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Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma

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World Journal of Gastroenterology 2023年第17期29卷 2571-2599页

作者： Fernanda Villarruel-Melquiades María Eugenia Mendoza-Garrido Claudia M García-Cuellar Yesennia Sánchez-Pérez Julio Isael Pérez-Carreón Javier Camacho departamento de Farmacología Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional(CINVESTAV-IPN)Mexico City 07360Mexico departamento de Fisiología Biofísica y NeurocienciasCentro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional(CINVESTAVIPN)Mexico City 07360Mexico Subdirección de Investigación Básica Instituto Nacional de Cancerología(INCan)Mexico City 14080Mexico Instituto Nacional de Medicina genómica Instituto Nacional de Medicina Genómica(INMEGEN)Mexico City 14610Mexico

Hepatocellular carcinoma(HCC)is one of the most lethal malignant tumours *** mortality-to-incidence ratio is up to 91.6%in many countries,representing the third leading cause of cancer-related *** drugs,including the multikinase inhibitors sorafenib and lenvatinib,are first-line drugs used in HCC ***,these therapies are ineffective in most cases due to late diagnosis and the development of tumour ***,novel pharmacological alternatives are urgently *** instance,immune checkpoint inhibitors have provided new approaches targeting cells of the immune ***,monoclonal antibodies against programmed cell death-1 have shown benefits in HCC *** addition,drug combinations,including first-line treatment and immunotherapy,as well as drug repurposing,are promising novel therapeutic ***,we review the current and novel pharmacological approaches to fight *** studies,as well as approved and ongoing clinical trials for liver cancer treatment,are *** pharmacological opportunities analysed here should lead to significant improvement in HCC therapy.

关键词： Liver cancer Systemic therapy Immunotherapy Drug repurposing Drug combinations Hepatocellular carcinoma

In Vitro Propagation of Agave guiengola gentry Using Semisolid Medium and Temporary Immersion Bioreactors

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Phyton-International Journal of Experimental Botany 2021年第3期90卷 1003-1013页

作者： Lucía Isabel Chávez-Ortiz JoséFrancisco Morales-Domínguez Araceli Rodríguez-Sahagún Eugenio Pérez-Molphe-Balch departamento de Química Centro de Ciencias BásicasUniversidad Autónoma de AguascalientesAguascalientes20131México Laboratorio de Biología Molecular Vegetal Centro Universitario de la CiénegaUniversidad de GuadalajaraOcotlán47820México

Agave guiengola gentry is an endemic plant from a very small locality in Oaxaca,*** conservation status is fragile and can rapidly *** of its scarcity,this agave has been used solely for ornamental purposes,but it could have other uses if more plants were *** vitro propagation by enhanced axillary sprouting from stem segments was attained using Murashige and Skoog Basal Medium(MS)as well as basal medium supplemented with cytokinins 6-Benzylaminopurine(BA)or 6-(γ,γ-Dimethylallylamino)purine(2iP).The best treatment for shoot induction in semisolid medium consisted in MS supplemented with 2 mg l^(–1) BA,obtaining a mean of 3.7 shoots per *** interesting responses were observed,such as nodular callus induction using combinations of BA and 2,4-Dichlorophenoxyacetic acid(2,4-D);root induction without Plant Growth Regulators(PGR);and generation of shoot *** clusters constituted an excellent explant for micropropagation in temporary immersion bioreactors,obtaining a propagation rate of 43 shoots per explant with 1 min immersion and 6 h immersion *** new plants rooted and survived the transfer to *** study developed an in vitro propagation scheme to produce individuals that can be used either for reforestation,economical purposes,or to carry out studies in this species to assess its full potential,avoiding exploitation from wild plants.

关键词： Agavaceae temporary immersion systems callus induction micropropagation

Antibacterial activity and inhibition against Staphylococcus aureus NorA efflux pump by ferulic acid and its esterified derivatives

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Asian Pacific Journal of Tropical Biomedicine 2021年第9期11卷 405-413页

作者： Patrícia Gonçalves Pinheiro Gilvandete Maria Pinheiro Santiago Francisco Erivaldo Freitas da Silva Ana Carolina Justino de Araújo Cícera Rejane Tavares de Oliveira Priscilla Ramos Freitas Janaína Esmeraldo Rocha JoséBezerra de Araújo Neto Maria Milene Costa da Silva Saulo Relison Tintino Irwin Rose Alencar de Menezes Henrique Douglas Melo Coutinho JoséGalberto Martins da Costa departamento de Química Biológica Programa de Pos-Graduação em Química BiológicaUniversidade Regional do Cariri–URCACrato–CEBrazil Programa de Pós-Graduação em Química Centro de CiênciasUniversidade Federal do Ceará–UFCFortaleza–CEBrazil

Objective:To evaluate the inhibitory activity of ferulic acid and four of its esterified derivatives(methyl,ethyl,propyl,and butyl)against resistance mechanisms in Staphylococcus aureus ***:Ferulic acid derivatives were obtained by esterification with methanol,ethanol,propanol,and butanol,and then characterized by hydrogen and carbon-13 nuclear magnetic resonance *** minimum inhibitory concentrations(MIC)of ferulic acid and its esterified derivatives,ethidium bromide,and norfloxacin were obtained using the microdilution test,while the efflux pump inhibition test was conducted by examining reduction in the MICs of norfloxacin and ethidium *** docking was also carried out using the Schrodinger Suite 2015 molecular modeling software.A three-dimensional model of NorA efflux pump was generated using *** best scoring model was used as a receptor for ligand-receptor ***:The methyl and butyl ester derivatives did not demonstrate significant antimicrobial ***,a significant synergic effect was evidenced when norfloxacin was combined with the ethyl and propyl esterified *** docking study demonstrated favorable energy of interaction between ferulate derivatives and NorA,and amino acid residues TYR57,TYR58,and LEU255 were present commonly in stabilizing all *** PCA analysis corroborated the docking hypothesis that the lipophilic character and hydrogen bond interactions were the most relevant characteristics involved with NorA *** pharmacokinetic parameters of ferulic acid derivatives showed good ADMET properties,demonstrating that they can be easily absorbed and have no effect or inhibit the cytochrome P450 enzyme complex,revealing their potential as drug ***:This study provides strong evidence that the molecular basis for this activity is potentially due to the NorA efflux pump.

关键词： Ferulic acid Esterified derivatives Efflux pump Staphylococcus aureus Resistance mechanisms

The endophytic mycobiota of Arabidopsis thaliana

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Fungal Diversity 2013年第3期60卷 71-89页

作者： Elena García Ángela Alonso Gonzalo Platas Soledad Sacristán centro de biotecnología y genómica de Plantas(UPM-INIA)and E.T.S.I.Agrónomos Universidad Politécnica de MadridCampus de MontegancedoAutopista M40(Km.38)28223 Pozuelo de Alarcón MadridSpain departamento de biotecnología E.T.S.I.AgrónomosUniversidad Politécnica de MadridAvda.Complutense s/n28040 MadridSpain Fundación centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía MEDINA Parque Tecnológico de las Ciencias de la Salud de GranadaAvda del Conocimiento 318100 ArmillaGranadaSpain Instituto de Recursos Naturales y Agrobiología Consejo Superior de Investigaciones CientíficasAvenida Reina Mercedes 1041012 SevillaSpain

Fungal endophytes are receiving increasing attention as resources to improve crop production and ecosystem ***,the biology and ecological significance of these symbionts remains poorly understood,due to a lack of model systems for more efficient *** this work,we have analyzed the culturable endophytic mycobiota associated,in the wild,with leaves and siliques of the model plant *** have studied the effect of biotic and abiotic factors in the frequency of fungal endophytes in plant specimens,and in the species composition of the endophytic *** results indicate that the frequency of Arabidopsis plants hosting endophytes depends on the time of the year and the phenological stage of the plant,and that the probability of endophyte colonization increases as the life cycle of the plant *** diversity of the endophytic assemblages of natural *** populations was high,and precipitation and temperature were the two main factors determining the diversity and species composition of the *** propose *** and its endophytes as a model system for an integral approach to the principles governing the endophytic lifestyle,taking advantage of the molecular tools and the abundant knowledge accessible from the host plant.

关键词： Endophyte Mycobiota Arabidopsis Wild populations Ecology

Precision medicine in pantothenate kinase-associated neurodegeneration

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Neural Regeneration Research 2019年第7期14卷 1177-1185页

作者： Mónica álvarez-Córdoba Marina Villanueva-Paz Irene Villalón-García Suleva Povea-Cabello Juan M.Suárez-Rivero Marta Talaverón-Rey Javier Abril-Jaramillo Ana Belén Vintimilla-Tosi José A.Sánchez-Alcázar centro Andaluz de Biología del desarrollo(CABD-CSIC-Universidad Pablo de Olavide) and Centro de Investigación Biomédica en Red:Enfermedades RarasInstituto de Salud Carlos Ⅲ centro de Neurología Avanzada centro Civet

Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas,mainly the basal *** predominant clinical symptoms include spasticity,progressive dystonia,Parkinson's disease-like symptoms,neuropsychiatric alterations,and retinal *** the neurodegeneration with brain iron accumulation disorders,the most frequent subtype is pantothenate kinase-associated neurodegeneration(PKAN) caused by defects in the gene encoding the enzyme pantothenate kinase 2(PANK2)which catalyzed the first reaction of the coenzyme A biosynthesis *** there is no effective treatment to prevent the inexorable course of these *** aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in ***,we have described that dermal fibroblasts obtained from PKAN patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules,mitochondrial dysfunction and a pronounced increase of markers of oxidative *** addition,PKAN fibroblasts showed a morphological senescence-like ***,pantothenate supplementation,the substrate of the PANK2 enzyme,corrected all pathophysiological alterations in responder PKAN fibroblasts with low/residual PANK2 enzyme ***,pantothenate treatment had no favourable effect on PKAN fibroblasts harbouring mutations associated with the expression of a truncated/incomplete *** correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAN *** observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PANK2 in s

关键词： neurodegeneration with brain iron accumulation pantothenate kinase-associated neurodegeneration pantothenate kinase 2 pantothenate induced neurons precision medicine induced neuron fibroblast

Identification of Soybean genes Involved in Circadian Clock Mechanism and Photoperiodic Control of Flowering Time by In Silico Analyses

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Journal of Integrative Plant Biology 2007年第11期49卷 1640-1653页

作者： VeraQuecini MariaI.Zucchi JoséBaldin NatalA.Vello InstitutoAgron mico de Campinas Centro de Pesquisa e Desenvolvimento de Recursos GenéticosCampinasSP 13075-630Brazil departamento de genética ESALQUniversidade de Sāo PauloPiracicabaSP 13400-970Brazil

Glycine max is a photoperiodic short-day plant and the practical consequence of the response is latitude and sowing period limitations to commercial crops. genetic and physiological studies using the model plants Arabidopsis thaliana and rice （Oryza sativa） have uncovered several genes and genetic pathways controlling the process, however information about the corresponding pathways in legumes is scarce. Data mining prediction methodologies, including multiple sequence alignment, phylogeneUc analysis, bioinformaUcs expression and sequence motif pattern identification, were used to identify soybean genes involved in day length perception and photoperiodic flowering induction. We have investigated approximately 330 000 sequences from open-access databases and have identified all bona fide central oscillator genes and circadian photoreceptors from A. thaliana in soybean sequence databases. We propose a working model for the photoperiodic control of flowering time in G. max, based on the identified key components. These results demonstrate the power of comparative genomics between model systems and crop species to elucidate the several aspects of plant physiology and metabolism.

关键词： circadian clock cryptochrome data mining flowering photoperiod phytochrome.

A simple and fast method to calculate the coil currents and the external poloidal flux and magnetic field for fixed boundary equilibria

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Plasma Science and Technology 2024年第11期26卷 65-70页

作者： Ricardo FARENGO Pablo L GARCÍA-MARTÍNEZ Hugo E FERRARI centro Atómico Bariloche Comisión Nacional de Energía AtómicaBariloche 8400Argentina Instituto Balseiro Universidad Nacional de CuyoBariloche 8400Argentina CONICET CCT-Patagonia Norte Bariloche 8400Argentina

A simple and fast method to calculate the coil currents and the external poloidal flux and magnetic field consistent with a given internal magnetohydrodynamic(MHD) equilibrium and coil geometry is presented. The constrained optimization technique employed allows to fix the exact position of the X-points. The external poloidal flux and field are calculated using Green's functions expressed in terms of elliptic integrals that are calculated using a fast and accurate *** calculation can be limited to the region between the plasma and the device wall. An example for a double null configuration is presented.

关键词： MHD equilibrium Green's functions tokamak

Together but not scrambled:A perspective on chaotic printing/bioprinting

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Aggregate

Aggregate 2024年第4期5卷 1-11页

作者： Grissel Trujillo-de Santiago Mario Moisés Alvarez centro de biotecnología-FEMSA Tecnologico de MonterreyMonterreyNuevo LeonMéxico departamento de Ingeniería Mecatrónica y Eléctrica Escuela de Ingeniería y CienciasTecnologico de MonterreyMonterreyNuevo LeonMéxico

Structures in nature are often multi-material,and their structures have aﬁne bal-ance between segregation and aggregation(mixed,but not scrambled)that provides *** fabrication,a technology that exploits the ability of chaotic advection to create predictable and reproducible multilayered structures,excels at producing materials where this balance can be achieved andﬁnely *** method is based on the use of chaotic mixing systems,which can produce constructs with highly organized internal micro-architecture in a simple and cost-effective *** manuscript provides a perspective on how chaotic printing can be a great enabler in the manufacture of advanced materials,including living *** printing may overcome many of the critical hurdles that are currently faced in man-ufacturing and biofabrication(e.g.,creating a wide array of interfaces,reaching high resolutions rapidly and at low cost,and producing densely vascularized tissues).The manuscript introduces the technology,explains how the idea originated,presents a timeline that provides a recapitulation of the milestones achieved so far,describes the main characteristics,advantages,limitations,and challenges of the technology,and concludes with future perspectives on the evolution and use of this versatile method.

关键词： advanced materials bioprinting chaotic bioprinting chaotic printing multilayered multimaterial

Melatonin modifies SOX2^+ cell proliferation in dentate gyrus and modulates SIRT1 and MECP2 in long-term sleep deprivation

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Neural Regeneration Research 2019年第10期14卷 1787-1795页

作者： Alan Hinojosa-Godínez Luis F. Jave-Suarez Mario Flores-Soto Alma Y. Gálvez-Contreras Sonia Luquín Edith Oregon-Romero Oscar González-Pérez Rocio E. González-Castaneda Laboratorio de Microscopía de Alta Resolución Departamento de NeurocienciasCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajaraMéxico Laboratorio de Neurociencias Facultad de PsicologíaUniversidad de ColimaColimaMéxico División de Inmunología Centro de Investigación Biomédica de OccidenteInstituto Mexicano del Seguro SocialGuadalajaraMéxico División de Neurociencias Centro de Investigación Biomédica de OccidenteInstituto Mexicano del Seguro SocialGuadalajaraMéxico Instituto de Investigación en Ciencias Biomédicas (IICB) Departamento de Biología Molecular y GenómicaCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajaraMéxico Unidad de Atención en Neurociencias Departamento de Neurociencias. Centro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajaraMéxico

Melatonin is a pleiotropic molecule that,after a short-term sleep deprivation,promotes the proliferation of neural stem cells in the adult ***,this effect has not been observed in long-term sleep *** precise mechanism exerted by melatonin on the modulation of neural stem cells is not entirely elucidated,but evidence indicates that epigenetic regulators may be involved in this *** this study,we investigated the effect of melatonin treatment during a 96-hour sleep deprivation and analyzed the expression of epigenetic modulators predicted by computational text mining and keyword *** results showed that the administration of melatonin under sleep-deprived conditions increased the MECP2 expression and reduced the SIRT1 expression in the dentate *** observed that let-7 b,mir-132,and mir-124 were highly expressed in the dentate gyrus after melatonin administration,but they were not modified by sleep *** addition,we found more Sox2^+/5-bromo-2’-deoxyuridine(BrdU)^+cells in the subgranular zone of the sleep-deprived group treated with melatonin than in the untreated *** findings may support the notion that melatonin modifies the expression of epigenetic mediators that,in turn,regulate the proliferation of neural progenitor cells in the adult dentate gyrus under long-term sleep-deprived *** procedures performed in this study were approved by the Animal Ethics Committee of the University of Guadalajara,Mexico(approval ***-16610)on January 2,2016.

关键词： sleep-deprivation melatonin microRNA neurogenesis Sirtuin 1 SIRT1 methyl-CpG-binding protein 2 MECP2 epigenetic text-mining mir-9 let-7b