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Molecular signaling mechanisms of apoptosis in hereditary non-polyposis colorectal cancer

World Journal of Gastrointestinal Pathophysiology 2012年第3期3卷 71-79页

作者： Samar Hassen nawab Ali Parimal Chowdhury Department of Applied Science College of Science and Mathematics University of ArkansasLittle Rock AR 72204 United States Department of Physiology and Biophysics University of Arkansas for Medical SciencesLittle Rock AR 72205 United States

Colorectal cancer is the second most leading cause of cancer related deaths in the western countries. One of the forms of colorectal cancer is hereditary non-polyposis colorectal cancer (HNPCC), also known as "Lynch syndrome". It is the most common hereditary form of cancer accounting for 5%-10% of all colon cancers. HNPCC is a dominant autosomal genetic disorder caused by germ line mutations in mismatch repair genes. Human mismatch repair genes play a crucial role in genetic stability of DNA, the inactivation of which results in an increased rate of mutation and often a loss of mismatch repair function. Recent studies have shown that certain mismatch repair genes are involved in the regulation of key cellular processes including apoptosis. Thus, differential expression of mismatch repair genes particularly the contributions of MLH1 and MSH2 play important roles in therapeutic resistance to certain cytotoxic drugs such as cisplatin that is used normally as chemoprevention. An understanding of the role of mismatch repair genes in molecular signaling mechanism of apoptosis and its involvement in HNPCC needs attention for further work into this important area of cancer research, and this review article is intended to accomplish that goal of linkage of apoptosis with HNPCC. The current review was not intended to provide a comprehensive enumeration of the entire body of literature in the area of HNPCC or mismatch repair system or apoptosis; it is rather intended to focus primarily on the current state of knowledge of the role of mismatch repair proteins in molecular signaling mechanism of apoptosis as it relates to understanding of HNPCC.

关键词： Colorectal cancer Hereditary non-polyposis colorectal cancer Apoptosis Molecular signaling mechanisms DNA mismatch repair proteins

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Geochemistry and in-situ U-Th/Pb Geochronology of the Jambil Meta-Carbonatites, Northern Pakistan: Implications on Petrogenesis and Tectonic Evolution

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Journal of Earth Science 2023年第1期34卷 70-85页

作者： Asad Khan Shah Faisal Kyle P.Larson Delores M.Robinson Huan Li Zaheen Ullah Mark Button Javed nawab Muhammad Farhan Liaqat Ali Muhammad Ali Department of Geology FATA UniversityFR Kohat26100Pakistan National Center of Excellence in Geology University of PeshawarPeshawar25130Pakistan Department of Earth Environmental and Geographic SciencesUniversity of British ColumbiaOkanaganKelownaBCVIV 1V7Canada Department of Geological Sciences the University of AlabamaBevill BuildingTuscaloosaAlabama35487USA Key Laboratory of Metallogenic Prediction of Nonferrous Metals and Geological Environment Monitoring Ministry of EducationSchool of Geosciences and Info-PhysicsCentral South UniversityChangsha410083China Department of Environmental Sciences Abdul Wali Khan UniversityMardan23200Pakistan Marine Science Department Zhejiang UniversityZhoushan316021China

The putative Jambil meta-carbonatites of Swat,northern Pakistan,occur as discrete intrusions into the Proterozoic Manglaur Formation,which are difficult to be distinguished from nearby calc-silicate marble because both rock types experienced regional metamorphism during Himalayan orogenesis that resulted in similar mosaic textures and mineral *** are often significant repositories of economic mineral resources and,therefore,are important to be distinguished from calc-silicate *** present new geochemical and geochronology data to distinguish between the two rock types and interpret the petrogenesis and tectonic evolution of the Jambil *** rock chemical data from the Jambil meta-carbonatites show characteristically high rare earth element(REE),Sr contents and lack of negative Eu anomaly,consistent with average calcio-carbonatite values worldwide and an igneous *** than 0.5 wt.% SrO in the metacarbonatites and SrO> 0.15 wt.% in constituent rock forming calcite are discriminating signatures of the Jambil ***,the Jambil meta-carbonatites are relatively depleted in Rb,Nb,Ta,Ti,Zr and Hf,relatively enriched in Ba,Th,Sr,and have a high LREE/HREE ratio when normalized to primitive *** carbon and oxygen isotope compositions vary from-3.5‰ to-4.3‰and from 9.7‰ to 12.3‰,*** geochemical characteristics indicate generation of the carbonatites through small degree of partial melting from a carbonated eclogitic ***-situ,U/Pb analysis of titanite indicates that the Jambil meta-carbonatites were emplacement at 438 ±3 *** combined with regional geological observations,we interpret the emplacement of the Jambil metacarbonatites to have taken place during the Silurian back arc extension within greater Gondwana and mark a transition from a compressional tectonic regime,brought about by collision of microcontinental blocks along the northern margin of Gondwana,to post-orogenic

关键词： Swat N Pakistan meta-carbonatites geochemistry LA-ICP-MS titanite&monazite UTh/Pb geochronology C and O isotopes Gondwana margin

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近红外成像技术对胃癌的示踪作用研究

近红外成像技术对胃癌的示踪作用研究

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作者： nawab Ali（阿里）南京大学

学位级别：硕士

实验目的探讨荧光染料靛青绿(ICG)在近红外成像仪器中对裸鼠胃癌移植瘤显影的最佳剂量;筛选出胃肿瘤在光学成像仪器中最佳显影时间;用光学成像系统确定肿瘤能够显影的最小瘤径比.实验方法采用人胃癌细胞株MKN-45建立裸鼠皮下移植瘤模型...

实验目的探讨荧光染料靛青绿(ICG)在近红外成像仪器中对裸鼠胃癌移植瘤显影的最佳剂量;筛选出胃肿瘤在光学成像仪器中最佳显影时间;用光学成像系统确定肿瘤能够显影的最小瘤径比.实验方法采用人胃癌细胞株MKN-45建立裸鼠皮下移植瘤模型;分别给荷瘤裸鼠尾静脉注射不同剂量的ICG (0.25mg/kg,0.5mg/kg,1mg/kg、2mg/kg、4mg/kg)来确定肿瘤显影的最佳剂量。利用近红外成像设备对荷瘤裸鼠进行不同时间间隔的成像,获得最佳显影时间。在裸鼠接种人胃癌细胞株时尾静脉注射ICG,以确定肿瘤能够显影的最小瘤径比。实验结果0.25mg/kg,0.5mg/kg,1.0mg/kg剂量的ICG在近红外成像仪上显示出低荧光强度,不适合用于肿瘤的显影,2.0mg/kg ICG肿瘤在近红外成像仪上荧光强度最高,更适合用于显影。近红外成像仪能够识别出直径在3.0mm3,5.0mm3以上的肿瘤。结论2mg/kg ICG是近红外成像仪器用于实验动物肿瘤的显影的最佳剂量,在荷瘤鼠注射ICG后120h-144h,近红外成像仪器可更好对实验动物肿瘤进行显影,近红外成像仪可检测到直径在3.0mm3以上的肿瘤。

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Prevalent fecal contamination in drinking water resources and potential health risks in Swat, Pakistan

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Journal of Environmental Sciences 2018年第10期30卷 1-12页

作者： Kifayatullah Khan Yonglong Lu Mian Abdal Saeed Hazrat Bilal Hassan Sher Hizbullah Khan Jafar Ali Pei Wang Herman Uwizeyimana Yvette Baninla Qifeng Li Zhaoyang Liu Javed nawab Yunqiao Zhou Chao Su Ruoyu Liang Department of Environmental and Conservation Sciences University of SwatSwat 19130 Pakistan State Key Lab of Urban and Regional Ecology Research Center for Eco-Environmental Sciences Chinese Academy of SciencesBeijing 100085 China University of Chinese Academy of Sciences Beijing 100049 China Center for Plant Science and Biodiversity University of SwatSwat 19130 Pakistan Department of Environmental Sciences University of Peshawar Peshawar 25120 Pakistan Laboratory of Environmental Nanomaterials Research Center for Eco-Environmental Sciences Chinese Academy of SciencesBeijing 100085 China Department of Environmental Sciences Abdul Wali Khan UniversityMardan Pakistan

Fecal bacteria contaminate water resources and result in associated waterborne *** study assessed drinking water quality and evaluated their potential health risks in Swat, Pakistan. Ground and surface drinking water were randomly collected from upstream to downstream in the River Swat watershed and analyzed for fecal contamination using fecal indicator bacteria（Escherichia coli） and physiochemical parameters（potential of hydrogen, turbidity, temperature, electrical conductivity, total dissolved solid, color, odor and taste）. The physiochemical parameters were within their safe limits except in a few locations, whereas, the fecal contaminations in drinking water resources exceeded the drinking water quality standards of Pakistan Environmental Protection Agency（Pak-EPA）,2008 and World Health Organization（WHO）, 2011. Multivariate and univariate analyses revealed that downstream urbanization trend, minimum distance between water sources and pit latrines/sewerage systems, raw sewage deep well injection and amplified urban,pastures and agricultural runoffs having human and animal excreta were the possible sources of contamination. The questionnaire survey revealed that majority of the local people using 10–20 years old drinking water supply schemes at the rate of 73% well supply,13% hand pump supply, 11% spring supply and 3% river/streams supply, which spreads high prevalence of water borne diseases including hepatitis, intestinal infections and diarrhea, dysentery, cholera, typhoid fever, jaundice and skin diseases in children followed by older and younger adults.

关键词： Drinking water Fecal contamination Health risks Pakistan

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早期认知障碍患者的认知功能和双重任务步态的临床研究

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中国康复医学杂志 2021年第5期36卷 546-552页

作者：钟倩朱奕吴含高雅新孙翠云 nawab Ali 吴希希王彤南京医科大学第一临床医学院江苏省南京市210029 南京医科大学第一附属医院康复医学中心南京大学医学院附属鼓楼医院康复医学科江苏省人民医院钟山康复分院

目的:探索早期认知障碍患者双重任务下步态参数与认知功能之间的关系。方法:本研究共纳入轻度认知障碍者(MCI)20例,主观认知下降者(SCD)34例,认知功能正常者(NC)24例,均采用三维运动捕捉系统及建模仿真分析软件进行单任务及双重任务下... 详细信息

目的:探索早期认知障碍患者双重任务下步态参数与认知功能之间的关系。方法:本研究共纳入轻度认知障碍者(MCI)20例,主观认知下降者(SCD)34例,认知功能正常者(NC)24例,均采用三维运动捕捉系统及建模仿真分析软件进行单任务及双重任务下步态参数(步长、步速、步频、步态周期)的采集与分析。结果:双重任务下MCI组步频(步/min)(102.173±11.941)小于SCD组步频(110.500±10.435)(P<0.01);MCI组步态周期(s)(1.209±0.133)较NC组步态周期(1.122±0.117)和SCD组步态周期长(1.116±0.102)(P<0.01)。NC组在双重任务下步长(m)及步速(m/s)下降(P<0.01);SCD组在双重任务下步长、步速及步频均下降(P<0.05);MCI组在双重任务下步速、步频及步态周期均下降(P<0.01)。相关性分析显示步速与记忆和语言功能存在正性相关(P=0.005,r=0.312;P=0.014,r=0.277;P=0.005,r=0.317),步频与记忆功能存在正性相关(P=0.010,r=0.289;P=0.012,r=0.283),步态周期与记忆功能存在负性相关(P=0.001,r=﹣0.354),与执行功能存在正性相关(P=0.022,r=0.258)。结论:双重任务下步态参数可作为早期评估认知功能的辅助指标。

关键词：轻度认知障碍主观认知下降双重任务步态分析

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Dichloroacetic Acid (DCA)-Induced Cytotoxicity in Human Breast Cancer Cells Accompanies Changes in Mitochondrial Membrane Permeability and Production of Reactive Oxygen Species

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Journal of Cancer Therapy 2014年第13期5卷 1234-1248页

作者： Zeiyad Alkarakooly Surya P. Kilaparty Qudes A. Al-Anbaky Mohammad Saeed Khan nawab Ali College of Science University of Diyala Baquba Iraq Department of Biology College of Arts Letters and Sciences University of Arkansas at Little Rock Little Rock USA Department of Internal Medicine Division of Rheumatology University of Arkansas for Medical Sciences Little Rock USA

Cancer cells utilize cytosolic glycolysis for their energy production even in the presence of adequate levels of oxygen (Warbug effect) due to mitochondrial defects. Dichloroacetic acid (DCA) shifts cytosolic glucose metabolism to aerobic oxidation by inhibiting mitochondrial pyruvate dehydrogenase kinase (PDK) and increasing pyruvate uptake. Therefore, DCA has potential in reversing the glycolytic metabolism defect in cancerous cells. DCA is also known to induce apoptosis in a number of cancer cell lines, the mechanism of which is not well understood. In this study, an attempt has been made to investigate the effects of DCA on aggressive human breast cancer (MCF-7) cells as compared with less aggressive mouse osteoblastic (MC3T3) cells. Cell cytotoxicity was determined by MTT, crystal violet and Trypan blue exclusion assays. Western blot was used to detect any changes in the expression of apoptotic markers. Flow cytometry was used to measure apoptotic and necrotic effects of DCA. Mitochondrial integrity was determined by change in mitochondrial membrane potential (Δψm), whereas oxidative damage was determined by production of reactive oxygen species (ROS). DCA caused a concentration-dependent cytotoxicity both in MCF-7 and MC3T3 cell lines. MCF-7 cells were most affected. Flow cytometry results showed a significantly higher apoptosis in MCF-7 even at lower concentrations of DCA. However, higher concentrations of DCA were necrotic. Western blotting showed an increased expression of Mn-SOD-1 upon DCA treatment. Further, DCA decreased Δψm and increased ROS production. The effects of DCA were more pronounced on MCF-7 cells as compared to MC3T3 cells. Our results suggest that DCA-induced cytotoxicity in cancerous cells is mediated via changes in Δψm and production of ROS.

关键词： Breast Cancer Dichloroacetic Acid DCA Cancer Therapy Anticancer Agents Apoptosis Mitochondrial Defects Reactive Oxygen Species (ROS)

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美国大学薪酬设计的市场模式研究

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中国科学院院刊 2008年第4期23卷 336-342页

作者：李晓轩刘莹 Samina nawab 中国科学院科技政策与管理科学研究所北京100190

大学是美国基础研究的主力,美国大学特别是研究型大学因其薪酬设计上的市场模式,在科研顶尖人才吸引和争夺上更具灵活性和竞争力。本文讨论了美国大学薪酬设计的市场模式,包括与公务员制的比较、主要特点、资金保障与管理机制等,并初步... 详细信息

大学是美国基础研究的主力,美国大学特别是研究型大学因其薪酬设计上的市场模式,在科研顶尖人才吸引和争夺上更具灵活性和竞争力。本文讨论了美国大学薪酬设计的市场模式,包括与公务员制的比较、主要特点、资金保障与管理机制等,并初步讨论了其运行的法制和文化环境。

关键词：美国大学薪酬设计市场模式

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Geochemistry and in-situ U-Th/Pb geochronology of the Jambil meta-carbonatites， northern Pakistan: Implications on petrogenesis and tectonic evolution

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Journal of Earth Science 2021年

作者： Asad Khan Shah Faisal Kyle P.Larson Delores M.Robinson Huan Li Zaheen Ullah Mark Button Javed nawab Muhammad Farhan Liaqat Ali Muhammad Ali Department of Geology， FATA University National Centre of Excellence in Geology， University of Peshawar Department of Earth， Environmental and Geographic Sciences， University of British Columbia Department of Geological Sciences， The University of Alabama， Bevill Building Key Laboratory of Metallogenic Prediction of Nonferrous Metals and Geological Environment Monitoring， Ministry of Education， School of Geosciences and Info-Physics， Central South University Department of Environmental Sciences， Abdul Wali Khan University Marine Science Department， Zhejiang University

The putative Jambil meta-carbonatites of Swat， northern Pakistan， occur as discrete intrusions into the Proterozoic Manglaur formation， which are difficult to be distinguished from nearby calc-silicate marble because both rock types experienced regional metamorphism during Himalayan orogenesis that resulted in similar mosaic textures and mineral assemblages. Carbonatites are often significant repositories of economic mineral resources and， therefore， are important to be distinguished from calc-silicate marble. We present new geochemical and geochronology data to distinguish between the two rock types and interpret the petrogenesis and tectonic evolution of the Jambil meta-carbonatites. Whole rock chemical data from the Jambil meta-carbonatites show characteristically high Rare Earth Element （REE）， Sr contents and lack of negative Eu anomaly， consistent with average calcio-carbonatite values worldwide and an igneous origin. More than 0.5 wt.% SrO in the meta-carbonatites and SrO >0.15 wt.% in constituent rock forming calcite are discriminating signatures of the Jambil meta-carbonatites. Chemically， the Jambil meta-carbonatites are relatively depleted in Rb， Nb， Ta， Ti， Zr and Hf， relatively enriched in Ba， Th， Sr， and have a high LREE/HREE ratio when normalized to primitive mantle. Their carbon and oxygen isotope compositions vary from -3.5‰ to -4.3‰ and from 9.7‰ to 12.3‰， respectively. These geochemical characteristics indicate generation of the carbonatites through small degree of partial melting from a carbonated eclogitic source. In-situ， U/Pb analysis of titanite indicates that the Jambil meta-carbonatites were emplacement at 438 ± 3 Ma. When combined with regional geological observations， we interpret the emplacement of the Jambil meta-carbonatites to have taken place during the Silurian back arc extension within greater Gondwana and mark a transition from a compressional tectonic regime， brought about by collision of micro-continental blocks along the norther

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认知障碍患者背外侧前额叶功能连接与认知-步行能力的关系研究

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中国康复医学杂志 2021年第12期36卷 1487-1495页

作者：高雅新王彤祁鸣唐银吴含钟倩张玲丁洪园孙翠云田慧芳 nawab Ali 朱奕南京医科大学姑苏学院苏州市立医院南京医科大学附属苏州医院江苏省苏州市215008 南京医科大学第一附属医院康复医学中心南京医科大学第一附属医院放射科南京医科大学医学影像学院南京大学附属鼓楼医院康复医学科南京医科大学康复医学院

目的:本研究采用功能磁共振研究主观认知下降(subjective cognitive decline,SCD)及轻度认知障碍(mild cognitive impairment,MCI)患者的背外侧前额叶(dorsal lateral prefrontal cortex,DLPFC)与运动控制相关脑区的功能连接的特征性改变,并探索其与认知评估及双重任务下步态参数之间的关系。方法:共纳入76例中老年人,根据分组标准分为MCI组(25例)、SCD组(29例)和正常对照(normal control,NC)组(22例)。对入组中老年人进行神经心理学测评、静息态功能磁共振扫描和双重任务步态采集。计算出左侧DLPFC和双侧额上回内侧部、楔前叶、颞中回的功能连接(functional connectivity,FC)值并采用多元线性回归分析其与认知-步行能力之间的关系。结果:三组间年龄、性别比、基础病等基本资料无显著性差异(P>0.05)。三组间多项神经心理学测试结果有显著性差异(P<0.05)。MCI组与SCD组及NC组相比,双侧DLPFC与多个脑区的功能连接增强,且功能连接增强受到执行功能和记忆功能下降、认知消耗增高和双重任务步速减慢的影响(P<0.05)。结论:相比于SCD患者和健康中老年人,MCI患者双侧DLPFC与额、颞、顶叶多个脑区之间的功能连接出现代偿性增强。静息状态下左侧DLPFC功能连接受到记忆、执行功能、双重任务消耗、双重任务步速及年龄影响。

关键词：认知障碍背外侧前额叶功能连接双重任务步行

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ω-3多不饱和脂肪酸抗肿瘤新途径——抑制具核梭杆菌黏附宿主细胞

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微生物学通报 2021年第3期48卷 820-829页

作者：其力格尔 Sadia nawab 范殊璇曹博李雨昕田明振张商浩马伟邓子新上海交通大学生命科学技术学院微生物代谢国家重点实验室上海200240 上海交通大学致远学院上海200240 上海市民办平和双语学校上海200000

【背景】大量文献报道ω-3多不饱和脂肪酸尤其是二十二碳六烯酸(Docosahexaenoic Acid,DHA)与二十碳五烯酸(Eicosapentaenoic Acid,EPA)具有抗肿瘤作用,但是其抗肿瘤机制还不够完善。【目的】探究ω-3多不饱和脂肪酸、具核梭杆菌以及结... 详细信息

【背景】大量文献报道ω-3多不饱和脂肪酸尤其是二十二碳六烯酸(Docosahexaenoic Acid,DHA)与二十碳五烯酸(Eicosapentaenoic Acid,EPA)具有抗肿瘤作用,但是其抗肿瘤机制还不够完善。【目的】探究ω-3多不饱和脂肪酸、具核梭杆菌以及结直肠癌三者之间的关联。【方法】在检测二十二碳六烯酸、二十碳五烯酸、α-亚麻酸(α-Linolenic Acid,ALA)等ω-3多不饱和脂肪酸对人结直肠腺癌细胞Caco-2、正常结肠上皮细胞NCM460生长影响的基础上,检测DHA等3种多不饱和脂肪酸对具核梭杆菌黏附人体细胞以及Fap2、FadA、RadD等具核梭杆菌毒力关键基因表达的影响。【结果】30μg/mL的DHA、EPA、ALA对Caco-2生长抑制分别为9.09%、4.95%、7.52%,而对NCM460生长抑制达31.15%、25.48%、29.11%,而且相关抑制作用仅具有浓度依赖性而无时间依赖性。经30μg/mL的DHA、EPA、ALA预处理的具核梭杆菌黏附Caco-2细胞的能力分别下降81.04%(P=0)、93.63%(P=0)和68.63%(P=0);而共培养时加入DHA、EPA、ALA对具核梭杆菌黏附Caco-2细胞的能力没有显著影响。同时,30μg/mLDHA处理导致***的Fap2基因显著下降10.22%(P=0.027);30μg/mL EPA处理导致FadA、Fap2基因分别显著下降23.49%(P=0)、15.09%(P=0.003);30μg/mL ALA处理导致FadA基因显著下降26.75%(P=0.012)。【结论】综合上述实验结果以及DHA、EPA、ALA仅能短时间抑制具核梭杆菌生长等文献报道,我们认为,DHA、EPA等ω-3多不饱和脂肪酸并非简单地直接杀伤或抑制肿瘤细胞和***;抑制FadA、Fap2等黏附相关基因表达,降低***黏附宿主细胞能力是其抗肿瘤作用的关键组成部分。ω-3多不饱和脂肪酸等活性物质对***等在结直肠肿瘤发生、发展中发挥重要作用的肠道细菌的影响与机制应深入开展研究。

关键词： ω-3多不饱和脂肪酸具核梭杆菌结直肠癌黏附

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