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Experimental bio-artificial liver:Importance of the architectural design on ammonia detoxification performance

World Journal of Hepatology 2018年第10期10卷 719-730页

作者： María Dolores Pizarro María Eugenia Mamprin Lucas Damián Daurelio Joaquín Valentín Rodriguez María Gabriela Mediavilla consejo Nacional de Investigaciones científicas y Técnicas(cONIcET) Rosario S2002 LRKArgentina Laboratorio de Investigaciones en Fisiología y biología Molecular Vegetal(LIFiBVe) Facultad de Ciencias AgrariasUniversidad Nacional del LitoralEsperanza 3080Argentina Facultad de ciencias Bioquímicas y Farmacéuticas Universidad Nacional de RosarioRosario S2002 LRKArgentina centro Binacional de criobiología clínica y Aplicada(cAIc) Universidad Nacional de RosarioRosario S2011 BXNArgentina Instituto de biología Molecular y celular de Rosario(IBR CONICET-UNR)Consejo Nacional de Investigaciones Científicas y Tecnológicasy Universidad Nacional de RosarioRosario S2002 LRKArgentina

AIM To determine the influence of the construction design over the biological component's performance in an experimental bio-artificial liver(BAL) *** Two BAL models for liver microorgans(LMOs) were constructed. First, we constructed a cylindrical BAL and tested it without the biological component to establish its correct functioning. Samples of blood and biological compartment(Bc) fluid were taken after 0, 60, and 120 min of perfusion. Osmolality, hematocrit, ammonia and glucose concentrations, lactate dehydrogenase(LDH) release(as a LMO viability parameter), and oxygen consumption and ammonia metabolizing capacity(as LMO functionality parameters) were determined. cPSI and OTc gene expression and function were measured. The second BAL, a "flat bottom" model, was constructed using a 25 cm2 culture flask while maintaining all other components between the models. The Bc of both BALs had the same capacity(approximately 50 cm3) and both were manipulated with the same perfusion system. The performances of the two BALs were compared to show the influence of *** The cylindrical BAL showed a good exchange of fluids and metabolites between blood and the Bc, reflected by the matching of osmolalities, and glucose and ammonia concentration ratios after 120 min of perfusion. No hemoconcentration was detected, the hematocrit levels remained stable during the whole study, and the minimal percentage of hemolysis(0.65% ± 0.10%) observed was due to the action of the peristaltic pump. When LMOs were used as biological component of this BAL they showed similar values to the ones obtained in a Normothermic Reoxygenation System(NRS) for almost all the parameters assayed. After 120 min, the results obtained were: LDH release(%): 14.7 ± 3.1 in the BAL and 15.5 ± 3.2 in the NRS(n = 6); oxygen consumption(μmol/min?g wet tissue): 1.16 ± 0.21 in the BAL and 0.84 ± 0.15 in the NRS(n = 6); relative expression of cps1 and Otc: 0.63 ± 0.12 and 0.67 ± 0.20, respectively,

关键词： Bio-artificial liver Ammonia detoxification device design Ornithine Transcarbamylase Rat liver microorgans carbamyl Phosphate SynthetaseⅠ

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icEMIGE: Integration of cEll-morphometrics, MIcrobiome, and GEne biomarker signatures for risk stratification in breast cancers

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World Journal of clinical Oncology 2022年第7期13卷 616-629页

作者： Xuan-Yu Mao Jesus Perez-Losada Mar Abad Marta Rodríguez-González cesar A Rodríguez Jian-Hua Mao Hang chang Division of biological Systems and Engineering Lawrence Berkeley National LaboratoryBerkeley94720United States Instituto de biología Molecular y celular del cáncer Universidad de SalamancaSalamanca 37007Spain department of Pathology Universidad de SalamancaSalamanca 37007Spain department of Medical Oncology Universidad de SalamancaSalamanca 37007Spain

BAcKGROUND The development of precision medicine is essential for personalized treatment and improved clinical outcome,whereas biomarkers are critical for the success of precision *** To investigate whether icEMIGE(integration of cEll-morphometrics,MIcro-biome,and GEne biomarker signatures)improves risk stratification of breast cancer(Bc)*** We used our recently developed machine learning technique to identify cellular morphometric biomarkers(cMBs)from the whole histological slide images in The cancer Genome Atlas(TcGA)breast cancer(TcGA-BRcA)*** cox regression was used to assess whether cell-morphometrics prognosis score(cMPS)and our previously reported 12-gene expression prognosis score(GEPS)and 15-microbe abundance prognosis score(MAPS)were independent prognostic *** was built upon the sparse representation learning *** icEMIGE scoring model performance was measured by the area under the receiver operating characteristic curve compared to cMPS,GEPS,or MAPS *** models were created to predict overall survival(OS)and progress-free survival(PFS)rates at 5-and 10-year in the TcGA-BRcA *** We identified 39 cMBs that were used to create a cMPS system in ***,GEPS,and MAPS were found to be significantly independently associated with *** then established an icEMIGE scoring system for risk stratification of Bc *** iGEMIGE score has a significant prognostic value for OS and PFS independent of clinical factors(age,stage,and estrogen and progesterone receptor status)and PAM50-based molecular ***,the icEMIGE score significantly increased the power to predict OS and PFS compared to cMPS,GEPS,or MAPS *** Our study demonstrates a novel and generic artificial intelligence framework for multimodal data integration toward improving prognosis risk stratification of Bc patients,which can be extended to other types of cancer.

关键词： Breast cancer Gene signature Microbiome signature cellular morphometrics signature Multimodal data integration Prognosis

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Epigenetic basis of Alzheimer disease

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World Journal of biological chemistry 2020年第2期11卷 62-75页

作者： Angeles c Tecalco-cruz JosuéO Ramírez-Jarquín María E Alvarez-Sánchez Jesus Zepeda-cervantes Programa en ciencias Genómicas Universidad Autónoma de la Ciudad de MéxicoMexico 03100Mexico División de neurociencias Instituto de Fisiología CelularUniversidad Nacional Autónoma de MéxicoMexico 04510Mexico Posgrado en ciencias Genómicas Universidad Autónoma de la CiudadMexico 03100Mexico biología celular y de desarrollo Instituto de Fisiología CelularUniversidad Nacional Autónoma de MéxicoMexico 04510Mexico

Alzheimer disease(AD)is the primary form of dementia that occurs spontaneously in older ***,the epigenetic profile of the cells forming the central nervous system changes during aging and may contribute to the progression of some neurodegenerative diseases such as *** this review,we present general insights into relevant epigenetic mechanisms and their relationship with aging and *** data suggest that some epigenetic changes during aging could be utilized as biomarkers and target molecules for the prevention and control of AD.

关键词： Epigenetics Aging Neurodegenerative diseases Alzheimer disease

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Exploring transposable element-based markers to identify allelic variations underlying agronomic traits in rice

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Plant communications 2022年第3期3卷 59-71页

作者： Haidong Yan David c.Haak Song Li Linkai Huang Aureliano Bombarely School of Plant and Environmental Sciences Virginia TechBlacksburgVA 24061USA Graduate Program in Genetics Bioinformatics and Computational Biology(GBCB)Virginia TechBlacksburgVA 24061USA department of Grassland Science Animal Science and Technology CollegeSichuan Agricultural UniversityChengdu 611130China department of Bioscience Universita degli Studi di Milano(UNIMI)20133 MilanoItaly Instituto de biologıa Molecular y celular de Plantas(IBMcP) UPV-CSIC46022 ValenciaSpain

Transposable elements(TEs)are a major force in the production of new alleles during domestication;nevertheless,their use in association studies has been limited because of their *** have developed a TE genotyping pipeline(TEmarker)and applied it to whole-genome genome-wide association study(GWAS)data from 176 Oryza sativa *** accessions to identify genetic elements associated with specific agronomic *** markers recovered a large proportion(69%)of single-nucleotide polymorphism(SNP)-based GWAS peaks,and these TE peaks retained ca.25%of the *** use of TEs in GWASs may reduce false positives associated with linkage disequilibrium(LD)among SNP markers.A genome scan revealed positive selection on TEs associated with agronomic *** found several cases of insertion and deletion variants that potentially resulted from the direct action of TEs,including an allele of LOc_Os11g08410 associated with plant height and panicle length ***,these findings reveal the utility of TE markers for connecting genotype to phenotype and suggest a potential role for TEs in influencing phenotypic variations in rice that impact agronomic traits.

关键词： transposable element marker agronomic trait rice GWAS

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Trichomonas vaginalis perturbs the junctional complex in epithelial cells

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cell Research 2005年第9期 29-41页

作者： Rodrigo Furtado MAdeIRO da cOSTA,Wanderley de SOUZA,Marlene BENcHIMOL,John F ALdeRETE,José Andrés MORGADO-DíAZ Programa de Pós Graduao em ciências Morfológicas Universidade Federal do Rio de Janeiro Rio de Janeiro RJ 20231- 050 Brazil Grupo de biologia Estrutural Diviso de biologia celular centro de Pesquisa Instituto Nacional de cancer Rio de Janeiro RJ 20231-050 Brazil Grupo de biologia Estrutural Diviso de biologia celular centro de Pesquisa Instituto Nacional de cancer Rio de Janeiro RJ 20231-050 Brazil Laboratório de Ultraestrutura celular Hertha Meyer Instituto de Biofísica carlos chagas Filho Universidade Federal do Rio de Janeiro centro de ciências da Saúde Rio de Janeiro RJ 21944-900 Brazil Laboratório de Ultraestrutura celular Universidade Santa úrsula Rio de Janeiro RJ 22231-010 Brazil department of Microbiology University of Texas Health Science center San Antonio TX 78229-3900 USA Grupo de biologia Estrutural Diviso de biologia celular centro de Pesquisa Instituto Nacional de cancer Rio de Janeiro RJ 20231-050 Brazil

Trichomonas vaginalis, a protist parasite of the urogenital tract in humans, is the causative agent of trichomonosis, which in recent years have been associated with the cervical cancer development. In the present study we analyzed the modifications at the junctional complex level of caco-2 cells after interaction with two isolates of T. vaginalis and the influence of the iron concentration present in the parasite’s culture medium on the interaction effects. Our results show that T. vaginalis adheres to the epithelial cell causing alterations in the junctional complex, such as: (a) a decrease in transepithelial electrical resistance; (b) alteration in the pattern of junctional complex proteins distribution as observed for E-cadherin, occludin and ZO-1; and (c) enlargement of the spaces between epithelial cells. These effects were dependent on (a) the degree of the parasite virulence isolate, (b) the iron concentration in the culture medium, and (c) the expression of adhesin proteins on the parasite surface.

关键词： Trichomonas vaginalis caco-2 junctional complex proteins transepithelial electrical resistance adhesins.

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Neuroprotective effects of meloxicam on transient brain ischemia in rats:the two faces of anti-inflammatory treatments

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Neural Regeneration Research 2023年第9期18卷 1961-1967页

作者： Irene Fernández Ugidos Paloma González-Rodríguez María Santos-Galdiano Enrique Font-Belmonte Berta Anuncibay-Soto Diego Pérez-Rodríguez JoséManuel Gonzalo-Orden Arsenio Fernández-López Área de biología celular Instituto de BiomedicinaCampus de Vegazana s/nUniversidad de LeónLeónSpain Neural Therapies SL.Edif.Institutos de Investigación.Planta baja.Local B43.campus de Vegazana s/n.León.Spain department of Medicina Cirugía y Anatomía VeterinariaUniversity of LeónLeónSpain department of Pharmacology Tulane University School of MedicineNew OrleansLAUSA department of Neurology David Geffen School of Medicine at University of California(UCLA)Los AngelesCAUSA department of Life Sciences Imperial College London(ICL)LondonUK department of clinical and Movement Neurosciences UCL Queen Square Institute of NeurologyLondonUK

The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic *** use of non-ste roidal anti-inflammatory drugs has been a matter of debate as to whether they have beneficial or detrimental *** this context,the effects of the anti-inflammatory agent meloxicam have been scarcely documented after stro ke,but its ability to inhibit both cyclooxygenase isoforms(1 and 2) could be a promising strategy to modulate postischemic *** study analyzed the effect of meloxicam in a transient focal cerebral ischemia model in rats,measuring its neuroprotective effect after 48 hours and 7 days of reperfusion and the effects of the treatment on the glial scar and regenerative events such as the generation of new progenitors in the subventricular zone and axonal sprouting at the edge of the damaged *** show that meloxicam’s neuroprotective effects remained after 7 days of reperfusion even if its administration was restricted to the two first days after ***,meloxicam treatment modulated glial scar reactivity,which matched with an increase in axonal ***,this treatment decreased the formation of neuronal progenitor *** study discusses the dual role of anti-inflammatory treatments after stro ke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies.

关键词： anti-inflammatories astrocyte axonal sprouting cylinder test doublecortin focal brain ischemia glial scar inflammation neuroprotection new neuron generation transient stroke

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Low-Dose Gamma Radiation Fields decrease cell Viability, Damage DNA, and Increase the Expression of Hsp70 and p53 Proteins in Human Leukocytes

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World Journal of Nuclear Science and Technology 2023年第4期13卷 55-72页

作者： Jessica Lizbeth Sifuentes Padilla David Alejandro García López consuelo Letechipia de León Hector Rene Vega-carrillo Sergio Hugo Sánchez Rodríguez Laboratorio de biología celular y Neurobiología Unidad Académica de Ciencias Biológicas Universidad Autónoma de Zacatecas Zacatecas México Laboratorio de Radiobiología Unidad Académica de Estudios Nucleares Universidad Autónoma de Zacatecas Zacatecas México

Ionizing radiations are tools in diagnosis and treatment of diseases. Leukopenia from exposure to ionizing radiation has been reported. Due to their radiosensitivity, leukocytes are a biological model to analyze cell damage. Therefore, cell viability, DNA damage, and Hsp70 and p53 expression in human leukocytes exposed to low-dose gamma radiation fields from a 137cs source were evaluated. A decrease in cell viability, DNA damage and an increase in the expression of Hsp70 and p53 proportional to the radiation dose received was found, which was 0.2, 0.4, 0.6, 0.8 and 1.0 mGy.

关键词： Leukocytes Gamma Radiation cell Damage DNA Hsp70 p53

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Medicinal properties of Angelica archangelica root extract: cytotoxicity in breast cancer cells and its protective effects against in vivo tumor development

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Journal of Integrative Medicine 2019年第2期17卷 132-140页

作者： carlos R.Oliveira Daniel G.Spindola Daniel M.Garcia Adolfo Erustes Alexandre Bechara caroline Palmeira-dos-Santos Soraya S.Smaili Gustavo J.S.Pereira André Hinsberger Ezequiel P.Viriato Maria cristina Marcucci Alexandra c.H.F.Sawaya Samantha L.Tomaz Elaine G.Rodrigues claudia Bincoletto departamento de Farmacologia Escola Paulista de Medicina (EPM) Universidade Federal de Sao Paulo (UNIFESP) Grupo de Fitocomplexos e Sinalizacao celular Escola de Ciências da Saúde Universidade Anhembi Morumbi Faculdade de ciências Farmacêuticas e Bioquímicas Oswaldo cruz Laboratório de Produtos Naturais e Quimiometria Programa de pós-graduacao em Farmácia e Biotecnologia Universidade Anhanguera de Sao Paulo Faculdade de ciências Farmacêuticas Universidade Estadual de Campinas (UNICAMP) Unidade de Oncologia Experimental EPM Universidade Federal de Sao Paulo (UNIFESP)

Objective: Although Angelica archangelica is a medicinal and aromatic plant with a long history of use for both medicinal and food purposes, there are no studies regarding the antineoplastic activity of its *** study aimed to evaluate the cytotoxicity and antitumor effects of the crude extract of A. archangelica root(cEAA) on breast ***: The cytotoxicity of cEAA against breast adenocarcinoma cells(4T1 and McF-7) was evaluated by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT) assay. Morphological and biochemical changes were detected by Hoechst 33342/propidium iodide(PI) and annexin V/PI staining. cytosolic calcium mobilization was evaluated in cells staining with FURA-4 NW. Immunoblotting was used to determine the effect of cEAA on anti-and pro-apoptotic proteins(Bcl-2 and Bax, respectively).The 4 T1 cell-challenged mice were used for in vivo ***: Using ultra-high-performance liquid chromatography–mass spectrometry analysis, angelicin, a constituent of the roots and leaves of A. archangelica, was found to be the major constituent of the cEAA evaluated in this study(73 mg/mL). The cEAA was cytotoxic for both breast cancer cell lines studied but not for human fibroblasts. Treatment of 4 T1 cells with the cEAA increased Bax protein levels accompanied by decreased Bcl-2 expression, in the presence of cleaved caspase-3 and cytosolic calcium mobilization, suggesting mitochondrial involvement in breast cancer cell death induced by the cEAA in this cell line. No changes on the Bcl-2/Bax ratio were observed in cEAA-treated McF7 cells. Gavage administration of the cEAA(500 mg/kg) to 4T1 cell-challenged mice significantly decreased tumor growth when compared with untreated ***: Altogether, our data show the antitumor potential of the cEAA against breast cancer cells in vitro and in vivo. Further research is necessary to better elucidate the pharmacological application of the cEAA in breast cancer therapy.

关键词： Angelica archangelica Umbelliferae Apoptosis cell death Breast cancer Angelicin

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Thinking outside the black box:are the brain endothelial cells the new main target in Alzheimer's disease?

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Neural Regeneration Research 2023年第12期18卷 2592-2598页

作者： Enrique Estudillo Adolfo López-Ornelas Alejandro Rodríguez-Oviedo Neptali Gutiérrez de la cruz Marco Antonio Vargas-Hernández Adriana Jiménez Laboratorio de Reprogramación celular Instituto Nacional de Neurología y Neurocirugía Manuel Velasco SuárezMexico CityMexico División de Investigación Hospital Juárez de MéxicoMexico CityMexico Hospital Nacional Homeopático Hospitales Federales de ReferenciaMexico CityMexico Facultad de ciencias Universidad Nacional Autónoma de MéxicoMexico CityMexico Laboratorio de Morfología Escuela Militar de Graduados de SanidadSecretaría de la Defensa NacionalBatalla de CelayaLomas de SoteloMiguel HidalgoMexico CityMexico Escuela Militar de Graduados de Sanidad Secretaría de la Defensa NacionalBatalla de CelayaLomas de SoteloMiguel HidalgoMexico CityMexico

The blood-brain barrier is the interface through which the brain interacts with the milieu and consists mainly of a sophisticated network of brain endothelial cells that forms blood vessels and selectively moves molecules inside and outside the brain through multiple mechanisms of *** brain endothelial cell function is crucial for brain homeostasis,their role in neurodegenerative diseases has historically not been considered with the same importance as other brain cells such as microglia,astroglia,neurons,or even molecules such as amyloid beta,Tau,or ***'s disease is the most common neurodegenerative disease,and brain endothelial cell dysfunction has been reported by several ***,its impairment has barely been considered as a potential therapeutic *** we review the most recent advances in the relationship between Alzheimer's disease and brain endothelial cells commitment and analyze the possible mechanisms through which their alterations contribute to this neurodegenerative disease,highlighting their inflammatory phenotype and the possibility of an impaired secretory pattern of brain endothelial cells that could contribute to the progression of this ***,we discuss why shall brain endothelial cells be appreciated as a therapeutic target instead of solely an obstacle for delivering treatments to the injured brain in Alzheimer's disease.

关键词： dementia endothelial cells neurodegeneration neuroinflammation neuronal death paracellular transport transcellular transport

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Altered Liver Gene Expression Due to Hypertension and Age in Rats

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Journal of Biosciences and Medicines 2023年第8期11卷 82-94页

作者： María Dolores Ronquillo-Sánchez Jorge Ramírez-Salcedo Itzell Alejandrina Gallardo-Ortíz Rafael Villalobos-Molina Unidad de Biomedicina Facultad de Estudios Superiores Iztacala Universidad Nacional Autónoma de México Tlalnepantla México departamento de biología celular y del desarrollo Instituto de Fisiología Celular Universidad Nacional Autónoma de México Ciudad de México México carrera de Enfermería Facultad de Estudios Superiores Iztacala Universidad Nacional Autónoma de México Tlalnepantla México

Hypertension and metabolic syndrome, both of which increase with age, are multifactorial disorders. Their etiology is complex, making it challenging to isolate involved genes. This study aimed to characterize the hepatic gene expression in spontaneously hypertensive rats (SHR) at different ages. Blood pressure in SHR was determined by tail-cuff method at one and three months of age. Hepatic RNA was isolated and gene expression was compared using microarrays. comparison between SHR and normotensive rats revealed significant variation in gene expression: 98 genes were upregulated and 122 were downregulated in SHR;while 88 genes were upregulated and 139 genes were downregulated in age-matched normotensive rats. Furthermore, within the SHR group, 110 genes were found to be upregulated and 168 genes downregulated across different ages. Analyses via the Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathways revealed that several genes are potentially implicated in both, hypertension and metabolic syndrome. The results suggest that SHR display variations in gene expression due to aging, and when compared to normotensive rats. These variations could contribute to the development of hypertension and metabolic syndrome. Microarray studies involving older rats are necessary to further validate these findings.

关键词： Hypertension Metabolic Syndrome Gene Expression SHR Microarray

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