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Prevention of hepatocellular carcinoma by correction of metabolic abnormalities: Role of statins and metformin

World Journal of Hepatology 2015年第8期7卷 1105-1111页

作者： Javier Ampuero Manuel Romero-Gomez Unit for the Clinical Management of Digestive Diseases Valme University Hospital

Hepatocellular carcinoma is the third leading cause of cancer-related deaths in the world. It is associated with an important mortality rate and the incidence is increasing. Patients showing metabolic syndrome seem to have higher incidence and mortality rates from hepatocellular carcinoma than healthy subjects, especially those with type 2 diabetes mellitus and obesity. Thus, metformin and statins, both to treat features of metabolic syndrome, have been proposed to decrease the risk of hepatocellular carcinoma. Otherwise, liver cancer is the result of a complex process which impairs several signaling cascades, such as RAS/RAF/mitogen-activated protein kinase kinase(MEK)/extracellularsignal-regulated kinase(ERK), phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)/AKT/mammalian target of rapamycin(m TOR) and Wnt/β-catenin signaling. Metformin(through 5′-adenosine monophosphateactivated protein kinase pathway activation) and statins(through 3-hydroxy-3-methylglutaryl coenzyme A inhibition) show anti-tumoral properties modifying several steps of RAS/RAF/MEK/ERK, PI3K/AKT/m TOR and Wnt/β-catenin signaling cascades. On the other hand, metformin and statins have been found to reduce the risk of hepatocellular carcinoma up to 50% and 60%, respectively. Furthermore, both drugs have shown a dose-dependent protective effect. However, information about chemopreventive role of metformin and statins is mainly obtained of observational studies,which could not take into account some bias. In conclusion, given the rising of incidence of hepatocellular carcinoma and the important morbidity and mortality rates associated with this cancer, looking for chemopreventive strategies is an essential task. Randomized controlled trials are needed to determine the definite role of metformin and statins on the prevention of hepatocellular carcinoma.

关键词： Hepatocellular carcinoma Metformin Metabolic syndrome Mammalian target of rapamycin Statin

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Hepatitis C virus genotype 3: Meta-analysis on sustained virologic response rates with currently available treatment options

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World Journal of Gastroenterology 2016年第22期22卷 5285-5292页

作者： Javier Ampuero K Rajender Reddy Manuel Romero-Gomez Inter-Centre Unit of Digestive Diseases and CIBERehd Virgen Macarena Virgen del Rocio University Hospitals University of Sevilla 41018 Sevilla Spain Instituto de Biomedicina de Sevilla 41018 Sevilla Spain Division of Gastroenterology and Hepatology Department of Medicine University of Pennsylvania Philadelphia PA 19107 United States

AIM: To address the therapeutic efficacy of various treatment regimens in genotype 3 selecting randomized clinical trials and prospective National Cohort Studies.METHODS:(1) PEG-INF-based therapy including sofosbuvir(SOF) + RBV for 12 wk vs SOF + RBV 24 wk;(2) SOF + RBV therapy 12 wk/16 wk vs 24 wk; and(3) the role of RBV in SOF + daclatasvir(DCV) and SOF + ledipasvir(LDV) combinations. This metaanalysis provides robust information with the intention of addressing treatment strategy for hepatitis C virus genotype 3.RESULTS: A combination treatment including SOF + RBV + PEG-IFN for 12 wk notes better SVR than with only SOF + RBV for 12 wk, although its association with more frequent adverse effects may be a limiting factor. Longer duration therapy with SOF + RBV(24 wk) has achieved higher SVR rates than shorter durations(12 or 16 wk). SOF + LDV are not an ideal treatment for genotype 3. CONCLUSION: Lastly, SOF + DCV combination is probably the best oral therapy option and the addition of RBV does not appear to be needed to increase SVR rates substantially.

关键词： Hepatitis C Genotype 3 Sofosbuvir Daclatasvir Ledipasvir

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Modulation of faecal metagenome in Crohn's disease:Role of microRNAs as biomarkers

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World Journal of Gastroenterology 2018年第46期24卷 5223-5233页

作者： María Rojas-Feria Teresa romero-García Jose Angel Fernández Caballero-Rico Helena Pastor Ramírez Marta Avilés-Recio manuel Castro-Fernandez Natalia Chueca Porcuna Manuel Romero-Gomez Federico García Lourdes Grande JoséA Del Campo Department of Digestive Diseases Valme University HospitalUGC Digestive Disease and CIBERehdServicio Andaluz de SaludSeville E-41014Spain Complejo Hospitalario Universitario de Granada MicrobiologyGranada E-18016Spain Institute of Biomedicine of Seville Digestive DiseasesHospital Universitario Virgen del Rocío and CIBERehdSeville E-41013Spain Facultad de ciencias de la salud.Universidad Europea Miguel de Cervantes Madrid E-28280Spain

BACKGROUND The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16 S rRNA gene sequencing has shown that the microbiota in inflammatory bowel disease(IBD) is abnormal and characterized by reduced diversity. Micro RNAs(miRNAs) have been explored as biomarkers and therapeutic targets, since they are able to regulate specific genes associated with Crohn's disease(CD). In this work, we aim to investigate the composition of gut microbiota of active treatment-na?ve adult CD patients, with miRNA profile from gut microbiota.AIM To investigate the composition of gut microbiota of active treatment-na?ve adult CD patients, with miRNA profile from gut microbiota.METHODS Patients attending the outpatient clinics at Valme University Hospital without relevant co-morbidities were matched according to age and gender. Faecal samples of newonset CD patients, free of treatment, and healthy controls were collected. Faecal samples were homogenized, and DNA was amplified by PCR using primers directed to the 16 S bacterial rRNA gene. Pyrosequencing was performed using GS-Junior platform. For sequence analysis, MGRAST server with the database Ribosomal Project was used. MiRNA profile and their relative abundance were analyzed by quantitative PCR.RESULTS Microbial community was characterized using 16 S rRNA gene sequencing in 29 samples(n = 13 CD patients, and n = 16 healthy controls). The mean Shannon diversity was higher in the healthy control population compared to CD group(5.5 vs 3.7). A reduction in Firmicutes and an increase in Bacteroidetes were found. Clostridia class was also significantly reduced in CD. Principal components analysis showed a grouping pattern, identified in most of the subjects in both groups, showing a marked difference between control and CD groups. A functional metabolic study showed that a lower metabolism of carbohydrates(P = 0

关键词： Crohn’s disease Dysbiosis microRNAs Firmicutes Bacteroidetes

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Influence of in vitro capacitation time on structural and functional human sperm parameters

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Asian Journal of Andrology 2020年第5期22卷 447-453页

作者： Paula Saez-Espinosa Natalia Huerta-Retamal Laura Robles-gomez manuel Aviles Jon Aizpurua Irene Velasco Alejandro romero Maria Jose gomez-Torres Department of Biotechnology Faculty of ScienceUniversity of AlicanteAlicante 03080Spain FISABI0-University Hospital of San Juan de Alicante Service of Gynecology and ObstetricsSan Juan de Alicante 03550Spain Departm ent of Cell Biology and Histology Faculty of MedicineUniversity of Murcia and IMIB-ArrixacaMurcia 30100Spain IVF Spain Reproductive MedicineAlicante 03540Spain University Hospital of San Juan de Alicante Service of Gynecology and ObstetricsSan Juan de Alicante 03550Spain Human Fertility Cathedra University of AlicanteAlicante 03080Spain.

A cascade of dramatic physiological events is linked to the sperm acrosome reaction and binding to the oocyte's zona pellucida during human sperm capacitation.However,structural and functional sperm changes during capacitation currently remain poorly defined.Here,we performed a multibiomarker approach based on the utilization of sperm concentration,motility,viability,morphology,acrosome reaction,tyrosine phosphorylation,DNA fragmentation,and lectin-binding sites to analyze the impact caused by swim-up selection times(uncapacitated,1 h capacitated,and 4 h capacitated)on sperm function and structure in normozoospermic samples.We found that a 4 h swim-up capacitation increased sperm quality,because a large number of cells with normal morphology and lower DNA fragmentation rates were recovered.Furthermore,the long-term capacitation induced a higher percentage of cells with tyrosine phosphorylation of the principal piece as well as a redistribution of lectin-binding sites.Overall,the multivariate biomarkers analyzed showed a less variable distribution on spermatozoa recovered after 4 h capacitation than that with the shorter capacitation time.These findings stress the importance of capacitation time as a relevant factor in sperm quality with potential biological reproductive implications both for basic research and in assisted reproduction techniques.

关键词： acrosome reaction capacitation DNA fragmentation glycocalyx lectin-binding sites membrane integrity protein phosphorylation sperm selection

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Association between vitamin D and hepatitis C virus infection: A meta-analysis

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World Journal of Gastroenterology 2013年第35期19卷 5917-5924页

作者： Livia Melo Villar José Antonio Del Campo Isidora Ranchal Elisabeth Lampe Manuel Romero-Gomez Laboratory of Viral Hepatitis Oswaldo Cruz Institute Fiocruz Rio de Janeiro RJ 210360-040 Brazil Unit for the Clinical Management of Digestive Diseases and CIBERehd Hospital Universitario de Valme41014 SevillaSpain

AIM:To evaluate the association between 25-hydroxyvitamin D[25(OH)D]and sustained virological response(SVR)in hepatitis C virus(HCV)infected individuals.METHODS:Relevant studies were identified by systematically searching MEDLINE databases up to March2012 and abstracts of the European and American Congress of Hepatology conducted in 2011.Studies must provide information on SVR and the levels of 25(OH)D3and/or 25(OH)D2[henceforth referred to as 25(OH)D]in sera samples from HCV infected individuals.The inclusion criteria were:clinical studies that included HCV infected patients aged older than 18 years regardless of HCV genotype or ethnic group;provided information on SVR rates;and were reported in the English languageas full papers.Due to the heterogeneity of studies in categorizing serum vitamin D levels,a cut-off value of30 ng/mL of serum 25(OH)D was used.Heterogeneity was assessed using I2statistics.The summary odds ratios with their corresponding 95%CI were calculated based on a random-effects model.RESULTS:Overall,11 studies(8 observational and 3interventional)involving 1575 individuals were included and 1117 HCV infected individuals(71%)showed low vitamin D levels.Most of the studies included monoinfected HCV individuals with the mean age ranging from 38 to 56 years.Four studies were conducted in human immunodeficiency virus/HCV infected individuals.Regarding vitamin D measurement,most of the studies employed radioimmunoassays(n=5)followed by chemiluminescence(n=4)and just one study employed high performance/pressure liquid chromatography(HPLC).Basal vitamin D levels varied from 17 to43 ng/mL in the studies selected,and most of the HCV infected individuals had genotype 1(1068/1575)with mean viral load varying from log 4.5-5.9 UI/mL.With regard to HCV treatment,most of the studies(n=8)included HCV individuals without previous treatment,where the pooled SVR rate was 46.4%.High rates of SVR were observed in HCV individuals with vitamin D levels above 30 ng/mL(OR=1.57;95%CI:1.12-2.2)and those supplemented with v

关键词： Vitamin D Hepatitis C Therapy Metaanalysis Sustained virological response

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Preliminary Design Study on Concentrated Solar Power PVRs to Operate with RCBC

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Journal of Energy and Power Engineering 2013年第1期7卷 88-95页

作者： Ramon Ferreiro Garcia manuel romero gomezt Alberto DeMiguel Catoira Javier romero gomez Industrial Engineering Department E.T.S.N.M. A Coruna University A Coruna 15011 Spain Energy and Propulsion Department E.T.S.N.M. A Coruna University A Coruna 15011 Spain

Parabolic through concentrators and parabolic dish concentrators followed by a PVR (pressurized volumetric receiver) are proposed, studying the performance behavior of a RCBC (regenerative closed Brayton cycle) operating with helium or hydrogen. A pressurized gas such as helium circulates along the volumetric receiver, capturing the concentrated thermal solar energy to be further converted into electric power via a thermal cycle. The overall efficiency of the plant has been computed under variable parameters to determine the operating conditions for which efficiency and specific power are acceptable. As consequence of the proposed analysis, it is concluded that direct coupling between volumetric receivers and thermal engines renders high efficiency while avoiding an intermediate heat transfer medium.

关键词：操作系统 PVR 太阳能发电布雷顿循环设计太阳能转换可变参数操作条件

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Adverse hepatic reactions associated with calcium carbimide and disulfiram therapy: Is there still a role for these drugs?

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World Journal of Gastroenterology 2006年第31期12卷 5078-5080页

作者： Carmen Verge M Isabel Lucena Enrique López-Torres M José Puche-García Enrique Fraga Manuel Romero-Gomez Raúl J Andrade Clinical Pharmacology ServiceVirgen de la Victoria University Hospital School of MedicineMálagaSpain Gastroenterology ServiceUniversity Hospital Reina Sofia CórdobaSpain Gastroenterology ServiceUniversity Hospital Virgen de Valme SevillaSpain Liver UnitDepartment of Gastroenterology University HospitalMálagaSpain

四乙秋兰姆化二硫和钙 carbimide 是二白酒威慑然而，广泛地在那里在酒精中毒治疗使用的狂言存在对他们的安全的大担心。hepatotoxicity 上的报告主要与四乙秋兰姆化二硫治疗有关，被出版了。钙 carbimide 的肝毒素的潜力是很好描绘的... 详细信息

四乙秋兰姆化二硫和钙 carbimide 是二白酒威慑然而，广泛地在那里在酒精中毒治疗使用的狂言存在对他们的安全的大担心。hepatotoxicity 上的报告主要与四乙秋兰姆化二硫治疗有关，被出版了。钙 carbimide 的肝毒素的潜力是很好描绘的更少。这里，我们描述与被提交到 hepatotoxicity 的一张注册表并且当规定这些混合物时，指出我们面对的限制的这个治疗学的组有关的肝损坏的四个案例。对在白酒依赖的管理的这些混合物的角色的重估清楚地被需要。

关键词：异氰酸脂肝中毒戒酒硫治疗

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Role of neutrophil-to-lymphocyte and platelet-tolymphocyte ratios in Peyronie’s disease: a new diagnostic approach to predict the stage of the disease?

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Asian Journal of Andrology 2021年第3期23卷 325-329页

作者： Esther Garda Rojo Borja Garda gomez Rocio Santos-Perez de la Blanca Celeste Manfredi manuel Alonso Isa Jose Medina Polo Alfredo Rodriguez Antolin Javier romero Otero Department of Urology Research Institute Hospital 12 de Octubre(Imasl2)Madrid 29041Spain Department of Urology University Hospital HM MonteprfncipeMadrid 28668Spain.

Neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)have been associated with multiple entities and several types of cancers.They can be assumed as markers of inflammatory imbalance.The objective of this study is to evaluate the NLR and PLR in Peyronie’s disease(PD)and to establish a comparison of its values in the acute and chronic stages.We recruited patients with PD from March 2018 to March 2019.The patients enrolled underwent medical and sexual history as well as a physical examination.The values of blood count of each patient were collected both in the acute and chronic stages.Wilcoxon test was used to compare the acute and chronic stage ratios.Kruskal-Wallis test was carried out to evaluate the impact of treatments on the ratios.To identify cutoff values,we used sensibility and specificity tables and receiver operating characteristic(ROC)curves.A total of 120 patients were enrolled.Their mean age was 55.85(range:18-77)years and the mean penile curvature was 48.43°(range:10°-100°).In the acute stage,the mean NLR was 2.35 and the mean PLR was 111.22.These ratios,in the chronic stage,were 1.57 and 100.00,respectively.Statistically significant differences between acute and stable stages for both indices were found(NLR:P<0.0001;PLR:P=0.0202).The optimal cutoff for classification in acute or stable stage was 2 for NLR and 102 for PLR.According to our results,with an ordinary blood count,we could have important indications regarding the disease stage of the patient,and consequently on the most appropriate type of therapy to choose.

关键词： diagnosis inflammation neutrophil-to-lymphocyte ratio Peyronie^disease platelet-to-lymphocyte ratio

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Arabidopsis SWC4 Binds DNA and Recruits the SWR1 Complex to Modulate Histone H2A.Z Deposition at Key Regulatory Genes

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Molecular Plant 2018年第6期11卷 815-832页

作者： Angeles gomez-Zambrano Pedro Crevillen Jose M. Franco-Zorrilla Juan A. Lopez Jordi Moreno-romero Pawel Roszak Juan Santos-Gonzalez Silvia Jurado Jesus Vazquez Claudia Kohler Roberto Solano manuel Pineiro Jose A. Jarillo Centro de Biotecnologia y Genomica de Plantas Universidad Politecnica de Madrid (UPM) - Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria (INIA) Campus Montegancedo UPM Pozuelo de Alarcon 28223 Madrid Spain Plant Molecular Genetics Department and Genomics Unit Centro Nacional de Biotecnologia Consejo Superior de Investigaciones Cientfficas 28049 Madrid Spain Proteomics Unit Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) 28029 Madrid Spain Department of Plant Biology Uppsala BioCenter Swedish University of Agricultural Sciences and Linnean Center for Plant Biology Uppsala 75652 Sweden Laboratory of Cardiovascular Proteomics Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) 28029 Madrid Spain Instituto de Bioquimica Vegetal y Fotosintesis Consejo Superior de Investigaciones Cientfficas and Universidad de Sevilla 41092 Sevilla Spain Centre for Research in Agricultural Genomics (CRAG) CSIC-IRTA-UAB-UB Campus UAB Bellaterra Barcelona Spain The Sainsbury Laboratory Cambridge CB2 1LR UK

Deposition of the H2A.Z histone variant by the SWR1 complex （SWRI-C） in regulatory regions of specific loci modulates transcription. Characterization of mutations in Arabidopsis thaliana homologs of yeast SWRI-C has revealed a role for H2A.Z exchange in a variety of developmental processes. Nevertheless, the exact composition of plant SWRI-C and how it is recruited to target genes remains to be established. Here we show that SWC4, the Arabidopsis homolog of yeast SANT domain protein Swc4/Eaf2, is a DNA-binding protein that interacts with SWR1-C subunits. We demonstrate that the swc4-1 knockout mutant is embryo- lethal, while SWC4 RNAi knockdown lines display pleiotropic phenotypic alterations in vegetative and repro- ductive traits, including acceleration of flowering time, indicating that SWC4 controls post-embryonic processes. Transcriptomic analyses and genome-wide profiling of H2A.Z indicate that SWC4 represses tran- scription of a number of genes, including the floral integrator FT and key transcription factors, mainly by modulating H2A.Z deposition. Interestingly, SWC4 silencing does not affect H2A.Z deposition at the FLC locus nor expression of this gene, a master regulator of flowering previously shown to be controlled by SWR1-C. Importantly, we find that SWC4 recognizes specific AT-rich DNA elements in the chromatin regions of target genes and that SWC4 silencing impairs SWRI-C binding at FT. Collectively, our data suggest that SWC4 regulates plant growth and development by aiding SWR1-C recruitment and modulating H2A.Z deposition.

关键词： Arabidopsis SWC4 chromatin SWR1 complex H2A.Z deposition flowering time

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Improved Non-Covalent Biofunctionalization of Multi-Walled Carbon Nanotubes Using Carbohydrate Amphiphiles with a Butterfly-Like Polyaromatic Tail

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Nano Research 2010年第11期3卷 764-778页

作者： Mohyeddin Assali manuel Pernía Leal Inmaculada Fernández Pablo romero-gomez Rachid Baati Noureddine Khiar Instituto de Investigaciones Químicas C.S.I.C-Universidad de Sevillac/.Américo Vespucio49Isla de la CartujaSevilla 41092Spain Departamento de Química Orgánica y Farmacéutica Facultad de FarmaciaUniversidad de SevillaSevilla 41012Spain Instituto de Ciencias de Materiales de Sevilla C.S.I.C-Universidad de Sevillac/.Américo Vespucio49Isla de la CartujaSevilla 41092Spain Universitéde Strasbourg Facultéde Pharmacie CNRS/UMR 7199 Laboratoire des Systèmes Chimiques Fonctionnels BP 6002474 route du Rhin67400 IllkirchFrance

We have developed an efficient strategy for the non-covalent functionalization of multi-walled carbon nanotubes(MWCNTs)which allows a biomimetic presentation of carbohydrates on their surface byπ-πstacking interactions.The strategy is based on the use of sugar-based amphiphiles functionalized with tetrabenzo[a,c,g,i]fluorene(Tbf),a polyaromatic compound with a topology that resembles a butterfly with open wings.The new carbohydrate-tethered Tbf amphiphiles have been synthesized in a straightforward manner using click chemistry.The reported method has been developed in order to improve the rather low ability of pyrene-based systems to exfoliate MWCNTs in water.By means of thermogravimetric analysis(TGA),ultraviolet(UV),infrared(IR),and fluorescence spectroscopies the interaction between MWCNTs and the Tbf group has been found to be stronger than those involving pyrene-based amphiphilic carbohydrates.The resulting aggregates with a multivalent sugar exposition on their surface are able to engage in specific ligand-lectin interactions similar to glycoconjugates on a cell membrane.

关键词： Carbon nanotubes non-covalent functionalization tetrabenzo[a c g i]fluorene carbohydrates click chemistry biocompatible system

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