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Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system

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Neural Regeneration Research 2025年第11期20卷 3209-3210页

作者： Marta García-Juan Mario Villa Irene Benito-Cuesta Lara Ordónez-Gutiérrez Francisco Wandosell Centro de Biología Molecular“Severo Ochoa”(CSIC-UAM) Nicolas Cabrera 1Universidad Autónoma de MadridMadridSpain Fisiología Animal Departamento de BiologíaFacultad de CienciasUniversidad Autónoma de MadridMadridSpain department of Clinical Neuroscience CMM Karolinska Universitetssjukhuset SolnaStockholmSweden Departamento de Bioquímica y Biología Molecular Universidad Complutense de MadridMadridSpain Centro de Investigación biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED) MadridSpain

Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and *** cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino *** process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein *** of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).

关键词： homeostasis system hereafter

Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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Neural Regeneration Research 2025年第8期20卷 2395-2407页

作者： María Norte-Muñoz María Portela-Lomba Paloma Sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro Gallego-Ortega Mar Pérez JoséMCabrera-Maqueda Javier Sierra Manuel Vidal-Sanz María Teresa Moreno-Flores Marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of Neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

Trimetazidine:Is it a promising drug for use in steatotic grafts?

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World Journal of Gastroenterology 2006年第6期12卷 908-914页

作者： IsmailBenMosbah AraníCasillas-Ramírez CarmeXaus AnnaSerafín JoanRoselló-Catafau CarmenPeralta department of Experimental Pathology Instituto de Investigaciones biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas Instituto de Investigaciones Biomédicas de Barcelona August Pii SunyerBarcelonaSpain

AIM： Chronic organ-donor shortage has led to the acceptance of steatotic livers for transplantation, despite the higher risk of graft dysfunction or nonfunction associated with the ischemic preservation period of these organs. The present study evaluates the effects of trimetazidine （TMZ） on an isolated perfused liver model. METHODS： Steatotic and non-steatotic livers were preserved for 24 h in the University of Wisconsin （UW） solution with or without TMZ. Hepatic injury and function （transaminases, bile production and sulfobromophthalein （BSP） clearance） and factors potentially involved in the susceptibility of steatotic livers to ischemia-reperfusion （I/R） injury, including oxidative stress, mitochondrial damage, microcirculatory diseases, and ATP depletion were evaluated. RESULTS： Steatotic livers preserved in UW solution showed higher transaminase levels, lower bile production and BSP clearance compared with non-steatotic livers. Alterations in perfusion flow rate and vascular resistance, mitochondrial damage, and reduced ATP content were more evident in steatotic livers. TMZ addition to UW solution reduced hepatic injury and ameliorated hepatic functionality in both types of the liver and protected against the mechanisms potentially responsible for the poor tolerance of steatotic livers to I/R. CONCLUSION： TMZ may constitute a useful approach in fatty liver surgery, limiting the inherent risk of steatotic liver failure following transplantation.

关键词： Steatotic liver Ischemia-reperfusion UW preservation solution

Polyethylene glycol 35 ameliorates pancreatic inflammatory response in cerulein-induced acute pancreatitis in rats

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World Journal of Gastroenterology 2020年第39期26卷 5970-5982页

作者： Ana Ferrero-Andrés Arnau Panisello-Roselló Joan Roselló-Catafau Emma Folch-Puy Experimental Pathology department Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones científicasBarcelona 08036CataloniaSpain Experimental Pathology department Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones científicasCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasInstitut d'Investigacions Biomèdiques August Pi i SunyerBarcelona 08036CataloniaSpain

BACKGROUND Acute pancreatitis(AP)is a sudden inflammatory process of the pancreas that may also involve surrounding tissues and/or remote *** and parenchymal cell death are common pathological features of this condition and determinants of disease *** glycols(PEGs)are nonimmunogenic,non-toxic water-soluble polymers widely used in biological,chemical,clinical and pharmaceutical *** To evaluate the protective effect of a 35-kDa molecular weight PEG(PEG35)on the pancreatic damage associated to cerulein-induced acute pancreatitis in vivo and in *** Wistar rats were assigned at random to a control group,a cerulein–induced AP group and a PEG35 treatment *** was induced by five hourly intraperitoneal injections of cerulein(50μg/kg/bw),while the control animals received saline ***35 was administered intraperitoneally 10 minutes before each cerulein injection in a dose of 10 mg/*** AP induction,samples of pancreatic tissue and blood were collected for ***42J pancreatic acinar cells were treated with increasing concentrations of PEG35 prior to exposure with tumor necrosis factorα(TNFα),staurosporine or *** severity of AP was determined on the basis of plasma levels of lipase,lactate dehydrogenase activity,pancreatic edema and histological *** evaluate the extent of the inflammatory response,the gene expression of inflammation-associated markers was determined in the pancreas and in AR42J-treated ***-induced cell death was also measured in models of in vivo and in vitro pancreatic *** Administration of PEG35 significantly improved pancreatic damage through reduction on lipase levels and tissue edema in cerulein-induced AP *** increased associated inflammatory response caused by cerulein administration was attenuated by a decrease in the gene expression of inflammation-related cytokines and inducible nitric oxide synthase enzyme in the *** contr

关键词： Acute pancreatitis Inflammation Polyethylene glycols Cytokines AR42J cells Cell death

Real time in-vivo miniature endoscopic surveillance system for imaging of nasopharynx

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2020年第1期6卷 4-9页

作者： Chwee Ming Lim Gangodu Nagaraja Rao Hongliang Ren Departm ent of Otolaryngology-Head and Neck Surgery Notional University Health SystemSingapore department of Otolaryngology Yong Loo Lin School of MedicineNational University of Singapore department of Otorhinolaryngology-Head and Neck Sursery Singapore General HospitalSingapore department of biom edical engineering National University of SingaporeSingapore

Objective:To test the feasibility of a real time miniature endoscope system for imaging the *** design:Preclinical assessment on skull model and ***:A 3.5 mm miniature endoscope was fabricated and the image capture of the nasopharynx was investigated by positioning the miniature camera system at the posterior free edge of the vomer *** real time transmission of the images and quality was tested in a skull ***,three nasopharyngeal surveillance miniature camera system were developed for possible clinical *** prototypes were anchored on the nasal septum and the last prototype was designed using a patient self-administered surveillance *** prototypes were tested for feasibility on both the phantom skull and cadaveric *** assessments were also performed to assess risk,safety and validate the reliability of the material utilized for clinical ***:Insertion and anchorage of the miniature surveillance endoscope prototypes at the vomer bone were feasible on all 3 *** quality of captured images was reasonable and miniaturized camera was responsive to pan at different angles so that the entire nasopharynx may be *** assessments on the material such as pull out test,breaking force analysis,finite element test and tensile strength test were reliable for possible clinical ***:Real time miniature endoscope system for surveillance of nasopharyngeal cancer is *** translation of this technology was possible but requires further refinement in enhancing image quality and wireless transmission of the captured images.

关键词： Nasopharyngeal carcinoma In vivo miniature endoscope Imaging

Effectiveness of infliximab after adalimumab failure in Crohn's disease

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World Journal of Gastroenterology 2012年第37期18卷 5219-5224页

作者： María Chaparro Montserrat Andreu Manuel Barreiro-de Acosta Esther García-Planella Elena Ricart Eugeni Domènech María Esteve Olga Merino Pilar Nos Mireia Pealva Javier P Gisbert department of Gastroenterology Hospital Universitario de La PrincesaInstituto de Investigación Princesa(IP)and Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas(CIBEREHD)28006 MadridSpain Americio 17 portal E 2℃28021 Madrid department of Gastroenterology Hospital del Mar department of Gastroenterology Hospital Clínico Universitario de Santiago department of Gastroenterology Hospital Santa Creui Sant Pau department of Gastroenterology Hospital ClínicBarcelonaand Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas department of Gastroenterology Hospital Germans Triasi Pujol and Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas(CIBEREHD) department of Gastroenterology Hospital Mutua de Terrassa department of Gastroenterology Hospital de Cruces department of Gastroenterology Hospital Universitario La Fe and Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas(CIBEREHD) department of Gastroenterology Hospital de Bellvitge department of Gastroenterology Hospital Universitario de La PrincesaInstituto de Investigación Princesa(IP)and Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas(CIBEREHD)

AIM:To evaluate the effectiveness of infliximab as a second-line therapy in Crohn's disease patients after adalimumab failure. METHODS:A historical cohort study in a community-based gastroenterology practice evaluated Crohn's disease patients treated with infliximab (induction plus maintenance) after adalimumab failure. Patients were identified using a large Spanish database (ENEIDA). RESULTS:We included 15 Crohn's disease patients who received infliximab after adalimumab failure. Five patients discontinued adalimumab due to loss of response, 3 due to adverse events and 7 due to partial response. After infliximab therapy was started, all patients who had interrupted adalimumab due to loss of efficacy regained response. All patients who discontinued adalimumab due to adverse events responded to infliximab and maintained this response; one of these patients had an uneventful course on infliximab, but 2 developed adverse events. None of the 7 patients who interrupted adalimumab due to partial response reached remission with infliximab. CONCLUSION:Switching from adalimumab to infliximab may be useful in patients who develop adverse effects or loss of response, however, the benefit of infliximab in primary nonresponders was not established.

关键词： Adalimumab Biologics Crohn's disease In-fliximab Switch

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

Endoscopic response to tumor necrosis factor inhibitors predicts long term benefits in Crohn's disease

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World Journal of Gastroenterology 2019年第14期25卷 1764-1774页

作者： Ignacio Alfaro Maria Carme Masamunt Nuria Planell Alicia López-García Jesús Castro Marta Gallego Rebeca Barastegui Angel Giner Alejandro Vara Azucena Salas Elena Ricart Julián Panés Ingrid Ordás Gastroenterology department Hospital Clínic de Barcelona Institut d'Investigacions biomèdiques August Pi i Sunyer (IDIBAPS) University of Barcelona

BACKGROUND Identifying predictors of therapeutic response is the cornerstone of personalized *** To identify predictors of long-term mucosal healing(MH) in patients with Crohn's disease(CD) treated with tumor necrosis factor α(TNF-α) *** Prospective single center study. Consecutive patients with clinically active CD requiring treatment with a TNF-α inhibitor were included. A baseline segmental CD Endoscopic Index of Severity(CDEIS) ≥ 10 in at least one segment or the presence of ulcerations were required for inclusion. Clinical, biological and endoscopic data were obtained at baseline, weeks 14 and 46. Endoscopic response(ER) was defined as a decrease ≥ 50% from baseline CDEIS and MH as partial CDEIS ≤ 5 in all *** Of 62 patients were included. At baseline, median CD Activity Index and CDEIS were 201 and 6.7, respectively with a significant reduction after one year of treatment(53 and 3.0 respectively, P biomarkers did not predict MH. A decrease from baseline CDEIS at week 14 of at least 80% was the best predictor of MH at week 46(59% sensitivity and 91% specificity; area under the curve =0.778).CONCLUSION Clinical and biomarker data are not useful predictors of response to TNF-αinhibitors in CD, whereas ER to induction therapy, defined as 80% reduction in global CDEIS, is a robust predictor of long-term MH. Achievement of this endoscopic endpoint may be considered as a therapeutic target for anti-TNF-αtherapy.

关键词： Crohn’s disease Endoscopy Mucosal healing Crohn’s Disease Endoscopic Index of Severity Tumor necrosis factor

Phosphate-activated glutaminase activity is enhanced in brain, intestine and kidneys of rats following portacaval anastomosis

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World Journal of Gastroenterology 2006年第15期12卷 2406-2411页

作者： Manuel Romero-Gómez María Jover Daniel Díaz-Gómez Laura Collantes de Terán Regina Rodrigo Inés Camacho Miriam Echevarría Vicente Felipo Juan D Bautista Unit for the Clinical Management of Digestive Diseases Hospital Universitario de Valme SevillaSpain department of Biochemistry Bromatology and Toxicology Faculty of PharmacyUniversity of SevilleSpain Laboratory of Neurobiology Fundación Valenciana de Investigaciones biomédicas ValenciaSpain Biochemistry Unit Hospital Universitario de Valme SevillaSpain Instituto de Investigaciones biomédicas Departament of Physiology University of SevilleSpain Laboratory of Neurobiology Fundación Valenciana de Investigaciones biomédicas ValenciaSpain

AIM： To assess whether portacaval anastomosis （PCA） in rats affects the protein expression and/or activity of glutaminase in kidneys, intestines and in three brain areas of cortex, basal ganglia and cerebellum and to explain the neurological alterations found in hepatic encephalopathy （HE）. METHODS： Sixteen male Wistar rats weighing 250-350 g were grouped into sham-operation control （n=8） or portacaval shunt （n = 8）. Twenty-eight days after the procedure, the animals were sacrificed. The duodenum, kidney and brain were removed, homogenised and mitochondria were isolated. Ammonia was measured in brain and blood. Phosphate-activated glutaminase （PAG） activity was determined by measuring ammonia production following incubation for one hour at 37 ℃ with O-phthalaldehyde （OPA） and specific activity expressed in units per gram of protein （pkat/g of protein）. Protein expression was measured by immunoblotting. RESULTS： Duodenal and kidney PAG activities together with protein content were significantly higher in PCA group than in control or sham-operated rats （duodenum PAG activity was 976.95±268.87μkat/g of protein in PCA rats vs 429.19±126.92.μkat/g of protein in shamoperated rats; kidneys PAG activity was 1259.18±228.79 μkat/g protein in PCA rats vs 669.67±400.8 μkat/g of protein in controls, P〈0.05; duodenal protein content： 173% in PCA vs sham-operated rats; in kidneys the content of protein was 152% in PCA vs sham-operated rats）. PAG activity and protein expression in PCA rats were higher in cortex and basal ganglia than those in shamoperated rats （cortex： 6646.6 ±1870.4 μkat/g of protein vs 3573.8± 2037.4 μkat/g of protein in control rats, P〈 0.01; basal ganglia, PAG activity was 3657.3± 1469.6 μkat/g of protein in PCA rats vs 2271.2±384 μkat/g of protein in sham operated rats, P〈0.05; In the cerebellum, the PAG activity was 2471.6±701.4 μkat/g of protein vs 1452.9 ±567.8 μkat/g of protein in the PCA and sham rats, respectively, P〈0.05; content of protein： cerebral co

关键词： Hyperammonaemia Minimal hepaticencephalopathy Glutamine Protein content Shamoperated