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Immunoregulatory and Anti-cancer Activities of Combination Treatment of Novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice

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Chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-Yu Kan Ben chung-Lap Chan Grace Gar-Lee Yue LI Pei-ting Sharon Sze-Man Hon HUANG Dan-qi Miranda Sin-Man Tsang Clara Bik-San Lau Ping-chung Leung chun-kwok wong Institute of Chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Chemical Pathology The Chinese University of Hong KongHong Kong SARChina China-Australia International Research Centre for Chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary ***-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4T1 cells resuspended in 100µL of normal saline in the mammary fat *** from the day of tumor cell inoculation,tumors were grown for 6 *** LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,*** LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a *** control group received daily oral gavage of 0.2 mL double-distilled *** treatment period was 30 *** the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota *** Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(P<0.05),altered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological ***,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(P<0.05).4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment

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Hyaluronic acid association with bacterial,fungal and viral infections:Can hyaluronic acid be used as an antimicrobial polymer for biomedical and pharmaceutical applications?

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Bioactive Materials 2023年第1期19卷 458-473页

作者： Fernanda Zamboni chun kwok wong Maurice N.Collins Bernal Institute School of EngineeringUniversity of LimerickIreland Health Research Institute University of LimerickIreland Department of Chemical Pathology The Chinese University of Hong KongHong Kong Special Administrative Region

The relationships between hyaluronic acid(HA)and pathological microorganisms incite new understandings on microbial infection,tissue penetration,disease progression and lastly,potential *** understandings are important for the advancement of next generation antimicrobial therapeutical strategies for the control of healthcare-associated ***,this review will focus on the interplay between HA,bacteria,fungi,and *** review will also comprehensively detail and discuss the antimicrobial activity displayed by various HA molecular weights for a variety of biomedical and pharmaceutical applications,including microbiology,pharmaceutics,and tissue engineering.

关键词： Hyaluronic acid Hyaluronidase Virulence Antibacterial Antifungal Antiviral

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Novel insights into the role of anti-inflammatory IL-38 in immunity against infection

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Cellular & Molecular Immunology 2022年第11期19卷 1322-1324页

作者： Xun Gao Guoqiu Wu Miranda Sin-Man Tsang Danqi Huang Christopher Wai-Kei Lam chun kwok wong Department of Chemical Pathology The Chinese University of Hong KongHong KongChina Center of Clinical Laboratory Medicine Zhongda HospitalSoutheast UniversityNanjingChina 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 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 and D Centre for Chinese Medicine The Chinese University of Hong KongHong KongChina

Since the identification and cloning of interleukin(IL)-38 in 2001,a plethora of studies have focused on its essential roles as a novel IL-1 family cytokine in both innate and acquired *** on the shared traits with IL-36 receptor antagonist(IL-36Ra)and IL-1 receptor antagonist(IL-1Ra),IL-38 constitutes one of the most important anti-inflammatory cytokines within the IL-36 subfamily and thus elicits its antagonistic effects through binding to IL-36 receptor(IL-36R)and to IL-R1 with a relatively low affinity[1,2].IL-38 has been proven to bind to X-linked interleukin-1 receptor accessory protein-like 1(IL1RAPL1)[1],and IL1RAPL1 therefore serves as a novel receptor of IL-38.

关键词： immunity antagonist insight

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NOD2 and TLR2 ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation

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Cellular & Molecular Immunology 2016年第4期13卷 535-550页

作者： Delong Jiao chun-kwok wong Huai-Na Qiu Jie Dong Zhe Cai Man Chu Kam-Lun Hon Miranda Sin-Man Tsang Christopher Wai-Kei Lam Department of Chemical Pathology The Chinese University of Hong Kong Prince of Wales Hospital Shatin NT Hong Kong China Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China The Chinese University of Hong Kong Hong Kong China Department of Paediatrics The Chinese University of Hong Kong Prince of Wales Hospital Shatin NT Hong Kong China State Key Laboratory of Quality Research in Chinese Medicine Macao institute for Applied Research in Medicine and Health Macao University of Science and Technology Taipa Macao People's Republic of China

The skin of patients with atopic dermatitis （AD） has a unique predisposition for colonization by Staphylococcus aureus （S. aureus）, which contributes to the inflammation and grim prognosis of AD. Although the mechanism underlying the S. aureus-induced exacerbation of AD remains unclear, recent studies have found a pivotal role for pattern recognition receptors in regulating the inflammatory responses in S. aureus infection. In the present study, we used a typical mouse model of AD-like skin inflammation and found that S. aureus-associated nucleotide-binding oligomerization domain-containing protein 2 （NOD2） and toll-like receptor 2 （TLR2） ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. Subsequent histological analyses revealed that dermal fibroblasts were pervasive in the AD-like skin lesions, Co-culture of human dermal fibroblasts with basophils and eosinophils resulted in a vigorous cytokine/chemokine response to the NOD2/TLR2 ligands and the enhanced expression of intercellular adhesion molecule-1 on the dermal fibroblasts. Basophils and eosinophils were primarily responsible for the AD-related cytokine/chemokine expression in the co-cultures. Direct intercellular contact was necessary for the crosstalk between basophils and dermal fibroblasts, while soluble mediators were sufficient to mediate the eosinophil-fibroblast interactions. Moreover, the intracellular p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and nuclear factor-kappa B signaling pathways were essential for NOD2/TLR2 ligand-mediated activation of basophils, eosinophils, and dermal fibroblasts in AD-related inflammation. This study provides the evidence of NOD2/TLR2-mediated exacerbation of AD through activation of innate immune cells and therefore sheds light on a novel mechanistic pathway bv which S. aureus contributes to the DathoDhvsiology of AD.

关键词： atopic dermatitis basophils, eosinophils NOD2 TLR2

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A Commentary: Herbal Medicine Offers Great Potential in Support of Metronomic Cancer Therapy

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Journal of Cancer Therapy 2017年第2期8卷 86-95页

作者： Clara Bik-San Lau chun-kwok wong Ping-chung Leung Partner State Key Laboratory of Phytochemistry and Plant Resources in West China The Chinese University of Hong Kong Hong Kong Institute of Chinese Medicine The Chinese University of Hong Kong Hong Kong Department of Chemical Pathology The Chinese University of Hong Kong Hong Kong Metronomic Global Health Initiative Marseille France

Background: In spite of the advances in Cancer treatment, limitations exist. Refractory cases and late presentations are particularly worrying. The uncertainty of cure and the high costs have led to the popularly of complementary and alternative medicine in cancer treatment. Herbal medicine has particular attraction because it has been shown to be working on a multi-targets direction: promoting apoptosis of cancer cells, anti-angiogenesis and immunomodulating. Research on creating a simple herbal formula with multiple effects of cancer control has started and showed in laboratory platforms promising results. Metronomic Chemotherapy: Attention on the use of old oral cytotoxic drugs in small doses for refractory and late cancer cases has started more than a decade. Satisfactory and good results have been found to be related to anti-angiogenesis, immunomodulations and cancer cell apoptosis. These findings are comparable to the use of multiple targets herbal medicine. Conclusion: Assumption is made that metronomic chemotherapy, combined with herbal medicine could be achieving synergistic effects and would be affordable to all patients.

关键词： Cancer Metronomic Treatment Herbal Medicine

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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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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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Sheng Jiang San, traditional multi-herb formulation, exerts anti-influenza effects in vitro and in vivo via neuraminidaseinhibition and immune regulation

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中国药理学与毒理学杂志 2019年第9期33卷 738-739页

作者： ZHANG Tian-bo XIAO Meng-jie chun-kwok wong Ka-Pun CHRIS MOK ZHAO Xin TI Hui-hui Pang-Chui SHAW State Key Laboratory of Respiratory Disease Guangdong Provincial Key Laboratory of Molecular Target&Clinical PharmacologySchool of Pharmaceutical Sciences and The Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhouChina The School of Life Sciences The Chinese University of Hong KongHong KongChina School of Public Health Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina

OBJECTIVE Sheng Jiang San(SJS),a multi-herb formulation,is used in treating high fever,thirsty and anxiety in ancient China and it is sometimes used to treat seasonal influenza in ***,there is no evidencebased investigation and mechanism research to support SJS′s anti-influenza *** study aims to investigate the anti-influenza effect of SJS and its possible *** In this study,we examined the inhibitory effect of SJS against different influenza viruses on Madin-Darby canine kidney *** virus infected BALB/c mice were employed as in vivo model to evaluate the *** challenged with A/PR/8/34(H1N1)were orally administrated SJS 1 g·kg^-1 daily for seven days and monitored for 14 *** survival rate,body mass changes,lung index,lung viral load,histopathologic changes and immune-regulation of the mice were *** underlying anti-influenza virus mechanisms were studied by a series of biological assays in vitro to determine if hemagglutinin,ribonucleoprotein complex or nerauminidase were targets of *** SJS exerted a broad spectrum of inhibitory effects on multiple influenza strains in a dose-dependent *** IC50 of SJS against A/WSN/33(H1N1)was lower than 35 mg·L^-*** also protected 50%of mice from influenza virus PR8 *** lung index and the lung viral load of SJS treated mice were signifi⁃cantly decrease compared with untreated *** 2 g·L^-1 inhibited 80%of neuraminidase enzymatic *** also up-regulated TNF-αand IFN-αand down-regulated IL-2 of influenza virus induced *** SJS is a useful formulation for treating influenza virus infection.

关键词： Sheng Jiang San anti-influenza activity neuraminidase inhibition immuno-regulation

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The electroweak monopole–antimonopole pair in the standard model

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Communications in Theoretical Physics 2024年第3期76卷 113-119页

作者： Dan Zhu Khai-Ming wong Guo-Quan wong School of Physics Universiti Sains Malaysia11800 USMPenangMalaysia

We present the first numerical solution that corresponds to a pair of Cho–Maison monopoles and antimonopoles(MAPs) in the SU(2) × U(1) Weinberg–Salam(WS) *** monopoles are finitely separated,while each pole carries a magnetic charge ±4π/*** positive pole is situated in the upper hemisphere,whereas the negative pole is in the lower *** Cho–Maison MAP is investigated for a range of Weinberg angles,0.4675≤ tan θ_(W)≤10,and Higgs self-coupling,0 ≤ β ≤ *** magnetic dipole moment(μm) and pole separation(d_(z)) of the numerical solutions are calculated and *** total energy of the system,however,is infinite due to point singularities at the locations of monopoles.

关键词： magnetic monopole Cho-Maison monopole Weinberg-Salam model

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Synthetic brochosomes:Design,synthesis,and applications

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Nano Research 2024年第2期17卷 734-742页

作者： Lin Wang Jinsol Choi Tak-Sing wong Department of Mechanical Engineering The Pennsylvania State UniversityUniversity ParkPA 16802USA Materials Research Institute The Pennsylvania State UniversityUniversity ParkPA 16802USA Department of Biomedical Engineering The Pennsylvania State UniversityUniversity ParkPA 16802USA

Brochosomes,which are nanoscopic buckyball-shaped granules produced by leafhoppers,are one of the most intricate structures discovered in *** functions of brochosomes have been proposed but only a few have been experimentally validated due to the challenge of fabricating their synthetic *** in micro-and nanofabrication have recently led to the emergence of synthetic brochosomes,opening up new possibilities for innovative *** review explores the early discovery of natural brochosomes and their geometrical features,followed by the recent progress in fabricating synthetic brochosomes and their *** on future applications and challenges in the scalable manufacturing of synthetic brochosomes are discussed.

关键词： synthetic brochosomes leafhopper antireflection superhydrophobicity surface-enhanced Raman scattering photocatalyst energy harvesting

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