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Metabolic memory:mechanisms and diseases

Signal Transduction and Targeted Therapy 2024年第3期9卷 1086-1114页

作者： Hao Dong Yuezhang Sun Lulingxiao Nie Aimin Cui Pengfei Zhao wai keung leung Qi Wang State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduChina Department of Prosthodontics West China Hospital of StomatologySichuan UniversityChengduChina Periodontology and Implant Dentistry Division Faculty of DentistryThe University of Hong KongHong KongChina

Metabolic diseases and their complications impose health and economic burdens *** from past experimental studies and clinical trials suggests our body may have the ability to remember the past metabolic environment,such as hyperglycemia or hyperlipidemia,thus leading to chronic inflammatory disorders and other diseases even after the elimination of these metabolic *** long-term effects of that aberrant metabolism on the body have been summarized as metabolic memory and are found to assume a crucial role in states of health and *** molecular mechanisms collectively participate in metabolic memory management,resulting in different cellular alterations as well as tissue and organ dysfunctions,culminating in disease progression and even affecting *** elucidation and expansion of the concept of metabolic memory provides more comprehensive insight into pathogenic mechanisms underlying metabolic diseases and complications and promises to be a new target in disease detection and ***,we retrace the history of relevant research on metabolic memory and summarize its salient *** provide a detailed discussion of the mechanisms by which metabolic memory may be involved in disease development at molecular,cellular,and organ levels,with emphasis on the impact of epigenetic ***,we present some of the pivotal findings arguing in favor of targeting metabolic memory to develop therapeutic strategies for metabolic diseases and provide the latest reflections on the consequences of metabolic memory as well as their implications for human health and diseases.

关键词： diseases metabolism alterations

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p53-independent pRB degradation contributes to a drug-induced apoptosis in AGS cells

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Cell Research 2005年第9期 20-28页

作者： wai keung leung,Joseph Jao-Yiu SUNG Shatin Hong Kong SAR China Department of Medicine and Therapeutics The Chinese University of Hong Kong Prince of Wales Hospital Shatin Hong Kong SAR China Department of Medicine and Therapeutics The Chinese University of Hong Kong Prince of Wales Hospital

The retinoblastoma (RB) tumor suppressor protein, pRB, plays an important role in the regulation of mammalian cell cycle. Furthermore, several lines of evidence suggest that pRB also involves in the regulation of apoptosis. In the present study, the degradation of pRB was observed in apoptotic gastric tumor cells treated with a new potent anti-tumor component, tripchlorolide (TC). The inhibition of pRB degradation by a general cysteine protease inhibitor IDAM resulted in the reduction of the apoptotic cells. Furthermore, the survival of the gastric tumor cells under the TC treatment was enhanced by an over-expression of exogenous pRB. These results suggest that the pRB degradation of the gastric tumor cells under the TC treatment involves in the apoptotic progression. In addition, the same extent of TC- induced pRB-degradation was detected in the gastric tumor cells containing a p53 dominant-negative construct, indicat- ing that this kind of pRB degradation is p53-independent.

关键词： pRB degradation p53 apoptosis.

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Icteric flare of chronic hepatitis B in a 95-year old patient

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World Journal of Gastroenterology 2003年第12期9卷 2876-2877页

作者： WS Wong wai keung leung Henry L Y Chan Department of Medicine and Therapeutics the Prince of Wales HospitalHong Kong SARThe Chinese University of Hong Kong

A 95-year old gentleman developed fatal icteric flare of chronic hepatitis B despite lamivudine treatment. This article highlights the atypical presentations of chronic hepatitis B in elderly patient and the need to c... 详细信息

关键词：慢性乙型肝炎高龄患者黄疸拉米夫定急性暴发性肝炎

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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

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Follow up of serial urea breath test results in patients after consumption of antibiotics for non-gastric infections

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World Journal of Gastroenterology 2002年第4期8卷 703-706页

作者： wai-keung leung Lawrence Cheung-Tsui Hung Carrie Ka-Li Kwok Rupert Wing-Loong Leong Daniel Kwok-keung Ng Joseph Jao-Yiu Sung Department of Medicine & Therapeutics Prince of Wales Hospitalthe Chinese University of Hong KongShatinHong KongChina Department of Paediatrics Kwong Wah HospitalKowloonHong KongChina

AIM: The widespread use of antibacterial therapy hasbeen suggested to be the cause for the decline in theprevalence of Helicobacter pyloriinfection. This studyexamine the serial changes of urea breath test resultsin a group of hospitalized patients who were givenantibacterial therapy for non-gastric ***: Thirty-five hospitalized patients who weregiven antibacterial therapy for clinical infections,predominantly chest and urinary infections, werestudied. Most (91%) patients were given singleantibiotic of either a penicillin or cephalosporin *** 13C-urea breath tests were performed within 24hours of initiation of antibiotics, at one-week and atsix-week post-therapy. H. pylori infection wasdiagnosed when one or more urea breath tests ***: All 35 patients completed three serial ureabreath tests and 26 (74 %) were H. pylori-positive. Ten(38 %) H. pylori-infected patients had at least onenegative breath test results during the study *** medium delta 13C values were significantly lowerat baseline (8.8) than at one-week (20.3) and six-week(24.5) post-treatment in H. pylori-positive individuals(P=0.022). Clearance of H. pyloriat six-week was onlyseen in one patient who had received anti-helicobactertherapy from another ***: Our results suggested that one-third ofH. pylori-infected individuals had transient false-negative urea breath test results during treatment withantibacterial agent. However, clearance of H. pyloriinfection by regular antibiotic consumption is rare.

关键词：抗生素 HP感染连续尿素呼吸试验耐药

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Prostate health index can stratify patients with Prostate Imaging Reporting and Data System score 3 lesions on magnetic resonance imaging to reduce prostate biopsies

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Asian Journal of Andrology 2024年第1期26卷 20-24页

作者： John Shung-Lai leung wai-Kit Ma Brian Sze-Ho Ho Stacia Tsun-Tsun Chun Rong Na Yongle Zhan Chi-Yuen Ng Chi-Ho Ip Ada Tsui-Lin Ng Yiu-Chung Lam Division of Urology Department of SurgeryQueen Mary HospitalUniversity of Hong KongHong KongChina Division of Urology Department of SurgeryPrincess Margaret HospitalHongKongChina

We aim to evaluate prostate health index as an additional risk-stratification tool in patients with Prostate Imaging Reporting and Data System score 3 lesions on multiparametric magnetic resonance *** with biochemical or clinical suspicion of having prostate cancer who underwent multiparametric magnetic resonance imaging in two tertiary centers(Queen Mary Hospital and Princess Margaret Hospital,Hong Kong,China)between January 2017 and June 2022 were ***-magnetic resonance imaging fusion biopsies were performed after prostate health index *** who only had Prostate Imaging Reporting and Data System score 3 lesions were further stratified into four prostate health index risk groups and the cancer detection rates were *** of the 747 patients,47.3%had Prostate Imaging Reporting and Data System score 3 lesions *** detection rate of clinically significant prostate cancer in this group was 15.0%.The cancer detection rates of clinically significant prostate cancer had statistically significant differences:5.3%in prostate health index<25.0,7.4%in prostate health index 25.0-34.9,17.9%in prostate health index 35.0-54.9,and 52.6%in prostate health index≥55.0(P<0.01).Among the patients,26.9%could have avoided a biopsy with a prostate health index<25.0,at the expense of a 5.3%risk of missing clinically significant prostate *** health index could be used as an additional risk stratification tool for patients with Prostate Imaging Reporting and Data System score 3 *** could be avoided in patients with low prostate health index,with a small risk of missing clinically significant prostate cancer.

关键词： biopsy fusion biopsy magnetic resonance imaging prostate cancer prostate health index

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Clinical significance of hepatic derangement in severe acute respiratory syndrome

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World Journal of Gastroenterology 2005年第14期11卷 2148-2153页

作者： Henry Lik-Yuen Chan Ambrose Chi-Pong Kwan Ka-Fai To Sik-To Lai Paul Kay-Sheung Chan wai-keung leung Nelson Lee Alan Wu Joseph Jao-Yiu Sung Department of Medicine and Therapeutics Chinese University of Hong Kong Hong Kong SARChina Department of Medicine Princess Margaret Hospital Hong Kong SARChina Department of Anatomical and Cellular Pathology Chinese University of Hong Kong Hong Kong SARChina Department of Microbiology Chinese University of Hong Kong Hong Kong SARChina

AIM: Elevation of alanine aminotransferase (ALT) level is commonly seen among patients suffering from severe acute respiratory syndrome (SARS). We report the progression and clinical significance of liver derangement in a large cohort of SARS ***: Serial assay of serum ALT was followed in patients who fulfilled the WHO criteria of SARS. Those with elevated ALT were compared with those with normal liver functions for clinical outcome. Serology for hepatitis B virus (HBV) infection was checked. Adverse outcomes were defined as oxygen desaturation, need of intensive care unit (ICU) and mechanical ventilation and ***: Two hundred and ninety-four patients were included in this study. Seventy (24%) patients had elevated serum ALT on admission and 204 (69%) patients had elevated ALT during the subsequent course of illness. Using peak ALT >5×ULN as a cut-off and after adjusting for potential confounding factors, the odds ratio of peak ALT>5x ULN for oxygen desaturation was 3.24 (95%CI 1.23-8.59, P = 0.018), ICU care was 3.70 (95% CI 1.38-9.89, P = 0.009), mechanical ventilation was 6.64 (95%CI 2.22-19.81, P = 0.001) and death was 7.34(95%CI 2.28-24.89, P = 0.001). Ninety-three percent of the survived patients had ALT levels normalized or were on the improving trend during follow-up. Chronic hepatitis B was not associated with worse clinical ***: Reactive hepatitis is a common complication of SARS-coronavirus infection. Those patients with severe hepatitis had worse clinical outcome.

关键词：肝功能紊乱严重急性呼吸综合症丙胺酸转氨酶并发症

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Within-Cluster Variability Exponent for Identifying Coherent Structures in Dynamical Systems

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Communications in Computational Physics 2023年第3期33卷 824-848页

作者： wai Ming Chau Shingyu leung Department of Mathematics The Hong Kong University of Science and TechnologyClear Water BayHong Kong

We propose a clustering-based approach for identifying coherent flow structuresin continuous dynamical systems. We first treat a particle trajectory over a finitetime interval as a high-dimensional data point and then cluster these data from differentinitial locations into groups. The method then uses the normalized standarddeviation or mean absolute deviation to quantify the deformation. Unlike the usualfinite-time Lyapunov exponent (FTLE), the proposed algorithm considers the completetraveling history of the particles. We also suggest two extensions of the method. To improvethe computational efficiency, we develop an adaptive approach that constructsdifferent subsamples of the whole particle trajectory based on a finite time interval. Tostart the computation in parallel to the flow trajectory data collection, we also developan on-the-fly approach to improve the solution as we continue to provide more measurementsfor the algorithm. The method can efficiently compute the WCVE over adifferent time interval by modifying the available data points.

关键词： Dynamical system visualization finite time Lyapunov exponent numerical methods for differential equations k-means clustering

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Contents of four active components in different commercial crude drugs and preparations of Danshen (Salvia miltiorrhiza)

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Acta Pharmacologica Sinica 2002年第12期23卷 110-115页

作者： Susan wai Sum leung,Yaw Loong SIOW,Ricky Ying keung MAN 21 Sassoon Road Hong Kong China Department of Pharmacology Faculty of Medicine University of Hong Kong 21 Sassoon Road Hong Kong China Department of Pharmacology University of Hong Kong Department of Pharmacology 21 Sassoon Road Hong Kong China Faculty of Medicine University of Hong Kong 21 Sassoon Road Hong Kong China Department of Pharmacology Faculty of Medicine University of Hong Kong

AIM: To detect the contents of four active components of Salvia miltiorrhiza in various commercially available danshen crude drugs and preparations. METHODS: Commercially available danshen crude drugs from different sources, as well as danshen pills and intravenous injection preparations containing danshen alone or in combination with other herbs were collected. The composition of these danshen samples was analyzed using HPLC. Specifically, the amounts of magnesium tanshinoate B (MTB), danshensu, isotanshinone IIA, and ctyptotanshinone were determined. In some of these samples, the content of MTB was further confirmed by liquid chromatography-tandem mass spectrometer (LC-MS)/MS method. RESULTS: There were great variations in the amount of the four active ingredients in the commercially available danshen crude drugs and drug preparations in this study. The amount of MTB was the highest among the four components measured in the crude drugs. However, the amounts of MTB in all danshen preparations were much

关键词： Salvia miltiorrhiza magnesium tanshinoate B (MTB) high pressure liquid chromatography

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Development of a dual targeting scaffold of SET7/MLL inhibitor for castration-resistant prostate cancer treatment

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Genes & Diseases 2023年第6期10卷 2260-2262页

作者： Guodong Li Qi Huang Vincent Kam wai Wong Wanhe Wang Chung-Hang leung Institute of Chinese Medical Sciences and State Key Laboratory of Quality Research in Chinese Medicine University of MacaoMacao SAR 999078China Dr.Neher's Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao SAR 999078China Institute of Medical Research Northwestern Polytechnical UniversityXi'anShaanxi 710072China Macao Centre for Research and Development in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China Department of Biomedical Sciences Faculty of Health SciencesUniversity of MacaoMacao SAR 999078China Zhuhai UM Science and Technology Research Institute ZhuhaiGuangdong 519000China

Histone methyltransferase enzyme SET7 and mixed-lineage leukemia protein(MLL)complex are crucial co-activators of androgen receptor(AR)and have recently emerged as potential therapeutic targets for advanced castration-resistant prostate cancer(CRPC).In this study,we described the identification of a rhodium-based hybrid complex(SM_1)as a potent blocker of AR activity via simultaneously inhibiting SET7 and MLL complex activity,which makes it a potential lead scaffold for CPRC drug development.

关键词： cancer inhibiting treatment

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