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Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

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Neural Regeneration Research 2025年第4期20卷 973-989页

作者： María Belén Cieri Alberto javier Ramos Laboratorio de Neuropatología Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a global health crisis,causing significant death and disability *** that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this *** traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain *** astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are *** altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive *** addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional *** therapeutic strategies for traumatic brain injury are focused on preventing acute ***,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of *** this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.

关键词： astrocyte glial scar innate immunity neuroinflammation stab injury Toll-like receptors

Beyond neurodegeneration:engineering amyloids for biocatalysis

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Neural Regeneration Research 2025年第10期20卷 2915-2916页

作者： Andrea Bartolomé-Nafría javier García-Pardo Salvador Ventura Institut de Biotecnologia i de Biomedicina(IBB)and Departament de Bioquímica i Biologia Molecular Universitat Autònoma de BarcelonaBellaterraBarcelonaSpain Hospital Universitari Parc Taulí Institut d’Investigaciói InnovacióParc Taulí(I3PT-CERCA)Universitat Autònoma de BarcelonaSabadellSpain

Amyloid fibrils are highly organized protein or peptide aggregates,often characterized by a distinctive supramolecular cross-β-sheet *** formation and accumulation of these structures have been traditionally associated with neural or systemic human diseases,such as Alzheimer’s disease,Parkinson’s disease,type-2 diabetes,or amyotrophic lateral sclerosis(Wei et al.,2017;Wittung-Stafshede,2023).

关键词： structure amyloid

Long-term survival after liver transplantation for alcoholic liver disease

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World Journal of Gastroenterology 2013年第48期19卷 9198-9208页

作者： Paula Iruzubieta javier crespo Emilio Fábrega Gastroenterology and Hepatology Unit Marqués de Valdecilla University Hospital Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV) 39008 Santander Cantabria Spain

Currently,alcoholic cirrhosis is the second leading indication for liver transplantation in the United States and *** quality of life and survival after a liver transplantation(LT)in patients with alcoholic liver disease(ALD)are similar to those in patients with other cirrhosis *** alcoholic relapse rate after a LT varies from 10%-50%,and these relapse patients are the ones who present a reduced long-term survival,mainly due to cardiovascular diseases and the onset of de novo neoplasms,including lung and upper aerodigestive *** 40%of ALD recipients resume smoking and resume it early ***,our pre-and post-LT follow-up efforts regarding ALD should be focused not only on alcoholic relapse but also on treating and avoiding other modifiable risk factors such as *** psychiatric and psychosocial pre-LT evaluation and the post-LT follow-up with physicians,psychiatrists and addiction specialists are important for reversing these problems because these professionals help to identify patients at risk for relapse as well as those patients who have relapsed,thus enabling responsive actions.

关键词： Alcoholic liver disease Alcohol recidivism Alcohol relapse prevention Long term survival Liver transplantation

Updates on the hepatocyte growth factor/c-Met axis in hepatocellular carcinoma and its therapeutic implications

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World Journal of Gastroenterology 2018年第33期24卷 3695-3708页

作者： javier A García-Vilas miguelángel Medina Department of Pediatrics University of AlbertaEdmonton T6G 2S2Canada Departamento de Biología Molecular y Bioquímica Facultad de CienciasAndalucía TechUniversidad de MálagaMálaga 29071Spain Unidad 741 de CIBER“de Enfermedades Raras”(CIBERER) Málaga 29071Spain Institute of Biomedical Research in Málaga Málaga 29071Spain

Hepatocellular carcinoma(HCC) is the fifth most common cancer and is the second leading cause of cancer death. Since the diagnosis of HCC is difficult, in many cases patients with HCC are diagnosed advanced stage of development. Hepatocyte growth factor(HGF)/c-mesenchymal-epithelial transition receptor(c-Met) axis is a key signaling pathway in HCC, either via canonical or non-canonical pathways. Available treatments against HCC based upon HGF/c-Met inhibition can increase patient lifespan, but do not reach the expected therapeutic benefits. In HCC, c-Met monomers can bind other receptor monomers, activating several noncanonical signaling pathways, leading to increased cell proliferation, invasion, motility, and drug resistance. All of these processes are enhanced by the tumor microenvironment, with stromal cells contributing to boost tumor progression through oxidative stress, angiogenesis, lymphangiogenesis, inflammation, and fibrosis. Novel treatments against HCC are being explored to modulate other targets such as microR NAs, methyltransferases, and acetyltransferases, which are all involved in the regulation of gene expression in cancer. This review compiles basic knowledge regarding signaling pathways in HCC, and compounds already used or showing potential to be used in clinical trials.

关键词： Hepatocellular carcinoma Hepatocyte growth factor/c-MET Tumor microenvironment c-Met

The Tower of Nisida as centre of 17^(th)century fortified naples system

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Frontiers of Architectural Research 2023年第2期12卷 308-318页

作者： Ignacio-javier Gil-crespo Concetta Cusano Claudia Cennamo Research Center“Jose´Joaquı´n de Mora”/Ca´rdenas Foundation MadridSpain Dipartimento di Architettura e Disegno Industriale Universita`degli Studi della Campania“Luigi Vanvitelli”Aversa(CE)Italy

The paper investigates the territorial layout of the fortified system of Naples that developed during the Spanish Vice Kingdom in the 16th-17th *** existing castles and towers,and constructions built for the purpose,were included in the *** Tower of Nisida is one of the existing ancient towers that became part of the impressive 17th century defense system of *** study focus is on the strategic importance acquired by Nisida and its Tower in those years,when it became a key location in the fortified system,both evidencing its cruciality through the study of the field of vision that widens from the location and dealing the issue with the point of view landscape and territorial defense,recalling the concept that the defense architecture is part of architectural heritage.

关键词： Fortification Architectural heritage Territory and landscape Artillery Military architecture

Paediatric non-alcoholic fatty liver disease: a more complex disease than in the adulthood?

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Hepatobiliary Surgery and Nutrition 2019年第3期8卷 270-273页

作者： María Teresa Arias-Loste Paula Iruzubieta javier crespo Department of Gastroenterology and Hepatology University Hospital Marqués de ValdecillaSantanderSpain Investigation Institute Marques de Valdecilla InfectionImmunity and Digestive Diseases GroupIDIVALSantanderSpain

While the association between obesity,type 2 diabetes(T2D)and the presence of steatosis has been established since the beginning of the last century(1),it was not until 1980 that the first references were made about a form of histologic liver lesion designated as non-alcoholic steatohepatitis(NASH).NASH is characterised by the presence of a variable degree of steatosis accompanied by lobular inflammatory infiltrate and hepatocellular damage with or without ***,the broader term of non-alcoholic fatty liver disease(NAFLD)was accepted,which more accurately encompass the entire spectrum of lesions that appear in these patients(2).Ever since then,NAFLD has become progressively the primary cause of chronic liver disease in developed countries(3).

关键词： liver NAFLD damage

Li2SnO3 branched nano- and microstructures with intense and broadband white-light emission

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Nano Research 2019年第2期12卷 441-448页

作者： miguel Garcia-Tecedor javier Bartolome David Maestre Achim Trampert Ana Cremades Dpt. Fisica de Materials Facultad de CC. Fisicas Universidad Complutense de Madrid Madrid 28040 Spain Paul-Drude-Institut fur Festkorperelektronik Hausvogteiplatz 5-7 Berlin 10117 Germany Institute of Advanced Materials (INAM) Universitat Jaume I Castello 12006 Spain Dpt. Fisica de Materiales Facultad de CC. Ftsicas Universidad Complutense de Madrid Madrid 28040 Spain

Exploiting the synergy between microstructure, morphology and dimensions by suitable nanomaterial engineeri ng, can effectively upgrade the physical properties and material performances. Li2SnO3 elongated nano- and microstructures in form of belts, wires, rods and branched structures have been fabricated by a vapor-solid method at temperatures ranging from 700 to 900℃ using metallic Sn and Li2CO3 as precursors. The achievement of these new morphologies can face challenging applications for Li2SnO3, not only in the field of energy storage, but also as building blocks in optoelectronic devices. The micro? and nanostructures grown at 700 and 800℃ correspond to monoclinic Li2SnO3, while at 900℃ complex Li2S nO/SnO2 core-shell microstructures are grow n, as con firmed by X-ray diffractio n and Rama n spectroscopy. Transmission electron microscopy reveals structural disorder related to stacking faults in some of the branched structures, which is associated with the prese nee of the low-temperature phase of L12S nO3. The luminescent resp onse of these structures is domi nated by in tense emissi ons at 2, 2.5 and 3 eV, almost completely covering the whole range of the visible light spectrum. As a result, white-light emission is obtained without the need of phosphors or complex quantum well heterostructures. Enhanced functionality in applications such as in light-emitting devices could be exploited based on the high luminescenee intensity observed in some of the analysed Li2SnO3 structures.

关键词： lithium oxides white light emitters nanostructures luminescenee

Periprocedural management of hemostatic alterations in patients with cirrhosis and vascular liver disorders: a step forward of the American Association for the Study of Liver Diseases

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Hepatobiliary Surgery and Nutrition 2023年第1期12卷 105-109页

作者： Jose Ignacio Fortea Angela Puente javier crespo Emilio Fabrega Gastroenterology and Hepatology Department Clinical and Translational Research in Digestive DiseasesValdecilla Research Institute(IDIVAL)Marques de Valdecilla University HospitalSantanderSpain

“Time flies over us,but leaves its shadow behind”(Nathaniel Hawthorne,1860,The Marble Faun).The shadow that separates the latest guidance on vascular liver disorders of the American Association for the Study of Liver Diseases(AASLD)from its former counterpart is 12 years long(1,2).Along the course,several guidelines from different societies have been published on this topic(3-7).As acknowledged in the preamble,the lack of high-quality evidence in the field led the AASLD to commission a guidance from an expert panel based on formal review and analysis of the *** thus differs from other guidelines that perform systematic reviews with explicit methods of searching,selection,and rating the quality of evidence and,if appropriate,meta-analysis on certain clinical questions(2).

关键词： Portal hypertension cirrhosis vascular liver disorders hemostasis bleeding thrombosis

Clinical significance of donor-specific human leukocyte antigen antibodies in liver transplantation

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World Journal of Gastroenterology 2015年第39期21卷 11016-11026页

作者： Antonio Cuadrado David San Segundo Marcos López-Hoyos javier crespo Emilio Fábrega Gastro- enterology and Hepatology Unit Marqués de Valdecilla University Hospital Instituto de Investigación Marqués de Valdecilla Immunology Unit Marqués de Valdecilla University Hospital. Instituto de Investigación Marqués de Valdecilla

Antibody-mediated rejection(AMR) caused by donorspecific anti-human leukocyte antigen antibodies(DSA) is widely accepted to be a risk factor for decreased graft survival after kidney transplantation. This entity also plays a pathogenic role in other solid organ transplants as it appears to be an increasingly common cause of heart graft dysfunction and an emerging issue in lung transplantation. In contrast, the liver appears relatively resistant to DSA-mediated injury. This "immune-tolerance" liver property has been sustained by a low rate of liver graft loss in patients with preformed DSA and by the intrinsic liver characteristics that favor the absorption and elimination of DSA; however, alloantibody-mediated adverse consequences are increasingly being recognized, and several cases of acute AMR after ABO-compatible liver transplant(LT) have been reported. Furthermore, the availability of new solid-phase assays, allowing the detection of low titers of DSA and the refinement of objective diagnostic criteria for AMR in solid organ transplants and particularly in LT, have improved the recognition and management of this entity. A cost-effective strategy of DSA monitoring, avoidance of class Ⅱ human leukocyte antigen mismatching, judicious immunosuppression attached to a higher level of clinical suspicion of AMR, particularly in cases unresponsive to conventional antirejection therapy, can allow a rational approach to this threat.

关键词： Donor-specific anti-human leukocyte antigen antibo