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The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

Neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： Jennifer M.Colón-Mercado Aranza I.Torrado-Tapias Iris K.Salgado Jose M.Santiago Samuel E.Ocasio Rivera dina P.Bracho-Rincon Luis H.Pagan Rivera jorge d.miranda department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA National Institutes of Health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of Neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

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Tamoxifen:an FdA approved drug with neuroprotective effects for spinal cord injury recovery

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Neural Regeneration Research 2016年第8期11卷 1208-1211页

作者： Jennifer M.Colón jorge d.miranda department of Physiology School of MedicineUniversity of Puerto Rico Medical Sciences Campus

Spinal cord injury（SCI） is a condition without a cure,affecting sensory and/or motor *** physical trauma to the spinal cord initiates a cascade of molecular and cellular events that generates a non-permissive environment for cell survival and axonal *** these complex set of events are damage of the blood-brain barrier,edema formation,inflammation,oxidative stress,demyelination,reactive gliosis and *** multiple events activated after SCI require a multi-active drug that could target most of these events and produce a permissive environment for cell survival,regeneration,vascular reorganization and synaptic ***,a selective estrogen receptor modulator,is an FdA approved drug with several neuroprotective properties that should be considered for the treatment of this devastating *** investigators using different animal models and injury parameters have demonstrated the beneficial effects of this drug to improve functional locomotor recovery after *** suggest that the mechanism of action of Tamoxifen administration is to modulate anti-oxidant,anti-inflammatory and anti-gliotic responses.A gap of knowledge exists regarding the sex differences in response to Tamoxifen and the therapeutic window available to administer this *** addition,the effects of Tamoxifen in axonal outgrowth or synapse formation needs to be *** review will address some of the mechanisms activated by Tamoxifen after SCI and the results recently published by investigators in the field.

关键词： selective estrogen receptor modulator trauma antioxidant anti-inflammatory regeneration reactive gliosis demyelination, estradiol

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Tamoxifen and Src kinase inhibitors as neuroprotective/neuroregenerative drugs after spinal cord injury

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Neural Regeneration Research 2015年第3期10卷 385-390页

作者： Iris K.Salgado Aranza I.Torrado Jose M.Santiago jorge d.miranda department of Physiology School of MedicineUniversity of Puerto Rico Medical Sciences Campus University of Puerto Rico Carolina Campus Department of Natural Sciences

Spinal cord injury （SCI） is a devastating condition that produces significant changes in the life- style of patients. Many molecular and cellular events are triggered after the initial physical impact to the cord. Two major phases have been described in the field of SCI： an acute phase and late phase. Most of the therapeutic strategies are focused on the late phase because this provides an opportunity to target cellular events like apoptosis, demyelination, scar formation and axonal outgrowth. In this mini-review, we will focus on two agents （tamoxifen and a Src kinase family inhibitor known as PP2） that have been shown in our laboratory to produce neuroprotective （increase cell survival） and/or regenerative （axonal outgrowth） actions. The animal model used in our laboratory is adult female rat （N250 g） with a moderate contusion （12.5 mm） to the spinal cord at the T10 level, using the MASCIS impactor device. Tamoxifen or PP2 was administered by implantation of a 15 mg pellet （Innovative Research of America, Sarasota, FL, USA） or by intraperitoneal injections （1.5 mg/kg, every 3 days）, respectively, to produce a long-term effect （28 days）. Tamoxifen and the Src kinase inhibitor, PP2, are drugs that in rats with a moderate spinal cord injury promote functional locomotor recovery, increase spared white matter tissue, and stimulate axonal outgrowth. Moreover, tamoxifen reduces the formation of reactive oxygen species. Therefore, these drugs are possible therapeutic agents that have a neuroprotective/regen- erative activity in vertebrates with SCI.

关键词： tamoxifen Src kinase PP2 trauma regeneration neuroprotection

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Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue

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Neural Regeneration Research 2014年第24期9卷 2164-2173页

作者： Odrick R.Rosas Aranza I.Torrado Jose M.Santiago Ana E.Rodriguez Iris K.Salgado jorge d.miranda department of Physiology School of Medicine University of Puerto Rico Medical Sciences Campus department of Natural Sciences University of Puerto Rico Carolina Campus

The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase （SFK） activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-（4- chlorophenyl）-7-（t-butyl）pyrazolo[3,4-d]pyramidine （PP2）, a selective SFK inhibitor, after spinal cord contusion with the New York University （NYU） impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-iniury in the Basso, Beattie, and Bresnahan open field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin （a guanine nudeotide exchange factor） phosphorylation in the acute phase （4 days post-injury） after trauma. Together, these findings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiology generated after spinal cord injury. Our study also points out that ephexinl phosphorylation （activation） by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury.

关键词： nerve regeneration trauma regeneration Src family kinase Eph receptors ephexin spared tissue locomotor recovery GFAP Ed1 serotonin fibers neural regeneration

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Endoscopic techniques for the diagnosis of pancreatic cystic lesions

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World Journal of Gastroenterology 2025年第1期31卷 1-7页

作者： Sahib Singh Saurabh Chandan Rakesh Vinayek Jahnvi dhar Jayanta Samanta Gabriele Capurso Ivo Boskoski Cristiano Spada jorge d Machicado Stefano Francesco Crinò Antonio Facciorusso department of Internal Medicine Sinai HospitalBaltimoreMD 21215United States division of Gastroenterology and Hepatology Creighton University School of MedicineOmahaNE 68131United States department of Gastroenterology Sinai Hospital of BaltimoreBaltimoreMD 21215United States department of Gastroenterology Postgraduate Institute of Medical Education and ResearchChandigarh 160012India division of Pancreato-Biliary Endoscopy and Endosonography Pancreas Translational and Clinical Research CenterIRCCS San Raffaele Scientific InstituteVita-Salute San Raffaele UniversityMilano 20132Italy digestive Endoscopy Unit Fondazione Policlinico Universitario Agostino Gemelli IRCSSUniversitàCattolica del Sacro Cuore di RomaCenter for Endoscopic Research Therapeutics and TrainingRoma 00168Italy department of Gastroenterology and Endoscopy Catholic UniversityRoma 00168Italy department of Gastroenterology University of Michigan HealthAnn ArborMI 48107United States department of Endoscopy University of VeronaVerona 37121VenetoItaly Gastroenterology Unit Department of Medical and Surgical SciencesUniversity of FoggiaFoggia 71122Italy

Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other *** accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced *** studies have reported varying diagnostic and adverse event rates with these *** addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different *** this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.

关键词： Endoscopic ultrasound Fine needle aspiration Needle confocal laser endomicroscopy Through-the-needle biopsy Contrast-enhanced endoscopic ultrasound

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Lithium bis(trifluoromethanesulfonyl)imide blended in polyurethane acrylate photocurable solid polymer electrolytes for lithium-ion batteries

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Journal of Energy Chemistry 2021年第11期30卷 485-496,I0011页

作者： Cristian Mendes-Felipe J.C.Barbosa R.Gonsalves d.miranda C.M.Costa J.L.Vilas-Vilela S.Lanceros-Mendez BCMaterials Basque Center for MaterialsApplications and NanostructuresUPV/EHU Science Park48940 LeioaSpain Macromolecular Chemistry Group(LABQUIMAC) Department of Physical ChemistryFaculty of Science and TechnologyUniversity of the Basque Country(UPV/EHU)Barrio Sarriena s/nE-48940 LeioaSpain Center of Physics University of MinhoCampus of Gualtar4710-057 BragaPortugal Center of Chemistry University of MinhoCampus of Gualtar4710-057 BragaPortugal Ai–School of Technology IPCABarcelosPortugal Ikerbasque Basque Foundation for Science48009 BilbaoSpain

The increased demand of electronic devices promotes the development of advanced and more efficient energy storage devices, such as batteries. Lithium-ion batteries (LIBs) are the most studied battery systems due to their high performance. Among the different battery components, the separator allows the control of lithium ion diffusion between the electrodes. To overcome some drawbacks of liquid electrolytes, including safety and environmental issues, solid polymer electrolytes (SPEs) are being developed. In this work, a UV photocurable polyurethane acrylate (PUA) resin has been blended with lithium bis(trifluoromethanesulfonyl) imide (LiTFSI) up to 30 wt% LiTFSI content to reach a maximum ionic conductivity of 0.0032 mS/cm at room temperature and 0.09 mS/cm at 100 ℃. Those values allowed applying the developed materials as photocurable SPE in Swagelok type Li/C-LiFePO_(4) half-cells, reaching a battery discharge capacity value of 139 mAh.g^(−1) at C/30 rate. Those results, together with the theoretical studies of the discharge capacity at different C-rates and temperatures for batteries with LiTFSI/PUA SPE demonstrate the suitability of the developed photocurable SPE for LIB applications.

关键词： Solid polymer electrolytes Photocuring Polyurethane acrylate LiTFSI Li-ion batteries

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Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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Neural Regeneration Research 2025年第9期20卷 2454-2463页

作者： Victoria Jiménez Carretero IrisÁlvarez-Merz jorge Hernández-Campano Sergei A.Kirov Jesús M.Hernández-Guijo department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain Ramón y Cajal Institute for Health Research(IRYCIS) Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain Institute of Neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany department of Neuroscience and Regenerative Medicine&department of Neurosurgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-d-aspartate *** N-methyl-d-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-d-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.

关键词： cell swelling N-methyl-d-aspartate receptor non-excitatory amino acids stroke synaptic transmission

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Agronomic evaluation of eight 41 B×110 richter grapevine genotypes as rootstock candidates for mediterranean viticulture

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Horticultural Plant Journal 2023年第4期9卷 720-728页

作者： diana Marín Carlos miranda Francisco Javier Abad jorge Urrestarazu Blanca Mayor Ana Villa-Llop Luis Gonzaga Santesteban department of Agronomy Biotechnology and Food SciencePublic University of NavarreCampus ArrosadiaPamplona 31006NavarraSpain Institute for Multidisciplinary Research in Applied Biology(IMAB-UPNA) Public University of NavarreCampus ArrosadiaPamplona 31006NavarraSpain Institute for Agri-food Technology and Infrastructure of Navarre(INTIA) Edificio de PeritosAvda.Serapio Huici 22Villava 31610NavarraSpain

Choosing the most appropriate rootstock(s)is a key decision for the profitability of vineyards;therefore,there must be a sufficient range of rootstocks in the market adapted to different environmental conditions and production ***,rootstock-breeding programs have been scarce in recent decades,and most of the rootstocks used today were bred a century ago,when the needs of the sector were very different from *** this work,we aimed to evaluate new rootstock candidates before their introduction in the *** agronomic evaluation was conducted on eight novel rootstock genotypes obtained from the first generation of the cross-pollination of 41 B Millardet et de Grasset(41 B)and 110 Richter(110 R)grafted with‘Syrah’and‘Tempranillo’and planted in a typical vineyard of the Ebro Valley in *** the four consecutive growing seasons(2016–2019),growth,yield and berry composition parameters at harvest were collected.A linear mixed-effects model was constructed,considering year and block as random *** factor analysis and hierarchical clustering on principal components were performed to establish clusters of genotypes with similar *** rootstock candidates showed a very wide performance range compared to their *** trial allowed us to identify two very promising candidates(RG8 and RG10),whose registration as commercial rootstocks is already in progress.

关键词： Vitis vinifera Graft Phenolic quality Vigour Yield

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Combination of hydrotreating and delayed coking technologies for conversion of residue

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Chinese Journal of Chemical Engineering 2023年第11期63卷 209-219页

作者： José A.d.Munoz Gabriel Páez jorge Ancheyta Instituto Mexicano del Petróleo Eje Central Lázaro Cárdenas Norte 152Col.San Bartolo AtepehuacanMéxico City 07730México

Residue conversion by combining catalytic hydrotreating and delayed coking has been evaluated comparatively with both processes *** operating conditions are defined to achieve the greatest economic benefit for upgrading an atmospheric residue from a heavy crude oil.A literature model was adapted to simulate the hydrotreating reactor,and for delayed coking,correlations reported in the literature were *** results with both approaches were employed to calculate the techno-economic feasibility of the combined process *** combination of hydrotreating and delayed coking presented an increase in light fractions of 29% and a reduction in coke production of 47.8%.Based on the calculated net benefit values,it was demonstrated that the combination of hydrotreating and delayed coking is technically and economically better than using each process alone,with highest benefit of 57.7 USd·m^(-3).

关键词： Economic benefit Heavy oil Hydrotreating delayed coking

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Corneal collagen cross‑linking epithelium‑on ***‑off:a systematic review and meta‑analysis

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Eye and Vision 2021年第6期8卷 338-352页

作者： Francesco d’Oria Antonio Palazón jorge L.Alio Vissum Innovation c/Cabañal103016 AlicanteSpain division of Ophthalmology Universidad Miguel HernándezAlicanteSpain Section of Ophthalmology Department of Basic Medical ScienceNeuroscience and Sense OrgansUniversity of BariBariItaly department of Clinical Medicine Miguel Hernández UniversitySan Juan de AlicanteSpain

Background:The purpose of the study was to determine the advantages and disadvantages of epi-on corneal crosslinking(CXL)techniques compared with standard epi-off ***:We searched MEdLINE and EMBASE for randomized controlled trials(RCTs)and non-randomized studies of interventions(NRSIs)and we evaluated the selected papers according to the Cochrane risk of bias *** considered,as primary outcomes,average Kmax flattening,changes in uncorrected and corrected distance visual acuity(UdVA and CdVA);as secondary outcomes,we considered changes in pachymetry values and endothelial cell density(ECd).We also investigated adverse events related to the treatments and treatment ***-analysis was conducted with a fixed or random-effects model using weighted mean difference(Md)with 95%confidence interval(CI)as the effect ***:A total of 15 studies were included and among these 15 trials,9 were RCTs and 6 were NRSIs,but only 4 studies showed no high risk of bias and were included in this *** analysis revealed significant postoperative differences in CdVA(Md=0.07;95%CI 0.04 to 0.10;Pd no significative differences in UdVA,Kmax,central corneal thickness(CCT)and ECd(P>0.05).Epi-on CXL protocol was found to be significantly less prompt to have risks of delay in epithelial healing(P=0.035)and persistent stromal haze(P=0.026).Conclusion:Epi-on CXL is as effective as epi-off *** for a higher significant improvement in CdVA with current epi-on protocols,our meta-analysis demonstrates that epi-on and epi-off CXL have comparable effects on visual,topographic,pachymetric,and endothelial ***-on CXL has clinical advantages in terms of comfort and avoidance of complications as it reduces the risk of developing delay in epithelial healing and persistent stromal haze.

关键词： Corneal collagen cross-linking Keratoconus Transepithelial CXL Epithelium-off CXL Epithelium-on CXL Iontophoresis

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