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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 disorders.Mitochondrial dysfunction,lipofuscin accumulation,autophagy disruption,and ferroptosis have been implicated as the critical pathomechanisms of lipid peroxidation and iron accumulation in these disorders.Currently,the connection between lipid peroxidation and iron accumulation and the initial cause or consequence in neurodegeneration processes is unclear.In 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 function.The vicious cycle established between both pathological alterations may lead to the development of neurodegeneration.Therefore,the investigation of these mechanisms is essential for exploring therapeutic strategies to restrict neurodegeneration.In 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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A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities

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Military Medical Research 2024年第2期11卷 228-267页

作者： Miguel A.Ortega Oscar Fraile-Martinez Cielo García-Montero Sergio Haro Miguel Ángel Álvarez-Mon Diego de Leon-Oliva Ana M.Gomez-Lahoz Jorge Monserrat Mar Atienza-Pérez David Díaz Elisa Lopez-Dolado Melchor Álvarez-Mon department of Medicine and Medical Specialities University of Alcala28801 Alcala de HenaresSpain Ramón y Cajal Institute of Sanitary Research(IRYCIS) 28034 MadridSpain department of Psychiatry and Mental Health Hospital Universitario Infanta Leonor28031 MadridSpain Service of Rehabilitation National Hospital for Paraplegic PatientsCarr.de la PeraledaS/N45004 ToledoSpain Immune System Diseases‑Rheumatology Service and Internal Medicine University Hospital Príncipe de Asturias(CIBEREHD)28806 Alcala de HenaresSpain

Spinal cord injury(SCI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI,explaining the progression and detrimental consequences related to this condition.Psychoneuroimmunoendocrinology(PNIE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a whole.The initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and well-being.In the present review,we will explore the most important local and systemic consequences of SCI from a PNIE perspective,defining the changes occurring in each system and how all these mechanisms are interconnected.Finally,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.

关键词： Spinal cord injury(SCI) Psychoneuroimmunoendocrinology(PNIE) Secondary injury Immunoinflammatory dysfunction Gut microbiota Translational opportunities

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Dietary(poly)phenol intake is associated with cardiometabolic health parameters in adolescents

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Food Science and Human Wellness 2024年

作者： Emily P.Laveriano-Santos Sara Castro-Barquero Camila Arancibia-Riveros Ana María Ruiz-León Rosa Casas Ramón Estruch Patricia Bodega Mercedes de Miguel Amaya de Cos-Gandoy Jesús Martínez-Gómez Gloria Santos-Beneit Juan M.Fernández-Alvira Rodrigo Fernández-Jiménez Rosa M.Lamuela-Raventós Anna Tresserra-Rimbau The Zena and Michael A.Wiener Cardiovascular Institute Icahn School of Medicine at Mount Sinai department de Nutrició Ciències de l'Alimentació I Gastronomia XIA Facultat de Farmàcia i Ciències de l'alimentació Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB) Universitat de Barcelona department of Internal Medicine Hospital Clínic Institutd'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) University of Barcelona Consorcio CIBER M.P.Fisiopatología de la Obesidad y Nutrición (CIBERObn) instituto de salud carlos iii (ISCiii) Mediterranean Diet Foundation 5. Foundation for Science Health and Education (SHE) 6. Centro Nacional de Investigaciones Cardiovasculares (CNIC) CIBER de Enfermedades Cardiovasculares (CIBERCV) 9. Hospital Universitario Clínico San carlos

Background: The protective role of (poly)phenols against metabolic disorders has been extensively studied in adults but not in adolescents.Objective: To assess associations of dietary (poly)phenols and their subclasses with cardiometabolic health parameters in adolescents. Methods: A cross-sectional study was conducted in 944 individuals aged 11 to 14 years enrolled in the SI! Program for Secondary Schools trial (NCT03504059). (Poly)phenol intake was assessed using semi-quantitative food frequency questionnaires and the Phenol-Explorer database. The measured cardiometabolic parameters were waist circumference (WC) age-sex z-score， blood pressure (BP) age-sex z-score， blood glucose (BG)， triglycerides (TG)， and high-density lipoprotein cholesterol (HDL-c). Multilevel mixed-effect linear regression models were applied to examine the association between (poly)phenol quintiles and cardiometabolic health parameters.Results: Compared to the lowest quintile， adolescents in the highest quintile of total (poly)phenol intake had lower WC z-scores (β=-0.09， 95%CI=-0.09;-0.08， P-for trend=0.002)， mean arterial pressure z-scores (β =-0.11， 95%CI=-0.12;-0.09， P-for trend=0.206)， and HDL-c (β=-1.52， 95%CI=-2.90;-0.14， P-for trend=0.108)， after multivariable adjustment. The WC z-scores (β=-0.11， 95%CI=-0.19;-0.03， P-for trend=0.013) and HDL-c (β=-2.16， 95%CI=-3.78;-0.53， P-for trend=0.046) were lower in the highest quintile of flavonoid intake compared to the lowest quintile. The highest quintile of phenolic acid intake was associated with a lower WC z-score (β=-0.14， 95%CI=-0.26;-0.02， P-for trend=0.011) and TG levels (β=-8.83， 95%CI=-12.37;-5.30， P-for trend <0.001)， and the highest quintile of stilbene intake with lower BG (β=-1.83， 95%CI= -3.103;-0.64， P-for trend <0.001) and TG (β=-3.22， 95%CI= -4.95;-1.49， P-for trend=0.034)， and with higher HDL-c (β=2.328， 95%CI= 1.40;3.17， P-for trend=0.466) compared to the lowest quintile. Conclusion: A higher intake of (poly)phenols， especially flavonoids， phenolic acids， and stilbenes

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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 cord.The proof-ofprinciple of cell therapy is that replacing damaged cells with new healthy ones will restore the lost function.Isolating 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 system.NSCs are immature cells present,not only during embryonic development,but also in the adult brain of all mammalian species,including humans.The 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 gyrus.Typically,NSCs are defined as self-renewing multipotent cells that can generate neurons,astrocytes and oligodendrocytes.The major barrier to isolating adult NSCs in humans is the inaccessibility of living tissue.For 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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Feature importance:Opening a soil-transmitted helminth machine learning model via SHAP

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Infectious Disease Modelling 2022年第1期7卷 262-276页

作者： carlos Matias Scavuzzo Juan Manuel Scavuzzo Micaela Natalia Campero Melaku Anegagrie Aranzazu Amor Aramendia Agustín Benito Victoria Periago instituto de Altos Estudios Espaciales Mario Gulich Univesidad Nacional de Cordoba-Comision Nacional de Actividades EspacialesArgentina Fundacion Mundo Sano MadridSpain National Centre for Tropical Medicine Institute of Health Carlos IIIMadridSpain Fundacion Mundo Sano Buenos AiresArgentina Consejo Nacional de Investigaciones Científicasy Tecnicas(CONICET) Buenos AiresArgentina

In the field of landscape epidemiology,the contribution of machine learning(ML)to modeling of epidemiological risk scenarios presents itself as a good alternative.This study aims to break with the”black box”paradigm that underlies the application of automatic learning techniques by using SHAP to determine the contribution of each variable in ML models applied to geospatial health,using the prevalence of hookworms,intestinal parasites,in Ethiopia,where they are widely distributed;the country bears the third-highest burden of hookworm in Sub-Saharan Africa.XGBoost software was used,a very popular ML model,to fit and analyze the data.The Python SHAP library was used to understand the importance in the trained model,of the variables for predictions.The description of the contribution of these variables on a particular prediction was obtained,using different types of plot methods.The results show that the ML models are superior to the classical statistical models;not only demonstrating similar results but also explaining,by using the SHAP package,the influence and interactions between the variables in the generated models.This analysis provides information to help understand the epidemiological problem presented and provides a tool for similar studies.

关键词： Shap Shapley Machine learning Remote sensing Hookworm Ethiopia

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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 examined.RESULTS: 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：锚固装置组织封闭猪闭合时间设备使用胃扩张锚定装置

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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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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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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 Munoz-Garach Miguel Damas-Fuentes Jose carlos Fernfindez-Garcia Francisco J inahones department of Endocrinology and Nutrition Virgen de la Victoria Universitary Hospital Malaga 29010 Spain Institute of Biomedical Research in Malaga (IBIMA) Virgen de la Victoria Universitary Hospital Malaga 29010 Spain CIBER Pathophysiology of Obesity and Nutrition (CB06/003) Institute of Health Carlos Ⅲ (ISCⅢ) Madrid 28029 Spain.

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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No Effects of Meteorological Factors on the SARS-CoV-2 Infection Fatality Rate

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Biomedical and Environmental Sciences 2021年第11期34卷 871-880页

作者： SOLANES Aleix LAREDO carlos GUASP Mar FULLANA Miquel Angel FORTEA Lydia GARCIA-OLIVE Ignasi SOLMI Marco SHIN Jae II URRA Xabier RADUA Joaquim Institut d'lnvestigacions Biomediques August Pi i Sunyer(IDIBAPS) BarcelonaSpain department of Psychiatry and Forensic Medicine Autonomous University of BarcelonaBarcelonaSpain Neurosciences Unit Hospital ClinicBarcelonaSpain Adult Psychiatry and Psychology department Institute of NeurosciencesHospital ClinicBarcelonaSpain Biomedical Network Research Centre on Mental Health(CIBERSAM) Instituto de Salud Carlos IIIMadridSpain department of Medicine University of BarcelonaBarcelonaSpain department of Medicine Autonomous University of BarcelonaBarcelonaSpain Pneumology department Hospital Germans Trias i PujolBadalonaSpain Neurosciences department University of PaduaPaduaItaly Padua Neuroscience Center PaduaItaly department of Psychosis Studies Institute of PsychiatryPsychology and NeuroscienceKing's College LondonLondonUK department of Pediatrics College of MedicineYonsei UniversitySeoul 03722Korea Centre for Psychiatric Research and Education Department of Clinical NeuroscienceKarolinska InstitutetStockholmSweden

Objective Previous studies have shown that meteorological factors may increase COVID-19 mortality,likely due to the increased transmission of the virus.However,this could also be related to an increased infection fatality rate(IFR).We investigated the association between meteorological factors(temperature,humidity,solar irradiance,pressure,wind,precipitation,cloud coverage)and IFR across Spanish provinces(n=52)during the first wave of the pandemic(weeks 10–16 of 2020).Methods We estimated IFR as excess deaths(the gap between observed and expected deaths,considering COVID-19-unrelated deaths prevented by lockdown measures)divided by the number of infections(SARS-CoV-2 seropositive individuals plus excess deaths)and conducted Spearman correlations between meteorological factors and IFR across the provinces.Results We estimated 2,418,250 infections and 43,237 deaths.The IFR was 0.03%inder provinces’aging population.Conclusion The association between meteorological factors and adjusted COVID-19 IFR is unclear.Neglecting age differences or ignoring COVID-19-unrelated deaths may severely bias COVID-19 epidemiological analyses.

关键词： Climate COVID-19 Infection fatality rate SARS-CoV-2 Temperature Weather

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