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1Translational pancreatic cancer research:a comparative study on patient-derived xenograft models显示文摘AIM To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice.METHODS This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations(intraperitoneal, subcutaneous and pancreatic). Histological analysis(haematoxylin-eosin and Masson's trichrome staining) and immunohistochemical assessment of apoptosis(TUNEL), proliferation(Ki-67), angiogenesis(CD31) and fibrogenesis(α-SMA) were performed. When a tumour xenograft reached the target size, it was reimplanted in a new nude mouse. Three sequential tumour xenograft generations were generated(F1, F2 and F3).RESULTS The overall tumour engraftment rate was 61.1%. The subcutaneous model was most effective in terms of tissue growth(69.9%), followed by intraperitoneal(57.6%) and pancreatic(55%) models. Tumour development was faster in the subcutaneous model(17.7 ± 2.6 wk) compared with the pancreatic(23.1 ± 2.3 wk) and intraperitoneal(25.0 ± 2.7 wk) models(P = 0.064). There was a progressive increase in the tumour engraftment rate over successive generations for all three models(F1 28.1% vs F2 71.4% vs F3 80.9%, P < 0.001). There were no significant differences in tumour xenograft differentiation and cell proliferation between human samples and the three experimental models among the sequential generations of tumour xenografts. However, a progressive decrease in fibrosis, fibrogenesis, tumour vascularisation and apoptosis was observed in the three experimental models compared with the human samples. All three pancreatic patient-derived xenograft models presented similar histological and immunohistochemical characteristics.CONCLUSION In our experience, the faster development andgreatest number of viable xenografts could make the subcutaneous model the best option for experimentation in pancreatic cancer.Mercedes Rubio-Manzanares Dorado Luis Miguel Marín Gómez Daniel Aparicio Sánchez Sheila Pereira Arenas Juan Manuel Praena-Fernández Juan Jose Borrero Martín Francisco Farfán López Miguel ángel Gómez Bravo Jordi Muntané Relat Javier Padillo Ruiz 2018World Journal of Gastroenterology2018,24,7:2
2Modifi cation of sleep architecture in an animal model of experimental cirrhosis显示文摘AIM: To analyze the polygraphic sleep patterns during cirrhosis progression in a rat model by repeated CCl4 administration. METHODS: Male Wistar rats received three weekly injections of CCl4 for 11 wk, and were analyzed before and during the induction of cirrhosis. Rats were implanted with electrodes to record their sleep patterns. Polygraph recordings were made weekly over 11 wk for 8 h, during the light period. After a basal recording, rats received three weekly injections of CCl4. Histological conf irmation of cirrhosis was performed after 11 wk.RESULTS: The results showed a progressive decrease in total wake time that reached statistical signif icance from the second week of treatment. In addition, there was an increase in total time of slow wave sleep (SWS) and rapid eye movement sleep (REM sleep) in most of the 11 wk. SWS showed no signif icant variations.During the final weeks, a significant increase in REM sleep frequency was also observed. Histological analyses of the livers showed unequivocal signs of cirrhosis. CONCLUSION: These data suggest that hepatic failure produced by CCl4 administration is capable of modifying the sleep pattern even after only a few doses.Anabel Jiménez-Anguiano Vanessa Díaz-Medina Blanca Eugenia Farfán-Labonne Gloria Giono-Chiang David Kersenobich Mario García-Lorenzana Maria Concepción Gutiérrez-Ruiz Javier Velázquez-Moctezuma 2009World Journal of Gastroenterology2009,15,41:2
3查看详情显示文摘H?pfl H Galván M Farfán N Santillan R 0,,:1
4查看详情显示文摘H?pfl H Farfán N Castillo D Santillan R Gutierrez A Daran J C 0,,:1
5Acetaldehyde-induced mitochondrial dysfunction sensitizes hepatocytes to oxidative damage显示文摘Blanca Eugenia Farfán Labonne Mario Gutiérrez Luis Enrique Gómez-Quiroz Mina Konigsberg Fainstein Leticia Bucio Verónica Souza Oscar Flores Victor Ortíz Elizabeth Hernández David Kershenobich María Concepción Gutiérrez-Ruíz 2009Cell Biology and Toxicology2009,,6:1
6Preparation of degraded human DNA under controlled conditions显示文摘Bender K Farfár MJ Schneider PM 2004Forensic Sci Int2004,139,23:1
7Long-Term Changes in Game Species Over a Long Period of Transformation in the Iberian Mediterranean Landscape显示文摘Miguel Delibes-Mateos Miguel ángel Farfán Jesús Olivero Ana Luz Márquez Juan Mario Vargas 2009Environmental Management2009,,6:1
8Divergent evolution and purifying selection of the flaA gene sequences in Aeromonas显示文摘FARF N M MIIqANA-GALBIS D FUSTE M C 2009Biology Direct2009,4,1:1
9Increased production of soluble TLR2 by lamina propria mononuclear cells from ulcerative colitis patients显示文摘Enzo Candia David Díaz-Jiménez Patricia Langjahr Lucía E. Nú?ez Marjorie de la Fuente Nancy Farfán Francisco López-Kostner Mario Abedrapo Manuel Alvarez-Lobos George Pinedo Caroll J. Beltrán Carlos González María-Julieta González Rodrigo Quera Marcela A. 2011Immunobiology2011,,6:1
10Reduction of fungi and mycotoxins formation in seeds by gamma-radiation显示文摘AZIZ N H MOUSSAL A A FARF M E 2004Journal of Food Safety2004,24,2:1
11查看详情显示文摘H?pfl H Farfán N Castillo D Santillan R Contreras R Martínez-Martínez F J Galván M Alvarez R Fernández L Halut S Daran J C 0,,:1
12Effect of tibolone pretreatment on kinases and phosphatases that regulate the expression and phosphorylation of Tau in the hippocampus of rats exposed to ozone显示文摘Oxidative stress(OS) is a key process in the development of many neurodegenerative diseases, memory disorders, and other pathological processes related to aging. Tibolone(TIB), a synthetic hormone used as a treatment for menopausal symptoms, decreases lipoperoxidation levels, prevents memory impairment and learning disability caused by ozone(O_3) exposure. However, it is not clear if TIB could prevent the increase in phosphorylation induced by oxidative stress of the microtubule-associated protein Tau. In this study, the effects of TIB at different times of administration on the phosphorylation of Tau, the activation of glycogen synthase kinase-3β(GSK3β), and the inactivation of Akt and phosphatases PP2 A and PTEN induced by O_3 exposure were assessed in adult male Wistar rats. Rats were divided into 10 groups: control group(ozone-free air plus vehicle [C]), control + TIB group(ozone-free air plus TIB 1 mg/kg [C + TIB]); 7,15, 30, and 60 days of ozone exposure groups [O_3] and 7, 15, 30, and 60 days of TIB 1 mg/kg before ozone exposure groups [O_3 + TIB]. The effects of O_3 exposure and TIB administration were assessed by western blot analysis of total and phosphorylated Tau, GSK3β, Akt, PP2 A, and PTEN proteins and oxidative stress marker nitrotyrosine, and superoxide dismutase activity and lipid peroxidation of malondialdehyde by two different spectrophotometric methods(Marklund and TBARS, respectively). We observed that O_3 exposure increases Tau phosphorylation, which is correlated with decreased PP2 A and PTEN protein levels, diminished Akt protein levels, and increased GSK3β protein levels in the hippocampus of adult male rats. The effects of O_3 exposure were prevented by the long-term treatment(over 15 days) with TIB. Malondialdehyde and nitrotyrosine levels increased from 15 to 60 days of exposure to O_3 in comparison to C group, and superoxide dismutase activity decreased. Furthermore, TIB administration limited the changes induced by O_3 exposure. Our results suggest a beneficial use of hormone replacement therapy with TIB to prevent neurodegeneration caused by O_3 exposure in rats.Rodolfo Pinto-Almazán Julia J. Segura-Uribe Marvin A. Soriano-Ursúa Eunice D. Farfán-García Juan M. Gallardo Christian Guerra-Araiza 2018Neural Regeneration Research2018,13,3:0
13Scope of translational medicine in developing boroncontaining compounds for therapeutics显示文摘The ubiquitousness of naturally occurring boron-containing compounds(BCCs) has led to their constant contact with humankind.Recently,many synthetic BCCs have been elaborated for a broad spectrum of purposes,especially boric,boronic and borinic acids.Although BCCs were once employed primarily as antiseptics and later as antibiotics,they have become an increasingly relevant therapeutic tool.Nevertheless,this potential of BCCs has been drastically limited due to some unfortunate intra-hospital accidents in the 1940 s and 1950 s.The increasing use of BCCs as insecticides,antimicrobials,and other agents is providing new insights into their role in the physiology of several living species and in the pathophysiology of humans.It is becoming clear that BCCs act through a wide range of mechanisms,as do their corresponding boron-free counterparts.When comparing BCCs and similar boron-free compounds,in many cases the former show advantages in the medical field.The current minireview focuses on how BCCs have been developed by means of translational medicine,a process connecting biomedical research with clinical applications.This process of discovery is currently in an exponential stage.Ana Karen García-ávila Eunice Dalet Farfán-García Juan Alberto Guevara-Salazar José Guadalupe Trujillo-Ferrara Marvin Antonio Soriano-Ursúa 2017World Journal of Translational Medicine2017,6,1:0
14More than boric acid:Increasing relevance of boron in medicine显示文摘Although boron has been a chemical element of interest since the ancient times,only a few boron-containing compounds(BCCs)had been used for medicinal purposes before the 21^(st) century.Among these,only boric acid has been explored in multiple therapeutic applications.Hence,it is common to extrapolate from boric acid to all BCCs,supposing a similar biological effect.However,boric acid is just one of dozens of BCCs in nature and thousands available from chemical synthesis.Nowadays,there is a boom in research on new BCCs as potential tools in the prevention,diagnosis and therapy of human disease.We herein discuss the new role of BCCs in drug development,with emphasis on the compounds for which a mechanism of action has been proposed or demonstrated.Because of data gathered in recent years,BCCs have expanded beyond the well-known fields of antimicrobial and antineoplastic agents,now being explored for their possible use as enzyme inhibitors,regulators of protein expression and modulators of the immune response,as well as in biomaterials.We suggest that translational medicine can accelerate the medicinal applications of BCCs,which is especially important for the human diseases that are generating a high global burden.Eunice D Farfán-García Emily L Castillo-García Marvin A Soriano-Ursúa 2018World Journal of Translational Medicine2018,7,1:0
15Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes显示文摘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 selectivity 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 orthosteric 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 dopamine 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 muscarinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.Farfán-García Eunice Dalet Trujillo-Ferrara José Guadalupe Castillo-Hernández María del Carmen Guerra-Araiza Christian Humberto Soriano-Ursúa Marvin Antonio 2013Neural Regeneration Research2013,8,24:0
16Global longitudinal strain is superior to ejection fraction for detecting myocardial dysfunction in end-stage renal disease with hyperparathyroidism显示文摘BACKGROUND The estimation of left ventricular ejection fraction(LVEF)by 2D echocardiography(2D-ECHO)is the most used tool to assess LV systolic function(LVSF).Global longitudinal strain(GLS)has recently been suggested as a superior method for several evaluations.This study explored the association and prevalence of LV systolic dysfunction(LVSD)by using these methods in patients with end-stage renal disease(ESRD)and severe hyperparathyroidism(SHPTH);both associated with cardiovascular events(CEs).AIM To evaluate the myocardial function in patients with ESRD and SHPTH by using the GLS and LVEF measured through conventional 2D-ECHO.METHODS In 62 patients with ESRD and SHPTH,asymptomatic,and without a history of CEs,LVSF was evaluated by 2D-ECHO,obtaining the EF,by the Simpson biplane method,and GLS by speckle tracking.RESULTS The total patients with ESRD had a preserved LVEF(>50%)but abnormal GLS(<13.55%).Additionally,multivariate analysis showed an independent association of GLS and serum parathyroid hormone(PTH),LV mass index,and hemoglobin.Also,PTH was independently associated with lateral e'wave and tricuspid regurgitation velocity.CONCLUSION In patients with SHPTH linked to ESRD,the use of GLS by 2D-ECHO is a more sensitive tool than LVEF for detecting LVSD.Maria Fernanda Carrasco-Ruiz Antonio Ruiz-Rivera Marvin A Soriano-Ursúa Carlos Martinez-Hernandez Leticia Manuel-Apolinar Carmen Castillo-Hernandez Gustavo Guevara-Balcazar Eunice D Farfán-García Ana Mejia-Ruiz Ivan Rubio-Gayosso Teresa Perez-Capistran 2022World Journal of Cardiology2022,14,4:0
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