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Vicious cycle of lipid peroxidation and iron accumulation in neurodegeneration

Neural Regeneration Research 2023年第6期18卷 1196-1202页

作者： instituto de salud carlos iii Irene Villalón-García Suleva Povea-Cabello MónicaÁlvarez-Córdoba Marta Talaverón-Rey Juan MSuárez-Rivero Alejandra Suárez-Carrillo Manuel Munuera-Cabeza Diana Reche-López Paula Cilleros-Holgado Rocío Piñero-Pérez JoséA.Sánchez-Alcázar Centro Andaluz de Biología del desarrollo(CABD-CSIC-Universidad Pablo de Olavide de Sevilla) and Centro de Investigación Biomédica en Red:Enfermedades RarasInstituto de Salud Carlos IIISevillaSpain

Lipid peroxidation and iron accumulation are closely associated with neurodegenerative diseases,such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,or neurodegeneration with brain iron accumulation *** dysfunction,lipofuscin accumulation,autophagy disruption,and ferroptosis have been implicated as the critical pathomechanisms of lipid peroxidation and iron accumulation in these ***,the connection between lipid peroxidation and iron accumulation and the initial cause or consequence in neurodegeneration processes is *** this review,we have compiled the known mechanisms by which lipid peroxidation triggers iron accumulation and lipofuscin formation,and the effect of iron overload on lipid peroxidation and cellular *** vicious cycle established between both pathological alterations may lead to the development of ***,the investigation of these mechanisms is essential for exploring therapeutic strategies to restrict *** addition,we discuss the interplay between lipid peroxidation and iron accumulation in neurodegeneration,particularly in PLA2G6-associated neurodegeneration,a rare neurodegenerative disease with autosomal recessive inheritance,which belongs to the group of neurodegeneration with brain iron accumulation disorders.

关键词： 4-hidroxynonenal ferroptosis iron lipid peroxidation lipofuscin neurodegeneration neurodegeneration with brain iron accumulation oxidative stress PLA2G6-associated neurodegeneration

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Neural Regeneration Research 2021年第1期16卷 123-124页

作者： carlos Bueno Salvador Martínez instituto de Neurociencias de Alicante(UMH-CSIC) San JuanAlicanteSpain

Human neurological disorders and spinal cord injuries are caused by a loss of neurons and glial cells in the brain or spinal *** proof-ofprinciple of cell therapy is that replacing damaged cells with new healthy ones will restore the lost *** and manipulating autologous neural stem cells(NSCs)could provide an ideal source of cells for use in cell replacement and the transfer of genes to a diseased central nervous *** are immature cells present,not only during embryonic development,but also in the adult brain of all mammalian species,including *** presence of NSCs in the adult mammalian brain has been described in two neurogenic niches,the ventricular-subventricular zone(V-SVZ)of the anterolateral ventricle wall and the subgranular zone of the hippocampal dentate ***,NSCs are defined as self-renewing multipotent cells that can generate neurons,astrocytes and *** major barrier to isolating adult NSCs in humans is the inaccessibility of living *** this reason,an enormous effort has been made to derive neurons from human adult stem cells isolated from various tissue sources.

关键词： injuries ventricular adult

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Preferences for participation in shared decision making of psychiatric outpatients with affective disorders

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Open Journal of Psychiatry 2014年第1期4卷 16-23页

作者： carlos de las Cuevas Wenceslao Penate department of Psychiatry University of La LagunaSan Cristobal de La LagunaSpain REDISSEC(Red de Investigacion en Servicios de salud y Enfermedades Cronicas) Santa Cruz de TenerifeSpain department of Personality Assessment and Psychological TreatmentsUniversity of La LagunaSan Cristobal de La LagunaSpain

Objective: To assess preferences for participation in shared decision making in a representative sample of psychiatric outpatients with affective disorders and to understand how clinical and socio-demographic variables influence patients’ preferences for participation. Method: A cross-sectional survey of 172 consecutive psychiatric outpatients with affective disorders attending at Community Mental Health Care setting was carried out. Patients expressed preferences on each of 3 aspects of decision making (seeking information, discussing options, making the final decision). The “CGI Severity and Improvement Scales” and the “Beck depression Inventory” scale were used for severity assessment. Additionally the “Drug Attitude Inventory”, the “Beliefs about Medicine Questionnaire” and the “Leeds Attitude toward Concordance Scale” were applied to all participants. Effects of variables considered on preferences were assessed using proportional odds regression models. Results: We registered a high response rate of 85%. Nearly all patients (91%) preferred to leave final decisions to their treating psychiatrists and 87% preferred to rely on psychiatrists for medical knowledge rather than seeking their own information. In contrast, 81% of patients preferred to be offered options and to be asked their opinion by their doctors. Gender, age, educational level, number of psychotropics used and belief about psychiatric medication overuse were significant predictors in decision making dimensions considered. Conclusion: Shared decision making approach of patients with affective disorder must take into consideration a more doctor-directed approach preferred by the patients in which the desire to be offered options is not automatically linked with the willingness of taking decisions or getting more knowledge.

关键词： Patients Preferences Shared decision Making Psychiatric Outpatients Affective Disorders

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Gastrotomy closure with a new tissue anchoring device:A porcine survival study

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World Journal of Gastroenterology 2011年第13期17卷 1732-1738页

作者： carlos Guarner-Argente Henry Córdova Graciela Martínez-Pallí Ricard Navarro-Ripoll Antonio Rodríguez-d’Jesús Cristina Rodríguez de Miguel Mireia Beltrán Gloria Fernández-Esparrach Endoscopy Unit Hospital Clínic CIBERehd Barcelona 08026 Spain Anesthesiology department Hospital Clínic CIBERehd Barcelona 08026 Spain

AIM: To evaluate the feasibility, reproducibility and efficacy of a new tissue anchoring device in a porcine survival model. METHODS: Gastrotomies were performed using a needle-knife and balloon dilator in 10 female Yorkshire pigs weighing 30-35 kg. Gastric closure was attempted using a new tissue anchoring device. The tightness of the closure was confirmed by means of air insufflation and the ability to maintain gastric distension with stability in peritoneal pressure measured with a Veress needle. All animals were monitored daily for signs of peritonitis and sepsis over 14 d. During necropsy, the peritoneal cavity and the gastric access site were ***: Transgastric access, closure and 14 d survival was achieved in all pigs. The mean closure time was 18.1 ± 19.2 min and a mean of 2.1 ± 1 devices were used. Supplementary clips were necessary in 2 cases. The closure time was progressively reduced (24.8 ± 13.9 min in the first 5 pigs vs 11.4 ± 5.9 min in the last 5, P = NS). At necropsy, the gastric access site was correctly closed in all cases with all brace-bars present. One device was misplaced in the mesocolon. Minimal adhesions were observed in 3 pigs and signs of mild peritonitis and adhesions in one. CONCLUSIONS: The use of this new tissue anchoring device in porcine stomachs is feasible, reproducible and effective and requires a short learning curve.

关键词： Gastrotomy Closure Suture Survival Porcine model Notes

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New insights into Wnt signaling alterations in amyotrophic lateral sclerosis: a potential therapeutic target?

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Neural Regeneration Research 2020年第9期15卷 1580-1589页

作者： carlos González-Fernández Pau González Francisco Javier Rodríguez Laboratory of Molecular Neurology Hospital Nacional de Parapléjicos (HNP)

Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder characterized by upper and lower motor neuron degeneration, which leads to progressive paralysis of skeletal muscles and, ultimately, respiratory failure between 2–5 years after symptom onset. Unfortunately, currently accepted treatments for amyotrophic lateral sclerosis are extremely scarce and only provide modest benefit. As a consequence, a great effort is being done by the scientific community in order to achieve a better understanding of the different molecular and cellular processes that influence the progression and/or outcome of this neuropathological condition and, therefore, unravel new potential targets for therapeutic intervention. Interestingly, a growing number of experimental evidences have recently shown that, besides its well-known physiological roles in the developing and adult central nervous system, the Wnt family of proteins is involved in different neuropathologica conditions, including amyotrophic lateral sclerosis. These proteins are able to modulate, at least, three different signaling pathways, usually known as canonical(β-catenin dependent) and non-canonical(β-catenin independent) signaling pathways. In the present review, we aim to provide a general overview of the current knowledge that supports the relationship between the Wnt family of proteins and its associated signaling pathways and amyotrophic lateral sclerosis pathology, as well as their possible mechanisms of action. Altogether, the currently available knowledge suggests that Wnt signaling modulation might be a promising therapeutic approach to ameliorate the histopathological and functional deficits associated to amyotrophic lateral sclerosis, and thus improve the progression and outcome of this neuropathology.

关键词： ALS astrocytes Frizzled human microglia motor neuron neurodegeneration neuroinflammation spinal cord Wnt

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Animal models of portal hypertension

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World Journal of Gastroenterology 2006年第41期12卷 6577-6584页

作者： Juan G Abraldes Marcos Pasarín Juan carlos García-Pagán Hepatic Hemodynamic Laboratory Liver UnitICMDiMHospital ClinicIDIBAPSUniversity of BarcelonaSpain

Animal models have allowed detailed study of hemodynamic alterations typical of portal hypertension and the molecular mechanisms involved in abnormalities in splanchnic and systemic circulation associated with this syndrome. Models of prehepatic portal hypertension can be used to study alterations in the splanchnic circulation and the pathophysiology of the hyperdynamic circulation. Models of cirrhosis allow study of the alterations in intrahepatic microcirculation that lead to increased resistance to portal flow. This review summarizes the currently available literature on animal models of portal hypertension and analyzes their relative utility. The criteria for choosing a particular model, depending on the specific objectives of the study, are also discussed.

关键词： Cirrhosis Nitric Oxide Portal vein

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Secondary male hypogonadism： a prevalent but overlooked comorbidity of obesity

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Asian Journal of Andrology 2018年第6期20卷 531-538页

作者： Maria Molina-Vega Araceli Mufioz-Garach Miguel Damas-Fuentes JosO carlos Fernfindez-Garcia Francisco J inahones department of Endocrinology and Nutrition Virgen de la Victoria Universitary HospitalMalaga 29010Spain Institute of Biomedical Research in Malaga（IBIMA） Virgen de la Victoria Universitary HospitalMalaga 29010Spain CIBER Pathophysiology of Obesity and Nutrition（CB06/003） Institute of Health Carlos III（ISClII）Madrid 28029Spain.

Male hypogonadism associated with obesity is a very prevalent condition and is increasing in parallel with the epidemic prevalence of obesity. Low testosterone levels promote higher fat mass with reduced lean mass. Male hypogonadism is related to an increase in associated cardiometabolic complications, such as hypertension, type 2 diabetes mellitus, the metabolic syndrome, and cardiovascular disease. Its influence as a comorbidity of obesity is becoming more evident and should be evaluated and treated in at-risk patients. Mechanisms involved in this relationship include body composition changes, the presence of adipokines, insulin resistance, and other factors, some of which are still unknown. Weight loss and treatment to replace testosterone levels improve the metabolic profile and quality of life in patients with obesity and hypogonadism; these beneficial effects depend on treatment modality and duration of therapy. The use of testosterone replacement therapy may be indicated, as it has not been shown to increase cardiovascular risk, and retrospective studies suggest a reduction in events in men with metabolic syndrome and type 2 diabetes.

关键词： adipose tissue male hypogonadism obesity testosterone

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Mathematical modeling for estimating influenza vaccine efficacy:A case study of the Valencian Community,Spain.

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Infectious Disease Modelling 2024年第3期9卷 744-762页

作者： carlos Andreu-Vilarroig Rafael J.Villanueva Gilberto González-Parra instituto de Matemática Multidisciplinar Universitat Politècnica de ValènciaValenciaSpain department of Mathematics New Mexico TechSocorroNMUSA

Vaccine efficacy and its quantification is a crucial concept for the proper design of public health vaccination *** this work we proposed a mathematical model to estimate the efficacy of the influenza vaccine in a real-word *** particular,our model is a SEIR-type epidemiological model,which distinguishes vaccinated and unvaccinated ***,its dynamics is governed by a nonlinear system of ordinary differential equations,where the non-linearity arises from the effective contacts between susceptible and infected *** key aspects of this study is that we use a vaccine distribution over time that is based on real data specific to the elderly people in the Valencian Community and the calibration process takes into account that over one influenza season a specific proportion of the population becomes infected with *** consider the effectiveness of the vaccine,the model incorporates a parameter,the vaccine attenuation factor,which is related with the vaccine efficacy against the influenza *** this framework,in order to calibrate the model parameters and to obtain an influenza vaccine efficacy estimation,we considered the 2016–2017 influenza season in the Valencian Community,Spain,using the influenza reported cases of vaccinated and *** order to ensure the model identifiability,we choose to deterministically calibrate the parameters for different scenarios and we find the one with the minimum error in order to determine the vaccine *** calibration results suggest that the influenza vaccine developed for 2016–2017 influenza season has an efficacy of approximately 76.7%,and that the risk of becoming infected is five times higher for an unvaccinated individual in comparison with a vaccinated *** estimation partially agrees with some previous studies related to the influenza *** study presents a new integrated mathematical approach to study the influenza vaccine efficacy and gives f

关键词： Mathematical modeling Epidemiology SEIR Vaccine efficacy Influenza Valencian community

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Attitudes towards prescribing psychiatric medicines: Do the views of psychology and medical students differ?

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Open Journal of Psychiatry 2011年第3期1卷 115-121页

作者： carlos de las Cuevas Wenceslao Penate Lilisbeth Perestelo Amado Rivero Jeanette Perez Marien Gonzalez Alia Perez-Wehbe department of Psychiatry University of La LagunaSan Cristobal de La LagunaCanary IslandsSpain CIBER en Epidemiologia y salud Publica(CIBERESP) Santa Cruz de TenerifeSpain department of Personality Assessment and Psychological TreatmentsUniversity of La LagunaCanary IslandsSpain Evaluation Unit of the Canary Islands Health Service(SESCS) Santa Cruz de TenerifeSpain Fundacion Canaria de Investigacion y salud(FUNCIS) Santa Cruz de TenerifeSpain

Concordance has been suggested as a process of the consultation in which prescribing process is based on partnership. The aim of this cross-sectional study was to compare attitudes towards psychiatric medication and concordance in medicine taking between medical and psychology students, as they represent future members of mental health teams. Two hundred and sixteen medical students and 222 psychology students completed the Leeds Attitudes toward Concordance scale (LATCon) and the Beliefs about Medication Questionnaire (BMQ) (both adapted for psychiatric medication). Psychology students saw psychiatric medicines as more harmful and were also most likely to believe that psychiatrists overprescribed these medicines. They also scored higher than medical students on attitudes towards concordance, although this difference remained at the limit of statistical significance.

关键词： Leeds Attitude toward Concordance Scale (LATCon) Beliefs about Medication Questionnaire (BMQ) Medical Students Psychology Students

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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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