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1.
Cell Mol Neurobiol ; 36(5): 657-67, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26283493

RESUMO

Neurogenin2 (Ngn2) is a proneural gene that directs neuronal differentiation of progenitor cells during development. This study aimed to investigate whether the use of adipose-derived stem cells (ADSCs) over-expressing the Ngn2 transgene (Ngn2-ADSCs) could display the characteristics of neurogenic cells and improve functional recovery in an experimental rat model of SCI. ADSCs from rats were cultured and purified in vitro, followed by genetically modified with the Ngn2 gene. Forty-eight adult female Sprague-Dawley rats were randomly assigned to three groups: the control, ADSCs, and Ngn2-ADSCs groups. The hind-limb motor function of all rats was recorded using the Basso, Beattie, and Bresnahan locomotor rating scale for 8 weeks. Moreover, hematoxylineosin staining and immunohistochemistry were also performed. After neural induction, positive expression rate of NeuN in Ngn2-ADSCs group was upon 90 %. Following transplantation, a great number of ADSCs was found around the center of the injury spinal cord at 1 and 4 weeks, which improved retention of tissue at the lesion site. Ngn2-ADSCs differentiated into neurons, indicated by the expression of neuronal markers, NeuN and Tuj1. Additionally, transplantation of Ngn2-ADSCs upregulated the trophic factors (brain-derived neurotrophic factor and vascular endothelial growth factor), and inhibited the glial scar formation, which was indicated by immunohistochemistry with glial fibrillary acidic protein. Finally, Ngn2-ADSCs-treated animals showed the highest functional recovery among the three groups. These findings suggest that transplantation of Ngn2-overexpressed ADSCs promote the functional recovery from SCI, and improve the local microenvironment of injured cord in a more efficient way than that with ADSCs alone.


Assuntos
Adipócitos/citologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células-Tronco Mesenquimais/citologia , Proteínas do Tecido Nervoso/metabolismo , Traumatismos da Medula Espinal/metabolismo , Adipócitos/metabolismo , Animais , Diferenciação Celular/fisiologia , Modelos Animais de Doenças , Feminino , Transplante de Células-Tronco Mesenquimais , Neurônios/metabolismo , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/patologia , Células-Tronco/metabolismo
2.
Neurol Sci ; 36(4): 607-16, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25502174

RESUMO

Recently, the association between methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) G1958A polymorphism and neural tube defects (NTD) susceptibility has been widely investigated; however, the results remained inconclusive. Hence, we conducted a meta-analysis to evaluate the effect of MTHFD1 G1958A polymorphism on NTD. The relative literatures were identified by search of the electronic databases PubMed, MEDLINE, and EMBASE. The extracted data were statistically analyzed, and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to estimate the association strength using Stata version 11.0 software. Finally, ten studies met our inclusion criteria, including 2,132/4,082 in NTD infants and controls; 1,402/3,136 in mothers with NTD offspring and controls; and 993/2,879 in fathers with NTD offspring and controls. This meta-analysis showed that, compared with the mothers with GG genotype, the women with AA genotype had an increased risk of NTD in their offspring, with OR values and 95 % CI at 1.39 (1.16-1.68), p < 0.001. Interestingly, fathers with AG genotype had a significant decreased risk of NTD offspring (OR = 0.79, 95 % CI = 0.66-0.94, p = 0.009). However, there was no significant association between the MTHFD1 G1958A polymorphism in NTD patients and the risk of NTD. In conclusion, the present meta-analysis provided evidence of the association between maternal MTHFD1 G1958A polymorphism and NTD susceptibility.


Assuntos
Predisposição Genética para Doença/genética , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Defeitos do Tubo Neural/genética , Polimorfismo de Nucleotídeo Único/genética , Bases de Dados Bibliográficas/estatística & dados numéricos , Feminino , Estudos de Associação Genética , Humanos , Antígenos de Histocompatibilidade Menor , Defeitos do Tubo Neural/epidemiologia , Gravidez , Fatores de Risco
3.
J Nanosci Nanotechnol ; 15(12): 9834-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26682421

RESUMO

Capsaicin is recognized as a natural tumor preventive compound and exhibits a remarkable anticancer action. Strong inhibitory role of capsaicin on gliomas has been well documented. However, the use of capsaicin is limited due to its hydrophobicity, low affinity, and short half-life. The present study aimed to explore the physiochemical characteristics of the capsaicin-loading nanoparticles prepared by methoxy polyethylene glycol-poly(caprolactone) (mPEG-PCL) amphiphilic block copolymer. It also aimed to evaluate the ability of the nanoparticles to cross the blood-brain barrier. Additionally, the uptake of nanoparticles in the glioma cells and its ability to inhibit cell proliferation were tested in human glioblastoma U251 cells. mPEG-PCL amphiphilic block copolymer was synthesized using the ring-opening polymerization method, and the capsaicin-loading nanoparticles were prepared with the solvent diffusion method. In vitro drug release assay revealed that the capsaicin-loading nanoparticles presented a slow-release characteristic. Coculture of the human glioblastoma U251 cells and the fluorescein-loading nanoparticles showed the uptake of nanoparticles in U251 cells by endocytosis. We found that the NIR-797 isothiocyanate-loading nanoparticles can cross the blood-brain barrier. In addition, the capsaicin-loading nanoparticle showed a remarkable inhibition on the growth of U251 cells. The efficacy of the capsaicin-loading nanoparticles against tumor cells was significantly superior to the capsaicin at low concentrations. It is concluded that the capsaicin-loading nanoparticles can provide an extremely promising approach for chemotherapy of gliomas.


Assuntos
Capsaicina/farmacologia , Portadores de Fármacos/química , Glioma/tratamento farmacológico , Nanopartículas/química , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Glioblastoma/tratamento farmacológico , Humanos , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/química
4.
J Craniofac Surg ; 26(5): 1619-23, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26114539

RESUMO

OBJECTIVE: To investigate the surgical techniques of the modified presigmoid trans-partial bony labyrinth approach and the advantages in the exposure of the petroclival region and in the treatment of lesions in this area. METHODS: Between April and October of 2012, a study on modification of the surgical approach was performed on 15 cadaveric heads. On the basis of the traditional presigmoid approach, semicircular canals, and the petrous apex were partially resected. The detailed conditions of the exposure of important structures of the petroclival region were recorded. RESULTS: This approach provided a large operational space from the petroclival region to the posterior cavernous sinus. The range of presigmoid exposure (horizontal direction) was (19.41 ±â€Š1.58)  mm, the exposure range of the inferior temporal (vertical direction) was (14.18 ±â€Š1.88)  mm, the maximum exposure angle of the slope center depression was (60.54°â€Š±â€Š6.93°), and the depth of operation was (55.87 ±â€Š4.34)  mm. The vertebral-basilar artery, anterior inferior cerebellar artery, superior cerebellar artery, ipsilateral III-X cranial nerves, contralateral VI cranial nerve, Meckel cave, and posterior cavernous sinus were well exposed. CONCLUSION: The modified presigmoid trans-partial bony labyrinth approach was able to achieve excellent exposure of deep surfaces of the petroclival region and the posterior part of the cavernous sinus and showed advantages including a large range of exposure, multiple axes of visualization, preservation of hearing and facial nerve function, and early devascularization of tumors.


Assuntos
Seio Cavernoso/anatomia & histologia , Fossa Craniana Posterior/anatomia & histologia , Fossa Craniana Posterior/cirurgia , Orelha Interna/anatomia & histologia , Orelha Interna/cirurgia , Microcirurgia/métodos , Osso Petroso/anatomia & histologia , Osso Petroso/cirurgia , Adulto , Seio Cavernoso/cirurgia , Humanos , Valores de Referência
5.
Am J Epidemiol ; 179(3): 267-81, 2014 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-24243742

RESUMO

We performed a meta-analysis of the association of transforming growth factor α gene (TGFA) polymorphisms with the risk of cleft lip with or without cleft palate (CL/P) or cleft palate (CP). In total, data from 29 studies were pooled for the following 3 polymorphisms: TGFA/TaqI, TGFA/BamHI, and TGFA/RasI in the TGFA gene. A fixed-effects or random-effects model was used to calculate the pooled odds ratios based on the results from the heterogeneity tests. A significantly increased CL/P or CP risk was observed in persons carrying a C2 allele at the TaqI polymorphism (odds ratio (OR) = 1.70, 95% confidence interval (CI): 1.41, 2.05) compared with those with a C1 allele (OR = 1.57, 95% CI: 1.23, 2.01). For the TGFA/BamHI polymorphism, carriers of the minor A1 allele had an estimated relative decrease in CL/P risk (OR = 0.44, 95% CI: 0.30, 0.64). These associations remained significant when only high-quality studies were included. However, no significant association was observed between the TGFA/RasI variant and CL/P risk. In summary, this meta-analysis provided a robust estimate of the positive association of the TGFA/TaqI polymorphism with both CL/P and CP and suggests that persons with an A1 allele may have a markedly decreased risk of CL/P.


Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Polimorfismo de Fragmento de Restrição , Fator de Crescimento Transformador alfa/genética , Estudos de Associação Genética , Marcadores Genéticos , Humanos , Modelos Estatísticos , Razão de Chances , Medição de Risco , Fatores de Risco
6.
Open Life Sci ; 18(1): 20220615, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37250841

RESUMO

Cell-free circulating tumor DNA (ctDNA) is synthesized by tumor cells, including metastatic tumors, and circulates in the bloodstream. Evidence suggests that ctDNA is a potential predictive and prognostic biomarker for colorectal cancer (CRC), but its predictive efficacy in detecting CRC liver metastasis (CLM) remains unclear. Additionally, its utility in the clinical setting needs further investigation. We conducted a meta-analysis to determine the utility of ctDNA as a biomarker for predicting the prognosis of CLM and investigate the relationship between CLM and ctDNA positivity. A literature search was performed in electronic databases to identify relevant studies published up to March 19, 2022. We retrieved data on overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) for both ctDNA-positive and ctDNA-negative colorectal liver metastasis (CLM) patients from the selected articles. Hazard ratios (HRs) were also calculated for these survival outcomes analysis was also performed. The stability of the combined meta-analysis was verified by sensitivity analysis and publication bias evaluation. Ten trials were included, and 615 patients were evaluated. In patients with CLM, pooled HRs revealed a substantial link between ctDNA positivity and RFS/DFS. Subgroup analysis revealed that ctDNA had a prospective detection value. Sensitivity analysis and publication bias evaluation indicated stable results. Although the results on pooled HR for OS suggested that ctDNA-positive patients had a shorter survival time, their pooled HRs had a relatively evident heterogeneity, and sensitivity analysis and publication bias evaluation indicated that pooled HRs were extremely unstable. In conclusion, our results demonstrate that ctDNA appears to be a prognostic biomarker for resectable CLM patients.

7.
Front Neurol ; 14: 1045929, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37188306

RESUMO

Background and objective: Post-operative pneumonia (POP), a common complication, may be associated with prolonged hospitalization and long-term mortality in aneurysmal subarachnoid hemorrhage (aSAH) patients. This study aimed to explore the association between pre-operative prognostic nutrition index (PNI) and POP in aSAH patients. Methods: A total of 280 aSAH patients were enrolled from Nanjing Drum Tower Hospital. PNI was calculated as follows: [10 × albumin(gr/dl)] + [0.005 × absolute pre-operative lymphocyte count (per mm3)]. We utilized multivariate analyses, restricted cubic spline, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) to elucidate the role of PNI in POP. Results: Pre-operative PNI levels in the POP group were higher, compared with the non-POP group (41.0 [39.0, 45.4] vs. 44.4 [40.5, 47.3], P = 0.001). When we included PNI as a categorical variable in the multivariate analysis, the levels of PNI were associated with POP (odds ratio, 0.433; 95% confidence interval, 0.253-0.743; P=0.002). In addition, when we included PNI as a continuous variable in the multivariate analysis, the PNI levels were also associated with POP (odds ratio, 0.942; 95% confidence interval, 0.892-0.994; P = 0.028). The level of albumin was also a predictor of the occurrence of POP, with a lower diagnostic power than PNI [AUC: 0.611 (95% confidence interval, 0.549-0.682; P = 0.001) for PNI vs. 0.584 (95% confidence interval, 0.517-0.650; P = 0.017) for albumin]. Multivariable-adjusted spline regression indicated a linear dose-response association between PNI and POP in aSAH participants (P for linearity = 0.027; P for non-linearity = 0.130). Reclassification assessed by IDI and NRI was significantly improved with the addition of PNI to the conventional model of POP in aSAH patients (NRI: 0.322 [0.089-0.555], P = 0.007; IDI: 0.016 [0.001-0.031], P = 0.040). Conclusion: The lower levels of pre-operative PNI may be associated with the higher incidence of POP in aSAH patients. Neurosurgeons are supposed to pay more attention to pre-operative nutrition status in aSAH patients.

8.
J Clin Med ; 11(3)2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35160123

RESUMO

OBJECTIVE: The present study aimed to investigate the clinical significance of multiparameter intracranial pressure (ICP) monitoring in the prediction of the prognosis of hypertensive intracerebral hemorrhage (HICH). METHODS: A retrospective analysis was performed on the clinical data of 53 HICH patients. The patients underwent removal of intracranial hemorrhage and decompressive craniectomy after admission. A ventricular ICP monitoring probe was used to continuously and invasively monitor mean arterial pressure (MAP) and ICP after surgery. The NEUMATIC system was used to collect ICP data, including pressure reactivity index (PRx), ICP dose (DICP), amplitude and pressure regression (RAP), and cerebral perfusion pressure (CPP). The mean PRx, CPP, RAP, ICP, and DICP20 mmHg × h were calculated with 1 h as the time segment. According to the Glasgow outcome scale (GOS) scores after discharge, the patients were grouped into the poor prognosis group (GOS I-III) and the good prognosis group (GOS IV and V). The two groups were compared in terms of GOS scores in the treatment and prediction of prognosis of patients. RESULTS: The good prognosis group showed significantly lower values of mean ICP, DICP20 mmHg × h, RAP, and PRx than the poor prognosis group, while CPP was significantly higher (p < 0.001). CONCLUSIONS: PRx, DICP, RAP, and CPP could reflect intracranial changes in patients and were significantly correlated with the prognosis of the patients. Mean ICP, PRx, DICP20 mmHg × h, and RAP were negatively correlated with prognosis, while CPP was positively correlated with prognosis.

9.
J Int Med Res ; 48(8): 300060520941291, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32854551

RESUMO

OBJECTIVE: To analyze the significance of intracranial pressure (ICP)-related parameters on outcome in patients with severe traumatic brain injury. The ICP-related parameters included ICP, ICP dose (DICP), regression of the correlation coefficient between amplitude and pressure (RAP), pressure reactivity index (PRx), and cerebral perfusion pressure (CPP). METHODS: A retrospective analysis was performed using clinical information from 29 patients with severe traumatic brain injury who were admitted to the Department of Neurosurgery from January 2018 to January 2019. All patients underwent ICP probe implantation after admission. Patients were followed up for 6 months after discharge, and were categorized into either the favorable or unfavorable outcome group based on their Glasgow Outcome Scale score. The differences in ICP, DICP, RAP, PRx, and CPP between the two groups were analyzed for their effects on outcome. RESULTS: The average ICP, DICP, PRx, and RAP values in patients with favorable outcomes were significantly lower than in patients with unfavorable outcomes, while CPP values were significantly higher in the favorable outcome group. CONCLUSION: Average ICP, DICP, PRx, RAP, and CPP values may indicate disease status and relate to patient outcomes. It is important to use multiple parameters to predict patients' disease severity and prognosis.


Assuntos
Lesões Encefálicas Traumáticas , Pressão Intracraniana , Lesões Encefálicas Traumáticas/diagnóstico , Circulação Cerebrovascular , Escala de Resultado de Glasgow , Humanos , Estudos Retrospectivos , Resultado do Tratamento
10.
Int J Nanomedicine ; 15: 8495-8506, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33154639

RESUMO

OBJECTIVE: Traumatic brain injury (TBI) is a serious health problem with few available treatment options. Rh-erythropoietin (rh-EPO) is a potential therapeutic drug for TBI, but it cannot cross the blood-brain barrier (BBB) directly. In this regard, a novel strategy to deliver rh-EPO for enhanced TBI treatment is via the development of Tween 80 modified albumin nanoparticles using electrostatic spray technology. METHODS: The rh-EPO loaded Tween 80 modified albumin nanoparticles (rh-EPO-Tw-ABNPs) were prepared by electrostatic spray technology, while the process parameters were optimized via a single factor design. Investigation of physicochemical properties, bioactivity and stability of rh-EPO-Tw-ABNPs was carried out. The in vitro release and biocompatibility with nerve cells were also analyzed. The in vivo brain targeting efficiency, brain edema relieving effect and the expression of aquaporin 4 (AQP4) and glial fibrillary acidic protein (GFAP) in the brain were evaluated in TBI model rats. RESULTS: The particle size of optimal rh-EPO-Tw-ABNPs was about 438 ± 45 nm, with a zeta potential of -25.42 ± 0.8 mv. The average drug loading ratio of rh-EPO-Tw-ABNPs was 21.3± 3.7 IU/mg with a relative bioactivity of 91.6 ± 4.1%. The in vitro release of rh-EPO from the nanoparticles was rather slow, while neither the blank Tw-ABNPs nor rh-EPO-Tw-ABNPs exhibited toxicity on the microglia cells. Furthermore, in vivo experiments indicated that the rh-EPO-Tw-ABNPs could enhance the distribution of EPO in the brain and relieve brain edema more effectively. Moreover, compared with an rh-EPO injection, the rh-EPO-Tw-ABNPs could increase the AQP4 level but reduced GFAP expression in the brain with more efficiency. CONCLUSION: The rh-EPO-Tw-ABNPs could enhance the transport of rh-EPO into the brain with superior therapeutic effect for TBI.


Assuntos
Albuminas/química , Lesões Encefálicas Traumáticas/tratamento farmacológico , Eritropoetina/uso terapêutico , Nanopartículas/química , Proteínas Recombinantes/uso terapêutico , Animais , Aquaporina 4/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Edema Encefálico/tratamento farmacológico , Liberação Controlada de Fármacos , Eritropoetina/farmacologia , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Masculino , Nanopartículas/ultraestrutura , Neurônios/patologia , Tamanho da Partícula , Ratos Sprague-Dawley , Proteínas Recombinantes/farmacologia , Reologia , Eletricidade Estática
11.
Arch Med Sci ; 16(1): 177-188, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32051722

RESUMO

INTRODUCTION: Aberrant expression of long non-coding RNAs (lncRNAs) has been implicated in various diseases, including cancer. However, little is known about lncRNAs in human brain gliomas. MATERIAL AND METHODS: We examined lncRNA profiles from three glioma specimens using lncRNA expression profiling microarrays. Quantitative real-time RT-PCR was used to analyze the differential expression of raw intensities of lncRNA expression in glioma and peritumoral tissues. RESULTS: We found 4858 lncRNAs to be differentially expressed between tumor tissue and peritumoral tissue. Of these, 2845 lncRNAs were up-regulated (fold change > 3.0) and 2013 were down-regulated (fold change < 1/3). A total of 4084 messenger RNAs were also differentially expressed, including 2280 up-regulated transcripts (fold change > 3.0) and 1804 that were down-regulated (fold change < 1/3). Consistent with the microarray data, qPCR confirmed differential expression of these 6 lncRNAs (ak125809, ak098473, uc002ehu.1, bc043564, NR_027322, and uc003qmb.2) between tumor and peritumoral tissue. We next established co-expression networks of differentially expressed lncRNAs and mRNAs. Many mRNAs, such as LOC729991, NUDCD1, SHC3, PDGFA, and MDM2, and lncRNAs, such as ENST00000425922, ENST00000455568, uc002ukz.1, ENST00000502715, and NR_027873, have been shown to play important roles in glioma development. Consistent with this, pathway analysis revealed that "GLIOMA" (KEGG Pathway ID: hsa05214) was significantly enriched in tumor tissue. CONCLUSIONS: Our data suggest that altered expression of lncRNAs may be a critical determinant of tumorigenesis in glioma patients.

12.
World Neurosurg ; 97: 58-63, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27693766

RESUMO

OBJECTIVE: This study aimed to summarize the clinical characteristics of Rosai-Dorfman disease primarily involving the central nervous system and to explore diagnosis and treatment. METHODS: We analyzed the clinical, imaging, and pathologic characteristics; treatment; and prognosis in 3 cases of Rosai-Dorfman disease primarily involving the central nervous system. We also performed a literature review. RESULTS: The largest of multiple intracranial lesions was totally resected, and steroid administration and radiotherapy were performed in phases for the remaining lesions. During the 1-year follow-up period, the excised lesion did not recur, and no obvious variations were observed in the other lesions. Subtotal resection was performed of the largest of another group of multiple intracranial lesions, and the residual did not show any obvious variations during the 1-year follow-up period. The isolated lesion was totally resected and did not recur during a 2-year follow-up period. CONCLUSIONS: Rosai-Dorfman disease with multiple lesions primarily involving the central nervous system is rare. Imaging characteristics are similar to meningiomas, and the pathological features include lymphocytes and plasma cells reaching tissue cells with large volume and abundant cytoplasm. Surgery is the preferred treatment, as the effects of steroid administration and radiotherapy are not apparent.


Assuntos
Sistema Nervoso Central/diagnóstico por imagem , Histiocitose Sinusal/patologia , Histiocitose Sinusal/terapia , Procedimentos Neurocirúrgicos/métodos , Adulto , Idoso , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/efeitos da radiação , Sistema Nervoso Central/cirurgia , Feminino , Histiocitose Sinusal/diagnóstico por imagem , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Radioterapia/métodos , Esteroides/uso terapêutico , Tomógrafos Computadorizados
13.
Neurosci Lett ; 621: 1-8, 2016 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-27057731

RESUMO

Nowadays peripheral nerve injurie occurs more common, the outcome is often poor because of the ineffective treatment. Recent researches revealed the duration of BDNF administration acts a positive role during the nerve regeneration, but its potential mechanisms beneath the behavioral recovery and axonal regrowth after peripheral nerve injury are still controversial. To observe the potential mechanisms we established sciatic nerve injury model and detected the expression of several axonal regeneration and function related genes. The results showed that, BDNF promotes axonal regrowth through increasing the activation of neuronal intrinsic growth capacity and strengthening the deference effects against distal portion atrophy. To further study, we determined the expression of protein associated to neuronal intrinsic growth capacity and investigated the ultrastructure of the distal portion of the injured nerve were analyzed. These data revealed that BDNF triggers multiple effects including neuronal intrinsic growth capacity improvement and distal portion atrophy protection to promote behavioral recovery following sciatic nerve crush injury in mouse.


Assuntos
Axônios/fisiologia , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Regeneração Nervosa , Neurônios/fisiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervo Isquiático/lesões , Animais , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/patologia , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia
14.
Brain Res ; 1615: 51-60, 2015 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-25912433

RESUMO

Direct lineage reprogramming of human fibroblasts into functional neurons holds great promise for biomedical applications such as regenerative medicine and cellbased disease modelling. However, clinical applications must consider how to increase neuronal conversion efficiency and at the same time reduce the number of required transcription factors. Here, we investigated whether Neurogenin 2 (Ngn2), which is a proneural gene that directs neuronal differentiation of progenitor cells during development, can enhance the generation of patient-specific induced neuronal cells. In this study, we transfected Ascl1, Sox2 and Ngn2 into human fibroblasts from the patients' scalp by lentivirus. Morphological analysis, immunocytochemistry, gene expression and electrophysiological analysis were performed to identify the similarity of induced neuronal cells (iNCs) to human neuronal cells. Ngn2 increase the conversion efficiency from 4% to 13.4%. iNCs express neuronal cell markers and resemble wild-type neurons in their morphology, gene expression profiles and exhibit functional membrane properties of mature neurons. Implanted iNCs can survive and integrate in mouse brains and, unlike iPS cell-derived neural cells, do not generate tumours.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Reprogramação Celular , Células-Tronco Pluripotentes Induzidas/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Células-Tronco Neurais/fisiologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Encéfalo/citologia , Encéfalo/fisiologia , Encéfalo/cirurgia , Células Cultivadas , Expressão Gênica , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/transplante , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/transplante , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/fisiologia , Transplante Heterólogo
15.
Int J Clin Exp Med ; 8(3): 3291-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26064218

RESUMO

Hemangiopericytoma (HPC) and meningioma, for their morphology immunohistochemical markers similarity, were usually confused especially before surgery. This study aimed to develop a panel of biomarkers to differentiate HPC from meningioma. Real-time PCR and immunohistochemical staining were employed to determine the levels of p53, bcl-2, c-myc, vimentin, CD34, FVIIIa, MGMT and reticular fiber in 15 meningiomas, HPCs and their normal controls. We found that, in the mRNA expression level, both Bcl-2 and c-myc were high in HPC and meningiomas, but bcl-2 was higher in HPC than in meningiomas, c-myc was lower in HPC than in meningiomas. In protein expression level, reticular fibers were around most HPC tumor cells but observed null in meningiomas; CD34 and FVIIIa were both found positive in HPCs but negative in meningiomas; MGMT was weak focal in HPC but strong diffuse in meningiomas. In conclusion, bcl-2, c-myc, and MGMT could be employed as the new panels of biomarkers for distinguishing HPC from meningiomas.

16.
Gene ; 533(1): 26-31, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24076350

RESUMO

BACKGROUND: Evidence showed that the SCN1A IVS5N+5G>A polymorphism might be associated with susceptibility to epilepsy with febrile seizures (EFS), however, the published data were inconclusive. Therefore, a meta-analysis was performed to estimate the overall EFS risk with the polymorphism. METHODS: The PubMed and Medline were searched up to March, 2013 for studies on the association between SCN1A IVS5N+5G>A polymorphism and EFS risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by means of a genetic model free approach. The heterogeneity and sensitivity of each report and the publication bias were also performed. All the statistical analyses were done using the STATA 11.0 software. RESULT: A total of 6 studies with 2719 cases and 2317 controls met the selection criteria. We found significant association between SCN1A polymorphism and EFS (A vs. G: OR=1.498, 95%CI=1.138-1.972; AA vs. GG: OR=2.292, 95%CI=1.620-3.243; AG vs. GG: OR=1.414, 95%CI=1.010-1.978; recessive model: OR=1.747, 95%CI=1.119-2.728 and dominant model: OR=1.730, 95%CI=1.259-2.376). When compared with the epilepsy without febrile seizure (EWFS), the subgroup analysis stratified by ethnicity showed that the SNP was significantly associated with EFS in Caucasian (A vs. G: OR=1.505, 95%CI=1.218-1.861; AA vs. GG: OR=2.081, 95%CI=1.358-3.189; recessive model: OR=1.715, 95%CI=1.273-2.310 and dominant model: OR=1.625, 95%CI=1.096-2.410), but not in Indian and Chinese. When applying Bonferroni correction (significance was set at 0.05/20), the Caucasian still has robust association with EFS and epilepsy. CONCLUSION: The present meta-analysis suggests that SCN1A IVS5N+5G>A polymorphism is a risk factor of EFS and epilepsy, especially in Caucasian.


Assuntos
Epilepsia/genética , Predisposição Genética para Doença , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Polimorfismo de Nucleotídeo Único , Convulsões Febris/genética , Heterogeneidade Genética , Humanos
17.
Sci Rep ; 4: 3924, 2014 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-24473197

RESUMO

Polymorphisms in NKX2-3 gene have been inconsistently associated with Crohn's disease (CD) and ulcerative colitis (UC). To generate large-scale evidence on whether NKX2-3 polymorphisms are associated with CD or UC susceptibility we have conducted a meta-analysis of 17 studies involving 17329 patients and 18029 controls. A significantly increased CD or UC risk was observed in persons carrying a G allele at rs10883365 polymorphism (A/G) compared with those with a A allele. (OR = 1.226, 95%CI: 1.177-1.277 and OR = 1.274, 95%CI: 1.175-1.382 respectively). In the subgroup analysis, a significantly increased CD risk was found in both Europeans and Asians. For rs11190140 polymorphism (C/T) and CD risk, the risk estimate for the allele contrast was OR = 1.201 (1.136-1.269). This meta-analysis provided a robust result that persons with a G or T allele may have a moderately increased risk of CD, and suggested that rs10883365 polymorphism was also a candidate gene polymorphism for UC susceptibility.


Assuntos
Predisposição Genética para Doença/genética , Proteínas de Homeodomínio/genética , Doenças Inflamatórias Intestinais/genética , Polimorfismo Genético/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Idoso , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Branca/genética , Adulto Jovem
18.
Clin Neurol Neurosurg ; 112(3): 199-203, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20004511

RESUMO

OBJECTIVE: The epidemiology of Moyamoya disease in mainland China has not been documented. Therefore, the present study was designed to examine the epidemiological and clinical features of Moyamoya disease in Nanjing, a provincial capital in China. METHODS: Patient records from multiple hospitals in Nanjing from January 2000 to December 2007 were collected. The clinical features of Moyamoya disease were retrospectively analyzed. RESULTS: A total of 202 patients were identified. There were 94 males and 108 females, with ages ranging from 2 to 78 years. There was a dual age peak, one in the group of patients 5-9 years of age and another in the group of patients 35-39 years of age. The initial symptoms included cerebral ischemia (81 patients, 40%), cerebral hemorrhage (113 patients, 55.9%) and asymptomatic disease (8 patients, 3.9%). An increasing incidence rate of Moyamoya disease was observed during the period of 2000-2007, with an average detection rate of 0.43cases/100,000 persons/year (prevalence 3.92/100,000 persons). The incidence of ischemia associated with the disease was 0.16cases/100,000 people-years and the incidence of hemorrhage was 0.22cases/100,000 people-years. CONCLUSION: This first study on the epidemiological and clinical features of Moyamoya disease in mainland China indicated an increasing incidence of Moyamoya disease with bimodal incidence distribution appearing more frequently in adults.


Assuntos
Isquemia Encefálica/epidemiologia , Hemorragia Cerebral/epidemiologia , Doença de Moyamoya/epidemiologia , Doença de Moyamoya/fisiopatologia , Adolescente , Adulto , Fatores Etários , Idoso , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/fisiopatologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Doença de Moyamoya/complicações , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
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