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determinants of PHGPx Expression in a Cultured Endothelial Cell Line

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Biomedical and Environmental Sciences 1997年第2期10卷 163-176页

作者： regina BRIGELIUS-FLOHE B■RBEL FRIEdRICHS STEFANIE MAURER ANd RUdIGER STREICHER (German Institute of Human Nutrition,d-14558 Potsdam-Rehbrucke, Germany) German Institute of Human Nutrition Potsdam-Rehbrücke Germany.

Selenoprotein biosynthesis may not only be affected by the availability of selenium and the transcription rate of pertinent genes but also by the activity of components of the selenocysteine incorporation complex, SelA, B, C, or d. Incorporation of selenocysteine into selenoproteins requires a complex co-translational mechanism guaranteeing the correct recoding of the termination codon TGA as selenocysteine codon. A particular tRNASer(Sec) is enzyrnatically transformed by selenophosphate into tRNAsec which recognizes the UGA codon by means of a specific elongation factor (SelB) and a peculiar mRNA secondary structure. Selenophosphate is formed from selenide and ATP by the Seld gene product, selenophosphate synthase (Seld). To further elucidate the biological role of phospholipid hydroperoxide GPx (PHGPx), we transformed cells with a heterologous (pig) PHGPx gene and/or an additional (human) Seld gene and studied the behaviour of these cells under selenium depletion and repletion. Transfection of the endothelial cell line ECV 304 with either PHGPx cdNA or Seld cdNA did not result in a substantial increase of PHGPx activities, independent of selenium supply. However, cells co-trans fected with both, PHGPx and Seld cdNA, expressed significantly higher PHGPx activlty. This effect was much more pronounced under selenium limiting conditions. The enhanced PHGPx activity correlated with two functional pararneters, increased capability to reduce hydroperoxides and less sensitivity against H2O2-induced cytotoxicity. Thus, the ECV cells, stably transfected with PHGPx and Seld cdNA, provide a model to specifically investigate the role of PHGPx in endothelial cell function

关键词： ECV determinants of PHGPx Expression in a Cultured Endothelial Cell Line

An update on the histological subtypes of hepatocellular carcinoma

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Hepatoma Research 2019年第11期5卷 17-23页

作者： regina Cheuk-Lam Lo department of Pathology The University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina

Hepatocellular carcinoma(HCC)is one of the top-ranking cancers worldwide and in Southeast Asia.The high propensity for tumor recurrence,distant metastasis and chemoresistance remain major hurdles in the treatment of HCC.With advances on genetics and genomics research,molecular targeted therapies are emerging as a hope for better disease control.On the histological perspective,microscopic review of clinical samples has led to subclassification of HCC and establishment of new entities.In this review,latest understanding on macrotrabecular-massive HCC,steatohepatitic HCC,lymphocyte-rich HCC,scirrhous HCC,fibrolamellar carcinoma and combined hepatocellular-cholangiocarcinoma will be discussed,emphasizing on the clinical relevance of these pathological entities.Further delineation of the histological,immunohistochemical,molecular and biological phenotypes of primary liver cancer would to further enhance an integrated morphological-molecular classification that better predicts clinical outcome and guides clinical management.

关键词： Liver cancer subtype histology

Islet amyloid polypeptide & amyloid beta peptide roles in Alzheimer’s disease:two triggers, one disease

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Neural Regeneration Research 2021年第6期16卷 1127-1130页

作者： Sofia Ferreira Ana F.Raimundo regina Menezes Ivo C.Martins iBET-Instituto de Biologia Experimental e Tecnológica OeirasPortugal CEdOC-Chronic diseases Research Center Faculdade de Ciências MédicasUniversidade Nova de LisboaLisboaPortugal ITQB-NOVA Instituto de Tecnologia Química e Biológica António XavierUniversidade Nova de LisboaOeirasPortugal Instituto de Medicina Molecular Faculdade de MedicinaUniversidade de LisboaLisbonPortugal

Alzheimer’s disease(Ad)is a neurodegenerative disorder that affects millions worldwide.due to population ageing,the incidence of Ad is increasing.Ad patients develop cognitive decline and dementia,features for which is known,requiring permanent care.This poses a major socio-economic burden on healthcare systems as Ad patients’relatives and healthcare workers are forced to cope with rising numbers of affected people.despite recent advances,Ad pathological mechanisms are not fully understood.Nevertheless,it is clear that the amyloid beta(Aβ)peptide,which forms amyloid plaques in Ad patients’brains,plays a key role.Type 2 diabetes,the most common form of diabetes,affects hundreds of million people globally.Islet amyloid polypeptide(IAPP)is a hormone coproduced and secreted with insulin in pancreatic β-cells,with a key role in diabetes,as it helps regulate glucose levels and control adiposity and satiation.Similarly to Aβ,IAPP is very amyloidogenic,generating intracellular amyloid deposits that causeβ-cell dysfunction and death.It is now clear that IAPP can also have a pathological role in Ad,decreasing cognitive function.IAPP harms the blood-brain barrier,directly interacts and co-deposits with Aβ,promoting diabetes-associated dementia.IAPP can cause a metabolic dysfunction in the brain,leading to other diabetes-related forms of Ad.Thus,here we discuss IAPP association with diabetes,Aβand dementia,in the context of what we designate a“diabetes brain phenotype”Ad hypothesis.Such approach helps to set a conceptual framework for future IAPP-based drugs against Ad.

关键词： aggregation Alzheimer amylin amyloid diabetes islet amyloid polypeptide

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基于文献计量分析的中国乡村生态学研究综述

生态学报 2022年第17期42卷 6922-6936页

作者：郭青海仇铂添王鹏飞 Soebekti Chatarina regina 浙江理工大学建筑工程学院杭州310018 浙江省生态文明研究院杭州310018 浙江理工大学经济管理学院杭州310018

我国已全面建成了小康社会,新发展阶段对乡村生态环境保护治理提出更高要求,乡村生态振兴既要提升生态环境质量,又要促进农民农村共同富裕的实现。在时代发展需求中,乡村生态学的研究成果不断丰富,概念内涵不断扩展,有必要对过去20年中... 详细信息

我国已全面建成了小康社会,新发展阶段对乡村生态环境保护治理提出更高要求,乡村生态振兴既要提升生态环境质量,又要促进农民农村共同富裕的实现。在时代发展需求中,乡村生态学的研究成果不断丰富,概念内涵不断扩展,有必要对过去20年中国乡村生态学研究进行梳理和总结,为美丽乡村建设、自然资源保护、乡村可持续发展提供理论依据。对中国乡村生态学研究进行文献计量和可视化分析,通过绘制可视化知识图谱,梳理了20年以来中国乡村生态学研究的发展脉络,提出人类感知与社会需求的层级递进是推动乡村生态学研究发展的一个主要驱动力;针对乡村生态热点,提出4个方面的研究趋势,即乡村生态环境精细化治理与预警、乡村建设中的生态环境政策和制度、乡村景观规划与乡村生态文化建设和农村生产生活消费绿色化发展与可持续性;最后,围绕需求层级理论和乡村生态系统服务,构建了乡村生态学学科边界框架,强调在多学科交叉的基础上,针对乡村生态研究的多层次多尺度的特征,重点开展乡村生态系统中社会、经济、生态多要素对乡村生态系统的综合作用及其之间相互影响关系的研究。

关键词：乡村生态学需求层级理论生态系统服务乡村可持续性

Importance of complementary data to histopathological image analysis of oral leukoplakia and carcinoma using deep neural networks

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Intelligent Medicine 2023年第4期3卷 258-266页

作者： Leandro Muniz de Lima Maria Clara Falcão Ribeiro de Assis Júlia Pessini Soares Tânia regina Grão-Velloso Liliana Aparecida Pimenta de Barros danielle Resende Camisasca Renato Antonio Krohling Nature-inspired Computing Lab Federal University of Espirito SantoVitoriaBrazil Graduate Program in Computer Science Federal University of Espirito SantoVitoriaBrazil School of dentistry Departamento de Clinica OdontologicaFederal University of Espirito SantoVitoriaBrazil Graduate Program in Clinical dentistry Federal University of Espirito SantoVitoriaBrazil

Background Oral cancer is one of the most common types of cancer in men causing mortality if not diagnosedearly.In recent years,computer-aided diagnosis(CAd)using artificial intelligence techniques,in particular,deepneural networks have been investigated and several approaches have been proposed to deal with the automateddetection of various pathologies using digital images.Recent studies indicate that the fusion of images with thepatient’s clinical information is important for the final clinical diagnosis.As such dataset does not yet exist fororal cancer,as far as the authors are aware,a new dataset was collected consisting of histopathological images,demographic and clinical data.This study evaluated the importance of complementary data to histopathologicalimage analysis of oral leukoplakia and carcinoma for CAd.Methods A new dataset(NdB-UFES)was collected from 2011 to 2021 consisting of histopathological imagesand information.The 237 samples were curated and analyzed by oral pathologists generating the gold standardfor classification.State-of-the-art image fusion architectures and complementary data(Concatenation,MutualAttention,MetaBlock and MetaNet)using the latest deep learning backbones were investigated for 4 distincttasks to identify oral squamous cell carcinoma,leukoplakia with dysplasia and leukoplakia without dysplasia.We evaluate them using balanced accuracy,precision,recall and area under the ROC curve metrics.Results Experimental results indicate that the best models present balanced accuracy of 83.24%using images,demographic and clinical information with MetaBlock fusion and ResNetV2 backbone.It represents an improvement in performance of 30.68%(19.54 pp)in the task to differentiate samples diagnosed with oral squamous cellcarcinoma and leukoplakia with or without dysplasia.Conclusion This study indicates that cured demographic and clinical data may positively influence the performance of artificial intelligence models in automated classification of oral cancer.

关键词： Leukoplakia Squamous carcinoma Pathology deep learning Transfer learning

Implementation of a High-Risk Outpatient Clinic for Children with Complex Congenital Heart disease in a Reference Service in Brazil

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Congenital Heart disease 2023年第6期18卷 649-656页

作者： Gustavo Foronda Vanessa Ferreira Amorim de Melo Claudia regina Pinheiro de Castro Grau Ingrid Magatti Piva Glaucia Maria Penha Tavares Ana Cristina Sayuri Tanaka Nana Miura department of Pediatric Cardiology and Adult Congenital Heart diseases Heart Institute of the University of São PauloSão PauloBrazil Foronda Clinic São PauloBrazil Institute of Orthopedics and Traumatology University of São PauloSão PauloBrazil department of Echocardiography Heart Institute of the University of São PauloSão PauloBrazil

Background:Children with congenital heart disease(CHd),even after surgical approaches,and especially those who undergo staged procedures in theﬁrst months of life,remain vulnerable to readmissions and complications,requiring very close monitoring and differentiated intervention strategies.Methods:descriptive and exploratory study,of the experience report type,which presents the process of building the high-risk outpatient clinic for complex congenital heart diseases(AAR)at the Instituto do Coração(InCor).Results:Report of the path taken to structure the AAR,demonstrating the organization,interface with the multidisciplinary team,admission and discharge criteria,training,and patient proﬁle.In theseﬁve years of care,275 patients were treated,59.65%with biventricular interstage physiology,followed by univentricular interstage physiology(34.55%),residual defects after surgical procedures(3.63%),tumors with risk of mechanical obstruction(1.45%)and patients with an intrauterine approach(0.72%).The signiﬁcant number of critical patients who were successfully discharged from hospital(44.72%),the low mortality rate due to sudden deaths at home and the high adherence to follow-up cor-roborate the impact of this specialized assistance.Conclusions:despite the limitations of the study,this experi-ence report showed that with few resources,there is the possibility of organizing an AAR with differentiated care,with the objective of early detection and treatment of residual injuries,identiﬁcation of early interventions,edu-cation of parents for follow-up of their children,resulting in individualized treatment,promoting a better quality of life for this population.

关键词： Congenital heart defects ambulatory care heart defects

Poly(phenylene oxide) and Renewable Polyamide 11 Blends Compatibilized by Ethylene-n-Octene Copolymer

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Journal of Renewable Materials 2018年第7期6卷 772-783页

作者： regina Jeziorska Agnieszka Abramowicz Agnieszka Szadkowska Anna Pasnik Ewa Spasowka department of Polymer Technology and Processing Industrial Chemistry Research InstituteRydygiera 801-793 WarsawPoland

Poly(phenylene oxide)/renewable polyamide 11 (PPO/PA11 20/80) blends toughened with glycidylmethacrylate grafted ethylene-n-octene copolymer (GEOC) were prepared in a co-rotating twin-screwextruder. The reaction between GEOC and PPO/PA11 blend was analyzed by gel content tests. Themorphology of PPO/PA11/GEOC blends was observed by scanning electron microscope. The SEMresults showed that PPO formed the continuous phase, though it is a minority component of blends. Withincreasing GEOC content from 5 to 15 wt% the morphology of the blends transformed from droplet-matrix toco-continuous structure, in which both PA11 and PPO phases are continuous. The blend with co-continuousmorphology had better mechanical properties than those with droplet-matrix morphology. The impactstrength of the PPO/PA11/GEOC blends was much higher compared to the one without GEOC as well asPA11 due to the compatibilizing effect, which was also proved by dSC analysis, rheological behavior (MFR,dMTA) and tensile properties.

关键词： Compatibilization elastomer PPO/PA11 blends toughening

The host-targeting compound peruvoside has a broad-spectrum antiviral activity against positive-sense RNA viruses

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2039-2055页

作者： Kan Xing Wu Thinesshwary Yogarajah Marcus Wing Choy Loe Parveen Kaur regina Ching Hua Lee Chee Keng Mok Yi Hao Wong Patchara Phuektes Li Sze Yeo Vincent T.K.Chow Yong Wah Tan Justin Jang Hann Chu department of Microbiology and Immunology Yong Loo Lin School of MedicineNational University Health SystemNational University of SingaporeSingapore 117597Singapore department of Pathobiology Faculty of Veterinary MedicineKhonkaen UniversityKhonkaen 40002Thailand Infectious disease Programme Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research(A∗STAR)Singapore 138648Singapore Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore 308232Singapore NUSMed Biosafety Level 3 Core Facility Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore

Positive-sense RNA viruses modify intracellular calcium stores,endoplasmic reticulum and Golgi apparatus(Golgi)to generate membranous replication organelles known as viral factories.Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity.Here,we identified the vital role of a broadspectrum antiviral,peruvoside in limiting the formation of viral factories.Mechanistically,we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1(GBF1)phosphorylation and Golgi vesiculation by peruvoside treatment.The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation.Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337(T1337).We also showed 100%of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum.These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside,host-directed antivirals for positive-sense RNA virus-mediated disease,in the interim where no vaccine is available.

关键词： Positive-sense RNA viruses Peruvoside Antiviral CdKI signaling Viral factories Calcium efflux Broad-spectrum Golgi apparatus

Propranolol hydrochloride degradation using La@TiO_(2) functionalized with CMCd

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Journal of Rare Earths 2022年第4期40卷 579-585,I0003页

作者： Gustavo Lopes Colpani Vitor Follmann Santos Rubieli Carla Frezza Zeferino Micheli Zanetti Josiane Maria Muneron de Mello Luciano Luiz Silva Natan Padoin regina de Fatima Peralta Muniz Moreira Márcio Antônio Fiori Cíntia Soaresc Post-Graduate Program in Technology and Innovation Management Community University of ChapecóRegionChapecó89809-900Brazil department of Chemical Engineering Community University of ChapecóRegionChapecó89809-900Brazil Laboratory of Materials and Scientific Computing(LabMAC) Department of Chemical and Food EngineeringFederal University of Santa CatarinaFlorianópolis88040-900Brazil

Propranolol hydrochloride can be considered a persistent and bioaccumulative pharmaceutical in the environment.This drug and its by-products are potentially toxic and have adverse effects,since these compounds have been associated with endocrine-disrupting effects,reproductive deficiencies,embryo abnormalities and pericardial oedema.TiO_(2)–La 0.05%–carboxymethyl-β-cyclodextrin(CMCd)nanoparticles were successfully prepared by a simple two-step method,which consists of sonification and functionalization.The characterization analyses reveal that lanthanum is dispersed on the semiconductor surface,probably forming Ti–O–La bonds,which can induce oxygen vacancies and surface defects that effectively restrain the recombination of photogenerated electron/holes pairs.The efficiency of TiO_(2)–La 0.05%–CMCd samples in degradation of propranolol under UV-light irradiation is higher than that of pristine TiO_(2) within 20 min reaction,probably due to complex formation between theβ-blocker and the oligosaccharide,which allows us to propose a photocatalytic mechanism based on the formation of intermediates and competition of these compounds to the radicals and CMCd cavities.

关键词： TiO_(2) Lanthanum CMCd Propranolol Photocatalysis Functionalization