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Neural Regeneration Research 2023年第7期18卷 1493-1494页

作者： Jorge pascual-Guerra joséA.Rodríguez-Navarro Carlos L.paíno Service of Neurobiology-Research Ramón y Cajal University Hospital-IRYCISMadridSpain Department of Cellular Biology Complutense UniversityMadridSpain

Cell replacement therapy has long been proposed as a treatment for the damaged nervous *** of the most challenging aspects of such a strategy,however,is finding sources of donor cells for *** neural cells are rarely an option as every cell in the nervous system has a defined function that would be lost if that cell was to be *** possibility would be sourcing precursor or differentiated cells from fetal tissues;however,aside from ethical issues,heterologous cells are at risk of immunological rejection in the long *** improvements over the past 15 years have led to the possibility that autologous non-neural cells could be used for cell transplantation through their conversion into neural derivatives.

关键词： neural programming removed

Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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Neural Regeneration Research 2025年第8期20卷 2395-2407页

作者： María Norte-Muñoz María Portela-Lomba paloma Sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro Gallego-Ortega Mar Pérez joséMCabrera-Maqueda Javier Sierra Manuel Vidal-Sanz María Teresa Moreno-Flores 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 SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of Neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

Characterization and evolutionary dynamics of complex regions in eukaryotic genomes

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Science China(Life Sciences) 2019年第4期62卷 467-488页

作者： josé Ranz Bryan Clifton Department of Ecology and Evolutionary Biology University of California Irvine

Complex regions in eukaryotic genomes are typically characterized by duplications of chromosomal stretches that often include one or more genes repeated in a tandem array or in relatively close proximity. Nevertheless, the repetitive nature of these regions,together with the often high sequence identity among repeats, have made complex regions particularly recalcitrant to proper molecular characterization, often being misassembled or completely absent in genome assemblies. This limitation has prevented accurate functional and evolutionary analyses of these regions. This is becoming increasingly relevant as evidence continues to support a central role for complex genomic regions in explaining human disease, developmental innovations, and ecological adaptations across phyla. With the advent of long-read sequencing technologies and suitable assemblers, the development of algorithms that can accommodate sample heterozygosity, and the adoption of a pangenomic-like view of these regions, accurate reconstructions of complex regions are now within reach. These reconstructions will finally allow for accurate functional and evolutionary studies of complex genomic regions, underlying the generation of genotype-phenotype maps of unprecedented resolution.

关键词： complex genomic regions sequencing technologies genome assembly structural variation tandem gene duplicates,evolutionary novelty

Evaluation of the potential of coastal cliffs as geosites for the promotion of geotourism

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Geography and Sustainability 2023年第4期4卷 356-371页

作者： Fernando Morante-Carballo María joséDomínguez-Cuesta Nataly paz-Salas Jenifer Malavé-Hernández Jairo Dueñas-Tovar paúl Carrión-Mero Centro de Investigación y Proyectos Aplicados a las Ciencias de la Tierra(CIpaT) ESPOL Polytechnic UniversityP.O.Box 09-01-5863GuayaquilEcuador Facultad de Ciencias Naturales y Matemáticas(FCNM) ESPOL Polytechnic UniversityP.O.Box 09-01-5863GuayaquilEcuador Geo-Recursos y Aplicaciones GIGA ESPOL Polytechnic UniversityP.O.Box 09-01-5863GuayaquilEcuador Departamento de Geologí1 University of OviedoCalle Jesús Arias de Velascos/n33005 OviedoSpain Facultad de Ingeniería en Ciencias de la Tierra(FICT) ESPOL Polytechnic UniversityP.O.Box 09-01-5863GuayaquilEcuador

Coastal zones, with their significant geodiversity, are vital areas for geotourism. Effective management is crucial to harness the geological interest of these sites as geotourism resources while ensuring their conservation. ManabíProvince is one of the most representative regions along the Ecuadorian coast due to its beaches and coastal cliffs, offering a wealth of tourist attractions and cultural elements. This study aims to evaluate the geosite potential of six cliffs in ManabíProvince through quantitative and qualitative analyses to propose geotourism promotion strategies. The methodology involves (i) inventory and characterisation of the cliffs, (ii) assessment of the sites by the Spanish Inventory of Places of Geological Interest method (IELIG), and (iii) qualitative evaluation through focus group discussions and Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis. The results reveal that all six sites boast diverse geological assets, including geomorphological, stratigraphic, sedimentological, and tectonic elements. They are characterised by “high ”scientific, didactic, and tourist interest, while also being sus- ceptible to degradation due to natural and anthropic threats. The SWOT analysis demonstrates that the valuable geological and geomorphological heritage of potential geosites provides an opportunity to foster geotourism and boost the province’s economy, incorporating geoconservation and geoeducation strategies. This study proposes a georoute called “Ruta Acantilados del Sol ”, a 245 km journey encompassing all six sites, incorporating diverse tourist and cultural activities. Our research lays the foundation for fostering geotourism along the Manabícoast and strengthening the connection between nature, heritage, and the welfare of residents within a global resilience plan.

关键词： Georoute Geotourism Touristic cliffCoastal geosites Geoconservation Geoeducation

Effects of epoxyeicosatrienoic acids on levels of eNOS phosphorylation and relevant signaling transduction pathways involved

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Science China(Life Sciences) 2005年第5期48卷 495-505页

作者： CHEN Ruijuan1, JIANG Jiangang1, XIAO Xiao2 & WANG Daowen1 1. The Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China 2. Departments of Molecular genetics and Biochemistry & gene Therapy Center, University of Pittsburgh, Pittsburgh, pa, USA The Institute of Hypertension and Department of Internal Medicine Tongji Hospital Tongji Medical College Huazhong University of Science & Technology Wuhan China Departments of Molecular genetics and Biochemistry & gene Therapy Center University of Pittsburgh Pittsburgh USA

Endothelial nitric oxide synthase (eNOS) is a key enzyme responsible for the regu-lation of vascular homeostasis. Many humor factors and mechanical forces can affect eNOS ac-tivity via phosphorylation modification but the mechanisms involved vary with stimuli applied. We have demonstrated that cytochrome P450 (CYP) epoxygenase-dependent metabolites of ara-chidonic acid, epoxyeicosatrienoic acids (EETs), can robustly up-regulate eNOS expression and its activity, however the relevant signaling pathways responsible for activity regulation are not well known. In this study, we explored the role of PI3 kinase (PI3K)/protein kinase B (Akt) sig-naling pathway in eNOS expression and its phosphorylation in response to EETs via direct addi-tion of EETs into cultured bovine aorta endothelial cells (BAECs) and recombinant adeno- asso-ciated virus-mediated transfection of CYP epoxygenase genes CYPF87V and CYP2C11 to pro-duce endogenous EETs followed by co-treatment with PI3K or Akt inhibitor. Results show that both exogenous and endogenous EETs could remarkably enhance eNOS expression and its phosphorylation at Ser1179 and Thr497 residues; PI3K inhibitor LY294002 could inhibit EETs-induced increase in eNOS-Ser(P)1179 but had no effect on the change of eNOS-Thr(P)497, while Akt inhibitor could attenuate the increase in phosphor-eNOS at both residues; both of the two inhibitors could block EETs-enhanced eNOS expression. These results lead to conclusions: (i) EETs-mediated regulation of eNOS activity may be related with the changes of phosphoryla-tion level at eNOS-Ser1179 via PI3K/Akt and eNOS-Thr497 via Akt; (ii) PI3K/Akt signaling pathway is involved in the up-regulation of eNOS expression by EETs.

关键词： epoxyeicosatrienoic acids, endothelial nitric oxide synthase (eNOS), PI3 kinase, Protein kinase B (Akt), phosphorylation.

Highlights of ASS234: a novel and promising therapeutic agent for Alzheimer’s disease therapy

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Neural Regeneration Research 2020年第1期15卷 30-35页

作者： Alejandro Romero joséMarco-Contelles Eva Ramos Department of Pharmacology&Toxicology Faculty of Veterinary MedicineComplutense University of MadridMadridSpain Laboratory of Medicinal Chemistry Institute of General Organic Chemistry(CSIC)MadridSpain

There is no effective treatment to face Alzheimer’s disease *** molecules are a good approach against the multiple physiopathological events associated with its development and *** this context,N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine(ASS234)has been tested achieving promising ***234 has demonstrated to cross the blood-brain barrier in vivo,and a good in silico safety profile being less toxic than ***,ASS234 reversibly inhibits human acetyl-and butyryl-cholinesterase,and irreversibly inhibits human monoamine oxidase A and ***,this multitarget molecule has antioxidant and neuroprotective properties,and inhibitsΑβ1–42 andΑβ1–40 *** about the mechanism of action,several signaling pathways related to Alzheimer’s disease had been explored showing that ASS234 induces the wingless-type MMTV integration site(Wnt)family and several members of the heat shock proteins family and moreover counteracts neuroinflammatory and oxidative stress-related genes promoting the induction of several key antioxidant ***,in vivo experiments with ASS234 in C57BL/6J mice displayed its ability to reduce amyloid plaque burden and gliosis in the cortex and hippocampus,ameliorating scopolamine-induced learning *** we gather the information regarding ASS234 evaluated so far,showing its ability to face different targets,necessary to counteract a neurodegenerative disease as complex as the Alzheimer’s disease.

关键词： AChE BuChE gene expression heat shock proteins inflammation in silico toxicology MAO A/B neuroprotection oxidative stress Wnt signaling

Intramuscular delivery of rAAV-mediated kallikrein gene reduces hypertension and prevents cardiovascular injuries in model rats

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Acta Pharmacologica Sinica 2007年第12期28卷 1898-1906页

作者： Yao WANG~(2,3),Ling-bo HOU~(2,3),Zhen-jun LIU~2,Yan WANG~2,Chun-lian CHEN~2,Xiao XIAO~(2,4),Dao-wen WANG~(2,5)~2 Institute of Hypertension and Department of Internal Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science andTechnology,Wuhan 430030,China ~4 Departments of Molecular genetics and Biochentistry and gene Therapy Center University of Pittsburgh,Pittsburgh,pa 15261,USA Institute of Hypertension and Department of Internal Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China Departments of Molecular genetics and Biochemistry and gene Therapy Center University of Pittsburgh Pittsburgh USA

Aim:The overexpression of the human tissue kallikrein （HK） gene can reduceblood pressure and ameliorate the secondary syndromes associated with hyper-tension in animal *** current study was designed to investigate hy-potensive effect of intramuscular delivery of HK ***:We generatedan recombinant adeno-associated virus （rAAV） vector expressing human tissuekallikrein under the control of a cytomegalovirus promoter and administered therAAV-HK vector to a spontaneously hypertensive rat model at a dose of 1×1010virons/rat through intramuscular ***:A persistent,high-level ex-pression of HK post-gene delivery was confirmed by *** systolic bloodpressure in the rats receiving rAAV-LacZ and saline increased from 171.3 mmHg to182.3 mmHg 28 weeks' post *** contrast,the delivery of the HK gene byAAV vectors attenuated the increase of the systolic blood pressure in the *** systolic blood pressure was only slightly lowered （from a level of 174mmHg to 170.5 mmHg） post-vector *** difference in blood pres-sure between the treated group and the control groups is statistically significantat 12.6 *** hypotensive effect of rAAV-HK persisted until the end of thetesting *** addition,a significant amelioration of cardiovascularhypertrophy,renal injury,and collagen depositions in the rAAV-HK-treated ani-mals were also ***:All the effects are comparable with thoseof intravenous ***,the intramuscular administration of rAAV-HKmay be used in gene therapy for hypertension.

关键词： recombinant adeno-associated virus vector human tissue kallikrein intramuscular administration hypertension gene therapy cardiovascular remodeling spontaneously hypertensive rat

Steatosis and insulin resistance in hepatitis C: A way out for the virus?

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World Journal of Gastroenterology 2009年第40期15卷 5014-5019页

作者： josé A Del Campo Manuel Romero-Gómez Unit for The Clinical Management of Digestive Diseases and CIBERehd Hospital Universitario de Valme

The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. The pathogenesis of steatosis is due to both viral and host factors. Viral steatosis is mostly reported in patients with genotype 3a, whereas meta-bolic steatosis is often associated with genotype 1 and metabolic syndrome. Several molecular mechanisms responsible for steatosis have been associated with the HCV core protein, which is able to induce gene expres-sion and activity of sterol regulatory element binding protein 1 (SREBP1) and peroxisome proliferator-activat-ed receptor γ (PpaRγ), increasing the transcription of genes involved in hepatic fatty acid synthesis. Steatosis has been also implicated in viral replication. In infected cells, HCV core protein is targeted to lipid droplets which serve as intracellular storage organelles. These studies have shown that lipid droplets are essential for virus assembly. Thus, HCV promotes steatosis as an eff icient mechanism for stable viral replication. Chronic HCV in-fection can also induce insulin resistance. In patients with HCV, insulin resistance is more strongly associated with viral load than visceral obesity. HCV seems to lead to insulin resistance through interference of intracellular insulin signalling by HCV proteins, mainly, the serine phosphorylation of insulin receptor-1 (IRS-1) and im-pairment of the downstream Akt signalling pathway. The HCV core protein interferes with in vitro insulin signal-ling by genotype-specif ic mechanisms, where the role of suppressor of cytokine signal 7 (SOCS-7) in genotype 3aand mammalian target of rapamycin (mTOR) in geno-type 1 in IRS-1 downregulation play key roles. Steatosis and insulin resistance have been associated with f ibrosis progression and a reduced rate of sustained response to peginterferon plus ribavirin.

关键词： Steatosis Insulin resistance Hepatitis Cvirus

Severity of ulcerative colitis is associated with a polymorphism at diamine oxidase gene but not at histamine N-methyltransferase gene

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World Journal of Gastroenterology 2006年第4期12卷 615-620页

作者： ElenaGarcía-Martín JuanLMendoza CarlosTaxonera joséMLadero ManuelDíaz-Rubio CarmenMartínez joséAGAgúndez ElenaUrcelay EmilioGdelaConcha Department of Biochemistry & Molecular Biology & genetics University of ExtremaduraBadajozSpain Service of Gastroenterology Hospital Clinico San CarlosComplutense UniversityMadridSpain Department of Pharmacology University of ExtremaduraBadajozSpain Service of Immunology Hospital Clinico San CarlosComplutense UniversityMadridSpain

AIM： To analyse the role of two common polymorphisms in genes coding for histamine metabolising enzymes as it relates to the risk to develop ulcerative colitis （UC） and the clinical course of these patients. METHODS： A cohort of 229 unrelated patients with UC recruited from a single centre and 261 healthy volunteers were analysed for the presence of Thr105Ile and His645Asp amino acid substitutions at histamine N-methyltransferase （HNMT） and diamine oxidase （ABP1） enzymes, respectively, by amplification-restriction procedures. All patients were phenotyped and followed up for at least 2 years （mean time 11 years）. RESULTS： There were no significant differences in the distribution of ABP1 alleles between ulcerative colitis patients and healthy individuals [OR （95% CI） for variant alleles = 1.22 （0.91-1.61）]. However, mutated ABP1 alleles were present with higher frequency among the 58 patients that required immunosuppresive drugs [OR （95 % CI） for carriers of mutated alleles 2.41 （1.21-4.83; P=0.006）], with a significant gene-dose effect （P= 0.0038）. In agreement with the predominant role of ABP1 versus HNMT on local histamine metabolism in human bowel, the frequencies for carriers of HNMT genotypes or mutated alleles were similar among patients,regardless clinical evolution, and control individuals. CONCLUSION： The His645Asp polymorphism of the histamine metabolising enzyme ABP1 is related to severity of ulcerative colitis.

关键词： Ulcerative colitis Pharmacogenetics Histamine N-Methyltransferase Diamine Oxidase

Anchor Root Development: A World within Worlds

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Molecular Plant 2020年第8期13卷 1105-1107页

作者： joséManuel Pérez-Pérez Instituto de Bioingeniería Universidad Miguel Hernández03202 ElcheSpain

Many plant species develop shoot-borne adventitious roots(ARs)with specialized functions that contribute to plant adaptability by enhancing resource capture and stress *** Arabidopsis,as in many dicots,the postembryonic root system is primarily composed of lateral roots(LRs),which originate from the xylem pole pericycle cells through a process that involves periodic oscillation in gene expression mediated by a β-carotenoidderived signal(Dickinson et al.,2019).Our understanding of the key molecular and signaling events regulating AR initiation has recently been obtained from studies in Arabidopsis,where ARs are formed on etiolated hypocotyls upon transfer to light(Lakehal et al.,2019)or from excised leaf explants(Zhang et al.,2019).Anchor roots(ANRs)are a type of AR that originate immediately below the root-hypocotyl junction in an auxindependent manner and that require a diapocarotenoid-derived signal(anchorene)to emerge(Jia et al.,2019).ANR primordia activation may represent a generic mechanism to compensate for the loss of the growth potential of the primary root(PR),as it is enhanced by mutations affecting PR growth,by whole-root excision or by nitrogen deficiency(Jia et al.,2019).A recent paper by Bai et al.(2020)provides direct evidence that a regulatory module involving the AP2/ERF transcription factor ABSCISIC ACID INSENSITIVE 4(ABI4),the mitogen-activated protein kinases(MAPKs)MPK3 and MPK6,and the phosphatase PP2C12 controls ANR emergence in Arabidopsis.

关键词： roots Arabidopsis Root