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Cellular & Molecular Immunology 2014年第2期11卷 141-149页

作者： kam-leung siu Chi-Ping Chan Kin-Hang Kok Patrick Chiu-Yat Woo Dong-Yan Jin Department of Biochemistry The University of Hong Kong Pokfulam Hong Kong Department of Microbiology The University of Hong KongPokfulam Hong Kong

Coronaviruses have developed various measures to evade innate immunity, We have previously shown that severe acute respiratory syndrome （SARS） coronavirus M protein suppresses type I interferon （IFN） production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain （TM 1） located at the N terminus. M protein from human coronavirus HKU 1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM 1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM 1 is capable of binding with RIG-I, TRAF3, TBK1 and IKK~, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M orotein reouired for suooression of innate antiviral re^nnn^e.

关键词： human coronavirus HKU1 innate antiviral response SARS coronavirus TRAF3 type I interferons

Broad-spectrum ginsentides are principal bioactives in unraveling the cure-all effects of ginseng

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Acta Pharmaceutica Sinica B 2024年第2期14卷 653-666页

作者： Shining Loo Antony kam Bamaprasad Dutta Xiaohong Zhang Nan Feng siu Kwan Sze Chuan-Fa Liu Xiaoliang Wang James P.Tam School of Biological Sciences Nanyang Technological UniversitySingapore 637551Singapore Academy of Pharmacy Xi’an Jiaotong-Liverpool UniversitySuzhou 215123China Department of Biological Sciences Xi’an Jiaotong-Liverpool UniversitySuzhou 215123China Institute of Materia Medica Chinese Academy of Medical SciencesBeijing 100050China Department of Health Sciences Brock UniversityNiagara RegionON L2S 3A1Canada

Stress and illness connection is complex and involves multiple physiological *** ginsengs,reputed for their broad-spectrum“cure-all”effect,are widely prescribed to treat stress and related ***,the identity of ginseng’s“cure-all”medicinal compounds that relieve stress remains ***,we identify ginsentides as the principal bioactives that coordinate multiple systems to restore homeostasis in response to *** are disulfide-rich,cell-penetrating and proteolytic-stable *** affinity-enrichment mass spectrometry target identification together with in vitro,ex vivo and in vivo validations,we show that highly purified or synthetic ginsentides promote vasorelaxation by producing nitric oxide through endothelial cells via intracellular PI3K/Akt signaling pathway,alleviate a1-adrenergic receptor overactivity by reversing phenylephrine-induced constriction of aorta,decrease monocyte adhesion to endothelial cells via CD166/ESAM/CD40 and inhibit P2Y12 receptors to reduce platelet *** administered ginsentides were effective in animal models to reduce ADP-induced platelet aggregation,to prevent collagen and adrenalineinduced pulmonary thrombosis as well as anti-stress behavior of tail suspension and forced swimming tests in ***,these results strongly suggest that ginsentides are the principal panacea compounds of ginsengs because of their ability to target multiple extra-and intra-cellular proteins to reverse stress-induced damages.

关键词： Ginseng Cysteine-rich peptides Microproteins Cure-all Stress Homeostasis

How Schisandrae Fructus Benefits the Body: Mechanisms in Traditional Chinese Medicine and Modern Medicine

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Chinese Medicine 2024年第3期15卷 75-81页

作者： kam Ming Ko Hoi Yan leung Division of Life Science Hong Kong University of Science & Technology Hong Kong SAR China

Schisandrae chinensis Fructus (SF) is a commonly used herb in Traditional Chinese Medicine (TCM). According to TCM theory, SF can invigorate Qi in the liver and other visceral organs through the meridian system. Furthermore, the liver’s pivotal role in regulating the functions of various visceral organs helps explain how SF can promote holistic health benefits. The main active ingredient of SF, schisandrin B (Sch B), has been found to improve mitochondrial ATP production and enhance glutathione redox status in multiple organs. This could account for the overall protective effects of Sch B on organs. Due to its stronger impact on liver function, the positive influence of Sch B on different organs may be facilitated by signal molecules originating from the liver.

关键词： Schisandrae chinensis Fructus Schisandrin B Mitochondrial Glutathione Redox Status Liver

An Ultimate Approach to Retarding the Aging Process by Integrating Traditional Chinese Medicine and Western Medicine

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Chinese Medicine 2024年第3期15卷 35-48页

作者： kam Ming Ko Hoi Yan leung Division of Life Science Hong Kong University of Science & Technology Hong Kong SAR China

Aging and death are unavoidable in life. While immortality may be impossible, many people dream of living a long and healthy life. Throughout history, humans have searched for ways to stay young, but have not found an effective way. This may be because the methods used do not target the causes of aging directly. To address this, we investigated how to delay aging using traditional Chinese medicine (TCM) and Western medicine approaches. In this article, we will explain the causes of aging in the context of TCM and Western medicine and suggest methods to delay it. By integrating TCM and Western medicine, I hope to help everyone age healthily and enjoy a long life.

关键词： Aging Traditional Chinese Medicine Zang Xiang System Zheng Qi Western Medicine Mitochondria Mitophagy Senolytics Glutathione Antioxidant Response

The Essential Role of Zheng Qi in Promoting Health: From the Perspective of Chinese Medicine and Modern Medicine

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Chinese Medicine 2024年第2期15卷 27-33页

作者： kam Ming Ko Hoi Yan leung Division of Life Science Hong Kong University of Science & Technology Hong Kong SAR China

The concept of Zheng Qi in traditional Chinese medicine (TCM) refers to the vital energy produced by the interaction of Yin and Yang forces in the body. Zheng Qi performs two main functions: Wei Qi (defensive Qi), which shields the body from external pathogens, and Ying Qi (nutritive Qi), which sustains the internal organs and enhances their functionality. In TCM, Chinese tonifying herbs can help restore the balance of Yin/Yang and Qi/Blood function in visceral organs (i.e., optimal physiological functions), thereby fostering the efficient production of Zheng Qi and enhancing health. To ensure the quality of Chinese herbal products, functional assays to measure Yin/Yang, Qi/Blood functions, and Zheng Qi production should be implemented. The efficacy of Yang and Qi herbs can be evaluated by their ability to increase mitochondrial ATP in cultured mouse cardiomyocytes, while Yin and Blood herbs are tested through their immunostimulatory effects on antigen-induced T/B cell proliferation in mouse splenocytes and the production of erythropoietin/nitric oxide in hepatocytes/vascular endothelial cells, respectively. Additionally, Zheng Qi’s effect can be gauged by examining natural killer cell activity and antigen-induced T/B cell proliferation in mice ex vivo. These assays act as biomarkers for assessing the quality and effectiveness of herbal health products within TCM theory.

关键词： Traditional Chinese Medicine Zheng Qi Immunity Biomarkers Functional Assays

Pharmacological Investigation on the Qi-Invigorating Action of Schisandrin B: Effects on Mitochondrial ATP Generation in Multiple Tissues and Innate/Adaptive Immunity in Mice

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Chinese Medicine 2024年第2期15卷 15-26页

作者： Hoi Yan leung Suen Chit Sze kam Ming Ko Division of Life Science Hong Kong University of Science & Technology Hong Kong SAR China

Schisandrae Fructus, containing schisandrin B (Sch B) as its main active component, is recognized in traditional Chinese medicine (TCM) for its Qi-invigorating properties in the five visceral organs. Our laboratory has shown that the Qi-invigorating action of Chinese tonifying herbs is linked to increased mitochondrial ATP generation and an enhancement in mitochondrial glutathione redox status. To explore whether Sch B can exert Qi-invigorating actions across various tissues, we investigated the effects of Sch B treatment on mitochondrial ATP generation and glutathione redox status in multiple mouse tissues ex vivo. In line with TCM theory, which posits that Zheng Qi generation relies on the Qi function of the visceral organs, we also examined Sch B’s impact on natural killer cell activity and antigen-induced splenocyte proliferation, both serving as indirect measures of Zheng Qi. Our findings revealed that Sch B treatment consistently enhanced mitochondrial ATP generation and improved mitochondrial glutathione redox status in mouse tissues. This boost in mitochondrial function was associated with stimulated innate and adaptive immune responses, marked by increased natural killer cell activity and antigen-induced T/B cell proliferation, potentially through the increased generation of Zheng Qi.

关键词： Zheng Qi Schisandrin B Mitochondria ATP Generation Glutathione Redox Innate Immunity Adaptive Immunity Natural Killer Cell Activity Splenocyte Proliferation

Cellular zinc metabolism and zinc signaling:from biological functions to diseases and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 401-441页

作者： Bonan Chen Peiyao Yu Wai Nok Chan Fuda Xie Yigan Zhang Li Liang kam Tong leung Kwok Wai Lo Jun Yu Gary M.K.Tse Wei Kang Ka Fai To Department of Anatomical and Cellular Pathology State Key Laboratory of Translational OncologyPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina State Key Laboratory of Digestive Disease Institute of Digestive DiseaseThe Chinese University of Hong KongHong KongChina CUHK-Shenzhen Research Institute The Chinese University of Hong KongShenzhenChina Department of Pathology Nanfang Hospital and Basic Medical CollegeSouthern Medical UniversityGuangdong Province Key Laboratory of Molecular Tumor PathologyGuangzhouChina Institute of Biomedical Research Taihe HospitalHubei University of MedicineShiyanChina Department of Pediatrics The Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

Zinc metabolism at the cellular level is critical for many biological processes in the body.A key observation is the disruption of cellular homeostasis,often coinciding with disease *** an essential factor in maintaining cellular equilibrium,cellular zinc has been increasingly spotlighted in the context of disease *** research suggests zinc’s involvement in promoting malignancy and invasion in cancer cells,despite its low tissue *** has led to a growing body of literature investigating zinc’s cellular metabolism,particularly the functions of zinc transporters and storage mechanisms during cancer *** transportation is under the control of two major transporter families:SLC30(ZnT)for the excretion of zinc and SLC39(ZIP)for the zinc ***,the storage of this essential element is predominantly mediated by metallothioneins(MTs).This review consolidates knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression,with a special focus on *** also compile a summary of clinical trials involving zinc *** the main localization of zinc transporters at the cell membrane,the potential for targeted therapies,including small molecules and monoclonal antibodies,offers promising avenues for future exploration.

关键词： metabolism invasion involvement

Schisandrin B decreases the sensitivity of mitochondria to calcium ioninduced permeability transition and protects against ischemia-reperfusion injury in rat hearts

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Acta Pharmacologica Sinica 2007年第10期28卷 1559-1565页

作者： Po-yee CHIU Hoi-yan leung Ada HL siu Michel KTPOON kam-ming KO Department of Biochemistry Hong Kong University of Science and Technology Hong Kong SAR China

Aim:In order to elucidate the molecular mechanism underlying the cardioprotectionafforded by schisandrin B （Sch B）,the effect of Sch B treatment on the sensitivityof mitochondria to Ca2+-stimulated permeability transition （PT） was investigatedin rat hearts under normal and ischemia-reperfusion （I-R） ***:Myocardial I-R injury caused an increase in the sensitivity of mitochondria toCa2+-stimulated PT in *** enhanced sensitivity to mitochondrial PT wasassociated with increases in mitochondrial Ca2+content as well as the extent ofreactive oxidant species production in vitro and cytochrome c release in *** cardioprotection afforded by Sch B pretreatment against I-R-induced injurywas paralleled by the decrease in the sensitivity of myocardial mitochondria toCa2+-stimulated PT,particularly under I-R ***:The resultssuggest that Sch B treatment increases the resistance of myocardial mitochondriato Ca2+-stimulated PT and protects against I-R-induced tissue injury.

关键词： schisandrin B mitochondria permeability transition calcium myocardial ischemiareperfusion

TRANSFECTION AND CELL FUSION BY FEMTOSECOND LASERS

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Journal of Innovative Optical Health Sciences 2011年第2期4卷 113-125页

作者： HAO HE siu KAI KONG kam TAI CHAN Department of Electronic Engineering The Chinese University of Hong Kong ShatinN.T.Hong Kong Department of Biochemistry The Chinese University of Hong Kong ShatinN.T.Hong Kong

Biophotonics is an exciting and fast-expanding frontier which involves the fusion of advanced photonics and *** has not only created many novel methodologies for biomedical research,but also achieved many significant results as an *** to femtosecond(fs)laser technologies,important progresses have been made regarding the manipulation,imaging,and engineering of biological samples ranging from single molecules to tissues in the last 20 *** ultrashort pulses at near-infrared band provide many advantages:high nonlinear efficiency,low absorption by biological samples,high spatial and temporal resolution and confinement,and low *** are noninvasive and easy to *** the mechanism of how fs laser pulses interact with cells remains unclear,experimental results have shown that they could open up the cell membrane and hence made optical transfection and optical cell fusion *** this review,some of the seminal works on transfection and cell fusion by fs lasers are *** ideas behind and the experimental details will be described together with a highlight on their ***,the thermal effect is analyzed based on multiphoton excitation and plasma formation in an aqueous environment to explain the nontoxic characteristic of fs laser ***,some applications of fs laser induced transfection and cellcell fusion with potential major impact in biomedical sciences are proposed.

关键词： Biophotonics transfection cell fusion femtosecond laser

Luminescent cyclometalated iridium(Ⅲ) dipyridoquinoxaline indole complexes as biological probes

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Science China Chemistry 2010年第10期53卷 2091-2098页

作者： LO Kenneth kam-Wing leung Arthur Ho-Hon Department of Biology and Chemistry City University of Hong Kong

Four luminescent cyclometalated iridium(Ⅲ) dipyridoquinoxaline complexes appended with an indole moiety [Ir(N^C)2(N^N)] (PF6) (HN^C = 2-phenylpyridine, Hppy; N^N = 2-(N-(2-(indole-3-acetamido)ethyl)aminocarbonyl)dipyrido[3,2-f:2′,3′-h]quinox- aline, dpqC2indole (1a), N^N = 2-(N-(6-(indole-3-acetamido)hexyl)aminocarbonyl)dipyrido[3,2-f:2′,3′-h]quinoxaline, dpqC6indole (1b); HN^C = 7,8-benzoquinoline, Hbzq, N^N = dpqC2indole (2a), N^N = dpqC6indole (2b)) have been synthesized and characterized. Upon irradiation, all the complexes displayed moderately intense and long-lived luminescence under ambient condi-tions and in 77 K glass. On the basis of the photophysical data, the emission of the complexes has been assigned to an excited state of triplet metal-to-ligand charge-transfer (3MLCT) ((dπ(Ir)→π*(N^N)) character. Cyclic voltammetric studies revealed indole-based and iridium-based oxidations at ca. +1.10 V and +1.24 V vs. SCE, respectively, and ligand-based reductions at ca. -1.07 to-2.29 V vs. SCE. The interactions of the complexes with an indole-binding protein, bovine serum albumin (BSA), have been examined by emission titrations.

关键词： binding indole iridium luminescence probes