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The protein-protein interaction landscape of transcription factors during gynoecium development in Arabidopsis

Molecular Plant 2023年第1期16卷 260-278页

作者： Humberto Herrera-Ubaldo Sergio e.Campos Pablo López-Gómez Valentín Luna-García Víctor M.Zúñiga-Mayo Gerardo E.Armas-Caballero Karla L.González-Aguilera Alexander DeLuna Nayelli Marsch-Martínez Carlos espinosa-Soto Stefan de Folter Unidad de Genómica Avanzada(UGA-LANGeBIO) Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional(CINVESTAV-IPN)IrapuatoGuanajuato 36824México Departamento de Biotecnología y Bioquímica Unidad IrapuatoCINVESTAV-IPNIrapuatoGuanajuato 36824México Instituto de Física Universidad de San Luis PotosíSan Luis PotosíSLP 78290México Present address:Department of Plant Sciences University of CambridgeCambridgeUK Present address:Department of Molecular and Cellular Biology University of California DavisDavisCAUSA Present address:CONACYT Instituto de FitosanidadColegio de PostgraduadosCampus MontecilloTexcocoMéxico

Flowers are composed of organs whose identity is defined by the combinatorial activity of transcription factors(TFs).The interactions between MADS-box TFs and protein complex formation have been schematized in the floral quartet model of flower development.The gynoecium is the flower’s female reproductive part,crucial for fruit and seed production and,hence,for reproductive success.After the establishment of carpel identity,many tissues arise to form a mature gynoecium.TFs have been described as regulators of gynoecium development,and some interactions and complexes have been identified.However,broad knowledge about the interactions among these TFs and their participation during development remains scarce.In this study,we used a systems biology approach to understand the formation of a complex reproductive unit—as the gynoecium—by mapping binary interactions between well-characterized TFs.We analyzed almost 4500 combinations and detected more than 250 protein-protein interactions(PPIs),resulting in a process-specific interaction map.Topological analyses suggest hidden functions and novel roles for many TFs.In addition,we observed a close relationship between TFs involved in auxin and cytokinin-signaling pathways and other TFs.Furthermore,we analyzed the network by combining PPI data,expression,and genetic data,which helped us to dissect it into several dynamic spatio-temporal subnetworks related to gynoecium development processes.Finally,we generated an extended PPI network that predicts new players in gynoecium development.Taken together,all these results serve as a valuable resource for the plant community.

关键词： interactome networks transcription factors gynoecium development

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Safety and efficacy of Oral Mirodenafil in Mexican with erectile Dysfunction

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International Journal of Clinical Medicine 2016年第9期7卷 628-638页

作者： Juan gerardo Reyes-García Noemí Santos-caballero Francisco Javier Flores-Murrieta Sección de estudios de Posgrado e Investigación Escuela Superior de Medicina Instituto Politécnico Nacional Ciudad de México Mexico Landsteiner Scientific S.A. de C.V. Ciudad de México Mexico Unidad de Investigación en Farmacología Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas” Ciudad de México Mexico

erectile dysfunction is treated with 5-phospodiesterase inhibitors as Mirodenafil, which has shown its efficacy and safety in Koreans, however;no information in other populations is available. An open clinical trial study was designed to evaluate the efficacy and safety in real life of a fixed-dose of Mirodenafil in Mexican patients with erectile dysfunction. Forty-seven male patients received a 100 mg tablet of Mirodenafil, during 12 weeks. Primary outcome efficacy measure was the percentage of male patients with successful intercourse. Secondary outcomes measures included patient satisfaction, mood and self-esteem level. Safety assessments included laboratory tests, vital signs, physical examination, 12-lead electrocardiogram recordings, and incidence of adverse events by patients. Oral administration of Mirodenafil improved in an 80% - 90% the number of successful intercourses from 7 to 84 days of treatment. Moreover, patients reported a significant increment in their sexual satisfaction, mood and self-esteem. Mirodenafil treatment did not modify vital signs nor anthropometric parameters during 84 days. Mild headache was the most frequent adverse event (17.0%) and there were no severe adverse events during pharmacological treatment. Data suggest that oral Mirodenafil is safety, well tolerated and effective in the Mexican population with erectile dysfunction.

关键词： efficacy erectile Dysfunction Mexicans Mirodenafil Safety

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Oral Pharmacokinetics of Mirodenafil in Mexican Healthy Volunteers

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Pharmacology & Pharmacy 2014年第1期5卷 112-116页

作者： Miriam del Carmen Carrasco-Portugal Francisco Javier Flores-Murrieta Juan gerardo Reyes-García Noemí Santos-caballero Landsteiner Scientific S.A. de C.V. México DF México Sección de estudios de Posgrado e Investigación Escuela Superior de Medicina Instituto Politécnico Nacional México DF México Unidad de Investigación en Farmacología Insituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas” México DF México Unidad de Investigación en Farmacología Insituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas” México DF México Sección de estudios de Posgrado e Investigación Escuela Superior de Medicina Instituto Politécnico Nacional México DF México

Mirodenafil is a 5-phosphodiesterase inhibitor that is currently marketed in Korea for the treatment of erectile dysfunction;however, no information in other populations is available. It has been described that Mirodenafil is metabolized by CYP3A4, a metabolic pathway in which interethnic differences have been reported. The purpose of this study was to characterize the oral pharmacokinetics of Mirodenafil in Mexicans. Seventeen male healthy volunteers were enrolled in this study. After an overnight fast, volunteers received an oral 100 mg dose and blood samples were collected at selected times during 24 h. Plasma was stored frozen and analyzed by an HPLC method. Pharmacokinetic parameters obtained were: Cmax 331.129 ± 32.689 ng/mL, tmax 1.574 ± 0.293 h, AUC24h 883.293 ± 104.088 ng·h/mL, AUC￥ 976.477 ± 108.812 ng·h/mL and t1/2 1.807 ± 0.171 h. Parameter values observed in this study are similar to those reported in Koreans. Since efficacy and safety studies of Mirodenafil have been conducted in Koreans, it is expected that dosage regime to employ in Mexicans should be similar to the approved for Korean population.

关键词： erectile Dysfunction Healthy Volunteers Mexican Mirodenafil Pharmacokinetic

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