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Involvement of Met receptor pathway in aggressive behavior of colorectal cancer cells induced by parathyroid hormone-related peptide

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World Journal of Gastroenterology 2022年第26期28卷 3177-3200页

作者： María Belén Novoa Díaz Pedro Carriere Graciela Gigola Ariel Osvaldo Zwenger Natalia Calvo Claudia Gentili departamento de Biología Bioquímica y FarmaciaUniversidad Nacional del Sur(UNS)-INBIOSUR(CONICET-UNS)Bahía Blanca 8000Buenos AiresArgentina Centro de Estudios Clínicos SAGA CEC SAGASantiago de Chile 8320000Chile

BACKGROUND Parathyroid hormone-related peptide(PTHrP)plays a key role in the development and progression of many *** found that in colorectal cancer(CRC)HCT116 cells,the binding of PTHrP to its receptor PTHR type 1(PTHR1)activates events associated with an aggressive *** HCT116 cell xenografts,PTHrP modulates the expression of molecular markers linked to tumor *** evidence suggests that the Met receptor is involved in the development and evolution of *** on these data,we hypothesized that the signaling pathway trigged by PTHrP could be involved in the transactivation of Met and consequently in the aggressive behavior of CRC *** To elucidate the relationship among PTHR1,PTHrP,and Met in CRC *** For in vitro assays,HCT116 and Caco-2 cells derived from human CRC were incubated in the absence or presence of PTHrP(1-34)(10-8 M).Where indicated,cells were pre-incubated with specific kinase inhibitors or dimethylsulfoxide,the vehicle of the *** protein levels were evaluated by Western blot ***-time polymerase chain reaction(RT-qPCR)was carried out to determine the changes in gene *** healing assay and morpho logical monitoring were performed to evaluate cell migration and changes related to the epithelialmesenchymal transition(EMT),*** number of viable HCT116 cells was counted by trypan blue dye exclusion test to evaluate the effects of irinotecan(CPT-11),oxaliplatin(OXA),or doxorubicin(DOXO)with or without *** in vivo tests,HCT116 cell xenografts on 6-wk-old male N:NIH(S)_nu mice received daily intratumoral injections of PTHrP(40μg/kg)in 100μL phosphate-buffered saline(PBS)or the vehicle(PBS)as a control during 20 *** slaughter was carried out and the tumors were removed,weighed,and fixed in a 4%formaldehyde solution for subsequent treatment by *** evaluate the expression of molecular markers in human tumor samples,we studied 23 specimens ob

关键词： PTHrP MET receptor tyrosine kinase Parathyroid hormone receptor type 1 Colorectal cancer Drug resistance

Impact of chitosan-based nanocarriers on cytoskeleton dynamics:Current status and challenges

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BIOCELL 2022年第4期46卷 885-891页

作者： M.CAROLINA DI SANTO AGUSTINA ALAIMO ANA PAULA DOMÍNGUEZ RUBIO OSCAR E.PÉREZ departamento de Química Biológica Facultad de Ciencias Exactas y NaturalesUniversidad de Buenos AiresBuenos AiresArgentina Instituto de Química Biológica de la facultad de Ciencias Exactas y Naturales Consejo Nacional de Investigaciones Científicas y Técnicas(IQUIBICENCONICET)Buenos AiresArgentina

Chitosan-based nanocarriers(CS-NCs)show a promising role in improving drugs and bioactive compounds delivery for ***,the effects exerted by CS-NCs at the cellular level,including their recognition and uptake,have not been fully investigated *** factors,including size,shape,concentration,and surface chemistry of CS-NCs,play an important role in determining the types of intracellular signals *** mechanism of uptake and the involvement of the cytoskeleton during the CS-NCs endocytosis variates among the different cell types as well as further effects observed inside *** the present work,we discuss the effects induced by CS-NCs per se on the cytoskeleton,a key component in cell architecture and *** focus of this report is made on tumoral and normal biological models in which CS-NCs could differentially affect the cell *** recent years reports regarding the impact of CS-NCs on cytoskeleton dynamics and the current techniques for its evaluation are summarized and *** mechanisms underlying cytoskeletal impact after cell exposure to CS-NCs is critical for the design of safest value-added formulations in the biomedical ***,this revision points out some interesting aspects of cytoskeletal changes and cell death encompassing anti-tumoral effects.

关键词： Cytoskeletal dynamics Cellular uptake Endocytosis Nanocarriers Chitosan Bioactive compounds

Astrocytes protect dopaminergic neurons against aminochrome neurotoxicity

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Neural Regeneration Research 2022年第9期17卷 1861-1866页

作者： Juan Segura-Aguilar Bengt Mannervik JoséInzunza Mukesh Varshney Ivan Nalvarte Patricia Muñoz Molecular and Clinical Pharmacology ICBM Faculty of Medicine University of Chile SantiagoChile department of Biochemistry and Biophysics Arrhenius LaboratoriesStockholm UniversityStockholmSweden department of Biosciences and Nutrition Karolinska InstitutetStockholmSweden Nucleo de Química y bioquímica Facultad de Estudios InterdisciplinariosUniversidad MayorSantiagoChile

Astrocytes protect neurons by modulating neuronal function and *** support neurons in several *** provide energy through the astrocyte-neuron lactate shuttle,protect neurons from excitotoxicity,and internalize neuronal lipid droplets to degrade fatty acids for neuronal metabolic and synaptic support,as well as by their high capacity for glutamate uptake and the conversion of glutamate to glutamine.A recent reported astrocyte system for protection of dopamine neurons against the neurotoxic products of dopamine,such as aminochrome and other o-quinones,were generated under neuromelanin synthesis by oxidizing dopamine catechol *** secrete glutathione transferase M2-2 through exosomes that transport this enzyme into dopaminergic neurons to protect these neurons against aminochrome *** role of this new astrocyte protective mechanism in Parkinson´s disease is discussed.

关键词： aminochrome astrocytes dopamine dopaminergic neurons exosomes glutathione transferase M2-2 neuroprotection Parkinson’s disease

Highly graphitized carbon nanosheets with embedded Ni nanocrystals as anode for Li-ion batteries

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Nano Research 2020年第1期13卷 86-94页

作者： Francisco Javier Soler-Piña Celia Hernández-Rentero Alvaro Caballero Julián Morales Enrique Rodríguez-Castellón Jesús Canales-Vázquez Dpto.Química Inorgánica e Ingeniería Química Instituto de Química Fina y NanoquímicaUniversidad de Córdoba14071CórdobaSpain Dpto.Química Inorgánica Cristalografía y MineralogíaFacultad de CienciasUniversidad de Málaga29071MálagaSpain Instituto de Energías Renovables Universidad de Castilla-La ManchaPaseo de La Investigación 102071AlbaceteSpain

A C/Ni composite was prepared via thermal decomposition of a nickel oleate complex at 700℃,yielding disperse Ni nanocrystals with an average size of 20 nm,encapsulated by carbon nanosheets as deduced from transmission electron microscopy(TEM)images and confirmed from X-ray photoelectron spectroscopy(XPS).Furthermore,the X-ray diffraction pattern revealed a good ordering of the carbon layers,forced by the Ni encapsulation to adopt a bending *** the close interaction between the graphitized framework and the metallic nanoparticles we have studied the properties of the composite as an anode for Li-ion *** with other nanostructured synthetic carbons,this carbon composite has a low voltage hysteresis and a modest irreversible capacity value,properties that play a significant role in its behaviour as electrodes in full cell *** moderate rate values,0.25 C,the electrode delivers an average capacity value around 723 mAh·g^−1 on cycling,among the highest values so far reported for this carbon *** higher rate values,1 C,the average capacity values delivered by the cell on cycling decrease,around 205 mAh·g^−1,but it maintains good capacity retention,a coulombic efficiency close to 100%after the first cycles and recovery of the capacity values when the rate is restored from 3 to 0.1 C.

关键词： carbon nanosheets nickel nanoparticles anode lithium batteries

Involvement of parathyroid hormone-related peptide in the aggressive phenotype of colorectal cancer cells

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World Journal of Gastroenterology 2021年第41期27卷 7025-7040页

作者： María Belén Novoa Díaz Pedro Matías Carriere María Julia Martín Natalia Calvo Claudia Gentili departamento de Biología Bioquímica y FarmaciaUniversidad Nacional del Sur(UNS)-INBIOSUR(CONICET-UNS)Bahía Blanca 8000Buenos AiresArgentina departamento de Química Universidad Nacional del Sur(UNS)-INQUISUR(CONICET-UNS)Bahía Blanca 8000Buenos AiresArgentina

Colorectal cancer(CRC)remains one of the leading causes of mortality from malignant diseases *** general terms,CRC presents high heterogeneity due to the influence of different genetic and environmental factors;also,the neoplastic cells are strongly influenced by the extracellular matrix and several surrounding cells,known together as the tumor microenvironment(TME).Bidirectional communication takes place between the tumor and the TME through the release of autocrine and paracrine *** hormone-related peptide(PTHrP)is a cytokine secreted by a wide variety of tissues and is able to regulate several cellular functions both in physiological as well as in pathological *** exerts its effects as a paracrine/autocrine factor,although its mode of action is mainly *** has been shown that this peptide is expressed by several tumors and that the tumor secretion of PTHrP is responsible for the malignant humoral *** years ago,when our research group started studying PTHrP effects in the experimental models derived from intestinal tumors,the literature available at the time addressing the effects of PTHrP on colorectal tumors was limited,and no articles had been published regarding to the paracrine action of PTHrP in CRC *** on this and on our previous findings regarding the role of PTH in CRC cells,our purpose in recent years has been to explore the role of PTHrP in *** analyzed the behavior of CRC cells treated with exogenous PTHrP,focalizing in the study of the following events:Survival,cell cycle progression and proliferation,migration,chemoresistance,tumor-associated angiogenesis,epithelial to mesenchymal transition program and other events also associated with invasion,such us the induction of cancer stem cells *** work summarizes the major findings obtained by our investigation group using in vitro and in vivo CRC models that evidence the participation of PTHrP in the acquisition of an aggressiv

关键词： Parathyroid hormone-related protein Colorectal cancer Tumor biomarkers Neoplastic processes Drug resistance Tumor microenvironment

Biorefinery of Rice Husk to Obtain Functionalized Bioactive Compounds

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Journal of Renewable Materials 2019年第4期7卷 313-324页

作者： M.Lopretti N.Lecot A.Rodriguez G.Lluberas F.Orozco L.Bolaños G.Montes de Oca H.Cerecetto J.Vega-Baudrit Laboratorio de Técnicas Nucleares Aplicadas a bioquímica y Biotecnología Centro de Investigaciones Nucleares-Facultad de CienciasMataojo 2055Montevideo CP 11400Uruguay Área de Radiofarmacia Centro de Investigaciones Nucleares-Facultad de CienciasMataojo 2055Montevideo CP 11400Uruguay Química Bioanalítica Instituto Polo Tecnológico de Pando-Facultad de QuímicaUdelaRBy Pass de Pando y Ruta 8Pando-Canelones CP 91000Uruguay Laboratorio de Nacional de Nanotecnología-CeNAT-CONARE Costa Rica 1174-1200San JoséCP 10109Costa Rica Laboratorio de Polímeros POLIUNA-Escuela de Química Universidad NacionalHerediaSan JoséCP 86-3000Costa Rica

The biomass industrialization valorisation of grains and cereals is considered an opportunity for the countries where agro-industrial activity is one of its main economic activities,rendering new higher-value products with a concomitant solution to waste accumulation *** that end,in this work we describe and characterise bioactive compounds generation from rice husk by semisolid fermentation,obtained from 500 g of the material at room temperature and 60%humidity with mixed cultures of Phanerochaete chrysosporium and Gloeophyllum *** extract was evaluated in different situations:murine mammary tumour cells(4T1),normal cells(NIH 3T3)and in Lactobacillus acidophilus,and Trichoderma *** results exhibited that the extract inhibited 4T1 cells at concentrations higher than 20μg/mL,but did not inhibit normal cells,and displayed germicide activity after 3 days *** propose that these functionalized compounds have a potential application in industry/agriculture/medicine obtained from rice husk waste.

关键词： Biorefinery rice husk bioactive compounds valorisation of biomass veratryl alcohol

HASTy modulates miRNA biogenesis by linking pri-miRNA transcription and processing

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Molecular Plant 2021年第3期14卷 426-439页

作者： Damian A.Cambiagno Axel J.Giudicatti Agustin L.Arce delfina Gagliardi Lei Li Wei yuan derek S.Lundberg detlef Weigel Pablo A.Manavella Instituto de Agrobiotecnologı´a del Litoral(CONICET-UNL) Ca´tedra de Biologı´a Celular y MolecularFacultad de Bioquı´mica y Ciencias Biolo´gicasUniversidad Nacional del Litoral3000 Santa FeArgentina department of Molecular Biology Max Planck Institute for Developmental Biology72076 T€ubingenGermany

Post-transcriptional gene silencing mediated by microRNAs(miRNAs)modulates numerous developmental and stress response *** the last two decades,HASTy(HST),the ortholog of human EXPORTIN 5,was considered to be a candidate protein that exports plant miRNAs from the nucleus to the ***,we report that HST functions in the miRNA pathway independent of its cargo-exporting activity in *** found that Arabidopsis mutants with impaired HST shuttling exhibit normal subcellular distribution of ***,protein-protein interaction and microscopy assays showed that HST directly interacts with the microprocessor core component DCL1 through its N-terminal ***,mass spectrometry analysis revealed that HST also interacts independently of its N-terminal domain with the mediator complex subunit *** experiments revealed that HST could act as a scaffold to facilitate the recruitment of DCL1 to genomic MIRNA loci by stabilizing the DCL1-MED37 complex,which in turn promotes the transcription and proper processing of primary miRNA transcripts(primiRNAs).Taken together,these results suggest that HST is likely associated with the formation of the miRNA biogenesis complex at MIRNA genes,promoting the transcription and processing of primiRNAs rather than the direct export of processed miRNAs from the nucleus.

关键词： microRNA gene silencing miRNA nuclear export HASTy miRNA biogenesis

New 5-Alkenyl Resorcinols from <i>Lithraea molleoides</i>(Vell). Eng.

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American Journal of Plant Sciences 2020年第6期11卷 861-868页

作者： Alejandra Catalano Beatriz Lantaño Lucas Fabián Paula López Universidad de Buenos Aires Facultad de Farmacia y Bioquímica Cátedra de Farmacognosia Ciudad Autónoma de Buenos Aires Argentina CONICET Instituto de la Química y Metabolismo del Fármaco (IQUIMEFA) Cuidad Autónoma de Buenos Aires Argentina Universidad de Buenos Aires Facultad de Farmacia y Bioquímica Cátedra de Química Orgánica Cuidad Autónoma de Buenos Aires Argentina Universidad de Buenos Aires Facultad de Farmacia y Bioquímica Cátedra de Química Medicinal Cuidad Autónoma de Buenos Aires Argentina

Lithraea molleoides (Anacardiaceae) is a tree that grows in South America including Southern Brazil, Southern, and Eastern Bolivia, Southern Paraguay, Northern, and Central Argentina. Infusions, decoctions, or tinctures from its aerial parts (leaves, buds, and young stems) are employed in ethnomedicine mainly against respiratory, and digestive inflammations and illnesses. Antibacterial, antiviral, antioxidant, anti-inflammatory, and antinociceptive activities, among others, have been reported for L. molleoides. Many of its biological activities have been associated with the reported presence of 5-alkenyl resorcinols. Alkyl/alkenyl catechols and alkyl/alkenyl resorcinols are very common in members of the Anacardiaceae family and several activities have been attributed to them. This work describes the isolation and the structural elucidation of three new 5-alkenyl resorcinols isolated from Lithraea molleoides reported in nature for the first time.

关键词： Lithraea molleoides 5-Alkenyl Resorcinol (Z Z)-5-(Pentadeca-6 9-Dienyl)-Resorcinol (Z Z)-5-(Trideca-5 8-Dienyl)-Resorcinol (Z)-5-(Heptadec-6-Enyl)-Resorcinol

A Comparative Study on the Structural and Vibrational Properties of Two Potential Antimicrobial and Anticancer Cyanopyridine derivatives

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Open Journal of Synthesis Theory and Applications 2015年第1期4卷 1-19页

作者： María J. Márquez María B. Márquez Pablo G. Cataldo Silvia A. Brandán Cátedra de Química General Instituto de Química Inorgánica Facultad de Bioquímica Química y Farmacia Universidad Nacional de Tucumán Tucumán Argentina

2-Hydroxy-4,6-dimethylpyridine-3-carbonitrile and 2-chloro-4,6-dimethylpyridine-3-carbonitrile compounds have been studied from a theoretical point of view in order to know their structural and vibrational properties in gas and aqueous solution phases by means of density Functional Theory (DFT) calculations. The stable structures in both media were optimized by using the hybrid B3LyP/6-31G* method and the solvent effects in aqueous solution were studied by using the integral equation formalism of the polarizable continuum model (IEFPCM) employing the selfconsistent reaction field (SCRF) method. detailed vibrational analyses for both compounds in the two phases were performed combining the DFT calculations with Pulay’s Scaled Quantum Mechanics Force Field (SQMFF) methodology. The different interactions for both compounds were analyzed by means of the bond orders, atomic charges, solvation energies, dipole moments, molecular electrostatic potentials and force constants parameters. The nature of the interactions was studied by using different descriptors.

关键词： Cyanopyridine Vibrational Spectra Molecular Structure Force Field DFT Calculations