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Beyond neurodegeneration:engineering amyloids for biocatalysis

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Neural Regeneration Research 2025年第10期20卷 2915-2916页

作者： Andrea Bartolomé-Nafría javier García-Pardo Salvador Ventura Institut de Biotecnologia i de Biomedicina(IBB)and departament de Bioquímica i Biologia Molecular Universitat Autònoma de BarcelonaBellaterraBarcelonaSpain Hospital Universitari Parc Taulí Institut d’Investigaciói InnovacióParc Taulí(I3PT-CERCA)Universitat Autònoma de BarcelonaSabadellSpain

Amyloid fibrils are highly organized protein or peptide aggregates,often characterized by a distinctive supramolecular cross-β-sheet *** formation and accumulation of these structures have been traditionally associated with neural or systemic human diseases,such as Alzheimer’s disease,Parkinson’s disease,type-2 diabetes,or amyotrophic lateral sclerosis(Wei et al.,2017;Wittung-Stafshede,2023).

关键词： structure amyloid

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Chemotherapy for gastric cancer

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World Journal of Gastroenterology 2006年第2期12卷 204-213页

作者： javier Sastre Jose Angel García-Saenz Eduardo d.az-Rubio Servicio de Oncologia Médica HCU San Carlosc/Martín Lagos s/n 28040 MadridSpain Servicio de Oncologia Médica HCU San Carlosc/Martía Lagos s/n 28040 MadridSpain

Metastatic gastric cancer remains a non-curative disease. Palliative chemotherapy has been demonstrated to prolong survival without quality of life compromise. Many single-agents and combinations have been confirmed to be active in the treatment of metastatic disease. Objective response rates ranged from 10-30% for single-agent therapy and 30-60% for polychemotherapy. Results of phase Ⅱ and Ⅲ studies are reviewed in this paper as well as the potential efficacy of new drugs. For patients with localized disease, the role of adjuvant and neoadjuvant chemotherapy and radiation therapy is discussed. Most studies on adjuvant chemotherapy failed to demonstrate a survival advantage, and therefore, it is not considerecl as standard treatment in most centres. Adjuvant immunochemotherapy has been developed fundamentally in Korea and Japan. A meta-analysis of phase Ⅲ trials with OK-432 suggested that immunochemotherapy may improve survival of patients with curatively resected gastric cancer. Based on the results of US Intergroup 0116 study, postoperative chemoradiation has been accepted as standard care in patients with resected gastric cancer in North America. However, the results are somewhat confounded by the fact that patients underwent less than a recommended d1 lymph node dissection and the pattern of recurrence suggested a positive effect derived from local radiotherapy without any effect on micrometastatic disease. Neoadjuvant chemotherapy or chemoradiation therapy remains experimental, but several phase Ⅱ studies are showing promising results. Phase Ⅲ trials are needed.

关键词： Gastric cancer Chemotherapy Adjuvant treatment

Interaction network between frugivorous birds and zoochorous plants in cloud forest riparian strips immersed in anthropic landscapes

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Avian Research 2022年第3期13卷 311-320页

作者： Omar A.Hernández-dávila javier Laborde Vinicio J.Sosa Cecilia d.az-Castelazo Instituto de Ecología A.C.Red de Ecología FunctionalCarretera Antigua a CoatepecNo.351El HayaXalapaVeracruz C.P91073Mexico Instituto de Ecología A.C.Red de Interacciones Multitr oficasCarretera Antigua a CoatepecNo.351El HayaXalapaVer.C.P91073Mexico

Worldwide,tropical montane cloud forest is one of the most important and biodiverse ecosystems;however,it is also one of those most threatened by anthropic *** activities lead to a fragmented,deforested landscape with narrow riparian forest strips immersed in an agricultural matrix dominated by ***,we characterize the interaction network between frugivorous birds and zoochorous plants in riparian strips of cloud forest in deforested landscapes of Central Veracruz,*** characterize the network of this mutualistic interaction,we estimated network-and species-level metrics using the Bipartite R ***,modularity and robustness were used to describe network *** measures of degree,closeness,betweenness centrality and their relative contribution to nestedness were used to determine the importance of each bird/plant species to the network’s *** interaction network has 24 species of birds and 30 species of plants,with low connectance(0.11),low nestedness(11.53),and intermediate but not significant modularity(0.49).The bird species most important to network stability were Chlorospingus flavopectus,Myadestes occidentalis,and Catharus *** most important plants were Conostegia xalapensis,***,and Rubus *** robustness varied from 0.36 to 0.86 and its stability is compromised when species of birds or plants with the highest values of centrality are removed,with plant removal more *** strips of cloud forest crossing deforested areas maintain a relatively rich set of birds that disperse the seeds of many forest plants,thus they are crucial to the preservation of this mutualistic network in anthropic *** stability is severely undermined by the loss of any of the few species—whether birds or plants—with high centrality *** most important plants for this stability are pioneer tree and shrub species that provide food for several bird species,and they

关键词： Frugivory Keystone species Riparian corridors Seed dispersal Vegetation corridors

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Should capecitabine replace 5-fluorouracil in the first-line treatment of metastatic colorectal cancer?

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World Journal of Gastroenterology 2014年第20期20卷 6092-6101页

作者： Carlos Aguado Beatriz García-Paredes Miguel Jhonatan Sotelo javier Sastre Eduardo d.az-Rubio department of Medical Oncology Hospital Clínico San Carlos 28040 Madrid Spain

Fluoropyrimidines play a central role in the first-line treatment of metastatic colorectal cancer. Our aim was to review whether capecitabine was a safer, non-inferior, economically superior and more convenient alternative to 5-fluorouracil. Capecitabine has previously been compared to 5-fluorouracil-either as a monotherapy or in combination with oxaliplatin, irinotecan, or biological drugs-and has been found to have comparable efficacy and safety profiles. Furthermore, pharmacoeconomic data and patients’ preferences for oral chemotherapy further favor capecitabine. Therefore, capecitabine appears to be an effective and safe alternative to fluorouracil in the first-line treatment of metastatic colorectal cancer.

关键词： Capecitabine 5-Fluorouracil Metastatic colorectal cancer

Role of cetuximab in first-line treatment of metastatic colorectal cancer

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World Journal of Gastroenterology 2014年第15期20卷 4208-4219页

作者： Miguel Jhonatan Sotelo Beatriz García-Paredes Carlos Aguado javier Sastre Eduardo d.az-Rubio Center affiliate to the "Red Temática de Investigación Cooperativa (Rd12/0036/006)" Instituto Carlos ⅢSpanish Ministry of Economy and Competitivity. Oncology DepartmentHospital Clínico San Carlos28040 MadridSpain department of Medicine School of MedicineUniversidad Complutense de Madrid28040 MadridSpain

The treatment of metastatic colorectal cancer(mCRC)has evolved considerably in the last decade,currently allowing most mCRC patients to live more than two *** antibodies targeting the epidermal growth factor receptor(EGFR)and vascular endothelial growth factor play an important role in the current treatment of these ***,only antibodies directed against EGFR have a predictive marker of response,which is the mutation status of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS).Cetuximab has been shown to be effective in patients with KRAS wild-type *** CRYSTAL study showed that adding cetuximab to FOLFIRI(regimen of irinotecan,infusional fluorouracil and leucovorin)significantly improved results in the first-line treatment of KRAS wildtype ***,results that evaluate the efficacy of cetuximab in combination with oxaliplatin-based chemotherapy in this setting are *** the other hand,recent advances in the management of colorectal liver metastases have improved survival in these *** cetuximab to standard chemotherapy increases the response rate in patients with wild-type KRAS and can thus increase the resectability rate of liver metastases in this group of *** this paper we review the different studies assessing the efficacy of cetuximab in the first-line treatment of mCRC.

关键词： Cetuximab First-line Metastatic colorectal cancer Colorectal liver metastases Elderly patients

Evaluation of redox-sensitive metals in marine surface sediments influenced by the oxygen minimum zone of the Humboldt Current System, Northern Chile

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International Journal of Sediment Research 2019年第2期34卷 178-190页

作者： Alexis Castillo Jorge Valdés Abdel Sifeddine Sue-Ellen Vega javier d.az-Ochoa Yery Marambio Phd Program in Applied Sciences Mention Marine Coastal Systems Faculty of Marine Sciences and Biological Resources University of Antofagasta Laboratory of Sedimentology and Palaeoenvironments Alexander von Humboldt InstituteFaculty of Marine Sciences and Biological Resources University of Antofagasta International Joint Laboratory PALEOTRACES (Research Institute for development Federal Fluminense University University of Antofagasta Peruvian University Cayetano Heredia) Network for Extreme Environments Research (University of Antofagasta University of the Frontera University of Magallanes) department of Geochemistry Federal Fluminense University IRd-Sorbonne University (UPMC CNRS-MNHN) department of Sciences and Natural Resources Faculty of SciencesUniversity of Magallanes

Upwelling coastal systems can be used to understand how dissolved oxygen and biological productivity control the accumulation of redox-sensitive metals in marine *** aluminium(Al),cadmium(Cd),iron(Fe),nickel(Ni),molybdenum(Mo),vanadium(V),total organic carbon(TOC),total nitrogen(TN)and total sulfur(TS)contents in surficial sediment collected from different water depths(30,70,and 120 m)in three northern Chilean bays influenced by coastal upwelling and oxygen minimum zones(OMZs)were *** component analysis(PCA),cluster analysis,and Spearman’s rank correlation were used to identify the mechanisms responsible for the redox-sensitive metal *** content of redox-sensitive metals and organic components in sediment increased with increasing water column depth,whereas lithogenic metals *** the Mejillones del Sur and Caldera bays,the enrichment factors of the redox-sensitive metals showed enrichment for all metals with *** Cd and V enrichments are mainly the product of biogenic flow to the seabed,and the Mo and Ni enrichments are due to preservation under low subsurface oxygen *** reduction is not an important mechanism in the accumulation of redox-sensitive metals in the sediment of the three *** PCA showed that the behaviors of the redox-sensitive metals and organic components reflect differences in the effects of the OMZ in sediment along the coast of northern Chile,with a more intense OMZ in Mejillones del Sur bay and weaker OMZs in Caldera and Inglesa ***,the high degree of enrichment in redox-sensitive metals in Caldera Bay can be attributed to the intense activity of the mining industry near the bay,a situation that produces geochemical behavior similar to that observed in Mejillones del Sur Bay.

关键词： Redox sensitive-metals Atacama desert Enrichment factor Mejillones del Sur Bay Caldera Bay system PCA

Update in lean metabolic dysfunction-associated steatotic liver disease

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World Journal of Hepatology 2024年第3期16卷 452-464页

作者： Karina Sato-Espinoza Perapa Chotiprasidhi Mariella R Huaman javier d.az-Ferrer division of Gastroenterology and Hepatology Department of MedicineMayo ClinicRochesterMN 55902United States Obesity and Metabolic Center for Obesity and Metabolic HealthLima 02002LimaPeru Hepatology Service Department of Digestive DiseasesHospital Nacional Edgardo Rebagliati MartinsLima 02002LimaPeru Medicine Faculty Universidad San Martin de PorresLima 02002LimaPeru Gastroenterology Service Clinica InternacionalLima 02002LimaPeru

BACKGROUNd A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLd)and metabolic dysfunction-associated fatty liver disease(MAFLd).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLd),which includes cardiometabolic criteria in *** condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase *** patients account for approximately 10%-15%of the MASLd ***,the pathogenesis is complex and is not well *** To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLd patients and provide an interpretation of these new *** We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLd,MAFLd,or MASLd *** include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian *** We include 85 studies in our *** findings revealed that,for lean NAFLd patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic *** risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean *** non-invasive tools,Fibrosis-4 index outperformed the NAFLd fibrosis score in lean *** modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser ***,lean NAFLd patients ex

关键词： Lean Non-obese Non-alcoholic fatty liver disease Metabolic dysfunction-associated fatty liver disease Metabolic dysfunction-associated steatotic liver disease Guidelines diagnosis Management Pathogenesis Treatment

MicroRNA-630:A promising avenue for alleviating inflammation in diabetic kidney disease

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World Journal of diabetes 2024年第7期15卷 1398-1403页

作者： javier donate-Correa Ainhoa González-Luis Jésica d.az-Vera Juan Ramón Hernandez-Fernaud Research Unit University Hospital Nuestra Señora de Candelaria(UHNSC)Santa Cruz de Tenerife 38010Spain department of Biochemistry MicrobiologyCell Biology and GeneticsInstituto de Tecnologías BiomédicasUniversidad de La LagunaSanta Cruz de Tenerife 38000Spain

diabetic kidney disease(dKd)is one of the complications of diabetes,affecting millions of people *** relentless progression of this condition can lead to kidney failure,requiring life-altering interventions such as dialysis or *** evidence suggests that immunologic and inflammatory elements play an important role in initiating and perpetuating the damage inflicted on renal tissues,exacerbating the decline in organ ***-like receptors(TLRs)are a family of receptors that play a role in the activation of the innate immune system by the recognition of pathogen-associated molecular *** data from in vitro and in vivo studies have highlighted the critical role of TLRs,mainly TLR2 and TLR4,in the pathogenesis of *** the diabetic milieu,these TLRs recognize diabetic-associated molecular signals,triggering a proinflammatory cascade that initiates and perpetuates inflammation and fibrogenesis in the diabetic *** non-traditional strategies targeting TLR signaling with potential therapeutic implications in dKd have been *** of these approaches is the use of microRNAs,small non-coding RNAs that can regulate gene *** editorial comments on the results of this approach carried out in a rat model of diabetes by Wu et al,published in this issue of the World Journal of *** results of the experimental study by Wu et al shows that microRNA-630 decreased levels compared to non-diabetic ***,microRNA-630 exerted anti-inflammatory effects in the kidneys of diabetic rats through the modulation of *** findings indicate that the microRNA-630/TLR4 axis might represent a pathological mechanism of dKd and a potential therapeutic target capable of curbing the destructive inflammation characteristic of dKd.

关键词： diabetes diabetic kidney disease Inflammation Toll-like receptor 4 microRNA-630

Whole-genome amplification/preimplantation genetic testing for propionic acidemia of successful pregnancy in an obligate carrier Mexican couple:A case report

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World Journal of Clinical Cases 2021年第29期9卷 8797-8803页

作者： Adina Neumann Miguel Angel Alcantara-Ortigoza Ariadna González-del Angel Nestor Alejandro Zarate d.az javier Sam Santana Leonardo M Porchia Esther López-Bayghen Laboratorio de Investigación y diagnóstico Molecular IngenesMexico City 05320Mexico Laboratorio de Biología Molecular Subdirección de Investigación MédicaInstituto Nacional de PediatríaMexico City 04530Mexico dNA-GEN S.C.Centro de Alta Especialidad en Genética Humana Mexico City 14070Mexico Investigación Clínica IngenesPuebla 72820Mexico departamento de Toxicología Centro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalMexico City 07360Mexico

BACKGROUNd Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities'current methodology for screening,which focuses on the detecting multiple genetic disorders at ***,we report the successful application of a low-cost and fast preimplantation genetic testing for monogenic/single gene defects(PGT-M)approach for detecting propionic acidemia(PA)in embryos obtained from a confirmed heterozygous propionyl-CoA carboxylase alpha subunit(PCCA)*** SUMMARY A fertile 32-years old Mexican couple with denied consanguinity sought antenatal genetic *** were suspected obligate PA carriers due to a previous deceased PA male newborn with an unknown PCCA/propionyl-CoA carboxylase beta subunit(PCCB)***-Generation Sequencing revealed a heterozygous genotype for a pathogenic PCCA variant(c.2041-1G>T,ClinVar:RCV-000802701.1;dbSNP:rs1367867218)in both *** couple requested in vitro fertilization(IVF)and PGT-M for *** IVF,12 oocytes were collected and fertilized,of which two resulted in high-quality *** biopsies and Whole Genome Amplification by a fragmentation/amplification-based method were performed and revealed that the two embryos were *** polymerase chain reaction and further Sanger sequencing of the exon-intron borders revealed a wild-type PCCA male embryo and a heterozygous c.2041-1G>T female *** embryos were transferred,resulting in a clinical pregnancy and the delivery of a healthy male newborn(38 wk,weight:4080 g,length:49 cm,APGAR 9/9).The absence of PA was confirmed by expanded newborn *** We show that using PGT-M with Whole Genome Amplification templates,coupled with IVF,can reduce the transmission of a pathogenic variant of the PCCA gene.

关键词： Propionic acidemia Autosomal recessive Propionyl-CoA carboxylase alpha subunit(PCCA)gene Preimplantation genetic testing Next-generation sequencing Embryo transfer