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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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Phytochemical Guttiferone K Triggers Apoptosis Through Inducing Endoplasmic Reticulum Stress Aggravation in Colorectal Cancer Cells

Phytochemical Guttiferone K Triggers Apoptosis Through Induc...

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第十四届全国中药和天然药物学术研讨会

作者： kai-kei miu Kenneth Kin-Wah To Hong-Xi Xu Ge Lin School of Biomedical Sciences The Chinese University of Hong Kong School of Pharmacy The Chinese University of Hong Kong Shanghai University of Traditional Chinese Medicine

＜正＞Guttiferone K（GutK）is a polycyclic polyprenylated acylphloroglucinol（PPAP）isolated from Garcinia *** group had previously confirmed that GutK can trigger apoptosis in colorectal cancer cells,however,the mechanism underlying GutK-induced apoptosis is *** present study demonstrated that GutK elicited endoplasmic reticulum（ER）stress in a variety

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Risk of ischaemic and haemorrhagic stroke in Chinese undergoing percutaneous coronary intervention treated with potent P2Y12 inhibitor versus clopidogrel

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Stroke & Vascular Neurology 2022年第4期7卷 310-318,I0015-I0019页

作者： Andrew kei-Yan Ng Pauline Yeung Ng April Ip Kui kai Lau Chung-Wah Siu Cardiac Medical Unit Grantham HospitalHong KongHong Kong Department of Adult Intensive Care Queen Mary HospitalHong KongHong Kong Department of Medicine The University of Hong KongHong KongHong Kong The State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong KongHong Kong

Background Stroke after acute coronary syndrome(ACS)can be *** is uncertain whether the risks of ischaemic stroke or intracranial haemorrhage(ICH)are associated with different choices of P2Y12 inhibitors(potent P2Y12 inhibitors such as ticagrelor and prasugrel vs clopidogrel).Even though East Asians are known to have different thrombotic and haemorrhagic profiles from Caucasians,data on Chinese patients are *** This was a retrospective cohort study conducting in Chinese patients with ACS who underwent first-ever percutaneous coronary intervention from 14 hospitals in Hong Kong between 2010 and *** primary efficacy endpoint was ischaemic *** secondary efficacy endpoint was a composite outcome of thrombotic events including all-cause mortality,non-fatal myocardial infarction and ischaemic *** primary safety endpoint was *** secondary safety endpoint was a composite of major bleeding *** After adjustment of baseline characteristics by 1:1 propensity score matching,a total of 6220 patients(3110 on each group)were *** with clopidogrel,potent P2Y12 inhibitors were associated with a lower risk of ischaemic stroke(HR 0.57;95%CI 0.37 to 0.87;p=0.008)and a lower risk of thrombotic events(HR 0.77;95%CI 0.66 to 0.90;p=0.001).Potent P2Y12 inhibitor was associated with similar risk of ICH(HR 0.65;95%CI 0.34 to 1.25,p=0.20)and major bleeding(HR 0.83;95%CI 0.68 to 1.01,p=0.069).Conclusions Potent P2Y12 inhibitors were associated with a lower adjusted risk of ischaemic stroke and thrombotic events,compared with *** risks of ICH and major bleeding were similar.

关键词： P2Y12 coronary haemorrhagic

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NOD-like receptors mediated activation of eosinophils interacting with bronchial epithelial cells： a link between innate immunity and allergic asthma

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Cellular & Molecular Immunology 2013年第4期10卷 317-329页

作者： Churl Kwok Wong Shuiqing Hu Karen Ming-Lam Leungt Jie Dong Lan He Yi Jun Chu Ida miu-Ting Chu Huai-Na Qiu Kelly Yan-Ping Liu ChristopherWai-kei Lam Department of Chemical Pathology The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong China Department of Medicine and Therapeutics The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong China Macao Institute for Applied Research in Medicine and Health Macao University of Science and Technology Taipa Macao China

Key intracytosolic pattern recognition receptors of innate immunity against bacterial infections are nucleotide-binding oligomerization domain （NOD）-Iike receptors （NLRs）. We elucidated the NOD1 and NOD2-mediated activation of human eosinophils, the principal effector cells for allergic inflammation, upon interacting with human bronchial epithelial BEAS-2B cells in allergic asthma. Eosinophils constitutively expressed NOD1,2 but exhibited nonsignificant responses to release chemokines upon the stimulation by NOD1 ligand 7-D-glutamyl-meso-diaminopimelic acid （iE-DAP） and NOD2 ligand muramyl dipeptide （MDP）. However, iE-DAP and MDP could significantly upregulate cell surface expression of CD18 and intercellular adhesion molecule （ICAM）-I on eosinophils and ICAM-1 on BEAS-2B cells, as well as induce chemokines CCL2 and CXCL8 release in the coculture system （all P〈0.05）. Both eosinophils and BEAS-2B cells were the main source for CXCL8 and CCL2 release in the coculture system upon iE-DAP or MDP stimulation. Direct interaction between eosinophils and BEAS-2B cells is responsible for CCL2 release, and soluble mediators are implicated in CXCL8 release. ERK and NF-KB play regulatory roles for the expression of adhesion molecules and chemokines in coculture. Treatment with NOD1,2 ligand could induce the subepithelial fibrosis and significantly enhance the serum concentration of total IgE, chemokine CCL5 for eosinophils and T helper type 2 （Th2） cells and asthma Th2 cytokine IL-13 in bronchoalveolar lavage fluid of ovalbumin-sensitized allergic asthmatic mice （all P〈0.05）. This study provides further evidence of bacterial infection-mediated activation of NOD1,2 in triggering allergic asthma via the activation of eosinophils interacting with bronchial epithelial cells at inflammatory airway.

关键词： allergy bronchial epithelial cells chemokines eosinophils signal transduction

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《文心雕龙·原道》之“道-德-圣-文”含义及其关系疏解

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文艺理论研究 2018年第6期38卷 159-168页

作者：李凯缪勇四川师范大学文学院

通过细读文本并结合中西哲学有关理论,文章评述了前人对《原道》之"道"的不同解释及其存在的缺憾;重新解读了《原道》之"道"的内涵并梳理了《原道》之"道"与儒释道之道的区别与联系;分析了刘勰征儒家之圣、宗儒家之经与视老子为贤、《... 详细信息

通过细读文本并结合中西哲学有关理论,文章评述了前人对《原道》之"道"的不同解释及其存在的缺憾;重新解读了《原道》之"道"的内涵并梳理了《原道》之"道"与儒释道之道的区别与联系;分析了刘勰征儒家之圣、宗儒家之经与视老子为贤、《道德经》为子书的理由。通过上述工作,文章重新梳理了《原道》之"道—德—圣—文"内涵及其关系。

关键词：《文心雕龙·原道》道德圣文自然

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Anti-inflammatory mechanisms of the novel cytokine interleukin-38 in allergic asthma

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Cellular & Molecular Immunology 2020年第6期17卷 631-646页

作者： Xiaoyu Sun Tianheng Hou Edwin Cheung Tiffany Nga-Teng Iu Victor Wai-Hou Tam Ida miu-Ting Chu Miranda Sin-Man Tsang Paul Kay-Sheung Chan Christopher Wai-kei Lam Chun-Kwok Wong Department of Chemical Pathology The Chinese University of Hong KongHong KongChina Cancer Centre/Centre of Precision Medicine Research and Training Faculty of Health SciencesUniversity of MacaoMacaoChina Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Microbiology The Chinese University of Hong KongHong KongChina Faculty of Medicine and State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong KongHong KongChina

We elucidated the anti-inflammatory mechanisms of IL-38 in allergic *** bronchial epithelial cells and eosinophils were cocultured upon stimulation with the viral RLR ligand poly(I:C)/LyoVec or infection-related cytokine TNF-αto induce expression of cytokines/chemokines/adhesion *** dust mite(HDM)-induced allergic asthma and humanized allergic asthma NOD/SCID murine models were established to assess anti-inflammatory mechanisms in ***-38 significantly inhibited induced proinflammatory IL-6,IL-1β,CCL5,and CXCL10 production,and antiviral interferon-βand intercellular adhesion molecule-1 expression in the coculture *** cytometry and RNA-sequencing analysis revealed that IL-38 could antagonize the activation of the intracellular STAT1,STAT3,p38 MAPK,ERK1/2,and NF-κB pathways,and upregulate the expression of the host defense-related gene POU2AF1 and anti-allergic response gene *** injection of IL-38 into HDM-induced allergic asthma mice could ameliorate airway hyperreactivity by decreasing the accumulation of eosinophils in the lungs and inhibiting the expression of the Th2-related cytokines IL-4,IL-5,and IL-13 in the bronchoalveolar lavage fluid(BALF)and lung *** examination indicated lung inflammation was alleviated by reductions in cell infiltration and goblet cell hyperplasia,together with reduced Th2,Th17,and innate lymphoid type 2 cell numbers but increased proportions of regulatory T cells in the lungs,spleen,and lymph ***-38 administration suppressed airway hyperreactivity and asthma-related IL-4 and IL-5 expression in humanized mice,together with significantly decreased CCR3^(+) eosinophil numbers in the BALF and lungs,and a reduced percentage of human CD4^(+)CRTH2^(+)Th2 cells in the lungs and mediastinal lymph ***,our results demonstrated the anti-inflammatory mechanisms of IL-38 and provided a basis for the development of a regulatory cytokine-based treatment for allergic

关键词： allergic asthma eosinophils IL-38 ILC2s Tregs

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Triazole Ureas Covalently Bind to Strigolactone Receptor and Antagonize Strigolactone Responses

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Molecular Plant 2019年第1期12卷 44-58页

作者： Hidemitsu Nakamura kei Hirabayashi Takuya Miyakawa Ko Kikuzato Wenqian Hu Yuqun Xu kai Jiang Ikuo Takahashi Ruri Niiyama Naoshi Dohmae Masaru Tanokura Tadao Asami Graduate School of Agricultural and Life Sciences The University of Tokyo1-1-1 YayoiBunkyo-kuTokyo 113-8657Japan ar Characterization Unit RIKEN Center for Sustainable Resource ScienceWakoSaitamaJapan Department of Biochemistry Faculty of ScienceKing Abdulaziz UniversityP.O.Box 80203Jeddah 21589Saudi Arabia

Strigolactones,a class of plant hormones with multiple functions,mediate plant-plant and plantmicroorganism communications in the *** this study,we developed potent strigolactone antagonists,which covalently bindto the strigolactone receptor D14,by preparing an array of triazole urea *** yeast two-hybrid and rice-tillering assays,we identified a triazole urea compound KK094 as a potent inhibitor of strigolactone *** chromatography-tandem mass spectrometry analysis and X-ray crystallography revealed that KK094 was hydrolyzed by D14,and that a reaction product of this degradation covalently binds to the Ser residue of the catalytic triad of ***,we identified two triazole urea compounds KK052 and KK073,whose effects on D14-D53/D14-SLR1 complex formation were opposite due to the absence (KK052)or presence (KK073)of a trifluoromethyl group on their phenyl *** results demonstrate that triazole urea compounds are potentially powerful tools for agricultural application and may be useful for the elucidation of the complicated mechanism underlying strigolactone perception.

关键词： strigolactone covalent antagonist triazole urea crystal structure

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MELAS, MIDD and Beyond: m.3243A>G MT-TL1 Mutation in Adult Patients

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International Journal of Clinical Medicine 2016年第7期7卷 487-495页

作者： Bun Sheng Man kei Fong Wing Kwan Ng Sammy Pak Lam Chen Chloe miu Mak Department of Medicine & Geriatrics Princess Margaret Hospital Hong Kong China Department of Pathology Princess Margaret Hospital Hong Kong China

m.3243A>G MT-TL1 mutation is the most common mitochondrial DNA mutation that results in a wide spectrum of disorders in a maternally inherited pedigree. In adult patients, many present with symptoms and signs indistinguishable from acquired diseases and the correct diagnosis is often delayed after many years. Nevertheless, clues suggesting m.3243A>G usually exist early in the disease course but are only realized late. These hints, from the evolution of symptoms and signs, family background, investigation results, or a combination of these, enable the physician to make the correct diagnosis early, which is important for appropriate treatment and better patient care. As with other inheritable diseases, genetic counselling should be offered regarding the disease management, inheritance mode, recurrence risk, usefulness and limitations of genetic testing and reproductive options.

关键词： Mitochondrial Disease MELAS m.3243A>G

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Meteorin-β/Meteorin like/IL-41 attenuates airway inflammation in house dust mite-induced allergic asthma

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Cellular & Molecular Immunology 2022年第2期19卷 245-259页

作者： Xun Gao Ting-Fan Leung Gary Wing-Kin Wong Wing-Hung Ko Mengyun Cai Ellie Jiayi He Ida miu-Ting Chu Miranda Sin-Man Tsang Ben Chung-Lap Chan Jiawei Ling Xiao Fan Liwei Lu Christopher Wai-kei Lam Chun-Kwok Wong Department of Chemical Pathology The Chinese University of Hong KongHong KongChina Department of Paediatrics The Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Emory College of Arts and Sciences Emory UniversityAtlantaGAUSA Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Pathology and Shenzhen Institute of Research and Innovation The University of Hong KongHong KongChina Faculty of Medicine and State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong KongHong KongChina

We sought to examine the regulatory effect of Meteorin-β(Metrnβ)/Meteorin like(Metrnl)/IL-41 on lung inflammation in allergic *** found that Metrnβwas elevated significantly in asthmatic patients and in mice with allergic asthma induced by house dust mite(HDM)*** exposure to HDM,Metrnβwas secreted predominantly by airway epithelial cells and inflammatory cells,including macrophages and *** increased Metrnβeffectively blocked the development of airway hyperreactivity(AHR)and decreased inflammatory cell airway infiltration and type 2 cytokine production,which was associated with downregulated DC-mediated adaptive immune ***,Metrnβimpaired the maturation and function of bone marrow-derived dendritic cells in *** mice adoptively transferred with dendritic cells isolated from Metrnβ-treated allergic mice displayed decreased AHR,airway inflammation,and lung ***βalso displayed anti-inflammatory properties in immunodeficient SCID mice with allergic asthma and in in vitro 3D ALI airway ***,blockade of Metrnβby anti-Metrnβantibody treatment promoted the development of allergic *** results revealed the unappreciated protective roles of Metrnβin alleviating DC-mediated Th2 inflammation in allergic asthma,providing the novel treatment strategy of therapeutic targeting of Metrnβin allergic asthma.

关键词： Metrnβ Eosinophils Dendritic cells Allergic asthma Air-liquid interface

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The interaction effects of rocker angle and apex location in rocker shoe design on foot biomechanics and Achilles tendon loading

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Medicine in Novel Technology and Devices 2022年第1期13卷 96-101页

作者： Tony Lin-Wei Chen Duo Wai-Chi Wong Yinghu Peng Yan Wang Ivy Kwan-kei Wong Tsz-Kit Lam Wing-kai Lam Ming Zhang Department of Biomedical Engineering Faculty of EngineeringThe Hong Kong Polytechnic UniversityHong Kong The Hong Kong Polytechnic University Shenzhen Research Institute ShenzhenChina Li Ning Sports Science Research Center Li Ning(China)Sports Goods Co.LtdBeijingChina Department of Kinesiology Shenyang Sports InstituteShenyangChina

The influences of rocker shoes on foot biomechanics were controversial because the interaction between two design factors—rocker angle and apex location,was usually *** study investigated the interaction effects of rocker angle and apex location on plantar foot pressure,metatarsophalangeal/ankle angle,and Achilles tendon force during *** participants performed walking trials under six rocker shoe conditions:2 rocker angles(mild and severe)×3 apex locations(distal,standard,and proximal),wherein the plantar foot pressure was measured and the movement data were processed by musculoskeletal modeling to report joint angle and Achilles tendon force.A two-way ANOVA repeated measures was used for *** interaction effects were reported in examinations of forefoot pressure,midfoot pressure,and metatarsophalangeal *** standard apex significantly reduced peak forefoot and midfoot pressures(p=0.008–0.034,Hedges'g=0.75–0.84),which was further decreased by a severe rocker angle(p=0.006,Hedges'g=0.51–0.81).Moving the apex proximally reduced Achilles tendon forces(p<0.001,Hedges'g=0.80)and facilitated both metatarsophalangeal dorsiflexion and ankle plantarflexion during push-off(p=0.003–0.006,Hedges'g=0.03–0.82).Rocker angle seemed to have fewer effects on ankle joint angle and Achilles tendon *** concluded that apex location was likely the dominant design factor of the rocker sole in influencing foot biomechanics,yet its interactions with rocker angle should be *** configuration of the two features could be varied to possess different therapeutic merits and adapt to specific application purposes.

关键词： Gait Rocker shoe Biomechanics Computer simulation Plantar pressure

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