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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

幽门螺杆菌慢性感染诱导胃上皮细胞产生凋亡耐受

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中华医学杂志 2003年第1期83卷 42-45页

作者：何兴祥胡品津 benjamin chun yu wong Shiu Kum Lam Harry Hua Xiang Xia 中山医科大学第一附属医院消化内科广州510080 DepartmentofMedicine TheUniversityofHongKongQueenMaryHospital

目的　建立幽门螺杆菌 (Hp)慢性感染胃上皮细胞模型 ,并分析Hp慢性感染与胃上皮细胞凋亡的关系。方法　用HpSS1与人非肿瘤性胃上皮细胞株GES 1共培养 16周 ,建立GES 1模型细胞 ,然后采用流式细胞术分析这种模型细胞对Hp和其它肠道细菌... 详细信息

目的　建立幽门螺杆菌 (Hp)慢性感染胃上皮细胞模型 ,并分析Hp慢性感染与胃上皮细胞凋亡的关系。方法　用HpSS1与人非肿瘤性胃上皮细胞株GES 1共培养 16周 ,建立GES 1模型细胞 ,然后采用流式细胞术分析这种模型细胞对Hp和其它肠道细菌以及抗肿瘤药物凋亡诱导剂的应答。结果　成功获得了Hp慢性感染胃上皮细胞模型 (GES 1模型细胞 )。这种模型细胞不仅对Hp诱导的凋亡耐受 ,而且对其他肠道细菌和一些凋亡诱导剂也是耐受的。结论　幽门螺杆菌慢性感染诱导胃上皮细胞产生凋亡耐受 ,由此可能增加了胃上皮细胞癌变的危险性。

关键词：胃上皮细胞细胞凋亡幽门螺杆菌感染胃癌

Antralization at the edge of proximal gastric ulcers:Does Helicobacter pylori infection play a role?

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World Journal of Gastroenterology 2003年第6期9卷 1265-1269页

作者： Harry Hua-Xinag Xia Shiu Kum Lam Wai Man wong Wayne Hsing Cheng Hu Kam Chuen Lai Sau Hing wong Suet Yi Leung Siu Tsan yuen Nicholas A.Wright benjamin chun-yu wong Department of Medicine The University of Hong KongHong Kong SARChina Department of Pathology The University of Hong KongHong Kong SARChina Histopathology Unit London Research InstituteCancer ResearchUK

AIM: To determine the prevalence of antralization at the edge of proximal gastric ulcers, and the effect ofH. pylori eradication on the mucosal appearances.METHODS: Biopsies were taken from the antrum, body and the ulcer edge of patients with benign proximal gastric ulcers before and one year after treatment. Gastric mucosa was classified as antral, transitional or body type.H. pylori positive patients receivedeither triple therapy, or omeprazole.RESULTS: Patients with index ulcers in the incisura, body or fundus (n=116) were analyzed. Antral-type mucosa was more prevalent at the ulcer edge inH. pylori-positive patients ***-negative patients (93% vs 60%, OR=8.95,95%CI: 2.47-32.4, P=0.001). At one year, there was a significant reduction in the prevalence of antralization (from 93 % to 61%, P=0.004) at the ulcer edge in patients with H. pyloribeing eradicated. However, there was no difference in the prevalence of antralization at the ulcer edge in those with persistent infection.CONCLUSION: H. pylori infection is associated with antralization at the edge of proximal gastric ulcers, which may be reversible in some patients after eradication of the infection.

关键词：胃溃疡幽门螺杆菌感染胃粘膜活组织检查

Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng Mu yuet chung Tsun Ming Lau Manni Wang Wenyue Zhang Yanmei Zhang Howard H.W.wong Leo C.H.Tsang Sara Chaothai Tsz chun Kwan John K.C.Li Karl C.K.Chan Leo L.H.Luk Jenson C.H.Ho Wing Yan Li Amos M.T.Lee Jennifer H.Y.Lam Sau Man Chan Wilfred H.S.wong Issan Y.S.Tam Masashi Mori Sophie A.Valkenburg Malik Peiris Wenwei Tu yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina HKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and Infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is *** dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is *** study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in *** Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days *** and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,*** Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),SNM-specific IL-2^(+)CD8^(+),S-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and M-specific IL-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was *** ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to *** estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,*** ID groups reported more local,mild adverse *** This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

幽门螺杆菌慢性感染诱导胃上皮细胞产生凋亡耐受

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现代消化及介入诊疗 2002年第3期7卷 34-38页

作者：何兴祥胡品津 benjamin chun yu wong~2 Shiu Kum~2 Lam Harry Hua Xiang Xia~2 广州中山医科大学第一附属医院消化科 510080 Departments of Medicine The University of Hong KongQueen MaryHospitalHong Kong

目的建立幽门螺杆菌(***)慢性感染胃上皮细胞模型,并分析***慢性感染与胃上皮细胞凋亡的关系.方法首先用*** SSI与人非肿瘤性胃上皮细胞株GES-1共培养16周,建立GES-1模型细胞,然后采用流式细胞术分析这种模型细胞对***和其它肠道细菌以... 详细信息

目的建立幽门螺杆菌(***)慢性感染胃上皮细胞模型,并分析***慢性感染与胃上皮细胞凋亡的关系.方法首先用*** SSI与人非肿瘤性胃上皮细胞株GES-1共培养16周,建立GES-1模型细胞,然后采用流式细胞术分析这种模型细胞对***和其它肠道细菌以及抗肿瘤药物凋亡诱导剂的应答.结果成功获得了***慢性感染胃上皮细胞模型(GES-1模型细胞).这种模型细胞不仅对***诱导的凋亡耐受,而且对其他肠道细菌和一些凋亡诱导剂也是耐受的。结论幽门螺杆菌慢性感染诱导胃上皮细胞产生凋亡耐受,由此可能增加了胃上皮细胞癌变的危险性.

关键词：幽门螺杆菌慢性感染诱导胃上皮细胞产生凋亡耐受

MHC class I-LILRB3 delivers a punch to eliminate precancerous cells

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Cellular & Molecular Immunology 2022年第6期19卷 655-656页

作者： Chi chun wong Jun yu Institute of Digestive Disease Department of Medicine and TherapeuticsState Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina

In the study by Ayukawa et al.[1],the authors presented an innate defense mechanism whereby normal epithelial cells actively remove precancerous cells from the epithelium via mechanical extrusion(Fig.1).

关键词： precancerous epithelium

Macrophage migration inhibitory factor stimulated by He/icobacter py/oriincreases proliferation of gastric epithelial cells

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World Journal of Gastroenterology 2005年第13期11卷 1946-1950页

作者： Harry Hua-Xiang Xia Shiu Kum Lam Annie O.O.Chan Marie Chia Mi Lin Hsiang Fu Kung Keiji Ogura Douglas E.Berg benjamin chun-yu wong Department of Medicine Institute of Molecular Biology Department of Molecular Microbiology

AIM: Helicobacter pylori (H pylori) is associated with increased gastric inflammatory and epithelial expression of macrophage migration inhibitory factor (MIF) and gastric epithelial cell proliferation. This study aimed at determining whether H pylori directly stimulates release of MIF in monocytes, whether the cay pathogenicity island (PAI) is involved for this function, and whether MIF stimulated by H pylori increases gastric epithelial cell proliferation in ***: A cytotoxic wild-type H pylori strain (TN2),its three isogenic mutants (TN2△cag, TN2△cagA and TN2△cagE) were co-cultured with cells of a human monocyte cell line, THP-1, for 24 h at different organism/cell ratios. MIF in the supernatants was measured by an ELISA. Cells of a human gastric cancer cell line, MKN45,were then co-cultured with the supernatants, with and without monoclonal anti-MIF antibody for 24 h. The cells were further incubated for 12 h after addition of 3H-thymidine, and the levels of incorporation of 3H-thymidine were measured with a liquid scintillation ***: The wild-type strain and the isogenic mutants,TN2△cagA and TN2△cagE, increased MIF release at organism/cell ratios of 200/1 and 400/1, but not at the ratios of 50/1 and 100/1. However, the mutant TN2△cag did not increase the release of MIF at any of the four ratios.3H-thymidine readings for MKN-45 cells were significantly increased with supernatants derived from the wild-type strain and the mutants TN2△cagA and TN2△cagE, but not from the mutant TN2△cag. Moreover, in the presence of monoclonal anti-MIF antibody, the stimulatory effects of the wild-type strain on cell proliferation ***: H pylori stimulates MIF release in monocytes, likely through its cag PAI, but not related to cagA or cagE. H pylori-stimulated monocyte culture supernatant increases gastric cell proliferation, which is blocked by anti-MIF antibody, suggesting that MIF plays an important role in H pylori-induced gastric epithelia

关键词：巨噬细胞细胞移植抑制因子胃上皮细胞细胞增殖幽门螺杆菌

Data-driven placemaking: Public space canopy design through multi-objective optimisation considering shading, structural and social performance

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Frontiers of Architectural Research 2022年第2期11卷 308-323页

作者： Jeroen van Ameijde chun yu Ma Garvin Goepel Clive Kirsten Jeff wong School of Architecture The Chinese University of Hong KongHong KongChina Lightweight Works Hong KongChina APS Research Ltd. Hong KongChina

In the context of ongoing densification of cities and aging urban populations,public spaces are a crucial infrastructure to support the physical and mental wellbeing of urban *** design of public space furniture elements is often standardised,and not considered in relation to environmental conditions and mechanisms of social *** article presents a digital workflow to generate site-specific designs for shaded public seating,considering the relationships of local public places to their surroundings.A strategy for customised and site-specific design is developed through the use of multiple software tools,employing evolutionary algorithms and multi-objective *** method is applied to a small public space canopy prototype installed within a public housing estate in Hong Kong,incorporating additional criteria to achieve a low-cost and light-weight *** multiple stages of refinement and optimisation,a material,structural and social performance-driven outcome was achieved that creates a shaded space for public seating,people watching and social *** part of a larger research agenda exploring architectural form-finding and environmental psychology,the project represents potential new applications in the emerging field of socially driven computational design.

关键词： Public space Tensile membrane structures Structural design Environmental performance Multi-objective optimisation Evolutionary algorithms

Verification of tropical cyclones(TC)wind structure forecasts from global NWP models and ensemble prediction systems(EPSs)

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Tropical Cyclone Research and Review 2022年第2期11卷 88-102页

作者： Xiaoqin Lu Wai Kin wong Kin chung Au-Yeung chun Wing Choy Hui yu Shanghai Typhoon Institute and Laboratory of Typhoon Forecast Technique China Meteorological AdministrationShanghaiChina Hong Kong Observatory Hong KongChina

Forecasting wind structure of tropical cyclone(TC)is vital in assessment of impact due to high winds using Numerical Weather Prediction(NWP)*** usual verification technique on TC wind structure forecasts are based on grid-to-grid comparisons between forecast field and the actual ***,precision of traditional verification measures is easily affected by small scale errors and thus cannot well discriminate the accuracy or effectiveness of NWP model *** this study,the Method for Object-Based Diagnostic Evaluation(MODE),which has been widely adopted in verifying precipitation fields,is utilized in TC’s wind field verification for the first *** TC wind field forecast of deterministic NWP model and Ensemble Prediction System(EPS)of the European Centre for Medium-Range Weather Forecasts(ECMWF)over the western North Pacific and the South China Sea in 2020 were evaluated.A MODE score of 0.5 is used as a threshold value to represent a skillful(or good)*** is found that the R34(radius of 34 knots)wind field structure forecasts within 72 h are good regardless of DET or *** performance of R50 and R64 is slightly worse but the R50 forecasts within 48 h remain good,with MODE exceeded *** R64forecast within 48 h are worth for reference as well with MODE of around *** study states that the TC wind field structure forecast by ECMWF is skillful for TCs over the western North Pacific and the South China Sea.

关键词： Verification Tropical cyclones wind structure forecasts Numerical weather prediction models Ensemble prediction system