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C3G contributes to platelet activation and aggregation by regulating major signaling pathways

Signal Transduction and Targeted Therapy 2020年第1期5卷 2103-2117页

作者： Sara Gutiérrez-Herrero cristina fernández-infante Luis Hernández-Cano Sara Ortiz-Rivero Carlos Guijas Víctor Martín-Granado JoséRamón González-Porras Jesús Balsinde Almudena Porras Carmen Guerrero Instituto de Biología Molecular y Celular del Cáncer(IMBCC) University of Salamanca-CSICSalamancaSpain Instituto de Investigación Biomédica de Salamanca(IBSAL) SalamancaSpain Instituto de Biología y Genética Molecular(IBGM) Consejo Superior de Investigaciones Científicas(CSIC)University of ValladolidValladolidSpain Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas(CIBERDEM) MadridSpain Departamento de Hematologiá Hospital Universitario de Salamanca(HUS)SalamancaSpain Departamento de Bioquímica y Biología Molecular Facultad de FarmaciaComplutense University of Madrid.Instituto de Investigación Sanitaria del Hospital Clínico San Carlos(IdISSC)MadridSpain Departamento de Medicina University of SalamancaSalamancaSpain

C3G is a GEF(guanine nucleotide exchange factor)for Rap GTPases,among which the isoform Rap1b is an essential protein in platelet *** transgenic mouse models with platelet-specific overexpression of C3G or mutant C3GΔCat,we have unveiled a new function of C3G in regulating the hemostatic function of platelets through its participation in the thrombin-PKCRap1b pathway.C3G also plays important roles in angiogenesis,tumor growth,and metastasis through its regulation of the platelet *** addition,C3G contributes to megakaryopoiesis and ***,we used a platelet-specific C3G-KO mouse model to further support the role of C3G in hemostasis.C3G-KO platelets showed a significant delay in platelet activation and aggregation as a consequence of the defective activation of Rap1,which resulted in decreased thrombus formation in ***,we explored the contribution of C3G-Rap1b to platelet signaling pathways triggered by thrombin,PMA or ADP,in the referenced transgenic mouse model,through the use of a battery of specific *** found that platelet C3G is phosphorylated at Tyr504 by a mechanism involving *** phosphorylation was shown to be positively regulated by ERKs through their inhibition of the tyrosine phosphatase ***,C3G participates in the ADP-P2Y12-PI3K-Rap1b pathway and is a mediator of thrombin-TXA2 ***,it inhibits the synthesis of TXA2 through cPLA2 *** together,our data reveal the critical role of C3G in the main pathways leading to platelet activation and aggregation through the regulation of Rap1b.

关键词： C3G platelet activation

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Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

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Cellular & Molecular Immunology 2021年第9期18卷 2128-2139页

作者： Alberto Pérez-Gómez Joana Vitallé Carmen Gasca-Capote Alicia Gutierrez-Valencia María Trujillo-Rodriguez Ana Serna-Gallego Esperanza Muñoz-Muela María de los Reyes Jiménez-Leon Mohamed Rafii-El-Idrissi Benhnia Inmaculada Rivas-Jeremias Cesar Sotomayor cristina Roca-Oporto Nuria Espinosa Carmen infante-Domínguez Juan Carlos Crespo-Rivas Alberto fernández-Villar Alexandre Pérez-González Luis fernando López-Cortés Eva Poveda Ezequiel Ruiz-Mateos JoséMiguel Cisneros Sonsoles Salto-Alejandre Judith Berastegui-Cabrera Pedro Camacho-Martínez Carmen infante-Domínguez Marta Carretero-Ledesma Juan Carlos Crespo-Rivas Eduardo Márquez JoséManuel Lomas Claudio Bueno Rosario Amaya JoséAntonio Lepe Jerónimo Pachón Elisa Cordero Javier Sánchez-Céspedes Manuela Aguilar-Guisado Almudena Aguilera Clara Aguilera Teresa Aldabo-Pallas Verónica Alfaro-Lara cristina Amodeo Javier Ampuero María Dolores Avilés Maribel Asensio Bosco Barón-Franco Lydia Barrera-Pulido Rafael Bellido-Alba Máximo Bernabeu-Wittel Candela Caballero-Eraso Macarena Cabrera Enrique Calderón Jesús Carbajal-Guerrero Manuela Cid-Cumplido Yael Corcia-Palomo Juan Delgado Antonio Domínguez-Petit Alejandro Deniz Reginal Dusseck-Brutus Ana Escoresca-Ortega Fátima Espinosa Nuria Espinosa Michelle Espinoza Carmen Ferrándiz-Millón Marta Ferrer Teresa Ferrer Ignacio Gallego-Texeira Rosa Gámez-Mancera Emilio García Horacio García-Delgado Manuel García-Gutiérrez María Luisa Gascón-Castillo Aurora González-Estrada Demetrio González Carmen Gómez-González Rocío González-León Carmen Grande-Cabrerizo Sonia Gutiérrez Carlos Hernández-Quiles Inmaculada Concepción Herrera-Melero Marta Herrero-Romero Luis Jara Carlos Jiménez-Juan Silvia Jiménez-Jorge Mercedes Jiménez-Sánchez Julia Lanseros-Tenllado Carmina López Isabel López Álvaro López-Barrios Luis F.López-Cortés Rafael Luque-Márquez Daniel Macías-García Guillermo Martín-Gutiérrez Luis Martín-Villén JoséMolina Aurora Morillo María Dolores Navarro-Amuedo Dolores Nieto-Martín Francisco Ortega María Paniagua-García Amelia Peña-Rodríguez E Clinical Unit of Infectious Diseases Microbiology and Preventive MedicineInstitute of Biomedicine of Seville(IBiS)Virgen del Rocío University HospitalCSICUniversity of SevilleSevilleSpain Department of Medical Biochemistry Molecular Biologyand ImmunologySchool of MedicineUniversity of SevilleSevilleSpain Pneumology Service Galicia Sur Health Research Instituto(IIS Galicia Sur)SERGAS-UVigoVigoSpain Infectious Diseases Unit Department of Internal MedicineComplexo HospitalarioUniversitario de VigoIIS Galicia SurSERGAS-UVigoVigoSpain Group of Virology and Pathogenesis Galicia Sur Health Research Institute(IIS Galicia Sur)-Complexo Hospitalario Universitario de VigoSERGAS-UVigoVigoSpain Unit of Infectious Diseases Microbiologyand Preventive MedicineVirgen del Rocío University HospitalSevilleSpain Institute of Biomedicine of Seville(IBiS) Virgen del Rocío University Hospital/CSIC/University of SevilleSevilleSpain Medico-Surgical Unit of Respiratory Diseases Virgen del Rocío University HospitalSevilleSpain Unit of Emergencies Virgen del Rocío University HospitalSevilleSpain Intensive Care Unit Virgen del Rocío University HospitalSevilleSpain Department of Medicine University of SevilleSevilleSpain Cardiology and Cardiovascular Surgery Unit Virgen del Rocío University HospitalSevilleSpain Rheumatology Unit Virgen del Rocío University HospitalSevilleSpain Internal Medicine Unit Virgen del Rocío University HospitalSevilleSpain Digestive and Hepatobiliary Unit Virgen del Rocío University HospitalSevilleSpain Neurology and Clinical Neurophysiology Unit Virgen del Rocío University HospitalSevilleSpain Endocrinology and Nutrition Unit Virgen del Rocío University HospitalSevilleSpain Urology and Nephrology Unit Virgen del Rocío University HospitalSevilleSpain Unit of Clinical Investigation and Clinical Trials Virgen del Rocío University HospitalSevilleSpain

Severe Acute Respiratory Syndrome Coronavirus(SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity *** cells(DCs)play a key role in the defense against viral infections,for instance plasmacytoid DCs(pDCs),have the capacity to produce vast amounts of interferon-alpha(IFN-α).In COVID-19 there is a deficit in DC numbers and IFN-αproduction,which has been associated with disease *** this work,we described that in addition to the DC deficiency,several DC activation and homing markers were altered in acute COVID-19 patients,which were associated with multiple inflammatory ***,previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+myeloid DCs and pDCs seven months after SARS-CoV-2 ***,the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients,while no restoration of integrinβ7 and indoleamine 2,3-dyoxigenase(IDO)levels were *** findings contribute to a better understanding of the immunological sequelae of COVID-19.

关键词： SARS-CoV-2 COVID-19 Dendritic cell Long-COVID

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Essential Oils of Lavandula stoechas *** as Antifungal Agent against Fungi from Strawberry Tree Fruit

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Journal of Pharmacy and Pharmacology 2021年第3期9卷 98-106页

作者： Joana Domingues fernanda Delgado JoséCarlos Gonçalves cristina Santos Pintado CBPBI-Plant Biotechnology Centre of Beira Interior Quinta da Senhora de MérculesApartado 1196001-909Castelo BrancoPortugal CICS-UBI-Health Sciences Research Centre Universidade da Beira InteriorAv.Infante D.Henrique 6200-506CovilhãPortugal IPCB-ESA-Instituto Politécnico de Castelo Branco Escola Superior AgráriaQuinta da Senhora de MérculesApartado 1196001-909Castelo BrancoPortugal CERNAS-IPCB-Research Centre for Natural Resources Environment and SocietyInstituto Politécnico de Castelo BrancoPortugal

*** *** is one of the five spontaneous species of the genus Lavandula that occurs spontaneously in *** chemical profile and antifungal activity of *** *** essential oils were *** essential oil of two phenological stages was isolated by hydrodistillation and their chemical components analyzed by GC-FID/*** minimum inhibitory concentration(MIC)and the minimum fungicidal concentration(MFC)of both essential oils were determinate to verify antifungal activity against different strains of fungi isolated from strawberry *** fungi tested were Aspergillus carbonarius,Rhizopus stolonifer,Penicillium brevicompactum,Aureobasidium pullulans and Saccothecium *** oils were characterized by a high percentage of oxygenated monoterpenes(46-64%)such as trans-α-necrodyl acetate(12.58%),fenchone(5.97%),1,8-cineole(4.84%)and 5-methylene-2,3,4,4-tetramethylcyclopenten-2-enone(10.97%)were the major compounds in essential oil from dormancy stage,while the main compounds in flowering stage were trans-α-necrodyl acetate(26.90%),trans-α-necrodol(13.02%),lavandulyl acetate(6.53%)and linalool(5.82%).A strong antifungal activity of the essential oils was found against all strains,with MIC and MFC values ranged from 0.07-0.29μL/mL and 0.58-9.33μL/mL,respectively.

关键词： Portuguese short-stalked lavender Hydrodistillation Gas Chromatography Chemical characterization Minimum inhibitory concentration Minimum fungicidal concentration.

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