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Molecular diagnosis of Chagas disease:a systematic review and meta-analysis

Infectious Diseases of Poverty 2023年第5期12卷 93-93页

作者： Guillermo Pascual-Vázquez Montserrat Alonso-Sardón Beatriz Rodríguez-Alonso Javier Pardo-Lledías Angela Romero Alegría Pedro Fernández-Soto juan luis muñoz bellido Antonio muro Moncef Belhassen-García Infectious and Tropical Diseases Group (E-INTRO) Biomedical Research Institute of Salamanca (IBSAL) Tropical Diseases Research Center of the University of Salamanca (CIETUS) Faculty of Pharmacy University of Salamanca Salamanca Spain Area of Preventive Medicine Epidemiology and Public Health Department of Biomedical and Diagnostic Sciences Faculty of Medicine E-INTRO IBSAL CIETUS University of Salamanca Salamanca Spain Internal Medicine Service University Health Care Complex of Salamanca (CAUSA) E-INTRO IBSAL CIETUS Salamanca Spain Internal Medicine Department Hospital Marqués de Valdecilla University of Cantabria IDIVAL (Valdecilla Research Institute) Santander Spain Internal Medicine Service CAUSA. E-INTRO IBSAL CIETUS Salamanca Spain Infectious and Tropical Diseases Group (E-INTRO) IBSAL. CIETUS. Faculty of Pharmacy University of Salamanca Salamanca Spain Microbiology and Parasitology Service CAUSA IBSAL CIETUS CSIC Department of Biomedical and Diagnostic Sciences University of Salamanca Salamanca Spain Internal Medicine Service. Infectious Diseases Section CAUSA IBSAL CIETUS University of Salamanca Salamanca Spain

Background The complexity of the Chagas disease and its phases is impossible to have a unique test for both phases and a lot of different epidemiological scenarios.Currently,serology is the reference standard technique;occasionally,results are inconclusive,and a different diagnostic technique is needed.Some guidelines recommend molecular testing.A systematic review and meta-analysis of available molecular tools/techniques for the diagnosis of Chagas disease was performed to measure their heterogeneity and efficacy in detecting Trypanosoma cruzi infection in blood samples.Methods A systematic review was conducted up to July 27,2022,including studies published in international databases.Inclusion and exclusion criteria were defined to select eligible studies.Data were extracted and presented according to PRISMA 2020 guidelines.Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2(QUADAS-2).A random-effects model was used to calculate pooled sensitivity,specificity,and diagnostic odds ratio(DOR).Forest plots and a summary of the receiving operating characteristics(SROC)curves displayed the outcomes.Heterogeneity was determined by I^(2)and Tau^(2)statistics and P values.Funnel plots and Deek's test were used to assess publication bias.A quantitative meta-analysis of the different outcomes in the two different clinical phases was performed.Results We identified 858 records and selected 32 papers.Studies pertained to endemic countries and nonendemic areas with adult and paediatric populations.The sample sizes ranged from 17 to 708 patients.There were no concerns regarding the risk of bias and applicability of all included studies.A positive and nonsignificant correlation coefficient(S=0.020;P=0.992)was obtained in the set of studies that evaluated diagnostic tests in the acute phase population(ACD).A positive and significant correlation coefficient(S=0.597;P<0.000)was obtained in the case of studies performed in the chronic phase population(CCD).This resulted in high heterogeneity between

关键词： Chagas disease Trypanosoma cruzi Molecular diagnosis Polymerase chain reaction Loop-mediated isothermal amplification

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Nickel-based cerium zirconate inorganic complex structures for CO_(2)valorisation via dry reforming of methane

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Journal of Environmental Sciences 2024年第6期140卷 12-23页

作者： juan luis Martín-Espejo Loukia-Pantzechroula Merkouri Jesús Gándara-Loe José Antonio Odriozola Tomas Ramirez Reina Laura Pastor-Pérez Department of Inorganic Chemistry and Material Sciences Institute of Seville University of Seville-CSICSeville 41092Spain Department of Chemical and Process Engineering University of SurreyGuildford GU27XHUnited Kingdom

The increasing anthropogenic emissions of greenhouse gases(GHG)is encouraging extensive research in CO_(2)utilisation.Dry reforming of methane(DRM)depicts a viable strategy to convert both CO_(2)and CH4into syngas,a worthwhile chemical intermediate.Among the different active phases for DRM,the use of nickel as catalyst is economically favourable,but typically deactivates due to sintering and carbon deposition.The stabilisation of Ni at different loadings in cerium zirconate inorganic complex structures is investigated in this work as strategy to develop robust Ni-based DRM catalysts.XRD and TPR-H2analyses confirmed the existence of different phases according to the Ni loading in these materials.Besides,superficial Ni is observed as well as the existence of a CeNiO_(3)perovskite structure.The catalytic activity was tested,proving that 10 wt.%Ni loading is the optimum which maximises conversion.This catalyst was also tested in long-term stability experiments at 600and 800℃in order to study the potential deactivation issues at two different temperatures.At 600℃,carbon formation is the main cause of catalytic deactivation,whereas a robust stability is shown at 800℃,observing no sintering of the active phase evidencing the success of this strategy rendering a new family of economically appealing CO_(2)and biogas mixtures upgrading catalysts.

关键词： CO_(2)conversion Dry reforming of methane Nickel catalysts Pyrochlore Cerium zirconate

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Lifestyles of Older Adults in Castilla-La Mancha(Spain):Influence of Sex,Age,and Habitat

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Fudan Journal of the Humanities and Social Sciences 2024年第2期17卷 313-335页

作者： Esther Portal Martínez juan Lirio Castro David Alonso González Joséluis Gómez Ramos University of Castilla-La Mancha Talavera de la ReinaSpain Complutense University MadridSpain

This paper presents the quantitative research results of a comprehensive study titled“Current Profle of Older Adults in Castilla-La Mancha(Spain).”The study aims to understand and describe the characteristics of individuals aged 65 and above within this autonomous region,with a focus on the variables of sex,age,and habitat.A cross-sectional approach was employed,utilizing quantitative methods to collect data.To gather information,a customized questionnaire was developed to address the study objectives,covering various aspects such as sociodemographic factors,living conditions,leisure activities,social participation,and cultural interests.The survey was conducted via telephone,ensuring representation by employing gender quotas,age-group stratifcation,and considerations for habitat size.A representative sample of 1,065 participants was included in the study.The fndings reveal a degree of homogeneity in the lifestyles of older adults,with discernible variations infuenced by factors such as sex,habitat,and age.These results shed light on the diverse habits and experiences of older adults,emphasizing the signifcance of habitat conditions,social participation,and the aging process.

关键词： Lifestyle habits Older adults Habitat conditions Social participation Aging experience

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muscle strength deficits are associated with low bone mineral density in young pediatric cancer survivors:The iBoneFIT project

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Journal of Sport and Health Science 2024年第3期13卷 419-427页

作者： Andres Marmol-Perez Jose J.Gil-Cosano Esther Ubago-Guisado Francisco J.Llorente-Cantarero juan Francisco Pascual-Gázquez Kirsten K.Ness Vicente Martinez-Vizcaino Jonatan R.Ruiz luis Gracia-Marco Department of Physical Education and Sports Faculty of Sport SciencesSport and Health University Research Institute(iMUDS)University of GranadaGranada 18011Spain Department of Epidemiology and Cancer Control St.Jude Children's Research HospitalMemphisTN 38105USA Department of Communication and Education Loyola University AndalusiaSeville 41704Spain Biosanitary Research Institute ibs.GranadaGranada 18012Spain Maimonides Biomedical Research Institute of Cordoba(IMIBIC) Cordoba 14004Spain CIBEROBN Biomedical Research Networking Center for Physiopathology of Obesity and NutritionCarlos III Health InstituteMadrid 28029Spain Department of Specific Didactics Faculty of EducationUniversity of CordobaCordoba 14071Spain Pediatric and adolescent hematology and oncology service Pediatrics and Pediatric Surgery Clinical Management UnitVirgen de las Nieves University HospitalGranada 18014Spain Health and Social Research Center Universidad de Castilla-La ManchaCuenca 13001Spain

Background Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density(aBMD).However,the prevalence of muscle strength deficits is not well documented,and the associations of muscle strength with aBMD are unknown in this population.Therefore,this study aimed to investigate the prevalence of upper-and lower-body muscle strength deficits and to examine the associations of upper-and lower-body muscle strength with age-,sex,and race-specific aBMD Z-scores at the total body,total hip,femoral neck,and lumbar spine.Methods This cross-sectional study included 116 pediatric cancer survivors(12.1±3.3 years old,mean±SD;42.2%female).Upper-and lower-body muscle strength were assessed by handgrip and standing long jump test,respectively.Dual‑energy X‑ray absorptiometry was used to measure aBMD(g/cm2).Associations between muscle strength and aBMD were evaluated in multivariable linear regression models.Logistic regression was used to evaluate the contribution of muscle strength(1-decile lower)to the odds of having low aBMD(Z-score≤1.0).All analyses were adjusted for time from treatment completion,radiotherapy exposure,and body mass index.Results More than one-half of survivors were within the 2 lowest deciles for upper-(56.9%)and lower-body muscle strength(60.0%)in comparison to age-and sex-specific reference values.muscle strength deficits were associated with lower aBMD Z-scores at all sites(B=0.133–0.258,p=0.001–0.032).Each 1-decile lower in upper-body muscle strength was associated with 30%–95%higher odds of having low aBMD Z-scores at all sites.Each 1-decile lower in lower-body muscle strength was associated with 35%–70%higher odds of having low aBMD Z-scores at total body,total hip,and femoral neck.Conclusion muscle strength deficits are prevalent in young pediatric cancer survivors,and such deficits are associated with lower aBMD Z-scores at all sites.These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added ben

关键词： Bone health Childhood cancer DXA Lean mass Resistance training

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A comprehensive review of genetic causes of obesity

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World Journal of Pediatrics 2024年第1期20卷 26-39页

作者： Marcio Jose Concepcion-Zavaleta juan Eduardo Quiroz-Aldave Maria del Carmen Durand-Vasquez Elman Rolando Gamarra-Osorio juan del Carmen Valencia de la Cruz Claudia Mercedes Barrueto-Callirgos Susan Luciana Puelles-Leon Elena de Jesus Alvarado-Leon Frans Leiva-Cabrera Francisca Elena Zavaleta-Gutierrez luis Alberto Concepcion-Urteaga Jose Paz-Ibarra Universidad Cientifica del Sur Bolivar 2150 AvenuePueblo Libre15084LimaPeru Division of Medicine Hospital de Apoyo ChepénChepenPeru Division of Family Medicine Hospital de Apoyo ChepénChepenPeru Division of Endocrinology Hospital Victor Lazarte EchegarayTrujilloPeru Division of Pediatrics Hospital de Apoyo ChepenChepenPeru Division of Internal Medicine Hospital de Apoyo ChepenChepenPeru Division of Genetics Universidad Nacional de TrujilloTrujilloPeru Division of Neonatology Hospital Belen de TrujilloTrujilloPeru Division of Internal Medicine Universidad Nacional de TrujilloTrujilloPeru Department of Medicine School of MedicineUniversidad Nacional Mayor de San MarcosLimaPeru

Background Obesity is a multifactorial chronic disease with a high,increasing worldwide prevalence.Genetic causes account for 7%of the cases in children with extreme obesity.Data sources This narrative review was conducted by searching for papers published in the PubMed/MEDLINE,Embase and SciELO databases and included 161 articles.The search used the following search terms:"obesity","obesity and genetics","leptin","Prader-Willi syndrome",and"melanocortins".The types of studies included were systematic reviews,clinical trials,prospective cohort studies,cross-sectional and prospective studies,narrative reviews,and case reports.Results The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body weight.However,several important aspects of the pathophysiology of obesity remain unknown.Genetic causes of obesity can be grouped into syndromic,monogenic,and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years,hyperphagia,or a family history of extreme obesity.A microarray study,an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this purpose.There are three therapeutic levels:lifestyle modifications,pharmacological treatment,and bariatric surgery.Conclusions Genetic study technologies are in constant development;however,we are still far from having a personalized approach to genetic causes of obesity.A significant proportion of the affected individuals are associated with genetic causes;however,there are still barriers to its approach,as it continues to be underdiagnosed.

关键词： Leptin Melanocortin Obesity Prader-Willi syndrome Precision medicine

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Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1705-1724页

作者： Damián Sánchez-Ramírez Mónica G Mendoza-Rodríguez Omar R Alemán Fernando A Candanedo-González Miriam Rodríguez-Sosa juan JoséMontesinos-Montesinos Mauricio Salcedo Ismael Brito-Toledo Felipe Vaca-Paniagua luis I Terrazas Unidad de Investigacion en Biomedicina Facultad de Estudios Superiores IztacalaUniversidad Nacional Autonoma de MexicoTlalnepantla 54090Estado de MexicoMexico Department of Biology Facultad de QuimicaUniversidad Nacional Autonoma de MexicoCiudad UniversitariaMexico City 04510Mexico Department of Pathology National Medical Center Century XXIInstituto Mexicano del Seguro SocialMexico City 06720Mexico Laboratorio de Células Troncales Mesenquimales Unidad de Investigación Médica en Enfermedades OncológicasHospital de Oncología Centro Medico Nacional Siglo XXIInstituto Mexicano del Seguro SocialMexico City 06720Mexico Unidad de Investigacion en Biomedicina y Oncologia Genomica Instituto Mexciano del Seguro SocialMexico City 07300Mexico Servicio de Colon y Recto Hospital de Oncología Centro Medico Nacional Siglo XXIInstituto Mexicano del Seguro SocialMexico City 06720Mexico Laboratorio Nacional en Salud Facultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla 54090Estado de MexicoMexico

Colorectal cancer(CRC)remains one of the most commonly diagnosed and deadliest types of cancer worldwide.CRC displays a desmoplastic reaction(DR)that has been inversely associated with poor prognosis;less DR is associated with a better prognosis.This reaction generates excessive connective tissue,in which cancer-associated fibroblasts(CAFs)are critical cells that form a part of the tumor microenvironment.CAFs are directly involved in tumorigenesis through different mechanisms.However,their role in immunosuppression in CRC is not well understood,and the precise role of signal transducers and activators of transcription(STATs)in mediating CAF activity in CRC remains unclear.Among the myriad chemical and biological factors that affect CAFs,different cytokines mediate their function by activating STAT signaling pathways.Thus,the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors.Here,we analyze the impact of different STATs on CAF activity and their immunoregulatory role.

关键词： Cancer-associated fibroblasts Signal transducer and activator of transcription signaling Colorectal cancer Immunity Immunosuppression

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Microsurgical management of radicular cyst using guided tissue regeneration technique:A case report

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World Journal of Clinical Cases 2024年第7期12卷 1346-1355页

作者： juan Carlos Gómez Mireles Eugenia Karina Martínez Carrillo Katia Alcalá Barbosa Evangelina Gutiérrez Cortés Javier González Ramos luis Antonio González Gómez Rubén Alberto Bayardo González Sarah Monserrat Lomelí Martínez Periodontics Specialty Department of Integral Dentistry ClinicsCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340Mexico Endodontics Specialty Department of Integral Dentistry ClinicsCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340Mexico Endodontics Specialty Department of ClinicsCentro Universitario de Los AltosUniversidad de GuadalajaraTepatitlán de Morelos 47620Mexico Specialty in Oral Pathology Surgical-Stomatological DepartmentAutonomous University of GuadalajaraZapopan 45129Mexico Independent Researcher Guadalajara 44340Mexico Department of Integral Dentistry Clinics Centro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajara 44340Mexico Department of Medical and Life Sciences Centro Universitario de la CiénegaUniversidad de GuadalajaraOcotlán 47810Mexico Master of Public Health Department of Well-being and Sustainable DevelopmentCentro Universitario del NorteUniversidad de GuadalajaraColotlán 46200Mexico

BACKGROUND Radicular cyst is a lesion of odontogenic origin that arises from epithelial remains due to periapical periodontitis caused by inflammatory reactions generated at the apex of affected teeth with infected or necrotic pulps.The therapeutic mana gement of radicular cysts is controversial.There is only one case report of enucleation of a radicular cyst managed with microsurgery and apicoectomy,but without the use of the guided tissue regeneration(GTR)technique in the same surgical procedure.The present clinical case describes the management of a radicular cyst with microsurgical approach,performance of an apicoectomy of the tooth associated with the entity,application of GTR technique,use of a resorbable membrane of type I bovine collagen,and bovine xenograft.CASE SUMMARY A 68-year-old patient presented with a radicular cyst from an upper lateral incisor.The microsurgical management used was aimed at enucleating the chemical membrane,performing apicoectomy of the tooth along with careful and precise retrograde filling,and implementing GTR technique using a resorbable collagen membrane and bovine xenograft.The diagnosis of radicular cyst was confirmed using histopathological analysis.The patient underwent follow-up evaluations at 10 and 30 d postoperatively.At 4 months postoperative evaluation,she remained asymptomatic,and radiographs showed significant periapical healing with adequate bone formation.CONCLUSION These results suggest that microsurgical management using the GTR technique with collagen membrane and xenograft,contributes to bone regeneration.

关键词： Odontogenic cysts Apical periodontal cyst Dental root end cyst Case report

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From liver to hormones:The endocrine consequences of cirrhosis

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World Journal of Gastroenterology 2024年第9期30卷 1073-1095页

作者： juan Eduardo Quiroz-Aldave Elman Rolando Gamarra-Osorio María del Carmen Durand-Vásquez Luciana del Pilar Rafael-Robles Jhean Gabriel Gonzáles-Yovera María Alejandra Quispe-Flores luis Alberto Concepción-Urteaga Alejandro Román-González José Paz-Ibarra Marcio José Concepción-Zavaleta Non-communicable Diseases Endocrinology Research LineHospital de Apoyo ChepénChepén 13871Peru Department of Endocrinology Hospital Víctor Lazarte EchegarayTrujillo 13006Peru Department of Endocrinology Clínica Javier PradoLima 15046Peru Department of Gastroenterology Hospital Nacional Guillermo Almenara IrigoyénLima 15018Peru Department of Endocrinology Hospital de Emergencias GrauLima 15001Peru Internal Medicine Hospital Regional Docente de TrujilloTrujillo 13011Peru Department of Endocrinology Hospital Universitario de San Vicente FundaciónMedellin 050010Colombia Internal Medicine Universidad de AntioquiaMedellín 050010Colombia School of Medicine Universidad Nacional Mayor de San MarcosLima 15081Peru Department of Endocrinology Hospital Nacional Edgardo Rebagliati MartinsLima 15072Peru Carrera de Medicina Humana Universidad Científica del SurLima 15067Peru

Hepatocrinology explores the intricate relationship between liver function and the endocrine system.Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption.Despite its importance,assessing endocrine issues in cirrhotic patients is frequently neglected.This article provides a comprehensive review of the epidemiology,pathophysiology,diagnosis,and treatment of endocrine disturbances in liver cirrhosis.The review was conducted using the PubMed/Medline,EMBASE,and Scielo databases,encompassing 172 articles.Liver cirrhosis is associated with endocrine disturbances,including diabetes,hypoglycemia,sarcopenia,thyroid dysfunction,hypogonadotropic hypogonadism,bone disease,adrenal insufficiency,growth hormone dysfunction,and secondary hyperaldosteronism.The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system,respectively.Sarcopenia can be assessed through imaging and functional tests,while other endocrine disorders are evaluated using hormonal assays and imaging studies.Treatment options include metformin,glucagon-like peptide-1 analogs,sodium-glucose co-transporter-2 inhibitors,and insulin,which are effective and safe for diabetes control.Established standards are followed for managing hypoglycemia,and hormone replacement therapy is often necessary for other endocrine dysfunctions.Liver transplantation can address some of these problems.

关键词： Diabetes mellitus Hypoglycemia Thyroid diseases Hypogonadism Metabolic bone diseases Liver cirrhosis

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MicroRNA-630:A promising avenue for alleviating inflammation in diabetic kidney disease

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World Journal of Diabetes 2024年第7期15卷 1398-1403页

作者： Javier Donate-Correa Ainhoa González-luis Jésica Díaz-Vera juan Ramón Hernandez-Fernaud Research Unit University Hospital Nuestra Señora de Candelaria(UHNSC)Santa Cruz de Tenerife 38010Spain Department of Biochemistry MicrobiologyCell Biology and GeneticsInstituto de Tecnologías BiomédicasUniversidad de La LagunaSanta Cruz de Tenerife 38000Spain

Diabetic kidney disease(DKD)is one of the complications of diabetes,affecting millions of people worldwide.The relentless progression of this condition can lead to kidney failure,requiring life-altering interventions such as dialysis or transplants.Accumulating evidence suggests that immunologic and inflammatory elements play an important role in initiating and perpetuating the damage inflicted on renal tissues,exacerbating the decline in organ function.Toll-like receptors(TLRs)are a family of receptors that play a role in the activation of the innate immune system by the recognition of pathogen-associated molecular patterns.Recent data from in vitro and in vivo studies have highlighted the critical role of TLRs,mainly TLR2 and TLR4,in the pathogenesis of DKD.In the diabetic milieu,these TLRs recognize diabetic-associated molecular signals,triggering a proinflammatory cascade that initiates and perpetuates inflammation and fibrogenesis in the diabetic kidney.Emerging non-traditional strategies targeting TLR signaling with potential therapeutic implications in DKD have been proposed.One of these approaches is the use of microRNAs,small non-coding RNAs that can regulate gene expression.This editorial comments on the results of this approach carried out in a rat model of diabetes by Wu et al,published in this issue of the World Journal of Diabetes.The results of the experimental study by Wu et al shows that microRNA-630 decreased levels compared to non-diabetic rats.Additionally,microRNA-630 exerted anti-inflammatory effects in the kidneys of diabetic rats through the modulation of TLR4.These findings indicate that the microRNA-630/TLR4 axis might represent a pathological mechanism of DKD and a potential therapeutic target capable of curbing the destructive inflammation characteristic of DKD.

关键词： Diabetes Diabetic kidney disease Inflammation Toll-like receptor 4 microRNA-630

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Unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neuropathology and behavioral deficits in parkinsonian rats withα-synucleinopathy

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Neural Regeneration Research 2024年第9期19卷 2057-2067页

作者： Bismark Gatica-Garcia Michael J.Bannon Irma Alicia Martínez-Dávila luis O.Soto-Rojas David Reyes-Corona Lourdes Escobedo Minerva Maldonado-Berny ME Gutierrez-Castillo Armando J.Espadas-Alvarez Manuel A.Fernandez-Parrilla juan U.Mascotte-Cruz CP Rodríguez-Oviedo Irais E.Valenzuela-Arzeta Claudia Luna-Herrera Francisco E.Lopez-Salas Jaime Santoyo-Salazar Daniel Martinez-Fong Departamento de Fisiología Biofísica y NeurocienciasCentro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico Department of Pharmacology Wayne State University School of MedicineDetroitMIUSA Laboratorio de Patogénesis Molecular Carrera Médico CirujanoFacultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla de BazMéxico Red de Medicina para la Educación y Desarrollo y la Investigación Científica de Iztacala(Red MEDICI) Carrera Médico CirujanoFacultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla de BazMéxico Nanoparticle Therapy Institute AguascalientesMéxico Departamento de Biociencias e Ingeniería Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y DesarrolloInstituto Politécnico NacionalCiudad de MéxicoMéxico Escuela Nacional de Medicina y Homeopatía Instituto Politécnico NacionalCiudad de MéxicoMéxico Departamento de Fisiología Escuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalCiudad de MéxicoMéxico Departamento de Biología Molecular y Biotecnología Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoCiudad de MéxicoMéxico Departamento de Física Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico Programa de Nanociencias y Nanotecnología Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico

Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate t

关键词： A1 astrocytes A2 astrocytes gene therapy microglia motor deficits nanoparticles neurodegeneration neuroinflammation senescence α-synuclein aggregates

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