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Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes

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Neural Regeneration Research 2013年第24期8卷 2290-2302页

作者： Farfán-García Eunice Dalet Trujillo-Ferrara José Guadalupe Castillo-Hernández maría del carmen Guerra-Araiza Christian Humberto Soriano-Ursúa marvin Antonio Escuela Superior de Medicina Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón s/n Col. Casco de Santo Tomas

In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and or- thosteric binding sites on dopamine receptors for the treatment of Parkinson＇s disease, and on muscarinic receptors for Alzheimer＇s disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopa- mine receptor holds promise as a relevant therapeutic strategy for Parkinson＇s disease. Regarding the treatment of Alzheimer＇s disease, the design of dualsteric ligands for mono-oligomeric mus- carinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.

关键词： neural regeneration G-Protein coupled receptors structural biology drug design neurodegenera-tive disorders , oligomedzation biased signaling Parkinson's disease Alzheimer's disease dopa-mine receptors muscarinic receptors grants-supported paper neuroregeneration

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The role of clinical diagnosis criteria on the frequency of accommodative insufficiency

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International Journal of Ophthalmology(English edition) 2019年第4期12卷 647-653页

作者： maría García-Montero Beatriz Antona Ana Rosa Barrio carmen Nieto-Zayas Irene martínez-Alberquilla José Luis Hernández-Verdejo Department of Optometry and Vision Faculty of Optics and Optometry Complutense University of Madrid Department of Statistics and Operations Research Ⅲ Faculty of Statistical Studies Complutense University of Madrid

AIM: To estimate and compare the frequency of accommodative insufficiency(AI) within the same clinical population sample depending on the type of clinical criteria used for diagnosis. Comparing the frequency within the same population would help to minimize bias due to sampling or methodological variability. METHODS: Retrospective study of 205 medical records of symptomatic subjects free of any organic cause and symptoms persisting despite optical compensation evaluated. Based on the most commonly clinical diagnostics criteria found in the literature, four diagnostics criteria were established for AI(Ⅰ, Ⅱ, Ⅲ and Ⅳ) based on subjective accommodative tests: monocular accommodative amplitude two or more diopters below Hofstetter's minimum value [15-(0.25×age)](Ⅰ, Ⅱ, Ⅲ, Ⅳ); failing monocular accommodative facility with minus lens, establishing the cut-off in 0 cycles per minute(cpm)(Ⅰ) and in 6 cpm(Ⅱ, Ⅲ); failing binocular accommodative facility with minus lens, establishing the cut-off in 0 cpm(Ⅰ) and in 3 cpm(Ⅱ).RESULTS: The proportion of AI(95%CⅠ) for criteria Ⅰ, Ⅱ, Ⅲ and Ⅳ were 1.95%(0.04%-3.86%), 2.93%(0.31%-4.57%), 6.34%(1.90%-7.85%) and 41.95%(35.14%-48.76%) respectively, with a statistically significant difference shown between these values(χ2=226.7, P<0.001). A pairwise multiple comparison revealed that the proportion of AI detected for criterion Ⅳ was significantly greater than the proportion for the rest of the criteria(P-adjusted<0.05 in all cases).CONCLUSION: The prevalence of cases of AI within the same clinical population varies with the clinical diagnostic criteria selected. The variation is statistically significant when considering the monocular accommodative amplitude as the only clinical diagnostic sign.

关键词： epidemiology amplitude of accommodation accommodative facility

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Dynamics and cytokinic regulation of immune cell infiltration in genetically engineered mouse models of pancreatic cancer dictate the sensitivity to immunotherapy

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Cancer Communications 2024年第1期44卷 178-182页

作者： Okan Safak Shenghan Wang carmen Mota Reyes Ibrahim Halil Gürcinar Sergey Tokalov Nedim Can Cevik Kivanc Görgülü Bengi Su Yilmaz Emre Erdogan Linhan Ye Qiaolin Li Elif Arik Sever SamedÖzer Güldal Süyen Helmut Friess Güralp Onur Ceyhan Rouzanna Istvanffy Hana Algül Ihsan Ekin Demir Department of Surgery Klinikum rechts der IsarTechnical University of MunichSchool of MedicineMunichBavariaGermany Department of General Surgery HPB-UnitSchool of MedicineAcibadem Mehmet Ali Aydinlar UniversityIstanbulIstanbulTurkey Comprehensive Cancer Center München Klinikum rechts der IsarTechnical University of MunichSchool of MedicineMunichBavariaGermany Department of Hematology Oncology and Tumor ImmunologyCharitéUniversity Medicine BerlinCampus Virchow ClinicBerlinBerlinGermany Graduate School of Health Sciences Acibadem Mehmet Ali Aydinlar UniversityIstanbulIstanbulTurkey Department of Physiology Acibadem Mehmet Ali Aydinlar UniversityIstanbulIstanbulTurkey Else Kröner Clinician Scientist Professorship for Translational Pancreatic Surgery MunichGermany Neural Influences in Cancer(NIC)International Research Consortium MunichGermany

Dear Editor,Targeting the immune compartment in pancreatic duc-tal adenocarcinoma(PDAC)holds promise for prognostic improvement,yet our knowledge on the spatial and tem-poral dynamics and the molecular modulators of t... 详细信息

关键词： immune adenocarcinoma immunotherapy

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Reactive oxygen species and antioxidant properties from mushrooms

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Synthetic and Systems Biotechnology 2017年第1期2卷 13-22页

作者： carmen Sanchez Laboratory of Biotechnology Research Centre for Biological SciencesUniversidad Autonoma de TlaxcalaIxtacuixtlaTlaxcalaCP.90062Mexico

Preventive medicine and food industry have shown an increased interest in the development of natural antioxidants,since those most commonly used synthetic antioxidants may have restricted use in *** could explain why there is currently much research on the antioxidant properties from natural products such as *** mushrooms have been reported to possess antioxidant properties,which enable them to neutralize free *** oxygen molecule is a free radical,which lead to the generation of the reactive oxygen species and can damage the *** damage caused by free radicals appears to be a major contributor to aging and degenerative *** antioxidant components are found in fruit bodies,mycelium and culture both,which include polysaccharides,tocopherols,phenolics,carotenoids,ergosterol and ascorbic acid among *** bodies or mycelium can be manipulated to produce active compounds in a relatively short period of time,which represent a significant advantage in antioxidant compounds extraction from *** compounds may be extracted to be used as functional additives or mushrooms can be incorporated into our food regime,representing an alternative source of food to prevent damage caused by oxidation in the human body.

关键词： Antioxidant Fruit body Mushroom Mycelium Reactive oxygen species

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Enhanced depth OCT imaging of the lamina cribrosa for 24 hours

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International Journal of Ophthalmology(English edition) 2017年第2期10卷 306-309页

作者： Pedro Naranjo Bonilla Rafael Giménez Gómez David Ríos Jiménez maría Luísa Varas Fabra maría del carmen Munoz Villanueva Rocío García Catalán Pilar Font Ugalde maría Soledad Poblador Fernández JoséLuís Lancho Alonso Josémaría Gallardo Galera Department of Ophthalmology Reina Sofia University HospitalCordoba 14004Spain Methodological Support to Research Maimonides Institute for Biomedical ResearchReina Sofia University HospitalCordoba 14004Spain Department of Medicine UCO Maimonides Institute for Biomedical ResearchReina Sofia University HospitalCordoba 14004Spain Department of Morphological Sciences Faculty of MedicineCordoba 14004Spain

The lamina cribrosa thickness（LCT） could be affected by dynamic changes in its *** spectral-domainoptical coherence tomography（SD-OCT）,we have studied the behaviour of the laminar region in 14 young subjects over 24 *** changes in LCT were observed,depending on the time at which the measurement was taken,with the maximum thickness being observed at 7.30 p.m.,and the minimum at 7.30 *** finding could suggests a circadian pattern in the LCT thickness in healthy subjects,which could have implications for the classification,diagnosis and prognosis of both normal and glaucomatous subjects.

关键词： lamina cribrosa laminar region glaucoma optical coherence tomography twenty-four-hours

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Umbilical cord as a mesenchymal stem cell source for treating joint pathologies

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World Journal of Orthopedics 2011年第6期2卷 43-50页

作者： maría carmen Arufe Alexandre De la Fuente Isaac Fuentes Francisco Javier De Toro Francisco Javier Blanco Department of Medicine Area of Anatomy and Human EmbryologyCampus Oza s/nFac.of Health ScienceUniversity of A Coruna15006 A CorunaSpain Osteoarticular and Aging Research Lab Cellular Therapy UnitINIBIC-CH Universitario A Coruna15006 A CorunaSpain Rheumatology Division INIBIC-CH Universitario A Coruna15006 A CorunaSpain Cathedra Bioiberica Universidad de A Coruna15006 A CorunaSpain CIBER-BBN-Instituto de Salud Carlos III 15006 A CorunaSpain Centro de Investigacion Biomedica Hospital Universitario A CorunaC/Xubias 8415006 A CorunaSpain

Articular cartilage disorders and injuries often result in life-long chronic pain and compromised quality of ***,the regeneration of articular cartilage is a continuing challenge for biomedical *** of the most promising therapeutic approaches is cellbased tissue engineering,which provides a healthy population of cells to the injured site but requires differentiated chondrocytes from an uninjured *** use of healthy chondrocytes has been found to have limitations.A promising alternative cell population is mesenchymal stem cells(MSCs),known to possess excellent proliferation potential and proven capability for differentiation into ***“immunosuppressive”property of human MSCs makes them an important candidate for allogeneic cell *** use of allogeneic MSCs to repair large defects may prove to be an alternative to current autologous and allogeneic tissue-grafting *** allogeneic cell-based approach would enable MSCs to be isolated from any donor,expanded and cryopreserved in allogeneic MSC banks,providing a readily available source of progenitors for cell replacement *** possibilities have spawned the current exponential growth in stem cell research in pharmaceutical and biotechnology *** objective in this review is to summarize the knowledge about MSCs from umbilical cord stroma and focus mainly on their applications for joint pathologies.

关键词： Human Mesenchymal stem cell Umbilical cord Cartilage degeneration

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Effect of Water Stress Induced by Polyethylene Glycol on Growth, Proline Accumulation in Agave americana L.

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Phyton-International Journal of Experimental Botany 2023年第2期92卷 629-643页

作者： Alfaro-Corres Arnoldo Enrique Lecona-Guzman Carlos Alberto Gutiérrez-Miceli Federico Antonio martínez-Esteves Manuel Silverio-Gómez maría del carmen Medina-Lara maría de Fátima Ruiz-Lau Nancy Laboratorio de Biotecnología vegetal Instituto Tecnológico de Tuxtla GutiérrezTuxtla Gutiérrez29050México Centro de Investigación Científica de Yucatán Unidad de Bioquímica y Biología Molecular de PlantasMérida97205México Insituto Nacional de Investigaciones Forestales Agrícolas y PecuariasHuimanguilloTabasco86400México CONACYT-Tecnológico Nacional de México/Instituto Tecnológico de Tuxtla Gutiérrez Tuxtla Gutiérrez29050México

The effect of water deficit was determined on both in vitro and soil seedling as well as in cells in suspension of Agave americana *** order to do the establishment of cells,the formation of callus was induced;for it two auxins were evaluated:2,4-dichlorophenoxyacetic acid(2,4-D)and 4-mino-3,5,6-trichloropicolinic acid(picloram)at three concentrations(0.25,0.5 and 0.75 mg L−1)in three explants(leaf,root and meristems)cultured in MS semisolid *** callogenesis response was related to the type and section of the explant,as well as the regulator used,and a cell suspension was established using 0.5 mg L−1 naphthaleneacetic acid(NAA)+0.5 mg L−1 Benzylaminopurine(BAP).Seedlings were exposed to polyethyleneglycol(15%and 30%w/v)with a water potential of−0.87 and−2.67 MPa,respectively,under soil *** stress was applied through restricted *** weight,root system growth,and chlorophyll concentration were some of the parameters that were affected by the effect of water deficit on *** *** concentration values were significantly decreased by 15 at 30%PEG(19.6 SPAD units)compared to the control *** in vitro plants,the highest concentration of proline was found in the roots,being the treatment with 30%polyethylene glycol where the highest concentration of this osmoregulator was obtained(62.5 mg g−1 DW).Under restricted irrigation conditions,an increase in proline concentration was observed both in the aerial part(2.2μg 100 g−1 DW)and in the root system(1.8μg 100 g−1 DW).However,the concentrations found were approximately ten times greater,less than those found under in vitro ***,the accumulation of proline can be considered an indicator of stress in Agave Americana *** in vitro.

关键词： Agave americana water deficit proline

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Selectivity in feeding preferences and ranging patterns in spider monkeys Ateles geoffroyi yucatanensis of northeastern Yucatan peninsula, Mexico

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Current Zoology 2013年第1期59卷 125-134页

作者： carmen SCHERBAUM Alejandro ESTRADA Department of Animal Ecology and Tropical Biology Biozentrum University of Wiirzburg Germany Estacion de Biologia Tropical Los Tuxtlas Instituto de Biologfa Universidad Nacional Aut6noma de M6xico Apartado Postal94 San Andres Tuxtla Veracruz M6xico C. P. 95700

The spider monkey, a fruit specialist and important seed dispersal agent in the Neotropics, is an endangered primate due to habitat loss, hunting and the pet trade. Spider monkeys have been the subject of a few studies in Central and South Ame- rica, but little is known about the diet and ranging for this primate in southern Mexico. Here we report the results of a six-month long study （October 2010 to march 2011） of the feeding preferences and ranging patterns of the Yucatan spider monkey Ateles geoffroyi yucatanensis living in the ＂Ya＇ax＇che＂ reserve by the Caribbean coast in northeast Yucatan peninsula. Focal animal and scan sampling as well as GPS tracking were used to document spider monkey feeding behavior, location of food trees and ranging in the reserve. The spider monkeys used 36 species of plants （94% trees; n = 432） and six non tree morphospecies as a source of food. Six tree species accounted for 〉~80% of total feeding time and for 74% of all trees used. Fruits accounted for 59% of total feeding time, followed by leaves （35%）, palm piths （5%） and other plant parts （1%）. Total range used by the monkeys was esti- mated at 43% of semievergreen rainforest habitat available （ca 40ha）. Range use was not random with segments showing light, moderate and heavy use; the use of different areas of their range varied monthly and was closely linked to the spatial dispersion of the trees used for food [Current Zoology 59 （1）： 125-134, 2013].

关键词： Primates Frugivory Neotropics Conservation Seed dispersal

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Narcea—an unknown,ancient cultivated rose variety from northern Spain

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Horticulture Research 2020年第1期7卷 2217-2228页

作者： maría-carmen martínez José-Luis Santiago Susana Boso Pilar Gago InmaculadaÁlvarez-Acero maría-Estela De Vega Miguel martínez-Bartolomé RafaelÁlvarez-Nogal Pilar Molíst Matteo Caser Valentina Scariot Daniel Gómez-García Misión Biológica de Galicia(CSIC) Carballeira 8Salcedo 36143 PontevedraSpain Instituto de Ciencia y Tecnología de Alimentos y Nutrición(CSIC)(Spain) C/JoséAntonio Novais 1028040 MadridSpain Departamento de Biología Molecular-Área de Biología Celular Universidad de LeónCampus de Vegazana s/n24071 LeónSpain Grupo Neurolamb Biología funcional y Ciencias de la SaludUniversidad de Vigo(Spain)36310 As Lagoas-MarcosendeSpain Department of Agricultural Forest and Food SciencesUniversity of TorinoLargo Paolo Braccini 210095 GrugliascoTurinItaly Instituto Pirenaico de Ecología(CSIC) Dpto.Conservación de Ecosistemas NaturalesAvda.Montaña S/NZaragoza50016 ZaragozaSpain

The present work reports the discovery and the complete characterisation of an ancient cultivated rose variety found growing in a private garden in the southwest of the Principality of Asturias(northern Spain).The variety is here given the name *** majority of roses currently cultivated belong to the so-called group of‘Modern Roses’,all of which were obtained after 1867 via artificial crosses and improvement *** are destined for ornamental *** the 19th century,the great majority of the many ancient cultivated roses in Europe were used in perfumery and cosmetics,or had medicinal *** damascena and Rosa centifollia are still grown and used by the French and Bulgarian perfume *** Asturian Massif of the Cantabrian Mountain Range provides a natural habitat for some 75%of the wild members of the genus Rosa,but until now there was no evidence that this area was home to ancient cultivated roses.A complete botanical description is here provided for a discovered ancient *** is also characterised according to a series of sequence tagged microsatellite sites,and its agronomic features are *** addition,a histological description(optical and scanning electronic microscope studies)of the petals is offered,along with an analysis of the volatile compounds present in these organs as determined by solid phase microextraction and gas chromatography-mass *** results reveal the uniqueness of this ancient type of rose and suggest it may be of interest to the perfume industry.

关键词： ancient southwest majority

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Improving outcomes in pancreatic cancer: Key points in perioperative management

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World Journal of Gastroenterology 2014年第39期20卷 14237-14245页

作者： José M álamo Luis M marín Gonzalo Suarez carmen Bernal Juan Serrano Lydia Barrera Miguel A Gómez Jordi Muntané Francisco J Padillo Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREH o Ciberehd) Instituto de Salud Carlos Ⅲ 28029 Madrid Spain Francisco J Padillo Department of General Surgery Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla 41013 Seville Spain

This review focused in the perioperative management of patients with pancreatic cancer in order to improve the outcome of the disease. We consider that the most controversial points in pancreatic cancer management are jaundice management, vascular resection and neo-adjuvant therapy. Preoperative biliary drainage is recommended only in patients with severe jaundice, as it can lead to infectious cholangitis, pancreatitis and delay in resection, which can lead to tumor progression. The development of a phase III clinical trial is mandatory to clarify the role of neo-adjuvant radiochemotherapy in pancreatic adenocarcinoma. Venous resection does not adversely affect postoperative mortality and morbidity, therefore, the need for venous resection should not be a contraindication to surgical resection in selected patients. The data on arterial resection alone, or combined with vascular resection at the time of pancreatectomy are more heterogeneous, thus, patient age and comorbidity should be evaluated before a decision on operability is made. In patients undergoing R0 resection, arterial resection can also be performed.

关键词： Pancreatic cancer Obstructive jaundice Preoperative drainage Neo-adjuvant therapy Vascular resection

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