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Neural Regeneration Research 2019年第7期14卷 1196-1201页

作者： Darius Widera rocío martínez aguilar Graeme S.Cottrell Stem Cell Biology and Regenerative Medicine Group School of PharmacyUniversity of ReadingWhiteknights campus Unidad de Inmunología IBIMERUniversidad de Granada Cellular and Molecular Neuroscience School of PharmacyUniversity of Reading

Toll-like receptor 4(TLR4) and protease-activated receptor 2(PAR2) play pivotal roles in the mammalian innate immune ***,in addition to their involvement in detection of invading pathogens,PAR2 and TLR4 modulate the levels of cell death-induced sterile inflammation by activating pro-or anti-inflammatory downstream signaling *** the central nervous system,there is emerging evidence that both receptors are involved in synaptic transmission and brain ***,due to their prominent role in mediating neuroinflammation,PAR2 and TLR4 are associated with development and progression of neurodegenerative disorders including but not limited to Alzheimer's disease,Parkinson's disease and multiple *** this article,we summarise the current knowledge on the cooperation between PAR2 and TLR4,discuss the potential cross-talk levels and highlight the impact of the cross-coupling on neuroinflammation.

关键词： signaling inflammation proteases myeloid of differentiation primary response gene 88 TIR-domain containing adaptor inducing interferon lipopolysaccharide TLR4 PAR2

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso Josémartínez-Hernández Alejandro martín-Belmonte rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-martínez Mar Cuadrado-Tejedor Ana García-osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

Addition of phenolic compounds to bread: antioxidant benefits and impact on food structure and sensory characteristics

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Food Production, Processing and Nutrition 2021年第1期3卷 314-325页

作者： Yesica A.Czajkowska–González Emilio Alvarez–Parrilla Nina del rocío martínez–Ruiz Alma A.Vázquez–Flores Marcela Gaytán–martínez Laura Ade la Rosa Departament of Chemical Biological Sciences Institute of Biomedical SciencesUniversidad Autónoma de Ciudad JuárezAnillo Envolvente del PRONAF y Estocolmos/nC.P.32310 Cd.JuárezMéxico Programa de Posgrado en Alimentos del Centro de la República(PRoPAC) Research and Graduate Studies in Food ScienceSchool of ChemistryUniversidad Autónoma de QuerétaroCentro UniversitarioCerro de las Campanas S/NC.P.76010 Santiago de QuerétaroMexico

The use of flours or phenolic extracts obtained from non-traditional sources or agri-food industry by-products has been a strategy used to formulate new bakery products with characteristics of a functional ***,phenolic compounds present great structural diversity,as well as the ability to interact in a complex way with the macromolecules that constitute the bread ***,the addition of these flours,extracts or pure compounds produces various effects on the microstructure of bread,and several of its sensory *** is mainly due to interactions between phenolic compounds and gluten *** objective of this review is to analyze some of the most recent published works on the addition of phenolic compounds in wheat bread to identify the type of positive and negative effects that have been observed and how they can be related to the physicochemical interactions between phenolic compounds and the macromolecules that constitute the food matrix,mainly *** effect of monomeric and polymeric phenolic compounds on the strength of these interactions and on the properties of dough and bread are discussed.

关键词： condensed tannins hydrolysable tannins phenolic acids gluten food rheology food texture protein-phenolic interactions disulfide bonds non-covalent interactions

Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance

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World Journal of Gastroenterology 2016年第29期22卷 6573-6581页

作者： Miguel Jiménez-Pérez rocío González-Grande Pilar Espana Contreras Isabel Pinazo martínez Jesús de la Cruz Lombardo Raúl olmedo martín UGC de Aparato Digestivo Unidad de Hepatologia-Trasplante Hepatico Hospital Universitario Regional de Malaga 29010 Malaga Spain Liver transplantation and hepatology unit UGC de Aparato Digestivo Hospital Regional Universitario 29010 Malaga Spain

The use of direct-acting antivirals(DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response(around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants(RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These preexisting RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.

关键词： Direct-acting antivirals Resistance Treatment Hepatitis C virus

Management of recurrent hepatitis C virus after liver transplantation

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World Journal of Gastroenterology 2014年第44期20卷 16409-16417页

作者： Miguel Jiménez-Pérez rocío González-Grande Francisco Javier Rando-Mu?oz Liver transplantation and hepatology unit UGC de Aparato Digestivo Hospital Regional Universitario Department of Abdominal Diseases Hospital Nij Smellinghe Ziekenhuis

Chronic hepatitis C virus (HCV) infection is the leading cause of death from liver disease and the leading indication for liver transplantation (LT) in the United States and Western Europe. LT represents the best therapeutic alternative for patients with advanced chronic liver disease caused by HCV or those who develop hepatocarcinoma. Reinfection by HCV of the graft is universal and occurs in 95% of transplant patients. This reinfection can compromise graft function and patient survival. In a few cases, the histological recurrence is minimal and non-progressive; however, in most patients it follows a more rapid course than in immunocompetent persons, and frequently evolves into cirrhosis with graft loss. In fact, the five-year and ten-year survival of patients transplanted because of HCV are 75% and 68%, respectively, compared with 85% and 78% in patients transplanted for other reasons. There is also a pattern of recurrence that is very severe, but rare (osing cholestatic hepatitis, which often involves rapid graft loss. Patients who present a negative HCV viremia after antiviral treatment have better survival. Many studies published over recent years have shown that antiviral treatment of post-transplant HCV hepatitis carried out during the late phase is the best option for improving the prognosis of these patients. Until 2011, PEGylated interferon plus ribavirin was the standard of care, resulting in a sustained virological response in around 30% of recipients. The addition of protease inhibitors, such as boceprevir or telaprevir, to the standard of care, or the use of other direct-acting antiviral drugs may involve therapeutic changes in the context of HCV recurrence. This may result a better prognosis for these patients, particularly those with severe recurrence or factors predicting rapid progression of fibrosis. However, the use of these agents in LT still requires clarification in terms of safety and efficacy.

关键词： Hepatitis C virus Liver transplantation Recurrence Treatment

Chronic pain, posttraumatic stress disorder, and opioid intake: A systematic review

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World Journal of Clinical Cases 2019年第24期7卷 4254-4269页

作者： Alicia E López-martínez ángela Reyes-Pérez Elena rocío Serrano-Ibá?ez Rosa Esteve Carmen Ramírez-Maestre Facultad de Psicología Instituto de Investigaciones Biomédicas (IBIMA)Universidad de Málaga

BACKGRoUND The literature suggests that there is a high degree of co-occurrence between chronic pain and posttraumatic stress disorder(PTSD). An association has been found between PTSD and substance abuse. PTSD is a severe disorder that should be taken into account when opioids are prescribed. It has been found that the prevalence of opioid use disorder(oUD) in chronic pain patients is higher among those with PTSD than those without this *** To perform a systematic review on the association between PTSD, chronic noncancer pain(CNCP), and opioid intake(i.e., prescription, misuse, and abuse).METHoDS We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Patient, Intervention,Comparator, and outcomes(PICoS) criteria were formulated a priori in the protocol of the systematic review. A search was conducted of the PRoSPERo database. In March 2019, searches were also conducted of 5 other databases:Pub Med, MEDLINE, Psyc INFo, Web of Science, and PILoTS. The Scottish Intercollegiate Guidelines Network checklist for cohort studies was used to assess the selected studies for their methodological quality and risk of bias. Each study was evaluated according to its internal validity, participant sampling,confounding variables, and the statistical *** A total of 151 potentially eligible studies were identified of which 17 were retained for analysis. only 10 met the selection criteria. All the studies were published between 2008 and 2018 and were conducted in the United States. The eligible studies included a total of 1622785 unique participants. of these, 196516 had comorbid CNCP and PTSD and were consuming opiates. The participants had a cross-study mean age of 35.2 years. The majority of participants were men(81.6%). The most common chronic pain condition was musculoskeletal pain:back pain(47.14% across studies;range: 16%-60.6%), arthritis and joint pain(31.1%;range: 18%-67.5%), and

关键词： Posttraumatic stress disorder Chronic pain opioid prescription opioid misuse opioid abuse

Present and future management of viral hepatitis

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World Journal of Gastroenterology 2021年第47期27卷 8081-8102页

作者： rocío González Grande Inmaculada Santaella Leiva Susana López ortega Miguel Jiménez Pérez UGC de Aparato Digestivo.Unidad de Hepatología-Trasplante Hepático Hospital Regional Universitario de MálagaMálaga 29010Spain

Viral hepatitis can result in important morbidity and mortality,with its impact on health conditioned by the specific type of hepatitis,the geographical region of presentation and the development and access to new drugs,among other *** acute presentation forms are self-limiting and may even go unnoticed,with just a small percentage of cases leading to acute liver failure that may necessitate transplantation or even cause the death of the ***,when they become chronic,as in the case of hepatitis B virus and C virus,unless they are diagnosed and treated adequately they may have severe consequences,like cirrhosis or *** of the mechanisms of transmission,the pathogenesis,the presence of vaccinations and the development over recent years of new highly-efficient,potent drugs have meant that we are now faced with a new scenario in the management of viral hepatitis,particularly hepatitis B virus and hepatitis C *** spectacular advances in hepatitis C virus treatment have led the World Health organization to propose the objective of its eradication by *** key aspect to achieving this goal is to ensure that these treatments reach all the more vulnerable population groups,in whom the different types of viral hepatitis have a high prevalence and constitute a niche that may perpetuate infection and hinder its ***,microelimination programs assume special relevance at the present time.

关键词： Hepatitis viral Diagnosis Treatment Trend direct-acting antivirals Inhibiting recycling

Post-transcriptional regulation of seed dormancy and germination: Current understanding and future directions

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Plant Communications 2021年第4期2卷 1-22页

作者： rocío Soledad Tognacca Javier Francisco Botto Consejo Nacional de Investigaciones Científicas y Técnicas Universidad de Buenos AiresInstituto de FisiologíaBiología Molecular y Neurociencias(IFIBYNE)Facultad de Ciencias Exactas y NaturalesCP1428 Buenos AiresArgentina Universidad de Buenos Aires Consejo Nacional de Investigaciones Científicas y TécnicasInstituto de Investigaciones Fisiològicas y Ecològicas Vinculadas a la Agricultura(IFEVA)Facultad de AgronomíaCP1417 Buenos AiresArgentina

Seed dormancy is a developmental checkpoint that prevents mature seeds from germinating under conditions that are otherwise favorable for *** and light are themost relevant environmental factors that regulate seed dormancy and *** environmental cues can trigger molecular and physiological responses including hormone signaling,particularly that of abscisic acid and *** balance between the content and sensitivity of these hormones is the key to the regulation of seed *** and light tightly regulate the transcription of thousands of genes,as well as other aspects of gene expression such asmRNAsplicing,translation,and *** remodeling determines specific transcriptional outputs,and alternative splicing leads to different outcomes and produces transcripts that encode proteins with altered or lost *** regulation of chromatin remodeling and alternative splicing may be highly relevant to seed ***,microRNAs are also critical for the control of gene expression in *** review aims to discuss recent updates on post-transcriptional regulation during seed maturation,dormancy,germination,and post-germination *** propose future prospects for understanding howdifferent post-transcriptional processes in crop seeds can contribute to the design of genotypes with better performance and higher productivity.

关键词： alternative splicing chromatin remodeling dormancy germination microRNA(miRNA) seeds

Current trends in access to treatment for hepatitis B in immigrants vs non-immigrants

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Gastroenterology Report 2020年第5期8卷 362-366,I0002页

作者： Mireia Miquel Albert Pardo Montse Forné Gemma martínez-Alpin AdriàRodríguez-Castellano Meritxell Casas MercèRosinach MercèRoget Blai Dalmau rocío Temiño Joan Carlos Quer Jordi Sanchez-Delgado Jordi ortiz Mercedes Vergara Liver Unit Gastroenterology DepartmentParc TaulíUniversity HospitalInstitut d’Investigacio i InnovacióParc TaulíI3PTAutonomous University of BarcelonaSabadellSpain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadridSpain Gastroenterology Department University Hospital Joan XXIIITarragonaSpain Liver Unit Gastroenterology DepartmentUniversity Hospital Mútua TerrassaBarcelonaSpain Liver Unit Gastroenterology DepartmentConsorci Sanitari de TerrassaTerrassaSpainó

Background:Universal vaccination for hepatitis B virus(HBV)and migratory movements have changed the demographic characteristics of this disease in Spain and in ***,we evaluated the characteristics of the disease and the possible differences according to origin(immigrants vs non-immigrants)and access to ***:This is a multicenter cross-sectional study(June 2014 to May 2015)in which outpatients with a positive HBsAg were seen and followed in four Hepatology *** and clinical data and indication and access to treatment were collected in two different regions of Catalonia(Spain)where there are no barriers to treatment due to a comprehensive coverage under the National Health ***:A total of 951 patients were evaluated(48.1%men).of these,46.6%were immigrants(58.7%of them were born in Africa)and were significantly younger compared to *** proportions of patients with alcohol consumption,being overweight,and other indicators of metabolic co-morbidities were significantly higher in *** the 937 patients receiving HBeAg examination,91.7%were *** HBeAg-positive infection was significantly higher in immigrants(3.9%vs 0.6%,P=0.001)and chronic HBeAg-negative hepatitis was higher non-immigrants(31.7%vs 21.4%,Pot only was the proportion of patients who met treatment criteria significantly higher among nonimmigrants(38.4%vs 29.2%,P=0.003),but also the proportion of those with indication of effectively receiving therapy at the time of data collection(83.2%vs 57.8%,Ponclusions:The immigrant population with HBV is younger and has a lower prevalence of metabolic co-morbidities and a higher frequency of chronic HBeAg *** having access to care and an indication for treatment,some do not get adequately treated due to several factors including local adaptation that precludes access to treatment.

关键词： hepatitis B prevalence immigration access to treatment

Management of hepatitis B virus infection after liver transplantation

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World Journal of Gastroenterology 2015年第42期21卷 12083-12090页

作者： Miguel Jiménez-Pérez rocío González-Grande José Mostazo Torres Carolina González Arjona Francisco Javier Rando-Mu?oz Liver Transplantation and Hepatology Unit UGC de Aparato Digestivo Hospital Regional Universitario Department of Abdominals Diseases Hospital Nij Smellinghe Ziekenhuis

Chronic hepatitis B virus(HBV) infection is responsible for up to 30% of cases of liver cirrhosis and up to 53% of cases of hepatocellular carcinoma. Liver transplantation(LT) is the best therapeutic option for patients with end-stage liver failure caused by HBV. The success of transplantation, though, depends on receiving prophylactic treatment against post-transplant viral reactivation. In the absence of prophylaxis, liver transplantation due to chronic hepatitis B(CHB) is associated with high rates of viral recurrence and poor survival. The introduction of treatment with hepatitis B immunoglobulins(HBIG) during the 1990 s and later the incorporation of oral antiviral drugs have improved the prognosis of these patients. Thus, LT for CHB is now a universally accepted option, with an estimated 5 years survival of around 85% vs the 45% survival seen prior to the introduction of HBIG. The combination of lamivudine plus HBIG has for many years been the most widely used prophylactic regimen. However, with the appearance of new more potent oral antiviral agents associated with less resistance(e.g., entecavir and tenofovir) for the treatment of CHB, new prophylactic strategies are being designed, either in combination with HBIG or alone as a monotherapy. These advances have allowed for more personalized prophylaxis based on the individual risk profile of a given patient. In addition, the small pool of donors has required the use of anti-HBc-positive donors(with the resulting possibility of transmitting HBV from these organs), which has been made possible by suitable prophylactic regimens.

关键词： Hepatitis B virus Liver tra nsplantation Recurrence Prophylaxis Hepatitis B immunoglobulin