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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

Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet

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World Journal of Gastroenterology 2024年第11期30卷 1545-1555页

作者： Juan Pablo Stefanolo Verónica Segura Martina Grizzuti Abel Heredia Isabel Comino ana Florencia Costa Roberto Puebla María Paz Temprano Sonia Isabel Niveloni Gabriel de Diego María E Oregui Edgardo Gustavo Smecuol Mauricio C de Marzi Elena F Verdú carolina Sousa Julio César Bai Small Bowel Section Department of MedicineGastroenterology Hospital of Buenos Aires“Dr.C.Bonorino Udaondo”Buenos Aires 1264Argentina Department of Microbiology and Parasitology Faculty of PharmacyUniversity of SevilleSeville 41080Spain Department of Medicine Dr.C.Bonorino Udaondo Gastroenterology HospitalBuenos Aires 1264Argentina Basic and Applied Research Group in Immunology and Bioactives(GIBAIB) Institute of Ecology and Sustainable Development(INEDES)National University of LujanLuján 6700Buenos AiresArgentina Department of Medicine Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamilton L8S 4L8OntarioCanada Facultad de Medicina Universidad del SalvadorBuenos Aires C1051ABBArgentina

BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant *** To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual *** This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term *** a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or *** endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of *** samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and *** Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol ***,628/640(98.1%)stool samples were *** was undetectable(0.32μg/g)to potentially cause mucosal *** GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in ***-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP *** with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific *** This exploratory study conducted in a real-life setting revealed high adherence to the *** AN-PEP treatment did not significantly reduce the overall GIP stool ***,given the observation of a significantly lower prevale

关键词： Celiac disease Aspergillus niger prolyl endoprotease Gluten immunogenic peptides Trial Symptoms Real-life trial

围术期神经肌肉阻滞的管理:欧洲麻醉和重症监护学会临床指南

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中华麻醉学杂志 2024年第6期44卷 641-656页

作者： Thomas Fuchs-Buder carolina S.Romero Heidrun Lewald Massimo Lamperti Arash Afshari ana-Marjia Hristovska Denis Schmartz Jochen Hinkelbein Dan Longrois Maria Popp Hans Dde Boer Massimiliano Sorbello Radmilo Jankovic Peter Kranke 法国南锡大学医学院附属医院麻醉学、重症监护与围术期医学科法国南锡54000 巴伦西亚大学综合医院麻醉与重症监护科西班牙巴伦西亚46014 慕尼黑工业大学麻醉学与重症监护科德国慕尼黑80333 克利夫兰阿布扎比诊所麻醉学研究所阿联酋阿布扎比31250 哥本哈根大学医院小儿和产科麻醉科丹麦哥本哈根2100 哥本哈根大学医院麻醉学与重症监护科丹麦赫维德2650 布鲁塞尔自由大学Erasme医院麻醉科比利时布鲁塞尔1070 科隆大学医院麻醉学与重症监护科德国科隆50937 巴黎大学附属比查特克劳德伯纳德医院麻醉学与重症监护医学科法国巴黎75018 维尔茨堡大学医院麻醉学、危重病医学、急诊医学和疼痛医学科德国维尔茨堡97080 格罗宁根大学医院麻醉学、疼痛医学与程序性镇静与镇痛科荷兰格罗宁根9713 GZ 卡坦尼亚大学医院麻醉与重症监护科意大利卡坦尼亚95123 尼什大学医学院尼什临床中心麻醉学与重症治疗科塞尔维亚尼什18000

近来的研究表明,由于围术期神经肌肉阻滞管理不当,肌肉松弛药(肌松药)残留阻滞及其术后并发症的发生率居高不下。需要重视神经肌肉功能监测仪、肌松药及其拮抗剂的合理应用,以利于改善神经肌肉阻滞管理。欧洲麻醉和重症监护学会(Europea... 详细信息

近来的研究表明,由于围术期神经肌肉阻滞管理不当,肌肉松弛药(肌松药)残留阻滞及其术后并发症的发生率居高不下。需要重视神经肌肉功能监测仪、肌松药及其拮抗剂的合理应用,以利于改善神经肌肉阻滞管理。欧洲麻醉和重症监护学会(European Society of anaesthesiology and Intensive Care,ESAIC)首次发布围术期神经肌肉阻滞管理临床指南,旨在为临床医生提供最佳医疗管理的循证建议,以提高围术期患者安全。本指南主要聚焦在3个临床问题:肌松药是否有助于成人气管插管?神经肌肉阻滞深度是否影响腹部手术患者的预后?肌松药残留阻滞的诊断和治疗策略有哪些?根据PICO原则(患者、干预、对照、结局;patient,intervention,comparator,outcome;PICO)构建临床问题并进行文献检索。初始纳入的临床研究为24 000篇,采用逐步筛选策略,最终临床研究88篇纳入指南分析。应用GRADE方法学(Grading of Recommendations,Assessment,Development and Evaluation,GRADE)对结局指标证据、质量等级进行评价。运用两轮德尔菲法收集专家组建议并形成统一推荐:R1推荐应用肌松药辅助气管插管(1A)。R2推荐应用肌松药以减少气管插管导致的咽部和(或)喉部损伤(1C)。R3推荐在快速顺序诱导插管(rapid sequence induction intubation,RSII)时使用短效肌松药,例如琥珀胆碱1 mg/kg或罗库溴铵0.9~1.2 mg/kg(1B)。R4推荐在需要改善外科手术条件时,加深神经肌肉阻滞深度(1B)。R5尚无足够的证据推荐深度神经肌肉阻滞可减轻术后疼痛或降低围术期并发症的发生率(2C)。R6推荐在拇内收肌处刺激尺神经,定量监测神经肌肉阻滞深度以排除肌松药残留阻滞(1B)。R7推荐应用舒更葡糖钠逆转甾体类肌松药(罗库溴铵、维库溴铵)诱导的深、中及浅度神经肌肉阻滞(1A)。R8推荐在使用新斯的明前,TOFr自行恢复至>0.2,并继续定量监测神经肌肉功能,直至TOFr超过0.9(1C)。

关键词：神经肌肉阻滞神经肌肉功能肌松药临床指南罗库溴铵琥珀胆碱外科手术定量监测

Early detection of tomato bacterial canker by reflectance indices

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Information Processing in Agriculture 2022年第2期9卷 184-194页

作者： Gabriela Cordon carolina Andrade Lucia Barbara ana Maria Romero Universidad de Buenos Aires Consejo Nacional de Investigaciones Cientı´ficas y Te´cnicasInstituto de Investigaciones Fisiolo´gicas y Ecolo´gicas Vinculadas a la Agricultura(IFEVA)Facultad de Agronomı´aBuenos AiresArgentina Universidad de Buenos Aires Facultad de Agronomı´aA´rea de Educacio´n AgropecuariaBuenos AiresArgentina Universidad de Buenos Aires Facultad de Agronomı´aCa´tedra de Fitopatologı´aBuenos AiresArgentina

Early detection of infected asymptomatic plants could prevent the dissemination of tomatobacterial canker throughout the crop and, thus, reduce associated economic losses. Reflectance spectroscopy has been proposed for the detection of diseases in plants, mainlycaused by foliar fungal pathogens. In contrast, bacterial canker is a vascular disease thatdoes not produce visible foliar symptoms until it is too late to avoid contagion to otherplants. The effects of the disease on the conductivity of the xylem have an impact onthe water content of the leaves;initially, a subtle effect that cannot be assessed with thenaked eye but can be evaluated by reflectance spectroscopy. The objective of this workwas to identify indices, based on the reflectance spectral signature of the plants, for thedetection of tomato plants affected by bacterial canker prior to the appearance of symptoms. To verify that the proposed methodology is applicable to a broad range of tomatogenotypes, two experiments were carried out with different tomato cultivars grown in potsand another on the ground in a greenhouse. Plants were inoculated with the pathogenicbacteria and the reflectance spectrum of the apical leaflet of two leaves per plant wereobtained before symptoms expression;several spectral indices were calculated from thereflectance spectra. Three indices, of the shortwave-infrared zone, allowed the detectionof bacterial canker inoculated plants in a fast and non-destructive way, up to one weekbefore symptoms were visible: Normalized Difference Water Index (NDWI), Simple Ratioof Water Index (SRWI) and Water Index 1 180 (WI1180). Our research demonstrates, forthe first time, the usefulness of spectral indices sensitive to water content for the identifi-cation of diseased plants. These indices arise as a promising tool for the early detection ofvascular plant diseases, that could be integrated into sustainable management plans.

关键词： Clavibacter michiganensis subsp. michiganensis Bacterial wilt Reflectance indices Solanum lycopersicum L

The peptide fraction of Bothrops jararaca snake venom induces toxicological effects on the male reproductive system after local envenomation in mice

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BIOCELL 2023年第2期47卷 289-295页

作者： CARLOS ALBERTO-SILVA ana carolina DE ARAUJO RODRIGO SIMÃO BONFIM JOYCE MEIRE GILIO Natural and Humanities Sciences Center Experimental Morphophysiology LaboratoryFederal University of ABC(UFABC)São Bernardo do Campo09606-070Brazil Departamento de Biofísica Universidade Federal de São PauloSão Paulo04023-062Brazil

Bothrops envenomation is complex and provokes prominent local tissue damage and systemic disturbances,but little is known about their effects on the male reproductive *** intratesticular injection,the bioactive peptide fraction(Bj-PF)obtained from Bothrops jararaca snake venom changes the structure of different stages of the seminiferous epithelium cycle in adult *** the first time,we investigated whether local envenomation of Bj-PF induces toxicological effects on the male reproductive system,particularly on the seminiferous epithelium and Sertoli *** adult mice were treated with 0.24 ***^(-1) by intramuscular(i.m.)injection for 24 *** testes samples were collected for morphological and morphometric *** toxicological effects of Bj-PF were also analyzed on mitochondrial metabolism and nitrite(NO2)production in 15P-1 Sertoli cell ***-PF changed the structure and function of the seminiferous epithelium,particularly the disruption of the epithelium and the presence of degenerated germ cells in the adluminal compartment,but there were no alterations in the basal ***-PF increased the thickness of the seminiferous epithelium and decreased the lumen diameter of the *** histological assessment of the degree of tubule degeneration revealed that Bj-PF also increased the number of hypospermatogenic tubules compared to ***-PF reduced NO2 levels in 15P-1 Sertoli cells without changing the mitochondrial ***,the fact that Bj-PF alters the structure and function of the seminiferous epithelium suggests that bioactive peptides found in *** snake venom can have toxicological effects on the reproductive systems of affected male mice,providing new insight into the biological characteristics of snake venom and therapeutic strategies for envenomation inflammation.

关键词： Snake venom Bothrops jararaca Reproductive toxicology Seminiferous epithelium

Comparison of grain protein profiles of Brazilian cowpea (Vigna unguiculata) cultivars based on principal component analysis

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Food Production, Processing and Nutrition 2022年第1期4卷 172-182页

作者： Tuany Camila Honaiser Gabriela Barbosa Rossi Maurisrael de Moura Rocha ana carolina Maisonnave Arisi Food Science and Technology Department CAL CCA UFSCFederal University of Santa CatarinaRod.Admar GonzagaFlorianópolisSanta Catarina134688034-001Brazil Embrapa Meio-Norte Caixa Postal 001TeresinaPiauí64008-780Brazil

This study aims to compare the grain protein profile of four Brazilian cowpea cultivars (BRS Aracê, BRS Itaim, BRS Pajeú, and BRS Xiquexique) by two-dimensional electrophoresis (2-DE) and principal component analysis (PCA). 2-DE efficiently separate cowpea protein profiles, showing high homogeneity among the four cultivars. In addition, the principal component analysis indicated that there is a difference in abundance of proteins among the cultivars. The cultivars BRS Aracê and BRS Xiquexique, both biofortified in iron and zinc, were separated from the cultivars BRS Itaim and BRS Pajeú. These results demonstrate that protein profiles can be used to discriminate cowpea varieties.

关键词： Vigna 2-DE PCA Legumes

Development of a Ready-to-Use PSMA-11 Kit Formulation and Biological Evaluation of Binding Affinity

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Advances in Molecular Imaging 2024年第2期13卷 7-22页

作者： Maria Renata Valente Brandão Freire Natália Marchesan Bexiga Marco Antonio Stephano João Ezequiel Oliveira Carlos Roberto Jorge Soares ana Cláudia Camargo Miranda Anna carolina de Alcântara Barbosa Marycel Figols de Barboza Laura Fernanda Garcia Luiz Felipe S. Teixeira Maria Helena Marumo Bellini Natanael Gomes da Silva Luiza Mascarenhas Balieiro Joel Mendes Elaine Bortoleti de Araújo Centro de Radiofarmcia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil Departamento de Tecnologia Farmacutica Faculdade de Cincias Farmacuticas (USP) Cidade Universitria So Paulo Brasil Centro de Biotecnologia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil Departamento de Medicina Nuclear do Hospital Israelita Albert Einstein So Paulo/SP Brasil

Introduction: 68Ga-PSMA-11 is considered the gold standard in detection of micro and oligometastases in advanced prostate cancer, being used for therapeutic planning, as well as, potentially, for evaluating response to treatment. The development of ready-to-use lyophilized kit of PSMA-11 adds quality and safety to the routine use of this radiopharmaceutical and represents a pharmacotechnical challenge as it must preserve the integrity and specificity of the ligand. Methods: PSMA-11 kit formulation was proposed, considering radiolabeling parameters and the preservation of the peptide during the lyophilization process, using mannitol as an excipient. Critical temperature characterization studies were carried out using DSC equipment and the freeze-drying process was developed. The direct radiolabeling conditions were evaluated and standardized using 68Ge/68Ga generator eluate from two different manufacturers (ITG and Eckert & Ziegler). The radiochemical purity was evaluated by TLC and HPLC. Biological evaluation was carried out with lyophilized PSMA-11 to demonstrate the integrity of the peptide and preservation of biological activity after the lyophilization process. Results: Based on critical temperature characterization studies, the freeze-drying cycle was designed to reach a freezing temperature of around −40˚C and primary drying at 2˚C. Using 20 mg of mannitol, an intact and elegant lyophilized cake was obtained. PSMA-11 lyophilized kit was directly labeled with 68Ga eluate from 68Ge/68Ga GMP generators (ITG and Eckert & Ziegler) resulting in % RP > 95% at pH 4.0 to 4.5. The results obtained from in vitro and in vivo biological competition studies confirmed the preservation of PSMA-11 affinity for the receptor after lyophilization. Conclusion: A lyophilized formulation (Kit) of PSMA-11 was successfully obtained, which preserved the integrity and biological activity of the peptide and guaranteed radiolabeling efficiency.

关键词： 68Ga-PSMA-11 Prostate-Specific Membrane Antigen (PSMA) Ready-to-Use Kit GMP-Grade Generators Metastatic Prostate Cancer PET Imaging

Epidemio-toxicological profile of suicide cases:analysis from a forensic unit in Brazil

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Forensic Sciences Research 2022年第4期7卷 643-649页

作者： carolina de Castro Martins Yara Viera Lemos Maycoln Leoni Martins Teodoro ana Paula Drummond-Lage Department of Phsycology Universidade Federal de Minas GeraisBelo HorizonteMGBrazil Department of Forensic Anthropology Polícia Civil de Minas GeraisBelo HorizonteMGBrazil School of Medicine Faculdade de Ciências Médicas de Minas GeraisBelo HorizonteMGBrazil Post-Graduation Department Faculdade de Ciências Médicas de Minas GeraisBelo HorizonteMGBrazil

The suicide phenomenon involves complex interactions between psychological,biological,cultural and socio-environmental *** study aimed to assess the epidemiological and toxicological profiles of officially confirmed suicide *** study was performed using autopsy reports,forensic anthropology examinations and police summaries of all suicide cases that underwent toxicological analysis at an Official Forensic Laboratory(Minas Gerais,Brazil)in 1 *** sample set was composed of 351 suicide victims,predominantly men(70.32%),most of them were adults between 31 and 64 years old(62.11%),with mixed skin colour(48.89%)and low educational level(66.44%).The most common suicide method was hanging(57.79%),followed by intoxication(30.45%).Most victims presented positive toxicological results(56.41%),especially for the presence of medicines(37.6%),illicit drugs(36.3%)and pesticides(26.1%).Our study corroborated previous data that most suicide victims have low educational *** most common toxicological findings were medicines,especially prescription drugs,followed by illicit drugs and *** hope this study contributes to reflections and planning of preventive suicide programmes,considering the described profiles of victims.

关键词： Forensic sciences forensic toxicology forensic medicine forensic anthropology suicide

Impact of chitosan-based nanocarriers on cytoskeleton dynamics:Current status and challenges

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BIOCELL 2022年第4期46卷 885-891页

作者： M.carolina DI SANTO AGUSTINA ALAIMO ana PAULA DOMÍNGUEZ RUBIO OSCAR E.PÉREZ Departamento de Química Biológica Facultad de Ciencias Exactas y NaturalesUniversidad de Buenos AiresBuenos AiresArgentina Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales Consejo Nacional de Investigaciones Científicas y Técnicas(IQUIBICENCONICET)Buenos AiresArgentina

Chitosan-based nanocarriers(CS-NCs)show a promising role in improving drugs and bioactive compounds delivery for ***,the effects exerted by CS-NCs at the cellular level,including their recognition and uptake,have not been fully investigated *** factors,including size,shape,concentration,and surface chemistry of CS-NCs,play an important role in determining the types of intracellular signals *** mechanism of uptake and the involvement of the cytoskeleton during the CS-NCs endocytosis variates among the different cell types as well as further effects observed inside *** the present work,we discuss the effects induced by CS-NCs per se on the cytoskeleton,a key component in cell architecture and *** focus of this report is made on tumoral and normal biological models in which CS-NCs could differentially affect the cell *** recent years reports regarding the impact of CS-NCs on cytoskeleton dynamics and the current techniques for its evaluation are summarized and *** mechanisms underlying cytoskeletal impact after cell exposure to CS-NCs is critical for the design of safest value-added formulations in the biomedical ***,this revision points out some interesting aspects of cytoskeletal changes and cell death encompassing anti-tumoral effects.

关键词： Cytoskeletal dynamics Cellular uptake Endocytosis Nanocarriers Chitosan Bioactive compounds