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Combined cell-based therapy strategies for the treatment of Parkinson's disease:focus on mesenchymal stromal cells

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Neural Regeneration Research 2023年第3期18卷 478-484页

作者： Jannette Rodríguez-Pallares María García-Garrote Juan A.Parga JoséLuis Labandeira-García Laboratory of Cellular and Molecular Neurobiology of Parkinson´s Disease Research Center for Molecular Medicine and Chronic Diseases(CiMUS)IDISDepartment of Morphological SciencesUniversity of Santiago de CompostelaSantiago de CompostelaSpain Networking Research Center on Neurodegenerative Diseases(CIBERNED) MadridSpain

Parkinson’s disease is a neurodegenerative condition characterized by motor impairments caused by the selective loss of dopaminergic neurons in the substantia *** is an effective and well-tolerated dopamine replacement ***,levodopa provides only symptomatic improvements,without affecting the underlying pathology,and is associated with side effects after long-term ***-based replacement is a promising strategy that offers the possibility to replace lost neurons in Parkinson’s disease *** studies of transplantation of human fetal ventral mesencephalic tissue have provided evidence that the grafted dopaminergic neurons can reinnervate the striatum,release dopamine,integrate into the host neural circuits,and improve motor *** of the limiting factors for cell therapy in Parkinson’s disease is the low survival rate of grafted dopaminergic *** factors could cause cell death of dopaminergic neurons after grafting such as mechanical trauma,growth factor deprivation,hypoxia,and *** factors play an essential role in the survival of grafted ***,direct,timely,and controllable delivery of neurotrophic factors into the brain faces important *** types of cells secrete neurotrophic factors constitutively and co-transplantation of these cells with dopaminergic neurons represents a feasible strategy to increase neuronal *** this review,we provide a general overview of the pioneering studies on cell transplantation developed in patients and animal models of Parkinson’s disease,with a focus on neurotrophic factor-secreting cells,with a particular interest in mesenchymal stromal cells;that co-implanted with dopaminergic neurons would serve as a strategy to increase cell survival and improve graft outcomes.

关键词： brain repair cell replacement co-grafts dopaminergic neurons fetal ventral mesencephalic tissue mesenchymal stem cells neural grafting neural transplantation neuroblasts neurotrophic factors

Improving colorectal cancer screening programs

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World Journal of Gastroenterology 2024年第22期30卷 2849-2851页

作者： Oscar J Cordero Lucia Mosquera-Ferreiro Iria Gomez-Tourino Department of Biochemistry and Molecular Biology University of Santiago de CompostelaSantiago de Compostela 15782Spain Centre for Research in Molecular Medicine and Chronic Diseases(cimus) University of Santiago de CompostelaSantiago de Compostela 15782GaliciaSpain

In this editorial we comment on the article by Agatsuma et al published in the World Journal of *** suggest policies for more effective colorectal *** is the main policy that has led to lower mortality rates in later years among the population that was eligible for *** is the gold standard tool for screening and has preventive effects by removing precancerous or early malignant ***,colonoscopy is an invasive process,and fecal tests such as the current hemoglobin immunodetection were developed,followed by endoscopy,as the general tool for population screening,avoiding logistical and economic *** so,participation and adherence rates are *** screening options are being developed with the idea that if people could choose between the ones that best suit them,participation in population-based screening programs would *** tests,such as a recent one that detects cell-free DNA shed by tumors called circulating tumor DNA,showed a similar accuracy rate to stool tests for cancer,but were less sensitive for advanced precancerous *** the time when the crosstalk between the immune system and cancer was being established as a new hallmark of cancer,novel immune system-related biomarkers and information on patients’immune parameters,such as cell counts of different immune populations,were studied for the early detection of colorectal cancer,since they could be effective in asymptomatic people,appearing earlier in the adenoma-carcinoma development compared to the presence of fecal ***26,for example,detected 80.37%of advanced *** reach as many eligible people as possible,starting at an earlier age than current programs,the direction could be to apply tests based on blood,urine or salivary fluid to samples taken during routine visits to the primary health system.

关键词： Mortality rates Colorectal cancer Screening Biomarker Fecal hemoglobin immunodetection Soluble sCD26 Colonoscopy Immunoscores

New insights into the relevance of mobile DNA to cancer resistance in blind mole rats:new lessons for cancer therapy

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Cellular & Molecular Immunology 2022年第4期19卷 458-459页

作者： Victor M.Arce Jose A.Costoya Molecular Oncology Laboratory MOL Departamento de FisioloxíaCentro Singular de Investigación en Medicina Molecular e Enfermidades Crónicas(CiMUS)Facultade de MedicinaUniversidade de Santiago de CompostelaInstituto de Investigación Sanitaria de Santiago de Compostela(IDIS)15782Santiago de CompostelaSpain

Although mammals differ substantially in their cancer incidence rates and in the importance of age as a cancer risk factor,there is a scaling of cancer incidence to the lifespan in most *** evolution has selected strategies that maximize reproductive success,which include the development of efficient mechanisms to defer the initiation of cancer until postreproductive age[1].Owing to this,cancers are very rare among wild animals(which do not typically live beyond their reproductive ages).

关键词： cancer insight resistance

Cancer cells escape the immune system by increasing stemness through epigenetic reprogramming

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Cellular & Molecular Immunology 2023年第1期20卷 6-7页

作者： Jose A.Costoya Victor M.Arce Molecular Oncology Laboratory MOL Departamento de FisioloxíaCentro Singular de Investigación en Medicina Molecular e Enfermidades Crónicas(CiMUS)Facultade de MedicinaUniversidade de Santiago de CompostelaInstituto de Investigación Sanitaria de Santiago de Compostela(IDIS)15782Santiago de CompostelaSpain

Cancer stem cells(CSCs),also known as tumor initiating cells,are a minority subpopulation of undifferentiated cancerous cells within the entire tumor that hold self-renewal capacity and differentiation *** are critical for tumor progression,heterogeneity and metastasis and play a major role in chemo-and radiation-resistance and tumor recurrence[1].Although the molecular mechanisms underlying the ability of CSCs to give rise to new tumors and promote resistance to many cancer therapies are not completely understood,increasing knowledge suggests potential roles for these cells in the evasion of immune surveillance[2,3].

关键词： Cancer programming initiating

SARS-CoV-2 infection in K18-ACE2 transgenic mice replicates human pulmonary disease in COVID-19

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Cellular & Molecular Immunology 2021年第3期18卷 513-514页

作者： Victor M.Arce Jose A.Costoya Molecular Oncology Laboratory(MOL) Departamento de FisioloxfaCentro Singular de Investigacibn en Medicina Molecular e Enfermidades Cr6nicas(CiMUS)Facultade de MedicinaUniversidade de Santiago de CompostelaInstituto de Investigaci6n Sanitaria de Santiago de Compostela(IDIS)15782 Santiago de CompostelaSpain

Over the last several months,a global pandemic has developed due to the emergence of the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which is capable of infecting *** lack of preexisting immunity to SARSCoV-2 in humans has prompted the scientific community to strive to understand the mechanisms underlying SARS-CoV-2 pathogenesis and to test new therapeutic agents and vaccines for the clinical management of coronavirus disease 2019(COVID-19).In these efforts,the development of appropriate animal models of the disease is one of the most valuable strategies.

关键词： ACE2 immunity acute

Parkinson’s disease and diabetes mellitus: common mechanisms and treatment repurposing

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Neural Regeneration Research 2022年第8期17卷 1652-1658页

作者： Carmen M.Labandeira Arturo Fraga-Bau David Arias Ron Elena Alvarez-Rodriguez Pablo Vicente-Alba Javier Lago-Garma Ana I.Rodriguez-Perez Department of Clinical Neurology Hospital Alvaro CunqueiroUniversity Hospital ComplexVigoSpain Laboratory of Cellular and Molecular Neurobiology of Parkinson’s Disease Research Center for Molecular Medicine and Chronic Diseases(CIMUS)IDISUniversity of Santiago de CompostelaSantiago de CompostelaSpain Department of Clinical Oncology University Hospital ComplexOurenseSpain Department of Endocrinology Hospital MeixoeiroUniversity Hospital ComplexVigoSpain Networking Research Center on Neurodegenerative Diseases(CiberNed) MadridSpain

In the last decade,attention has become greater to the relationship between neurodegeneration and abnormal insulin signaling in the central nervous system,as insulin in the brain is implicated in neuronal survival,plasticity,oxidative stress and *** mellitus and Parkinson’s disease are both aging-associated diseases that are turning into epidemics *** mellitus and insulin resistance not only increase the possibility of developing Parkinson’s disease but can also determine the prognosis and progression of Parkinsonian ***,there are no available curative or disease modifying treatments for Parkinson’s disease,but the role of insulin and antidiabetic medications in neurodegeneration opens a door to treatment repurposing to fight against Parkinson’s disease,both in diabetic and nondiabetic Parkinsonian ***,it is essential to comprehend how a frequent and treatable disease such as diabetes can influence the progression of neurodegeneration in a challenging disease such as Parkinson’s ***,we review the present evidence on the connection between Parkinson’s disease and diabetes and the consequential implications of the existing antidiabetic molecules in the severity and development of Parkinsonism,with a particular focus on glucagon-like peptide-1 receptor agonists.

关键词： antidiabetic diabetes mellitus dopamine exenatide glucagon-like peptide-1 insulin neurodegeneration neuroinflammation Parkinson’s disease repurposing

Dominance of transposable element‑related satDNAs results in great complexity of“satDNA library”and invokes the extension towards“repetitive DNA library”

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Marine Life Science & Technology 2024年第2期6卷 236-251页

作者： Monika Tunjić‑Cvitanić Daniel García‑Souto Juan J.Pasantes EvaŠatović‑Vukšić Division of Molecular Biology Ruđer BoškovićInstitute10000 ZagrebCroatia Genomes and Disease Centre for Research in Molecular Medicine and Chronic Diseases(CIMUS)Universidade de Santiago de Compostela15706 Santiago de CompostelaSpain Department of Zoology Genetics and Physical AnthropologyUniversidade de Santiago de Compostela15706 Santiago de CompostelaSpain Centro de Investigación Mariña Dpto de BioquímicaXenética e InmunoloxíaUniversidade de Vigo36310 VigoSpain

Research on bivalves is fast-growing,including genome-wide analyses and genome *** characteristics qualify oysters as a valuable model to explore repetitive DNA sequences and their genome *** we char-acterize the satellitomes of five species in the family Ostreidae(Crassostrea angulata,***,***,***,Ostrea edulis),revealing a substantial number of satellite DNAs(satDNAs)per genome(ranging between 33 and 61)and peculiarities in the composition of their *** satDNAs were either associated to or derived from transposable elements,displaying a scarcity of transposable element-unrelated satDNAs in these *** to the non-conventional satellitome constitution and dominance of Helitron-associated satDNAs,comparative satellitomics demanded more in-depth analyses than standardly *** analyses(including ***,the first bivalve species with a defined satellitome)revealed that 13 satDNAs occur in all six oyster genomes,with Cg170/HindIII satDNA being the most abundant in all of *** the“satDNA library model”highlighted the necessity to adjust this term when studying tandem repeat evolution in organisms with such *** repetitive sequences with potential variation in the organizational form and repeat-type affiliation are examined across related species,the introduction of the terms“TE library”and“repetitive DNA library”becomes essential.

关键词： Satellitome Comparative satellitomics Helitron Bivalves “Dark matter of the genome”

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