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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

Vulvar Swelling in a 12-Year-Old Girl: An Early Manifestation of crohn’s Disease

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case Reports in clinical Medicine 2024年第7期13卷 219-226页

作者： Stefania Rendina dolores Ferrara Rosanna Mamone Sara Isoldi Massimo Zeccolini Francesco Esposito Department of Radiology Universit degli studi di Napoli Luigi Vanvitelli Naples Italy Department of Radiology A.O.R.N. Santobono-Pausilipon Children Hospital Naples Italy Pediatric Gastroenterology and Hepatology Unit Santobono-Pausilipon Childrens Hospital Naples Italy

Vulvar crohn’s disease (VcD) is a rare complication of crohn’s disease, especially in pediatric population. An early diagnosis can result difficult if the complication does not present in conjunction with the classic gastrointestinal symptoms that characterize this disease. In this study we present the case of a 12-year-old girl whose initial symptom of crohn’s disease was a symptomatic vulvar swelling promoted by a rectovaginal fistula. We also provide an overview of crohn’s disease and the vulvar changes found in the course of this disease.

关键词： Recto-Vaginal Fistula Vulvar Swelling Metastatic crohn’s Disease

Dendritic spine degeneration:a primary mechanism in the aging process

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Neural Regeneration Research 2025年第6期20卷 1696-1698页

作者： Gonzalo Flores Leonardo Aguilar-Hernández Fernado García-dolores Humberto Nicolini Andrea Judith Vázquez-Hernández Hiram Tendilla-Beltrán Instituto de Fisiología Benemérita Universidad Autónoma de Puebla(BUAP)PueblaMexico Instituto de ciencias Forenses(INcIFO) Tribunal Superior de Justicia de la Ciudad de México(TSJCDMX).Mexico CityMexico Instituto Nacional de Medicina Genómica(INMEGEN) Mexico CityMexico

Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;AguilarHernández et al., 2023).

关键词： aging process stress

Phagocytosis: A Practical Approach for Evaluating Neutrophil Function in Health and Disease

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Modern Research in Inflammation 2024年第2期13卷 9-28页

作者： Oscar Rojas-Espinosa Patricia Arce-Paredes Sergio Islas-Trujillo Luis Enrique Becerril-Villanueva María dolores Ponce-Regalado Departamento de Inmunologa Escuela Nacional de Ciencias Biolgicas Instituto Politcnico Nacional Ciudad de Mxico Mxico Laboratorio de Psicoinmunologa Instituto Nacional de Psiquiatra Ramn de la Fuente Ciudad de Mxico Mxico Departamento de ciencias de la Salud Centro Universitario de los Altos Universidad de Guadalajara Jalisco Mxico

Neutrophils, crucial players in the effector phase of the immune response, are recognized as important mediators of both innate and adaptive immune responses. Through the production of pro- and anti-inflammatory cytokines, they modulate the function of T and other lymphoid cells. countless reports have highlighted the importance of these cells as efficient antimicrobial agents and annotated their involvement in the pathology of infectious and noninfectious diseases. The development of modern, sophisticated technologies has allowed the study of the functions of these cells in clinical settings. These advanced technologies include fluorescence-activated cell sorters, confocal microscopy, automated cell image analyzers, and live cell analysis instruments. Unfortunately, the cost of these modern instruments, maintenance, reagents, and the need for qualified technicians prohibit their use in low-income laboratories and universities in developing countries. With this in mind, we propose a series of basic tests that can be used in low-input clinical laboratories and universities to evaluate the function of neutrophils in health and disease. Our methodology allows us to assess in a practical and low-cost manner the functions of neutrophils in the phagocytic process, including opsonization, ingestion, ROI production (NBT reduction), myeloperoxidase content, phagosome-lysosome fusion, microbicidal activity, and NET production. Thus, under a disadvantageous ambiance, this may guide physicians in deciding whether a patient’s illness involves phagocytic defects without imposing a heavy financial *** Abstract[-rId13-]

关键词： Phagocytosis Neutrophils Microbicidal Activity Netosis

利用强子探针研究奇特原子核的点质子分布半径及强子探针效应

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Science Bulletin 2024年第11期69卷 1647-1652页

作者：张寂潮孙保华 Isao Tanihata Rituparna Kanungo christoph Scheidenberger Satoru Terashima 王枫 Frederic Ameil Joel Atkinson Yassid Ayyad Soumya Bagchi dolores c.rtina-gil Iris Dillmann Alfredo Estradé Alexey Evdokimov Fabio Farinon Hans Geissel Giulia Guastalla Rudolf Janik Satbir Kaur Ronja Knöbel Jan Kurcewicz Yury Litvinov Michele Marta Magdalena Mostazo Ivan Mukha chiara Nociforo Hooi Jin Ong Stephane Pietri Andrej Prochazka Branislav Sitar Peter Strmen Maya Takechi Junki Tanaka Jossitt Vargas Helmut Weick John Stuart Winfield School of Physics Beihang UniversityBeijing 100191China Research center for Nuclear Physics(RcNP) Osaka UniversityOsaka 567-0047Japan Astronomy and Physics Department Saint Mary’s UniversityHalifax B3H 3C3Canada TRIUMF Vancouver V6T 4A3Canada GSI Helmholtzzentrum für Schwerionenforschung Darmstadt D-64291Germany Justus-Liebig University Gießn 35392Germany Helmholtz Research Academy Hesse for FAIR(HFHF) GSI Helmholtz Center for Heavy Ion ResearchGießn 35392Germany Universidad de Santiago de compostela Santiago de Compostella E-15706Spain Department of Physics Indian Institute of Technology(Indian School of Mines)Dhanbad 826004India Faculty of Mathematics and Physics Comenius UniversityBratislava 84215Slovakia Department of Physics and Atmospheric Science Dalhousie UniversityHalifax B3H 4R2Canada

We report the charge-changing cross sections(σ_(cc))of 24 p-shell nuclides on both hydrogen and carbon at about 900A MeV,of which^(8,9)Li,^(10–12)Be,^(10,14,15)B,^(14,15,17–22)N and^(16)O on hydrogen and^(8,9)Li on carbon are for the first *** from the data set,we found a new and robust relationship between the scaling factor of the Glauber model calculations and the separation energies of the nuclei of interest on both *** allows us to deduce proton radii(R_p)for the first time from the cross sections on *** identical R_p values are deduced from both target data for the neutron-rich carbon isotopes;however,the R_p from the hydrogen target is systematically smaller in the neutron-rich nitrogen *** calls for further experimental and theoretical investigations.

关键词： Exotic nuclei Nuclear size Reaction cross section Glauber model Radioactive ion beam

Breast cancer resistance protein （Bcrp） and the testis--an unexpected turn of events

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Asian Journal of Andrology 2013年第4期15卷 455-460,I0006页

作者： Xiaojing Qiin Yan-Ho cheng dolores D Mruk c Yan cheng The Mary M. Wohlford Laboratory for Male contraceptive Research Center for Biomedical Research Population Council New York NY 10065 USA Department of Anatomy Histology and Embryology School of Basic Medicine Peking Union Medical College Beijing 100005 China and Richmond University Medical center Staten Island NY 10301 USA

Breast cancer resistance protein （Bcrp） is an ATP-dependent efflux drug transporter. It has a diverse spectrum of hydrophilic and hydrophobic substrates ranging from anticancer, antiviral and antihypertensive drugs, to organic anions, antibiotics, phytoestrogens （e.g., genistein, daidzein, coumestrol）, xenoestrogens and steroids （e.g., dehydroepiandrosterone sulfate）. Bcrp is an integral membrane protein in cancer and normal cells within multiple organs （e.g., brain, placenta, intestine and testis） that maintains cellular homeostasis by extruding drugs and harmful substances from the inside of cells. In the brain, Bcrp is a major component of the blood- brain barrier located on endothelial cells near tight junctions （TJs）. However, Bcrp is absent at the Sertoli cell blood-testis barrier （BTB）; instead, it is localized almost exclusively to the endothelial TJ in microvessels in the interstitium and the peritubular myoid cells in the tunica propria. Recent studies have shown that Bcrp is also expressed stage specifically and spatiotemporally by Sertoli and germ cells in the seminiferous epithelium of rat testes, limited only to a testis-specific cell adhesion ultrastructure known as the apical ectoplasmic specialisation （ES） in stage VI-early VIII tubules. These findings suggest that Bcrp is equipped by late spermatids and Sertoli cells to protect late-stage spermatids completing spermiogenesis. Furthermore, Bcrp was found to be associated with F （filamentous）-actin and several actin regulatory proteins at the apical ES and might be involved in the organisation of actin filaments at the apical ES in stage VII-VIII tubules. These findings will be carefully evaluated in this brief review.

关键词： actin filaments breast cancer resistant protein ectoplasmic specialisation effux drugtransporter germ cells Sertoli cells spermatids spermatogenesis spermiogenesis testis

Semen analysis in 21st century medicine： the need for sperm function testing

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Asian Journal of Andrology 2010年第1期12卷 64-70页

作者： dolores J. Lamb Scott Department of Urology and the Department of Molecular and cellular Biology Baylor College of MedicineHouston TX 77030 USA

Sperm function testing, once commonly performed for the infertile couple before employing assisted reproductive technology （ART）, has fallen out of favour in many reproductive medicine centers throughout the world. Indeed, the most recent addition of the ＇World Health Organisation （WHO） Laboratory Manual for the Examination and Processing of Hu- man Semen＇ now groups many of these procedures into a section termed Research Procedures. In large part, this reflects the current clinical practice of bypassing the in-depth evaluation of the male partner, while assuming that if a spermatozoon can be found for intracytoplasmic sperm injection （IcSI）, it must be a healthy cell capable of achieving fertilization. Never- theless, sperm function testing can provide valuable clinical insights into defects causing male infertility. Admittedly, in some cases, functional sperm deficiencies can be overcome using an ART. In other cases, couples will be empowered by the knowledge of the cause of their infertility, and for some couples, perhaps even the likelihood of IcSI success （relative to the spermatozoa）. The knowledge allows them to make truly informed reproductive decisions, including （perhaps） the de- cision to seek donor insemination, to adopt or to remain childless. Knowledge of the cause of their infertility may provide closure for couples and a sense of confidence regarding their choice of reproductive treatment.

关键词： semen analysis sperm function tests

Molecular aspects of mammalian fertilization

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Asian Journal of Andrology 2001年第4期3卷 243-249页

作者： Hector Serrano dolores Garcia-Suarez Dept. Health Sciences Dept. Biology Universidad Autonoma Metropoliana-Iztapalapa Ave. Michoacan and Purisima Mexico City DF 09340 Mexico

Mammalian fertilization is a highly regulated process, much of which are not clearly understood. Here we presentsome information in order to elaborate a working hypothesis for this process, beginning with the sperm modifications inthe epidydimis up to sperm and egg plasmalemma interaction and fusion. We also discuss the still poorly understood ca-pacitation process, the phenomenon of sperm chemo-attraction that brings the capacitated sperm to interact with theoocyte vestments and certain aspects of the acrosome reaction. (Asian J Androl 2001 Dec; 3 : 243 - 249)

关键词： fertilization sperm maturation sperm capacitation sperm-ovum interactions membrane fusion

Functional traits:the pathways to riverine plant resistance in times of hydropeaking

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Ecological Processes 2023年第1期12卷 884-915页

作者： Alejandro Baladrón María dolores Bejarano Isabel Boavida cERIS Civil Engineering Research and Innovation for SustainabilityInstituto Superior TécnicoUniversidade de LisboaAv.Rovisco Pais1049-001 LisbonPortugal Natural Resources Department Universidad Politécnica de Madrid(UPM)Calle JoséAntonio Novais1028040 MadridSpain

Hydropeaking,which refers to rising or falling discharges caused by the turning on or off of hydro-turbines to generate electricity,is a topic of growing interest due to its impact on fluvial *** date,most hydropeaking studies have focused on the impact of peak fluctuations on invertebrate and fish communities,but little attention has been paid to its impact on riverine plants and how functional traits may make them resistant to *** performed a review to assess how a set of 32 plant functional traits can be expressed in riverine plant species,and found evidence of how such expression affects their capacity to cope with common sources of hydropeaking disturbance(i.e.,inundation,fast water drawdown,and rapid water fluctuations linked to up-ramping and down-ramping hydropeaking operations).The information here presented can simplify the evaluation of impacts on riverine plant communities worldwide,as well as to detect suitable species to successfully restore rivers affected by hydropower production.

关键词： Drought Flooding Waterlogging Hydropeaking Plant trait Riverine vegetation