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Influence of olive oil and its components on mesenchymal stem cell biology

World Journal of Stem Cells 2019年第12期11卷 1045-1064页

作者： antonio casado-díaz Gabriel dorado Jose Manuel Quesada-Gómez CIBER de Fragilidad y Envejecimiento Saludable(CIBERFES) Instituto Maimónides de Investigación Biomédica de Córdoba(IMIBIC)Hospital Universitario Reina SofíaCórdoba 14004Spain departement Bioquímica y Biología Molecular Campus Rabanales C6-1-E17Campus de Excelencia Internacional Agroalimentario(ceiA3)Universidad de CórdobaCIBERFESCórdoba 14071Spain Unidad de Gestión Clínica de Endocrinología y Nutrición CIBER de Fragilidad y Envejecimiento Saludable(CIBERFES)Instituto Maimónides de Investigación Biomédica de Córdoba(IMIBIC)Hospital Universitario Reina SofíaCórdoba 14004Spain

Extra virgin olive oil is characterized by its high content of unsaturated fatty acid residues in triglycerides,mainly oleic acid,and the presence of bioactive and antioxidant *** consumption is associated with lower risk of suffering chronic diseases and unwanted processes linked to aging,due to the antioxidant capacity and capability of its components to modulate cellular signaling *** of olive oil can alter the physiology of mesenchymal stem cells(MSCs).This may explain part of the healthy effects of olive oil consumption,such as prevention of unwanted aging *** date,there are no specific studies on the action of olive oil on MSCs,but effects of many components of such food on cell viability and differentiation have been *** objective of this article is to review existing literature on how different compounds of extra virgin olive oil,including residues of fatty acids,vitamins,squalene,triterpenes,pigments and phenols,affect MSC maintenance and differentiation,in order to provide a better understanding of the healthy effects of this ***,most studies have shown a positive effect of these compounds on *** collective findings support the hypothesis that at least part of the beneficial effects of extra virgin olive oil consumption on health may be mediated by its effects on MSCs.

关键词： Olive oil Mesenchymal stem cells Cellular differentiation Aging Cellular niche Mediterranean diet

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Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles

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World Journal of Stem Cells 2022年第7期14卷 453-472页

作者： Victoria Pulido-Escribano Bárbara Torrecillas-Baena Marta Camacho-Cardenosa Gabriel dorado MaríaÁngeles Gálvez-Moreno antonio casado-díaz Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17 Instituto Maimónides de Investigación Biomédica de CórdobaHospital Universitario Reina SofíaCórdoba 14004Spain dep.Bioquímica y Biología Molecular Campus Rabanales C6-1-E17Campus de Excelencia Internacional Agroalimentario(ceiA3)Universidad de CórdobaCIBERFESCórdoba 14071Spain

The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their *** properties include high expansion and differentiation in vitro,low immunogenicity,and modulation of biological processes,such as inflammation,angiogenesis and ***,the regenerative effect of MSC is partly due to their paracrine *** has prompted numerous studies,to investigate the therapeutic potential of their secretome in general,and specifically their extracellular vesicles(EV).The latter contain proteins,lipids,nucleic acids,and other metabolites,which can cause physiological changes when released into recipient ***,contents of EV can be modulated by preconditioning MSC under different culture *** them,exposure to hypoxia stands out;these cells respond by activating hypoxia-inducible factor(HIF)at low O_(2) *** has direct and indirect pleiotropic effects,modulating expression of hundreds of genes involved in processes such as inflammation,migration,proliferation,differentiation,angiogenesis,metabolism,and cell *** of these genes is reflected in the contents of secreted ***,numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under *** this review,we show the implications of hypoxia responses in relation to tissue *** addition,hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV,with a high potential for clinical use in regenerative medicine that can be applied to different pathologies.

关键词： Cell priming Extracellular vesicles Hypoxia Hypoxia-inducible factor Mesenchymal stemcells Regenerative medicine

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Effects of normobaric cyclic hypoxia exposure on mesenchymal stem-cell differentiation–pilot study on bone parameters in elderly

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World Journal of Stem Cells 2020年第12期12卷 1667-1690页

作者： Marta Camacho-Cardenosa JoséManuel Quesada-Gómez Alba Camacho-Cardenosa Alejo Leal Gabrieldorado Bárbara Torrecillas-Baena antonio casado-díaz Facultad Ciencias del deporte Universidad De ExtremaduraCáceres 10003Spain CIBER de Fragilidad Y Envejecimiento Saludable(CIBERFES) Unidad De Gestión Clínica De Endocrinología Y NutriciónInstituto Maimónides De Investigación Biomédica De CórdobaHospital Universitario Reina SofíaCórdoba 14004Spain Servicio de Traumatología Hospital de CáceresCáceres 10004Spain departamento Bioquímica y Biología Molecular Campus Rabanales C6-1-E17Campus de Excelencia Internacional Agroalimentario(ceiA3)Universidad de Córdoba-CIBERFES14071 CórdobaSpain

BACKGROUNd Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and *** tend to differentiate into adipocytes,instead of osteoblasts,with *** favors the loss of bone mass and development of *** induces hypoxia inducible factor 1αgene encoding transcription factor,which regulates the expression of genes related to energy metabolism and *** allows a better adaptation to low O2 *** hypoxia has negative effects on bone metabolism,favoring bone ***,surprisingly,cyclic hypoxia(CH),short times of hypoxia followed by long times in normoxia,can modulate MSC differentiation and improve bone health in *** To evaluate the CH effect on MSC differentiation,and whether it improves bone mineral density in *** MSC cultures were induced to differentiate into osteoblasts or adipocytes,in CH(3%O2 for 1,2 or 4 h,4 d a week).Extracellular-matrix mineralization and lipid-droplet formation were studied in MSC induced to differentiate into osteoblast or adipocytes,*** addition,gene expression of marker genes,for osteogenesis or adipogenesis,have been quantified by quantitative real time polymerase chain *** in vivo studies with elderly(>75 years old;n=10)were carried out in a hypoxia chamber,simulating an altitude of 2500 m above sea level,or in normoxia,for 18 wk(36 CH sessions of 16 min each).Percentages of fat mass and bone mineral density from whole body,trunk and right proximal femur(femoral,femoral neck and trochanter)were assessed,using dual-energy X-ray *** CH(4 h of hypoxic exposure)inhibited extracellular matrix mineralization and lipid-droplet formation in MSC induced to differentiate into osteoblasts or adipocytes,***,both parameters were not significantly affected by the other shorter hypoxia times *** longest periods of hypoxia downregulated the expression of genes related to extracellular matrix

关键词： Normobaric cyclic hypoxia Mesenchymal stem cells Cellular differentiation Osteoblasts Adipocytes Bone health

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digestive and breast cancer patients managed during the first wave of COVId-19 pandemic:Short and middle term outcomes

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World Journal of Methodology 2024年第2期14卷 107-126页

作者： Jacobo Trébol Ana Carabias-Orgaz María Carmen Esteban-Velasco Asunción García-Plaza Juan Ignacio González-Munoz Ana Belén Sánchez-casado Felipe Carlos Parreno-Manchado Marta Eguía-Larrea José antonio Alcázar-Montero Cirugía General y del Aparato digestivo Complejo Asistencial Universitario de SalamancaSalamanca 37007SalamancaSpain Cirugía Universidad de SalamancaSalamanca 37007SalamancaSpain Oftalmología Complejo Asistencial Universitario de SalamancaSalamanca 37007SalamancaSpain

BACKGROUNd The first wave of coronavirus disease 2019(COVId-19)pandemic in Spain lasted from middle March to the end of June *** population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable *** our centre,we managed patients previously and newly diagnosed with *** established a strategy based on limiting perioperative social contacts,preoperative screening(symptoms and reverse transcriptionpolymerase chain reaction)and creating separated in-hospital COVId-19-free pathways for non-infected *** also adopted some practice modifications(surgery in different facilities,changes in staff and guidelines,using continuously changing personal protective equipment…),that supposed new *** To analyse cancer patients with a decision for surgery managed during the first wave,focalizing on outcomes and pandemic-related *** We prospectively included adults with a confirmed diagnosis of colorectal,oesophago-gastric,liver-pancreatic or breast cancer with a decision for surgery,regardless of whether they ultimately underwent *** analysed short-term outcomes[30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection]and outcomes after 3 years(adjuvant therapies,oncological events,death,SARS-CoV-2 infection and vaccination).We also investigated modifications to usual *** From 96 included patients,seven didn’t receive treatment that period and four never(3 due to COVId-19).Operated patients:28 colon and 21 rectal cancers;laparoscopy 53.6%/90.0%,mortality 3.57%/0%,major complications 7.04%/25.00%,anastomotic leaks 0%/5.00%,3-years disease-free survival(dFS)82.14%/52.4%and overall survival(OS)78.57%/76.2%.Six liver metastases and six pancreatic cancers:no mortality,one major complication,three grade A/B liver failures,one bile leak;3-year dFS 0%/33.3%and OS 50.0%/33.3%(liver metastases/pancreatic carcinoma).5 g

关键词： COVId-19 SARS-CoV-2 Colon cancer Rectal cancer Breast cancer Liver cancer Pancreatic cancer Gastric cancer Oesophageal cancer Surgery

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CRISPR/Cas9 editing of the polygalacturonase FaPG1 gene improves strawberry fruit firmness

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Horticulture Research 2023年第3期10卷 201-210页

作者： Gloria López-casado Cristina Sánchez-Raya Pablo d.Ric-Varas Candelas Paniagua Rosario Blanco-Portales Juan Muñoz-Blanco Sara Pose antonio J.Matas Jose A.Mercado departamento de Botánica y Fisiología Vegetal Instituto de Hortofruticultura Subtropical y Mediterránea‘La Mayora’(IHSM-UMA-CSIC)Universidad de Málaga29071 MálagaSpain departamento de Bioquímica y Biología Molecular Universidad de Córdoba14071CórdobaSpain

Firmness is one of the most important fruit quality traits in *** postharvest shelf life of this soft fruit is highly limited by the loss of firmness,where cell wall disassembly plays an important *** studies demonstrated that the polygalacturonase FaPG1 has a key role in remodelling pectins during strawberry *** this study,FaPG1 knockout strawberry plants have been generated using the CRISPR/Cas9 system delivered via Agrobacterium *** independent lines,cv.“Chandler”,were obtained,and all of them were successfully edited as determined by PCR amplification and T7 endonuclease *** targeted mutagenesis insertion and deletion rates were analyzed using targeted deep *** percentage of edited sequences varied from 47%up to almost 100%,being higher than 95%for seven of the selected *** analyses showed that 7 out of the eight lines analyzed produced fruits significantly firmer than the control,ranging from 33 to 70%increase in *** was a positive relationship between the degree of FaPG1 editing and the rise in fruit *** changes were observed in other fruit quality traits,such as colour,soluble solids,titratable acidity or anthocyanin *** fruits showed a reduced softening rate during postharvest,displayed a reduced transpirational water loss,and were less damaged by Botrytis cinerea *** analysis of four potential off-target sites revealed no mutation *** conclusion,editing the FaPG1 gene using the CRISPR/Cas9 system is an efficient method for improving strawberry fruit firmness and shelf life.

关键词： fir straw PG1

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Gastrointestinal stromal tumors:a multidisciplinary challenge

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World Journal of Gastroenterology 2018年第18期24卷 1925-1941页

作者： Juan Manuel Sanchez-Hidalgo Manuel duran-Martinez Rafael Molero-Payan Sebastian Rufian-Pena Alvaro Arjona-Sanchez Angela casado-Adam antonio Cosano-Alvarez Javier Briceno-delgado department of General and digestive Surgery Reina Sofia University HospitalAvda.Menéndez Pidal s/nCordoba 14004Spain department of Intern Medicine Reina Sofia University HospitalAvda.Menéndez Pidal s/nCordoba 14004Spain Lipids and Atherosclerosis Research Unit IMIBIC/Hospital Universitario Reina Sofía/Universidad de CórdobaCordoba 14004Spain

Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors located in the alimentary tract. Its usual manifestation is gastrointestinal bleeding. However, small asymptomatic lesions are frequently detected as incidental finding. Characteristically, most GISTs(> 95%) are positive for the KIT protein(Cd117) by IHC staining and approximately 80%-90% of GISTs carry a mutation in the c-KIT or PdGFRA genes. Mutational analysis should be performed when planning adjuvant and neoadjuvant therapy, due to its possible resistance to conventional treatment. The arise of tyrosine kinase inhibitor has supposed a revolution in GISTs treatment being useful as adjuvant, neoadjuvant or recurrence disease treatment. That is why a multidisciplinary approach to this disease is required. The correct characterization of the tumor at diagnosis(the diagnosis of recurrences and the evaluation of the response to treatment with tyrosine kinase inhibitors) is fundamental for facing these tumors and requires specialized Endoscopist, Radiologists and Nuclear Medicine Physician. Surgery is the only potentially curative treatment for suspected resectable GIST. In the case of high risk GISTs, surgery plus adjuvantImatinib-Mesylate for 3 years is the standard treatment. Neoadjuvant imatinib-mesylate should be considered to shrink the tumor in case of locally advanced primary or recurrence disease, unresectable or potentially resectable metastasic tumors, and potentially resectable disease in complex anatomic locations to decrease the related morbidity. In the case of Metastatic GIST under Neoadjuvant treatment, when there are complete response, stable disease or limited disease progression, complete cytoreductive surgery could be a therapeutic option if feasible.

关键词： Gastrointestinal stromal tumors Surgery Oncology Radiology Endoscopy Nuclear medicine Pathology disease management Tyrosine kinase inhibitors Gastroenterology

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Colorectal peritoneal metastases:Optimal management review

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World Journal of Gastroenterology 2019年第27期25卷 3484-3502页

作者： Juan Manuel Sánchez-Hidalgo Lidia Rodríguez-Ortiz Alvaro Arjona-Sánchez Sebastián Rufián-Pena Angela casado-Adam antonio Cosano-Alvarez Javier Briceno-delgado department of General and digestive Surgery Reina Sofia University HospitalCordoba 14004Spain

The peritoneum is a common site of dissemination for colorrectal cancer, with a poorer prognosis than other sites of metastases. In the last two decades, it has been considered as a locoregional disease progression and treated as such with curative intention treatments. Cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) is the actual reference treatment for these patients as better survival results have been reached as compared to systemic chemotherapy alone, but its therapeutic efficacy is still under debate. Actual guidelines recommend that the management of colorectal cancer with peritoneal metastases should be led by a multidisciplinary team carried out in experienced centers and consider CRS + HIPEC for selected patients. Accumulative evidence in the last three years suggests that this is a curative treatment that may improve patients disease-free survival, decrease the risk of recurrence, and does not increase the risk of treatment-related mortality. In this review we aim to gather the latest results from referral centers and opinions from experts about the effectiveness and feasibility of CRS + HIPEC for treating peritoneal disease from colorectal malignancies.

关键词： Peritoneal metastases Colorectal cancer Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Peritoneal carcinomatosis

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Severe trauma in the geriatric population

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World Journal of Critical Care Medicine 2017年第2期6卷 99-106页

作者： Juan antonio Llompart-Pou Jon Pérez-Bárcena Mario Chico-Fernández Marcelino Sánchez-casado Joan Maria Raurich Servei de Medicina Intensiva Hospital Universitari Son Espases Servicio de Medicina Intensiva UCI Trauma y EmergenciasHospital Universitario 12 de Octubre Servicio de Medicina Intensiva Hospital Virgen de la Salud

Geriatric trauma constitutes an increasingly recognized problem. Aging results in a progressive decline in cellular function which leads to a loose of their capacity to respond to injury. Some medications commonly used in this population can mask or blunt the response to injury. Falls constitute the most common cause of trauma and the leading cause of trauma-related deaths in this population. Falls are complicated by the widespread use of antiplatelets and anticoagulants, especially in patients with brain injury. Under-triage is common in this population. Evaluation of frailty could be helpful to solve this issue. Appropriate triaging and early aggressive management with correction of coagulopathy can improve outcome. Limitation of care and palliative measures must be considered in cases with a clear likelihood of poor prognosis.

关键词： Geriatric trauma Elderly patients Severe trauma Triage Outcome

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Tenofovir vs lamivudine plus adefovir in chronic hepatitis B:TENOSIMP-B study

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World Journal of Gastroenterology 2017年第41期23卷 7459-7469页

作者： Manuel Rodríguez Juan Manuel Pascasio Enrique Fraga Javier Fuentes Martín Prieto Gloria Sánchez-Antolín Jose Luis Calleja Esther Molina María Luisa García-Buey María Angeles Blanco Javier Salmerón María Lucía Bonet Jose antonio Pons Jose Manuel González Miguel Angel casado Francisco Jorquera 无 division of Gastroenterology and Hepatology.Hospital Universitario Central de Asturias Unit for the Clinical Management of digestive diseases IBISHospital Universitario Virgen del Rocío Liver Transplantation and Hepatology Unit Gastroenterology ServiceHospital Universitario Reina Sofía digestive Medicine Service Hospital Universitario Miguel Servet Hepatology Unit Digestive Medicine ServiceHospital Universitari i Politècnic La Fe Hepatology Unit Hospital Universitario Rio Hortega Liver Unit Hospital Universitario Puerta de Hierro de MajadahondaUniversidad Autónoma de Madrid digestive Medicine Service Hospital Clínico de Santiago de Compostela Liver Unit Hospital Universitario de La Princesa digestive Medicine Service Hospital General Universitario Gregorio Maranon digestive Medicine Unit Complejo Hospitalario de Granada digestive Medicine Service Hospital Universitario Son Espases Hepatology Unit IMIB Hospital Universitario Virgen de la Arrixaca digestive Medicine Service Hospital Clínico Universitario de Valladolid Pharmacoeconomics and Outcomes Research Iberia division of Gastroenterology and Hepatology Complejo Asistencial Universitario de León the TENOSIMP-B Research Group

AIM To demonstrate the non-inferiority(15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate(TdF) vs the combination of lamivudine(LAM) plus adefovir dipivoxil(AdV) in the maintenance of virologic response in patients with chronic hepatitis B(CHB) and prior failure with *** This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups(TdF and LAM+AdV) of adult patients with hepatitis B e antigen(HBe Ag)-negative CHB, prior failure with LAM, on treatment with LAM+AdV for at least 6 mo, without prior resistance to AdV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were *** Forty-six patients were evaluated [median age: 55.4 years(30.2-75.2); 84.8% male], including 22 patients with TdF and 24 with LAM+AdV. during study development, hepatitis B virus dNA(HBV-dNA) remained undetectable, all patients remained HBe Ag negative, and hepatitis B surface antigen(HBs Ag) positive. Alanine aminotransferase(ALT) values at the end of the study were similar in the 2 groups(25.1± 7.65, TdF vs 24.22 ± 8.38, LAM+AdV, P = 0.646). No significant changes were observed in creatinine or serum phosphorus values in either group. No significant differences between the 2 groups were noted in the identification of adverse effects(AEs)(53.8%, TdF vs 37.5%, LAM+AdV, P = 0.170), and none of the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in the TdF and the LAM+AdV groups, respectively(P = 0.488). The costs associated with hospital resource consumption were significantly lower with the TdF treatment than the LAM+AdV treatment(€4943 ± 1059 vs €5811 ± 1538, respectively, P dF monotherapy proved to be safe

关键词： Tenofovir Lamivudine+Adefovir Efficacy Safety Adherence Costs Hepatitis B

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Acute necrotizing pancreatitis: Surgical indications and technical procedures

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World Journal of Clinical Cases 2014年第12期2卷 840-845页

作者： José Manuel Aranda-Narváez antonio Jesús González-Sánchez María Custodia Montiel-casado Alberto Titos-García Julio Santoyo-Santoyo General Digestive and Transplantation Surgery Department University Regional Hospital 29010 Málaga Spain

Necrosis of pancreatic parenchyma or extrapancreatic tissues is present in 10%-20% of patients with acute pancreatitis, defining the necrotizing presentation frequently associated with high morbidity and mortality rates. during the initial phase of acute necrotizing pancreatitis the most important pillars of medical treatment are fluid resuscitation, early enteral nutrition, endoscopic retrograde colangiopancreatography if associated cholangitis and intensive care unit support. When infection of pancreatic or extrapancreatic necrosis occurs, surgical approach constitutes the most accepted therapeutic option. In this context, we have recently assited to changes in time for surgery(delaying the indication if possible to around 4 wk to deal with "walledoff" necrosis) and type of access for necrosectomy: from a classical open approach(with closure over large-bore drains for continued postoperative lavage or semiopen techniques with scheduled relaparotomies), trends have changed to a "step-up" philosophy with initial percutaneous drainage and posterior minimally invasive or endoscopic access to the retroperitoneal cavity for necrosectomy if no improvement has been previously achieved. These approaches are progressively gaining popularity and morbidity and mortality rates have decreased significantly. Therefore, a staged, multidisciplinary, step-up approach with minimally invasive or endoscopic access for necrosectomy is widely accepted nowadays for management of pancreatic necrosis.

关键词： Acute pancreatitis Necrotizing pancreatitis Surgery Open necrosectomy Minimal access retroperitoneal pancreatic necrosectomy Video-assisted retroperitoneal debridement

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