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Human embryonic stem cells as an in vitro model for studying developmental origins of type 2 diabetes

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World Journal of Stem Cells 2020年第8期12卷 761-775页

作者： Andy Chun-Hang Chen Kai Fai Lee William Shu Biu Yeung Yin Lau Lee Department of Obstetrics and Gynaecology The University of Hong KongHong KongChina shenzhen key laboratory of fertility regulation The University of Hong Kong Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina

The developmental origins of health and diseases(DOHaD)is a concept stating that adverse intrauterine environments contribute to the health risks of *** the theory emerged more than 30 years ago,many epidemiological and animal studies have confirmed that in utero exposure to environmental insults,including hyperglycemia and chemicals,increased the risk of developing noncommunicable diseases(NCDs).These NCDs include metabolic syndrome,type 2 diabetes,and complications such as diabetic *** the effects of different environmental insults on early embryo development would aid in understanding the underlying mechanisms by which these insults promote NCD *** stem cells(ESCs)have also been utilized by researchers to study the *** have pluripotent characteristics and can be differentiated into almost every cell lineage;therefore,they are excellent in vitro models for studying early developmental *** importantly,human ESCs(hESCs)are the best alternative to human embryos for research because of ethical *** this review,we will discuss different maternal conditions associated with DOHaD,focusing on the complications of maternal ***,we will review the differentiation protocols developed to generate different cell lineages from ***,we will review how hESCs are utilized as a model for research into the *** effects of environmental insults on hESC differentiation and the possible involvement of epigenetic regulation.will be discussed.

关键词： Development origins of health and diseases Maternal diabetes Environmental insults Type 2 diabetes Human embryonic stem cells Epigenetics

The novel male meiosis recombination regulator coordinates the progression of meiosis prophase Ⅰ

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Journal of Genetics and Genomics 2020年第8期47卷 449-464页

作者： Miao Li Haiwei Feng Zexiong Lin Jiahuan Zheng Dongteng Liu Rui Guo Junshi Li Raymond H.W.Li Ernest H.Y.Ng Michael S.Y.Huen P.Jeremy Wang William S.B.Yeung Kui Liu shenzhen key laboratory of fertility regulation Center of Assisted Reproduction and EmbryologyThe University of Hong Kong-Shenzhen HospitalShenzhen518000China Department of Obstetrics and Gynecology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong999077China Department of Biomedical Sciences University of Pennsylvania School of Veterinary MedicinePhiladelphiaPA19104USA School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong999077China

Meiosis is a specialized cell division for producing haploid gametes in sexually reproducing *** this study,we have independently identified a novel meiosis protein male meiosis recombination regulator(MAMERR)/4930432 K21 Rik and showed that it is indispensable for meiosis prophase I progression in male *** super-resolution structured illumination microscopy,we found that MAMERR functions at the same double-strand breaks as the replication protein A and meiosis-specific with OB domains/spermatogenesis associated 22 *** generated a Mamerr-deficient mouse model by deleting exons 3 e6 and found that most of Mamerrà/àspermatocytes were arrested at pachynema and failed to progress to diplonema,although they exhibited almost intact synapsis and progression to the pachytene stage along with XY body *** mechanistic studies revealed that the recruitment of DMC1/RAD51 and heat shock factor 2 ebinding protein in Mamerrà/àspermatocytes was only mildly impaired with a partial reduction in double-strand break repair,whereas a substantial reduction in ubiquitination on the autosomal axes and on the XY body appeared as a major phenotype in Mamerrà/à*** propose that MAMERR may participate in meiotic prophase I progression by regulating the ubiquitination of key meiotic proteins on autosomes and XY chromosomes,and in the absence of MAMERR,the repressed ubiquitination of key meiotic proteins leads to pachytene arrest and cell death.

关键词： Meiosis 4930432K21Rik Recombination Ubiquitination

Caseinolytic mitochondrial matrix peptidase X is essential for homologous chromosome synapsis and recombination during meiosis of male mouse germ cells

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Asian Journal of Andrology 2024年第2期26卷 165-174页

作者： Hai-Wei Feng Yu Zhao Yan-Ling Gao Dong-Teng Liu Li-Jun Huo key laboratory of Agricultural Animal Genetics Breeding and ReproductionEducation Ministry of ChinaCollege of Animal Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China shenzhen key laboratory of fertility regulation Reproductive Medicine CenterThe University of Hong Kong-Shenzhen HospitalShenzhen 518053China Maternal-Fetal Medicine Institute Department of Obstetrics and GynaecologyShenzhen Baoan Women's and Children's HospitalJinan UniversityShenzhen 518100China Department of Obstetrics and Gynaecology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina

Meiosis is the process of producing haploid gametes through a series of complex chromosomal events and the coordinated action of various *** mitochondrial protease complex(ClpXP),which consists of caseinolytic mitochondrial matrix peptidase X(ClpX)and caseinolytic protease P(ClpP)and mediates the degradation of misfolded,damaged,and oxidized proteins,is essential for maintaining mitochondrial *** has been implicated in meiosis regulation.but its precise role is currently *** this study,we engineered an inducible male germ cell-specific knockout caseinolytic mitochondrial matrix peptidase X(Clpx^(cKO))mouse model to investigate the function of ClpX in *** found that disrupting Clpx in male mice induced germ cell apoptosis and led to an absence of sperm in the ***,it caused asynapsis of homologous chromosomes and impaired meiotic recombination,resulting in meiotic arrest in the zygotene-to-pachytene transition *** loss of ClpX compromised the double-strand break(DSB)repair machinery by markedly reducing the recruitment of DNA repair protein RAD51 homolog 1(RAD51)to DSB *** dysfunction may be due to an insufficient supply of energy from the aberrant mitochondria in Clpx^(cKO) spermatocytes,as discerned by electron ***,ubiquitination signals on chromosomes and the expression of oxidative phosphorylation subunits were both significantly attenuated in Clpx^(cKO) *** together,we propose that ClpX is essential for maintaining mitochondrial protein homeostasis and ensuring homologous chromosome pairing,synapsis,and recombination in spermatocytes during meiotic prophase I.

关键词： ClpX homologous chromosome meiosis mitochondrial recombination synapsis

Discovery of plasma biomarkers for Parkinson's disease diagnoses based on metabolomics and lipidomics

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Chinese Chemical Letters 2024年第11期35卷 260-265页

作者： Xiaoxiao Wang Bolun Wang Fenfen Ji Jie Yan Jiacheng Fang Doudou Zhang Ji Xu Jing Ji Xinran Hao Hemi Luan Yanjun hong Shulan Qiu Min Li Zhu Yang Wenlan Liu Xiaodong Cai Zongwei Cai State key laboratory of Environmental and Biological Analysis Department of ChemistryHong Kong Baptist UniversityHong KongChina Department of Neurosurgery Shenzhen Key Laboratory of Neurosurgerythe First Affiliated Hospital of Shenzhen UniversityShenzhen Second People's HospitalShenzhen 518035China The Central laboratory the First Affiliated Hospital of Shenzhen UniversityShenzhen Second People's HospitalShenzhen 518035China Mr.and Mrs.Ko Chi Ming Centre for Parkinson's Disease Research School of Chinese MedicineHong Kong Baptist UniversityHong KongChina

Parkinson's disease(PD) is an aging-associated neurodegenerative movement disorder with increasing morbidity and mortality *** current gold standard for diagnosing PD is clinical evaluation,which is often challenging and *** and lipidomics approaches have been extensively applied because of their potential in discovering valuable biomarkers for medical ***,we used comprehensive untargeted metabolomics and lipidomics methodologies based on liquid chromatographymass spectrometry to evaluate metabolic abnormalities linked with *** well-characterized cohorts of288 plasma samples(143 PD patients and 145 control subjects in total) were used to examine metabolic alterations and identify diagnostic *** multivariate and univariate studies were combined to identify the promising metabolic signatures,based on which the discriminant models for PD were established by integrating multiple machine learning algorithms.A 6-biomarker predictive model was constructed based on the omics profile in the discovery cohort,and the discriminant performance of the biomarker panel was evaluated with an accuracy over 81.6% both in the discovery cohort and validation *** results indicated that PC(40:7),eicosatrienoic acid were negatively correlated with severity of PD,and pentalenic acid,PC(40:6p) and aspartic acid were positively correlated with severity of *** summary,we developed a multi-metabolite predictive model which can diagnose PD with over81.6% accuracy based on this unique metabolic *** clinical diagnosis of PD may benefit from the biomarker panel reported in this study.

关键词： Parkinson's disease Metabolomics Lipidomics Machine learning Biomarker

A construct of adipose-derived mesenchymal stem cells—laden collagen scaffold for fertility restoration by inhibiting fibrosis in a rat model of endometrial injury

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Regenerative Biomaterials 2023年第1期10卷 1481-1495页

作者： Yangyang Dai Liaobing Xin Sentao Hu Shiqian Xu Dong Huang Xiaoying Jin Jianmin Chen Rachel Wah Shan Chan Ernest Hung Yu Ng William Shu Biu Yeung Lie Ma Songying Zhang Assisted Reproduction Unit Department of Obstetrics and GynecologySir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China key laboratory of Reproductive Dysfunction Management of Zhejiang Province Hangzhou 310016China MOE key laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China Department of Obstetrics and Gynaecology School of Clinical MedicineLKS Faculty of MedicineThe University of Hong KongHong Kong SAR 999077China shenzhen key laboratory of fertility regulation The University of Hong Kong Shenzhen HospitalShenzhen 518000China

Severe endometrium damage causes pathological conditions such as thin endometrium and intrauterine adhesion,resulting in uterine factor *** stem cell(MSC)therapy is a promising strategy in endometrial repair;yet,exogenous MSCs still raise concerns for safety and ethical *** adipose-derived mesenchymal stem cells(ADMSCs)residing in adipose tissue have high translational potentials due to their autologous *** harness the high translation potentials of ADMSC in clinical endometrium regeneration,here we constructed an ADMSCs composited porous scaffold(CS/ADMSC)and evaluated its effectiveness on endometrial regeneration in a rat endometrium-injury *** found that CS/ADMSC intrauterine implantation(i)promoted endometrial thickness and gland number,(ii)enhanced tissue angiogenesis,(iii)reduced fibrosis and(iv)restored *** ascertained the pro-proliferation,pro-angiogenesis,immunomodulating and anti-fibrotic effects of CS/ADMSC in vitro and revealed that the CS/ADMSC influenced extracellular matrix composition and organization by a transcriptomic *** results demonstrated the effectiveness of CS/ADMSC for endometrial regeneration and provided solid proof for our future clinical study.

关键词： adipose-derived mesenchymal stem cells collagen scaffold endometrium fibrosis regeneration

Single-cell RNA Sequencing Deciphers Immune Landscape of Human Recurrent Miscarriage

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Genomics, Proteomics & Bioinformatics 2021年第2期19卷 169-171页

作者： Chunyu Huang Yong Zeng Wenwei Tu Department of Paediatric and Adolescent Medicine Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina shenzhen key laboratory of Reproductive Immunology for Peri-implantation Fertility CenterShenzhen Zhongshan Urology HospitalShenzhen 518045China

Introduction Pregnancy is a mysterious biological process that presents great challenges to the maternal immune *** the early 1950s,the‘‘fetal allograft”concept was described for the first time by Peter Medawar,and the unique immunology of the maternal-fetal interface was recognized[1].Correct and precise interaction between mother and fetus plays an important role during pregnancy process,such as the apposition,adhesion,implantation,and growth of embryo in uterus[2].In 1991,Colbern and Main proposed that the maternal immune cells directly interact with placenta but not the fetus[3].Therefore,information concerning the cross-talk between maternal immune cells and placenta during normal pregnancy will provide clues to explore the underlying mechanism of pathological *** cells,such as natural killer(NK),macrophage,T,and dendritic cells,have been demonstrated to play important roles during normal pregnancy[4].With the development of single-cell RNA sequencing(scRNA-seq)technologies,researchers are devoted to providing a whole picture about the immune cellular composition and inter-cellular communication events during normal pregnancy[5,6].These foundational studies reveal that immune cell subsets,which are classified based on different markers at high resolution,exert specific function during pregnancy ***,the panoramic analysis of immune subsets at high resolution in pathological pregnancy remains lacking.

关键词： fetus Immune mother

Engineered polycaprolactone–magnesium hybrid biodegradable porous scaffold for bone tissue engineering

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Progress in Natural Science:Materials International 2014年第5期24卷 561-567页

作者： Hoi Man Wong Paul K.Chu Frankie K.L.Leung Kenneth M.C.Cheung Keith D.K.Luk Kelvin W.K.Yeung Department of Orthopaedics and Traumatology The University of Hong Kong shenzhen key laboratory for Innovative Technology in Orthopaedic Trauma The University of Hong Kong Shenzhen Hospital Department of Physics and Materials Science City University of Hong Kong Peking university shenzhen Institution

In this paper, we describe the fabrication of a new biodegradable porous scaffold composed of polycaprolactone(PCL) and magnesium(Mg)micro-particles. The compressive modulus of PCL porous scaffold was increased to at least 150% by incorporating 29% Mg particles with the porosity of 74% using Micro-CT analysis. Surprisingly, the compressive modulus of this scaffold was further increased to at least 236% when the silane-coupled Mg particles were added. In terms of cell viability, the scaffold modified with Mg particles significantly convinced the attachment and growth of osteoblasts as compared with the pure PCL scaffold. In addition, the hybrid scaffold was able to attract the formation of apatite layer over its surface after 7 days of immersion in normal culture medium, whereas it was not observed on the pure PCL scaffold. This in vitro result indicated the enhanced bioactivity of the modified scaffold. Moreover, enhanced bone forming ability was also observed in the rat model after 3 months of implantation. Though bony in-growth was found in all the implanted scaffolds. High volume of new bone formation could be found in the Mg/PCL hybrid scaffolds when compared to the pure PCL scaffold. Both pure PCL and Mg/PCL hybrid scaffolds were degraded after 3 months. However, no tissue inflammation was observed. In conclusion, these promising results suggested that the incorporation of Mg micro-particles into PCL porous scaffold could significantly enhance its mechanical and biological properties. This modified porous bio-scaffold may potentially apply in the surgical management of large bone defect fixation.

关键词： Magnesium Polycaprolactone Biodegradability Biocompatibility Mechanical properties

Gas marbles: ultra-long-lasting and ultra-robust bubbles formed by particle stabilization

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Frontiers of Chemical Science and Engineering 2022年第11期16卷 1681-1687页

作者： Xuxin Zhao Kunling Yang Zhou Liu Ho Cheung Shum Tiantian kong College of Chemistry and Environmental Engineering Shenzhen UniversityShenzhen 518000China Department of Mechanical Engineering University of Hong KongHong KongChina Advanced Biomedical Instrumentation Centre Hong KongChina Department of Biomedical Engineering School of MedicineShenzhen UniversityShenzhen 518000China Department of Urology The Institute of Translational MedicineThe First Affiliated Hospital of Shenzhen UniversityShenzhen Second People’s HospitalShenzhen 518000China

Bubbles and foams are ubiquitous in daily life and industrial *** their dynamic behaviors is of key importance for foam manufacturing processes in food packaging,cosmetics and *** bubbles are inherently fragile and transient;enhancing their robustness and shelf lives is an ongoing *** rupture can be attributed to liquid evaporation,thin film drainage and the nuclei of environmental *** by particle-stabilized interfaces in Pickering emulsions,armored bubbles and liquid marble,bubbles are protected by an enclosed particle-entrapping liquid thin film,and the resultant soft object is termed gas *** gas marble exhibits mechanical strength orders of magnitude higher than that of soap bubbles when subjected to overpressure and underpressure,owing to the compact particle monolayer straddling the surface liquid *** using a water-absorbent glycerol solution,the resulting gas marble can persist for 465 d in normal atmospheric *** particle-stabilizing approach not only has practical implications for foam manufacturing processes but also can inspire the new design and fabrication of functional biomaterials and biomedicines.

关键词： bubble particles interfaces armored bubble liquid marble gas marble Pickering emulsion

Avian influenza virus directly infects human natural killer cells and inhibits cell activity

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Virologica Sinica 2017年第2期32卷 122-129页

作者： Huawei Mao Yinping Liu Sin Fun Sia JS Malik Peiris Yu-Lung Lau Wenwei Tu Department of Paediatrics The University of Hong Kong - Shenzhen Hospital Shenzhen 518000 China Department of Paediatrics & Adolescent Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong SAR China Department of Microbiology The University of Hong Kong Hong Kong SAR China shenzhen Engineering laboratory of PID Diagnosis & Therapy Technology Shenzhen 518000 China

Natural killer （NK） cell is a key component of innate immunity and plays an important role in host defense against virus infection by directly destroying infected cells. Influenza is a respiratory disease transmitted in the early phase of virus infection. Evasion of host innate immunity including NK cells is critical for the virus to expand and establish a successful acute infection. Previously, we showed that human influenza HIN1 virus infects NK cells and induces cell apoptosis, as well as inhibits NK cell activity. In this study, we further demonstrated that avian influenza virus also directly targeted NK cells as an immunoevasion strategy. The avian virus infected human NK cells and induced cell apoptosis. In addition, avian influenza virion and HA protein inhibited NK cell cytotoxicity. This novel strategy has obvious advantages for avian influenza virus, allowing the virus sufficient time to expand and subsequent spread before the onset of the specific immune response. Our findings provide an important clue for the immunopathogenesis of avian influenza, and also suggest that direct targeting NK cells may be a common strategy used by both human and avian influenza viruses to evade NK cell immunity.

关键词： natural killer (NK) cell avian influenza virus (AIV) immunoevasion directioninfection inhibition cytotoxicity