RESUMO
Aralia elata is an Araliaceae woody plant species found in Northeastern Asia. To understand how genetic pools are distributed for A.elata clones, we were to analyze the population structure of A.elata cultivars and identify how these are correlated with thorn-related phenotype which determines the utility of A.elata. We found that the de novo assembled genome of 'Yeongchun' shared major genomic compartments with the public A.elata genome assembled from the wild-type from China. To identify the population structure of the 32 Korean and Japanese cultivars, we identified 44 SSR markers and revealed three main sub-clusters using ΔK analysis with one isolated cultivar. Machine-learning based clustering with thorn-related phenotype correlated moderately with population structure based on SSR analysis suggested multi-layered genetic regulation of thorn-related phenotypes. Thus, we revealed genetic lineage of A.elata and uncovered isolated cultivar which can provide new genetic material for further breeding.
Assuntos
Aralia , Genoma de Planta , Repetições de Microssatélites , Fenótipo , Aralia/genética , Melhoramento Vegetal , Aprendizado de MáquinaRESUMO
BACKGROUND: The present multicenter retrospective study aimed to compare the outcome of carotid artery stenting (CAS) versus carotid endarterectomy (CEA) among Korean patients with symptomatic extracranial carotid stenosis. METHODS: Between January 2008 and December 2011, 677 patients underwent either CAS (346, 51.1%) or CEA (331, 48.9%). The primary end point included the occurrence of major adverse cardiovascular events (MACEs), defined as fatal or nonfatal stroke and myocardial infarction, and all-cause mortality during the periprocedural period and within 4 years after CAS or CEA. RESULTS: Although patients undergoing CAS and CEA did not differ significantly in MACE incidence within 4 years (15.3% vs. 11.5%, P = 0.14), CEA showed lower periprocedural MACE incidence than CAS with clinical significance (6.1% vs. 3.0%, P = 0.06). During the periprocedural period, the incidence of any stroke was significantly higher in patients undergoing CAS (5.5% vs. 2.4%, P = 0.04) but not the incidence of myocardial infarction (0.6% vs. 0.3%, P > 0.99). Kaplan-Meier survival analysis showed similar MACE-free (P = 0.16), stroke-free (P = 0.24), and overall survival (P = 0.25) rates in both groups. On subgroup analysis, patients older than 70 years undergoing CAS had a significantly higher incidence of MACE at 4 years (22.7% vs. 13.7%, P = 0.03). CONCLUSIONS: Although the risk of MACE did not differ significantly within 4 years in this Korean population undergoing CAS and CEA, there was a higher risk of stroke with CAS during the periprocedural period.
Assuntos
Estenose das Carótidas/terapia , Endarterectomia das Carótidas , Stents , Idoso , Estenose das Carótidas/complicações , Estenose das Carótidas/mortalidade , Estenose das Carótidas/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Blood pressure (BP) was reported to decrease significantly after carotid endarterectomy (CEA) or carotid stenting (CAS) up to the 1-year follow-up. We evaluated changes in BP for 3 years after treating hypertensive patients with symptomatic carotid artery stenosis by either CEA or CAS and determined predisposing factors for normotensive BP at the 3-year follow-up. METHODS: A total of 123 hypertensive patients with at least 3 years of clinical and radiographic follow-up after treatment were included in this study and placed in the CEA (n = 65) or CAS group (n = 58). BP changes for 3 years, the number of patients with a normotensive BP (≤120/80 mmHg), and the percentage decrease in BP were evaluated and compared between groups. RESULTS: Compared to pretreatment BP, the CEA group had significantly decreased BP at the 1- and 2-year follow-up (p < 0.05), but not the 3-year follow-up. The CAS group had significantly decreased BP at the 1-, 2-, and 3-year follow-up (p < 0.05). Stenosis location (body lesions over apical lesions; OR = 1.526, 95 % CI, 1.341 to 6.224; p = 0.034) was an independent predisposing factor for normotensive BP at the 3-year follow-up. CONCLUSIONS: For hypertensive patients with symptomatic carotid artery stenosis, BP was lowered at 3 years after both CEA and CAS compared to pretreatment BP. CAS might lower BP better over the long term than did CEA, and hypertensive patients with stenosis at body lesions might be normotensive at 3 years after CEA or CAS.
Assuntos
Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/efeitos adversos , Hipertensão/cirurgia , Stents/efeitos adversos , Idoso , Pressão Sanguínea , Estenose das Carótidas/complicações , Feminino , Seguimentos , Humanos , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-OperatóriasRESUMO
Clubroot, caused by Plasmodiophora brassicae, is one of the diseases that causes major economic losses in cruciferous crops worldwide. Although prevention strategies, including soil pH adjustment and crop rotation, have been used, the disease's long persistence and devastating impact continuously remain in the soil. CR varieties were developed for clubroot-resistant (CR) Chinese cabbage, and 'Akimeki' is one of the clubroot disease-resistant cultivars. However, recent studies have reported susceptibility to several Korean pathotypes in Akimeki and the destruction of the resistance to P. brassicae in many Brassica species against CR varieties, requiring the understanding of more fine-tuned plant signaling by fungal pathogens. In this study, we focused on the early molecular responses of Akimeki during infection with two P. brassicae strains, Seosan (SS) and Hoengseong2 (HS2), using RNA sequencing (RNA-seq). Among a total of 2358 DEGs, 2037 DEGs were differentially expressed following SS and HS2 infection. Gene ontology (GO) showed that 1524 and 513 genes were up-regulated following SS and HS2 inoculations, respectively. Notably, the genes of defense response and jasmonic acid regulations were enriched in the SS inoculation condition, and the genes of water transport and light intensity response were enriched in the HS2 inoculation condition. Moreover, KEGG pathways revealed that the gene expression set were related to pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) mechanisms. The results will provide valuable information for developing CR cultivars in Brassica plants.
RESUMO
We analyzed the results of a multiphasic personal inventory test to confirm whether Moyamoya disease (MMD) affects the psychopathology in a group of young male Koreans. The authors manually reviewed the results of the Korean military multiphasic personal inventory (KMPI) for the examination of conscripts in Korea from July 2006 to May 2010. The normal volunteers group (N = 200) was composed of those males who do not have any brain disease or brain trauma. The MMD group (N = 37) was composed of those with MMD. There were more abnormal results in the MMD group (32.4 %) than in the normal volunteers group (13.0 %, p < 0.001). Results of the Neurosis Set showed that the anxiety scale, the depression scale and the somatization scale were more increased in the MMD group than that in the normal volunteer group (p = 0.014, 0.002 and 0.006, respectively). Results of the Social Relation Set showed that the aggregation scale was more increased in the MMD group than that in the normal volunteers group (p = 0.017). Young males with MMD may have more tendencies to have abnormal results of a multiphasic personal inventory test as compared to that of normal volunteers, suggesting that MMD may cause psychopathology in young Korean males.
Assuntos
Transtorno da Personalidade Antissocial/etiologia , Doença de Moyamoya/complicações , Inventário de Personalidade , Estudos Transversais , Humanos , Angiografia por Ressonância Magnética , Masculino , Militares , Doença de Moyamoya/diagnóstico , Doença de Moyamoya/psicologia , República da Coreia , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomógrafos Computadorizados , Adulto JovemRESUMO
BACKGROUND: To explore the therapeutic outcomes of CyberKnife based fractionated stereotactic radiotherapy (CKFRT) for patients with cerebral arteriovenous malformations (AVM). METHODS: Between January 2008 and October 2020, 45 patients underwent CKFRT for cerebral AVMs as a first treatment. The delineation of AVM targets included AVM nidus. The mean target volume was 4.07 cm3, and 9 lesions (20%) were larger than 10.0 cm3. The mean marginal dose was 24 Gy (range, 20-35 Gy). CKFRT was delivered in median 3 fractions (range, 2 â¼ 5 fractions). AVM obliteration following CKFRT was confirmed by magnetic resonance imaging or angiography. RESULTS: During a median follow-up of 47 (5-148) months, complete obliteration and partial obliteration of AVM after CKFRT were obtained in 23 (51%) and 13 (29%) patients, respectively. Median time to complete obliteration was 39 (15-63) months. The cumulative probability of complete obliteration rate at 3 years was 47%. Complete obliteration rate of AVM was associated with Radiosurgery-based AVM score, which was consisted of AVM volume, patients age, and AVM location. One (2%) patient had hemorrhage during the follow-up period. CONCLUSIONS: CKFRT is an effective primary treatment for patients with cerebral AVMs with a low hemorrhage risk.
Assuntos
Malformações Arteriovenosas Intracranianas , Radiocirurgia , Humanos , Radiocirurgia/métodos , Seguimentos , Resultado do Tratamento , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/radioterapia , Malformações Arteriovenosas Intracranianas/cirurgia , Hemorragia Pós-Operatória/etiologia , Estudos RetrospectivosRESUMO
Recently, many studies have shown that granulocyte macrophage-colony stimulating factor (GM-CSF) has anti-apoptotic activity and regulates the expression of anti-apoptotic genes including Bcl-2 family proteins in neuronal cells in vitro and in vivo. This study investigated detailed mechanism of GM-CSF involved in its anti-apoptotic activity and regulation of Bcl-2 expression in neural progenitor cells (NPCs) as a model. NPCs were cultured from the brain of E13 ICR mouse. When NPCs were treated with staurosporine at 1 µM, apoptosis occurred in more than 30% of cells in TUNEL assay. However, apoptosis was significantly inhibited by pre-treatment with GM-CSF at 10 ng/ml. Under the same experimental condition, the expression of both Bcl-2 and Bcl-xl was clearly induced by GM-CSF regardless of staurosporine treatment in RT-PCR and Western blot analyses. GM-CSF was shown to induce the expression of Bcl-2 and Bcl-xl via Janus tyrosine kinase (JAK) but not via phosphatidylinositol 3-kinase (PI3K) or RAS-mitogen activated protein kinase kinase-1 (MEK-1) using specific signal pathway inhibitors. Further analyses showed that the expression of Bcl-2 and Bcl-xl was induced by GM-CSF via signal transducers and activators of transcription 5 (STAT5) and STAT3, respectively. In addition, JAK/STAT5-Bcl-2 pathway but not JAK/STAT3-Bcl-xl pathway was responsible for the anti-apoptotic activity of GM-CSF in NPCs in TUNEL assay. To our knowledge, this study is the first report that shows differential roles of Bcl-2 and Bcl-xl, and their regulation mechanism involved in the anti-apoptotic activity of GM-CSF in NPCs.
Assuntos
Proteínas Reguladoras de Apoptose/fisiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Janus Quinases/metabolismo , Neurônios/citologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição STAT5/metabolismo , Células-Tronco/citologia , Animais , Apoptose , Proteínas Reguladoras de Apoptose/genética , Western Blotting , Regulação da Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Marcação In Situ das Extremidades Cortadas , Janus Quinases/genética , MAP Quinase Quinase 1/metabolismo , Camundongos , Neurônios/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT5/genética , Transdução de Sinais/genética , Estaurosporina/farmacologia , Células-Tronco/metabolismoRESUMO
BACKGROUND: There has been little reported on the endovascular experience of basilar artery (BA) trunk aneurysms due to its low incidence. The purpose of this study is to report the results of endovascular treatment (EVT) of BA trunk aneurysms. METHODS: Between 2004 and 2008, eight BA trunk aneurysms were treated by EVT. Five patients presented with subarachnoid hemorrhage, one had intracranial mass effect, and in two of the patients the aneurysms were found incidentally. Four lesions were saccular aneurysms, three of them were found with BA fenestration. Three lesions were dissecting aneurysms and one was a giant fusiform aneurysm. The mean follow-up period of clinical outcome was 17.1 months (range, 6-32 months). Angiographic follow-up data was obtained in six patients for period of a mean of 15.6 months (range, 6-25 months). RESULTS: Four patients with saccular aneurysms were treated by stent-assisted coil embolization except for one patient that was treated without a stent. Three patients with dissecting aneurysms were treated by a single stent placement. One of these dissecting aneurysms rebled in 4 days after stent placement and was secured by BA occlusion. One giant fusiform aneurysm was treated by bilateral vertebral artery (VA) occlusion after balloon test occlusion. Six patients (75.0%) had excellent or good clinical outcomes, one patient whose aneurysm rebled became vegetative, and one patient with bilateral VA occlusion died. Follow-up angiograms showed that four lesions had complete occlusion and two had neck remnant. CONCLUSIONS: The endovascular catheterization of these lesions tends to be relatively simple compared to more complex neurosurgical approaches. EVT, especially using a stent, could be a valuable therapeutic method in treating BA trunk aneurysms.
Assuntos
Implante de Prótese Vascular/instrumentação , Implante de Prótese Vascular/métodos , Embolização Terapêutica/instrumentação , Embolização Terapêutica/métodos , Aneurisma Intracraniano/terapia , Adulto , Idoso , Prótese Vascular , Implante de Prótese Vascular/mortalidade , Embolização Terapêutica/mortalidade , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/patologia , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The Korean Diagnosis-Related Groups (KDRG) was revised in 2003, modifying the complexity adjustment mechanism of the Australian Refined Diagnosis-Related Groups (AR-DRGs). In 2014, the Complication and Comorbidity Level (CCL) of the existing AR-DRG system was found to have very little correlation with cost. OBJECTIVE: Based on the Australian experience, the CCL for KDRG version 3.4 was reviewed. METHOD: Inpatient claim data for 2011 were used in this study. About 5,731,551 episodes, which had one or no complication and comorbidity (CC) and met the inclusion criteria, were selected. The differences of average hospital charges by the CCL were analysed in each Adjacent Diagnosis-Related Group (ADRG) using analysis of variance followed by Duncan's test. The patterns of differences were presented with R 2 in three patterns: The CCL reflected the complexity well (VALID); the average charge of CCL 2, 3, 4 was greater than CCL 0 (PARTIALLY VALID); the CCL did not reflect the complexity (NOT VALID). RESULTS: A total of 114 (19.03%), 190 (31.72%) and 295 (49.25%) ADRGs were included in VALID, PARTIALLY VALID and NOT VALID, respectively. The average R 2 for hospital charge of CCL was 4.94%. The average R 2 in VALID, PARTIALLY VALID and NOT VALID was 4.54%, 5.21%, and 4.93%, respectively. CONCLUSION: The CCL, the first step of complexity adjustment using secondary diagnoses, exhibited low performance. If highly accurate coding data and cost data become available, the performance of secondary diagnosis as a variable to reflect the case complexity should be re-evaluated. IMPLICATIONS: Lack of reviewing the complexity adjustment mechanism of the KDRG since 2003 has resulted in outdated CC lists and levels that no longer reflect the current Korean healthcare system. Reliable cost data (vs. charge) and accurate coding are essential for accuracy of reimbursement.
Assuntos
Grupos Diagnósticos Relacionados/classificação , Preços Hospitalares , Austrália , Comorbidade , Confiabilidade dos Dados , Humanos , Pacientes Internados , Classificação Internacional de Doenças , República da Coreia/epidemiologiaRESUMO
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that has the potential for clinical application. The biological effects of GM-CSF have been well characterized, and include stimulation of bone marrow hematopoietic stem cell proliferation and inhibition of apoptosis of hematopoietic cells. In contrast, the therapeutic effects of GM-CSF on the central nervous system in acute injury such as stroke and spinal cord injury have been reported only recently. To better understand the protective effect of GM-CSF on dopaminergic neurons in Parkinson's disease (PD), we investigated the effect of GM-CSF on the survival of dopamine neurons and changes in locomotor behavior in a murine PD model. We investigated the neuroprotective effects of GM-CSF in 1-methyl-4-phenylpyridinium (MPP+)-treated PC12 cells as well as in embryonic mouse primary mesencephalic neurons (PMNs) in vitro. To investigate the role of GM-CSF in vivo, we prepared a mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD model, and examined the effects of GM-CSF on dopaminergic neuron survival in the substantia nigra and on locomotor behavior. Treatment with GM-CSF significantly reduced MPP+-induced dopaminergic cell death in PC12 cells and PMNs in vitro. GM-CSF modulated the expression of apoptosis-related proteins, Bcl-2 and Bax, in vitro. Furthermore, administration of GM-CSF (50 microg/kg body weight/day) in vivo for 7 days protected dopaminergic neurons in the substantia nigra and improved locomotor behavior in a mouse MPTP model of PD.
Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Dopamina/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Neurônios/efeitos dos fármacos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/prevenção & controle , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida de Alta Pressão/métodos , Corpo Estriado/citologia , Corpo Estriado/efeitos dos fármacos , Modelos Animais de Doenças , Embrião de Mamíferos , Comportamento Exploratório/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Locomoção/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Doença de Parkinson Secundária/fisiopatologia , Técnicas de Patch-Clamp/métodos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Receptor de Fator Estimulador de Colônias de Macrófagos/metabolismo , Substância Negra/patologia , Fatores de Tempo , Tirosina 3-Mono-Oxigenase/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECT: This study investigated the effects of granulocyte macrophage-colony stimulating factor (GM-CSF) on the scar formation and repair of spinal cord tissues in rat spinal cord injury (SCI) model. METHODS: Sprague-Dawley male rats (8 weeks old) were randomly divided into the sham-operated group, spinal cord injury group, and injury with GM-CSF treated group. A spinal cord injury was induced at T9/10 levels of rat spinal cord using a vascular clip. GM-CSF was administrated via intraperitoneal (IP) injection or on the dural surface using Gelfoam at the time of SCI. The morphological changes, tissue integrity, and scar formation were evaluated until 4 weeks after SCI using histological and immunohistochemical analyses. RESULTS: The administration of GM-CSF either via IP injection or local treatment significantly reduced the cavity size and glial scar formation at 3-4 weeks after SCI. GM-CSF also reduced the expression of core proteins of chondroitin sulfate proteoglycans (CSPGs) such as neurocan and NG2 but not phosphacan. In particular, an intensive expression of glial fibriallary acidic protein (GFAP) and neurocan found around the cavity at 4 weeks was obviously suppressed by GM-CSF. Immunostaining for neurofilament (NF) and Luxol fast blue (LFB) showed that GM-CSF preserved well the axonal arrangement and myelin structure after SCI. The expression of GAP-43, a marker of regenerating axons, also apparently increased in the rostral grey matter by GM-CSF. CONCLUSION: These results suggest that GM-CSF could enhance long-term recovery from SCI by suppressing the glial scar formation and enhancing the integrity of axonal structure.
Assuntos
Cicatriz/prevenção & controle , Gliose/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Axônios/efeitos dos fármacos , Axônios/patologia , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Cicatriz/patologia , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/patologiaRESUMO
OBJECT: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hematopoietic growth factor that both enhances the survival and drives the differentiation and proliferation of myeloid lineage cells. Recent studies have suggested that GM-CSF has a neuroprotective effect against CNS injury. In this paper, the authors investigated the neuroprotective effect of GM-CSF on neuron survival and locomotor behavior in a rat model of focal cerebral ischemic injury. MATERIALS: To understand its neuroprotective effect in vitro, GM-CSF was administered to a glutamate-induced excitotoxicity neuronal injury cell culture model that mimics the pathophysiology of focal hypoxic cerebral injury. In the animal study, the authors prepared a rat focal cerebral ischemia model by occluding the unilateral middle cerebral artery. They then examined the effects of GM-CSF administration on changes in infarct volume, apoptosis-related gene expression, and improvement in locomotor behavior. RESULTS: Treatment with GM-CSF significantly increased cell viability in a cell culture model of glutamate-induced neuronal injury. Furthermore, in vivo administration of GM-CSF at 60 microg/kg body weight daily for 5 consecutive days beginning immediately after injury decreased infarction volume, altered the expression of several apoptosis-related genes (Bcl-2, Bax, caspase 3, and p53), and improved locomotor behavior in the focal cerebral ischemia model. CONCLUSIONS: The GM-CSF had neuroprotective effects in in vitro and in vivo experiments and resulted in decreased infarction volume and improved locomotor behavior. Although the specific mechanism involved in stroke recovery was not fully elucidated as it was not the primary focus of this study, administration of GM-CSF appeared to decrease the extent of neuronal apoptosis by modulating the expression of several apoptosis-related genes such as Bcl-2, Bax, caspase 3, and p53. Further investigations are necessary to better understand the role of GM-CSF on neural regeneration during the recovery phase of a stroke, as well as the intracellular signal transduction pathways that mediate neuroprotection.
Assuntos
Apoptose/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/patologia , Fármacos Neuroprotetores/farmacologia , Animais , Linhagem Celular Tumoral , Infarto Cerebral/tratamento farmacológico , Infarto Cerebral/metabolismo , Infarto Cerebral/patologia , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Humanos , Ataque Isquêmico Transitório/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Neuroblastoma , Neurotoxinas/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacosRESUMO
BACKGROUND: Despite increasing usage of endovascular treatments for intracranial aneurysms, few research studies have been conducted on the incidence of unruptured aneurysm (UA) and subarachnoid hemorrhage (SAH), and could not show a decrease in the incidence of SAH. Moreover, research on socioeconomic disparities with respect to the diagnosis and treatment of UA and SAH is lacking. METHOD: Trends in the incidences of newly detected UA and SAH and trends in the treatment modalities used were assessed from 2005 to 2015 using the nationwide database of the Korean National Health Insurance Service in South Korea. We also evaluated the influence of demographic characteristics including socioeconomic factors on the incidence and treatment of UA and SAH. RESULT: The rates of newly detected UA and SAH were 28.3 and 13.7 per 100 000 of the general population, respectively, in 2015. The incidence of UA increased markedly over the 11-year study period, whereas that of SAH decreased slightly. UA patients were more likely to be female, older, employee-insured, and to have high incomes than SAH patients. In 2015, coiling was the most common treatment modality for both UA and SAH patients. Those who were female, employee-insured, or self-employed, with high income were likely to have a higher probability to be treated for UA and SAH. CONCLUSION: The marked increase in the detection and treatment of UA might have contributed to the decreasing incidence of SAH, though levels of contribution depend on socioeconomic status despite universal medical insurance coverage.
Assuntos
Disparidades em Assistência à Saúde/economia , Aneurisma Intracraniano/economia , Fatores Socioeconômicos , Hemorragia Subaracnóidea/economia , Cobertura Universal do Seguro de Saúde/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Bases de Dados Factuais/economia , Bases de Dados Factuais/tendências , Procedimentos Endovasculares/economia , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/tendências , Feminino , Disparidades em Assistência à Saúde/tendências , Humanos , Incidência , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/terapia , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/terapia , Resultado do Tratamento , Cobertura Universal do Seguro de Saúde/tendênciasRESUMO
The pluripotent human embryonic carcinoma cell line NTERA2 readily differentiates into neurons when exposed to retinoic acid in vitro. These neurons show characteristic morphology with long processes and they express neuronal markers TUJ-1 and NeuN. NTERA2-derived neurons can regulate Ca2+ signalling through ionotropic glutamate (iGluR) and muscarinic receptors (mAChRs). Little is known, however, about the role of metabotropic glutamate receptors (mGluRs) in these neurons. Here we show that NTERA2-derived neurons express functional mGluR5, which is involved in Ca2+ signalling. Blocking mGluR5 activity at early stages of differentiation leads to fewer dendrites and a reduction in miniature excitatory postsynaptic currents (mEPSCs). Furthermore, cells cultured in the presence of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) show reduced N-methyl-D-aspartate (NMDA) receptor-mediated Ca2+ mobilisation but increased alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor Ca2+ permeability. During normal neuronal development, the edited GluR2 renders AMPARs Ca2+ impermeable. The increased Ca2+ permeability of AMPARs in MPEP-treated neurons is due to the reduced expression of GluR2 subunit protein. Thus, mGluR5 activity at early stages of differentiation is likely to play a role in the development of multipotent cell-derived neurons.
Assuntos
Dendritos/fisiologia , Aminoácidos Excitatórios/fisiologia , Neurônios/fisiologia , Receptores de Glutamato Metabotrópico/fisiologia , Transmissão Sináptica/fisiologia , Western Blotting , Cálcio/metabolismo , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Eletroforese em Gel de Poliacrilamida , Ensaio de Desvio de Mobilidade Eletroforética , Eletrofisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Microscopia Confocal , Técnicas de Patch-Clamp , Receptor de Glutamato Metabotrópico 5 , Receptores de AMPA/biossíntese , Receptores de AMPA/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/biossíntese , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Recently, we reported that GM-CSF showed therapeutic effects on the spinal cord injury (SCI) in rat model possibly via its anti-apoptotic activity in the nervous system. This study investigated the molecular mechanism of its anti-apoptotic and neuroprotective effects in N2a neuroblastoma cells and in rat SCI model. GM-CSF inhibited staurosporine-induced cytotoxicity and apoptosis of N2a cells. Single administration of GM-CSF either intraperitoneally or locally using a gelfoam, clearly reduced the apoptotic events in the surrounding region of the injury site in rat SCI model. Immunohistochemical analysis showed that apoptosis of cells occurred mainly in the neurons, but not significantly in the astrocytes in the surrounding regions. In both N2a cells and in rat SCI model, GM-CSF actually reduced the expression of pro-apoptotic proteins (p53, p21(WAF1/CIP1) and Bax), while further induced that of an anti-apoptotic protein (Bcl-2). In the Basso-Beattie-Bresnahan (BBB) locomotor test, the single GM-CSF administration showed better behavioral recovery than the untreated control only at early times within 1 week after injury. Overall, GM-CSF was shown to exert its neuroprotective effect on the neural injury by regulating the expression of apoptosis related genes, providing the molecular basis on its anti-apoptotic activity. Longer administration of GM-CSF appeared to be necessary for the sustained functional recovery from SCI.
Assuntos
Proteínas Reguladoras de Apoptose/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Degeneração Neural/tratamento farmacológico , Neurônios/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Apoptose/fisiologia , Proteínas Reguladoras de Apoptose/metabolismo , Mapeamento Encefálico , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p21/antagonistas & inibidores , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Inibidores Enzimáticos/toxicidade , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Masculino , Camundongos , Degeneração Neural/etiologia , Degeneração Neural/fisiopatologia , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/agonistas , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Estaurosporina/antagonistas & inibidores , Estaurosporina/toxicidade , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia , Proteína X Associada a bcl-2/antagonistas & inibidores , Proteína X Associada a bcl-2/metabolismoRESUMO
Many neurologic disorders are accompanied by ischemic injury during the pathologic process. To develop a controllable and injury-specific gene therapy system for the neurologic disorders, we constructed a hypoxia inducible plasmid with the erythropoietin (Epo) 3' untranslated region (UTR), which can enhance the stability of target mRNAs in response to hypoxia. The Epo 3' UTR was inserted at the 3' flanking region of luciferase gene in pSV-Luc, resulting in the construction of pSV-Luc-EpoUTR. In pEpo-SV-Luc-EpoUTR, the Epo enhancer was inserted into the upstream of the SV40 promoter to increase the hypoxia inducibility. The plasmids were evaluated in N2a mouse neuroblastoma cells under hypoxic conditions and in a rat spinal cord injury (SCI) model. The results showed that the Epo 3' UTR alone showed a three-fold increase in luciferase activity in hypoxic N2a cells as well as in the rat SCI model when compared to the sham control. In contrast, the Epo 3' UTR showed no effect on the luciferase activity in the presence of the Epo enhancer, probably because the Epo enhancer was more sensitive to hypoxia and showed a dominant effect. However, the Epo enhancer itself showed high level of luciferase activity even in normoxia (about five to eight-folds increase), while the Epo 3' UTR did not show enhanced background activity. Immunohistochemical staining showed expression of luciferase from pSV-Luc-EpoUTR both in neurons and astrocytes around the injured spinal cord of rat. These results suggest that the Epo 3' UTR could provide a specific and safe system for the hypoxia-inducible gene therapy of the neurologic disorders including SCI.
Assuntos
Regiões 3' não Traduzidas/genética , Hipóxia Celular/genética , Eritropoetina/genética , Terapia Genética/métodos , Traumatismos da Medula Espinal/terapia , Isquemia do Cordão Espinal/terapia , Animais , Astrócitos/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Elementos Facilitadores Genéticos/genética , Ativação Enzimática/genética , Expressão Gênica/genética , Vetores Genéticos/genética , Vetores Genéticos/uso terapêutico , Luciferases/metabolismo , Masculino , Camundongos , Neurônios/metabolismo , Plasmídeos/genética , Plasmídeos/uso terapêutico , Regiões Promotoras Genéticas/genética , Ratos , Ratos Sprague-Dawley , Vírus 40 dos Símios/genética , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Isquemia do Cordão Espinal/genética , Isquemia do Cordão Espinal/metabolismo , Regulação para Cima/genéticaRESUMO
GM-CSF is recently being suggested to play important role(s) in the nervous system. Present study was intended to understand signal transduction pathways of GM-CSF in human neuroblastoma (SK-N-(BE)2) and glioblastoma (A172) cell lines. The expression of GM-CSF receptors on the surface of these cells was confirmed by immunocytochemistry, Western blot analysis and RT-PCR. When treated for 10min, GM-CSF activated the signal transducer and activator of transcription 5 (STAT5) and extracellular signal regulated kinase (ERK) in both cell lines. However, Janus kinase 2 (JAK2) was activated only in A172 cells but not in SK-N-(BE)2 cells by GM-CSF. The GM-CSF-activated cellular signal pathways were specifically inhibited by the pretreatment of GM-CSF receptor alpha antibody, suggesting the specificity of the signal activation. The experiment using specific inhibitors (AG490) to the JAK/STAT pathway showed that JAK2/STAT5 cascade was well preserved and activated by GM-CSF in A172 cells, while STAT5 was activated by GM-CSF without JAK2 activation in SK-N-(EB)2 cells. The ERK pathway was activated by GM-CSF independently of JAK2 in both cell lines. Finally, GM-CSF showed cytoprotective effect on these cell lines by inhibiting cytotoxicity of saturosporine. The results revealed the signal transduction pathways activated by GM-CSF in neural cells and suggested that GM-CSF might affect the neural functions via these signal pathways.
Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Neurônios/fisiologia , Transdução de Sinais/fisiologia , Animais , Western Blotting , Linhagem Celular , Linhagem Celular Tumoral , Eletrofisiologia , Inibidores Enzimáticos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Feminino , Humanos , Imuno-Histoquímica , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/metabolismo , L-Lactato Desidrogenase/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Gravidez , RNA/biossíntese , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT5/fisiologia , Transdução de Sinais/efeitos dos fármacos , Estaurosporina/farmacologia , Células-Tronco/fisiologiaAssuntos
Angioplastia/efeitos adversos , Estenose das Carótidas/cirurgia , Complicações Pós-Operatórias/etiologia , Hemorragia Retiniana/etiologia , Stents/efeitos adversos , Angioplastia/instrumentação , Angioplastia/métodos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/patologia , Radiografia , Hemorragia Retiniana/diagnóstico , Hemorragia Retiniana/patologia , SíndromeRESUMO
OBJECT: Vascular endothelial growth factor (VEGF) has been investigated as a therapy for many disorders and injuries involving ischemia. In this report, we constructed and evaluated a hypoxia-inducible VEGF expression system as a treatment for spinal cord injury (SCI). METHODS: The hypoxia-inducible VEGF plasmid was constructed using the erythropoietin (Epo) enhancer with the Simian virus 40 (SV40) promoter (pEpo-SV-VEGF) or the RTP801 promoter (pRTP801-VEGF). The expression of VEGF in vitro was evaluated after transfection into N2A cells. The plasmids were then injected into rat spinal cords with contusion injuries. The expression of VEGF in vivo was measured using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Locomotor recovery in the rats was evaluated using the Basso, Beattie and Bresnahan (BBB) scale for locomotor analysis. RESULTS: In vitro transfection showed that pEpo-SV-VEGF or pRTP801-VEGF induced VEGF expression under hypoxic conditions, whereas pSV-VEGF did not. The VEGF level was higher in the pEpo-SV-VEGF and pRTP801-VEGF groups than in the control group. The VEGF expression was detected in neurons and astrocytes of the spinal cord. Locomotor recovery was improved in the pEpo-SV-VEGF and pRTP801-VEGF groups, and BBB scores were higher than in the control group. Staining using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling showed that the number of apoptotic cells decreased in the plasmid-injected groups compared with the control group, and significant differences were observed between the hypoxia-responsive groups and the pSV-VEGF group. CONCLUSIONS: These results suggest that the hypoxia-inducible VEGF expression system may be useful for gene therapy of SCI.
Assuntos
Terapia Genética , Hipóxia/metabolismo , Traumatismos da Medula Espinal/terapia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Animais , Apoptose , Astrócitos/metabolismo , Linhagem Celular Tumoral , Elementos Facilitadores Genéticos , Eritropoetina/genética , Expressão Gênica , Vetores Genéticos , Masculino , Camundongos , Atividade Motora , Neurônios/metabolismo , Plasmídeos , Ratos , Ratos Sprague-Dawley , Vírus 40 dos Símios/genética , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Transfecção , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
OBJECTIVE: Decompressive craniectomy (DC) is a useful surgical method to achieve adequate decompression in hypertensive intracranial patients. This study suggested a new skin incision for DC, and analyzed its efficacy and safety. METHODS: In the retrograde reviews, 15 patients underwent a newly suggested surgical approach using n-shape skin incision technique (Group A) and 23 patients were treated with conventional question mark skin incision technique (Group B). Two groups were compared in the terms of the decompressed area of the craniectomy, protruded brain volume out of the skull layer, the operation time from skin incision to bone flap removal, and modified Rankin Scale (mRS) which was evaluated for 3 months after surgery. RESULTS: The decompressed area of craniectomy (389.1 cm2 vs. 318.7 cm2, p=0.041) and the protruded brain volume (151.8 cm3 vs. 116.2 cm3, p=0.045) were significantly larger in Group A compared to the area and the volume in Group B. The time interval between skin incision and bone flap removal was much shorter in Group A (23.3 minutes vs. 29.5 minutes, p=0.013). But, the clinical results were similar between 2 groups. Group A showed more favorable outcome proportion (mRS 0-3, 6/15 patients vs. 5/23 patients, p=0.225) and lesser mortality cases proportion 1/15 patients vs. 4/23 patients, but these differences were not significantly observed (p=0.225 and 0.339). CONCLUSION: DC using n-shaped skin incision was a feasible and safe surgical technique. It may be an easier and faster method for the purpose of training neurosurgeons.