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Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice

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Neural Regeneration Research 2017年第4期12卷 588-595页

作者： Teresa Neri-Gomez Judith Espinosa-Raya sofia diaz cintra Julia Segura-Uribe Sandra Orozco-Suarez Juan Manuel Gallardo Christian Guerra-Araiza Unidad de Investigación Médica en Farmacología Hospital de Especialidades Centro Médico Nacional Siglo XXI Instituto Mexicano del Seguro Social Ciudad de México México Laboratorio de Farmacología Conductual Escuela Superior de Medicina Instituto Politécnico Nacional Plan de San Luis y Díaz Mirón Col. Sto. Tomás Ciudad de México México Departamento de Neurobiología del Desarrollo y Neurofisiología Instituto de Neurobiología Universidad Nacional Autónoma de México Campus Juriquilla Querétaro Querétaro México Enfermedades Neurológicas (Neurological Diseases) Hospital de Especialidades Centro Médico Nacional Siglo XXI Instituto Mexicano del Seguro Social Ciudad de México México Enfermedades Nefrológicas (Kidney Diseases) Hospital de Especialidades Centro Medico Nacional Siglo XXI Instituto Mexicano del Seguro Social Ciudad de Mexico Mexico

Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles （NFTs）; these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone （TIB） have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB （0.01 mg/kg and 1mg/kg, intragastrically for 12 weeks） on the content of total and hyperphosphorylated Tau （PHF-1） proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB： it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.

关键词： nerve regeneration Tibolone hippocampus aged mice sex steroids Akt GSK3β PI3K neuralplasticity Tau neurofibrillary tangles neural regeneration

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Sensory neurons in the spinal cord of nominal female embryos in the marine turtle Lepidochelys olivacea respond to shifts in incubation temperature:implications for temperature dependent sex determination

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Advances in Bioscience and Biotechnology 2011年第1期2卷 1-7页

作者： Francisco Jimenez-Trejo Leonora Olivos-Cisneros Julieta Mendoza-Torreblanca sofia diaz-cintra Esperanza-Melendez-Herrera Armida Baez-Saldana Patricia Padilla Cortes Gabriel Gutierrez-Ospina Alma Lilia Fuentes-Farias Departamento de Biologia Facultad de QuimicaUniversidad Nacional Autonoma de MexicoMexico D.F.Mexico 04510 Departamento de Biologia Celular y Fisiologia Instituto de Investigaciones BiomedicasUniversidad Nacional Autonoma de MexicoMexico D.F.Mexico 04510 Departamento de Neuroquimica Instituto Nacional de PediatriaMexicoDF.Mexico 04530 Departamento de Neurobiologia del Desarrollo y Neurofisiologia Instituto de NeurobiologiaUniversidad Nacional Autonoma de MexicoCampus UNAM-JuriquillaJuriquillaQueretaro Mexico AP.1-1141 Laboratorio de Invertebrados y Ecofisiologia Animal Facultad de BiologiaUniversidad Michoacana de San Nicolas de HidalgoMoreliaMichoacanMexico 58040 Unidad de Cromatografia Liquida de Alta Resolucion Instituto de Investigaciones BiomedicasUniversidad Nacional Autonoma de MexicoMexico D.F.Mexico 04510

Gonadal determination in marine turtles depends on incubation temperature. The mechanisms that spark off this process remain unclear. Previously, we proposed that sensory nerves reaching the gonadal primordium in nominal female embryos of Lepidochelys (L) olivacea may sense and signal incubation temperature. These nerves could later trigger ovarian determination by releasing neurotransmitters in a code constructed based on the thermal information (Gutierrez-Ospina et al., Acetylcholinesterase-positive innervation is present at the undifferentiated stages of the sea turtle Lepidochelys olivacea embryo gonads: implications for temperature-dependent sex determination, J. Comp. Neurol. 410 (1999) 90-98). The hypothesis briefly described, however, has been recently refuted under weak theoretical grounds and experimental misinterpretations (see introduction). Here, we present preliminary results that show that nominal female embryos have sensory neurons located in the dorsal horn laminae I and II of the lumbar spinal cord that display increased c-Fos-like immuno-staining after being incubated either at 15°C or 50°C. Because these spinal neurons are the primary central target of dorsal root ganglion neurons that innervate the urogential crest, these observations keep open the possibility that gonadal sensory nerves indeed signal thermal information that could later be used to trigger or instruct ovarian specification in marine turtles.

关键词： Reptiles Ovarian Determination c-Fos Incubation Temperature Sensory Neurons

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Lid scrubbing with a gel combining natural extracts for dry eye treatment

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International Journal of Ophthalmology(English edition) 2023年第7期16卷 1053-1059页

作者： Blanca diaz-Vega Carlos Rodriguez-Fabuel sofia Vitores-Mate Carlos Carpena-Torres Gran Visión Oftalmología Madrid 28026Spain e-Health Vision Department of OphthalmologyMadrid 28232Spain Gran Óptica Madrid Department of Dry EyeMadrid 28026Spain Ocupharm Research Group Department of Optometry and VisionFaculty of Optics and OptometryComplutense University of MadridMadrid 28037Spain

AIM:To evaluate the effect of lid scrubbing using a gel combining different natural extracts on ocular signs and symptoms of dry eye ***:A retrospective study was performed on 19 dry eye patients(51.1±16.0y).Non-invasive tear break-up time,tear meniscus height,meibomian gland loss,lipid layer thickness,conjunctival redness,corneal staining,ocular surface disease index(OSDI),and ocular pain intensity were measured before(baseline),1wk,and 2mo after lid scrubbing with a gel containing different natural extracts(okra extract,aloe vera leaf juice,hydrolysed soy protein,caffeine,citrus unshiu peel extract,and raspberry seed oil).RESULTS:Compared with the baseline,there was a statistically significant improvement in both first(P=0.048)and average(P=0.026)non-invasive tear break-up time 2mo after treatment,as well as in corneal staining(P=0.043,0.012),OSDI(P<0.001),and ocular pain intensity(P<0.001)after 1wk and *** addition,there was no correlation between ocular signs and ***:The lid scrubbing with a gel combining different natural extracts show beneficial effects on tear film stability,corneal damage,and ocular symptoms,which is the reason why this therapeutic procedure is proposed as an alternative for dry eye ***,it is not possible to attribute this beneficial effect solely to the presence of the natural extracts in the gel,primarily due to the absence of a negative control group.

关键词： lid hygiene natural extracts okra aloe vera soy dry eye

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Nanoengineered Shear-Thinning Hydrogel Barrier for Preventing Postoperative Abdominal Adhesions

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Nano-Micro Letters 2021年第12期13卷 452-467页

作者： Guillermo U.Ruiz-Esparza Xichi Wang Xingcai Zhang sofia Jimenez-Vazquez Liliana diaz-Gomez Anne-Marie Lavoie Samson Afewerki Andres AFuentes-Baldemar Roberto Parra-Saldivar Nan Jiang Nasim Annabi Bahram Saleh Ali K.Yetisen Amir Sheikhi Thomas H.Jozefiak Su Ryon Shin Nianguo Dong Ali Khademhosseini Biomaterials Innovation Research Center Division of Engineering in MedicineDepartment of MedicineBrigham and Women’s HospitalHarvard Medical SchoolCambridgeMA 02139USA Division of Health Sciences and Technology Harvard University-Massachusetts Institute of TechnologyCambridgeMA 02139USA Department of Cardiovascular Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022People’s Republic of China School of Engineering and Applied Sciences Harvard UniversityCambridgeMA 02138USA School of Engineering and Science Tecnologico de MonterreyCampus MonterreyMonterreyNuevo Leon 64849Mexico School of Medicine and Health Science Campus GuadalajaraZapopanJalisco 45201Mexico West China School of Basic Medical Sciences and Forensic Medicine Sichuan UniversityChengdu 610041China Department of Chemical and Biomolecular Engineering University of CaliforniaLos AngelesLos AngelesCA 90095USA Department of Chemical Engineering Northeastern UniversityBostonMA 02115USA Department of Chemical Engineering Imperial College LondonLondon SW72AZUK Department of Chemical Engineering The Pennsylvania State UniversityUniversity ParkPA 16802USA Department of Biomedical Engineering The Pennsylvania State UniversityUniversity ParkPA 16802USA Terasaki Institute for Biomedical Innovation 11570 W Olympic BlvdLos AngelesCA 90024USA

More than 90%of surgical patients develop postoper-ative adhesions,and the incidence of hospital re-admissions can be as high as 20%.Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive *** solve thisclinical limitation,we developed an injectable and sprayable shear-thinning hydrogel barrier(STHB)composed of silicate nanoplatelets and poly(ethylene oxide).We optimized this technology to recover mechanical integrity after stress,enabling its delivery though inject-able and sprayable *** also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in *** STHB was then tested in a rodent model of peritoneal injury to determine its e cacy preventing the formation of postoperative *** two weeks,the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions,and STHB formulations presented superior e cacy compared to a commercially available adhesion *** and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB *** technology demonstrated increased e cacy,ease of use in complex anatomies,and compatibility with di erent delivery methods,providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions.

关键词： Postoperative adhesions Shear-thinning hydrogel Silicate nanoplatelets Nanotechnology Nanomedicine

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Portal hypertensive colopathy is associated with portal hypertension severity in cirrhotic patients

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World Journal of Gastroenterology 2009年第38期15卷 4781-4787页

作者： Antonio diaz-Sanchez Oscar Nuez-Martinez Cecilia Gonzalez-Asanza Ana Matilla Beatriz Merino Diego Rincon Inmaculada Beceiro Maria Vega Catalina Magdalena Salcedo Rafael Baares Gerardo Clemente Liver Unit-CIBEREHD.Hospital General Universitario Gregorio Maraón Madrid 28007Spain Gastroenterology Unit Hospital Infanta Leonor Gastroenterology Unit Hospital Infanta Sofia Department of Gastroenterology Hospital Universitario Príncipe de Asturias

AIM： To assess the prevalence of portal hypertension （PH） related colorectal lesions in liver transplant candidates, and to evaluate its association with the severity of PH. METHODS： Between October 2004 and December 2005, colonoscopy was performed in 92 cirrhotic liver transplant candidates. We described the lesions resulting from colorectal PH and their association with the grade of PH in 77 patients who underwent measurement of hepatic venous pressure gradient （HVPG）. RESULTS： Mean age was 55 years and 80.7% of patients were men. The main etiology of cirrhosis wasalcoholism （45.5%）. Portal hypertensive colopathy （PHC） was found in 23.9%, colonic varices in 7.6% and polyps in 38% of patients （adenomatous type 65.2%）. One asymptomatic patient had a well-differentiated adenocarcinoma. The manifestations of colorectal PH were not associated with the etiology of liver disease or with the Child-Pugh grade. Ninety percent of patients with colopathy presented with gastroesophageal varices （GEV）, and 27.5% of patients with GEV presented with colopathy （P = 0.12）. A relationship between higher values of HVPG and presence of colopathy was observed （19.9：1：6.2 mmHg vs 16.8 ± 5.4 mmHg, P = 0.045）, but not with the grade of colopathy （P = 0.13）. Preneoplastic polyps and neoplasm （P = 0.02） and spontaneous bacterial peritonitis （P = 0.006） were more prevalent in patients with colopathy. We did not observe any association between previous β-blocker therapy and the presence of colorectal portal hypertensive vasculopathy. CONCLUSION： PHC is common in cirrhotic liver transplant candidates and is associated with higher portal pressure.

关键词： Liver cirrhosis Portal hypertension Polyps Colopathy Liver transplantation

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