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Polyoxypregnanes as safe, potent, and specific AbCb1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo

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Acta Pharmaceutica Sinica b 2021年第7期11卷 1885-1902页

作者： Xu Wu Chun Yin Jiang Ma Stella Chai Chunyuan Zhang Sheng Yao Onat Kadioglu thomas Efferth Yang Ye Kenneth Kin-wah to Ge Lin School of biomedical Sciences Faculty of Medicinethe Chinese University of Hong KongHong Kong 999077China Joint Research Laboratory of Promoting Globalization of traditional Chinese Medicines between the Chinese University of Hong Kong and Shanghai Institute of Materia Medica Chinese Academy of SciencesHong Kong 999077China State Key Laboratory of Drug Research and Natural Products Chemistry Department Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Pharmaceutical biology Johannes Gutenberg UniversityMainz 55099Germany School of Pharmacy Faculty of Medicinethe Chinese University of Hong KongHong Kong 999077China Laboratory of Molecular Pharmacology Department of PharmacologySchool of PharmacySouthwest Medical UniversityLuzhou 646000China

Multidrug resistance(MDR)mediated by AtP binding cassette subfamily b member 1(AbCb1)is significantly hindering effective cancer ***,currently,no AbCb1-inhibitory drugs have been approved to treat MDR cancer clinically,mainly due to the inhibitor specificity,toxicity,and drug ***,we reported that three polyoxypregnanes(POPs)as the most abundant constituents of Marsdenia tenacissima(***)were novel AbCb1-modulatory pro-drugs,which underwent intestinal microbiota-mediated biotransformation in vivo to generate active *** metabolites at non-toxic concentrations restored chemosensitivity in AbCb1-overexpressing cancer cells via inhibiting AbCb1 efflux activity without changing AbCb1 protein expression,which were further identified as specific non-competitive inhibitors of AbCb1 showing multiple binding sites within AbCb1 drug *** POPs did not exhibit AbCb1/drug metabolizing enzymes interplay,and their repeated administration generated predictable pharmacokinetic interaction with paclitaxel without obvious toxicity in *** further showed that these POPs enhanced the accumulation of paclitaxel in tumors and overcame AbCb1-mediated *** results suggested that these POPs had the potential to be developed as safe,potent,and specific pro-drugs to reverse AbCb1-mediated *** work also provided scientific evidence for the use of *** in combinational chemotherapy.

关键词： Multidrug resistance AbCb1 Polyoxypregnane Combination chemotherapy Marsdenia tenacissima

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Investigations of photosynthetic electron flow in leaves using P700 redox kinetics

Investigations of photosynthetic electron flow in leaves usi...

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纪念殷宏章先生百年诞辰暨全国光合作用学术研讨会

作者： wah Soon CHOW Husen JIA Alexander b. HOPE Photobioenergetics Group Research School of Biological Sciences The Australian National University Canberra ACT 0200 Australia School of biological Sciences Flinders University Faculty of Science and Engineering GPO Box 2100 Adelaide SA 5001 Australia

＜正＞When P700, the special chlorophyll （Chl） pair in Photosystem I （PS I）, undergoes photo-oxidation, its absorbance at 810 nm increases. We utilized this near-infra-red signal （reference wavelength 870 nm） to... 详细信息

关键词： Photosynthetic electron flow P700 redox kinetics

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Effect of melting heat transfer on peristalsis in the presence of thermal radiation and Joule heating

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International Journal of biomathematics 2015年第6期8卷 37-56页

作者： t. Hayat Maimona Rafiq b. Ahmad H. Yasmin Department of Mathematics Quaid-i-Azam University 45320 Islamabad 44000 Pakistan Department of MathematicsFaculty of Science King Abdulaziz University Jeddah 21589 Saudi Arabia Department of MathematicsCOMSAtS Institute of Information technology G. t. Road Wah Cantt 47040 Pakistan

Mathematical model is developed for peristaltic flow of viscous fluid through a compliant wall channel subject to melting heat transfer. Fluid is incompressible and magnetohydrodynamic. Analysis has been performed in the presence of Joule heating and thermal radiation. Solutions for small wave number are obtained. Physical quantities of interest are examined for various parameters of interest.

关键词：焦耳加热热辐射蠕动传热热作用熔融粘性流体数学模型

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Validation of genetic variants associated with metabolic dysfunctionassociated fatty liver disease in an ethnic Chinese population

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World Journal of Hepatology 2020年第12期12卷 1228-1238页

作者： Guan Huei Lee wah wah Phyo Wai Mun Loo Raymond Kwok taufique Ahmed Asim Shabbir Jimmy So Calvin Jianyi Koh Juanda Leo Hartono Mark Muthiah Kieron Lim Poh Seng tan Yin Mei Lee Seng GeeLim Yock Young Dan Division of Gastroenterology and Hepatology Department of MedicineNational University Health SystemSingapore 119228Singapore Yong Loo Lin School of Medicine National University of SingaporeSingapore 117597Singapore Department of Medicine Khoo Teck Puat HospitalSingapore 768828Singapore Department of Surgery National University Health SystemSingapore 119228Singapore

bACKGROUND Genetic factors play an important role in the pathogenesis and development of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM to study the association of single nucleotide polymorphisms(SNPs),previously identified in Western populations,with the risk of MAFLD in a Singapore Chinese population and their interactions with environmental and medical risk *** A retrospective case-control study was conducted with 72 MAFLD cases and 72 controls with no hepatic steatosis on computed tomography,magnetic resonance imaging,or controlled attenuation parameter *** were recruited from two tertiary *** alleles such as NCAN,GCKR,LYPLAL1,PNPLA3,PPP1R3b,FDFt1,COL13A1,EFCAb4b,PZP,and tM6SF2 were genotyped using the taqMan®Predesigned SNP Genotyping *** Weight and body mass index(bMI)were 1.2-times higher in patients(70.6 kg,95%confidence interval[CI]:57.1-84.1 vs 60.8 kg,95%CI:48.5-73.1,Ptively).the prevalence of diabetes mellitus in patients was 40.3%and 20.8%in controls(P=0.011).Patients had higher mean triglycerides than controls(Pto be associated with MAFLD(43.4%CC vs 69.7%GG,P=0.017,and 44.8%CG vs 69.7%GG,P=0.022).In multivariable analysis,hypertriglyceridemia(odds ratio[OR]:2.0495%CI:1.3-3.1,P=0.001),bMI(OR:1.295%CI:1.1-1.4,Pted with MAFLD(area under the receiver operating characteristic curve of 0.823).CONCLUSION Among the Chinese population of Singapore,PNPLA3 homozygous GG allele is a strong predictor of MAFLD,whereas LYPLAL1,GCKR,FDFt1,COL13A1,PZP,and tM6SF2 are not significantly ***,high bMI,and PNPLA3 GG are independent predictors of MAFLD.

关键词： Single nucleotide polymorphism PNPLA3 Genotyping Metabolic dysfunction-associated fatty liver disease Non-alcoholic steatohepatitis Hypertriglyceridemia body mass index Waist-hip ratio,Screening Hepatic steatosis

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Expression and prognostic role of molecular markers in 99 KIt-positive gastric stromal tumors in taiwan Residents

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World Journal of Gastroenterology 2006年第4期12卷 595-602页

作者： tsung-Hui Hu Seng-Kee Chuah Jui-Wei Lin Yi-Chun Chiu Chi-Sin Changchien Chih-Chi Wang Yaw-Sen Chen Li-Na Yi King-wah Chiu Chuan-Mo Lee Division of Gastroenterology Department of Internal MedicineChanggung Memorial Hospital Kaohsiung Taiwan China Department of Pathology Chang Gung Memorial Hospital Kaohsiung Taiwan China Department of Surgery Chang Gung Memorial Hospital Kaohsiung Taiwan China

瞄准：为了阐明，象肿瘤那样的三个分子的标记的预示的角色和关系压制，增殖或基因 p53 房间原子抗原(PCNA ) 和在胃的基质肿瘤的 Ki-67。方法：108 的一个总数通过手术 resected 胃的平滑肌肿瘤标本从 1987 年 1 月被收集到 1999 年 12... 详细信息

瞄准：为了阐明，象肿瘤那样的三个分子的标记的预示的角色和关系压制，增殖或基因 p53 房间原子抗原(PCNA ) 和在胃的基质肿瘤的 Ki-67。方法：108 的一个总数通过手术 resected 胃的平滑肌肿瘤标本从 1987 年 1 月被收集到 1999 年 12 月。Immunohistochemical 研究与 p53， PCNA，和 Ki-67 的抗体在 108 个 CD117 积极的肿瘤中的 99 个的石蜡节上被执行。三个分子的标记的 Immunoreactivity 被把索引标记记录(李， %) 并且为临床病理和幸存关联被分析。结果：99 个盒子，染色的免疫表明 52 个病人(52.5%) 有 p53，并且 37 个病人(37.3%) 有 Ki-67 免疫反应(定义为李的 >10%) 。所有病人(100%) 有 PCNA 免疫反应从 12% ～ 93% 李，划分了成由高或低中部。统计表明三个标记的李断然相关到对方(P<0.01 ) 并且到显微镜的肿瘤有丝分裂的计数(P<0.001 ) 。由联合，有 >=2 标记的病人(积极或高) 在肿瘤有早肿瘤复发(P<0.001 ) 和相反的结果(P<0.001 ) 。Univariate 分析显示有肿瘤尺寸 >5 厘米(P=0.003 ) 的病人，肿瘤有丝分裂 >5/50 HPF (P<0.001 ) ， p53 免疫反应(P=0.001 ) ， Ki-67 免疫反应(P=0.026 ) ，高级李普克纳(P=0.015 ) 和男性(P=0.036 ) 是为早疾病复发的六个预言者。随后多，变量分析表明有丝分裂的计数，肿瘤尺寸，和 p53 免疫反应是为免费的疾病和外套的三个独立预示的因素病人的幸存。由为组织的三个独立预示的因素的联合，我们发现更高的肿瘤再发率(P<0.001 ) 和更短的幸存(P<0.001 ) 与增加因素在组存在。结论：我们首先在大意提供三个分子的标记的预示的价值和连接。三个因素(p53，肿瘤尺寸，和肿瘤有丝分裂) 的联合比任何单个因素提供预后的更强大的预言。

关键词：基因表达分子标记胃肿瘤台湾省中国

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Novel N-heteroaromatic dyes for textile substrates

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Chinese Chemical Letters 2014年第8期25卷 1165-1168页

作者： Kim-Hung Lam Sarah Sze-wah Ho Pik-Ling Lam Johnny Cheuk-On tang Zhao-Xiang bian Albert Sun-Chi Chan Hua Li Wai-Yeung Wong Chung-Hin Chui Department of Applied biology and Chemical technology Institute of Textile and Clothing The Hong Kong Polytechnic University Clinical Division School of Chinese Medicine Hong Kong Baptist University Institute of Molecular Functional Materials Department of Chemistry and Institute of Advanced Materials Hong Kong Baptist University College of Life and Environmental Sciences Minzu University of China HKbU Institute of Research and Continuing Education Shenzhen Virtual University Park

this study reports the synthesis and characterization of quinoline derivatives. the synthesized quinoline compounds were applied to the dyeing treatment of acrylic fabrics. the color fastness to washing and light of quinoline compound-dyed fabrics was examined. Human skin HaCat cell line was also used for the skin cytotoxicity evaluation of the quinoline compound-dyed acrylic fabrics.

关键词： Acrylic fabrics Fluorescent Quinoline dyes Skin cytotoxicity

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Inhibitory activities of microalgal extracts against Epstein-barr virus DNA release from lymphoblastoid cells

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Journal of Zhejiang University-Science b(biomedicine & biotechnology) 2011年第5期12卷 335-345页

作者： Yih-Yih KOK Wan-Loy CHU Siew-Moi PHANG Shar Mariam MOHAMED Rakesh NAIDU Pey-Jiun LAI Shui-Nyuk LING Joon-wah MAK Patricia Kim-Chooi LIM Pauline bALRAJ Alan Soo-beng KHOO Division of Human biology International Medical University Institute of biological Sciences Faculty of Scienceand Institute of Ocean and Earth Sciences(IOES)University of Malaya Faculty of Medicine University of Malaya School of Medicine and Health Sciences Monash University Molecular Pathology Unit Institute for Medical ResearchJalan Pahang

this study aimed to assess the inhibitory activities of methanol extracts from the microalgae Ankistrodesmus convolutus,Synechococcus elongatus,and Spirulina platensis against Epstein-barr virus(EbV) in three burkitt's lymphoma(bL) cell lines,namely Akata,b95-8,and *** antiviral activity was assessed by quantifying the cell-free EbV DNA using real-time polymerase chain reaction(PCR) *** methanol extracts from Ankistrodesmus convolutus and Synechococcus elongatus displayed low cytotoxicity and potent effect in re-ducing cell-free EbV DNA(EC50th a high therapeutic index(>28 000).After fractionation by column chromatography,the fraction from Synechococcus elongatus(SEF1) reduced the cell-free EbV DNA most effectively(EC50=2.9 μg/ml,therapeutic index>69).Upon further fractionation by high performance liquid chromatography(HPLC),the sub-fraction SEF1'a was most active in reducing the cell-free EbV DNA(EC50=1.38 μg/ml,therapeutic index>14.5).this study suggests that microalgae could be a potential source of antiviral compounds that can be used against EbV.

关键词： Microalgae Ankistrodesmus convolutus Synechococcus elongatus Spirulina platensis Lymphoblastoid cells Epstein-barr virus(EbV)

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Rociletinib(CO-1686) enhanced efficacy of chemotherapeutic agents in AbCG2-overexpressing cancer cells in vitro and in vivo

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中国药理学与毒理学杂志 2019年第10期 891-892页

作者： ZENG Fan-pu WANG Fang ZHENG Zong-heng CHEN Zhen Kenneth Kin wah to ZHANG Hong HAN Qian FU Li-wu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute Sun Yat-Sen University Cancer Center

the abnormal expression and function of AtP-binding cassette subfamily G member 2(AbCG2) is correlated with development of multidrug resistance(MDR), and lead to lower response to ***, there is no FDA-approved commercial MDR modulator for clinical use. Here, We found rociletinib(CO-1686), a mutant-selective epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(tKI), significantly improved the efficacy of substrate chemotherapeutic agents in AbCG2-overexpressing cancer cells and also in AbCG2-overexpressing S1-MI-80 cell xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in AbCG2-overexpressing cancer cells, rociletinib inhibited AbCG2-mediated drug efflux, and increased intracellular accumulation of AbCG2 probe substrates. Moreover, rociletinib, inhibited the AtPase activity, and competed with [125 I] iodoarylazidoprazosin(IAAP) photolabeling of AbCG2. the expression of AbCG2 at protein and m RNA levels was not altered when AbCG2-overexpressing cells were treated with rociletinib. In addition, rociletinib did not inhibit Erb b downstream signaling of AKt and ERK and their phosphorylations. the all results showed that rociletinib increased the accumulation of substrates in cells by inhibiting the efflux function of AbCG2, and reversed AbCG2-related MDR. therefore, rociletinib might be useful in developing combination chemotherapy in the patients with AbCG2-overexpressing MDR tumors.

关键词： rociletinib combination chemotherapy chemotherapeutic agents

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甲型流感病毒NS1抗原捕获ELISA的建立

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中华微生物学和免疫学杂志 2010年第6期30卷 566-569页

作者：丁细霞 Hoi-wah tsoi 丘立文王压娣袁国勇车小燕南方医科大学珠江医院医学检验中心广州510282 香港大学微生物系

目的建立基于单克隆抗体的甲型流感病毒非结构蛋白1（NS1）抗原检测的酶联免疫吸附（ELISA）法.方法用甲型流感病毒NS1特异性单克隆抗体,通过抗体的优化组合,建立双抗体夹心抗原捕获ELISA,检测不同来源的流感病毒及副流感病毒.结果 ... 详细信息

目的建立基于单克隆抗体的甲型流感病毒非结构蛋白1（NS1）抗原检测的酶联免疫吸附（ELISA）法.方法用甲型流感病毒NS1特异性单克隆抗体,通过抗体的优化组合,建立双抗体夹心抗原捕获ELISA,检测不同来源的流感病毒及副流感病毒.结果对多种抗体组合进行反复筛选,最终确定了特异性检测到甲型流感病毒的NS1蛋白,而与乙型流感病毒和副流感病毒不发生交叉反应的最佳抗体组合.该方法检测重组H5N1-NS1[A/HongKong/486/97（H5N1）-NS1和A/Vietnam/1194/04（H5N1）-NS1]蛋白的灵敏度最低检测值分别为15.6 ng/ml和240 pg/ml.结论成功建立了甲型流感病毒NS1抗原捕获ELISA,为建立甲型流感病毒感染早期诊断新方法奠定基础.

关键词：甲型流感病毒非结构蛋白单克隆抗体酶联免疫吸附试验

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Myeloid-derived suppressor cells promote b-cell production of IgA in a tNFR2-dependent manner

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Cellular & Molecular Immunology 2017年第7期14卷 597-606页

作者： Xia Xu Qinghong Meng Ulrike Erben Peigang Wang Rainer Glauben Anja A Kühl Hao Wu Chung wah Ma Minghua Hu Yuanyuan Wang Wei Sun Junying Jia Xinyi Wu Wei Chen britta Siegmund Zhihai Qin Key Laboratory of Protein and Peptide Pharmaceuticals Chinese Academy of Sciences-University of Tokyo Joint Laboratory of Structural Virology and ImmunologyInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Medical Department for Gastroenterology Infectious Diseases and Rheumatology/Research Center ImmunoSciencesCampus Benjamin FranklinCharité-Universitätsmedizin BerlinBerlin 12200Germany Infinitus Chinese Herbal Immunity Research Centre Guangzhou 510665China berlin Institute for Medical Systems biology Max Delbrück Center for Molecular Medicine Berlin-BuchBerlin 13125Germany

Myeloid-derived suppressor cells(MDSCs)are well known for their capacity to suppress antitumor t-cell responses,but their effects on b-cell function and antibody production remain ***,we found that MDSCs that accumulated around the germinal center in the spleen of tumor-bearing mice co-located with b *** the presence of MDSCs,the antibody reaction to a surrogate antigen was significantly enhanced in mice,especially the immunoglobulin(Ig)A ***-culture with MDSCs promoted both proliferation and differentiation of b cells into IgA-producing plasma cells in ***,the cross talk between MDSCs and b cells required cell-cell *** from tumor necrosis factor receptor(tNFR)2^(−/−)mice,but not from tNFR1^(−/−)mice,failed to promote b-cell *** investigation suggested that interleukin-10 and transforming growth factor-β1 were crucial for the MDSC-mediated promotion of IgA *** results demonstrate a novel mechanism of MDSC-mediated immune regulation during tumor growth.

关键词： b cells IgA MDSCs tNFR2

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