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preclinical evaluation of azathioprine plus buthionine sulfoximine in the treatment of human hepatocarcinoma and colon carcinoma

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World Journal of Gastroenterology 2011年第34期17卷 3899-3911页

作者： Borja Hernández-Breijo Jorge Monserrat Sara Ramírez-Rubio Eva p Cuevas diana Vara Inés d.az-Laviada M dolores Fernández-Moreno Irene d Román Javier p Gisbert Luis G Guijarro Molecular Hepatic Toxicology Unit Biochemistry and Molecular Biology Department University of Alcalá Networked Biomedical Research Center of Hepatic and Digestive Diseases (CIBEREHD) Medicine department University of Alcalá neuroendocrinology of Cannabinoid/Vanilloid System Unit Biochemistry and Molecular Biology Department University of Alcalá Gastroenterology Unit Hospital de la Princesa Institute of Health Research Princesa Networked Biomedical Research Center of Hepatic and Digestive Diseases (CIBEREHD)

AIM: To evaluate the efficacy and the safety of azathioprine (azA) and buthionine sulfoximine (BSO) bylocalized application into HepG2 tumor in ***: different hepatoma and colon carcinoma cell lines (HepG2, HuH7, Chang liver, LoVo, RKO, SW-48, SW-480) were grown in minimal essencial medium supplemented with 10% fetal bovine serum and 1% antibiotic/antimycotic solution and maintained in a humidified 37 ℃ incubator with 5% CO2. These cells were pretreated with BSO for 24 h and then with azA for different times. We examined the effects of this combination on some proteins and on cellular death. We also studied the eff icacy and the safety of azA (6 mg/kg per day) and BSO (90 mg/kg per day) in HepG2 tumor growth in vivo using athymic mice. We measured safety by serological markers such as aminotransferases and creatine ***: The in vitro studies revealed a new mechanism of action for the azA plus BSO combination in the cancer cells compared with other thiopurines (6-mercaptopurine, 6-methylmercaptopurine, 6-thioguanine and 6-methylthioguanine) in combination with BSO. The cytotoxic effect of azA plus BSO in HepG2 cells resulted from necroptosis induction in a mitochondrial-dependent manner. From kinetic studies we suggest that glutathione (GSH) depletion stimulates c-Jun amino-terminal kinase and Bax translocation in HepG2 cells with subsequent deregulation of mitochondria (cytochrome c release, loss of membrane potential), and proteolysis activation leading to loss of membrane integrity, release of lactate dehydrogenase and dnA degradation. Some of this biochemical and cellular changes could be reversed by n-acetylcysteine (a GSH replenisher). In vivo studies showed that HepG2 tumor growth was inhibited when azA was combined with ***: Our studies suggest that a combination of azA plus BSO could be useful for localizedtreatment of hepatocellular carcinoma as in the currently used transarterial chemoembolization method.

关键词： azathioprine Buthionine sulfoximine Transarterial chemoembolization Glutathione Apoptosis necrosis

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Liver histological changes and lipid peroxidation in the amphibian Ambystoma mexicanum induced by sediment elutriates from the Lake Xochimilco

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Journal of Environmental Sciences 2016年第8期28卷 156-164页

作者： Esperanza Ortiz-Ordonez Eugenia López-López Jacinto Elías Sedeno-d.az Esther Uría Ignacio Andrés Morales María Estela pérez Mineko Shibayama Instituto politécnico nacional Depto.de Formación Básica e InterdisciplinariaCICS-USTAv.de los Maestros s/n.Col.Sto Instituto politécnico nacional Laboratorio de Evaluación de la Salud de Ecosistemas AcuáticosENCBProl.de Carpio y Plan de Ayala s/n.Col.Sto Instituto politécnico nacional Coordinación Politécnica para la SustentabilidadEdificio de la Biblioteca Nacional3er PisoAv.Instituto Politécnico Nacional s/nesq.Wilfrido MassieuCol Instituto politécnico nacional Laboratorio de HistologíaENCBProl.de Carpio y Plan de Ayala s/n.Col.Sto Unidad de Servicio Académico Acuario BiologíaFacultad de CienciasUniversidad Autónoma de MéxicoCiudad Universitaria Laboratorio de Infectómica Centro de Investigación y de Estudios Avanzados del IPNAv.Instituto Politécnico Nacional

Lacustrine sediments accumulate pollutants that input from the lake watershed and can be released to the water column by sediment resuspension; thus, pollutants can change their bioavailability and exert adverse effects to aquatic biota. Shallow-urban lakes are particularly susceptible to receive pollutants from urban discharges and sediment resuspension. Lake Xochimilco, in Mexico City, an urban-shallow lake, faces multiple problems： urban sprawl, overexploitation of aquifers, drying of springs, discharge of wastewater from treatment plants, and sediment resuspension. The aquatic biota living in this ecosystem is continuously exposed to the release of pollutants from the sediments. We assessed the risk that pollutants released from sediments from Lake Xochimilco, Touristic（TZ） and Agriculture zone（az）, can exert on a native amphibian species of the lake（Ambystoma mexicanum） through exposure bioassays to sediment elutriates. We evaluate alterations in the amphibian by three approaches： biochemical（level of lipid peroxidation,LpO）, cellular（ultrastructure） and the liver histology of A. mexicanum and we compare them with a batch control. Additionally, we assessed heavy metals（pb, Cd and Hg） in *** from TZ showed the highest concentrations of the metals assessed. Organisms exposed to sediment elutriates from either study sites showed higher LpO values than control organisms（p 〈 0.05）. Organisms exposed to elutriates from the TZ showed the most conspicuous damages： hepatic vasodilation of sinusoids, capillaries with erythrocytes,leukocyte infiltration and cytoplasmic vacuolation in hepatocytes. The biological responses assessed reflected the risk that faces A. mexicanum when is exposed for prolonged periods to sediment resuspension in Lake Xochimilco.

关键词： Elutriates Amphibian Liver Histological alterations Ultrastructure Oxidative stress Metals Urban lake

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Surface properties of Fe_4n Compounds Layer on AISI 4340 Steel Modified by pulsed plasma nitriding

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Journal of Materials Science & Technology 2013年第3期29卷 287-290页

作者： J.C.d.az-Guillén G.Vargas-Gutiérrez E.E.Granda-Gutiérrez J.S.Zamarripa-pia S.I.pérez-Aguilar J.Candelas-Ramírez L.lvarez-Contreras Centro de Investigacin en Materiales Avanzados S.C.Miguel de Cervantes 120Complejo Industrial ChihuahuaC.P.31109 ChihuahuaChihuahuaMexico Corporacin Mexicana de Investigacin en Materiales S.A.de C.V.Ciencia y Tecnología No 790Fracc.Saltillo 400C.P.25290 SaltilloCoahuilaMexico Centro de Investigacin y Estudios Avanzados del Ipn Unidad SaltilloCarretera Saltillo Monterrey km 13Apdo.Postal 663C.P.25000 SaltilloCoahuilaMexico

In this work, the effect of nitriding current density on hardness, crystalline phase composition, layer thickness and corrosion rate of AlSl 4340 steel has been studied. X-ray diffraction analysis shows that thin layers formed during nitriding process are constituted of 7-Fe4n for samples processed between 1 and 2.5 mA/cm2. Thickness of nitrided layer increases proportionally to current density （0 μm for 0.5 mA/cm2 to 15 pm for 2.5 mA/cm2）. plasma nitriding increased the surface hardness from 300 HV50g for untreated sample, to around 800HV5og for nitrided samples at 1 mA/cm2. While the untreated samples exhibited a corrosion rate of 0.153 mm per year, the corrosion performance was improved up to 0.03 mm per year at current densities above 1 mA/cm2, which is about one fifth of the corrosion rate of the untreated sample.

关键词： plasma nitriding Current density Hardness Corrosion

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Hydrology and Estimation of Real Erosion in the patria nueva Micro-Basin for Five Return periods

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Journal of Water Resource and protection 2022年第12期14卷 783-789页

作者： Martín Mundo-Molina José Luis pérez-d.az Investigation Centre Faculty of Engineer Autonomous University of Chiapas Chiapas Mexico

This paper will discuss the actual erosion estimation of the patria nueva micro basin in tons/ha/year (E), located in Tuxtla Gutiérrez Chiapas, Mexico. We used the universal soil loss equation (USLE), considered one of the best theoretical tools for planning and soil preservation in the USA and other countries. The actual erosion rates were estimated for 5, 20, 50, 100, and 500 years return periods (Rp), with elevated results due to high degrees of anthropogenic alteration of the micro-basin, especially in the last 50 years. High erosion rates generate the following problems: loss of soil, which is unfavorable for plant life, due to the soil being a non-renewable resource, the undermine can never renovate, the hydraulic area in the main channel reduces during the rainy season (when the river overflows). The sediment accumulates at the lower part of the micro-basin along with waste, garbage, and mud.

关键词： Erosion Return periods Basins USLE Sediment

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3′-UTR of the SARS-CoV-2 genome as a possible source of piRnAs

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Genes & diseases 2023年第3期10卷 668-670页

作者： María Teresa Hernández-Huerta Laura pérez-Campos Mayoral Carlos Alberto Matias-Cervantes Carlos Romero d.az Eli Cruz parada Eduardo pérez-Campos Mayoral Rafael Baltiérrez-Hoyos Margarito Martínez Cruz Gabriel Mayoral Andrade Eduardo pérez-Campos COnACyT Faculty of Medicine and SurgeryAutonomous University“Benito Juárez”of Oaxaca(UABJO)Oaxaca 68020Mexico Research Center Faculty of Medicine UNAM-UABJOAutonomous University“Benito Juárez”of Oaxaca(UABJO)Oaxaca 8020Mexico national Technology of Mexico/IT Oaxaca Oaxaca de JuárezOaxaca 68030Mexico

SARS-CoV-2 is the causal agent of the COVId-19 pandemic. This is a single-stranded RnA beta-coronavirus that is comprised of a 5′ and 3′-untranslated region (UTR) in its non-coding RnA (ncRnA) region. The p-element-induced wimpy testis (pIWI)-interacting RnAs (piRnAs) are ncRnA sequences that bind to transposons and interfere with the translation of new genes. Here, we search for short sequences in the non-coding regions, corresponding to 28 nucleotides (nt). These start from a uracil and have a conserved region of at least 10 nt of homology with the previously reported piRnAs. The aim of this work was to identify piRnA-like sequences in the 3′-UTR of SARS-CoV-2 from the reported Wuhan patient's genome sequence (GenBank: Mn908947.3).

关键词： piRnA sequences piRnAs

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A private SUSY 4HdM with FCnC in the up-sector

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Chinese physics C 2021年第2期45卷 326-340页

作者： M.A.Arroyo-Ureña Lorenzo d.az-Cruz Bryan O.Larios-López M.A.pérez de León Facultad de Estudios Superiores Cuautitlan-UnAM Cuautitlan Edo de MexMéxico Mesoamerican Center for Theoretical physics UNACHChiapasMéxico CIFFU and Facultad de Ciencias Físico-Matemáticas Benemérita Universidad Autónoma de Puebla ApdoPostal 1364CP72000PueblaPueMéxico departamento de Gravitación y Altas Energías Facultad de Ciencias Universidad Nacional Autónoma de Honduras Ciudad UniversitariaTegucigalpa MDCHonduras

We present a SUSY model with four Higgs doublets of the"private type,"in which all fermion types(up,down,and charged leptons)obtain their masses from a different Higgs doublet H_f(f=u_1,d,e) .The conditions for anomaly cancellation imply that the remaining Higgs doublet of the model( H_(u_2) )must have the same hypercharge as H_(u_1) ,and thus,can only couple to up-type quarks,which opens the possibility to have FCnCs only in this *** study the Lagrangian of the model,and in particular,the Higgs potential,to identify the Higgs mass-eigenstates and their interactions;for the Yukawa matrices,we consider the four-texture *** obtain constraints on the model parameters by using LHC measurements on the properties of the 125 GeV Higgs boson(h),and identify viable regions of the parameter ***,these constraints are used to evaluate the prospects for detecting the FCnC decay mode t→ch at the future high-luminosity(HL)option for the LHC,which are compared with current limits from ***,we evaluate the FCnC decay of the next heavier Higgs boson H_(2)→tc ,which can typically reach BR(H_2→tc)≈(10^(-4)-10^(-5)) .The search for the signal at HL-LHC is also studied,and it is found that it may be detectable for specific regions of the model parameter space.

关键词： Higgs physics top quark supersymmetry collider physics

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proposed Equation to Estimate the Length of a Hydraulic Jump in a Rectangular Open Channel Hydraulic with Variable Slope, and Its Comparison with Seven Theoretical Equations of Specialized Literature

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Journal of Water Resource and protection 2019年第12期11卷 1481-1488页

作者： Martín Mundo-Molina José Luis d.az pérez Engineering Faculty Chiapas State University Chiapas Mexico

A hydraulic jump is a localized phenomenon that generates on an open hydraulic channel;however, its mathematical demonstration is not possible in the turbulent area of the phenomenon, especially in the area where the jump occurs and where its length is measured, so the data must be obtained with direct measurements in a laboratory and through empiric equations. This work presents the results of the generated hydraulic jumps and the measure of its length in a series of tests, where we input different flow rates in a transportable open channel hydraulic with a constant gate opening “a” and a slope of S = 0.0035, in the Engineering Faculty Research Centre of the Autonomous University of Chiapas. We also present the experimental method to generate a hydraulic jump, the measure of its length and a comparison with seven empirical equations, including the Sieñchi equation used in H-Canales, the most used software for hydraulic channels design in Latin America. The results show that the calculus of L with the proposed equation has a mean squared error (MSE) of 0.1337, a Bias of -0.0049, a model efficiency (ME) of 0.9991 and a determination coefficient (R2) of 0.9993 when compared with the experimental model. Meanwhile, the comparison of L calculated with the Sieñchi equation versus the experimental model resulted in a MSE of 0.1741, a bias of -0.0437, a ME of 0.9984 and a R2 of 0.9997. Both equations are highly recommended to estimate L in rectangular channels under the conditions presented in this paper, thus, the proposed equation can be applied if??y . Finally, it must be stated that we also proved that the pavlosky equation is comparable in precision and accuracy concerning to proposed equation and Sieñchi equation.

关键词： Hydraulic Jump Open Channel Hydraulic Hydraulics Experiments Length of the Stilling Basin

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The importance of functional diversity in the stability of Mediterranean shrubland communities after the impact of extreme climatic events

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Journal of plant Ecology 2017年第2期10卷 281-293页

作者： Enrique Gde la Riva Francisco Lloret Ignacio Mpérez-Ramos Teodoro Marañón Sandra Saura-Mas Ricardo d.az-delgado Rafael Villar Area de Ecología Facultad de CienciasUniversidad de Cordoba.14071 CordobaSpain CREAF Cerdanyola del Vallés08193 BarcelonaSpain Unitat d’Ecologia Dept.Biologia AnimalBiologia Vegetal i EcologiaUniversitat Autònoma BarcelonaEdifici CCampus UAB08193Cerdanyola del VallèsBarcelonaSpain IRnAS CSICAv.Reina Mercedes 10PO Box 1052.41080 SevillaSpain Estación Biológica de doñana CSIC.c/Americo Vespucios/nIsla de la Cartuja.41092 SevillaSpain

Aims Extreme climatic events may have important consequences for plant community structure and *** 2005,a severe drought together with a cold winter promoted extensive damage and mortal-ity in shrubland communities of southwest Spain(doñana national park).Here,we aim to identify the mechanisms underlying commu-nity stability(resistance and resilience)in response to this extreme climatic event,considering changes in the functional structure of these *** We used a trait-based approach,quantifying variations in 10 func-tional traits at the community level(community weighted means,CWM)and the functional diversity(functional richness,evenness and divergence)in 18 plots at three different times:predating the climatic event(estimated from the sum of the live and dead volume of each species in 2007),and 2 and 8 years after the 2005 *** also quantified the differences in functional traits and functional diversity between adult and recruit stages,which allowed us to bet-ter understand the contribution of the recruitment to the mainte-nance of the functional structure and diversity of the *** Findings Communities with higher functional divergence before the cli-matic event maintained nearly constant their levels of functional divergence 8 years after,but they were more prone to changes in species *** resistance in terms of vegeta-tion cover was positively correlated with root dry matter content,whereas community resilience was positively correlated with leaf chlorophyll(LChl).We also found that some values(weighted means)of functional community traits(such as root dry matter con-tent and LChl)had increased 2 years after the event,returning to the pre-event conditions after 8 *** addition,there was hardly any establishment of new species in the community and the recruits did not make substantial differences to the community functional *** seed mass differed significantly between the adult and se

关键词： climate change doñana drought functional trait recruitment resilience resistance

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Mitochondrial protection by low doses of insulin-like growth factor-Ⅰin experimental cirrhosis

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World Journal of Gastroenterology 2008年第17期14卷 2731-2739页

作者： Raquel pérez María García-Fernández Matías d.az-Sánchez Juan E puche Gloria delgado Marian Conchillo Jordi Muntané Inma Castilla-Cortázar departments of Human physiology and Internal Medicine University of Navarra department of Medical physiology School of Medicine University of Málaga department of Internal Medicine Liver Unit University of Córdoba

AIM： To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-Ⅰ （IGF-Ⅰ ） therapy （4 wk） is able to induce beneficial effects on damaged mitochondria leading to cellular protection. METHOdS： Wistar rats were divided into three groups： Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF-Ⅰ treatment （2 μg/1O0 g bw/d）. Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUnEL in the three expedmental groups. RESULTS： Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential （in status 4 and 3）; an increase of intramitochondrial reactive oxigen species （ROS） generation and a significant reduction of ATpase activity. IGF-Ⅰ therapy normalized mitochondrial function by increasing the membrane potential and ATpase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes Ⅰ and Ⅲ was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF- Ⅰ therapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis. COnCLUSIOn： These results show that IGF- Ⅰ exerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATp production.

关键词： Insulin-like growth factor- Ⅰ Cirrhosis Mitochondrial protection Caspases Apoptosis Oxidativedamage

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Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway:providing understanding of the complex mechanisms of chemoresistance

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World Journal of Gastroenterology 2022年第26期28卷 3027-3046页

作者： María Belén novoa d.az María Julia Martín Claudia Gentili departamento de Biología Bioquímica y FarmaciaUniversidad Nacional del Sur(UNS)-INBIOSUR(CONICET-UNS)Bahía Blanca 8000Argentina departamento de Química Universidad Nacional del Sur(UNS)-INQUISUR(CONICET-UNS)Bahía Blanca 8000Argentina

Colorectal cancer(CRC)continues to be one of the main causes of death from cancer because patients progress unfavorably due to resistance to current *** of the Wnt/β-catenin pathway plays a fundamental role in the genesis and progression of several types of cancer,including *** many subtypes of CRC,hyperactivation of theβ-catenin pathway is associated with mutations of the adenomatous polyposis coli ***,it can also be associated with other *** recent years,studies of the tumor microenvironment(TME)have demonstrated its importance in the development and progression of *** this tumor nest,several cell types,structures,and biomolecules interact with neoplastic cells to pave the way for the spread of the ***-communications between tumor cells and the TME are then established primarily through paracrine factors,which trigger the activation of numerous signaling *** advances in the field of oncology have been made in the last *** Minireview aims to actualize what is known about the central role of the Wnt/β-catenin pathway in CRC chemoresistance and aggressiveness,focusing on crosscommunication between CRC cells and the *** this analysis,our main objective was to increase the understanding of this complex disease considering a more global *** many treatments for advanced CRC fail due to mechanisms involving chemoresistance,the data here exposed and analyzed are of great interest for the development of novel and effective therapies.

关键词： Colorectal cancer β-catenin pathway Tumor stroma Tumor microenvironment factors Cancer progression drug resistance

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