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Neurologic orphan diseases:Emerging innovations and role for genetic treatments

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World Journal of Experimental medicine 2023年第4期13卷 59-74页

作者： Ivelina P Kioutchoukova Devon T Foster Rajvi N Thakkar marco A Foreman Brandon J Burgess Rebecca m Toms eduardo E molina Valero Brandon Lucke-Wold College of medicine University of FloridaGainesvilleFL 32611United States Florida International University Herbert Wertheim College of medicine Florida International University Herbert Wertheim College of MedicineMiamiFL 33199United States Department of Neurosurgery University of FloridaGainesvilleFL 32611United States

Orphan diseases are rare diseases that affect less than 200000 individuals within the United *** orphan diseases are of neurologic and genetic *** the current advances in technology,more funding has been devoted to developing therapeutic agents for patients with these *** our review,we highlight emerging options for patients with neurologic orphan diseases,specifically including diseases resulting in muscular deterioration,epilepsy,seizures,neurodegenerative movement disorders,inhibited cognitive development,neuron deterioration,and *** extensive literature review,gene therapy offers a promising route for the treatment of neurologic orphan *** use of clustered regularly interspaced palindromic repeats/Cas9 has demonstrated positive results in experiments investigating its role in several ***,the use of adeno-associated viral vectors has shown improvement in survival,motor function,and developmental milestones,while also demonstrating reversal of sensory ataxia and cardiomyopathy in Friedreich ataxia *** oligonucleotides have also been used in some neurologic orphan diseases with positive *** target of rapamycin inhibitors are currently being investigated and have reduced abnormal cell growth,proliferation,and *** innovations and the role of genetic treatments open a new window of opportunity for the treatment of neurologic orphan diseases.

关键词： Neurologic orphan diseases Gene therapy Clustered regularly interspaced palindromic repeats/Cas9 Antisense oligonucleotides Adeno-associated virus mTOR inhibitors

Green Tea(Camellia sinensis):Hypocholesterolemic Effects in Humans and Anti-Inflammatory Effects in Animals

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Food and Nutrition Sciences 2014年第22期5卷 2185-2194页

作者： márcia Reto Cristina Almeida Joao Rocha Bruno Sepodes maria-eduardo Figueira Research Institute for medicines(imed.ULisboa) Faculty of PharmacyUniversity of LisbonLisbonPortugal

In its essence, tea is an infusion of Camellia sinensis leaves and it is the most widely consumed beverage in the world, aside water. Animal and epidemiological studies have associated green tea consumption with several health benefits, which include hypocholesterolemic effect and anti-in-flammatory activity. In this study catechins levels of green tea and its effect on the lipid profile of humans were evaluated as well as the protective effects against H2O2-mediated damage in human fibroblasts and anti-inflammatory activity of (–)-epigallocatechingallate (EGCG). The daily consumption of 1200 mL of green tea for 30 days by 15 human volunteers promoted the decrease of cholesterol and LDL levels after 15 days, but this effect was not persistent after 30 days. No changes were observed in lipid profile after the consumption of green tea capsules. EGCG, a major green tea catechin, demonstrated an anti-inflammatory action in rats and an antioxidant effect in cultured human fibroblasts.

关键词： Green Tea Infusions Hypocholesterolemic Effect Anti-Inflammatory Activity Antioxidant Activity

Three-dimensional analysis of age and sex differences in femoral head asphericity in asymptomatic hips in the United States

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World Journal of Orthopedics 2024年第8期15卷 754-763页

作者： mahad m Hassan Aliya G Feroe Brenton W Douglass Andrew E Jimenez Benjamin Kuhns Charles F mitchell Robert L Parisien Daniel A maranho eduardo N Novais Young-Jo Kim Ata m Kiapour Department of Orthopedic Surgery University of MinnesotaMinneapolisMN 55454United States Department of Orthopedic Surgery TRIA Orthopaedic CenterBloomingtonMN 55122United States Department of Orthopedic Surgery Boston Children’s HospitalBostonMA 02115United States Department of Orthopedic Surgery Mayo ClinicRochesterMN 55901United States Department of Orthopaedics and Rehabilitation Yale School of MedicineNew HavenCT 06510United States Department of Orthopedic Surgery American Hip Institute Research FoundationDes PlainesIL 60018United States Department of Orthopedic Surgery Mount SinaiNew YorkNY 10029United States Department of Biomechanics Medicineand Rehabilitation of the Locomotor SystemRibeirao Preto Medical SchoolUniversity of São PauloRibeirao Preto 14048-900São PauloBrazil

BACKGROUND The sphericity of the femoral head is a metric used to evaluate hip pathologies and is associated with the development of osteoarthritis and femoral-acetabular *** To analyze the three-dimensional asphericity of the femoral head of asymptomatic pediatric *** hypothesized that femoral head asphericity will vary significantly between male and female pediatric hips and increase with age in both *** Computed tomography scans were obtained on 158 children and adolescents from a single institution in the United States(8-18 years;50%male)without hip *** femoral measurements including the femoral head diameter,femoral head volume,residual volume,asphericity index,and local diameter difference were used to evaluate femoral head *** In both sexes,the residual volume increased by age(Pmaller femoral head size in older ages(>13 years)in females,there were no sex-differences in residual volume and aspherity *** were no age-related changes in mean diameter difference in both sexes(P=0.07)with no significant sex-differences across different age groups(P=0.06).In contrast,there were significant increases in local aspherity(maximum diameter difference)across whole surface of the femoral head and all quadrants except the inferior regions in males(P=0.03).There were no sex-differences in maximum diameter difference at any regions and age group(P>0.05).Increased alpha angle was only correlated to increased mean diameter difference across overall surface of the femoral head(P=0.024).CONCLUSION There is a substantial localized asphericity in asymptomatic hips which increases with age *** 2D measured alpha angle can capture overall asphericity of the femoral head,it may not be sensitive enough to represent regional asphericity patterns.

关键词： Hip Femoral head Sphericity Skeletal growth Sex differences

Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

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World Journal of Hepatology 2024年第1期16卷 75-90页

作者： matheus Truccolo michalczuk Larisse Longo melina Belén Keingeski Bruno de Souza Basso Gabriel Tayguara Silveira Guerreiro Jessica T Ferrari Joséeduardo Vargas Cláudia P Oliveira Carolina Uribe-Cruz Carlos Thadeu Schmidt Cerski eduardo Filippi-Chiela mário ReisÁlvares-da-Silva Division of Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Graduate Program in Gastroenterology and Hepatology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Experimental Laboratory of Hepatology and Gastroenterology Hospital de Clínicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Laboratory of Inflammatory and Neoplastic Cells Universidade Federal do ParanáParaná81530900Brazil Department of Gastroenterology(LIm07) Faculdade de Medicina da Universidade de São PauloSão Paulo 01246903Brazil Facultad de Ciencias de la Salud Universidad Católica de las MisionesPosadasMisiones 3300Argentina Unit of Surgical Pathology Hospital de Clinicas de Porto AlegrePorto Alegre 90035-903Rio Grande do SulBrazil Center of Biotechnology Universidade Federal do Rio Grande do SulPorto Alegre 90035-003Rio Grande do SulBrazil Department of morphological Sciences Universidade Federal do Rio Grande do SulPorto Alegre 90.050-170Rio Grande do SulBrazil Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)ResearcherBrasília 71.605-001Brazil

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(mASLD).AIm To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in *** Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were *** All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop *** animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(mmp2),and metalloproteinases-9(mmp9)were significantly higher in the *** opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(map1 Lc3b),and p62/sequestosome-1(p62/SQSTm1)-*** with controls,map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(Pm1 was lower in HCC compared to RIF(Pmmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(Pm1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(PmiR-26b was lower in HCC compared to RIF,and the inverse was observed for miR-224(Pmong groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis throu

关键词： Animal model Autophagy Epigenetic Hepatocellular carcinoma metabolic dysfunction-associated steatotic liver disease Rifaximin

Conifer establishment after the eruption of the Paricutin volcano in central mexico

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Forest Ecosystems 2022年第1期9卷 71-82页

作者： Jesús eduardo Sáenz-Ceja Blanca Lizeth Sáenz-Ceja J.Trinidad Sáenz-Reyes Diego Rafael Pérez-Salicrup Instituto de Investigaciones en Ecosistemas y Sustentabilidad Universidad Nacional Autéonoma de MéxicoAntigua Carretera a Patzcuaro 8701 Col.Ex hacienda San Joséde la Huerta58190MoreliaMexico Escuela Nacional de Estudios Superiores Unidad morelia Universidad Nacional Autónoma de MéxicoAntigua Carretera a Patzcuaro 8701 Col.Ex hacienda San Joséde la Huerta58190MoreliaMexico Instituto Nacional de Investigaciones Forestales Agrícolas y PecuariasCampo Experimental UruapanAv.Latinoamericana 1101Col.Revolución60500UruapanMexico

Background:Volcanic eruptions have large effects on forest ecosystems and create new substrates,triggering primary succession *** Paricutín volcano,born in central-western mexico,erupted between 1943 and *** the cessation of the eruptive activity,plant colonization began on the lava flows and tephra deposits,including the conifer species that dominate the surrounding mature *** study aims to reconstruct the history of the establishment of conifer trees on the substrates created by the Paricutín ***:16 sampling plots were established along three transects with northern,southern,and south-western aspects,located every 250 m from the preserved forest to the volcanic *** cores from 400 conifer trees were extracted and their age was determined by cross-dating annual tree *** order of the species colonization and the tree establishment,abundance,and dominance patterns were ***,the influence of the distance from the mature forests and the inter-annual climatic conditions on the temporal tree establishment pattern was ***:Eight pine and one fir species have been established since 1970,only 18 years after the end of the eruptive ***,tree establishment increased by 12.9%annually after 1995,with the youngest tree in our sample getting established in *** did not find a well-defined temporal and spatial pattern of species arrival,which suggests that colonization occurred randomly,although the four pine species that were established early became the most abundant and *** establishment was not influenced by the distance from the mature forest,and wet inter-annual conditions did not enhance pulses of tree recruitment,exhibiting a continuous tree establishment ***:Conifer species have shown a great capacity for colonizing volcanic substrates created by the Paricutín eruption,which suggests that tropical montane conifers can regenerate rapidly under high-magni

关键词： Age structure Dendrochronology Lava flow Primary succession Tropical montane forest

Characterization of blood flow and the effects of exogenous estradiol benzoate on residual follicles formed after ultrasound-guided transvaginal follicle aspiration in cattle

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Journal of Animal Science and Biotechnology 2017年第1期8卷 51-56页

作者： Alberto mansur Ghetti Luiz Gustavo Bruno Siqueira eduardo Kenji Nunes Arashiro miller Pereira Palhao Felipe Zandonadi Brandao Joao Henrique moreira Viana Universidade Federal Fluminense Niteroi RJ 24230-340 Brazil Embrapa Gado de Leite Juiz de Fora MG 36038-330 Brazil Universidade Jose do Rosario Vellano Alfenas MG 37130-000 Brazil Embrapa Recursos Geneticos e Biotecnologia PqEB Av. W5 N Brasilia DF 70770-917 Brazil

Background： Removal of the follicular content by ultrasound-guided transvaginal follicle aspiration（TVFA） may fail to induce immediate atresia and loss of function, resulting in the occurrence of residual follicles（RF）. The aims of this study were to characterize the blood flow in RF and to determine the effects of the treatment with estradiol benzoate on RF fate. Lactating, cyclic Holstein-Gir crossbred cows were used. In Experiment 1, follicular wave emergence（D0） was synchronized in cows（n = 10） and follicular growth was then monitored by transrectal ultrasonography from D0 to D8, followed by TVFA of the largest follicle present on the ovaries 24 h later. Color Doppler ultrasound imaging was used to examine blood flow on the follicular wall, which was recorded immediately before and every 12 h after TVFA, up to 72 h. In experiment 2, cows（n = 22） were randomly allocated to receive either 2 mL of saline i.m.（Control group, n = 11） or 2 mL estradiol benzoate i.m.（EB group, n = 11）immediately after TVFA. Ovaries were scanned every 12 h to confirm the presence and to measure the diameter of RF. The contents of the RF, if present, were collected 72 h after the first TVFA, using the same aspiration *** fluid from original follicles and RF were stored at-20 °C until hormonal ***： In Experiment 1, there was no reduction（P 〉 0.05） of blood flow in the remaining follicle walls after TVFA and maximum blood flow values were observed at 49.5 ± 19.7 h post-TVFA. In Experiment 2, formation of RF after TVFA was proportionally similar between Controls（5/9） and EB（5/10） cows. Also, RF diameter did not differ between groups（P 〉 0.05）. Nonetheless, the content of RF from cows in the EB group had lower（P = 0.0004）estradiol（E2） concentration and lower（P = 0.0005） E2：P4 ratio compared with ***： In conclusion, 1） the persistence of vascularization in the remaining follicle wall may contribute to the formation of RF after follicle aspiration,

关键词： Doppler Ovary Ovum pick-up Steroidogenesis Vascularization

High Temperature and the Ethylene Antagonist 1-methylcyclopropene Alter Ethylene Evolution Patterns,Antioxidant Responses,and Boll Growth in Gossypium hirsutum

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American Journal of Plant Sciences 2013年第7期4卷 1400-1408页

作者： eduardo m.Kawakami Derrick m.Oosterhuis John L.Snider Toby R.FitzSimons Av.Antonio Teixeira dos Santos RondonópolisBrazil Department of Crop Soiland Environmental SciencesUniversity of Ar-kansasFayettevilleUSA Department of Crop and Soil Sciences University of GeorgiaTiftonUSA

The cotton (Gossypium hirsutum L.) crop experiences high temperatures during flowering and boll development, but information regarding the impact of ethylene inhibition and high temperature on early boll development is limited. The objective of this study was to determine the effects of high temperature and the anti-ethylene compound 1-methylcy-cloprone (1-mCP) on G. hirsutum boll development. Treatments consisted of temperature regime (38/20?C and 30/ 20?C), 1-mCP treatment, and days past anthesis (DPA). High temperature decreased ethylene synthesis by 61% at 2 DPA, and 1-mCP caused a 40% decrease in ethylene production at 1 DPA. Glutathione reductase activity increased under high temperature, whereas superoxide dismutase activity (SOD) and membrane peroxidation (malondialdehyde content) remained unchanged. 1-mCP treatment did not affect GR activity in developing bolls. High temperature and 1-mCP treatment increased the weight of cotton bolls collected 8 DPA with an increase of 0.7 and 1 g, respectively. We propose that increased GR activity in bolls exposed to high temperature may mitigate oxidative damage. Additionally, we conclude that ethylene inhibition (either high temperature or 1-mCP-induced) immediately after flowering (1 or 2 DPA) could potentially have positive impacts on early boll growth.

关键词： Ethylene Glutathione Reductase Gossypium hirsutum High Temperature 1-methylcyclopropene

Numerical Study on the Effect of Submerged Depth on the Horizontal Plate Wave Energy Converter

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China Ocean Engineering 2014年第5期28卷 687-700页

作者： Flávio medeiros SEIBT eduardo Costa COUTO Elizaldo Domingues dos SANTOS Liércio André ISOLDI Luiz Alberto Oliveira ROCHA Paulo Roberto de Freitas TEIXEIRA Graduate Program of Ocean Engineering Universidade Federal do Rio Grande96203-900 Rio Grande RS Brazil mechanical Engineering Department Universidade Federal do Rio Grande do Sul90050-170 Porto Alegre RS Brazil

The growing search for clean and renewable energy sources has given rise to the studies of exploring sea wave energy. This paper is concerned with the numerical evaluation of the main operational principle of a submerged plate employed for the conversion of wave energy into electrical one. The numerical model used to solve the conservation equations of mass, momentum and transport of volume fraction is based on the finite volume method （FVm）. In order to tackle with the flow of mixture of air-water and its interaction with the device, the multiphase model volume of fluid （VOF） is employed. The purpose of this study is the evaluation of a numerical model for improvement of the knowledge about the submerged plate wave energy converter, as well as the investigation of the effect of the distance from the plate to the bottom of the sea （HP） on the performance of the converter. The simulations for several distances of the plate from the seabed show that the optimal efficiency is 64%, which is obtained for HP=0.53 m （88% of the depth）. This efficiency is 17% larger than that found in the worst case （HP=0.46 m, 77% of the depth）.

关键词： numerical simulation submerged plate wave energy conversion efficiency

Evaluation of montreal cognitive assessment for the differential diagnosis of mild cognitive impairment and Alzheimer’s disease in elderly patients with more than 5 years of schooling: Data from a Brazilian sample

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Advances in Aging Research 2013年第4期2卷 121-129页

作者： José m. montiel Juliana F. Cecato Daniel Bartholomeu José eduardo martinelli FIEO University Center Osasco Brazil Jundiai medical School Jundiaí Brazil

Background: Diagnostic investigation of dementia is based on a series of tests which lie the neuropsychological evaluations. The montreal Cognitive Assessment (moCA) was developed as an instrument to recognize mild Cognitive Impairment (mCI) and initial cases of Alzheimer’s disease. The present study aims to evaluate the predictive value of Brazilian moCA test version in a sample of elderly above 5 years of education. methods: Cross-sectional study with 136 elderly, above 60 years old at least 5 years of education. Diagnostic criteria is based on clinical and neuropsychological data classified Alzheimer’s disease n = 52, mCI n = 45 e normal controls n = 39. moCA test was compared with Cambridge Cognitive Examination, mini-mental State Exam, Verbal Fluency, Clock Drawing Test, Geriatric Depression Scale and Pfeffer Functional Activities Questionnaire. Accuracy was evaluated by receiver operating characteristic (ROC) curve analyses. Pearson correlation coefficient was used to compare the moCA with the other tests. It was also used logistic regression analysis to identify the main risk factors for the diagnostic groups. Results: moCA was the best test to differentiate Alzheimer’s disease cases from mCI with 86.5% sensitivity and 75.6% specificity. Furthermore, analyzes of correlation test showed that moCA correlates robust way of already validated with other tests and wide application inBrazil. Conclusions: It can be concluded that moCA is a good screening tool for investigation of mCI among the elderly in Brazil with over 5 years of schooling. Studies with larger numbers of participants are needed to further validate the test also for elderly people with low education.

关键词： Elderly moCA mild Cognitive Impairment Alzheimer’s Disease Neuropsychological Tests