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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

microbial starch-binding domains are superior to granule-bound starch synthase I for anchoring luciferase to potato starch granules

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Progress in Natural Science:materials International 2006年第12期16卷 1295-1299页

作者： jean-Paul VINcKEN luc c.j.m. suurs Richard G.F. VISSER Laboratory of Plant Breeding Department of Plant Sciences Wageningen University Wageningen The Netherlands

microbial starch-binding domains (SBD) and granule-bound starch synthase I (GBSSI) are proteins which are accumulated in potato starch granules. The efficiency of SBD and GBSSI for targeting active luciferase reporter proteins to granules during starch biosynthesis was compared. GBSSI or SBD sequences were fused to the N- or c-terminus of the luciferase (luc) gene, via an artificial Pro-Thr encoding linker sequence. The genes were introduced into an amylose-free (amf) potato mutant. It appeared that SBD was superior to GBSSI as a targeting sequence, mainly because the luciferase retained higher activity in the SBD-containing fusion proteins than in the GBSSI-containing ones.

关键词： luciferase GBSS I SBD amf potato.

Plant cell wall-mediated disease resistance:current understanding and future perspectives

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molecular Plant 2024年第5期17卷 699-724页

作者： Antonio molina lucıa jorda miguel Angel Torres marina martın-Dacal Diego jose Berlanga Patricia Fernandez-calvo Elena Gomez-Rubio Sonsoles martın-Santamarıa centro de Biotecnología y Genómica de Plantas Universidad Politécnica de Madrid(UPM)-Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria(INIA/CSIC)Campus de Montegancedo UPMPozuelo de Alarcon(Madrid)Spain Departamento de Biotecnologıa-Biología Vegetal Escuela Técnica Superior de Ingenierıa AgronomicaAlimentarıa y de BiosistemasUPMMadridSpain centro de Investigaciones Biologicas margarita Salas Consejo Superior de Investigaciones Científicas(CSIC)Ramiro de Maeztu 928040 MadridSpain misión Biológica de Galicia Consejo Superior de Investigaciones Científicas(CSIC)Campus de Montegancedo UPMPozuelo de Alarcón(Madrid)Spain

Beyond their function as structural barriers,plant cell walls are essential elements for the adaptation of plants to environmental *** walls are dynamic structures whose composition and integrity can be altered in response to environmental challenges and developmental *** wall changes are perceived by plant sensors/receptors to trigger adaptative responses during development and upon stress *** cell wall damage caused by pathogen infection,wounding,or other stresses leads to the release of wall molecules,such as carbohydrates(glycans),that function as damage-associated molecular patterns(DAmPs).DAmPs are perceived by the extracellular ectodomains(EcDs)of pattern recognition receptors(PRRs)to activate pattern-triggered immunity(PTI)and disease ***,glycans released from the walls and extracellular layers of microorganisms interacting with plants are recognized as microbe-associated molecular patterns(mAmPs)by specific EcD-PRRs triggering PTI *** number of oligosaccharides DAmPs/mAmPs identified that are perceived by plants has increased in recent ***,the structural mechanisms underlying glycan recognition by plant PRRs remain ***,this knowledge is mainly focused on receptors of the Lysm-PRR family,which are involved in the perception of various molecules,such as chitooligosaccharides from fungi and lipo-chitooligosaccharides(i.e.,Nod/mYc factors from bacteria and mycorrhiza,respectively)that trigger differential physiological ***,additional families of plant PRRs have recently been implicated in oligosaccharide/polysaccharide *** include receptor kinases(RKs)with leucine-rich repeat and malectin domains in their EcDs(LRR-mAL RKs),catharanthus roseus REcEPTOR-LIKE KINASE 1-LIKE group(crRLK1L)with malectin-like domains in their EcDs,as well as wall-associated kinases,lectin-RKs,and *** characterization of structural basis of glycans recogniti

关键词： Arabidopsis thaliana cell wall damage-associated molecular patterns DAmPs disease resistance glycans oligosaccharides pattern-triggered immunity PTl pattern recognition receptor PRRs

mitochondrial ROS and Aging:Understanding Exercise as a Preventive Tool

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journal of Science in Sport and Exercise 2020年第1期2卷 15-24页

作者： Henver S.Brunetta Andrew m.Holwerda luc j.c.van Loon Graham P.Holloway Department of Human Health and Nutritional Sciences University of GuelphGuelphON NIG 2W1Canada Department of Physiological Sciences Federal University of Santa CatarinaFlorianopolisBrazil Department of Human Biology NUTRIM School of Nutrition and Translational Research in MetabolismMaastricht University Medical CentreMaastrichtThe Netherlands

Sarcopenia,which is characterized by reduction in muscle mass and strength,contributes to several age-related conditions,including insulin resistance and *** the importance of maintaining muscle mass for healthy aging,the mechanisms contributing to sarcopenia are not fully ***,mitochondria appear to play a key role in the underlying condition,and importantly,respond robustly to exercise *** are intracellular organelles largely attributed to maintaining ATP concentrations,however,the importance of this organelle in overall cellular homeostasis has been expanded in the last decades to include redox signaling,calcium homeostasis,inflammation,and *** lines of evidence suggest that mitochondrial bioenergetics are altered in aged skeletal muscle,resulting in an increase in reactive oxygen species(ROS)production,while conversely genetic/pharmacological approaches that attenuate mitochondrial ROS promote healthy aging and maintenance of muscle *** observations suggest that increased free radicals are one of the bases of the aging process and related ***,we reviewed the current knowledge regarding mitochondrial function and redox balance in aged human skeletal muscle,highlighting the implications of redox unbalance on skeletal muscle mass maintenance and muscle ***,we describe the benefits of exercise and nutrition interventions in the context of improving mitochondrial bioenergetics and functional outcomes regarding skeletal muscle mass and function.

关键词： mitochondria Redox state Aging Sarcopenia.Exercise Nutrition

Propylthiouracyl-induced severe liver toxicity:An indication for alanine aminotransferase monitoring?

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World journal of Gastroenterology 2006年第38期12卷 6232-6234页

作者： m Benyounes c Sempoux c Daumerie j Rahier AP Geubel Departments of Gastroenterology Endocrinology and Pathology St Luc University Hospital Université Catholique de Louvain Brussels 1200 Belgium

Propylthiouracyl (PTU)-related liver toxicity is likely to oc- cur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PTU-induced sub- acute hepatitis, in whom the delay between occurrence of liver damage after the initiation of treatment, the un- derestimation of its severity and the delayed withdrawal of the drug were all likely responsible for liver failure. The high incidence of liver toxicity related to PTU, its potential severity and delayed occurrence after initiation of treatment are in favor of monthly alanine aminotrans- ferase monitoring, at least during the first six months of therapy.

关键词： Hepatitis Drug-induced liver toxicity Propylthiouracil Alanine aminotransferase

Levels of Genotoxic and carcinogenic Ingredients in Plant Food Supplements and Associated Risk Assessment

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Food and Nutrition Sciences 2011年第9期2卷 989-1010页

作者： Suzanne j. P. L. van den Berg Patrizia Restani marelle G. Boersma luc Delmulle Ivonne m. c. m. Rietjens 不详

The present study describes the selection, analysis and risk assessment of genotoxic and carcinogenic ingredients of botanicals and botanical preparations which can be found in food and plant food supplements (PFS). First an inventory was made of botanical ingredients that are of possible concern for human health because of their genotoxic and/or carcinogenic properties. In total, 30 botanical ingredients were selected and subsequently judged for their actual genotoxic and/or carcinogenic potential. Among the 30 compounds considered, 18 compounds were judged to be both genotoxic and carcinogenic. Interestingly, the majority of these compounds belong to the group of alkenylbenzenes or unsaturated pyrrolizidine alkaloids. Subsequently, based on available carcinogenicity data and estimated daily human exposure that was determined focusing on the intake from PFS, the margin of Exposure (mOE) was calculated for the alkenylbenzenes estragole, methyleugenol, safrole and β-asarone. calculating the mOEs for intake estimates of these alkenylbenzenes from PFS resulted in mOE values that were generally lower than 10,000 and often lower than 100. In some cases the mOE was even below 10 meaning that the estimated daily intake is in the range of dose levels causing malignant tumors in experimental animals. This result indicates that the use of PFS containing the genotoxic carcinogens estragole, methyleugenol, safrole or β-asarone might raise a potential concern for human health and would be of high priority for risk management.

关键词： Plant Food Supplements Genotoxicity carcinogenicity Dietary Exposure Benchmark Dose modeling margin of Exposure Alkenylbenzenes chemical Analysis Risk Assessment

Pik3c3 deficiency in myeloid cells imparts partial resistance to experimental autoimmune encephalomyelitis associated with reduced IL-1βproduction

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cellular & molecular Immunology 2021年第8期18卷 2024-2039页

作者： Guan Yang Wenqiang Song jielin Xu jLuke Postoak Feixiong cheng jennifer martinez jianhua Zhang Lan Wu luc Van Kaer Department of Pathology Microbiology and ImmunologyVanderbilt University School of MedicineNashvilleTN37232USA Genomic medicine Institute Lerner Research InstituteCleveland ClinicClevelandOH44195USA Department of molecular medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOH44195USA case comprehensive cancer center Case Western Reserve University School of MedicineClevelandOH44106USA Immunity Inflammationand Disease LaboratoryNational Institute of Environmental Health SciencesResearch Triangle ParkDurhamNC27709USA Department of Pathology University of Alabama at BirminghamBirminghamAL35294USA Birmingham Veterans Affairs medical center BirminghamAL35233USA

The PIK3c3/VPS34 subunit of the class III phosphatidylinositol 3-kinase(PtdIns3K)complex plays a role in both canonical and noncanonical autophagy,key processes that control immune-cell responsiveness to a variety of *** previous studies found that PIK3c3 is a critical regulator that controls the development,homeostasis,and function of dendritic and T *** this study,we investigated the role of PIK3c3 in myeloid cell biology using myeloid cell-specific Pik3c3-deficient *** found that Pik3c3-deficient macrophages express increased surface levels of major histocompatibility complex(mHc)class I and class II *** addition,myeloid cell-specific Pik3c3 ablation in mice caused a partial impairment in the homeostatic maintenance of macrophages expressing the apoptotic cell uptake receptor ***3c3 deficiency caused phenotypic changes in myeloid cells that were dependent on the early machinery(initiation/nucleation)of the classical autophagy ***,myeloid cell-specific Pik3c3-deficient animals showed significantly reduced severity of experimental autoimmune encephalomyelitis(EAE),a primarily cD4^(^(+))T-cell-mediated mouse model of multiple sclerosis(mS).This disease protection was associated with reduced accumulation of myelin-specific cD4^(^(+))T cells in the central nervous system and decreased myeloid cell IL-1β***,administration of SAR405,a selective PIK3c3 inhibitor,delayed disease ***,our studies establish PIK3c3 as an important regulator of macrophage functions and myeloid cell-mediated regulation of *** findings also have important implications for the development of small-molecule inhibitors of PIK3c3 as therapeutic modulators of mS and other autoimmune diseases.

关键词： PIK3c3 Autophagy myeloid cells Experimental autoimmune encephalomyelitis IL-1β

Assessment of Genetic Diversity in contrasting Sugarcane Varieties Using Inter-Simple Sequence Repeat (ISSR) markers

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American journal of Plant Sciences 2011年第3期2卷 425-432页

作者： maria lucília m. da costa Lidiane L. Barbosa Amorim Alberto V. c. Onofre Luiz j. O. Tavares de melo maria Betania m. de Oliveira Reginaldo de carvalho Ana m. Benko-Iseppon 不详

Sugarcane is an important tropical crop, responsible for two thirds of the world sugar production, gaining actually importance as a source of biofuel. Drought tolerance is a very important feature considering the actual climate change scenario throughout the world. This study aimed to determine the genetic diversity between sugarcane varieties with contrasting features under drought. For this purpose, twelve ISSR primers were used to characterize nine sugarcane varieties under cultivation in different countries including selected drought resistant material from Northeast Brazil and two varieties from India as contrasting genotypes. 317 scorable bands were generated, among which 301 comprised polymorphic markers, with an average of 25 polymorphic bands per primer. In the generated dendrogram the accessions were placed in clusters, where cluster A included two varieties from India (co331 and co419), and B comprised plants eight Brazilian accessions and a ‘Barbado’ variety. Within this clade, drought tolerant and susceptible varieties were clearly separated. The present evaluation revealed important contrasting parental candidates regarding their drought response, very promising for future mapping approaches aiming the identification of quantitative trait loci (QTLs) associated to drought in sugarcane. The selected primers were used for the first time in sugarcane, representing valuable tools for future evaluations, with emphasis to diversity characterization and genetic mapping.

关键词： Saccharum Genetic Variability ISSR marker Drought Tolerance

Notes on the Variety of Ternary Algebras

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Advances in Pure mathematics 2014年第9期4卷 506-512页

作者： Aldo V. Figallo claudia m. Gomes lucía S. Sarmiento mario E. Videla Departamento de matemática Universidad Nacional de San Juan San Juan Argentina Instituto de ciencias Básicas Universidad Nacional de San Juan San Juan Argentina

In this work we review the class T of ternary algebras introduced by j. A. Brzozowski and c. j. Serger in [1]. We determine properties of the congruence lattice of a ternary algebra A. The most important result refers to the construction of the free ternary algebra on a poset. In particular, we describe the poset of the join irreducible elements of the free ternary algebra with two free generators.

关键词： De morgan Algebra Free Algebra congruence Variety