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Outlook of PINK1/Parkin signaling in molecular etiology of Parkinson's disease,with insights into Pink1 knockout models

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Zoological Research 2023年第3期44卷 559-576页

作者： Zhangting Wang See-Wing chan Hui Zhao Kai-Kei Miu wai-yee chan School of Biomedical Sciences Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina Kunming Institute of Zoology-The Chinese University of Hong Kong(KIZ-CUHK)Joint Laboratory of Bioresources and Molecular Research of Common Diseases Hong Kong SARChina Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics School of Biomedical SciencesThe Chinese University of Hong KongHong Kong SARChina Key Laboratory for Regenerative Medicine Ministry of EducationSchool of Biomedical SciencesThe Chinese University of Hong KongHong Kong SARChina

Parkinson’s disease(PD)relates to defective mitochondrial quality control in the dopaminergic motor *** studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to PD onset,pinpointing mitophagy and inflammation as the culprit pathways involved in neuronal loss in the substantia nigra(SNpc).In a reciprocal manner,LRRK2 functions in the regulation of basal flux and inflammatory responses responsible for PINK1/Parkin-dependent mitophagy *** intervention in these diseasemodifying pathways may facilitate the development of novel PD therapeutics,despite the current lack of an established drug evaluation *** such,we reviewed the feasibility of employing the versatile global Pink1knockout(KO)rat model as a self-sufficient,spontaneous PD model for investigating both disease etiology and drug *** rats retain clinical features encompassing basal mitophagic flux changes with PD *** demonstrate the versatility of this PD rat model based on the incorporation of additional experimental insults to recapitulate the proinflammatory responses observed in PD patients.

关键词： Parkinson’s disease Mitophagy Inflammatory response Genetic model Pink1 KO rats

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Microglia activation,classification and microglia-mediated neuroinflammatory modulators in subarachnoid hemorrhage

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Neural Regeneration Research 2022年第7期17卷 1404-1411页

作者： Junfan Chen Zhiyuan Vera Zheng Gang Lu wai yee chan Yisen Zhang George Kwok Chu Wong Division of Neurosurgery Department of SurgeryThe Chinese University of Hong KongHong Kong Special Administrative RegionChina Department of Neurosurgery Hainan Branch of Chinese People’s Liberation Army General HospitalSanyaHainan ProvinceChina CUHK-SDU Joint Laboratory on Reproductive Genetics School of Biomedical Sciencesthe Chinese University of Hong KongHong Kong Special Administrative RegionChina Bioinformatics Unit SDIVF R&D CentreHong Kong Science and Technology ParksHong Kong Special Administrative RegionChina Department of Interventional Neuroradiology Beijing Neurosurgical InstituteBeijing Tiantan HospitalCapital Medical UniversityBeijingChina

Subarachnoid hemorrhage is a devastating disease with significant mortality and morbidity,despite advances in treating cerebral *** has been recent progress in the intensive care management and monitoring of patients with subarachnoid hemorrhage,but the results remain ***,the resident immune cells of the brain,are increasingly recognized as playing a significant role in neurological diseases,including subarachnoid *** early brain injury following subarachnoid hemorrhage,microglial activation and neuroinflammation have been implicated in the development of disease complications and *** understand the disease processes following subarachnoid hemorrhage,it is important to focus on the modulators of microglial activation and the pro-inflammatory/anti-inflammatory cytokines and *** this review,we summarize research on the modulators of microglia-mediated inflammation in subarachnoid hemorrhage,including transcriptome changes and the neuroinflammatory signaling *** also describe the latest developments in single-cell transcriptomics for microglia and summarize advances that have been made in the transcriptome-based classification of microglia and the implications for microglial activation and neuroinflammation.

关键词： activation inflammation microglia modulator neuroinflammation sequencing signal pathway single-cell analysis stroke subarachnoid hemorrhage treatment

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促黄体激素受体突变导致的性器官发育异常(英文)

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北京大学学报（医学版） 2005年第1期37卷 32-38页

作者： wai-yee chan Laboratory of Clinical Genomics National Institute of Child Health and Human Development National Institutes of Health Bethesda Maryland 20892-4429 USA and Department of Pediatrics and Biochemistry & Molecular Biology Georgetown University Medical Center Washington District of Columbia 20007 USA

The Luteinizing hormone/chorionic gonadotropin receptor (LHR) plays a critical role in human male sexual development. Both gain-of-function and loss-of-function mutations of the LHR have been described. Gain-of-function mutations are dominant and cause constitutive activation of the receptor resulting in familial male-limited precocious puberty (FMPP). All activating mutations are single point mutations and are located in the transmembrane domain (TM). TM helix Ⅵ harbors the largest number of activating mutations with the codon of Asp-578 being the hot-spot of mutation. Besides causing abnormal sexual development, constitutively activated LHR may predispose an individual to the development of testicular neoplasia. The anti-thesis of FMPP is Leydig cell hypoplasia (LCH). This is caused by mutations that inactivate the LHR resulting in subnormal male sexual development or male pseudohermaphroditism. Inactivating mutations are recessive. The genetic cause of LCH is variable and there is no mutation hot-spot. Genotype-phenotype correlation can be identified in LCH with the milder form caused by mutated LHR with residual activity and the severe form caused by absence of signal transduction activity of the mutated receptor. Molecular diagnosis of the disorders caused by mutation of the LHR can be achieved by direct sequencing of the LHR gene.

关键词：受体 LH 青春期早熟发育不全 Leydig细胞

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Jump further,leap higher,and consolidate stronger:A brief review of the long-term partnership between Kunming Institute of Zoology(KIZ)and the Chinese University of Hong Kong(CUHK)in bioresources and molecular research

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Zoological Research 2023年第3期44卷 556-558页

作者： Nelson Tang Yong-Tang Zheng Hui Zhao wai-yee chan Yong-Gang Yao KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases The Chinese University of Hong KongHong Kong SARChina KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China

The molecular etiologies of many prevalent diseases stem from genetic variations that arise during evolution and natural selection,as well as from environmental *** study of genetic diversity in human populations and analysis of molecular evolution in primates and other animal species can provide important insights regarding the pathogenesis of common diseases in both human and animal populations.

关键词： molecular evolution solid

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Towards precision medicine: from quantitative imaging to radiomics

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2018年第1期19卷 6-24页

作者： U.Rajendra ACHARYA Yuki HAGIWARA Vidya K.SUDARSHAN wai yee chan Kwan Hoong NG Department of Electronics and Computer Engineering Ngee Ann Polytechnic Department of Biomedical Engineering School of Science and Technology Singapore University of Social Sciences Department of Biomedical Engineering Faculty of Engineering University of Malaya Department of Biomedical Imaging Faculty of Medicine University of Malaya

Radiology（imaging） and imaging-guided interventions, which provide multi-parametric morphologic and functional information, are playing an increasingly significant role in precision medicine. Radiologists are trained to understand the imaging phenotypes, transcribe those observations（phenotypes） to correlate with underlying diseases and to characterize the images. However, in order to understand and characterize the molecular phenotype（to obtain genomic information） of solid heterogeneous tumours, the advanced sequencing of those tissues using biopsy is required. Thus, radiologists image the tissues from various views and angles in order to have the complete image phenotypes, thereby acquiring a huge amount of data. Deriving meaningful details from all these radiological data becomes challenging and raises the big data issues. Therefore, interest in the application of radiomics has been growing in recent years as it has the potential to provide significant interpretive and predictive information for decision support. Radiomics is a combination of conventional computer-aided diagnosis, deep learning methods, and human skills, and thus can be used for quantitative characterization of tumour phenotypes. This paper discusses the overview of radiomics workflow, the results of various radiomics-based studies conducted using various radiological images such as computed tomography（CT）, magnetic resonance imaging（MRI）, and positron-emission tomography（PET）, the challenges we are facing, and the potential contribution of radiomics towards precision medicine.

关键词： Radiological imaging Personalised medicine Precision medicine Quantitative imaging Radiogenomics Radiomics

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An everlasting role of genetics and genomics in public health: a meeting report of ACGA-HKSMG International Conference on Genetic and Genomic Medicine 2008

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Journal of Genetics and Genomics 2009年第4期36卷 189-190页

作者： wai-yee chan Stephen T.S. Lam Bai-Lin Wu Section on Developmental Genomics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda Maryland 20892 USA Department of Pediatrics Biochemistry and Molecular & Cellular Biology Georgetown University Washington DC 20007 USA Clinical Genetic Service Department of Health Hong Kong SAR China Children's Hospital Boston Harvard University Boston MA 02115 USA Institutes of Biomedical Science Fudan University Shanghai 200032 China

The Association of Chinese Geneticists in America （ACGA） and the Hong Kong Society of Medical Genetics （HKSMG） held their first joint Conference on Genetic and Genomic Medicine in Hong Kong from June 9-11 in 2008 at the Cheung Kung Hai Conference Center, William MW Mong Block, Li Ka Shing Faculty of Medicine, the University of Hong Kong. Other co-organizers included the University of Hong Kong and Chinese Society of Medical Genetics. A satellite conference ＂ACGA-WZMC International Symposium of Genetics and Translational Medicine＂, co-organized with Wenzhou Medical College and Chinese Society of Medical Genetics, was held from June 12-14, 2008 at Wenzhou, Zhejiang Province of China.

关键词： In An everlasting role of genetics and genomics in public health a meeting report of ACGA-HKSMG International Conference on Genetic and Genomic Medicine 2008

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Insulin exerts direct, IGF-1 independent actions in growth plate chondrocytes

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Bone Research 2014年第2期2卷 121-130页

作者： Fengjie Zhang Qiling He Wing Pui Tsang W Timothy Garvey wai yee chan Chao Wan Ministry of Education Key Laboratory for Regenerative Medicine School of Biomedical Sciences Faculty of Medicine The Chinese University of Hong Kong School of Biomedical Sciences Core Laboratory Institute of Stem Cell Genomics and Translational Research Shenzhen Research Institute The Chinese University of Hong Kong Departments of Microbiology and Pathology University of Alabama at Birmingham AL USA Department of Nutrition Sciences University of Alabama at Birmingham AL USA

Insufficient insulin production or action in diabetic states is associated with growth retardation and impaired bone healing, while the underling mechanisms are unknown. In this study, we sought to define the role of insulin signaling in the growth plate. Insulin treatment of embryonic metatarsal bones from wild-type mice increased chondrocyte proliferation. Mice lacking insulin receptor （IR） selectively in chondrocytes （CartIR-/-） had no discernable differences in total femoral length compared to control littermates. However, CartIR-/- mice exhibited an increase in chondrocyte numbers in the growth plate than that of the controls. Chondrocytes lacking IR had elevated insulin-like growth factor （IGF）-IR mRNA and protein levels. Subsequently, IGF-1 induced phosphorylafion of Akt and ERK was enhanced, while this action was eliminated when the cells were treated with IGF-1R inhibitor Picropodophyllin. Deletion of the IR impaired chondrogenic differentiation, and the effect could not be restored by treatment of insulin, but partially rescued by IGF-1 treatment. Intriguingly, the size of hypertrophic chondrocytes was smaller in CartIR-/- mice when compared with that of the control littermates, which was associated with upregnlation of tuberous sclerosis complex 2 （TSC2）. These results suggest that deletion of the IR in chondrocytes sensitizes IGF-1R signaling and action, IR and IGF-1R coordinate to regulate the proliferation, differentiation and hypertrophy of growth plate chondrocytes.

关键词： IGF-1 independent actions in growth plate chondrocytes Insulin exerts direct

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Novel role of STAT3 in microglia-dependent neuroinflammation after experimental subarachnoid haemorrhage

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Stroke & Vascular Neurology 2022年第1期7卷 62-70页

作者： Zhiyuan Vera Zheng Junfan Chen Hao Lyu Sin Yu Erica Lam Gang Lu wai yee chan George K C Wong Department of Surgery The Chinese University of Hong KongShatinHong Kong Department of Surgery Hainan General HospitalHaikouHainanChina School of Biomedical Science The Chinese University of Hong KongShatinHong Kong

Background and purpose Signal transducer and activator of transcription 3(STAT3)may contribute to the proinflammation in the central nervous system diseases by modulating the microglial ***,this study was intended to investigate the effect of STAT3 on microglia-dependent neuroinflammation and functional outcome after experimental subarachnoid haemorrhage(SAH).Methods The SAH model was established by endovascular perforation in the ***-time PCR(RtPCR)and western blot were used to examine the dynamic STAT3 signalling pathway responses after *** clarify the role of the STAT3 signalling pathway in the microglia-dependent neuroinflammation after SAH,the microglia-specific STAT3 knockout(KO)mice were generated by the Cre-LoxP *** neurological functions were assessed by Catwalk and Morris water maze *** loss after SAH was determined by immunohistochemistry *** polarisation status after STAT3 KO was then examined by RtPCR and *** The STAT3 and Janus kinase-signal transducer 2 activated immediately with the upregulation and phosphorylation after *** factors and related mediators altered dynamically and *** STAT3 deletion ameliorated the neurological impairment and alleviated the early neuronal loss after *** investigate the underlying mechanism,we examined the microglial reaction after STAT3 ***3 deletion reversed the increase of microglia after *** of STAT3 triggered the early morphological changes of microglia and primed microglia from M1 to M2 ***,microglial STAT3 deletion suppressed the SAH-induced proinflammation and promoted the anti-inflammation in the early *** STAT3 is closely related to the microglial polarisation transition and modulation of microglia-dependent *** STAT3 deletion improved neurological function and neuronal survival probably through promoting M2 polarisation and anti-inf

关键词： STAT3 inflammation reversed

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Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ILK-PI3K/AKT pathway

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Zoological Research 2023年第3期44卷 620-635页

作者： Rui-Can Cao Yue Lv Gang Lu Hong-Bin Liu Wuming Wang Chunlai Tan Xian-Wei Su Zhiqiang Xiong Jin-Long Ma wai-yee chan Center for Reproductive Medicine Shandong UniversityJinanShandong 250012China Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics The Chinese University of Hong KongHong Kong SARChina CUHK-SDU Joint Laboratory on Reproductive Genetics School of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongHong Kong SARChina Key Laboratory of Reproductive Endocrinology of Ministry of Education Shandong UniversityJinanShandong 250012China Shandong Key Laboratory of Reproductive Medicine Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250012China SDIVF R&D Centre 12WHKSTPHong Kong SARChina Kunming Institute of Zoology-The Chinese University of Hong Kong(KIZ-CUHK)Joint Laboratory of Bioresources and Molecular Research of Common Diseases Hong Kong SARChina

Chemotherapy can significantly reduce follicle counts in ovarian tissues and damage ovarian stroma,causing endocrine disorder,reproductive dysfunction,and primary ovarian insufficiency(POI).Recent studies have suggested that extracellular vesicles(EVs)secreted from mesenchymal stem cells(MSCs)exert therapeutic effects in various degenerative *** this study,transplantation of EVs from human induced pluripotent stem cell-derived MSCs(iPSC-MSC-EVs)resulted in significant restoration of ovarian follicle numbers,improved granulosa cell proliferation,and inhibition of apoptosis in chemotherapy-damaged granulosa cells,cultured ovaries,and in vivo ovaries in ***,treatment with i PSC-MSC-EVs resulted in up-regulation of the integrinlinked kinase(ILK)-PI3K/AKT pathway,which is suppressed during chemotherapy,most likely through the transfer of regulatory microRNAs(miRNAs)targeting ILK pathway *** work provides a framework for the development of advanced therapeutics to ameliorate ovarian damage and POI in female chemotherapy patients.

关键词： Extracellular vesicles Premature ovarian insufficiency Human induced pluripotent stem cell-derived mesenchymal stem cells ILK-PI3K/AKT pathway

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New Year Address of Zoological Research

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Zoological Research 2017年第1期38卷 1-1页

作者： wai-yee chan Yong-Gang Yao School of Biomedical Sciences The Chinese University of Hong Kong Kunming Institute of Zoology Chinese Academy of Sciences

The year 2016 was a wonderful and important one for Zoological Research（ZR）.In recognition of its impressive progress and great potential to develop into a leading journal in the field,ZR is now supported by the“Pr... 详细信息

关键词： In New Year Address of Zoological Research ZR

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