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Translating new data to the daily practice in second line treatment of renal cell carcinoma:The role of tumor growth rate

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World Journal of Clinical Oncology 2017年第2期8卷 100-105页

作者： Enrique Grande olga martínez-sáez Pablo Gajate-Borau Teresa Alonso-Gordoa Medical Oncology Department Ramón y Cajal University Hospital

The therapeutic options for patients with metastatic renal cell carcinoma(mRCC) have completely changed during the last ten years. With the sequential use of targeted therapies, median overall survival has increased in daily practice and now it is not uncommon to see patients surviving kidney cancer for more than four to five years. Once treatment fails with the first line targeted therapy, head to head comparisons have shown that cabozantinib, nivolumab and the combination of lenvatinib plus everolimus are more effective than everolimus alone and that axitinib is more active than sorafenib. Unfortunately, it is very unlikely that we will ever have prospective data comparing the activity of axitinib, cabozantinib, lenvatinib or nivolumab. It is frustrating to observe the lack of biomarkers that we have in this field, thus there is no firm recommendation about the optimal sequence of treatment in the second line. In the absence of reliable biomarkers, there are several clinical endpoints that can help physicians to make decisions for an individual patient, such as the tumor burden, the expected response rate and the time to achieve the response to each agent, the prior response to the agent administered, the toxicity profile of the different compounds and patient preference. Here, we propose the introduction of the tumor-growth rate(TGR) during first-line treatment as a new tool to be used to select the second line strategy in m RCC. The rapidness of TGR before the onset of the treatment reflects the variability between patients in terms of tumor growth kinetics and it could be a surrogate marker of tumor aggressiveness that may guide treatment decisions.

关键词： Axitinib Everolimus Cabozantinib Kidney cancer Nivolumab Renal cell sequence second line sorafenib Tumor-growth rate

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Intestinal bile acid physiology and pathophysiology

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World Journal of Gastroenterology 2008年第37期14卷 5630-5640页

作者： olga martínez-Augustin Fermín sánchez de Medina Department of Biochemistry and Molecular Biology II School of Pharmacy University of Granada Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasGranada 18071 Spain Department of Pharmacology School of Pharmacy University of Granada Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasGranada 18071 Spain

Bile acids (BAs) have a long established role in fat digestion in the intestine by acting as tensioactives, due to their amphipatic characteristics. BAs are reabsorbed very efficiently by the intestinal epithelium and recycled back to the liver via transport mechanisms that have been largely elucidated. The transport and synthesis of BAs are tightly regulated in part by specific plasma membrane receptors and nuclear receptors. In addition to their primary effect, BAs have been claimed to play a role in gastrointestinal cancer, intestinal inflammation and intestinal ionic transport. BAs are not equivalent in any of these biological activities, and structural requirements have been generally identified. In particular, some BAs may be useful for cancer chemoprevention and perhaps in inflammatory bowel disease, although further research is necessary in this field. This review covers the most recent developments in these aspects of BA intestinal biology.

关键词： Colitis Bile acid absorption Colon cancer

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Origin of celiac disease:How old are predisposing haplotypes?

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World Journal of Gastroenterology 2012年第37期18卷 5300-5304页

作者： Giovanni Gasbarrini olga Rickards Cristina martínez-Labarga Elsa Pacciani Filiberto Chilleri Lucrezia Laterza Giuseppe Marangi Franco scaldaferri Antonio Gasbarrini Ricerca in Medicina Foundation NGO Falcone and Borsellino Gallery Center of Molecular Anthropology for Ancient DNA studies Department of BiologyUniversity of Rome Tor Vergata superintendence for the Archaeological Heritage of Tuscany Division of Gastroenterology Department Internal MedicineCatholic University of Sacred Heart Institute of Genetics Catholic University of Sacred Heart

We recently presented the case of a first century AD young woman, found in the archaeological site of Cosa, showing clinical signs of malnutrition, such as short height, osteoporosis, dental enamel hypoplasia and cribra orbitalia, indirect sign of anemia, all strongly suggestive for celiac disease (CD). However, whether these findings were actually associated to CD was not shown based on genetic parameters. To investigate her human leukocyte antigen (HLA) class Ⅱ polymorphism, we extracted DNA from a bone sample and a tooth and genotyped HLA using three HLA-tagging single nucleotide polymorphisms for DQ8, DQ2.2 and DQ2.5, specifically associated to CD. she displayed HLA DQ 2.5, the haplotype associated to the highest risk of CD. This isthe first report showing the presence of a HLA haplotype compatible for CD in archaeological specimens.

关键词： Celiac disease Human leukocyte antigen hap-Iotype Ancient DNA single nucleotide polymorphisms Malabsorption

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Identification and heterologous expression of the globomycin biosynthetic gene cluster

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synthetic and systems Biotechnology 2023年第2期8卷 206-212页

作者： Daniel Oves-Costales Tetiana Gren Eva Baggesgaard sterndorff Jesús martín Francisco Javier Ortiz-Lopez Tue s.Jørgensen Xinglin Jiang Fernando Roman-Hurtado Fernando Reyes olga Genilloud Tilmann Weber Fundacion MEDINA Centro de Excelencia en Investigaci´on de Medicamentos Innovadores en AndalucíaAvda del Conocimiento 3418016ArmillaGranadaSpain The Novo Nordisk Foundation Center for Biosustainability Technical University of DenmarkKemitorvetbuilding 2202800 Kgs.LyngbyDenmark

Globomycin is a cyclic lipodepsipeptide originally isolated from several streptomyces species which displays strong and selective antibacterial activity against Gram-negative *** mode of action is based on the competitive inhibition of the lipoprotein signal peptidase II(LspA),which is absent in eukaryotes and considered an attractive target for the development of new *** its interesting biological properties,the gene cluster encoding its biosynthesis has not yet been *** this study we employed a genome-mining approach in the globomycin-producing streptomyces ***-278952 to identify a candidate gene cluster responsible for its biosynthesis.A null mutant was constructed using CRIsPR base editing where production was abolished,strongly suggesting its involvement in the *** putative gene cluster was then cloned and heterologously expressed in streptomyces albus J1074 and streptomyces coelicolor M1146,therefore unambigu-ously linking globomycin and its biosynthetic gene *** work paves the way for the biosynthesis of new globomycin derivatives with improved pharmacological properties.

关键词： Globomycin signal peptidase II Cyclic lipodepsipeptide Genome mining CRIsPR-cBEsT Heterologous expression

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Anatomical, Histochemical and Cytogenetic Features of <i>Doryopteris triphylla</i>(Pteridaceae)

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American Journal of Plant sciences 2017年第4期8卷 907-920页

作者： Diego Armando Neira Aldo Rubén Andrada Valeria de los ángeles Páez Ana María Rodriguez Norma Fabiana Ríos olga Gladys martínez Marcela Alicia Hernández Herbario Pteridológico Fundación Miguel Lillo Tucumán Argentina Instituto de Genética Fundación Miguel Lillo Tucumán Argentina Inquinoa-Conicet Tucumán Argentina Facultad de Ciencias Naturales Universidad Nacional de Salta-IBIGEO Salta Argentina

Doryopteris triphylla (Pteridaceae-Cheilanthoideae) grows in xeric habitats in Brazil, Paraguay, Uruguay and Argentina. The aim of this study was to characterize D. triphylla anatomically, histochemically and cytogenetically. For anatomical characterization, rhizomes, roots, petioles and leaves were made and then stained using safranine-Astra Blue for further observations. Leaf blades were also cleared. For histochemical analysis, leaf cross sections were stained with different reagents to identify glandular trichomes compounds. For cytogenetic characterization, a karyogram was performed using laboratory cultivated roots. Results show a dictyostelic rhizome covered with scales with apical secreting gland;diarch roots;petiole cross-sections show thick cuticle, uniseriate epidermis, parenchymatic cortex cells with thick walls and a vascular bundle with two xylem groups;and hypostomatic fronds with glandular trichomes. Histochemical studies of secretion products of the glandular trichomes were positive for polysaccharides, pectins, lipids, acid lipids, dihydroxyphenols, phenols and flavonoids. Cytogenetically, D. triphylla is described as a diploid species (2n = 60), with chromosomes gradually decreasing in size. The apical glands in scales of rhizomes, the presence of two xylem groups in the vascular bundle in the petiole and the glandular trichomes on the abaxial surface are new contributions to the species. The type of chemical products secreted by glandular leaf trichomes and karyotype estimation is shown for the first time in this species.

关键词： Anatomy Histochemistry Karyogram Pteridaceae

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EEG Correlations during WCsT Performance in Female Adolescents with sexual Abuse-Related Post-Traumatic stress Disorder

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Journal of Behavioral and Brain science 2015年第7期5卷 239-250页

作者： Lucía Ester Rizo-martínez Araceli sanz-martin Miguel ángel Guevara Marisela Hernández-González olga Inozemtseva Francisco Abelardo Robles-Aguirre Instituto de Neurociencias CUCBA Universidad de Guadalajara Guadalajara México Centro Universitario del Norte Universidad de Guadalajara Colotlán México

Child sexual abuse (CsA) survivors can present post-traumatic stress disorder (PTsD) and alterations in EEG activity and cognition. The aim of this study was to evaluate EEG correlations in female adolescents with CsA-related PTsD during performance of the Wisconsin Card-sorting Test (WsCT). Inter- and intrahemispheric EEG correlations (INTERr and INTRAr) of those subjects were calculated at rest and during performance of WCsT. On this task, the PTsD group obtained higher scores than the control group for the number of correct responses and failure to maintain set. In the between-groups comparisons, the PTsD group presented a higher INTERr between frontal areas in the gamma and slow bands, as well as a higher correlation in the delta band at Fp1-F3;however, this group presented a lower INTRAr between Fp1-P3 and Fp2-P4 in the theta and alpha1 bands. In the comparison between conditions, the PTsD group presented an increased correlation during execution of the WCsT, mainly in the gamma band, while the control group showed a decrease of INTRAr in the slow bands. Results are discussed with respect to the influence of CsA- related PTsD on the development of cognition and functional connectivity in the brain.

关键词： Child sexual Abuse Post-Traumatic stress Disorder EEG Correlation WCsT Adolescents

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Discovery of gargantulides B and C,new 52-membered macrolactones from Amycolatopsis *** absolute stereochemistry of the gargantulide family

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Organic Chemistry Frontiers 2022年第2期9卷 462-470页

作者： Daniel Carretero-Molina Francisco Javier Ortiz-López Tetiana Gren Daniel Oves-Costales Jesús martín Fernando Román-Hurtado Tue sparholt Jorgensen Mercedes de la Cruz Caridad Díaz Francisca Vicente Kai Blin Fernando Reyes Tilmann Weber olga Genilloud Fundación MEDINA Centro de Excelencia en Investigación de Medicamentos Innovadores en AndalucíaAvda.del Conocimiento 3418016 ArmillaGranadaSpain The Novo Nordisk Foundation Center for Biosustainability Technical University of DenmarkKemitorvetbuilding 2202800 Kgs.LyngbyDenmark

Gargantulides B and C,two new and highly complex 52-membered glycosylated macrolactones,were isolated from Amycolatopsis *** CA-230715 during an antibacterial screening *** structures of these giant macrolides were elucidated by 2D NMR spectroscopy and shown to be related to gargantulide A,although containing additional β-glucopyranose and/orα-arabinofuranose monosaccharides separately attached to their *** sequencing allowed the identification of a strikingly large 216 kbp biosynthetic gene cluster,among the largest type Ⅰ PKs clusters described so far,and the proposal of a previously unreported biosynthetic pathway for gargantulides *** absolute configurations of gargantulides B and C were assigned based on a combination of NMR and bioinformatics analysis of ketoreductase and enoylreductase domains within the multimodular type Ⅰ *** addition,the absolute stereochemistry of gargantulide A has now been revised and *** B and C display potent antibacterial activity against a set of drug-resistant Gram-positive bacteria and moderate activity against the clinically relevant Gram-negative pathogen Acinetobacter baumannii.

关键词： absolute membered backbone

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Current trends of liver cirrhosis in Mexico: similitudes and differences with other world regions

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World Journal of Clinical Cases 2018年第15期6卷 922-930页

作者： Nahum Méndez-sánchez Felipe Zamarripa-Dorsey Arturo Panduro Emma Purón-González Edgar Ulises Coronado-Alejandro Carlos Alejandro Cortez-Hernández Fátima Higuera de la Tijera José Luis Pérez-Hernández Eira Cerda-Reyes Heriberto Rodríguez-Hernández Vania César Cruz-Ramón Oscar Lenin Ramírez-Pérez Nancy Edith Aguilar-Olivos olga Fabiola Rodríguez-martínez samantha Cabrera-Palma Guillermo Cabrera-álvarez Liver Research Unit Medica Sur Clinic and Foundation Department of Gastroenterology Hospital "Juárez" of México Department of Molecular Biology in Me-dicine Civil Hospital of Guadalajara "Fray Antonio Alcalde" Department of Internal Medicine "Christus Muguerza "Super Specialty" Hospital" Monterrey Department of Gas-troenterology "University Hospital "Jose Eleuterio González" Monterrey Department of Gastroenterology "General Hospital of Mexico "Dr.Eduardo Liceaga" Department of Gastroenterology "Central Military Hospital" Faculty of Medicine and Nutrition Juárez University of the State of Durango Liver Clinic Regional General Hospital IMSS 1

AIM To investigate the main current etiologies of cirrhosis in *** We performed a cross-sectional retrospective multicenter study that included eight hospitals in different areas of Mexico. These hospitals provide health care to people of diverse social classes. The inclusion criteria were a histological, clinical, biochemical, endoscopic, or imaging diagnosis of liver cirrhosis. Data were obtained during a 5-year period(January 2012-December 2017). REsULTs A total of 1210 patients were included. The mean age was 62.5 years(sD = 12.1), and the percentages of men and women were similar(52.0% vs 48.0%). The most frequent causes of liver cirrhosis were hepatitis C virus(HCV)(36.2%), alcoholic liver disease(ALD)(31.2%), and nonalcoholic steatohepatitis(23.2%), and the least frequent were hepatitis B virus(1.1%), autoimmune disorders(7.3%), and other conditions(1.0%).CONCLUsION HCV and ALD are the most frequent causes of cirrhosis in Mexico. However, we note that non-alcoholic fatty liver disease(NAFLD) as an etiology of cirrhosis increased by 100% compared with the rate noted previously. We conclude that NAFLD will soon become one of the most frequent etiologies of liver cirrhosis in Mexico.

关键词： Alcoholic liver disease Hepatitis C virus Nonalcoholic steatohepatitis Liver cirrhosis

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Recycling of Glass Fibers from Fiberglass Polyester Waste Composite for the Manufacture of Glass-Ceramic Materials

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Journal of Environmental Protection 2012年第8期3卷 740-747页

作者： Felix Antonio López Maria Isabel martín Irene García-Díaz olga Rodríguez Francisco Jose Alguacil Maximina Romero Centro Nacional de Investigaciones Metalúrgicas (CENIM) CSIC Avda. Gregorio del Amo 8 28040 Madrid Spain Centro Nacional de Investigaciones Metalúrgicas (CENIM-CsIC) Madrid Spain Instituto de Ciencias de la Construcción Eduardo Torroja (IETCC) CSIC Serrano Galvache 4 28033 Madrid Spain

This work presents the feasibility of reusing a glass fiber resulting from the thermolysis and gasification of waste composites to obtain glass-ceramic tiles. Polyester fiberglass (PFG) waste was treated at 550℃ for 3 h in a 9.6 dm3 thermolytic reactor. This process yielded an oil (≈24 wt%), a gas (≈8 wt%) and a solid residue (≈68 wt%). After the polymer has been removed, the solid residue is heated in air to oxidize residual char and remove surface contamination. The cleaning fibers were converted into glass-ceramic tile. A mixture consisting of 95 wt% of this solid residue and 5% Na2O was melted at 1450℃ to obtain a glass frit. Powder glass samples (s then sintered and crystallized at 1013℃, leading to the formation of wollastonite-plagioclase glass-ceramic materials for architectural applications. Thermal stability and crystallization mechanism have been studied by Differential Thermal Analysis. Mineralogy analyses of the glass-ceramic materials were carried out using X-ray Diffraction.

关键词： Valorisation Waste Composite Thermolysis Gasification Glass Fiber Glass-Ceramic

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