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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

Comparative analysis of two nonlethal methods for the study of the gut bacterial communities in wild lizards

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Integrative Zoology 2023年第6期18卷 1056-1071页

作者： Mauricio HERNÁNdEZ Sergio ANCONA Stephanie HEREIRA-pACHECO Aníbal Hd.az dE LA VEGA-pÉrez Yendi E.NAVARRO-NOYA doctorado en Ciencias Biológicas Centro de Tlaxcala de Biología de la ConductaUniversidad Autónoma de TlaxcalaTlaxcalaMexico departamento de Ecología Evolutiva Instituto de EcologíaUniversidad Nacional Autónoma de MéxicoMexico CityMexico Estación Científica la Malinche Centro de Tlaxcala de Biología de la ConductaUniversidad Autónoma de TlaxcalaTlaxcalaMexico Consejo Nacional de Ciencia y Tecnología—Centro Tlaxcala de Biología de la Conducta Universidad Autónoma de TlaxcalaTlaxcalaMexico Laboratorio de Interacciones Bióticas Centro de Investigación en Ciencias BiológicasUniversidad Autónoma de TlaxcalaTlaxcalaMexico

Fecal samples or cloacal swabs are preferred over lethal dissections to study vertebrate gut microbiota for ethical reasons,but it remains unclear which nonlethal methods provide more accurate information about gut *** compared the bacterial communities of three gastrointestinal tract(GIT)segments,that is,stomach,small intestine(midgut),and rectum(hindgut)with the bacterial communities of the cloaca and feces in the mesquite lizard Sceloporus *** hindgut had the highest taxonomic and functional alpha diversity,followed by midgut and feces,whereas the stomach and cloaca showed the lowest *** taxonomic assemblages of the GIT segments at the phylum level were strongly correlated with those retrieved from feces and cloacal swabs(rs>0.84 in all cases).The turnover ratio of Amplicon Sequence Variants(ASVs)between midgut and hindgut and the feces was lower than the ratio between these segments and the *** than half of the core-ASVs in the midgut(24 of 32)and hindgut(58 of 97)were also found in feces,while less than 5 were found in the *** the ASVs level,however,the structure of the bacterial communities of the midgut and hindgut were similar to those detected in feces and *** findings suggest that fecal samples and cloacal swabs of spiny lizards provide a good approximation of the taxonomic assemblages and beta diversity of midgut and hindgut microbiota,while feces better represent the bacterial communities of the intestinal segments at a single nucleotide variation level than cloacal swabs.

关键词： animal microbiome cloacal swabs fecal samples intestinal tract reptile gut microbiome

Cleaning properties of dry adhesives

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Science China(Technological Sciences) 2010年第11期53卷 2942-2946页

作者： J. p. d.az TéLLEZ d. SAMEOTO C. MENON MENRVA Group School of Engineering Science Simon Fraser University department of Mechanical Engineering University of Alberta

In this paper we present a study into the cleaning properties of synthetic dry adhesives. We have manufactured the adhesive micro-fibres through a low-cost, high yield fabrication method using Sylgard 184 polydimethylsiloxane (pdMS) as the structural material. We deliberately contaminated the adhesive samples with different sized particles in the micro and macro scales and tested different cleaning methods for their efficacy with respect to each particle size. We investigated different cleaning methods, which included the use of wax moulding, vibration and pressure sensitive adhesives. For adhesion testing we used a custom system with a linear stage and a force sensor indenting a hemispherical probe into the adhesive surface and measuring the pull-off force. To characterize the cleaning efficacy we visually inspected each sample in a microscope and weighed the samples with a microgram-accuracy analytical balance. Results showed that the moulding method induced adhesion recovery in a greater percentage than the other cleaning methods and even helped with the recovery of collapsed posts in some cases. On the other hand pressure sensitive adhesives seem to have the upper hand with regards to certain particle sizes that can potentially pose problems with the moulding method.

关键词： biomimetic dry adhesive pdMS self-cleaning gecko climbing

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

One ring is sufficient to inhibit α-synuclein aggregation

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Neural Regeneration Research 2022年第3期17卷 508-511页

作者： Samuel peña-d.az Salvador Ventura Institut de Biotecnologia i Biomedicina Universitat Autònoma de BarcelonaBellaterraSpain departament de Bioquímica i Biologia Molecular Universitat Autònoma de BarcelonaBellaterraSpain InstitucióCatalana de Recerca i Estudis Avançats(ICREA) BarcelonaSpain

parkinson's disease,the second most prevalent neurodegenerative disorder worldwide,is characterized by a progressive loss of dopaminergic neurons in substantia nigra pars compacta,causing motor *** disorder's main hallmark is the formation of intraneuronal protein inclusions,named Lewy bodies and *** major component of these arrangements is α-synuclein,an intrinsically disordered and soluble protein that,in pathological conditions,can form toxic and cell-to-cell transmissible amyloid *** α-synuclein aggregation has attracted significant effort in the search for a disease-modifying therapy for parkinson's *** molecules like Synu Clean-d,epigallocatechin gallate,trodusquemine,or anle138 b exemplify this therapeutic ***,we describe a subset of compounds containing a single aromatic ring,like dopamine,Zpdm,gallic acid,or entacapone,which act as molecular chaperones against α-synuclein *** simplicity of their structures contrasts with the complexity of the aggregation process,yet the block efficiently α-synuclein assembly into amyloid fibrils,in many cases,redirecting the reaction towards the formation of non-toxic off-pathway ***,some of these compounds can disentangle mature α-synuclein amyloid *** simple structures allow structure-activity relationship analysis to elucidate the role of different functional groups in the inhibition of α-synuclein aggregation and fibril dismantling,making them informative lead scaffolds for the rational development of efficient drugs.

关键词： amyloid aromatic rings dopamine inhibition neurodegeneration oligomers parkinson's disease protein aggregation α-synuclein

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World Journal of Gastroenterology 2006年第27期12卷 4392-4396页

作者： Andrés duarte-Rojo Ana Lezama-Barreda María Teresa Ramírez-Iglesias Mario peláez-Luna Guillermo Robles-d.az department of Internal Medicine Vasco de Quiroga 15Sectión ⅩⅥTlalpanCP 14000MéxicoDFMéxico department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránVasco de Quiroga 15Sección ⅩⅥTlalpanCP 14000MéxicoDFMéxico department of Experimental Medicine Facultad de MedicinaUniversidad Nacional Autónoma de MéxicoHospital General de MéxicoDr. Balmis 148 PB Colonia DoctoresCP 06726MexicoDFMéxico

AIM： To evaluate the relationship between leptin and systemic inflammation in acute pancreatitis. METHOdS： Consecutive patients with acute pancreatitis were included. Body mass index and serum samples were obtained at admission. Leptin, TNF-α, IL-6, -8 and -10 levels were determined by ELISA. Severity was defined according to Atlanta criteria. RESULTS： Fifty-two （29 females） patients were studied. Overall body mass index was similar between mild and severe cases, although women with severe pancreatitis had lower body mass index （p = 0.04） and men showed higher body mass index （p = 0.05）. No difference was found in leptin levels regarding the severity of pancreatitis, but higher levels tended to appear in male patients with increased body mass index and severe pancreatitis （p = 0.1）. A multivariate analysis showed no association between leptin levels and severity. The strongest cytokine associated with severity was IL-6. Correlations of leptin with another cytokines only showed a trend for IL-8 （p = 0.058）. CONCLUSION： High body mass index was associated with severity only in males, which may be related to android fat distribution. Serum leptin seems not to play a role on the systemic inflammatory response in acute pancreatitis and its association with severe outcome in males might represent a marker of increased adiposity.

关键词： Leptin Cytokines Obesity Acute pancreatitis prognosis

Exploring seven hundred years of transhumance, climate dynamic, fire and human activity through a historical mountain pass in central Spain

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Journal of Mountain Science 2016年第7期13卷 1139-1153页

作者： José Antonio LópEZ-SáEZ Francisca ALBA-SáNCHEZ Sandra ROBLES-LópEZ Sebastián pérez-d.az daniel ABEL-SCHAAd Silvia SABARIEGO-RUIZ Arthur GLAIS Research Group Archaeobiology Institute of History CSIC dept.Botany Faculty of Sciences University of Granada dept.of plant Biology Faculty of Biology Complutense University LETG CAEN GEOpHEN-UMR 6554 CNRS University of Caen-Normandie

A high-altitude peat sequence from the heart of the Spanish Central System(Gredos range) was analysed through a multi-proxy approach to determine the sensitivity of high-mountain habitats to climate, fire and land use changes during the last seven hundred years, providing valuable insight into our understanding of the vegetation history and environmental changes in a mountain pass close to a traditional route of transhumance. The pollen data indicate that the vegetation was dominated by shrublands and grasslands with scattered pines in high-mountain areas, while in the valleys cereals, chestnut and olive trees were cultivated. Strong declines of high-mountain pines percentages are recorded at 1540, 1675, 1765, 1835 and 1925 cal Ad, which may be related to increasing grazing activities and/or the occurrence of anthropogenic fires. The practice of mountain summer farming and transhumance deeply changed and redesigned the landscape of the high altitudes in central Spain(Gredos range) since the Middle Ages, although its dynamics was influenced in some way by climate variability of the past seven centuries.

关键词： Climate and human impacts Fire Late Holocene Gredos range Vegetation history

Endoscopic submucosal dissection training with pig models in a Western country

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World Journal of Gastroenterology 2010年第23期16卷 2895-2900页

作者： Adolfo parra-Blanco María Rosa Arnau david Nicolás-pérez Antonio Z Gimeno-García Nicolás González Juan A d.az-Acosta Alejandro Jiménez Enrique Quintero department of Gastroenterology University Hospital of the Canary Islands Ofra s/n Endoscopy Unit Department of GastroenterologyAsturias Central University HospitalCelestino Villamil s/n Research Animal Laboratory Ofra s/nLa Laguna University department of Gastroenterology Montevideo Clinic HospitalAvda Italia s/n Research Unit University Hospital of the Canary IslandsOfra s/n

AIM:To test a strategy for endoscopic submucosal dissection(ESd) training in animal models designed to overcome the initial learning ***:ESd was attempted in ex vivo and in vivo pig *** ESd procedures were attempted in the esophagus(n=9) or the stomach(n=21).The ex vivo model was used until initial competence was *** the in vivo model,several ESd procedures were performed in up to 3 *** following variables were analyzed:specimen size,complete and en bloc resection rate,time for circumferential incision,time for submucosal dissection,total ESd duration,and ***:Complete resection was achieved in 28 cases(en bloc 27);2 could not be completed(one perforation,one technical diff iculty).The mean ± Sd time for circumferential incision was 36.2±16.8 min(range:8-87 min),and the mean±Sd time for submucosal dissection was 45.1±35.7 min(range:9-196 min).The mean±Sd size of the resected specimens was 45.2±17.8 *** mean±Sd total resection time was signif icantly increased for the gastric cases performed in the f irst half of the study(n=13) than in the second half(n=8)(98.9±62.4 min vs 61.7±17.6 min,p=0.04),although the specimen size did not ***:Training in animal models could help endoscopists overcome the learning curve before starting ESd in humans.

关键词： Endoscopic submucosal dissection Training Animal model

Quantitative Assessment of Liver Fibrosis by Elastography in patients with Chronic Liver disease: A Cross-Sectional Study in Lomé (Togo)

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Open Journal of Radiology 2024年第2期14卷 42-54页

作者： Massaga dagbe Bidamin N’timon sonia Ekembe Rafiou El-Hadji Yakoubou pihou Gbande Lantam Sonhaye Lama Kegdigoma Agoda-Koussema Komlanvi Victor Adjenou department of Radiology and Medical Imaging Kara University Hospital Kara Kara Togo department of Radiology and Medical Imaging Lom University Hospital Lome Togo department of Hpato-gastroenterology Kara University Hospital Kara Togo department of Radiology and Medical Imaging Sokod Regional Hospital Sokode Togo department of Internal Medicine Kara University Hospital Kara Togo

Aim: To describe the two-dimensional elastographic profile according to the Shearwave (2d-SWE) technique in patients with chronic liver disease in Lom. Materials and method: Cross-sectional, descriptive study conducted over seven month at the Autel dElie Clinic in Lom, from January to August 2022, on adult patients with chronic liver disease who underwent abdominal ultrasound coupled with two-dimensional elastography. Results: The sample size was 54 patients. The mean age of the patients was 33 12 years, with extremes of 18 and 66 years. patients aged 30 years or less accounted for 48.1% (n = 26). All patients (n = 54) had at least one transaminase assay with a mean of 69.3 78.3 IU/l (AST) and 59.3 82.8 IU/l (ALT). There was no statistically significant association between the biological parameters and the presence of fibrosis. Viral liver disease was the main cause, accounting for 81.5% (n = 44) of cases, with no significant association with the degree of fibrosis. Ultrasound revealed a dysmorphic liver (57.4%;n = 31) and portal hypertension (18.5%, n = 10). Fibrosis stages F1, F2 and F4 accounted for (48.1%, n = 26), (24.1%, n = 13) and (13%, n = 7) of cases respectively. Liver dysmorphia was significantly associated with the presence of fibrosis (p = 0.012) and portal hypertension was significantly associated with the degree of fibrosis (p = 0.0063). Conclusion: Assessment of liver fibrosis in patients with chronic liver disease using 2d-SWE elastography is essential for patient follow-up.

关键词： Hepatic Fibrosis 2d-SWE Elastography Chronic Liver disease Lomé