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2,3-Diaryl-3H-imidazo[4,5-b]pyridine derivatives as potential anticancer and anti-inflammatory agents

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Acta Pharmaceutica Sinica B 2017年第1期7卷 73-79页

作者： Erin Marie Kirwen Tarun Batra Chandrabose Karthikeyan Girdhar Singh Deora Vandana Rathore Chaitanya Mulakayala Naveen Mulakayala Amy catherine Nusbaum Joel Chen Haneen Amawi Kyle mc Intosh Sahabjada Neelam Shivnath Deepak Chowarsia Nisha Sharma Md Arshad Piyush Trivedi Amit KTiwari Department of Pharmacology and Experimental Therapeutics College of Pharmacy & Pharmaceutical SciencesUniversity of Toledo School of Pharmaceutical Sciences Rajiv Gandhi Technical University The University of Queensland School of Pharmacy Dr. Reddy’s Institute of Life Sciences University of Hyderabad Campus The University of Queensland School of Biomedical Sciences Department of Biosciences Sri Satya Sai Institute of Higher LearningAnantapur campus Clearsynth Labs Ltd. Research CentreIDA-Mallapur Molecular Endocrinology Lab Department of ZoologyUniversity of Lucknow University Institute of Pharmacy Chhatrapati Shahu Ji Maharaj University

In this study we examined the suitability of the 3H-imidazo[4,5-b]pyridine ring system in developing novel anticancer and anti-inflammatory agents incorporating a diaryl pharmacophore. Eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives retrieved from our in-house database were evaluated for their cytotoxic activity against nine cancer cell lines. The results indicated that the compounds showed moderate cytotoxic activity against mcF-7, MDA-MB-468, K562 and SaOS2 cells, with K562 being the most sensitive among the four cancer cell lines. The eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives were also evaluated for their COX-1 and COX-2 inhibitory activity in vitro. The results showed that compound 3f exhibited 2-fold selectivity with IC_(50) values of 9.2 and 21.8 mmol/L against COX-2 and COX-1, respectively. Molecular docking studies on the most active compound 3f revealed a binding mode similar to that of celecoxib in the active site of the COX-2 enzyme.

关键词： 3H-Imidazo[4,5-b]pyridine Cytotoxicity MTT assay COX inhibitors Docking studies

Theobroma cacao improves bone growth by modulating defective ciliogenesis in a mouse model of achondroplasia

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Bone Research 2022年第1期10卷 137-149页

作者： Ludovic Martin Nabil Kaci catherine Benoist-Lasselin Marine Mondoloni Suzanne Decaudaveine Valentin Estibals Maxence Cornille Léa Loisay Justine Flipo Benoît Demuynck Maria de la Luz Cádiz-Gurrea Florent Barbault Salvador Fernández-Arroyo Laurent Schibler Antonio Segura-Carretero Emilie Dambroise Laurence Legeai-Mallet Universitéde Paris Imagine InstituteLaboratory of Molecular and Physiopathological Bases of OsteochondrodysplasiaINSERM UMR 1163F‑75015ParisFrance Inovarion ParisFrance Department of Analytical Chemistry University of GranadaGranadaSpain Research and Development of Functional Food Centre(CIDAF) GranadaSpain Universitéde Paris ITODYSCNRSUMR 708615 rue J-A de BaïfParisFrance Biomedical Research Unit Medicine and Surgery DepartmentRovira i Virgili UniversityTarragonaSpain ALLICE Maison Nationale des EleveursParisFrance

A gain-of-function mutation in the fibroblast growth factor receptor 3 gene(FGFR3)results in achondroplasia(ACH),the most frequent form of dwarfism.Constitutive activation of FGFR3 impairs bone formation and elongation and many signal transduction pathways.Identification of new and relevant compounds targeting the FGFR3 signaling pathway is of broad importance for the treatment of ACH,and natural plant compounds are prime drug candidate sources.Here,we found that the phenolic compound(-)-epicatechin,isolated from Theobroma cacao,effectively inhibited FGFR3’s downstream signaling pathways.Transcriptomic analysis in an Fgfr3 mouse model showed that ciliary mRNA expression was modified and influenced significantly by the Indian hedgehog and PKA pathways.(-)-Epicatechin is able to rescue mRNA expression impairments that control both the structural organization of the primary cilium and ciliogenesis-related genes.In femurs isolated from a mouse model(Fgfr3^(Y367C/+))of ACH,we showed that(-)-epicatechin eliminated bone growth impairment during 6 days of ex vivo culture.In vivo,we confirmed that daily subcutaneous injections of(-)-epicatechin to Fgfr3^(Y367C/+) mice increased bone elongation and rescued the primary cilium defects observed in chondrocytes.This modification to the primary cilia promoted the typical columnar arrangement of flat proliferative chondrocytes and thus enhanced bone elongation.The results of the present proof-of-principle study support(-)-epicatechin as a potential drug for the treatment of ACH.

关键词： inhibited arrangement eliminated

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蓝铁矿氧化过程的穆斯鲍尔谱研究

地球与环境 1982年第2期 39-42页

作者： catherine A.mc Cammon ,阚学敏

如所周知,蓝铁矿很容易在空气中氧化,在这个过程中它由实际上的无色变为深蓝（α）-淡绿（β,γ）多色性。虽然蓝铁矿是许多结晶化学与谱学研究的焦点,但是该矿物结构中Fe2+氧化的机理仍然是不清楚的。铁原子在蓝铁矿的晶体结构中占有... 详细信息

如所周知,蓝铁矿很容易在空气中氧化,在这个过程中它由实际上的无色变为深蓝（α）-淡绿（β,γ）多色性。虽然蓝铁矿是许多结晶化学与谱学研究的焦点,但是该矿物结构中Fe2+氧化的机理仍然是不清楚的。铁原子在蓝铁矿的晶体结构中占有两种不同的八面体位置。一种是孤立的FeA八面体,其中Fe2+的六个配位体是处于菱形平面上的四个H2O和两个顺排的氧（trans-O）,后者属于PO4-3四面体;另一种是FeB八面体,其中有两个配位体是反排的H2O（Cis-H2O）,

关键词：穆斯鲍尔谱铁原子结晶化学晶体化学晶体学蓝铁矿磷酸盐矿物机械研磨拟合结果配位体氧化过程

Large-scale forest inventories of the United States and China reveal positive effects of biodiversity on productivity

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Forest Ecosystems 2015年第4期2卷 272-287页

作者： James V Watson Jingjing Liang Patrick C Tobin Xiangdong Lei James S Rentch catherine E Artis Davis College of Agriculture Natural Resources and DesignWest Virginia University Forest Service U.S.Department of AgricultureNorthern Research Station School of Environmental and Forest Sciences University of Washington Research Institute of Forest Resource Information Techniques Chinese Academy of Forestry

Background： With the loss of species worldwide due to anthropogenic factors, especially in forested ecosystems, it has become more urgent than ever to understand the biodiversity-ecosystem functioning relationship （BEFR）. BEFR research in forested ecosystems is very limited and thus studies that incorporate greater geographic coverage and structural complexity are needed. Methods： We compiled ground-measured data from approx, one half million forest inventory sample plots across the contiguous United States, Alaska, and northeastern China to map tree species richness, forest stocking, and productivity at a continental scale. Based on these data, we investigated the relationship between forest productivity and tree species diversity, using a multiple regression analysis and a non-parametric approach to account for spatial autocorrelation. Results： In general, forests in the eastern United States consisted of more tree species than any other regions in the country. The highest forest stocking values over the entire study area were concentrated in the western United States and Central Appalachia. Overall, 96.4 % of sample plots （477,281） showed a significant positive effect of species richness on site productivity, and only 3.6 % （17,349） had an insignificant or negative effect. Conclusions： The large number of ground-measured plots, as well as the magnitude of geographic scale, rendered overwhelming evidence in support of a positive BEFR. This empirical evidence provides insights to forest management and biological conservation across different types of forested ecosystems. Forest timber productivity may be impaired by the loss of species in forests, and biological conservation, due to its potential benefits on maintaining species richness and productivity, can have profound impacts on the functioning and services of forested ecosystems.

关键词： Tree species diversity Forest management Biological conservation Continental map of forest diversity Spatial autocorrelation Bootstrap

Global Transcriptional Profile of Tranosema rostrale Ichnovirus Genes in Infected Lepidopteran Hosts and Wasp Ovaries

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Virologica Sinica 2009年第5期24卷 478-492页

作者： Asieh Rasoolizadeh Frédéric Dallaire Don Stewart catherine Béliveau Renée Lapointe Michel Cusson Natural Resources Canada Canadian Forest Service Laurentian Forestry Centre 1055 du PEPS P.O. Box 10380 Stn. Ste-Foy Québec QC G1V 4C7 Canada Département de biologie Université Laval Québec QC G1V 0A6 Canada Département de biochimie et microbiologie Université Laval Québec QC G1V 0A6 Canada

The ichnovirus TrIV, transmitted by the endoparasitic wasp Tranosema rostrale to its lepidopteran host during oviposition, replicates asymptomatically in wasp ovaries and causes physiological dysfunctions in parasitized caterpillars. The need to identify ichnoviral genes responsible for disturbances induced in lepidopteran hosts has provided the impetus for the sequencing and annotation of ichnovirus genomes, including that of TrIV. In the latter, 86 putative genes were identified, including 35 that could be assigned to recognized ichnoviral gene families. With the aim of assessing the relative importance of each TrIV gene, as inferred from its level of expression, and evaluating the accuracy of the gene predictions made during genome annotation, the present study builds on an earlier qPCR quantification of transcript abundance of TrIV rep ORFs, in both lepidopteran and wasp hosts, extending it to other gene families as well as to a sample of unassigned ORFs. We show that the majority (91%) of putative ORFs assigned to known gene families are expressed in infected larvae, while this proportion is lower (67%) for a sample taken among the remaining ORFs. Selected members of the TrV and rep gene families are shown to be transcribed in infected larvae at much higher levels than genes from any other TrIV gene family, pointing to their likely involvement in host subjugation. In wasp ovaries, the transcriptional profile is dominated by a rep gene and a member of a newly described gene family encoding secreted proteins displaying a novel cysteine motif, which we identified among previously unassigned ORFs.

关键词：鳞翅目 s基因黄蜂主机卵巢感染转录

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东南亚和东亚的地块转动

宝石和宝石学杂志(中英文) 1989年第3期 20-20页

作者： Robert mc cabe 李茂林

东南亚古地磁研究所展现的成果,忽视了地区构造的复杂性。例如,一些工作人员提出“异类他地区”的中生代古磁方位暗示了“异他克拉通”自中生代以来表现为一个独特的构造单元.这些研究忽视了这样的事实,即现今“异他克拉通”中的一部分... 详细信息

东南亚古地磁研究所展现的成果,忽视了地区构造的复杂性。例如,一些工作人员提出“异类他地区”的中生代古磁方位暗示了“异他克拉通”自中生代以来表现为一个独特的构造单元.这些研究忽视了这样的事实,即现今“异他克拉通”中的一部分是一些在新生代被熔接到克拉通上的外来块体,而其它大部分(如马来亚)被许多走滑断层所切割.这些走滑断层提供了新生代巨量位移的证据。除构造问题外,较老岩石可能被再磁化所混染.如果工作人员不将获得的较年轻岩石古地磁数据与从

关键词：走滑断层构造单元克拉通古地磁研究磁方位再磁化马来亚混染

Internal ribosome entry site-based vectors for combined gene therapy

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World Journal of Experimental Medicine 2015年第1期5卷 11-20页

作者： Edith Renaud-Gabardos Fransky Hantelys Florent Morfoisse Xavier Chaufour Barbara Garmy-Susini Anne-catherine Prats Université de Toulouse UPSTRADGENEEA4554BP 84225F-31432 ToulouseFrance Inserm U1048F-31432 ToulouseFrance and Université de ToulouseUPSI2MCF-31432 ToulouseFrance Centre Hospitalier Universitaire de Toulouse F-31059 Toulouse and Université de ToulouseUPSTRADGENEEA4554BP 84225F-31432 ToulouseFrance

Gene therapy appears as a promising strategy to treatincurable diseases. In particular, combined gene therapy has shown improved therapeutic efficiency. Internal ribosome entry sites(IRESs), RNA elements naturally present in the 5' untranslated regions of a few m RNAs, constitute a powerful tool to co-express several genes of interest. IRESs are translational enhancers allowing the translational machinery to start protein synthesis by internal initiation. This feature allowed the design of multi-cistronic vectors expressing several genes from a single m RNA. IRESs exhibit tissue specificity, and drive translation in stress conditions when the global cell translation is blocked, which renders them useful for gene transfer in hypoxic conditions occurring in ischemic diseases and cancer. IRES-based viral and non viral vectors have been used successfully in preclinical and clinical assays of combined gene therapy and resulted in therapeutic benefits for various pathologies including cancers, cardiovascular diseases and degenerative diseases.

关键词： Vector Gene transfer Internal ribosome entry site Gene therapy

使用数字化临床决策支持工具应对抗精神病药物的不良反应:一项焦点小组研究

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英国医学杂志中文版 2019年第8期22卷 483-483页

作者： catherine Henshall Andrea Cipriani David Ruvolo Orla Macdonald Leona Wolters Ivan Koychev 崔轶(译) 不详中华医学杂志英文版编辑部

背景在医学上,算法可以通过结合关于药物不良反应情况的最新证据,来提供治疗决策,这些证据在疗效上具有可比性。在开始治疗时,它们的使用为改善医生-患者共同决策提供了可能。我们设计了一种决策支持工具(DST),收录了关于抗精神病药物... 详细信息

背景在医学上,算法可以通过结合关于药物不良反应情况的最新证据,来提供治疗决策,这些证据在疗效上具有可比性。在开始治疗时,它们的使用为改善医生-患者共同决策提供了可能。我们设计了一种决策支持工具(DST),收录了关于抗精神病药物不良反应的最新证据。该工具可以让患者选择某种抗精神病药物常有的、也是他们想避免的不良反应;然后工具会给出一份建议用药和避免用药的清单。目的从患者和精神科医生的角度定性地探讨DST的可接受性和实用性。方法这项定性研究于2018年在英国牛津的一家精神卫生社区医院进行。4名患者/护理人员和4名精神科医生被招募到2个焦点小组,以探讨他们对该工具的看法。对数据进行主题分析。结果研究结果显示,DST对患者和精神科医生具有很高的可接受性和潜在的可用性。与DST相关的主要议题包括"处方偏好和实践""对不良反应的考虑和意识""应用程序的内容、界面和可访问性""对临床实践的影响"和"在决策中的角色"。结论一项概念验证临床研究将把本研究结果产生的建议纳入到工具的设计中。临床意义对于最新的药物不良反应信息,数字DST使其可能作为医生-患者共同决策的基础。该工具将有能力改善精神病药物治疗的依从性,对临床结果和医疗资源都有益处。

关键词：药物不良反应抗精神病药物数字化工具临床决策焦点精神科医生药物治疗