NSAIDs)for juvenile idiopathic arthritis(JIA).Herein,we outline the progress in drug therapy of *** have traditionally been the primary treatment for all forms of *** are symptom-relief medications,and well tolerated by ***,the availability of selective NSAIDs further lower the gastrointestinal adverse reactions compared with traditional *** is another kind of symptom-relief medications with potent anti-inflammatory ***,the frequent adverse events limit the clinical *** NSAIDs and glucocorticoid fail to ease or pre-vent joint damage,and the breakthrough comes along with the disease-mo-difying antirheumatic drugs(DMARDs).DMARDs can prevent disease pro-gression and reduce joint ***,the emergence of biologic DMARDs(bDMARDs)has truly revolutionized the therapeutics of JIA,compared with conventional synthetic *** a newly developed class of drugs,the places of most bDMARDs in the management of JIA remain to be well ***,the continuous evolution of bDMARDs raises hopes of improving long-term disease outcomes for JIA.

关键词： Juvenile idiopathic arthritis Treatment Non-steroidal anti-inflammatory drug Disease-modifying antirheumatic drug Evolution

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An Optimal Smooth Model based EEG Analysis Method

An Optimal Smooth Model based EEG Analysis Method

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第40届中国控制会议

作者： Chao Chen Tianxu Shang Abdelkader Nasreddine Belkacem Shanting Zhang Lin Lu Penghai Li Tianjin University of Technology Academy of medical Engineering and translational medicine Tianjin University Department of Computer and Network Engineering College of Information Technology UAE University Zhonghuan Information College Tianjin University of Technology

Aiming at the problem of unsatisfactory noise removal effect during the preprocessing of MI EEG signals,an optimal smooth model based on empirical mode decomposition is ***,use empirical mode decomposition（EMD）to decompose the complex signal into a certain number of intrinsic mode functions（IMFs） and a remainder function（r）,and then construct a smooth model function based on the mean square error and smoothing index,using different The function of the intrinsic mode is combined with the optimal smooth model function to reduce noise and obtain the optimal *** research results show that compared with several denoising methods commonly used in other literature,this method has improved SNR,RMSE,and PE three evaluation *** proposed method can provide a reference for the preprocessing of motor imagery signals.

关键词： Motor Imagery Electroencephalogram(EEG) EEG signal denoising

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The tumor immune microenvironment transcriptomic subtypes of colorectal cancer for prognosis and development of precise immunotherapy

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Gastroenterology Report 2020年第5期8卷 381-389,I0002页

作者： Yun-Qiang Tang Tu-Feng Chen Yan Zhang Xiao-Chen Zhao Yu-Zi Zhang Guo-Qiang Wang Meng-Li Huang Shang-Li Cai Jing Zhao Bo Wei Jun Huang Department of Hepatic-biliary Surgery Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityGuangzhouGuangdongP.R.China Department of gastrointestinal Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjingJiangsuP.R.China The Medical Department 3D Medicines Inc.ShanghaiP.R.China Department of Colorectal Surgery The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases the Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouP.R.China Guangdong Institute of Gastroenterology GuangzhouP.R.China

Background:Biomarkers based on immune context may guide prognosis prediction.T-cell inactivation,exclusion,or dysfunction could cause unfavorable tumor microenvironments,which affect immunotherapy and ***,none of the immuno-biomarkers reported to date can differentiate colorectal-cancer(CRC)***,we aimed to classify CRC patients according to the levels of T-cell activation,exclusion,and dysfunction in the tumor ***:RNAseq data of 618 CRC patients from The Cancer Genome Atlas and microarray data of 316 CRC patients from Gene Expression Omnibus were analysed using the Tumor Immune Dysfunction and Exclusion *** clustering was used to classify ***:Based on the expression signatures of myeloid-derived suppressor cells,cancer-associated fibroblasts,M2-like tumor-associated macrophages,cytotoxic T-lymphocytes,and PD-L1,all patients were clustered into four subtypes:cluster 1 had a high level of immune dysfunction,cluster 2 had a low level of immune activation,cluster 3 had intense immune exclusion,and cluster 4 had a high level of immune activation and a moderate level of both dysfunction and exclusion *** with cluster 1,the hazard ratios and 95%confidential intervals for overall survival were 0.63(0.35-1.13)for cluster 2,0.55(0.29-1.03)for cluster 3,and 0.30(0.14-0.64)for cluster 4 in multivariate Cox *** immune clustering and prognosis patterns were obtained upon validation in the GSE39582 *** subgroup analysis,immune clustering was significantly associated with overall survival among stage I/II patients,microsatellite stable/instability-low patients,and patients not treated with adjuvant ***:Our findings demonstrated that classifying CRC patients into different immune subtypes serves as a reliable prognosis predictor and may help to refine patient selection for personalized cancer immunotherapy.

关键词： colorectal cancer immune dysfunction immune exclusion prognosis

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Fargeted elimination of mutant mitochondria DNA in MELAS-iPSCs by mitoTALENs

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Protein & Cell 2018年第3期9卷 283-297页

作者： Yi Yang Han Wu Xiangjin Kang Yanhui Liang Ting Lan Tianjie Li Tao Tan Jiangyun Peng Quanjun Zhang Geng An Yali Liu Qian Yu Zhenglai Ma Ying Lian Boon Seng Soh Qingfeng Chen Ping Liu Yaoyong Chen Xiaofang Sun Rong Li Xiumei Zhen Yang Yu Xiaoping Li Yong Fan Key Laboratory for Major Obstetric Diseases of Guangdong Province Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes The Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 China Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou 510530 China Center of Reproductive Medicine Department of Obstetrics and Gynecology Peking University Third Hospital Beijing 100191 China Yunnan Key Laboratory of Primate Biomedical research Institute of Primate Translational Medicine Kunming University of Science and Technology Kunming 650500 China Disease Modeling and Therapeutics Laboratory A'STAR Institute of Molecular and Cell Biology 61 Biopolis Drive Proteos Singapore 138673 Singapore Department of Biological Sciences National University of Singapore Singapore 117543 Singapore

Mitochondrial diseases are maternally inherited hetero- geneous disorders that are primarily caused by mitochondrial DNA （mtDNA） mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruc- tion of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells （MiPSCs） that harbored a high proportion of m.3243A〉G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes （MELAS）. We engineered mitochondrial-targeted transcription activator-like effector nucleases （mitoTALENs） and successfully eliminated the m.3243A〉G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Further- more, we successfully achieved reduction in the human m.3243A〉G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.

关键词： mitochondria iPSCs TALEN MELAS

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A facile,versatile hydrogel bioink for 3D bioprinting benefits long-term subaqueous fidelity,cell viability and proliferation

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Regenerative Biomaterials 2021年第3期8卷 141-155页

作者： Hongqing Chen Fei Fei Xinda Li Zhenguo Nie Dezhi Zhou Libiao Liu Jing Zhang Haitao Zhang Zhou Fei Tao Xu Department of Neurosurgery Xijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Neurosurgery Central Theater General HospitalWuhan 430010China Department of Ophthalmology Xijing HospitalFourth Military Medical UniversityXi’an 710032China Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing Department of Mechanical EngineeringTsinghua UniversityBeijing 100084China Key Laboratory for Advanced Materials Processing Technology Ministry of EducationDepartment of Mechanical EngineeringTsinghua UniversityBeijing 100084China Department of Neurosurgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072China Chinese Academy of Sciences Sichuan translational Medicine research Hospital Chengdu 610072China Department of Orthopedics Fourth medical center of PLA general hospitalBeijing 100048China East China Institute of Digital Medical Engineering Shangrao 334000China Department of Precision Medicine and Healthcare Tsinghua-Berkeley Shenzhen InstituteShenzhen 518055China

Both of the long-term fidelity and cell viability of three-dimensional(3D)-bioprinted constructs are essential to precise soft tissue ***,the shrinking/swelling behavior of hydrogels brings about inadequate long-term fidelity of constructs,and bioinks containing excessive polymer are detrimental to cell ***,we obtained a facile hydrogel by introducing 1%aldehyde hyaluronic acid(AHA)and 0.375%N-carboxymethyl chitosan(CMC),two polysaccharides with strong water absorption and water retention capacity,into classic gelatin(GEL,5%)–alginate(ALG,1%)*** GEL–ALG/CMC/AHA bioink possesses weak temperature dependence due to the Schiff base linkage of CMC/AHA and electrostatic interaction of CMC/*** fabricated integrated constructs through traditional printing at room temperature and in vivo simulation printing at *** printed cell-laden constructs can maintain subaqueous fidelity for 30 days after being reinforced by 3%calcium chloride for only 20 *** cytometry results showed that the cell viability was 91.3861.55%on day 29,and the cells in the proliferation plateau at this time still maintained their dynamic renewal with a DNA replication rate of 6.0661.24%.This work provides a convenient and practical bioink option for 3D bioprinting in precise soft tissue repair.

关键词： bioink bioprinting subaqueous fidelity cell viability

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Confocal laser endomicroscopy for gastric neoplasm

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World Journal of gastrointestinal Endoscopy 2024年第9期16卷 540-544页

作者： Arkadeep Dhali Rick Maity Roger B Rathna Jyotirmoy Biswas Department of Gastroenterology Sheffield Teaching Hospitals NHS Foundation TrustRoyal Hallamshire HospitalSheffield S102JFUnited Kingdom School of Medicine and Population Health University of SheffieldSheffield S102HQUnited Kingdom General Medicine Institute of Post Graduate Medical Education and ResearchKolkata 700020India Department of Internal Medicine University Hospitals Leicester NHS TrustLeicester Royal InfirmaryLeicester LE15WWUnited Kingdom General Medicine College of Medicine and Sagore Dutta HospitalKolkata 700058India

Confocal laser endomicroscopy(CLE)is a novel endoscopic modality that provides real-time histological information via high-resolution magnified view of the *** has a higher sensitivity,specificity,and diagnostic accuracy in detecting atrophic gastritis as compared to chromoendoscopy and narrow-band *** can even predict low-grade and high-grade intraepithelial neoplasia by analyzing gastric pit *** may have some advantages over the standard biopsy protocol,such as higher diagnostic yield and fewer biopsy *** diagnostic accuracy in detecting superficial gastric cancer is higher than that of white-light *** limitations,such as a narrow field of vision,can be surpassed by technological advancements and integration with other detection *** intelligence holds promise in automated analysis of histopathological ***,CLE can be helpful in screening for early gastric cancer and may help reduce the risk of complications from repeated biopsies,such as mucosal damage,bleeding,and infection.

关键词： Confocal laser endomicroscopy Gastric cancer Narrow band imaging Diagnostic yield

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Efficacy and safety of tandem autologous stem cell transplantation in multiple myeloma:a retrospective single-center analysis

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Chinese Medical Journal 2023年第15期136卷 1873-1875页

作者： Shunquan Wu Zongjian Qiu Ting Lin Zhijuan Zhu Xiaofan Li Xianling Chen Ping Chen Yiting Wang Rong Zhan Nainong Li Department of Hematology Hematopoietic Stem Cell Transplantation CenterFujian Institute of HematologyFujian Provincial Key Laboratory on HematologyFujian Medical University Union HospitalFuzhouFujian 350001China translational Medicine Center on Hematology Fujian Medical UniversityFuzhouFujian 350001China

To the Editor:Upfront autologous stem cell transplantation(ASCT)has been an integral part of the management of young and eligible older patients with newly diagnosed multiple myeloma(NDMM)for over three *** stem cell transplantation was defined as two planned sequential ASCTs within 3 to 6 *** than two decades after its introduction,trials exploring the utility of tandem transplants have yielded mixed *** role of tandem ASCT in multiple myeloma(MM)remains unclear and *** the EMN02/HOVON95 study.

关键词： myeloma analysis stem

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Transdermal delivery of interleukin-12 gene targeting dendritic cells enhances the anti-tumour effect of programmed cell death protein 1 monoclonal antibody

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Biomaterials translational 2021年第2期2卷 151-164页

作者： Huoyan Hong Xiaoyun Wang Xinran Song Gomaa El Fawal Kaili Wang Di Jiang Yifei Pei Zhe Wang Hongsheng Wang Shanghai Engineering research Centre of Nano-Biomaterials and Regenerative Medicine Key Laboratory of Science&Technology of Eco-Textile(Ministry of Education)College of ChemistryChemical Engineering and BiotechnologyDonghua UniversityShanghaiChina Department of Obstetrics&Gynaecology Shanghai First People’s Hospital Affiliated to Shanghai Jiao Tong UniversityShanghaiChina Department of Polymer Materials research Advanced Technology and New Materials Research InstituteScientific Research and Technological Applications City(SRTA-City)New Borg El-Arab CityAlexandriaEgypt

Recent studies have suggested that the anti-tumour effect of the programmed cell death protein 1 monoclonal antibody(aPD-1)depends on the expression of interleukin-12(IL-12)by dendritic cells(DCs).Since DCs are abundant in skin tissues,transdermal delivery of IL-12 targeting DCs may significantly improve the anti-tumour effect of *** this study,a novel mannosylated chitosan(MC)-modified ethosome(Eth-MC)was obtained through electrostatic *** Eth-MC loaded with plasmid containing the IL-12 gene(pIL-12@Eth-MC)stimulated DCs to express mature-related molecular markers such as CD86,CD80,and major histocompatibility complex-II in a targeted *** pIL-12@Eth-MC was then mixed with polyvinyl pyrrolidone solution to make microspheres using the electrospray technique,and sprayed onto the surface of electrospun silk fibroin-polyvinyl alcohol nanofibres to obtain a PVP-pIL-12@Eth-MC/silk fibroin-polyvinyl alcohol composite nanofibrous patch(termed a transcutaneous immunization(TCI)patch).The TCI patch showed a good performance on transdermal drug *** experiments on melanoma-bearing mice showed that topical application of the TCI patches promoted the expression of IL-12 and inhibited the growth of ***,combined application of the TCI patch and aPD-1 showed a stronger anti-tumour effect than aPD-1 *** combination therapy significantly promoted the expression of IL-12,interferon-γand tumour necrosis factor-α,the infiltration of CD4+and CD8+T cells into tumour tissues,and thus promoted the apoptosis of tumour *** present study provides a convenient and non-invasive strategy for improving the efficacy of immune checkpoint inhibitor *** study was approved by the Institutional Animal Care and Use Committee at Donghua University(approval ***-NSFC-2020-11)on March 31,2020.

关键词： aPD-1 dendritic cells ethosome IL-12 transcutaneous immunization

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Microfluidic electrospray photo-crosslinkable κ-Carrageenan microparticles for wound healing

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Engineered Regeneration 2021年第1期2卷 257-262页

作者： Zhiqiang Luo Junyi Che Lingyu Sun Lei Yang Yan Zu Huan Wang Yuanjin Zhao Department of Rheumatology and Immunology Institute of Translational MedicineThe Affiliated Drum Tower HospitalNanjing University Medical SchoolNanjing 210008China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Oujiang Laboratory Zhejiang Lab for Regenerative MedicineVision and Brain HealthWenzhouZhejiang 325001China Wenzhou Institute University of Chinese Academy of SciencesWenzhouZhejiang 325001China The Eighth Affiliated Hospital Sun Yat-sen UniversityShenzhen 518033China

When organs,especially external organs are injured,pathogens and excessive water loss can threaten the wound healing process and cause local irreversible tissue ***,novel natural κ-Carrageenan microparticles(MPs)able to deliver bioactive proteins and small molecules to the wound surface for promoted regeneration were developed using microfluidic *** side chains of κ-Carrageenan were modified with methacrylate pendant groups to make the monomer photonic *** changing the concentration of methacrylated-κ-Carrageenan,different porosities of MPs with controllable drug loading were *** size of the MPs can also be tailored by adjusting the voltage of the applied electric *** endothelial growth factor(VEGF)and antimicrobial peptides Eumenitin were co-loaded into the microparticles(VEGF-Eumenitin-MPs)and released sustainedly in phosphate-buffered *** VEGF-Eumenitin-MPs had high biocompatibility and intensive antibacterial activities for ***,the antibacterial and angiogenetic properties of the VEGF-Eumenitin-MPs were demonstrated in a infectious wound model and the chronic wound healing process was significantly enhanced in ***,the developed porous MPs with sustained drug release properties have the potential to serve as a platform to deliver bioactive proteins and small molecules to the wound surface for promoted regeneration.

关键词： Microparticle Hydrogel Microfluidics Wound healing VEGF Antimicrobial peptide

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