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Prophylactic uses of integrin CD18-βA peptide in a murine polymicrobial peritonitis model

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World Journal of Gastroenterology 2010年第21期16卷 2648-2656页

作者： kwong-fai wong Jana Wo David Ho Ronnie T Poon José M Casasnovas John M Luk Department of Pharmacology and Surgery National University Hospital SystemNational University of SingaporeSingapore 117597Singapore Department of Surgery Queen Mary HospitalPokfulamHKSARHong KongChina Centro Nacional de Biotecnología CSICCampus Universidad Autónoma28049 MadridSpain

AIM:To evaluate the prophylactic properties of integrin CD18-βA peptide in a murine model of abdominal polymicrobial peritonitis and ***:Bacterial sepsis was induced in Institute of Cancer Research(ICR) mice by cecal ligation and puncture(CLP) *** mice were then injected with either sterile saline or CD18-βA peptide intraperitoneally at 2 h after surgery,and were sacrificed at 12 and 24 h after *** samples were immediately collected,and analyzed for endotoxin activity and tumor necrosis factor(TNF)-α and interleukin(IL)-*** and liver were studied for CD45+ leukocyte and CD3 mRNA *** expression of intercellular adhesion molecule(ICAM)-1,vascular cell adhesion molecule(VCAM) and E-selectin was also ***:Intraperitoneal injection of CD18-βA peptide significantly suppressed circulating endotoxin activity(P<0.01) at 24 h,as well as serum levels of TNF-α(P<0.05 at 12 and 24 h) and IL-6(P<0.01 at 12 h,P<0.05 at 24 h) in CLP-inflicted ***18-βA peptide also abrogated leukocyte infiltration into liver and lungs as unveiled by reduced CD45+ leukocyte and CD3 mRNA ***,the peptide significantly reduced pulmonary expression of VCAM(P<0.01 at 12 h,P<0.001 at 24 h),E-selectin(P<0.01 at 12 and 24 h),and ICAM-1(P<0.01 at 12 h,P<0.001 at 24 h).These actions of CD18-βA peptide collectively protected septic mice against lethality(P<0.01).CONCLUSION:CD18-βA peptide is a potent endotoxin antagonist that can protect surgical patients against sepsis-associated lethality.

关键词： Bacterial endotoxin Integrin CD18 Inflammation Biotherapeutic peptide

Garcinol suppresses the growth of human hepatocellular carcinoma by inducing abrogation of STAT3 phosphorylation,acetylation and dimerization

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中国药理学与毒理学杂志 2015年第S1期29卷 82-83页

作者： Muthu K SHANMUGAM Snehajyoti CHATTERJEE Peramaiyan RAJENDRAN Feng LI Parijat SENAPATI kwong fai wong Alan Prem KUMAR John MLUK Kam Man HUI Gautam SETHI Tapas K KUNDU Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Singapore 117957 Jawaharlal Nehru Centre for Advanced Scientific Research Molecular Biology and Genetics Unit Transcription and Disease Laboratory Jakkur P.O. Bangalore 560064 India Cancer Science Institute of Singapore National University of Singapore Singapore 117456 School of Biomedical Sciences Faculty of Health Sciences Curtin University Western Australia Division of Cellular and Molecular Research Humphrey Oei Institute of Cancer Research National Cancer Centre Singapore 169610 Institute of Molecular and Cell Biology Singapore 138673

OBJECTIVE Hepatocellular carcinoma(HCC)is the fifth most common malignancy worldwide and the third cause of global cancer *** of signal transducer and activator of transcription 3(STAT3)is commonly observed in tumor cells and is a critical mediator of on cogenic signaling in HCC and controls the expression of several genes involved in proliferation,survival,metastasis and *** drug-targeted therapies,besides being expensive,are associated with serious side effects and ***,novel agents that can suppress STAT3 activation have potential for both prevention and treatment of *** the present report,we investigated whether the potent HAT/KAT inhibitor,garcinol,(apolyisoprenylatedbenzophenone),could suppress STAT3 activation in HCC cells and in nude mice *** The effect of garcinol on HCC cell lines wasdetermined by MTT assay,immunoblotting,DNA binding assays,immuno-fluorescenceand immune-histochemical *** effect of garcinolon the inhibition of tumor growth in vivo was also investigated using HCCxenograft tumor modelin athymic nu/nu *** We found that garcinol could inhibit constitutive STAT3 activation in a dose-and time-dependent manner both by inhibiting STAT3 phosphorylation and acetylation in HCC *** investigated for molecular mechanism(s),we found that garcinol interferes with the dimer formation of STAT3 thereby inhibits its nuclear *** modeling showed that garcinol could bind to the SH2 domain of STAT3 and suppresses its dimerization in *** understand the cellular mechanism(s)of inhibition of STAT3 function by garcinol,we observed that upon inhibition of STAT3 dimerization bygarcinol,STAT3 DNA binding ability gets *** inhibition of STAT3 activation by garcinol led to the suppression of various gene products involved in proliferation,survival,and ***,when administered i.p.,garcinol inhibited the growth of human HCC xenograft tumors in

关键词： STAT3 HCC garcinol acetylation dimerization nude m

Role of LPS/CD14/TLR4-mediated inflammation in necrotizing enterocolitis:Pathogenesis and therapeutic implications

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World Journal of Gastroenterology 2009年第38期15卷 4745-4752页

作者： kwong L Chan kwong F wong John M Luk Department of Surgery The University of Hong Kong Division of Paediatric Surgery Queen Mary Hospital Department of Pharmacology and Department of Surgery National University Health SystemNational University of SingaporeMD11 #05-1210 Medical Drive

AIM:To establish the roles of lipopolysaccharide (LPS)/CD14/toll-like receptor 4 (TLR4)-mediated inflammation in a rat model of human necrotizing enterocolitis (NEC).METHODS: Six pairs of intestinal samples from human NEC were collected before and after recovery for histological and molecular analysis of inflammatory cytokines and signaling components. In the rat NEC model, we isolated 10-cm jejunum segments and divided them into six groups (n=6) for sham operation, treatment with LPS, bowel distension, combined bowel distension and LPS stimulation, and two therapeutic groups. The potential eff icacy of a recombinant CD18 peptide and a monoclonal CD14 antibody was evaluated in the latter two groups. The serum and tissue levels of several inflammatory mediators were quantified by real-time polymerase chain reaction, ELISA and ***: Human acute phase NEC tissues displayed significant increases (P<0.05) in levels of TLR4, CD14, myeloid differentiation protein (MD)-2, tumor necrosis factor (TNF)-α and nuclear factor-κB when compared to those after recovery. The histological and inflammatory picture of human NEC was reproduced in rats that were treated with combined bowel distension and LPS, but not in the sham-operated and other control rats. Serum levels of interleukin-6 and TNF-α were also elevated. The NEC pathology was attenuated by treating the NEC rats with a monoclonal CD14 antibody or an LPS-neutralizing ***:LPS and distension are required to produce the histological and inflammatory features of NEC. A potential treatment option is blocking LPS activation and leukocyte infi ltration.

关键词： CD14 antigen Lipopolysaccharide Necrotizing enterocolitis Pathogenesis Therapy Toll-like receptor 4

Enantioselective iridium-catalyzed allylic substitution with a Reformatsky reagent: direct construction of β-stereogenic homoallylic esters

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Science China Chemistry 2024年第11期67卷 3791-3797页

作者： Debasis Pal Kirana DVeeranna Yuk fai wong PAndrew Evans Department of Chemistry Queen’s University90 Bader LaneKingstonK7L 3N6Canada Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha410013China

The Reformatsky reagent derived from ethyl bromoacetate circumvents the challenge associated with the direct regio-and enantioselective iridium-catalyzed allylic alkylation with an unstabilized aliphatic ester enolate. Notably, this work represents the first example of using a Reformatsky reagent in a metal-allyl reaction, which permits the direct construction of enantioenriched β-stereogenic homoallylic esters without preactivation of the pronucleophile or post-reaction modification of the product(e.g., thermal decarboxylation of a 1,3-dicarbonyl). Moreover, the process allows the coupling of a broad range of sterically and electronically diverse electrophiles bearing aryl, heteroaryl and alkenyl derivatives, including the significantly more challenging alkyl-substituted allylic carbonates. The versatility of the ester product is exemplified by a series of functional group manipulations and the development of a concise and efficient enantioselective total synthesis of the natural product,(+)-descurainolide A. Finally, mechanistic studies indicate that the zinc enolate behaves as a soft nucleophile that undergoes outer-sphere alkylation.

关键词： allylic substitution asymmetric catalysis mechanistic studies natural product synthesis Reformatsky reagent

Effect of pipe installation and external load on buried steel pipe responses:Experimental and numerical investigations

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Underground Space 2024年第2期15卷 44-58页

作者： Yadong Zhang Ron Chik-kwong wong Jianfeng Chen Wei Su Department of Civil Engineering Schulich School of EngineeringUniversity of CalgaryCalgaryAB T2N 1N4Canada Department of Geotechnical Engineering College of Civil EngineeringTongji UniversityShanghai 200092China

During pipe installation,compacting soil at pipe sides causes an initial pipe deformation which is known as the"peaking"***,in conventional pipe design codes,only pipe deformation caused by vertical overburden is considered while the"peaking"effect is *** this study,a full-scale test was conducted on a Grade X52 steel pipe with a diameter of 600 mm to investigate the impacts of both soil compaction and vertical overburden on pipe *** compaction and external load were found to elongate and shorten the vertical pipe diameter,***"peaking"effect was observed during the installation procedure accompanied by the highest pipe stress measured at the pipe ***,a two-dimensional finite element model was created and validated based on the calculated pipe stresses from the experimental study.A parametric study was performed thereafter to numerically study the impacts of soil water content,pipe wall thickness,compaction pressure,and lift thickness on pipe responses due to soil compaction and external *** increase in the"peaking"effect is observed with increasing soil water content and compaction pressure,while an increase in pipe wall thickness or lift thickness would cause a decrease in the"peaking"effect.

关键词： X52 steel Soil compaction External load Peaking effect Pipe deflection Soil arching

Anti-cancer activities of S-allylmercaptocysteine from aged garlic

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Chinese Journal of Natural Medicines 2019年第1期17卷 43-49页

作者： LV Yi SO Kwok-fai wong Nai-Kei XIAO Jia Laboratory of Neuroendocrinology School of Biological SciencesFujian Normal University National Key Disciplines for Infectious Diseases Shenzhen Third People's HospitalThe Second Hospital Affiliated to Southern University of Science and Technology School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong Kong

While most types of malignancies remain recalcitrant to treatment, application of natural products or their analogs in daily life has offered some hopes as an effective prophylaxis against cancer onset and progression in the past decades. Emerging evidence supports a link between garlic consumption and decreased cancer incidence. Notably, aged garlic extract(AGE) exhibits stronger anti-cancer activities than that of fresh garlic, by virtue of enrichment of several AGE-specific organosulfur compounds, including S-allylmercaptocysteine(SAMC). In this review, we summarize the up-to-date mechanistic pathways associated with the anti-proliferative, anti-metastatic and pro-apoptotic effects of SAMC in various cancer models. Based upon the proven safety and improved understanding on its anti-neoplastic properties, SAMC has gained recognition as a promising daily food supplement for cancer prevention or management.

关键词： Aged garlic S-allylmercaptocysteine Cancer Molecular pathway Reactive oxygen species

A Second Main Theorem on P^n for difference operator

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Science China Mathematics 2009年第12期52卷 2751-2758页

作者： wong Pit-Mann LAW Hiu-fai wong Philip P.W. Department of Mathematics University of Notre Dame Department of Mathematics University of Hong Kong

The main result of this article is an extension of the Second Main Theorem,of Halburd and Korhonen,for meromorphic functions of finite *** result replaces the counting function of the ramification divisor Nramf(r)in the classical Second Main Theorem by the counting function of a finite difference divisor Npair(r).In this article,the Second Main Theorem of Halburd and Korhonen is extended to the case of holomorphic maps into Pn of finite order.

关键词： finite difference Second Main Theorem finite order ramification

On limit behavior of quasi-local mass for ellipsoids at spatial infinity

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Communications in Theoretical Physics 2020年第1期72卷 102-110页

作者： Xiaokai He Leong-fai wong Naqing Xie School of Mathematics and Computational Science Hunan First Normal UniversityChangsha 410205China School of Mathematical Sciences Fudan UniversityShanghai 200433China

We discuss the spatial limit of the quasi-local mass for certain ellipsoids in an asymptotically flat static spherically symmetric *** ellipsoids are not nearly round but they are of interest as an admissible parametrized foliation defining the Arnowitt–Deser–Misner *** Hawking mass of this family of ellipsoids tends to-∞.In contrast,we show that the Hayward mass converges to a finite ***,a positive mass type theorem is *** limit of the mass has a uniform positive lower bound no matter how oblate these ellipsoids *** result could be extended for asymptotically Schwarzschild *** numerical simulation in the Schwarzschild spacetime illustrates that the Hayward mass is monotonically increasing near infinity.

关键词： quasi-local mass asymptotically flat limit behavior

Late retroperitoneal recurrence of hepatocellular carcinoma 12 years after initial diagnosis

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World Journal of Gastroenterology 2010年第17期16卷 2187-2189页

作者： Tiffany Cho-Lam wong Ka-fai To Simon See-Ming Hou Sidney Kam-Hung Yip Chi-fai Ng Department of Surgery Prince of Wales HospitalThe Chinese University of Hong Kong Department of Anatomical and Cellular Pathology The Chinese University of Hong Kong

Hepatocellular carcinoma (HCC) is an aggressive tumor with poor long-term ***,we present an unusual patient with a solitary recurrence of HCC in the right kidney 12 years after the initial *** illustrates the importan... 详细信息

关键词： Hepatocellular carcinoma Late recurrence Metastasis Retroperitoneal