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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 m.ría medel Iker Arriaga Lucía Sanjurjo Cristian Huck-Iriart nicola G.A.Abrescia m.ría J.Vicent Defang Ouyang dolores Torres m.ría 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 Polym.r 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 mem.ranes 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 com.rising 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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Dendritic spine degeneration:a prim.ry 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(Am.rim 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

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machine perfusion and the prevention of ischemic type biliary lesions following liver transplant:What is the evidence?

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World Journal of Gastroenterology 2023年第20期29卷 3066-3083页

作者： manuel Durán rafael Calleja Angus Hann George Clarke ruben Ciria Anisa nutu rebeca Sanabria-mateos m.ría dolores ayllón Pedro López-Cillero Hynek m.rgental Javier Briceño m Tham.ra P r Perera Department of Liver Transplantation Reina Sofía University HospitalCórdoba 14004Spain The Liver Unit Queen Elizabeth Hospital BirminghamBirmingham B152THUnited Kingdom Centre for Liver and Gastrointestinal research Institute of Immunology and ImmunotherapyUniversity of BirminghamBirmingham B152THUnited Kingdom

The widespread uptake of different machine perfusion(mP)strategies for liver transplant has been driven by an effort to minimize graft *** to the cholangiocytes during the liver donation,preservation,or early posttransplant period may result in stricturing of the biliary tree and inadequate biliary *** problem continues to trouble clinicians,and may have catastrophic consequences for the graft and *** injury,as a result of com.romised hepatic artery flow,is a well-known cause of biliary strictures,sepsis,and graft ***,very similar lesions can appear with a patent hepatic artery and these are known as ischemic type biliary lesions(ITBL)that are attributed to microcirculatory dysfunction rather than main hepatic arterial *** the warm and cold ischemic period duration appear to influence the onset of *** of the commonly used mP techniques deliver oxygen to the graft cells,and therefore may minimize the cholangiocyte injury and subsequently reduce the incidence of *** clinical experience and published evidence grows for these modalities,the impact they have on ITBL rates is important to *** this review,the evidence for the three commonly used mP strategies(abdominal normothermic regional perfusion[A-nrP],hypothermic oxygenated perfusion[HOPE],and normothermic machine perfusion[nmP])for ITBL prevention has been critically *** with ITBL definitions used in trials,coupled with variations in techniques of mP,make interpretation ***,the evidence suggests that both HOPE and A-nrP prevent ITBL in donated after circulatory death grafts compared to cold *** evidence for ITBL prevention in donor after brain death grafts with any mP technique is weak.

关键词： Liver transplant Ischemic type biliary lesions Hypothermic oxygenated machine perfusion normothermic machine perfusion Abdominal normothermic regional perfusion Donation after circulatory death

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Spontaneous liver rupture as first sign of polyarteritis nodosa

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World Journal of Hepatology 2016年第32期8卷 1414-1418页

作者： Irene Gómez-Luque Felipe Alconchel rubén Ciria m dolores ayllón Antonio Luque m.rina Sánchez Pedro López-Cillero Javier Briceno General Surgery Reina Sofía University Hospital Department of Surgery Faculty of Medicine and NursingUniversity of Córdoba Unit of Hepatobiliary Surgery and Liver Transplant Reina Sofía University Hospital Department of Pathology Reina Sofía University Hospital

Polyarteritis nodosa(PAn) is one of the systemic vasculitis that affects the media wall of arteries of small and medium diameter. Diagnosis proves difficult due to the unspecific symptoms that dominate the clinical profile. Liver involvement is very diverse, ranging from the development of cirrhotic liver disease to acute abdomen presentation that requires surgery because of liver rupture. The management of these patients requires an expert multidisciplinary team. There are several cases in the literature that describe a sudden liver rupture as the first manifestation of a PAn. In this paper we present the case of a 75 years old patient without any previous disease, who is subjected to major hepatic resection for spontaneous liver rupture.

关键词： Polyarteritis nodosa Spontaneous liver rupture Liver surgery Vasculitis rheumatology

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Short-term outcomes of robotic liver resection: An initial singleinstitution experience

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World Journal of Hepatology 2022年第1期14卷 224-233页

作者： manuel Durán Javier Briceño Ana Padial Ferdinando massimiliano Anelli Juan manuel Sánchez-Hidalgo m.ría dolores ayllón rafael Calleja-Lozano Carmen García-Gaitan Unit of Hepatobiliary Surgery and Liver Transplantation General and Digestive Surgery DepartmentReina Sofia University HospitalCordoba 14004Spain GC18 Translational research in Surgery of Solid Organ Transplantation Maimonides Biomedical Research InstituteCórdoba 14004Spain GE09 research in Peritoneal and retroperitoneal Oncological Surgery Maimonides Biomedical Research InstituteCórdoba 14004Spain Department of Anesthesiology and resuscitation Reina Sofia University HospitalCordoba 14004Spain

BACKGrOUnD Liver surgery has traditionally been characterized by the complexity of its procedures and potentially high rates of m.rbidity and m.rtality in inexperienced *** robotic approach has gradually been introduced in liver surgery and has increased notably in recent ***,few centers currently perform.robotic liver surgery and experiences in robot-assisted surgical procedures continue to be limited compared to the laparoscopic *** To analyze the outcomes and feasibility of an initial robotic liver program implemented in an experienced laparoscopic hepatobiliary *** A total of forty consecutive patients underwent robotic liver resection(da Vinci Xi,***,United States)between June 2019 and January *** were prospectively followed and retrospectively *** characteristics and perioperative and short-term outcomes were *** are expressed as mean and standard *** study was approved by the Institutional review *** The mean age of patients was 59.55 years,of which 18(45%)were *** mean body mass index was 29.41 kg/m^(2).nine patients(22.5%)were *** were divided by type of resection as follows:Ten segmentectomies,three wedge resections,ten left lateral sectionectomies,six bisegmentectomies(two VVI bisegmentectomies and four IVb-V bisegmentectomies),two right anterior sectionectomies,five left hepatectomies and two right *** lesions occurred in twenty-nine(72.5%)of the *** mean operative time was 258.11 min and two patients were transfused intraoperatively(5%).Inflow occlusion was used in thirty cases(75%)and the mean total clamping time was 32.62 *** was a single conversion due to uncontrollable *** postoperative complications(Clavien–Dindo>Ⅲb)occurred in three patients(7.5%)and m.rtality in one(2.5%).no patient required readmission to the *** mean hospital stay was 5.6 *** Althou

关键词： robotics Hepatectomy minimally invasive surgery Liver surgery Da vinci

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male genitourinary schistosomiasis-related symptoms among long-term Western African migrants in Spain: a prospective population-based screening study

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贫困所致传染病(英文) 2024年第2期13卷 1-10页

作者： roure Sílvia Vallès Xavier Pérez-Quílez Olga López-mu?oz Israel Cham.rro Anna Abad Elena Valerio Lluís Soldevila Laura Espa?a Sergio Hegazy Alaa H. A. Fernández-rivas Gema Gorriz Ester Herena dolores Oliveira m.rio m.ralles m.ria Carme Conde Carmen montero-Alia Juan José Fernández-Pedregal Elia m.randa-Sánchez Jose Llibre Josep m. Isnard m.r Bonet Josep m.ria Estrada Oriol Prat núria Clotet Bonaventura The Schisto-Stop study group International Health Program (PrOSICS) Barcelona North Metropolitan Territorial Directorate for Infectious Diseases Catalan Institute for Health CAP La Salut Passatge dels Encants S/N Badalona Spain Fundació Lluita contra les Infeccions c/Can Ruti s/n Badalona Spain Infectious Diseases Department Hospital Universitari Germans Trias i Pujol c/Can Ruti s/n Badalona Spain Germans Trias i Pujol research Institute c/Can Ruti s/n Badalona Spain microbiology Department Germans Trias i Pujol University Hospital c/Can Ruti s/n Badalona Spain Department of Genetics and microbiology Universitat Autònoma de Barcelona c/Can Ruti s/n Badalona Spain Faculty of medicine University of Asyut El Fateh Assiut Governorate Egypt Department of Urology Germans Trias i Pujol University Hospital c/Can Ruti s/n Badalona Spain Canovelles Prim.ry Health Care Unit Barcelona North Metropolitan Health Directorate Catalan Institute for Health C/Indústria Canovelles Spain Prim.ry Health Care Unit mataró-(rocafonda-Palau) Barcelona North Metropolitan Health Directorate Catalan Institute for Health Camí Ral el Ravalet Mataró Barcelona Spain Barcelona north metropolitan Prim.ry Care Directorate Catalan Institute for Health Ctra. de Barcelona Sabadell Barcelona Spain Directorate for Innovation and Interdisciplinary Cooperation Barcelona North Metropolitan Health Directorate Catalan Institute for Health C/Can Ruti S/N Badalona Spain IrsiCaixa-AIDS research Institute Hospital Universitari Germans Trias i Pujol University Hospital c/Can Ruti s/n Badalona Spain Infectious Diseases Directorate Barcelona North Metropolitan Health Directorate Catalan Institute for Health C/Can Ruti S/N Badalona Spain

Background Schistosomiasis is highly endemic in sub-Saharan Africa and frequently imported to Europe. male urogenital manifestations are often neglected. We aimed to ascertain the prevalence of genitourinary clinical signs and symptoms among long-term African migrants in a non-endemic European country using a serology *** We carried out a prospective, community-based cross-sectional study of adult male migrants from sub-Saharan Africa living in *** serology tests and microscopic urine examinations were carried out, and clinical data were obtained from an electronic medical record search and a structured *** We included 388 adult males, mean age 43.5 years [Standard Deviation (SD) = 12.0, range: 18–76]. The median time since migration to the European Union was 17 [Interquartile range (IQr): 11–21] years. The most frequent country of origin was Senegal (n = 179, 46.1%). Of the 338, 147 (37.6%) tested positive forSchistosoma. Parasite eggs were present in the urine of only 1.3%. nine genitourinary clinical items were significantly associated with positiveSchistosoma serology results: pelvic pain (45.2%;Or = 1.57, 95%CI: 1.0–2.4), pain on ejaculation (14.5%;Or = 1.85, 95%CI: 1.0–3.5), dyspareunia (12.4%;Or = 2.45, 95%CI: 1.2–5.2), erectile dysfunction (9.5%;Or = 3.10, 95%CI: 1.3–7.6), self-reported episodes of infertility (32.1%;Or = 1.69, 95%CI: 1.0–2.8), haematuria (55.2%;Or = 2.37, 95%CI: 1.5–3.6), dysuria (52.1%;Or = 2.01, 95%CI: 1.3–3.1), undiagnosed syndromic STIs (5.4%), and orchitis (20.7%;Or = 1.81, 95%CI: 1.0–3.1). Clinical signs tended to *** Urogenital clinical signs and symptoms are prevalent among male African long-term migrants with a positiveSchistosoma serology results. Genital involvement can be frequent even among those with long periods of non-residence in their sub-Saharan African countries of origin. Further research is needed to develop diagnostic tools and validate therapeutic approaches to

关键词： Schistosomiasis Chronic schistosomiasis Urogenital schistosomiasis male genital schistosomiasis Longterm migrant

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The effects of advanced paternal age on fertility

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Asian Journal of Andrology 2013年第6期15卷 723-728,I0005页

作者： Jason r Kovac Josephine Addai ryan P Smith robert m Coward dolores J Lamb Larry I Lipshultz Scott Department of Urology Department of Molecular and Cellular Biology The Center for Reproductive Medicine Baylor College of Medicine Houston TX 77030 USA

modern societal pressures and expectations over the past several decades have resulted in the tendency for couples to delay conception. While women experience a notable decrease in oocyte production in their late thirties, the effect of age on spermatogenesis is less well described. While there are no known limits to the age at which men can father children, the effects of advanced paternal age are incompletely understood. This review summ.rizes the current state of knowledge regarding advanced paternal age and its implications on semen quality, reproductive success and offspring health. This review will serve as a guide to physicians in counseling men about the decision to delay paternity and the risks involved with conception later in life.

关键词： aging male fertility outcomes male infertility paternal age

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Stable niO-CeO_(2) nanoparticles with im.roved carbon resistance for methane dry reforming

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Journal of rare Earths 2022年第1期40卷 57-62页

作者： Andrea Cárdenas-Arenas Esther Bailón-García dolores Lozano-Castelló Patrick Da Costa Agustín Bueno-López Department of Inorganic Chemistry University of AlicanteCarretera de San Vicente s/nE03080AlicanteSpain Sorbonne Universite Institut Jean Le Rond d'AlembertCNRS UMR 71902 place de la gare de ceinture78210Saint Cyr L'EcoleFrance

High surface area mixed oxide 8.7%niO-CeO_(2) nanoparticles(122 m2/g;6-7 nm)were prepared using a reversed microemulsion method,and were tested for dry methane reforming(Drm).The catalytic activity of these nanoparticles remains stable under the severe conditions of Drm(700℃),and they show better carbon resistance than conventional niO-CeO_(2) catalysts prepared without control of the *** activity and selectivity of nanoparticles and reference catalyst are similar,but nanoparticles reduce the accumulation of carbon by 63%during the Drm tests,which is a key feature for this *** and H_(2)-TPr suggest that the im.roved carbon resistance of the nanoparticles is due to the better interaction and cooperation between niO and CeO_(2) mixed *** nanoparticles,the participation of cerium cations in the redox processes taking place during Drm stabilizes cationic species of *** the contrary,the catalyst prepared without control of the size suffers segregation of ni during Drm.reaction,and segregated ni explains the higher catalytic formation of carbon.

关键词： methane dry reforming nickel Ceria nanoparticle rare earths

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Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers

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World Journal of Gastroenterology 2006年第13期12卷 2070-2074页

作者： rafael Barcena Gloria m.raleda Javier m.reno m dolores m.rtín Emilio de Vicente Jesús nuo m Luisa mateos Santos del Campo Department of Gastroenterology Hospital ramón y Cajal Facultad de MedicinaUniversidad de AlcaláCtra. Colmenar Km 9.128034 MadridSpain Digestive Diseases Hospital Universitario La Paz 28034 MadridSpain Department of Surgery Hospital ramón y Cajal Facultad de MedicinaUniversidad de Alcalá28034 MadridSpain Department of microbiology Hospital ramón y Cajal Facultad de MedicinaUniversidad de Alcalá28034 MadridSpain

AIm： To analyze whether the presence of anti-HBs in liver transplant recipients is effective in preventing HBV infection. mETHODS： Twenty-three patients receiving anti-HBc positive liver were studied. nine recipients were anti-HBc positive as a result of previous HBV infection. Of them, one also received HBV vaccine during the pre-liver transplantation period. Fourteen recipients were anti-HBs positive due to HBV vaccine administered during the pretransplant period. Liver biopsy was obtained in 10/14 anti-HBc negative/anti-HBs positive recipients and in 4/9 anti-HBc positive recipients. rESULTS： After a mean foUow-up period of 46 months, 1 recipient with protective serum anti-HBs levels developed de novo HBV infection as a consequence of immune escape HBV mutants. Among the 14 vaccinated anti-HBc negative/anti-HBs positive recipients, 1/10 patients with available liver biopsy （10%） had liver HBV-DnA at 13 mo post-liver transplantation without serum viral m.rkers and did not develop de novo HBV *** vaccinated anti-HBc positive recipient without HBV vaccine response was HBV-DnA positive in serum and liver, viral DnA was continuously negative in the following tests, so a spontaneous seroconversion was diagnosed. COnCLUSIOn： The presence of anti-HBs as a result of HBV vaccine or past HBV infection seems to be effective at protecting patients receiving livers from anti-HBc positive donors. However, the em.rgence of immune escape HBV mutants, which can evade the anti-HBs protection, should be considered as a risk of HBV infection.

关键词： HBV vaccine Liver transplantation De novo HBV infection Hepatitis B core antibody

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role of T cell death in maintaining immune tolerance during persistent viral hepatitis

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World Journal of Gastroenterology 2013年第12期19卷 1877-1889页

作者： Juan ramón Larrubia megha Uttam Lokhande Silvia García-Garzón Joaquín miquel dolores Subirá Eduardo Sanz-de-Villalobos Translational Hepatology Unit Guadalajara University Hospital University of Alcalá

Virus-specific T cells play an important role in the resolution of hepatic infection. However, during chronic hepatitis infection these cells lack their effector functions and fail to control the virus. Hepatitis B virus and hepatitis C virus have developed several mechanisms to generate immune tolerance. One of these strategies is the depletion of virus-specific T cells by apoptosis. The immunotolerogenic liver has unique property to retain and activate na ve T cell to avoid the over reactivation of immune response against antigens which is exploited by hepatotropic viruses to persist. The deletion of the virus-specific T cells occurs by intrinsic (passive) apoptotic mechanism. The pro-apoptotic molecule Bcl-2 interacting mediator (Bim) has attracted increasing attention as a pivotal involvement in apoptosis, as a regulator of tissue homeostasis and an enhancer for the viral persistence. Here, we reviewed our current knowledge on the evidence showing critical role of Bim in viral-specific T cell death by apoptotic pathways and helps in the immune tolerance.

关键词： T cell death Specific cytotoxic T lymphocytes Hepatitis C virus immune tolerance Apoptosis Bcl-2 interacting mediator Liver tolerance Apoptotic pathways Viral hepatitis

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