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Are TrkB receptor agonists the right tool to fulfill the promises for a therapeutic value of the brain-derived neurotrophic factor?

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Neural Regeneration Research 2024年第1期19卷 29-34页

作者： marta Zagrebelsky Martin Korte Division of Cellular Neurobiology Zoological InstituteTU BraunschweigBraunschweigGermany Helmholtz Centre for Infection Research AG NINDBraunschweigGermany

Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological processes.It has been shown to act in the brain,promoting neuronal survival,growth,and plasticity as well as in the rest of the body where it is involved in regulating for instance aspects of the metabolism.Due to its crucial and very pleiotro pic activity,reduction of brain-derived neurotrophic factor levels and alterations in the brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling have been found to be associated with a wide spectrum of neurological diseases.Howeve r,because of its poor bioavailability and pharmacological properties,brain-derived neurotrophic factor itself has a very low therapeutic value.Moreover,the concomitant binding of exogenous brain-derived neurotrophic factor to the p75 neurotrophin receptor has the potential to elicit several unwanted and deleterious side effects.Therefo re,developing tools and approaches to specifically promote tropomyosin receptor kinase B signaling has become an important goal of translational research.Among the newly developed tools are different categories of tropomyosin receptor kinase B receptor agonist molecules.In this review,we give a comprehensive description of the diffe rent tro pomyosin receptor kinase B receptor agonist drugs developed so far and of the res ults of their application in animal models of several neurological diseases.Moreover,we discuss the main benefits of tropomyosin receptor kinase B receptor agonists,concentrating especially on the new tropomyosin receptor kinase B agonist antibodies.The benefits observed both in vitro and in vivo upon application of tropomyosin receptor kinase B receptor agonist drugs seem to predominantly depend on their general neuroprotective activity and their ability to promote neuronal plasticity.Moreover,tro pomyosin receptor kinase B agonist antibodies have been shown to specifically bind the tropomyosin receptor kinase B receptor and not p75 neurotrophin rec

关键词： Alzheimer's disease brain-derived neurotrophic factor depression Parkinson's disease tropomyosin receptor kinase B receptor

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Autophagy in neuroinflammation after traumatic brain injury

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Neural Regeneration Research 2024年第5期19卷 951-952页

作者： Chinmoy Sarkar marta M.Lipinski Shock Trauma and Anesthesiology Research(STAR)CenterDepartment of AnesthesiologyUniversity of Maryland School of MedicineBaltimoreMDUSA Department of Anatomy and Neurobiology University of Maryland School of MedicineBaltimoreMDUSA

Traumatic brain injury(TBI)is an acquired injury of the brain caused by the impact of external forces on the brain(Maas et al.,2008).It is a major cause of death and disability among people of all ages(Maas et al.,2008).The primary mechanical injury to the brain initiates a cascade of secondary biochemical events that lead to acute and chronic neurodegeneration and activation of inflammatory pathways(Maas et al.,2008).Both brain-resident microglia and blood-derived myeloid cells-macrophages and monocytes that infiltrate the brain due to injury-induced blood-brain barrier damage,contribute to the inflammatory responses after TBI(Morganti et al.,2015).

关键词： damage death after

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Gut microbial regulation of innate and adaptive immunity after traumatic brain injury

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Neural Regeneration Research 2024年第2期19卷 272-276页

作者： marta Celorrio Kirill Shumilov Stuart H.Friess Department of Pediatrics Washington University in St.Louis School of MedicineSt.LouisMOUSA

Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.

关键词： gut microbiome gut microbiota gut-brain axis macrophage microglia monocyte neuroinflammation short-chain fatty acids T cell traumatic brain injury

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Insights into adsorbent tortuosity across aqueous adsorption systems

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Particuology 2024年第5期88卷 71-88页

作者： Ackmez Mudhoo marta Otero Khim Hoong Chu Department of Chemical and Environmental Engineering Faculty of EngineeringUniversity of MauritiusRéduit 80837Mauritius Department of Applied Chemistry and Physics Universidad de LeónCampus de Vegazana 24071 LeónSpain Department of Chemical Engineering Faculty of EngineeringUniversity of MalayaKuala Lumpur 50603Malaysia

Pore network,pore connectivity,and the resulting effective adsorbate pore diffusivity within an adsorbent are critical physical considerations in mass transport modeling of aqueous adsorption.Tied to these three adsorbent features are the adsorbent tortuosity and tortuosity factor concepts.These concepts encompass the collective hindrance to intra-adsorbent adsorbate transport arising because of a disorderly adsorbent porous topology.It is crucial for materials scientists,chemists,chemical engineers,and water treatment specialists to understand the complex and variable connections among adsorbate chemistry,adsorbent chemistry,adsorbent porosity,pore shape,size,and tortuosity,pore wall effect,adsorbate-adsorbent interactions,and adsorbate-adsorbate interactions in competitively contaminated aqueous environments.Adsorbent tortuosity has been sporadically studied in aqueous adsorption models.Despite the small population of these studies,insightful observations and inferences have been reported.However,as it appears,no review has been published to compile,compare,and contrast these aspects.Hence,this review concisely brings up those observations and interpretations around adsorbent tortuosity for aqueous adsorption systems.The notion of an adsorbent's tortuosity being single-valued is argued to be imprecise.Finally,perspectives are aired on possible research and development directions for elucidating the dynamic attributes of adsorbent tortuosity and applying them in real-scale adsorption-oriented water purification.The data acquired by filling in these research gaps can enable the design of adsorbents more adapted for real-scale water purification.

关键词： Adsorbent Tortuosity Porosity Pore diffusion models Aqueous systems

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Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents

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Neural Regeneration Research 2024年第8期19卷 1835-1841页

作者： Irene Navarro-Lobato Mariam Masmudi-Martín Manuel F.López-Aranda Juan F.López-Téllez Gloria Delgado Pablo Granados-Durán Celia Gaona-romero marta Carretero-Rey Sinforiano Posadas María E.Quiros-Ortega Zafar U.Khan Laboratory of Neurobiology Centro de Investigaciones Médico Sanitarias(CIMES)University of MalagaMalagaSpain Department of Medicine Faculty of MedicineUniversity of MalagaMalagaSpain Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED) Institute of Health Carlos IIIMadridSpain the Donders Institute for Brain Cognition and Behaviour Radboud UniversityNijmegenThe Netherlands the Brain Metastasis Group National Cancer Research Centre(CNIO)MadridSpain the Department of Neurobiology University of California-Los AngelesLos AngelesCAUSA

Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

关键词： behavioral performance brain-derived neurotrophic factor cognitive dysfunction episodic memory memory circuit activation memory deficits memory enhancement object recognition memory prevention of memory loss regulator of G protein signaling

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Survival effects of antibiotic exposure during the larval and adult stages in the West Nile virus vector Culex pipiens

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Insect Science 2024年第2期31卷 542-550页

作者： marta Garrigos Mario Garrido Manuel Morales-Yuste JosuéMartinez-de la Puente Jesus Veiga Faculty of Pharmacy Department of ParasitologyUniversity of GranadaGranadaSpain CIBER de Epidemiologia y Salud Publica(CIBERESP) MadridSpain

The ability of mosquitoes to transmit a pathogen is affected,among other factors,by their survival rate,which is partly modulated by their microbiota.Mosquito microbiota is acquired during the larval phase and modified during their development and adult feeding behavior,being highly dependent on environmental factors.Pharmaceutical residues including antibiotics are widespread pollutants potentially being present in mosquito breeding waters likely affecting their microbiota.Here,we used Culex pipiens mosquitoes to assess the impact of antibiotic exposure during the larval and adult stages on the survival rate of adult mosquitoes.Wild-collected larvae were randomly assigned to two treatments:larvae maintained in water supplemented with antibiotics and control larvae.Emerged adults were subsequently assigned to each of two treatments,fed with sugar solution with antibiotics and fed only with sugar solution(controls).Larval exposure to antibiotics significantly increased the survival rate of adult females that received a control diet.In addition,the effect of adult exposure to antibiotics on the survival rate of both male and female mosquitoes depended on the number of days that larvae fed ad libitum in the laboratory before emergence.In particular,shorter larval ad libitum feeding periods reduced the survival rate of antibiotic-treated adult mosquitoes compared with those that emerged after a longer larval feeding period.These differences were not found in control adult mosquitoes.Our results extend the current understanding of the impact of antibiotic exposure of mosquitoes on a key component of vectorial capacity,that is the vector survival rate.

关键词： antibiotics avian malaria microbiota mosquitoes vector competence vector survival

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Venous Doppler flow patterns,venous congestion,heart disease and renal dysfunction:A complex liaison

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World Journal of Cardiology 2024年第1期16卷 5-9页

作者： Alessio Di Maria Rossella Siligato marta Bondanelli Fabio Fabbian Specialized Medicines Renal UnitUniversity Hospital St.Anna of FerraraFerrara I-44124Italy Department of Biomedical DentalMorphological and Functional Imaging SciencesUniversity of MessinaMessina I-98121Italy Department of Medical Sciences University of FerraraFerrara I-44124Italy Department of Medical Sciences University of FerraraFerrara 44124Italy

The World Journal of Cardiology published an article written by Kuwahara et al that we take the pleasure to comment on.We focused our attention on venous congestion.In intensive care settings,it is now widely accepted that venous congestion is an important clinical feature worthy of investigation.Evaluating venous Doppler profile abnormalities at multiple sites could suggest adequate treatment and monitor its efficacy.Renal dysfunction could trigger or worsen fluid overload in heart disease,and cardio-renal syndrome is a well-characterized spectrum of disorders describing the complex interactions between heart and kidney diseases.Fluid overload and venous congestion,including renal venous hypertension,are major determinants of acute and chronic renal dysfunction arising in heart disease.Organ congestion from venous hypertension could be involved in the development of organ injury in several clinical situations,such as critical diseases,congestive heart failure,and chronic kidney disease.Ultrasonography and abnormal Doppler flow patterns diagnose clinically significant systemic venous congestion.Cardiologists and nephrologists might use this valuable,noninvasive,bedside diagnostic tool to establish fluid status and guide clinical choices.

关键词： Cardio-renal syndrome Fluid overload Venous congestion Acute kidney injury Ultrasound Doppler flow patterns

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Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

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Neural Regeneration Research 2024年第3期19卷 542-547页

作者： María Norte-Muñoz David García-Bernal Diego García-Ayuso Manuel Vidal-Sanz marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain Grupo de Investigación Trasplante Hematopoyético y Terapia celular Departamento de Bioquímica e Inmunología.Facultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

关键词： adaptive immunity cell therapy central nervous system immune system innate immunity mesenchymal stromal cells neuroregeneration preclinical studies retina transplantation

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High-temperature tribological performance of functionally graded Stellite 6/WC metal matrix composite coatings manufactured by laser-directed energy deposition

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Friction 2024年第3期12卷 522-538页

作者： marta OSTOLAZA Alaitz ZABALA Jon Inaki ARRIZUBIETA Iñigo LLAVORI Nagore OTEGI Aitzol LAMIKIZ Department of Mechanical Engineering University of the Basque Country UPV/EHUPlaza Torres Quevedo 1Bilbo 48013Spain Faculty of Engineering Mechanics and Industrial ProductionMondragon UnibertsitateaLoramendi 4Mondragon 20500Spain

Wear-driven tool failure is one of the main hurdles in the industry.This issue can be addressed through surface coating with ceramic-reinforced metal matrix composites.However,the maximum ceramic content is limited by cracking.In this work,the tribological behaviour of the functionally graded WC-ceramic-particlereinforced Stellite 6 coatings is studied.To that end,the wear resistance at room temperature and 400°C is investigated.Moreover,the tribological analysis is supported by crack sensitivity and hardness evaluation,which is of utmost importance in the processing of composite materials with ceramic-particle-reinforcement.Results indicate that functionally graded materials can be employed to increase the maximum admissible WC content,hence improving the tribological behaviour,most notably at high temperatures.Additionally,a shift from abrasive to oxidative wear is observed in high-temperature wear testing.

关键词： friction coating metal matrix composite functionally graded materials high temperature laserdirected energy deposition

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Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

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Bio-Design and Manufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim Janos M.Kanczler Stuart Lanham Andrew Rawlings marta Roldo Gianluca Tozzi Jonathan I.Dawson Gianluca Cidonio Richard O.C.Oreffo Faculty of Medicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharmacy and Biomedical Science University of PortsmouthPortsmouth PO12DTUK School of Engineering Faculty of Engineering and ScienceUniversity of GreenwichGreenwich ME44TBUK Center for Life Nano-and Neuro-Science(CLN2S) Italian Institute of Technology00161 RomeItaly

Autograft or metal implants are routinely used in skeletal repair.However,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering alternative.The use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor tissueregeneration.Thus,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic lineage.In this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based deposition.The inclusion of the nanoﬁller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon printing.The composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)model.The inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven days.This study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular matrix Nanoclay Bone 3D bioprinting

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