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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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Estimating geographic variation of infection fatality ratios during epidemics

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infectious Disease Modelling 2024年第2期9卷 634-643页

作者： Joshua ladau Eoin l.Brodie Nicola Falco ishan Bansal Elijah B.Hoffman Marcin P.Joachimiak ana M.Mora Angelica M.Walker Haruko M.Wainwright Yulun Wu Mirko Pavicic Daniel Jacobson Matthias Hess James B.Brown Katrina Abuabara departments of Computational Precision Health and dermatology University of CaliforniaSan FranciscoCA94115USA Arva intelligence Inc.Salt Lake CityUT84101USA Computational Biosciences Group Lawrence Berkeley National LaboratoryBerkeleyCA94720USA Earth and Environmental Sciences Area Lawrence Berkeley National LaboratoryBerkeleyCA94720USA Graduate Group in Biostatistics University of CaliforniaBerkeleyCA94720USA Biosystems Data Science Environmental Genomics and Systems BiologyLawrence Berkeley National LaboratoryBerkeleyCA94720USA Center for Environmental Research and Community Health(CERCH) School of Public HealthUniversity of CaliforniaBerkeleyCA94720USA Bredesen Center for interdisciplinary Research and Graduate Education University of TennesseeKnoxvilleTN37996USA department of Nuclear Science and Engineering Massachusetts Institute of TechnologyBostonMA02139USA Biosciences Oak Ridge National LaboratoryOak RidgeTN37830USA University of California DavisCA95616USA Statistics department University of CaliforniaBerkeleyCA94720USA Division of Epidemiology and Biostatistics University of California Berkeley School of Public Health2121 Berkeley WayBerkeleyCA94720USA

Objectives We aim to estimate geographic variability in total numbers of infections and infection fatality ratios(iFR;the number of deaths caused by an infection per 1,000 infected people)when the availability and quality of data on disease burden are limited during an *** We develop a noncentral hypergeometric framework that accounts for differential probabilities of positive tests and reflects the fact that symptomatic people are more likely to seek *** demonstrate the robustness,accuracy,and precision of this framework,and apply it to the United States(U.S.)COViD-19 pandemic to estimate county-level SARS-CoV-2 *** The estimators for the numbers of infections and iFRs showed high accuracy and precision;for instance,when applied to simulated validation data sets,across counties,Pearson correlation coefficients between estimator means and true values were 0.996 and 0.928,respectively,and they showed strong robustness to model *** the county-level estimators to the real,unsimulated COViD-19 data spanning April 1,2020 to September 30,2020 from across the U.S.,we found that iFRs varied from 0 to 44.69,with a standard deviation of 3.55 and a median of *** The proposed estimation framework can be used to identify geographic variation in iFRs across settings.

关键词： infection fatality ratio infection fatality rate Noncentral hypergeometric distribution COViD-19 SARS-CoV-2

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intestinal anti-inflammatory activity of Ground Cherry(Physalis angulata l.)standardized CO2 phytopharmaceutical preparation

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World Journal of Gastroenterology 2017年第24期23卷 4369-4380页

作者： luiz domingues almeida junior ana elisa valencise quaglio celso acácio rodrigues de almeida costa luiz Claudio Di Stasi laboratory of phytomedicines pharmacology and biotechnology(phytopharmatech)department of pharmacologyinstitute of biosciencesuniversidade estadual paulista unespbotucatusao paulocep 18618-970

AiM To investigate the effects of Ground Cherry(Physalis angulata l.)standardized supercritical CO_2 extract in trinitrobenzenesulphonic acid(TNBS)model of rat intestinal *** The animals were divided into groups that received vehicle or *** extract(PacO_2)orally at the doses 25,50 and 100 mg/kg daily by 5 d before TNBS *** effects of PacO_2 were assessed by macroscopic analysis,biochemical determinations of the levels of myeloperoxidase(MPO),alkaline phosphatase(AlP),glutathione and cytokines(such as iNF-γ,il-1β,il-6,il-10 and TNF-α),gene expression evaluation(including Hsp70,heparanase,NF-κB,mitogenactivated protein kinases(Mapk)1,3,6 and 9,and the mucins genes Muc 1,2,3 and 4)and histopathological studies using optical,and electronic(transmission and scanning)*** PacO2 extract promoted a significant reduction in MPO and AlP activities,reducing oxidative stress and neutrophil *** effects were accompanied by significant reduction of colonic levels of iFN-γand il-6 and down-regulation of heparanase,Hsp70,Mapk3,Mapk9,Muc1 and Muc2 genes expression when compared with TNBS-control *** addition,protective effects were also evidenced by reduced neutrophil infiltration,recovery of cell architecture and replacement of mucin by histopathological and ultrastructural *** Physalis angulata supercritical CO2 extract is an intestinal anti-inflammatory product that modulates oxidative stress,immune response and expression of inflammatory mediators,with potentially utility for treating inflammatory bowel disease.

关键词： intestinal disease inflammatory bowel disease Physalis angulata l.trinitrobenzenesulphonic acid

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Multiple-population QTl mapping of maturity and fruit-quality traits reveals lG4 region as a breeding target in sweet cherry(Prunus avium l.)

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Horticulture Research 2020年第1期7卷 1290-1302页

作者： Alejandro Calle ana Wünsch Unidad de Hortofruticultura Centro de Investigación y Tecnología Agroalimentaria de Aragón(CITA).Avda.Montañana 93050059 ZaragozaSpain instituto Agroalimentario de Aragón-iA2(CiTA-Universidad de Zaragoza) ZaragozaSpain

Sweet cherry maturity date and fruit quality are relevant traits for its marketability,transport,and consumer *** this work,sweet cherry fruit development time,maturity date,and commercial fruit-quality traits(size,weight,firmness,soluble solid content,and titratable acidity)were investigated to improve the knowledge of their genetic control,and to identify alleles of breeding *** sweet cherry populations segregating for these traits were used for QTl *** populations descend from cross-and self-pollinations of local Spanish sweet cherries‘Ambrunés’and‘Cristobalina’,and breed cultivars(‘Brooks’,‘lambert’,or‘Vic’).The six populations(n=411),previously genotyped with RosBREED Cherry 6 K SNP array,were phenotyped for 2 *** analyses were conducted using a multifamily approach implemented by FlexQTl™.Fruit development time,soluble solid content,and titratable acidity QTls are first reported in sweet cherry in this *** QTls were detected for all the *** were more stable as they were detected for 2 *** these,nine are first reported in this *** major QTls for fruit development time,maturity date,firmness,and soluble solid content were identified on the same narrow region of linkage group *** traits also showed significant positive correlation(long fruit development time associated with late maturity,high firmness,and high SSC).Nac transcription factor genes identified on this lG4 region may be candidate genes for the regulation of these traits in sweet cherry,as previously described in syntenic regions of other Rosaceae *** of breeding interest on this lG4 genomic region were identified and will be useful for sweet cherry breeding from this and related plant material.

关键词： breeding fir maturity

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development of a standardized in vitro approach to evaluate microphysical,chemical,and toxicological properties of combustion-derived fine and ultrafine particles

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Journal of Environmental Sciences 2022年第3期34卷 104-117页

作者： ana Teresa Juarez-Facio Clement Castilla Cecile Corbiere Helene lavanant Carlos Afonso Christophe Morin Nadine Merlet-Machour laurence Chevalier Jean-Marie Vaugeois Jerome Yon Christelle Monteil Normandie Univ UNIROUENUNICAEN ABTE76000 RouenFrance Normandie Univ UNIROUENINSA RouenCNRSCOBRA76000 RouenFrance Normandie Univ UNIROUENINSA RouenCNRSGPM-UMR663476000 RouenFrance Normandie Univ UNIROUENINSA RouenCNRSCORIA76000 RouenFrance

Ultrafine particles represent a growing concern in the public health community but their precise role in many illnesses is still unknown. This lack of knowledge is related to the experimental difficulty in linking their biological effects to their multiple properties, which are important determinants of toxicity. Our aim is to propose an interdisciplinary approach to study fine(FP) and ultrafine(UFP) particles, generated in a controlled manner using a mini CAST(Combustion Aerosol Standard) soot generator used with two different operating conditions(CAST1 and CAST3). The chemical characterization was performed by an untargeted analysis using ultra-high resolution mass spectrometry. in conjunction with this approach, subsequent analysis by gas chromatography–mass spectrometry(GC–MS) was performed to identify polycyclic aromatic hydrocarbons(PAH). CAST1 enabled the generation of FP with a predominance of small PAH molecules, and CAST3 enabled the generation of UFP, which presented higher numbers of carbon atoms corresponding to larger PAH molecules. Healthy normal human bronchial epithelial(NHBE) cells differentiated at the air-liquid interface(Ali) were directly exposed to these freshly emitted FP and UFP. Expression of MUC5ac, FOXJ1, OClN and ZOi as well as microscopic observation confirmed the ciliated pseudostratified epithelial phenotype. Study of the mass deposition efficiency revealed a difference between the two operating conditions, probably due to the morphological differences between the two categories of particles. We demonstrated that only NHBE cells exposed to CAST3 particles induced upregulation in the gene expression of il-8 and NQO1. This approach offers new perspectives to study FP and UFP with stable and controlled properties.

关键词： in vitro Air-liquid interface MiniCAST Fine and ultrafine particles Organic compounds OC/TC

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influence of Saliva and Mucin on the Adhesion of <i>Candida</i>Oral Clinical isolates

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Journal of Encapsulation and Adsorption Sciences 2015年第4期5卷 217-227页

作者： Catarina l. Seabra Cláudia M. Botelho ana C. N. Oliveira Mariana Henriques instituto de investiga&ccedil&atildeo e inova&ccedil&atildeo em Saúde University of Porto Porto Portugal instituto de Engenharia Biomédica University of Porto Porto Portugal instituto de Patologia e imunologia Molecular da Universidade do Porto University of Porto Porto Portugal instituto de Ciências Biomédicas Abel Salazar University of Porto Porto Portugal Centre of Biological Engineering (CEB) Laboratório de Investiga&ccedil&atildeo em Biofilmes Rosário Oliveira University of Minho Braga Portugal Centre of Physics (CFUM) Department of Physics University of Minho Braga Portugal Centre of Molecular and Environmental Biology (CBMA) Department of Biology University of Minho Braga Portugal

Objectives: This research work intends to clarify the role of artificial saliva, in particularly the role of mucin, a salivary protein, on the surface properties and adhesion ability of Candida spp. oral clinical isolates to abiotic surfaces. Methods: Four oral clinical isolates of Candida spp. were used: two Candida albicans strains (ac;AM) and two Candida parapsilosis strains (AD;AM2). The strains were isolated from patients using oral prosthesis. The microorganisms were cultured in the absence or presence of mucin and artificial saliva, and their adhesion to an abiotic surface (coated with mucin and artificial saliva) was evaluated. Results: The presence of mucin per se onto the abiotic surface decreased the adhesion of all strains, although the combination of mucin with artificial saliva had reduced this effect. No direct correlation between adhesion and the surface free energies of adhesion of the microorganisms was found. Significance: Candida spp. were human commensal microorganisms that became pathogenic when the host immune defenses were compromised. Medical devices were colonized by Candida spp. particularly, oral prostheses, which might lead to the degradation of the prostheses and systemic infections. The salivary secretions that constantly cover the oral cavity influenced Candida spp. adhesion process. Therefore, it was important to understand the interactions between Candida spp., salivary proteins and the characteristic of oral prosthesis when developing materials for oral prostheses.

关键词： Candida Artificial Saliva Mucin Oral Adhesion Surface Properties

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Sirtuin 1 in rat orthotopic liver transplantation:An i Gl-1 preservation solution approach

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World Journal of Gastroenterology 2015年第6期21卷 1765-1774页

作者： Eirini Pantazi Mohamed Amine Zaouali Mohamed Bejaoui Emma Folch-Puy Hassen Ben Abdennebi ana Teresa Varela anabela Pinto Rolo Carlos Marques Palmeira Joan Roselló-Catafau Experimental Hepatic ischemia Reperfusion Unit Institute of Biomedical Research of Barcelona Faculty of Pharmacy Molecular Biology and Anthropology Applied to Development and Health department of life Sciences and Center for Neuroscience and Cell Biology University of Coimbra department of Biology University of Aveiro

AiM:To investigate the possible involvement of Sirtuin1(SiRT1)in rat orthotopic liver transplantation(OlT),when institute Georges lopez 1(iGl-1)preservation solution is enriched with trimetazidine(TMZ).METHODS:Male Sprague-Dawley rats were used as donors and *** were stored in iGl-1 preservation solution for 8h at 4℃,and then underwent OlT according to Kamada’s cuff technique without *** another group,livers were stored in iGl-1 preservation solution supplemented with TMZ,at10-6 mol/l,for 8 h at 4℃and then underwent *** were sacrificed 24 h after reperfusion,and liver and plasma samples were *** injury(transaminase levels),mitochondrial damage(glutamate dehydrogenase activity)oxidative stress(malondialdehyde levels),and nicotinamide adenine dinucleotide(NAD+),the cofactor necessary for SiRT1 activity,were determined by biochemical ***1 and its substrates(acFox O1,ac-p53),the precursor of NAD+,nicotinamide phosphoribosyltransferase(NAMPT),as well as the phosphorylation of adenosine monophosphate activated protein kinase(AMPK),p-m TOR,p-p70S6K(direct substrate of m TOR),autophagy parameters(beclin-1,lC3B)and MAP kinases(p-p38 and p-ERK)were determined by Western ***:liver grafts preserved in iGl-1 solution enriched with TMZ presented reduced liver injury and mitochondrial damage compared with those preservedin iGl-1 solution *** addition,livers preserved in iGl-1+TMZ presented reduced levels of oxidative *** was consistent with enhanced SiRT1 protein expression and elevated SiRT1 activity,as indicated by decreased acetylation of p53 and Fox *** elevated SiRT1 activity in presence of TMZ can be attributed to the enhanced NAMPT protein and NAD+/NADH ***-regulation of SiRT1 was consistent with activation of AMPK and inhibition of phosphorylation of m TOR and its direct substrate(p-p70S6K).As a consequence,autophagy mediators(beclin-1 and lC3B)were ***,MAP kinases w

关键词： Sirtuin 1 ischemia-reperfusion injury liver transp

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Preventative effects of a probiotic, lactobacillus salivarius ssp. salivarius, in the TNBS model of rat colitis

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World Journal of Gastroenterology 2005年第33期11卷 5185-5192页

作者： laura Peran desiree Camuesco Monica Comalada ana Nieto Angel Concha Maria Paz Diaz-Ropero Monica Olivares Jordi Xaus Antonio Zarzuelo Julio Galvez department of Pharmacology School of Pharmacy University of Granada Spain Health and Progress Foundation Granada Spain department of Pathology Hospital Universitario "Virgen de las Nieves" GranadaSpain department of immunology and Animal Sciences Puleva Biotech S.A.GranadaSpain department of immunology and Animal Sciences Puleva Biotech S.A. Granada Spain

AiM： To investigate the intestinal anti-inflammatory effect and mechanism of a probiotic lactobacillus salivarius ssp. salivariusCECT5713 in the TNBS model of rat colitis. METHODS： Female Wistar rats （180-200 g） were used in this study. A group of rats were administered orally the probiotic l. salivarius ssp. salivarius （5 × 10^8 CFU suspended in 0.5 ml of skimmed milk） daily for 3 wk. Two additional groups were used for reference, a non-colitic and a control colitic without probiotic treatment, which received orally the vehicle used to administer the probiotic. Two weeks after starting the experiment, the rats were rendered colitic by intracolonic administration of 10 mg of TNBS dissolved in 0.25 ml of 500 ml/l ethanol. One week after colitis induction, all animals were killed and colonic damage was evaluated both histologically and biochemically. The biochemical studies performed in colonic homogenates include determination of myeloperoxidase （MPO） activity, glutathione （GSH） content, leukotriene B4 （lTB4） and tumor necrosis factor α （TNF-α） levels, as well as inducible nitric oxide synthase （iNOS） expression. in addition, the luminal contents obtained from colonic samples were used for microbiological studies, in order to determine lactobacilli and Bifidobacteria counts. RESUlTS： Treatment of colitic rats with l. salivarius ssp. salivarius resulted in amelioration of the inflammatory response in colitic rats, when compared with the corresponding control group without probiotic treatment. This antiinflammatory effect was evidenced macroscopically by a significant reduction in the extent of colonic necrosis and/or inflammation induced by the administration of TNBS/ethanol （2.3±0.4 cm vs3.4±0.3 cm in control group, P〈0.01） and histologically by improvement of the colonic architecture associated with a reduction in the neutrophil infiltrate in comparison with non-treated colitic rats. The latter was confirmed biochemically by a significant reduction of colonic MPO ac

关键词： lactobacillus salivarius ssp. salivarius, TNBS rat colitis Probiotic Tumor necrosis factor α Nitric oxide

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DHAP胁迫对天山云杉种子萌发过程抗氧化酶活性影响的研究

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新疆农业大学学报 2015年第1期38卷 1-11页

作者：张玉竹刘润潘存德王强新疆农业大学林学与园艺学院乌鲁木齐830052 浙江大学宁波理工学院生物与化学工程学院宁波315100

通过对3,4-二羟基苯乙酮(DHAP)诱导天山云杉(Picea schrenkiana *** Mey.)种子萌发及幼苗生长过程抗氧化酶活性变化的分析阐明自毒物质发生作用的生理机制。选择3个浓度梯度DHAP溶液处理萌发中的天山云杉种子及生长的幼苗,以发芽率和发... 详细信息

通过对3,4-二羟基苯乙酮(DHAP)诱导天山云杉(Picea schrenkiana *** Mey.)种子萌发及幼苗生长过程抗氧化酶活性变化的分析阐明自毒物质发生作用的生理机制。选择3个浓度梯度DHAP溶液处理萌发中的天山云杉种子及生长的幼苗,以发芽率和发芽势为种子表观萌发参数,以胚芽长、胚根长、鲜重为幼苗生长表观参数,荧光素二乙酸酯-碘化丙啶(FDA-Pi)荧光双染色法测定胚根发育状况,分光光度法测定不同时间阶段采集样品中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、过氧化物酶(POD)、抗坏血酸过氧化物酶(APX)、谷胱甘肽还原酶(GR)、谷胱甘肽过氧化物酶(GPX)活性变化。荧光染色结果显示,1.0mmol/l DHAP处理加速种子萌发,根细胞组织营养胁迫过程提前出现,3.0和5.0mmol/l处理组发芽第3天种子根尖未突破种皮,比对照发芽延迟,5.0mmol/l处理组发芽第12天种子根弯曲程度提高出现畸变;酶活性分析结果显示,与对照相比,1.0mmol/l处理组SOD活性第2天、第10天峰值增大,3.0和5.0mmol/l处理组主峰出现时间提前且峰值减小;DHAP处理增强了CAT活性在第7天、第10天双峰峰值;1.0 mmol/l处理组POD活性第7天主峰峰值增大,3.0和5.0mmol/l处理组主峰出现时间延迟且峰值减小;1.0mmol/l处理组第4天、第8天APX活性主峰峰值增大,3.0mmol/l处理组主峰峰值减小,5.0mmol/l处理组主峰出现时间延迟且峰值减小;1.0mmol/l处理组第5天、第8天GR活性峰值增大,3.0和5.0mmol/l处理组峰值减小,第二个峰出现时间提前;1.0mmol/l处理组GPX活性第2天、第5天峰值增大第8天、第11天峰值减小,3.0 mmol/l处理组峰值减小且前两个峰时间延迟,5.0mmol/l处理组第6天、第9天出现强度减小双峰。DHAP处理诱导的种子萌发过程中抗氧化酶活性变化可能是延迟和抑制天山云杉种子萌发的原因之一。

关键词：天山云杉 3,4G二羟基苯乙酮(DHAP) 抗氧化酶种子萌发

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基于拓扑绝缘体纳米线约瑟夫森结的反常临界超流增强和半整数夏皮洛台阶

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物理学报 2023年第3期72卷 235-241页

作者：侯延亮王翔孙晓培吕力中国科学院物理研究所北京凝聚态物理国家实验室北京100190 中国科学院大学物理科学学院北京100049 松山湖材料实验室东莞523808

基于拓扑绝缘体材料的约瑟夫森结是寻找马约拉纳零能模的候选器件,因而受到拓扑量子计算研究领域的关注.这方面实验的关键之一,是制备具有优质结区的约瑟夫森器件.本工作在三维拓扑绝缘体Bi_(2)Te_(3)和Bi_(2)(Se_(x)Te_(1-x))_(3)纳米... 详细信息

基于拓扑绝缘体材料的约瑟夫森结是寻找马约拉纳零能模的候选器件,因而受到拓扑量子计算研究领域的关注.这方面实验的关键之一,是制备具有优质结区的约瑟夫森器件.本工作在三维拓扑绝缘体Bi_(2)Te_(3)和Bi_(2)(Se_(x)Te_(1-x))_(3)纳米线上制作了约瑟夫森结器件,研究了其结区的超导邻近效应、多重安德列夫反射和超流-相位关系,观测到了约瑟夫森结的临界超流随磁场增大而反常地增大、其交流约瑟夫森效应出现半整数的夏皮洛台阶的实验结果.本文还讨论了这些反常现象的可能来源,特别是与结区界面处超导电极的Ti缓冲层和拓扑绝缘体纳米线中的Te元素形成TiTe铁磁性合金层的关系.

关键词：拓扑绝缘体纳米线临界超流反常半整数夏皮洛台阶

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