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SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation

Signal Transduction and Targeted Therapy 2020年第1期5卷 2322-2331页

作者： Xavier Palomer MSilvia Román-Azcona Javier Pizarro-Delgado Ana Planavila Francesc villarroya Brenda valenzuela-Alcaraz Fátima Crispi Álvaro Sepúlveda-Martínez Irene Miguel-Escalada Jorge Ferrer JFrancisco Nistal Raquel García Mercy MDavidson Emma Barroso Manuel Vázquez-Carrera Department of Pharmacology Toxicology and Therapeutic ChemistryIBUB(Institut de Biomedicina de la Universitat de Barcelona)Research Institute-Pediatric Research InstituteHospital Sant Joan de Déuand CIBER de Diabetes y Enfermedades Metabólicas Asociadas(CIBERDEM)Faculty of Pharmacy and Food SciencesUniversity of BarcelonaBarcelonaSpain Department of Biochemistry and Molecular Biomedicine IBUB and CIBER Fisiopatología de la Obesidad y Nutrición(CIBEROBN)Faculty of BiologyUniversity of BarcelonaBarcelonaSpain aBCNatal-Barcelona Center for Maternal–Fetal and Neonatal Medicine(Hospital Clínic and Hospital Sant Joan de Deu) Institut d’Investigacions Biomèdiques August Pi i SunyerUniversitat de Barcelonaand Center for Biomedical Research on Rare Diseases(CIBER-ER)BarcelonaSpain Genomic Programming of Betacells Laboratory Institut d’Investigacions August Pi i Sunyer(IDIBAPS)and CIBERDEMBarcelonaSpain Section of Epigenomics and Disease Department of Medicineand National Institute for Health Research(NIHR)Imperial Biomedical Research CentreImperial College LondonLondonUK Servicio de Cirugía Cardiovascular Hospital Universitario Marqués de ValdecillaDepartamento de Ciencias Médicas y QuirúrgicasFacultad de MedicinaUniversidad de CantabriaInstituto de Investigación Marqués de Valdecilla(IDIVAL)Centro de Investigación Biomédica en Red Cardiovascular(CIBERCV)Instituto de Salud Carlos IIISantanderSpain Departamento de Fisiología y Farmacología Facultad de MedicinaUniversidad de CantabriaInstituto de Investigación Marqués de Valdecilla(IDIVAL)SantanderSpain Department of Radiation Oncology Columbia UniversityNew YorkNYUSA

Sirtuin 3(SIRT3)is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress.Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac disturbances.In this study,we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 cells.SIRT3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1.Consistent with this,SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-α.Notably,these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of AP-1.Finally,we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its promoter.These findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 pathway.Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy,heart failure,and diabetic cardiomyopathy,our results point to SIRT3 as a potential target for treating these diseases.

关键词： SIRT3 inflammation cardiac

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Association of objectively measured physical activity and sedentary time with health-related quality of life in women with fibromyalgia:The al-ándalus project

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Journal of Sport and Health Science 2019年第3期8卷 258-266页

作者： Blanca Gavilán-carrera víctor Segura-Jiménez Fernando Estévez-López Inmaculada C álvarez-Gallardo Alberto Soriano-Maldonado Milkana Borges-Cosic manuel Herrador-Colmenero Pedro Acosta-Manzano manuel Delgado-Fernández Department of Physical Education and Sport Faculty of Sport Sciences University of Granada Department of Physical Education Faculty of Education Sciences University of Cádiz Department of Psychology Faculty of Social and Behavioural Sciences Utrecht University Institute of Nursing and Health Research School of Health Sciences Ulster University Department of Education Faculty of Education Sciences University of Almería SPORT Research Group (CTS-1024) CERNEP Research Center University of Almería Teaching Centre La Inmaculada University of Granada

Purpose: To examine the association of physical activity(PA) intensity levels and sedentary time with health-related quality of life(HRQoL) in women with fibromyalgia and whether patients meeting the current PA guidelines present better HRQoL.Methods: This cross-sectional study included 407 women with fibromyalgia aged 51.4 ± 7.6 years. The time spent(min/day) in different PA intensity levels(light, moderate, and moderate-to-vigorous physical activity(MvPA) and sedentary time were measured with triaxial accelerometry. The proportion of women meeting the American PA recommendations(>150 min/week of MvPA in bouts >10 min) was also calculated.HRQoL domains(physical function, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health), as well as physical and mental components, were assessed using the 36-item Short-Form Health Survey.Results: All PA intensity levels were positively correlated with different HRQoL dimensions(r_(partial) between 0.10 and 0.23, all p vPA was independently associated with social functioning(p vitality, social functioning, and both the physical and mental component summary score(all p vs. mean = 20.4(95%CI: 18.9-21.9), p = 0.023)and better scores for social functioning(mean = 48.7(95%CI: 43.9-44.8) vs. mean = 42.3(95%CI: 39.8-44.8), p = 0.024).Conclusion: MvPA(positively) and sedentary time(negatively) are independently associated with HRQoL in women with fibromyalgia. Meeting the current PA recommendations is significantly associated with better scores for bodily pain and social functioning. These results highlight the importance of being physically active and avoiding sedentary behaviors in this population.

关键词： Accelerometry GT3X+ Mental health Physical health

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Laparoscopic and robot-assisted laparoscopic digestivesurgery:Present and future directions

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World Journal of Gastroenterology 2016年第6期22卷 1975-2004页

作者： Juan C Rodríguez-Sanjuán Marcos Gómez-Ruiz Soledad Trugeda-carrera Carlos manuel-Palazuelos Antonio López-Useros manuel Gómez-Fleitas Department of General Surgery University Hospital Marqués de Valdecilla39008 SantanderSpain Department of Medical and Surgical Sciences University of Cantabria39010 SantanderSpain

Laparoscopic surgery is applied today worldwide to most digestive procedures. In some of them, such as cholecystectomy, Nissen's fundoplication or obesity surgery, laparoscopy has become the standard in practice. In others, such as colon or gastric resection, the laparoscopic approach is frequently used and its usefulness is unquestionable. More complex procedures, such as esophageal, liver or pancreatic resections are, however, more infrequently performed, due to the high grade of skill necessary. As a result, there is less clinical evidence to support its implementation. In the recent years, robot-assisted laparoscopic surgery has been increasingly applied, again with little evidence for comparison with the conventional laparoscopic approach. This review will focus on the complex digestive procedures as well as those whose use in standard practice could be more controversial. Also novel robot-assisted procedures will be updated.

关键词： Laparoscopy Robotic surgery Colectomy Esophagectomy Gastrectomy Obesity surgery Liverresection Pancreatectomy Laparoscopic training

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Multitemporal landslide inventory analysis of an intertropical mountain in west-central Mexico——Basis for hazard management

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Journal of Mountain Science 2022年第6期19卷 1650-1669页

作者： Alejandro Cesar vALDES carrera manuel E.MENDOZA Teodoro CARLÓN ALLENDE Jose Luis MACIAS Centro de Investigaciones en Geografia Ambiental Universidad Nacional Autonoma de MexicoMorelia 58190Mexico Consejo Nacional de Ciencia y Tecnologia-Instituto de Geofisica-Unidad Michoacan Universidad Nacional Autonoma de MexicoMorelia 58190Mexico Instituto de Geofisica-Unidad Michoacan Universidad Nacional Autonoma de MexicoMorelia 58190Mexico

Landslides in intertropical mountainous areas of Mexico are a natural hazard that could potentially generate a disaster. Despite this, many areas lack landslide inventories, making it difficult to monitor and efficiently manage the associated risks for local populations. For this reason, the aim of this research was to undertake a multitemporal landslide inventory and analyze its conditioning factors in the Pico de Tancítaro stratovolcano, which, in recent decades, has presented several high-risk geomorphological events with disastrous consequences for nearby localities. The spatial distribution of landslides and its conditioning factors were mapped at a 1:50,000 scale for the 1995-2020 period, through visual interpretation of orthophotos and satellite images(Landsat, SPOT, and SENTINEL). The conditioning factors that link the most to landslides were Quaternary andesite and basaltic andesite rocks;volcanic cones, mountain river valleys, and very steep to steep slopes(30° to >45°), oriented to the South, North, and East;Andosols and Leptosols;and the oyamel fir and mixed forests. 505 landslide events classified into slides and flows that occurred in 1995, 2004, 2010, and 2015 were identified. New scars generated by the reactivation of landslide processes were also observed. The landslides in the study area were triggered by torrential rains caused by hurricanes and tropical storms;such as hurricanes Alex and Patricia. The inventory and analysis of conditioning factors highlighted the distribution and dynamics of slides and flows in the study area. In addition, the most important factors for studies of landslide susceptibility, hazards, and risks in the Pico de Tancítaro stratovolcano were identified, contributing to the management of geomorphological risks in intertropical mountain areas.

关键词： Geomorphology Mass wasting Natural hazards Pico de Tancítaro stratovolcano Risk management

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C-terminal variants of the P2X7 receptor are associated with prostate cancer progression and bonemetastasis–evidence from clinical and pre-clinical data

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Cancer Communications 2023年第3期43卷 400-404页

作者： Haiping Song Hector manuel Arredondo carrera Alexandria Sprules Ying Ji Tongsong Zhang Jiepei He Eleanor Lawrence Alison Gartland Jian Luo Ning Wang Department of Internal Medicine-Oncology Qingdao Tumor HospitalThe Second Affiliated Hospital of Medical College of Qingdao UniversityQingdaoShandong 266042P.R.China The Mellanby Centre for Musculoskeletal Research Department of Oncology and MetabolismThe University of SheffieldSheffieldSouth Yorkshire S102RXUK Yangzhi Rehabilitation Hospital(Sunshine Rehabilitation Centre) Tongji University School of MedicineShanghai 201619P.R.China

Dear Editor Bone is the most common site for metastasis in prostate cancer(PCa),and identifying clinically useful biomarkers to predict the risk of currently incurable bone metastases is a major priority in PCa research.Extracellular adenosine triphosphate(ATP)was shown to be a major biochemical constituent of the tumor microenvironment and regulates the tumor and host interactions by acting at P2 purinergic receptors.Among the P2 receptors,the ion channel P2X purinergic receptor 7(P2X7R)has an unusually long C-terminus containing 200 amino acids,which forms the molecular basis for the unique bi-function of P2X7R promoting cancer cell proliferation or inducing membrane permeabilization and apoptosis,upon activation by a low or high concentration of ATP,respectively.

关键词： metastasis cancer clinical

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Final Results of a Phase II Study of Bevacizumab, Cisplatin and Pemetrexed as First-Line Therapy for Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer

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Journal of Cancer Therapy 2016年第7期7卷 455-463页

作者： Guillermo López vivanco Eider Azkona Sergio carrera Aintzane Sancho Itziar Rubio Juan manuel Mañé Begoña Calvo Unai Aresti Aitziber Buque Inés Marrodán Alberto Muñoz Servicio de Oncología Médica Hospital de Cruces Bilbao Spain

Background: Efficacy and safety data for cisplatin and pemetrexed plus bevacizumabinnon squamousnon non-small cell lung cancer (NSCLC) are still limited. Nevertheless, either bevacizumab plus platinum doublet or pemetrexed plus platinum is approved options for first line therapy. Predictive factors for bevacizumab are needed. KRAS is one of the most common oncogenic drivers in lung cancer. Its prognostic and predictive value in NSCLC is under investigation. Patients and methods: This trial evaluates the addition of bevacizumab 7.5 mg/kg to cisplatin 75 mg/m2 plus pemetrexed 500 mg/m2 as first line treatment in stage Iv non-squamous NSCLC patients. Maintenance bevacizumab was received as monotherapy until progressive disease, unacceptable toxicityor consent with drawal. The primary objective was progression free survival (PFS). Secondary objectives included overall survival (OS), safety, global objective responses and the determination of KRAS mutation at baseline. Results: From March 2009 to March 2012, 31 patients were enrolled. Mean age was 59.19 (standard deviation (SD) 8.53). From all the patients included in this trial, 67.70% were men. KRAS was wild type in 19 patients (58.06%);in 7 (22.58%) was mutated and was unknown in 6 patients (19.35%). Median PFS for KRAS mutated patients was 4 months, whereas for the KRAS wild type it was 7.9 months (P = 0.0031). Median OS was 4 months for the KRAS population, and 16.1 months for the KRAS wild type (P = 0.0032). Twenty four patients (77.42%) experienced at least a grade 3 - 4 adverse event. The most common grade 3 - 4 toxicity was asthenia. Conclusions: Both PFS and OS were statistically longer for the KRAS wild type patients compared with the KRAS mutated population (P = 0.0031). Median OS was shorter than the reported in previous trials with bevacizumab. Nevertheless, focussing on the OS for KRAS wild type patients, this achieves a result or 16.1 months. Therefore, this would be a consistent data supporting to qualify this parameter as a pred

关键词： Non-Small-Cell Lung Cancer Bevacizumab Pemetrexed Predictive Biomarker KRAS

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Geological setting, mining and reduction of mercury vapor contamination in the gold-silver district of vetas-Calofornia （Santander, Colombia）

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Episodes 2005年第4期28卷 252-256页

作者： Erwin Wolff Carreno Juan manuel Pinzon Angel Rodolfo Contreras Moreno Christoph Bernardy Corporacion Autonoma Regional Para la Defensa de la Mescta de Bucaramanga Carrera 23 N°37-63 Bucaramanga Colombia Formely with Corporacidn Autonoma Regional Para la Defensa de la Mescta de Bucaramanga Carrera 23 N°37-63 Bucaramanga Colombia. Formerly with Federal Institute for Geosciences and Natural Resources Stilleweg 2 30655 Hannover Germany

Bucaramanga, with a population of about one million, is the capital of the Department of Santander (Colombia), and has the Río Suratá as its main source of drinking water. In the upper reaches of the river, small-scale gold mining has been going on for many centuries (vetas-California mining district). Geologically, the vetas-California mining district is part of the Santander Massif, which is composed of pre-Devonian metamorphic rocks and Mesozoic igneous rocks. The mineralisation is restricted to structurally controlled veins and is often associated with hydrothermal alteration. There is also disseminated mineralisation, but presently only the vein-type is mined. The processing residues are discharged into the nearby water-courses, contaminating the waters of the Suratá river basin. As part of a joint Colombian-German technical cooperation project, with the purpose of controlling the negative environmental effects of gold mining pollution, an integrated distillation system for the recovery of mercury has been designed and tested.

关键词：地质条件矿床哥伦比亚蒸发作用金银

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Acute kidney injury in severely injured patients admitted to the Intensive Care Unit

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Military Medical Research 2021年第2期8卷 141-147页

作者： Alberto F.García Ramiro Manzano-Nunez Juan G.Bayona Maria P.Naranjo Dary Neicce villa manuel Moreno Sebastian Ossa Juan M.Martinez Nathalia Martinez Juan C.Puyana Division of Trauma and Acute Care Surgery Department of SurgeryFundación Valle del LiliCaliColombia Clinical Research Center Fundación Valle del LiliCaliColombia Escuela de Medicina Ciencias de la SaludUniversidad del RosarioCarrera 98#18-49760001BogotaColombia Méderi Hospital Universitario Mayor Colombia School of Medicine Universidad ICESI(ICESI University)CaliColombia Department of Surgery University of PittsburghPittsburghPAUSA

Background:Our objective was to identify possible associations between clinical and laboratory variables and the risk of developing acute kidney injury(AKI)in severely injured patients admitted to the Intensive Care Unit(ICU)for whom creatine kinase(CK)levels were available.Methods:For this retrospective observational study,we analyzed adult trauma patients admitted to the ICU from 2011 to 2015 at Fundación valle del Lili(FvL)University Hospital.Our primary outcome was the incidence of AKI.Multivariate regression analysis was used to assess risk factors for this outcome.Results:A total of 315 patients were included.The trauma mechanisms were blunt(n=130),penetrating(n=66)and blast(n=44)trauma.The median[interquartile range,(IQR)of injury severity score(ISS)was 21(16–29).AKI developed in 75 patients(23.8%).Multivariate regression analysis revealed that the thoracic abbreviated injury scale(AIS)value(median(IQR)in the AKI group:3(0–4)],Acute Physiology and Chronic Health Evaluation(APACHE Ⅱ)score[median(IQR)in the AKI group:18(10–27)],CK greater than 5000 U/L,lactic acid concentration at admission,and dobutamine administration were independently associated with AKI.Conclusions:We found that age,APACHE Ⅱ score,thoracic trauma,lactic acidosis,and dobutamine administration were independently associated with AKI.Trauma surgeons need to be aware of the increased odds of AKI if one of these factors is identified during the evaluation and treatment of injured patients.

关键词： Rhabdomyolysis Wounds and injuries Acute kidney injury Critical care Trauma

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Unilateral rNurr1-v5 transgene expression in nigral dopaminergic neurons mitigates bilateral neuropathology and behavioral deficits in parkinsonian rats withα-synucleinopathy

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Neural Regeneration Research 2024年第9期19卷 2057-2067页

作者： Bismark Gatica-Garcia Michael J.Bannon Irma Alicia Martínez-Dávila Luis O.Soto-Rojas David Reyes-Corona Lourdes Escobedo Minerva Maldonado-Berny ME Gutierrez-Castillo Armando J.Espadas-Alvarez manuel A.Fernandez-Parrilla Juan U.Mascotte-Cruz CP Rodríguez-Oviedo Irais E.valenzuela-Arzeta Claudia Luna-Herrera Francisco E.Lopez-Salas Jaime Santoyo-Salazar Daniel Martinez-Fong Departamento de Fisiología Biofísica y NeurocienciasCentro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico Department of Pharmacology Wayne State University School of MedicineDetroitMIUSA Laboratorio de Patogénesis Molecular Carrera Médico CirujanoFacultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla de BazMéxico Red de Medicina para la Educación y Desarrollo y la Investigación Científica de Iztacala(Red MEDICI) Carrera Médico CirujanoFacultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla de BazMéxico Nanoparticle Therapy Institute AguascalientesMéxico Departamento de Biociencias e Ingeniería Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y DesarrolloInstituto Politécnico NacionalCiudad de MéxicoMéxico Escuela Nacional de Medicina y Homeopatía Instituto Politécnico NacionalCiudad de MéxicoMéxico Departamento de Fisiología Escuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalCiudad de MéxicoMéxico Departamento de Biología Molecular y Biotecnología Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoCiudad de MéxicoMéxico Departamento de Física Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico Programa de Nanociencias y Nanotecnología Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico

Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-v5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-v5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-v5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate t

关键词： A1 astrocytes A2 astrocytes gene therapy microglia motor deficits nanoparticles neurodegeneration neuroinflammation senescence α-synuclein aggregates

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