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Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery-design,characterization,and biological insights

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Nano Research 2024年第10期17卷 9111-9125页

作者： ana M.López-Estévez Y.Zhang María Medel Iker Arriaga Lucía Sanjurjo Cristian Huck-Iriart Nicola g.A.Abrescia María J.Vicent Defang Ouyang Dolores Torres María José Alonso Center for Research in Molecular Medicine and Chronic Diseases(CiMUS) University of Santiago de CompostelaSantiago de Compostela 15782Spain Department of Pharmacology Pharmacy and Pharmaceutical TechnologySchool of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Health Research Institute of Santiago de Compostela(IDIS) Santiago de Compostela 15782Spain State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Polymer Therapeutics Laboratory and CIBERONC Prince Felipe Research Centre Valencia E-46012Spain Structure and Cell Biology of Viruses Lab CIC bioGUNEBasque Research and Technology Alliance(BRTA)Derio 48160Spain ALBA Synchrotron Light Source Experiments DivisionCerdanyola del VallèsBarcelona 08290Spain IKERBASQUE Basque Foundation for ScienceBilbao 48009Spain

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).Despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular *** offers promising solutions to overcome this limitation,however,formulation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(Hanas)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).Hanas composed by an mAb,modified HA and phosphatidylcholine(PC)resulted in sizes of~100 nm and neutral surface *** modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and *** composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEM),asymmetrical flow field-flow fractionation(AF4),and small-angle X-ray scattering(SAXS).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic *** vitro experiments in cancer cell lines and macrophages confirmed Hanas’low toxicity and ability to transport mAbs to the intracellular *** reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was *** conclusion,these results underscore the suitability of Hanas technology to load and deliver biologicals,which holds promise for future clinical translation.

关键词： monoclonal antibody nanoparticles hyaluronic acid characterization particle size computational modeling

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Rainfall Trend analysis in the City of Villahermosa, Mexico

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Journal of geological Resource and Engineering 2019年第1期7卷 9-16页

作者： ana Victoria gómez Alejandro Heliodoro Daniel Cruz Suárez División Académica de Ciencias Básicas Universidad Juárez Autónoma de Tabasco Cunduacán 86690 México

In this paper, a study by means of linear regression of rainfall in Villahermosa is proposed, within the study area 5 meteorological stations distributed in the city were analyzed because it is one of the most populated areas of the state, once estimated the data, the non-parametric Mann-Kendall test was used to determine increasing or decreasing linear trends in precipitation. To determine the usefulness of statistical inference, the linear correlation coefficient (r) was calculated, which was 0.86 on average. Statistical efficiency (E) was also calculated, which in all the cases analyzed suggests the viability of statistical inference. As a result of this analysis, a complete rainfall database is presented and evaluated for increasing or decreasing trends for the 1980-2010 period.

关键词： Rainfall linear regression Mann Kendall trend analysis.

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WJBC 5^(th) Anniversary Special Issues(2): Proteomics In 2014, can we do better than CA125 in the early detection of ovarian cancer?

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World Journal of Biological Chemistry 2014年第3期5卷 286-300页

作者： Joshua g Cohen Matthew White ana Cruz Robin Farias-Eisner Division of gynecologic Oncology Department of Obstetrics and Gynecology University of California Los Angeles Medical Center

Ovarian cancer is a lethal gynecologic malignancy with greater than 70% of women presenting with advanced stage disease. Despite new treatments, long term outcomes have not significantly changed in the past 30 years with the five-year overall survival remaining between 20% and 40% for stage Ⅲ and Ⅳ disease. In contrast patients with stage Ⅰ disease have a greater than 90% five-year overall survival. Detection of ovarian cancer at an early stage would likely have significant impact on mortality rate. Screening biomarkers discovered at the bench have not translated to success in clinical trials. Existing screening modalities have not demonstrated survival benefit in completed prospective trials. Advances in high throughput screening are making it possible to evaluate the development of ovarian cancer in ways never before imagined. Data in the form of human "-omes" including the proteome, genome, metabolome, and transcriptome are now available in various packaged forms. With the correct pooling of resources including prospective collection of patient specimens, integration of high throughput screening, and use of molecular heterogeneity in biomarker discovery, we are poised to make progress in ovarian cancer screening. This review will summarize current biomarkers, imaging, and multimodality screening strategies in the context of emerging technologies.

关键词： Ovarian cancer Screening Biomarker Detection Diagnostic imaging Proteomics Adnexal mass

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Health 2020年第12期12卷 1562-1574页

作者： giovana Fumes-ghantous José Eduardo Corrente ana Flavia g. Tatis Basic Sciences Department Faculty of Animal Science and Food Engineering University of S&#227 o Paulo Pirassununga Brazil Research Support Office Botucatu Medicine School University of S&#227 o Paulo State Botucatu Brazil Faculty of Animal Science and Food Engineering University of S&#227 o Paulo Pirassununga Brazil

Introduction: It is a fact that the elderly population has been increasing all around the world and also in Brazil. This has been a challenge for governments and managers in the development of public policies to promo... 详细信息

g>Introduction:g> It is a fact that the elderly population has been increasing all around the world and also in Brazil. This has been a challenge for governments and managers in the development of public policies to promote healthy and quality aging. And one of the conditions for healthy aging is to assess the functional capacity and quality of life of elderly people. g>Objective:g> The aim of the present study was to evaluate the factors that influence the loss of functional capacity and the worsening of the quality of life of a representative sample of elderly people from a medium-sized city in the inner of São Paulo State, Brazil. g>Methodology:g> Questionnaires about activities of daily living (ADL), instrumental activities of daily living (IADL), Flanagan quality of life scale (FQOLS), sociodemographic and morbidities aspects were applied to the elderly people. In order to assess associated factors to functional capacity and quality of life, chi-square tests and logistic regression models were fitted including variables: gender, age group, marital status, income, education level, body mass index, abdominal circumference and some morbidities reported by the elderly people. The level of significance adopted for the statistical tests was 5%. g>Results:g> Elderly with age over 75 years old and not married had more risk to be dependent on ADL, while elderly with more than 75 years old, not married, income below one minimal wage, cardiovascular disease and be diabetic had more risk to be dependent by IADL. Already, people with excess of weight had smallest risk to be dependent by IADL, paradoxically. The elderly not married and with an income below a minimum wage had the worst quality of life. g>Conclusions: g>Population aging in Brazil is an evident factor, so it is hoped that this study will contribute to the greatest diligence on the issues of the elderly

关键词： Functional Capacity Life Quality Odds Ratio Risk Factors

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Application of Bioinspired Superhydrophobic Surfaces in Two-phase Heat Transfer Experiments

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Journal of Bionic Engineering 2017年第3期14卷 506-519页

作者： Emanuele Teodori ana Sofia Moita Miguel Moura Pedro Pontes Antonio Moreira Yuan Bai Xinlin Li Yan Liu IN+- Center for Innovation Technology and Policy Research Instituto Superior T~enico Universidade de Lisboa Av. Rovisco Pais 1049-001 Lisboa Portuga Key Laboratory of Bionic Engineering (Ministry of Education) Jilin University Changchun 130022 China

This paper addresses the potential to use Lotus leafbioinspired surfaces in applications involving heat transfer with phase change, namely pool boiling and spray impingement. Besides describing the role of bioinspired topographical features, using an innovative technique combining high-speed visualization and time-resolved infrared thermography, surface durability is also addressed. Water is used for pool boiling and for spray impingement systems （simplified as single droplet impact）, while HFE7000 is used in a pool boiling cooler for electronic components. Results show that surface durability is quickly compro- mised for water pool boiling applications, as the chemical treatment does not withstand high temperatures （T 〉 100 ℃） during long time intervals （3 h - 4 h）. For HFE7000 pool boiling （depicting lower saturation temperature - 34 ℃）, heat transfer en- hancement is governed by the topography. The regular hierarchical pattern of the bioinspired surfaces promotes the heat transfer coefficient to increase up to 22.2%, when compared to smooth surfaces, while allowing good control of the interaction mechanisms until a distance between micro-structures of 300 gm- 400 Ixm. Droplet impingement was studied for surface temperatures ranging between 60 ℃ - 100 ℃. The results do not support the use of superhydrophobic surfaces for cooling applications, but reveal great potential for other applications involving droplet impact on heated surfaces （e.g. metallurgy in- dustry）.

关键词： bioinspired surfaces surface micro-patterning two-phase heat transfer time resolved infrared thermography

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Downregulation of TNFR2 decreases survival gene expression,promotes apoptosis and affects the cell cycle of gastric cancer cells

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World Journal of gastroenterology 2022年第24期28卷 2689-2704页

作者： ana Flávia Teixeira Rossi Fernanda da Silva Manoel-Caetano Joice Matos Biselli Ágata Silva Cabral Marilia de Freitas Calmon Saiki Marcelo Lima Ribeiro ana Elizabete Silva Department of Biological Sciences Sao Paulo State University(UNESP)São Josédo Rio Preto 15054-000São PauloBrazil Clinical Pharmacology and gastroenterology Unit São Francisco University(USF)Bragança Paulista 12916-900São PauloBrazil

BACKgROUND Chronic inflammation due to Helicobacter pylori(***)infection promotes gastric *** necrosis factor-α(TNF-α),a key mediator of inflammation,induces cell survival or apoptosis by binding to two receptors(TNFR1 and TNFR2).TNFR1 can induce both survival and apoptosis,while TNFR2 results only in cell *** dysregulation of these processes may contribute to *** To evaluate the effects of TNFR1 and TNFR2 downregulation in AgS cells treated with *** extract on the TNF-α*** AgS cell lines containing TNFR1 and TNFR2 receptors downregulated by specific shRNAs and nonsilenced AgS cells were treated with *** extract for 6 ***,quantitative polymerase chain reaction with TaqMan®assays was used for the relative quantification of the mRNAs(TNFA,TNFR1,TNFR2,TRADD,TRAF2,CFLIP,NFKB1,NFKB2,CASP8,CASP3)and miRNAs(miR-19a,miR-34a,miR-103a,miR-130a,miR-181c)related to the TNF-αsignalling *** cytometry was employed for cell cycle analysis and apoptosis *** In nonsilenced AgS cells,*** extract treatment increased the expression of genes involved in cell survival and inhibited both apoptosis(NFKB1,NFKB2 and CFLIP)and the TNFR1 ***1 downregulation significantly decreased the expression of the TRADD and CFLIP genes,although no change was observed in the cellular process or miRNA *** contrast,TNFR2 downregulation decreased the expression of the TRADD and TRAF2 genes,which are both important downstream mediators of the TNFR1-mediated pathway,as well as that of the NFKB1 and CFLIP genes,while upregulating the expression of miR-19a and ***,a reduction in the number of cells in the g0/g1 phase and an increase in the number of cells in the S phase were observed,as well as the promotion of early *** Our findings mainly highlight the important role of TNFR2 in the TNF-αpathway in gastric cancer,indicating that silencing it can reduce the

关键词： gastric cancer Helicobacter pylori Tumour necrosis factor-αsignalling pathway TNFR1 TNFR2 miRNAs

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Prediction of Pulmonary Arterial Pressure Level after Repair of Congenital Cardiac Communications and Discharge from the Hospital: Role of Down Syndrome and Early Postoperative Hemodynamics

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Congenital Heart Disease 2022年第3期17卷 351-363页

作者： Eloisa Sassa Carvalho Maria Francilene SSouza Kelly Cristina O.Abud Claudia R.P.Castro Juliano g.Penha ana Maria Thomaz Vanessa A.guimaraes Antonio Augusto Lopes Heart Institute(InCor) University of Sao Paulo School of MedicineSão PauloBrazil

Background:Postoperative pulmonary hypertension limits the success of surgical treatment in some patients with unrestrictive congenital cardiac *** patients at risk of developing postoperative pulmonary hypertension is important to individualize follow-up ***:We analyzed a prospective cohort of 52 pediatric patients(age 3 to 35 months)looking for perioperative predictors of mildly elevated pulmonary arterial pressure 6 months after surgery,defined as a systolic pressure greater than 30 mmHg by transthoracic *** corresponds to a mean pulmonary arterial pressure of>20 ***,echocardiographic and hemodynamic parameters were *** hemodynamics was assessed by directly measuring pulmonary and systemic arterial pressures using indwelling *** postoperative pulmonary hemodynamics was defined as the mean pulmonary/systemic mean arterial pressure ratio(PAP/SAP)obtained per patient during the first 6 h of postoperative ***:Among the factors that were investigated as possible predictors,perioperative hemodynamics and the presence of Down syndrome were initially selected using univariate analysis(pg room just after cardiopulmonary bypass(r=0.70,pgher in subjects with Down syndrome than in nonsyndromic individuals(p=0.003).Early postoperative PAP/SAP was the only predictor selected using multivariate *** was characterized as an independent predictor after adjustments for possible *** early postoperative PAP/SAP of>0.35 was 76%sensitive and 74%specific at predicting a systolic pulmonary arterial pressure of>30 mmHg 6 months after surgery(hazard ratio with 95%CI 8.972[2.428–33.158],p=0.002).Conclusion:The hypertensive early postoperative behavior of the pulmonary circulation was strongly but not exclusively associated with Down syndrome,and it was char

关键词： Pulmonary hypertension congenital heart disease Down syndrome pediatric cardiac surgery

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A long-term record of land use change impacts on sediments in Oualidia lagoon,Morocco

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International Journal of Sediment Research 2014年第1期29卷 1-10页

作者： Mehdi MAanaN ana Carolina RUIZ-FERNNDEZ Mohamed MAanaN Paul FATTAL Bendahhou ZOURARAH Mohamed SAHABI géolittomer UMR 6554 LETg Université de Nantes Marine geosciences Laboratory URAC 45Earth Sciences departmentFaculty of Sciences Universidad Nacional Autónoma de México.Instituto de Ciencias del Mary Limnología

An integrated approach,involving land use patterns and heavy metal contents of the surficial and cored sediment,was proposed to detect the characteristic spatial and temporal scale of point and non-point source human disturbances on the Oualidia lagoon in *** and description of the temporal and spatial distributions of the main contamination sources of heavy metals are analyzed using statistics and gIS *** results show that surficial sediments are highly enriched in heavy metals compared to their preindustrial background ***-use types affected lagoon sediment pollution in different ways:1) agricultural areas had the highest potential for sediment contamination by heavy metals,particularly Pb,Cu and Hg,2) Ni and Cr are the main pollutants originating from urban sewage and 3) oyster farming and traditional land uses such as salt flats,pastures showed low levels of others *** enrichment factors(normalized by Al) obtained from the sediment cores indicated that the lagoon is(strongly/moderately) polluted by all metals which were attributed to agricultural activities and wastewater discharges from urbanized areas.

关键词： Land use change(LUC) geographical information systems(gIS) Sediment pollution Risk assessment

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Polyethylene glycol 35 ameliorates pancreatic inflammatory response in cerulein-induced acute pancreatitis in rats

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World Journal of gastroenterology 2020年第39期26卷 5970-5982页

作者： ana Ferrero-Andrés Arnau Panisello-Roselló Joan Roselló-Catafau Emma Folch-Puy Experimental Pathology Department Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones científicasBarcelona 08036CataloniaSpain Experimental Pathology Department Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones científicasCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasInstitut d'Investigacions Biomèdiques August Pi i SunyerBarcelona 08036CataloniaSpain

BACKgROUND Acute pancreatitis(AP)is a sudden inflammatory process of the pancreas that may also involve surrounding tissues and/or remote *** and parenchymal cell death are common pathological features of this condition and determinants of disease *** glycols(PEgs)are nonimmunogenic,non-toxic water-soluble polymers widely used in biological,chemical,clinical and pharmaceutical *** To evaluate the protective effect of a 35-kDa molecular weight PEg(PEg35)on the pancreatic damage associated to cerulein-induced acute pancreatitis in vivo and in *** Wistar rats were assigned at random to a control group,a cerulein–induced AP group and a PEg35 treatment *** was induced by five hourly intraperitoneal injections of cerulein(50μg/kg/bw),while the control animals received saline ***35 was administered intraperitoneally 10 minutes before each cerulein injection in a dose of 10 mg/*** AP induction,samples of pancreatic tissue and blood were collected for ***42J pancreatic acinar cells were treated with increasing concentrations of PEg35 prior to exposure with tumor necrosis factorα(TNFα),staurosporine or *** severity of AP was determined on the basis of plasma levels of lipase,lactate dehydrogenase activity,pancreatic edema and histological *** evaluate the extent of the inflammatory response,the gene expression of inflammation-associated markers was determined in the pancreas and in AR42J-treated ***-induced cell death was also measured in models of in vivo and in vitro pancreatic *** Administration of PEg35 significantly improved pancreatic damage through reduction on lipase levels and tissue edema in cerulein-induced AP *** increased associated inflammatory response caused by cerulein administration was attenuated by a decrease in the gene expression of inflammation-related cytokines and inducible nitric oxide synthase enzyme in the *** contr

关键词： Acute pancreatitis Inflammation Polyethylene glycols Cytokines AR42J cells Cell death

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giant cell arteritis: Current treatment and management

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World Journal of Clinical Cases 2015年第6期3卷 484-494页

作者： Cristina Ponte ana Filipa Rodrigues Lorraine O'Neill Raashid Ahmed Luqmani Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences Botnar Research Centre University of Oxford Oxford OX1 2JD United Kingdom Department of Rheumatology Hospital de Santa Maria CHLN Lisbon Academic Medical Centre 1649-035 Lisbon Portugal Department of Internal Medicine Hospital das Caldas da Rainha Centro Hospitalar Oeste 2500-176 Caldas da Rainha Portugal Department of Rheumatology St Vincent’s University Hospital Dublin Ireland

glucocorticoids remain the cornerstone of medicaltherapy in giant cell arteritis(gCA) and should be started immediately to prevent severe consequences of the disease, such as blindness. However, glucocorticoid therapy leads to significant toxicity in over 80% of the patients. Various steroid-sparing agents have been tried, but robust scientific evidence of their efficacy and safety is still lacking. Tocilizumab, a monoclonal IL-6 receptor blocker, has shown promising results in a number of case series and is now being tested in a multi-centre randomized controlled trial. Other targeted treatments, such as the use of abatacept, are also now under investigation in gCA. The need for surgical treatment is rare and should ideally be performed in a quiescent phase of the disease. Not all patients follow the same course, but there are no valid biomarkers to assess therapy response. Monitoring of disease progress still relies on assessing clinical features and measuring inflammatory markers(C-reactive protein and erythrocyte sedimentation rate). Imaging techniques(e.g., ultrasound) are clearly important screening tools for aortic aneurysms and assessing patients with largevessel involvement, but may also have an important role as biomarkers of disease activity over time or in response to therapy. Although gCA is the most common form of primary vasculitis, the optimal strategies for treatment and monitoring remain uncertain.

关键词： giant cell arteritis Therapy Disease management glucocorticoids Immunosuppressive agents

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