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Biased activity of soluble guanylyl cyclase:the Janus face of thymoquinone

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Acta Pharmaceutica Sinica B 2017年第4期7卷 401-408页

作者： Charlotte Detremmerie Paul m.Vanhoutte Susan leung Department of Pharmacology and Pharmacy and State Key Laboratory for Pharmaceutical Biotechnology Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina

The natural compound thymoquinone, extracted from Nigella sativa(black cumin), is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endotheliumindependent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress. Serendipitously,thymoquinone was found to augment contractions in isolated arteries with endothelium of both rats and pigs. The endothelium-dependent augmentation it causes counterintuitively depends on biased activation of soluble guanylyl cyclase(sGC) producing inosine 3',5'-cyclic monophosphate(cyclic ImP) rather than guanosine 3',5'-cyclic monophosphate. This phenomenon shows a striking mechanistic similarity to the hypoxic augmentation previously observed in porcine coronary arteries. The cyclic ImP preferentially produced under thymoquinone exposure causes an increased contractility of arterial smooth muscle by interfering with calcium homeostasis. This brief review summarizes the vascular pharmacology of thymoquinone, focussing in particular on how the compound causes endothelium-dependent contractions by biasing the activity of sGC.

关键词： Thymoquinone Endothelium-dependentcontraction Nitric oxide Soluble guanylyl cyclase Cyclic ImP NADPH:quinone oxidoreductase

Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin:Creation of an unnatural analogue with improved anticancer properties

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Acta Pharmaceutica Sinica B 2024年第1期14卷 421-432页

作者： Dexiu Yan Jemma Arakelyan Teng Wan Ritvik Raina Tsz Ki Chan Dohyun Ahn Vladimir Kushnarev Tsz Kiu Cheung Ho Ching Chan Inseo Choi Pui Yi Ho Feijun Hu Yujeong Kim Hill Lam Lau Ying Lo Law Chi Seng leung Chun Yin Tong Kai Kap Wong Wing Lam Yim Nikolay S.Karnaukhov Richard Y.C.Kong maria V.Babak Yudai matsuda Department of Chemistry City University of Hong KongHong Kong SARChina iGEm Team“VarieCure” City University of Hong KongHong Kong SARChina Department of Biomedical Engineering City University of Hong KongHong Kong SARChina moscow Clinical Research Center Named After A.S.Loginov Moscow 111123Russian Federation

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC *** production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 ***,the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic *** study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

关键词： Animal studies Anticancer properties Biosynthesis Natural products Sesterterpenoids Synthetic biology Terpene synthases Variecolin

Adaptive immunity in the liver

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Cellular & molecular Immunology 2016年第3期13卷 354-368页

作者： Zongwen Shuai miranda WY leung Xiaosong He Weici Zhang Guoxiang Yang Patrick SC leung m Eric Gershwin Division of Rheumatology Allergy and Clinical Immunology University of California Davis School of Medicine Davis CA 95616 USA Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical University Hefei 230022 China.

The anatomical architecture of the human liver and the diversity of its immune components endow the liver with its physiological function of immune competence. Adaptive immunity is a major arm of the immune system that is organized in a highly specialized and systematic manner, thus providing long-lasting protection with immunological memory. Adaptive immunity consists of humoral immunity and cellular immunity. Cellular immunity is known to have a crucial role in controlling infection, cancer and autoimmune disorders in the liver. In this article, we will focus on hepatic virus infections, hepatocellular carcinoma and autoimmune disorders as examples to illustrate the current understanding of the contribution of T cells to cellular immunity in these maladies. Cellular immune suppression is primarily responsible for chronic viral infections and cancer. However, an uncontrolled auto-reactive immune response accounts for autoimmunity. Consequently, these immune abnormalities are ascribed to the quantitative and functional changes in adaptive immune cells and their subsets, innate immunocytes, chemokines, cytokines and various surface receptors on immune cells. A greater understanding of the complex orchestration of the hepatic adaptive immune regulators during homeostasis and immune competence are much needed to identify relevant targets for clinical intervention to treat immunological disorders in the liver.

关键词： adaptive immunity T cells immunopathogenesis antiviral immunity

Hematopoietic cell transplantation for Crohn’s disease;is it time?

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World Journal of Gastroenterology 2006年第41期12卷 6665-6673页

作者： Y leung m Geddes J Storek R Panaccione PL Beck Gastrointestinal Mucosal Inflammation and Immunology Research Groups.Department of MedicineUniversity of Calgary CalgaryAlbertaCanada

AIm： To review all studies in the literature that have assessed Hematopoietic cell transplantation （HCT） and Crohn＇s disease （CD） with the ultimate aims of determining if this is a viable treatment option for those with CD. A secondary aim was to review the above literature and determine if the studies shed further light on the mechanisms involved in the pathogenesis of CD. mETHODS： An extensive medline search was performed on all articles from 1970 to 2005 using the keywords; bone marrow transplant, stem cell, hematopoietic cell, Crohn＇s disease and inflammatory bowel disease. RESULTS： We identified one case in which a patient developed CD following an allogeneic HCT from a sibling suffering with CD. Evidence for transfer of the genetic predisposition to develop CD was also identified with report of a patient that developed severe CD following an allogeneic HCT. Following HCT it was found that the donor （that had no signs or symptoms of CD） and the recipient had several haplotype mismatches in HLA class 111 genes in the IBD3 locus including a polymorphism of NOD2/CARD15 that has been associated with CD. Thirty three published cases of patients with CD who underwent either autologous or allogeneic HCT were identified. At the time of publication 29 of these 33 patients were considered to be in remission. The median follow-up time was seven years, and twenty months for allogeneic and autologous HCT respectively. For patients who underwent HCT primarily for treatment of their CD there have been no mortalities related to transplant complications. CONCLUSION： Overall these preliminary data suggest that both allogeneic and autologous HCT may be effective in inducing remission in refractory CD. This supports the hypothesis that the hematolymphatic cells play a key role in CD and that resetting of the immune system may be a critical approach in the management or cure of CD.

关键词： Crohn's disease Inflammatory bowel disease Bone marrow transplant Stem cells Hematopoietic cell transplantation

Innovating for Health in China’s Greater Bay Area

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China CDC weekly 2022年第1期4卷 1-3页

作者： Feichau Pang Puihong Chung Gabriel m leung School of Public Health LKS Faculty of MedicineThe University of Hong KongHong KongChina

The Success of World metropolitan and Bay Areas The Tokyo Bay Area,the New York metropolitan Area,and the San Francisco Bay Area are leading regions for science and *** share an economic transformation from industrial or manufacturing bases to predominantly service-based economies with this sector contributing 75%of their gross domestic product(GDP)in *** companies in these locations accounted for 60%of the revenue of the top 100 global tech companies in 2018(1).The success of these locations stems from the convergence of academia,technology giants,government support,and a high density of investors,as well as innovative entrepreneurs(2).

关键词： companies revenue bases

Treatment of pediatric refractory Crohn’s disease with thalidomide

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World Journal of Gastroenterology 2011年第10期17卷 1286-1291页

作者： Ying-Kit leung Department of Gastroenterology Children’s Hospital of Fudan University

AIm: To assess the efficacy and tolerability of thalidomide in pediatric Crohn's disease (CD). mETHODS: Six patients with refractory CD received thalidomide at an initial dose of 2 mg/kg per day for one month, then increased to 3 mg/kg per day or decreased to 1 mg/kg per day, and again further reduced to 0.5 mg/kg per day, according to the individual patient's response to the drug. RESULTS: Remission was achieved within three months. Dramatic clinical improvement was demonstrated after thalidomide treatment. Endoscopic and pathological improvements were also observed after thalidomide treatment, which was well tolerated by all patients. CONCLUSION: Thalidomide is a useful drug for pediatric refractory CD.

关键词： Inflammatory bowel disease Thalidomide Tumor necrosis factor-m Children

Evaluation and management of the child with hypothyroidism

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World Journal of Pediatrics 2019年第2期15卷 124-134页

作者： Alexander K.C.leung Alexander A.C.leung Department of Pediatrics The University of Calgaryand The Alberta Children's Hospital#200233-16th Avenue NWCalgaryAB T2M 0H5Canada Department of medicine The University of CalgaryCalgaryABCanada

Background Thyroid hormones are critical for early neurocognitive development as well as growth and development throughout *** recognition and treatment of hypothyroidism is,therefore,of utmost importance to optimize physical and neurodevelopmental *** sources A Pubmed search was completed in Clinical Queries using the key terms 'hypothyroidism'.Results Hypothyroidism may be present at birth (congenital hypothyroidism) or develop later in life (acquired hypothyroidism).Thyroid dysgenesis and dyshormonogenesis account for approximately 85% and 15% of permanent cases of congenital primary hypothyroidism,*** than 95% of infants with congenital hypothyroidism have few,if any,clinical manifestations of *** screening programs allow early detection of congenital *** developed countries,Hashimoto thyroiditis is the most common cause of goiter and acquired hypothyroidism in children and ***,iodine deficiency associated with goiter is the most common cause of *** hypothyroidism is uncommon and may be associated with other congenital syndromes and deficiencies of other pituitary *** of the clinical features would allow prompt diagnosis and institution of *** To optimize neurocognitive outcome in infants with congenital hypothyroidism,treatment with levothyroxine should be started as soon as possible,preferably within the first 2 weeks of *** with acquired hypothyroidism should also be treated early to ensure normal growth and development as well as cognitive *** target is to keep serum TSH mIU/L and to maintain serum free T4 or total T4 within the upper half of the age-specific reference range,with elimination of all symptoms and signs of hypothyroidism.

关键词： Dysgenesis Dyshormonogenesis Hashimoto thyroiditis Hypothyroidism Iodine deficiency Levothyroxine mental retardation Stunted growth

Recent advances and future challenges for mobile network virtualization

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Science China(Information Sciences) 2017年第4期60卷 5-16页

作者： Xiaofeng TAO Yan HAN Xiaodong XU Ping ZHANG Victor C.m.leung National Engineering Lab for mobile Network Technologies Beijing University of Posts and Telecommunications State Key Lab of Networking & Switching Technology Beijing University of Posts and Telecommunications Department of Electrical and Computer Engineering The University of British Columbia

Recently, network function virtualization(NFV) was proposed as a paradigm shift in the telecommunication industry. Both industry and academia have drawn significant attention in mobile network *** decouples the software implementation of network functions from the underlying hardware, leading to considerable reductions in operating expenses(OPEX) and capital expenses(CAPEX), and facilitating the network deployment. However, as an emerging technology, NFV brings both challenges and opportunities in developing new architectures, applying and deployment. In this paper, we first survey the related work of NFV, and then propose promising research directions in this area.

关键词： network function virtualization mobile networks software defined networking network functions 5G network slicing

Decontamination of Landfill Leachate by Soil Infiltration

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Biomedical and Environmental Sciences 1989年第4期2卷 341-357页

作者： m.H.WONG K.C.leung Department of Biology Hong Kong Baptist CollegeKowloonHong Kong Department of Biology The Chinese University of Hong KongShatinHong Kong

A soil column study was conducted to evaluate the efficiency of soil to attenuate pollutants in landfill *** was found that more than 60% of the initial alkalinity,COD,and total nitrogen was removed after the leachate had percolated through the soil *** effi- ciencies were observed for the removal of dissolved cations,ammonia nitrogen,and nitrate *** previously percolated leachate was recirculated through the soil column,sig- nificant removal(93.6%)of ammonia nitrogen was ***,a further reduction in COD,total nitrogen,nitrate nitrogen,and potassium was *** tests of seed germi- nation and root growth of Brassica chinensis were performed to compare the phytotoxicities of untreated,percolated,and recirculated *** phytotoxicity was reduced by both treatments,with the greatest detoxification observed in the leachate recirculation *** values ofpH and Olsen phosphorus were significantly reduced(Pmn *** significant increases(Pms of nitrogen,exchangeable sodium percentage(ESP),potassium,magnesium,zinc,and iron were ***,ESP,potassium,magnesium,sodium,iron,and various forms of nitrogen accu- mulated at the soil surface(10 cm).On the other hand,manganese was deposited at 20 to 50 cm below the soil surface of the treated column.1989 Academic ***.

关键词： In