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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.munoz Pareja Andrew Reisner laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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Current role of capsule endoscopy in Crohn's disease

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World Journal of Gastrointestinal Endoscopy 2016年第17期8卷 572-583页

作者： Marisol Luján-Sanchis laura Sanchis-Artero laura Larrey-Ruiz laura peno-munoz Paola Nunez-Martinez Génesis Castillo-López Lara González-González Carlos Boix Clemente Cecilia Albert Antequera Ana Durá-Ayet Javier Sempere-Garcia-Argüelles Digestive Diseases Unit General University Hospital of Valencia 46014 Valencia Spain

Capsule endoscopy(CE) currently plays an important role in Crohn's disease(CD). It is a noninvasive technique that has led to a breakthrough in the endoscopic diagnosis of diseases of the small intestine. Its superior diagnostic performance and excellent safety profile lead to its considerable acceptance on the part of the patient. This paper reviews current indications of CE in three stages of clinical practice: Suspected CD, unclassified colitis and its extensive role in diagnosed CD. The diagnostic and therapeutic impact of the results of CE on the monitoring of this disease is also reviewed. Knowledge of its applications, the interpretation of its results in an appropriate context and the existence of a validated endoscopic activity index could change the way in which these patients are managed. The definition of mucosal healing and postoperative recurrence by means of endoscopic scoring systems will endow CE with new applications in the management of CD in the near future.

关键词： Capsule endoscopy Inflammatory bowel disease Crohn’s disease

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Ligation or Occlusion of the Internal Iliac Arteries for the Treatment of Placenta Accreta Spectrum:Why Is This Technique Still Performed?

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Maternal-Fetal Medicine 2023年第3期5卷 131-136页

作者： Albaro José Nieto-Calvache José M.Palacios-Jaraquemada Rozi Aditya Aryananda Nicolas Basanta Juan Manuel Burgos-Luna Fernando Rodriguez Carlos Ordonez Daniela Sarria-Ortiz laura munoz-Cordoba Juan Carlos Quintero Valentina Galindo-Velasco Adriana Messa-Bryon Fundación Valle del Lili Departamento de Ginecología y ObstetriciaClínica de Espectro de Acretismo PlacentarioCali 760032Colombia Latin American Group for the Study of Placenta Accreta Spectrum Departamento de Ginecología y Obstetricia Hospital Universitario CEMICBuenos Aires C1431FWOArgentina Department of Obstetrics and Gynecology Dr.Soetomo Academic General HospitalUniversitas AirlanggaSurabaya 60131Indonesia Departamento de Ginecología y Obstetricia Hospital General de Agudos Juan A FernándezBuenos Aires 7011Argentina Fundación Valle del Lili Centro de Investigaciones ClínicasCali 760032Colombia Unidad de diagnóstico prenatal Clínica ImbanacoGrupo Quirón SaludCali 760042Colombia Departamento de ginecología y obstetricia Universidad del ValleCali 760042Colombia Universidad Icesi Facultad de Ciencias de la SaludCali 760031Colombia

Introduction The major complication of placenta accreta spectrum(PAS)disorder is massive bleeding;therefore,multiple vascular interventions have been described to prevent or treat pelvic *** of the internal iliac arteries(IIAs)was published more than 130 years ago,and although research relating to the physiology of this procedure has demonstrated poor vascular control over the last few decades,2-this technique has evolved into an established technique known as endovascular IIA balloon occlusion.

关键词： balloon Internal bleeding

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Trypanosoma rangeli:growth in mammalian cells in vitro and action of a repositioned drug(17-AAG)and a natural extract(Artemisia *** oil)

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BIOCELL 2019年第1期43卷 13-19页

作者： Ana laura CIMADOR Emeli Luciana GALANTE Lucila Ibel munoz Patricia Silvia ROMANO Antonella Denisse LOSINNO Maria Cristina VANRELL Facultad de Farmacia y Bioquimica Universidad Juan Agustin Maza.MendozaArgentina Facultad de Ciencias Medicas Universidad Nacional de Cuyo.MendozaArgentina Laboratorio de Biologia de Trypanosoma cruzi y la celula hospedadora-Instituto de Histologia y Embriologia“Dr.Mario H.Burgos”IHEM-CONICET-Universidad Nacional de Cuyo.Mendoza Argentina

Trypanosoma rangeli and *** are both parasitic unicellular species that infect *** ***,the causative agent of Chagas disease,*** is an infective and non-pathogenic parasite for humans,but pathogenic for vectors from the Rhodnius *** both species can coexist in different hosts and overlap their infective cycles but very little is known about the infection of *** in mammalian cells,we decided to characterize both the development of this parasite in cell culture and the effect of therapeutic agents with potential trypanocidal action on *** found that *** exhibits a cycle of infection in Vero cells similar to that for *** and that the repurposed drug,17-AAG,and the natural extract Artemisia *** oil produce a toxic effect on epimastigotes showing a trypanocidal action from the fifth day of *** treatments also affected the infection of trypomastigotes and reduced the capacity of replication of amastigotes of *** ***/*** coinfection cases have been reported,the finding of drugs with potential activity against both species could be significant in the ***,studies of susceptibility of both species to drugs could also help to know the different mechanisms of pathogenicity in humans displayed by *** that are absent in ***.

关键词： Life-cycle Treatment Trypanosoma rangeli

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Short-term effectiveness of golimumab for ulcerative colitis: Observational multicenter study

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World Journal of Gastroenterology 2016年第47期22卷 10432-10439页

作者： Marta Maia Bosca-Watts Xavier Cortes Marisa Iborra Jose Maria Huguet laura Sempere Gloria Garcia Rafa Gil Mari Fe Garcia Marga munoz Pedro Almela Nuria Maroto Jose Maria Paredes Inflammatory Bowel Disease Unit Digestive Disease DepartmentUniversity of ValenciaUniversity Clinic Hospital of Valencia46010 ValenceiaSpain Digestive Disease Department Hospital of Sagunto46010 ValenciaSpain Gastroenterology Department and CIBEREHD Hospital Universitari i Politecnic La Fe46026 ValenciaSpain Digestive Disease Department General Hospital of Valencia46014 ValenciaSpain Digestive Disease Department General Hospital of Alicante03010 AlacantSpain Digestive Disease Department San Juan University Hospital of Alicante46015 ValenciaSpain Digestive Disease Department Arnau Hospital of Valencia Digestive Disease Department General University Hospital of Elche03203 AlicaneSpain Digestive Disease Department General Hospital of Castellon12004 Castellón de la PlanaSpain Digestive Disease Department Hospital of Manises46940 ManisesSpain Digestive Disease Department Peset University Hospital of Valencia46017 ValenciaSpain

AIM To evaluate the real-world effectiveness of golimumab in ulcerative colitis(UC) and to identify predictors of *** We conducted an observational, prospective and multi-center study in UC patients treated with golimumab, from September 2014 to September 2015. Clinical activity was assessed at wk 0 and 14 with the physician's global clinical assessment(PGA) and the partial Mayo score. Colonoscopies and blood tests were performed, following daily-practice clinical criteria, and the results were recorded in an SPSS *** Thirty-three consecutive patients with moderately to severely active UC were included. Among them, 54.5% were female and 42 years was the average age. Thirty percent had left-sided UC(E2) and 70% had extensive UC(E3). All patients had an endoscopic Mayo score of 2 or 3 at baseline. Twenty-seven point three percent were anti-tumor necrosis factor(TNF) treatment na?ve, whereas 72.7% had previously received infliximab and/or adalimumab. Sixty-nine point seven percent showed clinical response and were steroid-free at wk 14(a decrease from baseline in the partial Mayo score of at least 3 points). Based on PGA, the clinical remission and clinical response rates were 24% and 55% respectively. Withdrawal of corticosteroids was observed in 70.8% of steroid-dependent patients at the end of the study. Three out of 10 clinical non-responders needed a colectomy. Mean fecal calprotectin value at baseline was 300 μg/g, and 170.5 μg/g at wk 14. Being anti-TNF treatment na?ve was a protection factor, which was related to better chances of reaching clinical remission. Twenty-seven point three percent of the patients required treatment intensification at 14 wk of followup. Only three adverse effects(AEs) were observed during the study; all were mild and golimumab was not *** This real-life practice study endorses golimumab's promising results, demonstrating its short-term effectiveness and confirming it as a safe drug during t

关键词： Golimumab Ulcerative 大肠炎真实结果

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Modified Vecchietti’s vaginoplasty with Remeex^(■) system in patient with chronic graft-versus-host disease

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Open Journal of Obstetrics and Gynecology 2012年第1期2卷 85-88页

作者： Melado Vidales laura munoz Muniz Mar Santisteban Padro Javier Medical Department Ginefiv ClinicMadridSpain Pelvic Floor Department La Paz Universitary HospitalMadridSpain

We present a case report of a chronic graft-versus-host disease manifestation in 33-year-old patient with an unusual complication of vaginal stenosis with complete obstruction after allogeneic bone marrow transplantation for myelocytic leukemia. The patient complained on a progressive dyspareunia and sexual intercourse inability. She has received hormone replacement therapy due to the ovarian failure after the chemotherapy treatment. The hormonal treatment was used in continuous combined manner and hematocolpos wasn’t seen during an abdominal ultrasound examination. The reconstructive surgery was performed by the modified Vecchietti’s neovagina technique with a Remeex®system after histological confirmation of main diagnosis. The immediate postoperative course was uneventful with gradual normalization of sexual function.

关键词： Graft-Versus-Host Disease Bone Marrow Transplantation Vaginal Stenosis

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Low-Dose Misoprostol versus Vaginal-Insert Dinoprostone for At-Term Labor Induction: A Prospective Cohort Study

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Open Journal of Obstetrics and Gynecology 2017年第8期7卷 824-834页

作者： laura Emilia munoz Saá María Dolores Martín Ríos María Rosario Noguero Meseguer Department of Obstetrics and Gynecology Rey Juan Carlos HospitalMadridSpain Department of Preventive Medicine Rey Juan Carlos HospitalMadridSpain

Introduction: Given the pharmacological change taking place in Spanish delivery rooms, we designed this study to compare the effectiveness and safety of misoprostol (25 mcg/4h) to 10 mg dinoprostone in its slow-releasing vaginalinsert form to induce at-term labor. Methods: In a prospective cohort study (2013-2015), 401 at-term pregnant women referred for induction (Bishop score ≤ 6), who gave birth at the Rey Juan Carlos Hospital in Móstoles (Madrid, Spain), of whom 241 participants were induced with misoprostol and 160 with dinoprostone. Patients were recruited by non-probabilistic sampling of consecutive cases as the inductions in the Obstetrics Block during the study period were indicated. Results: The cesarean section rate was 14% for the misoprostol group and 19% for the dinoprostone group [RR = 1.38 (95%CI: 0.89 - 2.13), p = 0.145]. No differences were found in the vaginal birth rate in <24 h from starting induction [44% vs. 53%, RR = 1.08 (0.90 - 1.29), p = 0.401], nor in the vaginal birth rate in <12 h, requiring oxytocin or meconium fluid, or for maternal-neonatal complications deriving from the method employed. The percentage of cesarean sections due to failed induction was lower in the misoprostol group (15% vs. 39%, p = 0.028). The time between induction and giving birth was shorter for the dinoprostone group (20 h vs. 23.4 h, p = 0.018). Conclusion: Inducing delivery by low-dose misoprostol offers similar effectiveness and safety to induction by dinoprostone in its slow-releasing vaginal-insert form. However, our sample is limited, and few studies are available on the subject. Further analyses to draw solid conclusions are required.

关键词： Labor Induction Cervical Ripening Misoprostol Dinoprostone

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Type XIX collagen: a promising biomarker from the basement membranes

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Neural Regeneration Research 2020年第6期15卷 988-995页

作者： Ana C.Calvo laura Moreno Leticia Moreno Janne M.Toivonen Raquel Manzano Nora Molina Miriam de la Torre Tresa López Francisco J.Miana-Mena María J.munoz Pilar Zaragoza Pilar Larrodé Alberto García-Redondo Rosario Osta Laboratory of Genetics and Biochemistry(LAGENBIO) University of ZaragozaFaculty of Veterinary SciencesInstituto de Investigación Sanitaria de Aragón(IIS)IA2CIBERNEDZaragozaSpain Hospital Clínico Universitario Lozano Blesa ZaragozaSpain Neurology Department ALS UnitCIBERER U-723Health Research InstituteMadridSpain

Among collagen members in the collagen superfamily,type XIX collagen has raised increasing interest in relation to its structural and biological *** XIX collagen is a Fibril-Associated Collagen with Interrupted Triple helices member,one main subclass of collagens in this *** collagen contains a triple helix composed of three polypeptide segments aligned in parallel and it is associated with the basement membrane zone in different *** molecular structure of type XIX collagen consists of five collagenous domains,COL1 to COL5,interrupted by six non-collagenous domains,NCI to *** most relevant domain by which this collagen exerts its biological roles is NCI domain that can be cleavage enzymatically to release matricryptins,exerting anti-tumor and anti-angiogenic effect in murine and human models of *** physiological conditions,type XIX collagen expression decreases after birth in different tissues although it is necessary to keep its basal levels,mainly in skeletal muscle and hippocampal and telencephalic interneurons in ***,in amyotrophic lateral sclerosis,altered transcript expression levels show a novel biological effect of this collagen beyond its structural role in basement membranes and its anti-tumor and anti-angiogenic *** XIX collagen can exert a compensatory effect to ameliorate the disease progression under neurodegenerative conditions specific to amyotrophic lateral sclerosis in transgenic SOD1 G93 A mice and amyotrophic lateral sclerosis *** novel biological role highlights its nature as prognostic biomarker of disease progression in and as promising therapeutic target,paving the way to a more precise prognosis of amyotrophic lateral sclerosis.

关键词： anti-tumor and anti-angiogenic properties C1 domain COL19A1 gene and protein levels compensatory effect FACIT collagens hippocampal interneurons matricryptins multiplexins NC1 domain regenerative response skeletal muscle type XIX collagen

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General Economic Analysis about the Wind Farms Repowering in Spain

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Journal of Energy and Power Engineering 2012年第7期6卷 1158-1162页

作者： laura Castro-Santos Almudena Filgueira Vizoso Eugenio munoz Camacho Luigi Piegiari Department of Industrial Engineering Ⅱ University of A Coruha Ferrol 15403 Spain Department of Electrical Engineering Polytechnic of Milan Milan 32-2013 Italy

Environmental pollution and emissions from greenhouse gases caused by fossil fuel use are a threat to sustainable development. With renewable energy sources, no polluting emissions are released into the atmosphere. Therefore, using these sources on a large-scale is a key to reducing emissions and meeting the commitments established by Kyoto Protocol. Moreover, EU wants that the 20% of energy consumption is renewable in 2020. This study describes economic aspects, such as net present value and internal profitability rate, of the repowering process for the wind farms. Repowering can generate considerably more power with fewer facilities. This process was the result of a growing demand for renewable energies, facilitated by the great potential of wind energy in the north of Spain. The wind farms studied in this work were set up before 1998 and they had obsolete machinery with low power. There are strong indications that repowering is a profitable endeavour.

关键词：经济分析风电场西班牙通电温室气体排放量可再生能源可持续发展污染排放物

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