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Design and redesign journey of a drug for transthyretin amyloidosis

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Neural Regeneration Research 2025年第4期20卷 1096-1097页

作者： Francisca pinheiro Salvador Ventura Institut de Biotecnologia i Biomedicina Departament de Bioquímica i Biologia MolecularUniversitat Autònoma de BarcelonaBellaterraSpain

The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as ***(TTR)is one of the>30 amyloidogenic proteins identified to date and is associated with a group of highly debilitating and life-threatening disorders called TTR amyloidosis(ATTR).ATTR comprises senile systemic amyloidosis,which is linked to wild-type(WT)TTR aggregation,and hereditary ATTR,a dominantly inherited disorder caused by the deposition of one of over 130 TTR genetic *** systemic amyloidosis is a prevalent age-related amyloidosis,affecting up to 25%of the population over 80 years of age,and is characterized by the build-up of TTR fibrils in the *** hereditary ATTR,the clinical presentation is highly heterogeneous,primarily affecting the peripheral nervous system(familial amyloid polyneuropathy-FAP)or the heart(familial amyloid cardiomyopathy).In rare cases,aggregation develops in the central nervous system,giving rise to a phenotype known as familial leptomeningeal amyloidosis(Carroll et al.,2022).

关键词： amyloid aggregation senile

Serological surveillance for SARS-CoV-2 antibodies among students,faculty and staff within a large university system during the pandemic

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World Journal of Virology 2025年第1期14卷 99-107页

作者： Marcos G pinheiro Gabriela G O Alves Maria Eduarda R Conde Sofia L Costa Regina C S Sant’Anna Isa M F Antunes Mônica C Carneiro Fabio S Ronzei Julia C Scaffo Felipe R pinheiro lialyz S Andre Helvecio C Povoa Valéria T Baltar Fabíola Giordani Eduarda S Hemerly Gisele C Alexandre Karla C de Paula Márcio Watanabe Antonio Claudio L da Nóbrega Jackeline Christiane P Lobato Fabio Aguiar-Alves Laboratory of Molecular Epidemiology and Biotechnology Rodolpho Albino University LaboratoryFluminense Federal UniversityNiterói 24241000Rio de JaneiroBrazil Estácio de SáUniversity Nova Friburgo 28611135Rio de JaneiroBrazil Pathology Program Medicine schoolFluminense Federal UniversityNiterói 24070090Rio de JaneiroBrazil Department of Pharmaceutical Sciences Lloyd L.Gregory School of PharmacyPalm Beach Atlantic UniversityWest Palm BeachFL 33401United States Health Institute of Nova Friburgo Fluminense Federal UniversityNova Friburgo 28613001Rio de JaneiroBrazil Department of Epidemiology and Biostatistics Institute of Collective Health(ISC)Fluminense Federal UniversityNiterói 24033900Rio de JaneiroBrazil Institute of Physical Education Fluminense Federal UniversityNiterói 24020005Rio de JaneiroBrazil Department of Statistics Fluminense Federal UniversityNiterói 24210200Rio de JaneiroBrazil Department of Physiology and Pharmacology Fluminense Federal UniversityNiterói 24210130Rio de JaneiroBrazil

BACKGROUND At the end of December 2019,the world faced severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2),which led to the outbreak of coronavirus disease 2019(COVID-19),associated with respiratory *** virus has shown significant challenges,especially for senior citizens,patients with other underlying illnesses,or those with a sedentary *** tests conducted early on have helped identify how the virus is transmitted and how to curb its *** study hypothesis was that the rapid serological test for SARS-CoV-2 antibodies could indicate the immunoreactive profile during the COVID-19 pandemic in a university *** To conduct active surveillance for serological expression of anti-SARS-CoV-2 antibodies in individuals within a university setting during the COVID-19 *** This sectional study by convenience sampling was conducted in a large university in Niteroi-RJ,Brazil,from March 2021 to July *** study population consisted of students,faculty,and administrative staff employed by the university.A total of 3433 faculty members,60703 students,and 3812 administrative staff were invited to *** were gathered through rapid serological tests to detect immunoglobulin(Ig)M and IgG against ***χ²or Fisher's exact test was used to conduct statistical analysis.A 0.20 significance level was adopted for variable selection in a multiple logistic regression model to evaluate *** A total of 1648 individuals were enrolled in the *** proportion of COVID-19 positivity was 164/1648(9.8%).The adjusted logistic model indicate a positive association between the expression of IgM or IgG and age[odds ratio(OR)=1.16,95%CI:1.02-1.31](Plikelihood of sho

关键词： Serological surveillance SARS-CoV-2 antibodies COVID-19 Serological rapid test Risk factors for COVID-19

Mitochondrial GPX1 silencing triggers differential photosynthesis impairment in response to salinity in rice plants

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Journal of Integrative Plant Biology 2016年第8期58卷 737-748页

作者： Yugo lima-Melo Fabricio E.L.Carvalho Márcio O.Martins Gisele Passaia Rachel H.V.Sousa Milton C.lima Neto Márcia Margis-pinheiro Joaquim A.G.Silveira Department of Biochemistry and Molecular Biology Federal University of Ceará Department of Genetics Federal University of Rio Grande do Sul

The physiological role of plant mitochondrial glutathione peroxidases is scarcely known. This study attempted to elucidate the role of a rice mitochondrial isoform（GPX1） in photosynthesis under normal growth and salinity conditions. GPX1 knockdown rice lines（GPX1s） were tested in absence and presence of 100 mM NaCl for 6 *** reduction of GPX1 s line under non-stressful conditions, compared with non-transformed（NT） plants occurred in parallel to increased H_2O_2 and decreased GSH contents. These changes occurred concurrently with photosynthesis impairment, particularly in Calvin cycle＇s reactions, since photochemical efficiency did not ***, GPX1 silencing and downstream molecular/metabolic changes modulated photosynthesis differentially. In contrast, salinity induced reduction in both phases of photosynthesis, which were more impaired in silenced *** changes were associated with root morphology alterations but not shoot growth. Both studied lines displayed increased GPX activity but H_2O_2 content did not change in response to salinity. Transformed plants exhibited lower photorespiration, water use efficiency and root growth, indicating that GPX1 could be important to salt tolerance. Growth reduction of GPX1 s line might be related to photosynthesis impairment, which in turn could have involved a cross talk mechanism between mitochondria and chloroplast originated from redox changes due to GPX1 deficiency.

关键词： CO2 assimilation glutathione peroxidase Oryza sativa photochemistry redox homeostasis

Inducing α-synuclein compaction: a new strategy for inhibiting α-synuclein aggregation?

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Neural Regeneration Research 2019年第11期14卷 1897-1898页

作者： Francisca pinheiro Salvador Ventura Institut de Biotecnologia i Biomedicina Universitat Autonoma de BarcelonaBellaterraSpainDepartament de Bioquimica i Biologia MolecularUniversitat Autonoma de BarcelonaBellaterraSpain

Proteins might misfold during translation and folding or even once they are in their native states, due to stochastic fluctuations, destabilizing mutations or cellular stress. Aberrant protein species are usually detected and either refolded or cleared by the protein quality control machinery (Ciechanover and Kwon, 2015). When misfolded protein conformers cannot be degraded, they tend to self-assemble to form aggregates, a characteristic of many neurodegenerative diseases.

关键词： inhibitingα-synuclein aggregation native states protein quality control machinery

Role of nickel-regulated small RNA in modulation of Helicobacter pylori virulence factors

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World Journal of Clinical Cases 2022年第31期10卷 11283-11291页

作者： Fabrício Freire de Melo Hanna Santos Marques Fabian Fellipe Bueno Lemos Marcel Silva Luz Samuel Luca Rocha pinheiro Lorena Sousa de Carvalho Cláudio lima Souza Márcio Vasconcelos Oliveira Institution Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094Brazil Campus Vitória da Conquista Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45083-900Brazil

Helicobacter pylori(***)is a Gram-negative bacterium that infects about half of the world's *** infection prevails by several mechanisms of adaptation of the bacteria and by its virulence factors including the cytotoxin associated antigen A(CagA).CagA is an oncoprotein that is the protagonist of gastric carcinogenesis associated with prolonged *** *** this sense,small regulatory RNAs(sRNAs)are important macromolecules capable of inhibiting and activating gene *** function allows sRNAs to act in adjusting to unstable environmental conditions and in responding to cellular stresses in bacterial *** discoveries have shown that nickelregulated small RNA(NikS)is a post-transcriptional regulator of virulence properties of ***,including the oncoprotein ***,high concentrations of nickel cause the reduction of NikS expression and consequently this increases the levels of *** addition,NikS expression appears to be lower in clinical isolates from patients with gastric cancer when compared to patients *** that in mind,this minireview approaches,in an accessible way,the most important and current aspects about the role of NikS in the control of virulence factors of *** and the potential clinical repercussions of this modulation.

关键词： Helicobacter pylori Small regulatory RNAs Nickel-regulated small RNA Virulence factors Cytotoxin associated antigen A Gastric cancer

Colon and rectal cancer:An emergent public health problem

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World Journal of Gastroenterology 2024年第7期30卷 644-651页

作者： Marina pinheiro David Nascimento Moreira Michele Ghidini LAQV REQUIMTEDepartment of ChemistryFaculty of PharmacyUniversity of Porto4050-313 PortoPortugal Unidade de Saúde Pública Unidade Local de Saúde Barcelos/EsposendeBarcelinhos 4755-069BragaPortugal Medical Oncology Unit Fondazione IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilan 20122Italy

Colorectal cancer ranks third globally,with a high mortality *** the United States,and different countries in Europe,organized population screenings exist and include people between 50 and 74 years of *** screenings have allowed an early diagnosis and consequently an improvement in health *** and rectal cancer(CRC)is a disease of particular interest due to the high global burden associated with it and the role attributed to prevention and early diagnosis in reducing morbidity and *** study is a review of CRC pathology and includes the most recent scientific evidence regarding this pathology,as well as a diagnosis of the epidemiological situation of ***,the recommendation from a public health perspective will be discussed in detail taking into account the context and the most current recommendations.

关键词： Colon and rectal neoplasia Colon and rectal tumor Mortality Morbidity

Stabilisation of estuarine sediments with an alkali-activated cement for deep soil mixing applications

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第4期16卷 1398-1410页

作者： Claver pinheiro Sara Rios António Viana da Fonseca Nuno Cristelo Centre of Physics of Minho and Porto Universities (CF-UM-UP) Azurém CampusUniversity of MinhoGuimarães4800-058Portugal CONSTRUCT-GEO Faculty of EngineeringUniversity of PortoRua Dr.Roberto FriasPortos/n 4200-465Portugal CQ-VR School of Science and TechnologyUniversity of Trás-os-Montes e Alto DouroVila Real5000-801Portugal

In this work,an alternative alkali-activated cement(AAC)made of ladle slag precursor mixed with sodium hydroxide and sodium silicate has been developed to enhance the bearing capacity of estuarine soils in coastal conditions via deep soil mixing(DSM).The AAC was optimized to use a low reactivity precursor(ladle slag)and to deal with a contaminated high-water content natural sediment cured under *** material performance was analysed by comparison to a mixture made with Portland cement and cured in the same *** and unconfined compressive strength tests as well as seismic waves measurements after 3-,7-,14-and 28-d curing were performed to obtain a relationship between elastic stiffness and strength with curing time for both ***,the AAC mix demonstrated superior strength results,exhibiting almost double flexural and compressive strengths after 28 d compared to the Portland cement *** AAC mix also showed a higher rate of stiffness increase than the Portland cement mix,which has a higher initial stiffness at young ages but lower stiffness *** analysis confirmed that the proposed AAC could effectively immobilise any contaminants from soil or *** effect of curing under stress was analysed in triaxial compression tests and found to be insignificant,indicating that laboratory data obtained without stress curing can represent the material's behaviour in a DSM column,which will cure under the weight of the column.

关键词： Alkaline-activation Steel slag Submerged curing Seismic wave measurements Leachate analysis Curing under stress

Structural optimization of patient-specific temporomandibular joint replacement implants for additive manufacturing:novel metrics for safety evaluation and biomechanical performance

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Bio-Design and Manufacturing 2022年第2期5卷 333-347页

作者： Manuel pinheiro Anouar Krairi Robin Willaert Maria C.Costa Wim Van Paepegem Mechanics of Materials and Structures(MMS) Ghent UniversityGhentBelgium Materials Innovation Institute(M2i) DelftThe Netherlands Department of Oral and Maxillofacial Surgery University Hospitals Leuven LeuvenBelgium 4 Department of Head and Neck SurgeryGhent University HospitalGhentBelgium

Total temporomandibular joint(TMJ)replacement is recommended only when there is irreversible damage to the joint and no conservative treatment can provide functional *** stock and custom-made TMJ implants have been made available;however,retrospective and comparative studies were unable to find significant differences between the two types of *** introduction of additive manufacturing(AM)techniques in medical practice allows for a greater freedom of design and a higher degree of device *** combination of AM with structural optimisation may streamline development and provide the key for fabricating biomechanic ally enhanced TMJ *** this study,structural optimis ation techniques were applied to develop and numerically validate a patient-specific TMJ *** biomechanical behaviour of each intermediate TMJ design was assessed under four different nominal and maximum biting tasks using finite element *** addition,a new set of metrics were proposed to compare each design regarding biomechanical performance and implant *** results suggest that 55-82%of the natural/intact strain patterns can be recovered with the finally selected TMJ *** represents an increase of 15%in biomechanical performance for incisor biting,15%for right molar biting,17%for left molar biting and a decrease of 2%for left group biting compared with the initial *** results also suggest that load transfer at the proximal ramus reduces the implant’s impact on the mandible’s strain ***,structural optimisation allows for a volume reduction of up to 44%with a minimum loss of implant safety and biomechanical performance.

关键词： Temporomandibular joint Additive manufacturing Implant safety Biomechanical performance Finite element analysis

Complex hepatic outflow reconstruction in domino liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2014年第1期13卷 98-100页

作者： Rafael S pinheiro Quirino Lai Carola Dahrenmoller Jan Lerut Starzl Unit of Abdominal Transplantation University Hospitals Saint Luc Université Catholique Louvain UCL Brussels Belgium Department of Gastroenterology So Paulo University School of Medicine So Paulo Brazil

Domino liver transplantation has been accepted as a safe procedure to further expand the organ donor pool. The most important technical challenge of the procedure resides in restoring a proper hepatic venous allograft outflow in the familial amyloidotic polyneuropathy-liver recipient. To overcome this issue, combined techniques were used to perform an innovative outflow reconstruction. A domino liver transplantation was successfully performed with reconstruction of complex venous outflow. The inferior vena cava sparing hepatectomy technique in the familial amyloidotic polyneuropathy-donor was used to cut the hepatic vein to the liver parenchyma. To overcome this issue the venous outflow tract was reconstructed using a longitudinally opened iliac vein graft from a post-mortem donor to create a new outflow tract using a diamond patch between the right and middle/left hepatic veins.

关键词： liver transplantation intraoperative anatomy hepatic vein