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Novel kdr mutations (K964R and A943V) in pyrethroid-resistant populations of Triatoma mazzottii and Triatoma longipennisUoro Mexico and detoxifying enzymes

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Insect Science 2019年第5期26卷 809-820页

作者： Jesus Davila-Barboza O.Karina Villanueva-Segura Beatriz Lopez-Monroy Gustavo Ponce-Garcia Cristina Bobadilla-Utrera Mayela Montes-Rincon Zinnia J.Molina-Garza Juan I.Arredondo-Jimenez Iram P.Rodriguez-Sanchez Pablo C.Manrique-Saide Adriana E.Flores Universidad Autonoma de Nuevo Leon (UANL) Facultad de Ciencias BiologicasSan Nicolas de los GarzaNLMexico Laboratorio Estatal de Salud Publica de los Servicios de Salud de Veracruz VeracruzMexico Campus de Ciencias Biologicas y Agropecuarias Unidad Colaborativa para Bioensayos EntomologicosUniversidad Autonoma de YucatanMeridaYucatanMexico

Although having five different ways of transmission the vector-borne is the principal way of transmission of Chagas disease, which involves insects of the subfamily Triatominae (Hemiptera: Reduviidae). Nineteen of the 31 species that occur in Mexico are associated with humans, and all are capable of transmitting the disease. Pyrethroids are the insecticides recommended for the control of these vectors in Mexico. We determined the susceptibility to the pyrethroids dcltamethrin and permethrin of peridomestic populations of Triatoma mazzottii Usinger and two populations of Triatoma longipetmis Usinger in comparison with a reference strain for each species. Bioassays were performed for the determination of the LD50 for both field populations and reference strains. A maximum of 27 fold resistance to deltamethrin was observed in T. mazzottii, meanwhile, for permethrin, T. longipennis from Jalisco show the highest value of 3.19 fold. There was significantly increased activity of esterases in field populations in comparison with their corresponding reference strain. The results of the search of kdr mutations related to the resistance to deltamethrin and permethrin in the evaluated species show the presence of mutations in the field populations, as is the case with individuals of T. mazzottii, for which the mutation was found A943V, and for the two populations of T. longipennis included in this study, we report the presence of the kdr mutation K964R. Evaluation of the various mechanisms involved in resistance to pyrethroids in triatomines from Mexico could guide us to the real justification for insecticide resistance monitoring.

关键词： detoxifying enzymes kdr pyrethroids Triatoma longipennis Triatoma mazzottii

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Expression of vascular endothelial growth factor and its receptors kdr and Fit-1 in gastric cancer cells

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World Journal of Gastroenterology 2002年第6期8卷 994-998页

作者： Hua Zhang Jian Wu Lin Meng Cheng-Chao Shou,Peking University School ofOncology,Beij ing Institute for Cancer Research,Beijing 100034,China Department of Biochemistry and Molecular Biology Peking University School of Oncology Beijing Institute for Cancer Research China.

AIM: The expression of vascular endothelial growth factor (VEGF) and its receptors kdr and Flt-1 by gastric carcinoma tissues and different gastric carcinoma cell lines was detected to elucidate the molecular mechanism of this growth factor in promoting tumor ***: The expression of VEGF, Flt-1 and kdr was determined by reverse transcription-polymerase chain reaction (RT-PCR) in gastric cancer cell lines RF-1, RF-48,AGS-1, NCI-N87, NCI-SNU-1, NCI-SNU-5, NCI-SNU-16 and KATO-Ⅲ. The expression of Flt-1 and kdr in paraffinembedded specimens of gastric cancer was determined by immunohistochemistry. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess the role of VEGF in tumor cell ***: All 8 gastric cancer cell lines analyzed expressed VEGF121 and VEGF16s and six of them expressed both Flt-1 and kdr, while cell line NCI-SNU-5 expressed Flt-1 only and cell line KATOⅢ expressed neither Flt-1 nor kdr. The gastric carcinoma tissues expressed Flt-1 and kdr widely,with the positive rate of expression of Flt-1 and kdr being 84.6 % and 70 % respectively. The exogenous VEGF stimulated the growth of kdr-positive cell lines NCI-N87 and AGS-1 in a dose-dependent manner but exhibited no effect on the growth of kdr-negative cell line ***: VEGF and its receptors kdr and Flt-1 were expressed widely in gastric carcinoma cells and the VEGF stimulated kdr-positive tumor cell growth directly. These results suggest that VEGF may play a role in promoting tumor growth and metastasis by participating in both paracrine and autocrine pathways.

关键词：血管内皮生长因子 VEGF受体 kdr Flt-1 胃癌细胞基因表达

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First report of L1014F kdr mutation in Culex quinquefasciatus in Mexico

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Insect Science 2016年第6期23卷 829-834页

作者： Gustavo Ponce Iram P. Sanchez Selene M. Garcia Jose M. Torrado Saul Lozano-Fuentes Beatriz Lopez-Monroy Adriana E. Flores Facultad de Ciencias Biologicas Universidad Autonoma de Nuevo Leon A v. Universidad sin Cd. Universitaria San Nicolas de los GarzaN.L. 66455 Mexico Department of Microbiology Immunology and Pathology Colorado State University Fort Collins CO USA

The L1014F mutation in the voltage-sodium channel gene has been associated with resistance to DDT and pyrethroids in various arthropod species including mosquitoes. We determined the frequency of the L1014F kdr mutation in 16 field populations of Culex quinquefasciatus from Northeastern Mexico collected between 2008 and 2013. The L1014F was present in all populations analyzed with the lowest frequency （3.33%） corresponding to the population from Monclova collected in 2012, and the highest frequency （63.63%） from the Monterrey population collected in 2012. The presence of a kdr mutation in populations of Cx. quinquefasciatus from northeastern Mexico provides evidence ofpyrethroid resistance. This requires a special attention, considering that pyrethroid-based insecticides are commonly used in vector-control campaigns, especially against Aedes aegypti （L.）.

关键词： Culex quinquefasciatus insecticide resistance kdr L 1014F mutation

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Common susceptibility variants of kdr and IGF-1R are associated with poststroke depression in the Chinese population

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General Psychiatry 2023年第1期36卷 36-42页

作者： Yingying Yue Linlin You Fuying Zhao Kezhong Zhang Yanyan Shi Hua Tang Jianxin Lu Shenghua Li Jinxia Cao Deqin Geng Aiqin Wu Yonggui Yuan Department of Psychosomatics and Psychiatry ZhongDa HospitalSoutheast UniversityNanjingChina Department of Psychiatry Suzhou High-Tech Development District Yangshan Community HospitalSuzhouChina Department of Neurology The First Affiliated Hospital of Nanjing Medical UniversityNanjingChina Department of Neurology Nanjing First HospitalNangjingChina Department of Neurology The Third People's Hospital of Huai'anHuai'anChina Department of Neurology People's Hospital of Gaochun CountyNanjingChina Department of Neurology The Affiliated Nanjing Jiangning Hospital of Nanjing Medical HospitalNanjingChina Department of Neurology The Second People's Hospital of LianyungangLianyungangChina Department of Neurology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina Department of Psychosomatics The Affiliated First Hospital of Soochow UniversitySoochowChina

Background Depression,one of the most frequent complications after stroke,increases the disease’s burden and physical *** depression(PSD)is a multifactorial disease with genetic,environmental and biological factors involved in its *** studies on PSD to date have mainly focused on the monoamine system and brain-derived neurotrophic ***,understanding is still limited about the influence of the single nucleotide polymorphism(SNP)of other neurotrophic factors on *** The present study aimed to investigate the relationship between seven vascular endothelial growth factor(VEGF)family gene variants that occur with *** A multicentre candidate gene study from five hospitals in Jiangsu Province from June 2013 to December 2014 involved 121 patients with PSD and 131 patients with *** characteristics and neuropsychological assessments were ***χ^(2)test was used to evaluate categorical variables,while the independent t-test was applied to continuous *** in seven genes(VEGFA,VEGFB,kdr,FLT-1,IGF-1,IGF-1R and PlGF)were ***-marker association for PSD was analysed byχ^(2)tests and logistic regression using SPSS and PLINK *** Patients with PSD included more women and those with lower education levels,lower body mass indexes,lower Mini-Mental State Examination scores,and higher scores on the 17-item Hamilton Depression Rating Scale than non-PSD ***-two SNPs with seven genes were genotyped and passed quality *** rs7692791 CC genotypes,the C allele of kdr and the rs9282715 T allele of IGF-1R increased the risk for PSD(χ^(2)=7.881,p=0.019;χ^(2)=4.259,p=0.039;χ^(2)=4.222,p=0.040,respectively).In addition,the SNP rs7692791 of kdr was significantly associated with PSD by the logistic regression of an additive model(p=0.015,OR=9.584,95%CI:1.549 to 59.31).Conclusions Patients with rs7692791 C allele carriers or the CC genotype of kdr and the rs9282715 T all

关键词： kdr susceptibility additive

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Evidence of increasing L1014F kdr mutation frequency in Anopheles gambiae *** resistant following a nationwide distribution of LLINs by the Beninese National Malaria Control Programme

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Asian Pacific Journal of Tropical Biomedicine 2014年第3期4卷 239-243页

作者： Nazairc Azoun Rock Akpon Martin Akogbéto Centre de Recherche Entomologique de Cotonou(CREC) 06 BP 2604CotonouBenin Faculte des Sciences et Techniques Universite d'Abomey CalaviCalaviBenin

Objective:To determine the susceptibility status to pyrethroid in Anopheles gambiae s.l.(***),the distribution of kdr"Leu-Phe"mutation in malaria vectors in Benin and to compare the current frequency of kdr"Leu-Phe"mutation to the previous frequency after long-lasting insecticide treated nets ***:Larvae and pupae of *** *** were collected from the breeding sites in Littoral,*** and Alibori *** susceptibility tests were conducted on unfed females mosquitoes aged 2-5 d *** mosquitoes were identified to species using PCR *** assays were also carried out to identify kdr mutations in individual ***:The results showed that *** Malanville and Suru-lere populations were resistant to *** *** Parakou and Bohicon populations,they were resistant to *** revealed 100%of mosquitoes tested were *** *** L1014F kdr mutation was found in *** *** and Parakou at various allelic *** increase of kdr allelic frequency was positively correlated with CDC bioassays ***:Pyrethroid resistance is widespread in malaria vector in Benin and kdr mutation is the main resistance mechanism *** attention may be paid for the future success of malaria control programmes based on LLINs with pyrethroids in the country.

关键词： Resistance Insecticide Vectors CDC bioassay Leu-Phe kdr mutation

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VEGF、VEGFR_2(kdr)、MMP-1以及转录调节因子Ets-1在子宫颈癌组织中的表达及其意义

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中国医学科学院学报 2003年第4期25卷 396-400,T001页

作者：许凤莲李玉林王占东丰有吉复旦大学附属妇产科医院妇科上海200011 Key Laboratory Rathobilolgy Ministry of Education Jilin University Department of Gynecology Second Hospital Affiliated to Jilin University

目的从分子水平观察肿瘤血管生成因子VEGF、VEGF受体kdr、基质金属蛋白酶-1(MMP-1)及其转录调节因子Ets-1(E26transformation-specific-1,Ets-1)在子宫颈癌中的表达并揭示其因子间相互关系,为判断患者预后和解释促血管生成因子间内在规... 详细信息

目的从分子水平观察肿瘤血管生成因子VEGF、VEGF受体kdr、基质金属蛋白酶-1(MMP-1)及其转录调节因子Ets-1(E26transformation-specific-1,Ets-1)在子宫颈癌中的表达并揭示其因子间相互关系,为判断患者预后和解释促血管生成因子间内在规律提供根据。方法利用原位杂交和免疫组织化学染色法检测87例子宫颈癌组织中VEGF、kdr、MMP-1以及Ets-1等因子mRNA和蛋白表达规律;患者生存曲线比较在阴性组和阳性组间进行;因子间分析利用Pearson相关分析法。结果VEGFmRNA和蛋白主要分布在癌细胞胞质中,阳性率分别为78.6%(68/87)和70.4%(61/87);kdrmRNA和蛋白主要在内皮细胞上表达,其表达率与VEGF表达率间存在密切的相关关系,r=0.892;MMP-1在肿瘤细胞和间质血管内皮细胞中表达,尤其在血管新生处表达明显;Ets-1主要分布在内皮细胞和肿瘤细胞中,其表达率与kdr和MMP-1表达率间的相关系数(r)分别为0.900和0.873;上述四因子表达与肿瘤分化度、淋巴结转移及5年存活率均有密切的相关性。结论VEGF、kdr、MMP-1以及Ets-1是参与子宫颈癌血管生成的重要因子,且彼此间存在密切的相关性,检测其表达规律可为判断子宫颈癌生物学行为和解释促血管生成因子间内在联系提供理论根据。

关键词：子宫颈癌血管生成 VEGF kdr MMP-1 Ets-1 原位杂交免疫组织化学

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The role of kdr in the interactions between human gastric carcinoma cell and vascular endothelial cell

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World Journal of Gastroenterology 2002年第4期8卷 596-601页

作者： Juan Ren Lei Dong Cang-Bao Xu Bo-Rong Pan Department of Oncological Radiotherapy First Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of Gastroenterology Second Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina Department of Pathophysiology Lund UniversitySweden Oncology Center Xijing HospitalFourth Militry Medical UniversityXi’an 710032Shaanxi ProvinceChina

AIM:To study the interactions between human gastriccarcinoma cell (HGCC) and human vascular endothelialcell (HVEC), and the role of kdr in these ***:Antisense oligodexynucleotide(ASODN)specific to kdr gene was devised and added to theculture medium of HGCC and HVEC. After the action ofASODN, the proliferation of two cells was measured byMTT *** role of kdr in regulating theproliferation of two kinds of cells was known throughobserving the effect of ASODN on them. The conditionedmediums (CMs) of HGCC and HVEC were prepared. TheCM of one kind of cell was added acting on the otherkind of cell, then the cell proliferation was measuredby MTT. After the action of ASODN or CM, the cellularexpression of kdr gene was detected with in situhybridization(ISH) for mRNA level and withimmunohistochemical staining for protein level. ABC-ELISA was used to detect/NEGF in the CMs of two ***: kdr ASODN could specifically inhibit theproliferation of HGCC and HVEC significantiy. The growthinhibitory rate amounted to 55.35 % and 54.83 %,respectively (P＜0.01). HGCC and HVEC could secret acertain level of hVEGF(92.06±1.69 ng/L, 77.70±8.04ng/L). The CM of HGCC could significantiy stimulate thegrowth(2.70±0.01 times) and kdr gene expression ofHVEC(P＜0.01) while the CM of HVEC could significantiyinhibit the growth(52.97±0.01%) and kdr geneexpression of HGCC (P ＜0.01).CONCLUSION: kdr plays a key role in regulating theproliferation of HGCC and HVEC. There existcomplicated interactions between HGCC and *** can significantly stimulate the growth of HVECwhile HVEC can significantly inhibit the growth of *** is involved in the interactions between them.

关键词：血管内皮生长因子 kdr 胃癌血管内皮细胞受体作用机理

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人血管内皮生长因子受体kdr胞外3区的表达与配体结合活性的鉴定

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生物工程学报 2008年第11期24卷 1962-1967页

作者：张娟张艳丽李海鑫陈卫张弢王旻中国药科大学生命科学与技术学院分子生物学教研室南京210009

血管内皮生长因子受体(VEGFR)是血管内皮生长因子的特异性受体,VEGFR-2在介导VEGF刺激内皮细胞增殖及血管通透性等生物学活性中起重要作用。在大肠杆菌中实现可溶性的人血管内皮生长因子受体kdr胞外3区的表达,并鉴定其与配体结合的活性... 详细信息

血管内皮生长因子受体(VEGFR)是血管内皮生长因子的特异性受体,VEGFR-2在介导VEGF刺激内皮细胞增殖及血管通透性等生物学活性中起重要作用。在大肠杆菌中实现可溶性的人血管内皮生长因子受体kdr胞外3区的表达,并鉴定其与配体结合的活性。采用重叠PCR的方法合成人血管内皮生长因子受体kdr胞外3区基因,将该基因与高效表达载体pET-32a重组,转化大肠杆菌Rosetta(DE3)中,表达产物依次经过CM阳离子交换树脂和镍柱亲和层析纯化。利用ELISA法和体外抑制VEGF刺激的人脐静脉内皮细胞增殖实验检测表达产物与配体结合的活性。SDS-PAGE显示,目的蛋白主要以可溶性Trx-kdr3融合蛋白表达于胞质,30oC时1 mmol/L IPTG诱导细菌5 h融合蛋白表达量约占胞质可溶性总蛋白的20%,经CM阳离子交换树脂和镍柱亲合层析纯化得到纯度为95%的产物,Western blotting鉴定是目的蛋白。ELISA和体外HUVEC细胞增殖实验显示,表达产物具有特异性结合hVEGF165的活性,且该作用呈一定的浓度依赖性。具有配体特异性结合活性的可溶性人血管内皮生长因子受体kdr胞外3区成功表达,为靶向血管抗肿瘤治疗和相关抗体的研究奠定了基础。

关键词：血管内皮生长因子 kdr 蛋白表达与纯化

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Effect of Weikangning on gastric cancer cell growth and expression of vascular endothelial growth factor and its receptors kdr and Flt-1

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World Journal of Gastroenterology 2005年第7期11卷 938-942页

作者： Qing-MingLi Fang-JuKan Cun-YunMin DepartmentofIntegrativeTraditionalChineseMedicine No.2AffiliatedHospitalofSunYat-SenUniversityGuangzhou510120GuangdongProvinceChina DepartmentofTraditionalChineseMedicine No.2AffiliatedHospitalofSunYat-SenUniversityGuangzhou510120GuangdongProvinceChina

AIM: To observe the effect of Chinese traditional herbal decoction Weikang-ning (WKN) on cell growth and expression of VEGF and its receptors kdr and Flt-1 in gastric cancer cell line MGC-803. METHODS: A total of 120 male Wistar rats were divided into control group, high dose, medium dose and low dose groups fed with natural saline, 20, 10, and 5 g/kg of WKN, respectively. The experimental animals were finally killed for the preparation of drug-containing serum. The gastric cancer cell MGC-803 was cultured with the drug-containing serum drawn from the rats in different groups. We observed the growth condition of the cancer cells with light microscope and flow cytometer. The expression of mRNA of VEGF and its receptors kdr and Flt-1 was detected with RT-PCR. RESULTS: The proportion of cells in G0-G1 phase was (65.40±0.41)%, (56.92±0.62)%, (55.89±0.69)% in high, medium and low dose groups respectively vs(41.35±0.55)% in control group (Pkdr and Flt-1.

关键词： Weikang-ning Gastric cancer VEGF kdr Flt-1 MGC-803

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kdr反义寡核苷酸对人血管内皮细胞的作用

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基础医学与临床 2002年第5期22卷 428-433页

作者：任娟董蕾徐仓宝李明众西安交通大学附一院肿瘤放疗科西安710061 西安交通大学附二院消化内科西安710061 瑞典Loud大学

VEGF及其受体kdr在肿瘤血管生成中起重要作用。我们用kdr特异性反义寡核苷酸作用于人血管内皮细胞 ,以阻断VEGF的自分泌作用通路 ,观察对细胞增殖的影响、细胞超微结构的变化及检测细胞DNA含量 ,测定细胞分泌VEGF的能力 ,并检测作用后KD... 详细信息

VEGF及其受体kdr在肿瘤血管生成中起重要作用。我们用kdr特异性反义寡核苷酸作用于人血管内皮细胞 ,以阻断VEGF的自分泌作用通路 ,观察对细胞增殖的影响、细胞超微结构的变化及检测细胞DNA含量 ,测定细胞分泌VEGF的能力 ,并检测作用后kdrmRNA和kdr蛋白的水平。结果发现未经处理的人血管内皮细胞能分泌一定量的VEGF ,kdrASODN能抑制人血管内皮细胞内kdr基因的表达 ,并显著抑制细胞的增殖 ,在一定剂量下还可诱导凋亡。结果说明kdrASODN能显著抑制血管内皮细胞的增殖。

关键词： kdr 反义寡核苷酸人血管内皮细胞血管内皮生长因子肿瘤血管生成

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