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1.
Exp Ther Med ; 18(5): 3737-3740, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31656537

RESUMO

Intellectual disability (ID) is a non-specific phenotype present in a genetically heterogeneous group of disorders. The genetic cause of ID remains elusive in the majority of patients due to this extreme heterogeneity. Whole exome sequencing technology has been applied to identify pathogenic gene variants responsible for ID. The present report described a 1.7-year-old female patient who had severe ID with the specific features of delayed motor development, language disorders and abnormal facial features. Exome analysis identified a novel pathogenic variant of the SETD5 gene [c.2025_2026delAG (p.Gly676Valfs*2)]. The variant was a frameshift mutation, causing termination of the protein in advance. These findings indicated that this mutation of the SETD5 gene may be a genetic cause for ID. The present study aimed to provide a meaningful exploration of ID and the identification of clinical core genetic pedigrees.

2.
Ital J Pediatr ; 45(1): 37, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30867013

RESUMO

BACKGROUND: Neural tube defects (NTDs) are birth defects of the brain, spine, or spinal cord invoked by the insufficient intake of folic acid in the early stages of pregnancy and have a complex etiology involving both genetic and environmental factors. So the study aimed to explore the association between alterations in maternal one-carbon metabolism and NTDs in the offspring. METHODS: We conducted a case-control study to get a deeper insight into this association, as well as into the role of genetic polymorphisms. Plasma concentrations of folate, homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and genotypes and alleles distributions of 52 SNPs in 8 genes were compared for 61 women with NTDs-affected offspring and 61 women with healthy ones. RESULTS: There were significant differences between groups with regard to plasma folate, SAM, SAH and SAM/SAH levels. Logistic regression results revealed a significant association between maternal plasma folate level and risk of NTDs in the offspring. For MTHFD1 rs2236225 polymorphism, mothers having GA genotype and A allele exhibited an increased risk of NTDs in the offspring (OR = 2.600, 95%CI: 1.227-5.529; OR = 1.847, 95%CI: 1.047-3.259). For MTHFR rs1801133 polymorphism, mothers having TT and CT genotypes were more likely to affect NTDs in the offspring (OR = 4.105, 95%CI: 1.271-13.258; OR = 3.333, 95%CI: 1.068-10.400). Moreover, mothers carrying T allele had a higher risk of NTDs in the offspring (OR = 1.798, 95%CI: 1.070-3.021). For MTRR rs1801394 polymorphism, the frequency of G allele was significantly higher in cases than in controls (OR = 1.763, 95%CI: 1.023-3.036). Mothers with NTDs-affected children had higher AG genotype in RFC1 rs1051226 polymorphism than controls, manifesting an increased risk for NTDs (OR = 3.923, 95%CI: 1.361-11.308). CONCLUSION: Folic acid deficiency, MTHFD1 rs2236225, MTHFR rs1801133, MTRR rs1801349 and RFC1 rs1051226 polymorphisms may be maternal risk factors of NTDs.


Assuntos
Deficiência de Ácido Fólico/genética , Predisposição Genética para Doença/epidemiologia , Defeitos do Tubo Neural/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Carbono/metabolismo , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China , Feminino , Ferredoxina-NADP Redutase/genética , Deficiência de Ácido Fólico/diagnóstico , Deficiência de Ácido Fólico/epidemiologia , Marcadores Genéticos/genética , Genótipo , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Antígenos de Histocompatibilidade Menor/genética , Defeitos do Tubo Neural/epidemiologia , Defeitos do Tubo Neural/fisiopatologia , Razão de Chances , Gravidez , Valores de Referência
3.
Nat Commun ; 10(1): 317, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30644394

RESUMO

In the original version of this Article, Haoping Liu, who conceptualized, designed and supervised the project and acquired funding, was inadvertently omitted from the author list. Furthermore, the affiliation of Jiaxin Gao and Haoping Liu with 'Department of Biological Chemistry, University of California, Irvine, CA 92697, USA' was omitted. Finally, funding from NIH grant GM117111, and contributions from Dr. Li-lin Du of NIBS for providing pPB[ura4] and pDUAL-PBase and Allan Bradley of Sanger for hyPBase, were not acknowledged. These errors have now been corrected in both the PDF and HTML versions of the Article.

4.
Turk Neurosurg ; 29(6): 957-960, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29757453

RESUMO

Intracranial medulloepithelioma is an extremely rare and highly malignant fast-growing tumor that shows a propensity to spread widely throughout the central nervous system. It most commonly occurs in infants and young children. We report a rare case of 2-year-old female patient with a large mass lesion diagnosed as medulloepithelioma. Although radiological examination was characteristic for the neoplasm, it was not sufficient to make a definite diagnosis. However, when it was combined with histopathological examination, we could diagnose medulloepithelioma and differentiate it from other central nervous system tumors. We intend to provide greater understanding and knowledge of intracranial medulloepithelioma by reporting this case.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Tumores Neuroectodérmicos Primitivos/diagnóstico por imagem , Tumores Neuroectodérmicos Primitivos/cirurgia , Pré-Escolar , Feminino , Humanos
5.
Nat Commun ; 9(1): 4495, 2018 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-30374049

RESUMO

Fungal infections by drug-resistant Candida albicans pose a global public health threat. However, the pathogen's diploid genome greatly hinders genome-wide investigations of resistance mechanisms. Here, we develop an efficient piggyBac transposon-mediated mutagenesis system using stable haploid C. albicans to conduct genome-wide genetic screens. We find that null mutants in either gene FEN1 or FEN12 (encoding enzymes for the synthesis of very-long-chain fatty acids as precursors of sphingolipids) exhibit resistance to fluconazole, a first-line antifungal drug. Mass-spectrometry analyses demonstrate changes in cellular sphingolipid composition in both mutants, including substantially increased levels of several mannosylinositolphosphoceramides with shorter fatty-acid chains. Treatment with fluconazole induces similar changes in wild-type cells, suggesting a natural response mechanism. Furthermore, the resistance relies on a robust upregulation of sphingolipid biosynthesis genes. Our results shed light into the mechanisms underlying azole resistance, and the new transposon-mediated mutagenesis system should facilitate future genome-wide studies of C. albicans.


Assuntos
Azóis/farmacologia , Candida albicans/fisiologia , Farmacorresistência Fúngica/efeitos dos fármacos , Esfingolipídeos/metabolismo , Sequência de Bases , Candida albicans/efeitos dos fármacos , Candida albicans/genética , Elementos de DNA Transponíveis/genética , Genes Fúngicos , Testes Genéticos , Haploidia , Mutagênese/genética , Mutação/genética , Esteróis/toxicidade
6.
G3 (Bethesda) ; 8(6): 2067-2077, 2018 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-29703785

RESUMO

The CRISPR/Cas9 system, which relies on RNA-guided DNA cleavage to induce site-specific DNA double-strand breaks, is a powerful tool for genome editing. This system has been successfully adapted for the fission yeast Schizosaccharomyces pombe by expressing Cas9 and the single-guide RNA (sgRNA) from a plasmid. In the procedures published to date, the cloning step that introduces a specific sgRNA target sequence into the plasmid is the most tedious and time-consuming. To increase the efficiency of applying the CRISPR/Cas9 system in fission yeast, we here developed a cloning-free procedure that uses gap repair in fission yeast cells to assemble two linear DNA fragments, a gapped Cas9-encoding plasmid and a PCR-amplified sgRNA insert, into a circular plasmid. Both fragments contain only a portion of the ura4 or bsdMX marker so that only the correctly assembled plasmid can confer uracil prototrophy or blasticidin resistance. We show that this gap-repair-based and cloning-free CRISPR/Cas9 procedure permits rapid and efficient point mutation knock-in, endogenous N-terminal tagging, and genomic sequence deletion in fission yeast.


Assuntos
Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Schizosaccharomyces/genética , Sequência de Bases , Clonagem Molecular , Reparo do DNA/genética , Técnicas de Introdução de Genes , Mutação Puntual/genética , Deleção de Sequência , Temperatura
7.
Chin J Integr Med ; 24(8): 606-612, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26272550

RESUMO

OBJECTIVE: To compare the angiogenesis behaviors of vascular endothelial growth factor (VEGF) and Chinese medicine Xuefu Zhuyu Decoction (, XZD) treatments. METHODS: Human microvascular endothelial cells (HMEC-1) were treated with various concentrations of either XZD-containing serum (XZD-CS) or VEGF for 24, 48, and 72 h, respectively. Cell viability, proliferation, migration, adhesion, and in vitro tube formation assays were used to assess their angiogenic effects. RESULTS: VEGF promoted all cellular phases involved in angiogenesis including cell viability, proliferation, migration, adhesion, and tube formation (<0.05 or <0.01). Unlike the continuous promotion effects of VEGF at the above stages, XZD inhibited cell viability and proliferation (<0.05 or <0.01) and only promoted tube formation in the early phase of angiogenesis (<0.01). CONCLUSIONS: These two medications promote different angiogenesis behaviors, which might be an important reason for their distinct therapeutic profile in clinical usage.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/farmacologia , Adesão Celular/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Microvasos/citologia
8.
Acta Neuropathol ; 134(2): 207-220, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28477083

RESUMO

Clearance of amyloid-beta (Aß) from the brain is an important therapeutic strategy for Alzheimer's disease (AD). Current studies mainly focus on the central approach of Aß clearance by introducing therapeutic agents into the brain. In a previous study, we found that peripheral tissues and organs play important roles in clearing brain-derived Aß, suggesting that the peripheral approach of removing Aß from the blood may also be effective for AD therapy. Here, we investigated whether peritoneal dialysis, a clinically available therapeutic method for chronic kidney disease (CKD), reduces brain Aß burden and attenuates AD-type pathologies and cognitive impairments. Thirty patients with newly diagnosed CKD were enrolled. The plasma Aß concentrations of the patients were measured before and after peritoneal dialysis. APP/PS1 mice were subjected to peritoneal dialysis once a day for 1 month from 6 months of age (prevention study) or 9 months of age (treatment study). The Aß in the interstitial fluid (ISF) was collected using microdialysis. Behavioural performance, long-term potentiation (LTP), Aß burden and other AD-type pathologies were measured after 1 month of peritoneal dialysis. Peritoneal dialysis significantly reduced plasma Aß levels in both CKD patients and APP/PS1 mice. Aß levels in the brain ISF of APP/PS1 mice immediately decreased after reduction of Aß in the blood during peritoneal dialysis. In both prevention and treatment studies, peritoneal dialysis substantially reduced Aß deposition, attenuated other AD-type pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, and synaptic dysfunction, and rescued the behavioural deficits of APPswe/PS1 mice. Importantly, the Aß phagocytosis function of microglia was enhanced in APP/PS1 mice after peritoneal dialysis. Our study suggests that peritoneal dialysis is a promising therapeutic method for AD, and Aß clearance using a peripheral approach could be a desirable therapeutic strategy for AD.


Assuntos
Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/sangue , Diálise Peritoneal/métodos , Doença de Alzheimer/sangue , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/sangue , Precursor de Proteína beta-Amiloide/genética , Animais , Apoptose/fisiologia , Ácido Aspártico Endopeptidases/sangue , Encéfalo/metabolismo , Proteínas de Ligação ao Cálcio , Estudos de Casos e Controles , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/terapia , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Potenciais Pós-Sinápticos Excitadores , Humanos , Camundongos , Camundongos Transgênicos , Proteínas dos Microfilamentos , Proteínas do Tecido Nervoso/metabolismo , Fenótipo , Presenilina-1/genética , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia
9.
Acta Pharmacol Sin ; 38(1): 110-119, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27641735

RESUMO

Previous studies have shown that microRNA-1304 (miR-1304) is dysregulated in certain types of cancers, including non-small cell lung cancer (NSCLC), and might be involved in tumor survival and/or growth. In this study we investigated the direct target of miR-1304 and its function in NSCLC in vitro. Human lung adenocarcinoma cell lines (A549 and NCI-H1975) were studied. The cell proliferation and survival were investigated via cell counting, MTT and colony-formation assays. Cell apoptosis and cell cycle were examined using annexin V-PE/7-AAD and PI staining assays, respectively. The dual-luciferase reporter assay was used to verify post-transcriptional regulation of heme oxygenase-1 (HO-1) by miR-1304. CRISPR/Cas9 was used to deplete endogenous miR-1304. Overexpression of MiR-1304 significantly decreased the number and viability of NSCLC cells and colony formation, and induced cell apoptosis and G0/G1 phase cell cycle arrest. HO-1 was demonstrated to be a direct target of miR-1304 in NSCLC cells. Restoration of HO-1 expression by hemin (20 µmol/L) abolished the inhibition of miR-1304 on cell growth and rescued miR-1304-induced apoptosis in A549 cells. Suppression of endogenous miR-1304 with anti-1304 significantly increased HO-1 expression and promoted cell growth and survival in A549 cells. In 17 human NSCLC tissue samples, miR-1304 expression was significantly decreased, while HO-1 expression was significantly increased as compared to normal lung tissues. MicroRNA-1304 is a tumor suppressor and HO-1 is its direct target in NSCLC. The results suggest the potential for miR-1304 as a therapeutic target for NSCLC.


Assuntos
Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/antagonistas & inibidores , MicroRNAs/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Heme Oxigenase-1/metabolismo , Hemina/farmacologia , Humanos , MicroRNAs/antagonistas & inibidores , RNA Interferente Pequeno/farmacologia , Ensaio Tumoral de Célula-Tronco , Regulação para Cima
10.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 37(2): 209-214, 2017 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30650275

RESUMO

Objective To observe moderate angiogenic effect of Xuefu Zhuyu Capsule (XFZYC) on human microvascular endothelial cell line 1 ( HMEC-1) , and its regulation effect on expression of EphB4/EphrinB2. Methods The moderate angiogenic effect of XFZYC was clarified by detecting XFZYC containing serum on cell viability, cell cycle, migration, adhesion and in vitro angiogenesis. Its effects on expressions of EphB4/EphrinB2 were detected by Real-time quantitative PCR and Western blot. Results XFZYC containing serum (XFZYC-CS) had no effect on the cell viability or cell ratio in phase S endothelial cells. Cell migration was significantly improved by 1.25% XFZYC-CS after 24, 48, and 72 h of action 2. 50% XFZYC-CS inhibited cell migration at the primary 24 h, but it significantly promoted cell migration at 48 and 72 h afterwards. It showed just an opposite tendency to 5. 00% XFZYC-CS. Cellular adhesion number was significantly reduced by 1. 25% XFZYC-CS at 72 h. Cellular adhesion number was significant- ly increased by 2. 50% XFZYC-CS at 24 and 48 h, but inhibited at 72 h 5. 00% XFZYC-CS showed inhibition at 24 h, but turned to promotion, and disappeared afterwards. In vessel formation aspect, only 2.50% XFZYC-CS showed vessel formation promotion 5. 00% XFZYC-CS showed inhibition on vessel formation at 48 and 72 h. Results of Real-time quantitative PCR and Western blot in 2. 50% XFZYC-CS showed EphB4 expression was up-regulated at 12 h; EphB4 expression was down-regulated while EphrinB2 expression was up-regulated at 24 h. Conclusions Only 2. 50% XFZYC-CS at 48 h had promotion of migration, adhe- sion, and in vitro angiogenesis of HMEC-1 , which was the optimal condition for vessel growth. These re- sults suggested XFZYC promoted angiogenesis in certain conditional limitations. But it regulated the ex- pression of EphB4/EphrinB2, which might be one of important factors.


Assuntos
Indutores da Angiogênese , Medicamentos de Ervas Chinesas , Efrina-B2 , Receptor EphB4 , Indutores da Angiogênese/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais , Efrina-B2/efeitos dos fármacos , Efrina-B2/metabolismo , Humanos , Receptor EphB4/efeitos dos fármacos , Receptor EphB4/metabolismo
11.
Chin J Integr Med ; 22(8): 605-10, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27299459

RESUMO

OBJECTIVE: To evaluate the effect of Xuefu Zhuyu Capsule ()-containing serum (XFZY-CS) on EphB4/ephrinB2 and its reverse signal in human microvascular endothelial cell-1 (HMEC-1). METHODS: XFZY-CS and the blank control serum were collected. HMEC-1 cells were randomly assigned to 6 groups including the concentration 1.25%, 2.5%, and 5% XFZY-CS groups and their blank serum control ones. The angiogenesis effect of XFZY-CS was tested with an in vitro tube formation assay and the best condition of pro-angiogenesis was determined. The effect of XFZY-CS on EphB4/ephrinB2 and the reverse signal were determined by Western blot and real-time quantitative polymerase chain reaction, respectively; we also confifirmed the results through activating and inhibiting the reverse signal by EphB4/fc and pyrophosphatase/ phosphodiesterase2 (PP2). RESULTS: XFZY-CS promoted angiogenesis at the concentration of 2.5% corresponding serum after being cultured for 48 h, while inhibited angiogenesis at the concentration of 5% after culturing for 48 and 72 h. Under the 2.5% serum concentration, XFZY up-regulated the expression of EphB4-mRNA at 12 h (P<0.05), and down-regulates its expression at 24 h (P<0.01). Protein expression of EphB4 was apparently up-regulated at 12 h and down-regulated at 24 h. The phosphorylation of ephrinB2 increased at 9 h (P<0.05). In addition, 2.5% XFZY-CS played a similar role as the reverse signaling activator EphB4/Fc ranging from 0.5 to 5 µg/mL (P>0.05). XFZY-CS also reduced the inhibitive effect of PP2 in limited periods. CONCLUSIONS: EphB4/ephrinB2 was the upstream signal in the process of angiogenesis and its reverse signaling was responsible for XFZY's effect on promoting angiogenesis.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/metabolismo , Efrina-B2/metabolismo , Microvasos/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Receptor EphB4/metabolismo , Soro/metabolismo , Adulto , Cápsulas , Células Endoteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Fisiológica/genética , Diester Fosfórico Hidrolases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor EphB4/genética , Fatores de Tempo , Adulto Jovem
12.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(5): 623-6, 2013 May.
Artigo em Chinês | MEDLINE | ID: mdl-23905380

RESUMO

OBJECTIVE: To explore the roles of basic fibroblast growth factor (bFGF) on tube formation induced by xuefu zhuyu decoction (XZD) under non-anoxia condition. METHODS: Using serum pharmacology technique, endothelial cell line ECV304 cells were incubated in routine 95% O2. ECV304 cells were intervened by 1.25%, 2.50%, and 5.00% XZD containing serums and the vehicle serum for 48 h. The effects of XZD on tube formation, bFGF contents and its transcription levels were assessed by in vitro tube formation assay, enzyme-linked immunosorbent assay (ELISA), and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. RESULTS: Three concentrations of XZD containing serums could not only obviously promote the tube formation bFGF level, but also up-regulate bFGF contents in the supernate and its transcription levels. The shapes of lumens were more regular in those induced by 1.25% and 2.50% XZD containing serums. CONCLUSION: XZD induced angiogenesis via up-regulating the bFGF expression under non-anoxia condition.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Animais , Linhagem Celular , Células Endoteliais/efeitos dos fármacos , Feminino , Humanos , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
13.
CNS Neurosci Ther ; 19(3): 183-90, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23441691

RESUMO

AIMS: To investigate effects of DNA methyltransferase (DNMT) inhibitors on dopaminergic neurons and its underlied mechanism. METHODS: The DNMT inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) was tested in cultured dopaminergic cells. Cell viability and apoptosis were assayed with 5-aza-dC alone. Neurotoxicity of 1-methyl-4-phenylpyridinium (MPP(+) ), 6-hydroxydopamine or rotenone was also assayed with 5-aza-dC pretreatment. And mRNA levels of several key PD-related genes were examined by semiquantitative RT-PCR. Furthermore, CpG methylation of α-synuclein promoter was examined by bisulfite sequencing. RESULTS: 5-aza-dC resulted in decreased cell viability and increased apoptosis in dopaminergic neuronal cells. Pretreatment with 5-aza-dC exacerbated neurotoxic damage to dopaminergic neurons induced by MPP(+) , 6-hydroxydopamine or rotenone. 5-aza-dC also induced transcriptional upregulation of the key PD-related genes tyrosine hydroxylase and α-synuclein. And demethylation of CpG in α-synuclein promoter was also induced by 5-aza-dC and MPP(+) . CONCLUSIONS: This DNMT inhibitor might influence pathogenesis of PD. And demethylation induced by DNMT inhibitor might contribute to dopaminergic neuron death, by increasing vulnerability of dopaminergic neurons to neurotoxins and by misregulating transcription of key PD-related genes. Our data also suggested DNMT inhibitors may cause multiple effects on dopaminergic neurons.


Assuntos
Azacitidina/análogos & derivados , Metilases de Modificação do DNA/antagonistas & inibidores , Neurônios Dopaminérgicos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , 1-Metil-4-fenilpiridínio/toxicidade , Animais , Apoptose/efeitos dos fármacos , Azacitidina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ilhas de CpG , Metilação de DNA , Decitabina , Humanos , Camundongos , Oxidopamina/toxicidade , Regiões Promotoras Genéticas , Ratos , Rotenona/toxicidade , alfa-Sinucleína/genética
14.
Zhonghua Zhong Liu Za Zhi ; 34(8): 577-81, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23158989

RESUMO

OBJECTIVE: To investigate the essential role and mechanism of TRPC6 gene in the development of gastric cancer. METHODS: The expression of TRPC6 protein was assessed in gastric cancer tissues and normal tissues adjacent to the cancer from 30 patients with gastric cancer. The inhibiting effect of TRPC6 activity on cell growth, cell cycle of a human gastric cancer cell line AGS cells, tumor progression and development of xenografted human gastric cancer in a mouse model was tested using dominant-negative mutant TRPC6 (DNC6). The survival of mice bearing xenografted tumors in the GFP and DNC6 was compared using Kaplan-Meier analysis. All statistical tests were two-sided. RESULTS: The TRPC6 protein in the tumor tissues and para-tumor tissues was (21.60 ± 8.32)% versus (7.14 ± 2.24)%. After transfection of DNC6 virus for 24 hours, 48 hours, 72 hours and 96 hours, the growth inhibition rates of gastric cancer cells were (36.90 ± 1.13)%, (44.06 ± 2.17)%, (52.12 ± 2.76)% and (50.89 ± 1.97)%, respectively. The clone formation rates of control group and DNC6 group were (14.70 ± 3.00)% versus (43.80 ± 7.00)%. After transfection with DNC6 virus for 0, 24, 36 and 48 hours, the G(2)/M phase arrest was (20.34 ± 1.98)%, (24.31 ± 2.37)%, (27.70 ± 2.36)%, (35.10 ± 3.0)% in the DNC6 group and (18.40 ± 2.01)%, (18.0% ± 1.72)%, (17.50 ± 1.74)%, (16.80 ± 1.71)% in the control group, respectively. Inhibition of TRPC6 activity also reduced the subcutaneous tumor volume in the mouse models with xenografted human tumors (P < 0.05). CONCLUSION: In the preclinical models tested, TRPC6 channels are essential for gastric cancer development via regulation of G(2)/M phase transition.


Assuntos
Ciclo Celular , Proliferação de Células , Neoplasias Gástricas/patologia , Canais de Cátion TRPC/metabolismo , Adenoviridae/genética , Animais , Proteína Quinase CDC2 , Linhagem Celular Tumoral , Ciclina B/metabolismo , Quinases Ciclina-Dependentes , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Proteínas Recombinantes/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Canal de Cátion TRPC6 , Transfecção , Carga Tumoral
15.
Biol Trace Elem Res ; 145(3): 355-60, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21882065

RESUMO

The experiment was conducted to evaluate the effect of copper-loaded chitosan nanoparticles on the small intestinal morphology and activities of digestive enzyme and mucosal disaccharase in rats. Forty male Sprague-Dawley rats, with average body weight of 82 g, were randomly allotted to five groups (n = 8). All rats were received a basal diet (control) or the same basal diet added with 80 mg/kg BW CuSO(4), 80 mg/kg BW chitosan (CS-I), 80 mg/kg BW copper-loaded chitosan nanoparticles (CSN-I), 160 mg/kg BW copper-loaded chitosan nanoparticles (CSN-II), respectively. The experiment lasted 21 days. The results showed that the villus heights of the small intestinal mucosa in groups CSN-I and CSN-II were higher than those of the control, group CuSO(4) or CS-I. The crypt depth of duodenum and ileum mucosa in group CSN-I or CSN-II was depressed. Compared with the control, there were no significant effects of CuSO(4) or CS-I on the villus height and crypt depth of small intestinal mucosa. Supplementation with CSN improved the activities of trypsin, amylase and lipase in the small intestinal contents and maltase, sucrase and lactase of duodenum, jejunum, and ileum mucosa while there were no significant effects of CuSO(4) on the digestive enzyme activities of the small content compared with the control. The results indicated that intestinal morphology, activities of digestive enzyme in digesta and mucosal disaccharase were beneficially changed by treatment of copper-loaded chitosan nanoparticles.


Assuntos
Quitosana/administração & dosagem , Cobre/administração & dosagem , Intestino Delgado/efeitos dos fármacos , Nanopartículas , Administração Oral , Animais , Intestino Delgado/anatomia & histologia , Intestino Delgado/enzimologia , Masculino , Ratos , Ratos Sprague-Dawley
16.
Neurosci Bull ; 26(5): 417-27, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20882069

RESUMO

Alzheimer's disease ranks the first cause for senile dementia. The amyloid cascade is proposed to contribute to the pathogenesis of this disease. In this cascade, amyloid ß peptide (Aß) is produced through a sequential cleavage of amyloid precursor protein (APP) by ß and γ secretases, while its cleavage by α secretase precludes Aß production and generates neurotrophic sAPPα. Thus, enhancing α secretase activity or suppressing ß and γ cleavage may reduce Aß formation and ameliorate the pathological process of the disease. Several regulatory mechanisms of APP cleavage have been established. The present review mainly summarizes the signaling pathways pertinent to the regulation of APP ß cleavage.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Doença de Alzheimer/enzimologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Amiloide/efeitos adversos , Amiloide/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/biossíntese , Precursor de Proteína beta-Amiloide/antagonistas & inibidores , Precursor de Proteína beta-Amiloide/biossíntese , Animais , Humanos , Transdução de Sinais/fisiologia
17.
Sci China Life Sci ; 53(3): 342-347, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20596929

RESUMO

The study of ion channels represents one of the most active fields in neuroscience research in China. In the last 10 years, active research in various Chinese neuroscience institutions has sought to understand the mechanisms responsible for sensory processing, neural development and neurogenesis, neural plasticity, as well as pathogenesis. In addition, extensive studies have been directed to measure ion channel activity, structure-function relationships, as well as many other biophysical and biochemical properties. This review focuses on the progress achieved in the investigation of ion channels in neuronal survival during the past 10 years in China.


Assuntos
Sobrevivência Celular , Canais Iônicos/metabolismo , Canais Iônicos/fisiologia , Neurônios/metabolismo , Animais , China , Plasticidade Neuronal , Neurônios/fisiologia
18.
Artigo em Chinês | MEDLINE | ID: mdl-21241569

RESUMO

OBJECTIVE: To evaluate the differentially expressed genes between the Stress fracture (SF) cases and controls. METHODS: Total RNA was extracted and purified from peripheral blood sample of 3 SF cases and 3 controls who conducted a 1:1 matched case-control study, then used for Human Genome Array analysis. The hybridization data were analyzed using SAM software. Parts of these genes were analyzed and identified by real-time PCR. RESULTS: Upregulated and downregulated genes were 22 and 1, respectively. Thus the highest ratio and most significant cytokine was tumor necrosis factor receptor superfamily, member 10c (TNFRSF10C). The result of real-time PCR shows that TNFRSF10C was over-expressed in 3 cases and low-expressed in 1 case. CONCLUSION: Obvious difference exists in gene expression between SF cases and controls, showing there may be a lot of genes involving in the occurrence and development of SF. Meanwhile, the identification of the specific genes is helpful for biomechanics study, early diagnosis and screening of SF.


Assuntos
Fraturas de Estresse/sangue , Perfilação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos , Receptores Chamariz do Fator de Necrose Tumoral/metabolismo , Estudos de Casos e Controles , DNA Complementar/genética , Fraturas de Estresse/metabolismo , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Expressão Gênica , Humanos , Masculino , Militares , Membro 10c de Receptores do Fator de Necrose Tumoral , Receptores Chamariz do Fator de Necrose Tumoral/genética , Adulto Jovem
19.
J Asian Nat Prod Res ; 11(4): 380-90, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19431020

RESUMO

Our goals were to examine the dual-directional regulation effects of resveratrol (1) in vitro by using MCF-7 cells (estradiol receptor-positive cells), study its mechanism of action, and give a systematical analysis of the regulatory networks of each related factor. An MTT test and growth curve showed that the proliferation of MCF-7 cells was inhibited by a high concentration of 1, and that its IC(50) was 8.70 x 10(-5) +/- 0.23 mol/l. However, 1 induced the proliferation of MCF-7 cells at 10(-7)-10(-5) mol/l, and resulted in a peak proliferation at 1.0 x 10(-7) mol/l. A high concentration of 1 arrested cell cycle progression at the G(1) phase, and a typical "sub-G(1) peak" of apoptotic cells was also observed by flow cytometry. The proliferation index of MCF-7 cells increased significantly with a low concentration of 1 (p < 0.05). 1 in high concentrations induced Bax, caspase-3, and cyclin-dependent kinase (CDK) inhibitor P21 expression, whereas the expressions of cyclin CDK2, Bcl-2, and proliferating cell nuclear antigen (PCNA) were decreased by 1 treatment. Conversely, treatment with low concentrations of 1 decreased the expression of P21 and Bax, while the expressions of cyclin CDK2, Bcl-2, and PCNA were increased. These results suggest that 1 had a dual-regulatory effect on MCF-7 cells. CDK-associated protein was a key factor at both the high and low concentrations used in this study.


Assuntos
Ciclo Celular/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Estilbenos/farmacologia , Caspase 3/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/efeitos dos fármacos , Feminino , Humanos , Estrutura Molecular , Resveratrol , Estilbenos/química , Células Tumorais Cultivadas
20.
J Asian Nat Prod Res ; 11(7): 663-9, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20183304

RESUMO

Osthole, 7-methoxy-8-[3-methylpent-2-enyl]coumarin (1), was extracted from a Chinese herb Cnidium monnieri (L.) Cuss. It showed immunity strengthening, anti-tumor, anti-hepatitis, and anti-osteoporosis activities in previous studies. Our goals are to study the effects of 1 on cell proliferation and TGF-beta of hypertrophic scar fibroblasts. Our results showed that 1 induced apoptosis and inhibited cell proliferation in hypertrophic scar fibroblasts. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that its IC(50) value toward hypertrophic scar fibroblasts was 15.5 +/- 2.2 micromol/l. Furthermore, the results of cell growth curve matched with the above results. Inducing apoptosis by 1 in hypertrophic scar fibroblasts was assessed by various morphological and biochemical characteristics, including cell shrinkage, chromatin condensation, membrane blebbing, formation of apoptotic bodies, and DNA ladder formation. A typical 'Sub-G(1) peak' was also checked through flow cytometry. We used immunohistochemistry to observe the expression of TGF-beta(1). Also, we found that 1 could obviously inhibit the expression of TGF-beta(1) of fibroblasts derived from hypertrophic scar compared with the control group (P < 0.05). These results suggest that 1 inhibits the growth of hypertrophic scar fibroblasts through apoptosis and decreases the expression of TGF-beta(1).


Assuntos
Cumarínicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Apoptose/efeitos dos fármacos , Cicatriz Hipertrófica/patologia , Cumarínicos/química , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Fibroblastos/efeitos dos fármacos , Humanos , Estrutura Molecular
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