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Interindividual Age-Independent Differences in Human CX43 Impact ventricular Arrhythmic Risk

Research 2024年第3期6卷 417-432页

作者： Laura García-Mendívil María Pérez-Zabalza Antoni Oliver-Gelabert JoséMaría vallejo-Gil Javier Fañanás-Mastral manuel v.zquez-sancho Javier AndréBellido-Morales Alexánder Sebastián vaca-Núñez Carlos Ballester-Cuenca Emiliano Diez Laura Ordovás Esther Pueyo Biomedical Signal Interpretation and Computational Simulation group(BSICoS) Aragón Institute of Engineering ResearchUniversity of ZaragozaZaragoza 50018Spain BSICoS Instituto de Investigación Sanitaria Aragón(IISA)Zaragoza 50018Spain Centro Universitario de la Defensa(CUD) Zaragoza 50090Spain. Department of Cardiovascular Surgery University Hospital Miguel ServetZaragoza 50009Spain. Institute of Experimental Medicine and Biology of Cuyo(IMBECU) CONICETMendoza 5500Argentina. Fundación Agencia Aragonesa para la Investigación y el Desarrollo(ARAID) Zaragoza 50018Spain. Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine(CIBER-BBN)Zaragoza 50018Spain.

Connexin 43 (CX43) is one of the major components of gap junctions, the structures responsible for the intercellular communication and transmission of the electrical impulse in the left ventricle. There is limited information on the histological changes of CX43 with age and their effect on electrophysiology, especially in humans. Here, we analyzed left ventricular biopsies from living donors starting at midlife to characterize age-related CX43 remodeling. We assessed its quantity, degree of lateralization, and spatial heterogeneity together with fibrotic deposition. We observed no significant age-related remodeling of CX43. Only spatial heterogeneity increased slightly with age, and this increase was better explained by biological age than by chronological age. Importantly, we found that CX43 features varied considerably among individuals in our population with no relevant relationship to age or fibrosis content, in contrast to animal species. We used our experimental results to feed computational models of human ventricular electrophysiology and to assess the effects of interindividual differences in specific features of CX43 and fibrosis on conduction velocity, action potential duration, and arrhythmogenicity. We found that larger amounts of fibrosis were associated with the highest arrhythmic risk, with this risk being increased when fibrosis deposition was combined with a reduction in CX43 amount and/or with an increase in CX43 spatial heterogeneity. These mechanisms underlying high arrhythmic risk in some individuals were not associated with age in our study population. In conclusion, our data rule out CX43 remodeling as an age-related arrhythmic substrate in the population beyond midlife, but highlight its potential as a proarrhythmic factor at the individual level, especially when combined with increased fibrosis.

关键词： CX43 rhythm Independent

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Metabolic profiling of four synthetic stimulants,including the novel indanyl-cathinone 5-PPDi,after human hepatocyte incubation

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Journal of Pharmaceutical Analysis 2020年第2期10卷 147-156页

作者： David Fabregat-Safont Marie Mardal Juan v.sancho Félix Hernández Kristian Linnet María Ibánez Research Institute for Pesticides and Water University Jaume IAvda.Sos Baynat s/n12071CastellónSpain Department of Forensic Medicine Section of Forensic ChemistryFaculty of Health and Medicinal SciencesUniversity of CopenhagenFrederik V's vej 112100KФbenhavnФDenmark Department of Occupational and Environmental Medicine University Hospital of Northern NorwaySykehusvegenTromsoeNorway

Synthetic cathinones are new psychoactive substances that represent a health risk *** most of the 130 reported compounds,information about toxicology and/or metabolism is not available,which hampers their detection(and subsequent medical treatment)in intoxication *** principles of forensic analytical chemistry and the use of powerful analytical techniques are indispensable for stab-lishing the most appropriate biomarkers for these *** metabolic fate of synthetic cathinones can be assessed by the analysis of urine and blood obtained from authentic consumers;however,this type of samples is limited and difficult to *** this work,the metabolic behaviour of three synthetic cathinones(4-CEC,4-CPrC and 5-PPDi)and one amphetamine(3-FEA)has been evalu-ated by incubation with pooled human hepatocytes and metabolite identification has been performed by high-resolution mass *** in vitro approach has previously shown its feasibility for obtaining excretory human metabolites.4-CEC and 3-FEA were not metabolised,and for 4-CPrC only two minor metabolites were *** the contrary,for the recently reported 5-PPDi,twelve phase I metabolites were *** to our knowledge,this is the first metabolic study of an *** reported in this paper will allow the detection of these synthetic stimulants in intoxi-cation cases,and will facilitate future research on the metabolic behaviour of other indanyl-based cathinones.

关键词： Synthetic cathinones 5-PPDi Metabolite identification In vitro metabolism Hepatocyte incubation High resolution mass spectrometry

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Glutathione metabolism is essential for self-renewal and chemoresistance of pancreatic cancer stem cells

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World Journal of Stem Cells 2020年第11期12卷 1410-1428页

作者： Petra Jagust Sonia Alcala Bruno Sainz Jr Christopher Heeschen Patricia sancho Molecular Pathology Programme Spanish National Cancer Research Centre(CNIO)Madrid 28029Spain Department of Biochemistry Autónoma University of MadridInstituto de Investigaciones Biomédicas"Alberto Sols"CSIC-UAMMadrid 28029Spain Center for Single-Cell Omics&Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteShanghai Jiao Tong University School of MedicineShanghai 200025China Hospital Universitario Miguel Servet IIS AragonZaragoza 50009Spain

BACKGROUND Cellular metabolism regulates stemness in health and disease.A reduced redox state is essential for self-renewal of normal and cancer stem cells(CSCs).However,while stem cells rely on glycolysis,different CSCs,including pancreatic CSCs,favor mitochondrial metabolism as their dominant energy-producing *** suggests that powerful antioxidant networks must be in place to detoxify mitochondrial reactive oxygen species(ROS)and maintain stemness in oxidative *** glutathione metabolism is critical for normal stem cell function and CSCs from breast,liver and gastric cancer show increased glutathione content,we hypothesized that pancreatic CSCs also rely on this pathway for ROS *** To investigate the role of glutathione metabolism in pancreatic *** Primary pancreatic cancer cells of patient-derived xenografts(PDXs)were cultured in adherent or CSC-enriching sphere conditions to determine the role of glutathione metabolism in ***-time polymerase chain reaction(PCR)was used to validate RNAseq results involving glutathione metabolism genes in adherent vs spheres,as well as the expression of pluripotency-related genes following *** TCGA and GTEx RNAseq data from pancreatic cancer vs normal tissue samples were analyzed using the webserver *** glutathione-sensitive fluorescent probe monochlorobimane was used to determine glutathione content by fluorimetry or flow *** inhibitors of glutathione synthesis and recycling[buthionine-sulfoximine(BSO)and 6-Aminonicotinamide(6-AN),respectively]were used to investigate the impact of glutathione depletion on CSC-enriched *** with propidium iodide(cell cycle),Annexin-v(apoptosis)and CD133(CSC content)were determined by flow ***-renewal was assessed by sphere formation assay and response to gemcitabine treatment was used as a readout for *** Analysis of our previously published RNAseq dataset E-MTAB-

关键词： Pancreatic cancer Cancer stem cells Glutathione Self-renewal Chemoresistance Redox

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Could Low Hdl-Cholesterol Levels Be an Unvalued Predictor of Cancer Risk?: A Retrospective Case Study

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International Journal of Clinical Medicine 2015年第12期6卷 984-992页

作者： Juan Antonio vílchez Natalia sancho-Rodríguez Ana Martínez-Ruiz Enrique Martínez-Sánchez Francisco Ruiz-Espejo Isabel Tovar-Zapata Jose Antonio Noguera-velasco Clinical Analysis Department Virgen de la Arrixaca Clinic University Hospital Murcia Spain Cardiology Department Virgen de la Arrixaca Clinic University Hospital Murcia Spain Laboratorios Unilabs S. L. Murcia Spain

Background: The relationship between serum lipid profile levels and cancer risk remained uncertain. Recently, it had been reported a significant inverse association between high-density lipoprotein cholesterol (HDL) and the risk of incident cancer that was independent of low-density lipoprotein cholesterol (LDL), age or sex. Objective: The aim of our study was to evaluate the behavior of HDL in cancer patients and in healthy population. Methods: We created a retrospectively search strategy in the laboratory information system (LIS). We filtered and searched those patients with CEA within 5 - 20 ng/ml and any value of HDL and corroborated the presence of cancer (Group 1 (G1)) or not (Group 2 (G2)). Moreover, we searched a control group (patients in outpatient oncology clinic) to observe the values of HDL. Comparisons and statistical logistic regression models were applied to link the levels of this biomarkers and cancer risk. Results: We examined 852 valid patients, median age 62 (50 - 73) years. Within the search strategy group, G2 showed highest levels of HDL (54 (43 - 67) mg/dl) and lowest CEA levels (6.7 (5.7 - 8.4) ng/ml) comparing with G1: HDL (47 (37 - 60) mg/dl) and the CEA (7.9 (6.2 - 10.9) ng/ml);p p r2: 0.092;p p = 0.001)] and CEA [OR: 1.115 (1.060 - 1.174), (p verse association of HDL levels between healthy populations and were diagnosed with cancer. Moreover, in a random population, patients with cancer presented lower HDL values compared to those without cancer. Therefore, it could demonstrate the possible positive predictive value of low HDL related to cancer risk.

关键词： High-Density Lipoprotein Cholesterol (HDL) Cancer Risk Lipid Profile Carcinoembryonic Antigen (CEA)

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Use of the Scar Acceleration Method/Método de Aceleração Cicatricial—MAC®—in the Treatment of Capsular Contracture: Case Report

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Open Journal of Therapy and Rehabilitation 2020年第4期8卷 131-142页

作者： Carolina Macedo Alves Moreira Carolina Gonçalves Pinheiro Aline Ronis Sampaio Michele Paula dos Santos Andres Felipe Mantilla Santamaria Miriam viviane Baron Cristine Brandenburg Nathália Ken Pereira Iketani Mara Alessandra Porto dos Reis Oliveira Alexandre sancho Esteban Fortuny Felice Picariello Marcus vinicius de Mello Pinto Dr. Daniel Thomaz Clinic Uberlandia Minas Gerais Brazil Postgraduate Program in Health Sciences of the Faculty of Medicine of ABC (FMABC) The Vale do Salgado Faculty (FVS) Ceará Brazil Celulare Institute Petrópolis Rio de Janeiro Brazil School of Medicine of the Pontifical Catholic University of Rio Grande do Sul (PUC/RS) Porto Alegre Brazil School of Medicine of the Industrial University of Santander (UIS) Bucaramanga Colombia School of Medicine of the Pontifical Catholic University of Rio Grande do Sul (PUC/RS) Porto Alegre Brazil Postgraduate Program in Medicine and Health Sciences of the Pontifical Catholic University of Rio Grande do Sul (PUC/RS) Por-to Alegre Brazil Brazilian Education of the Federal University of Ceará (UFC) Fortaleza Brazil Hospital Beneficiente Portuguesa of Belém Pará Brazil Clínica Instituto de Cirurgia Plástica vênus Barreiras Bahia Brazil Unigranrio Rio de Janeiro Brazil Universidad Finis Terrae and CEO of Diagnostra Santiago Chile Università degli Studi di Napoli Federico II Napoli Italy Ph.D. and Creator of the MAC® Method CEO and Researcher of the Celulare Institute Petrópolis Rio de Janeiro Brazil

Capsular contracture is a frequent complication in the postoperative period of breast implantation. It usually accompanies the appearance of a firm breast that can progress to pain, distortion, and asymmetry of the breasts, requiring surgical revision. The present study is a case report. A 58-year-old woman with a medical diagnosis of capsular contracture of the right breast evidenced by ultrasound. She was referred to the physiotherapy clinic in October 2019 with an initial complaint of pain on palpation, swelling, and stiffness in her right breast. The patient was evaluated and the MACò method was used to treat capsular contracture. For this, 12 sessions of photodynamic therapy were carried out. The treatment included the use of LED by doping: red (300 s), violet (60 s) and blue (120 s), with the use of 1% methylene blue in target areas, three times a week. The patient had the beginning of symptoms’ remission in the fourth visit and total remission in the 12th visit. It was concluded that the use of photodynamic therapy using the MACverdana;">

关键词： Breast Implants Fibroses Methylene Blue Semiconductor Diode Laser Photodynamic Therapy

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A Study of Laser Effectiveness in Injured Tissues Regeneration

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Journal of Biosciences and Medicines 2021年第3期9卷 55-63页

作者： Marcus vinicius de Mello Pinto Aline Ronis Sampaio Miriam viviane Baron Carolina Macedo Alves Moreira Carolina Gonçalves Pinheiro Michele Paula dos Santos Andres Felipe Mantilla Santamaria Cristine Brandenburg Nathália Ken Pereira Iketani Mara Alessandra Porto dos Reis Oliveira Alexandre sancho Felice Picariello Esteban Fortuny Juliano Tibola Nilton Petrone vilardi Junior Celulare Institute Petrópolis Rio de Janeiro Brazil School of Medicine Pontifical Catholic University of Rio Grande do Sul (PUC/RS) Porto Alegre Brazil Dr. Daniel Thomaz Clinic Uberlandia Minas Gerais Brazil Faculty of Medicine of ABC (FMABC) Santo André Brazil vale do Salgado Faculty (FvS) Ceará Brazil School of Medicine Industrial University of Santander (UIS) Bucaramanga Colombia Federal University of Ceará (UFC) Fortaleza Brazil Hospital Beneficiente Portuguesa of Belém Pará Brazil Clínica Instituto de Cirurgia Plástica vênus Barreiras Bahia Brazil Unigranrio Rio de Janeiro Brazil da Universita Federico II di Napoli Italia e Pesquisador do Internacional Research Group Rio Grande do Norte Brazil Universidad Finis Terrae Santiago Chile UDESC Florianopolis SC Brazil Fluminense Football Club Rio de Janeiro RJ Brazil

This study aimed to understand the use of low level laser in the regeneration of injured tissues. Also to design our own opinion on the subject, as chemists. Laser is nothing more than a light with very special characteristics that grant it therapeutic properties. We can observe the existence of three different types of laser, being one of them the therapeutic laser, which is used in substitution for medications or along with them. Another type of laser is the surgical one and, in addition to these, there is a diagnostic type. A great advantage is that, instead of taking the medicine, the patient’s own body can be activated by the laser to produce certain substances that can often replace the drugs. This is a literature review emphasizing the use of low level laser. Thus, the reflections from this study can contribute to the amplification of the production of knowledge that aims at the resignification of the use of laser in therapy. Greater attention was given to two types of laser radiation: He-Ne and As-Ga, both presenting a high therapeutic potential in superficial and deep injures. However, the He-Ne laser excels in superficial lesions, whereas the As-Ga laser does so in deep injures, such as articular, muscular, etc.

关键词： Laser Injury Regeneration

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