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1.
Cancer Med ; 9(1): 385-393, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31724329

RESUMO

Reproductive factors associated with breast cancer risk may also affect the prognosis. This study aimed to evaluate the associations of multiple reproductive factors with breast cancer prognosis and the modifying effects of menopausal status. We obtained data from 3805 breast cancer patients recruited between October 2008 and June 2016 in Guangzhou. The subjects were followed up until 30 June 2018. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using multivariate Cox models to estimate the associations. It was found that there were U-shaped patterns for the associations of age at first birth and durations from first/last birth to diagnosis with breast cancer prognosis. The adverse effects of old age at first birth [>30 years vs 23-30 years, HR (95% CI): 1.59 (1.01-2.50)] and long intervals from first [≥20 years vs 10-19 years, HR (95% CI): 1.55 (1.07-2.27)] or last [≥20 years vs 10-19 years, HR (95% CI): 1.63 (1.08-2.46)] birth to diagnosis on progression-free survival (PFS) were significantly more pronounced among premenopausal women. Additionally, long interval (>5 years) between first and second birth was associated with a better PFS [HR (95% CI): 0.64 (0.42-0.97)]. These results suggested that age at first birth, durations from first/last birth to diagnosis, and intervals between first and second birth should be taken into account when following the patients and assessing the prognosis of breast cancer, particularly for premenopausal patients. These findings would also have implications for further insight into the mechanisms of breast cancer development.

2.
Mol Biol Evol ; 36(5): 875-889, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30861529

RESUMO

The occurrence of parallel speciation strongly implies the action of natural selection. However, it is unclear how general a phenomena parallel speciation is since it was only shown in a small number of animal species. In particular, the adaptive process and mechanisms underlying the process of parallel speciation remain elusive. Here, we used an integrative approach incorporating population genomics, common garden, and crossing experiments to investigate parallel speciation of the wild rice species Oryza nivara from O. rufipogon. We demonstrated that O. nivara originated multiple times from different O. rufipogon populations and revealed that different O. nivara populations have evolved similar phenotypes under divergent selection, a reflection of recurrent local adaptation of ancient O. rufipogon populations to dry habitats. Almost completed premating isolation was detected between O. nivara and O. rufipogon in the absence of any postmating barriers between and within these species. These results suggest that flowering time is a "magic" trait that contributes to both local adaptation and reproductive isolation in the origin of wild rice species. Our study thus demonstrates a convincing case of parallel ecological speciation as a consequence of adaptation to new environments.


Assuntos
Especiação Genética , Oryza/genética , Adaptação Biológica , Ásia Sudeste , Ásia Ocidental , Ecossistema , Fenótipo , Filogeografia , Polimorfismo de Nucleotídeo Único , Isolamento Reprodutivo , Seleção Genética , Sequenciamento Completo do Genoma
3.
BMC Cancer ; 18(1): 989, 2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30333003

RESUMO

BACKGROUND: DNA methylation (DNAm) age was found to be an indicator for all-cause mortality, cancer incidence, and longevity, but no study has involved in the associations of DNAm age with the prognosis of breast cancer. METHODS: We retrieved information of 1076 breast cancer patients from Genomic Data Commons (GDC) data portal on March 30, 2017, including breast cancer DNAm profiling, demographic features, clinicopathological parameters, recurrence, and all-cause fatality. Horvath's method was applied to calculate the DNAm age. Cox proportional hazards regression models were used to test the associations between DNAm age of the cancerous tissues and the prognosis (recurrence of breast cancer and all-cause fatality) with or without adjusting for chronological age and clinicopathological parameters. RESULTS: The DNAm age was markedly decelerated in the patients who were premenopausal, ER or PR negative, HER2-enriched or basal-like than their counterparts. In the first five-year follow-up dataset for survival, every ten-year increase in DNAm age was associated with a 15% decrease in fatality; subjects with DNAm age in the second (HR: 0.52; 95%CI: 0.29-0.92), the third (HR: 0.49; 95%CI: 0.27-0.87) and the fourth quartile (HR: 0.38; 95%CI: 0.20-0.72) had significant longer survival time than those in the first quartile. In the first five-year follow-up dataset for recurrence, every ten-year increase in DNAm age was associated with a 14% decrease of the recurrence; in the categorical analysis, a clear dose-response was shown (P for trend =0.02) and the fourth quartile was associated with a longer recurrence free survival (HR: 0.32; 95%CI: 0.14-0.74). In the full follow-up dataset, similar results were obtained. CONCLUSIONS: DNAm age of breast cancer tissue, which associated with menopausal status and pathological features, was a strong independent predictor of the prognosis. It was suggested that the prognosis of breast cancer was related to intrinsic biological changes and specific molecular targets for treatment of breast cancer may be implicit.


Assuntos
Envelhecimento/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Metilação de DNA/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Bases de Dados Factuais/tendências , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida/tendências
4.
Cancer Med ; 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29761914

RESUMO

Young and elderly breast cancer patients are more likely to have a poorer outcome than middle-aged patients. The intrinsic molecular features for this disparity are unclear. We obtained data from the Cancer Genome Atlas (TCGA) on May 15, 2017 to test the potential mediation effects of the molecular features on the association between age and prognosis with a four-step approach. The relative contributions of the molecular features (PAM50 subtype, risk stratification, DNAm age, and mutations in TP53, PIK3CA, MLL3, CDH1, GATA3, and MAP3K1) to age disparities in survival were estimated by Cox proportional hazard models with or without the features. Young patients were significantly more likely to have basal-like subtype, GATA3 mutations, and younger DNA methylation (DNAm) age than middle-aged patients (P < .05). Both the young and elderly patients had a significantly increased risk of breast cancer recurrence after adjusted by race, tumor size, and node status (Hazard ratio [HR] (95% confidence interval [CI]): 2.81 [1.44, 5.45], 2.37 [1.45, 3.89], respectively). This increased risk was weakened in the young patients after further adjustments in the molecular features, particularly basal-like subtype, GATA3 mutations, and DNAm age (HR [95%CI]: 1.87 [0.81, 4.32]), resulting in 33.5% decreased risk of recurrence. Meanwhile, the adjustments of the molecular features did not alter the recurrence risk for the elderly patients. Compared with middle-aged patients of breast cancer, poorer prognosis of elderly patients may be caused by aging, while poorer prognosis of young patients was probably mediated through intrinsic characteristics, such as basal-like subtype, GATA3 mutations, and DNAm age of the cancerous tissues.

5.
Neuroscience ; 371: 288-295, 2018 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-29196028

RESUMO

Serum response factor (SRF), a transcription factor highly expressed in neurons, is involved in neuronal survival and the pathogenesis of some neurodegenerative disorders. The ablation of SRF renders the midbrain dopaminergic (DA) neurons vulnerable to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced neurotoxicity, however, the underlying mechanisms remain poorly understood. Here, we report decreased SRF levels in the substantia nigra (SN) of rotenone-treated rats that was associated with the loss of tyrosine hydroxylase (TH)-positive neurons. SRF expression was also reduced in rotenone-treated PC12 cells in vitro. In addition, Srf knockdown augmented rotenone-induced toxicity in PC12 cells. In contrast, overexpression of Srf attenuated the cells' sensitivity to rotenone and alleviated rotenone-induced α-synuclein accumulation. The protective effect of SRF was abolished when the expression of autophagy-related proteins Beclin 1 and Atg5 was suppressed. These results suggested that SRF may promote DA neuron survival by regulating autophagy, and thus serves as a critical molecule in PD progression.


Assuntos
Autofagia/fisiologia , Proteína Beclina-1/metabolismo , Neurônios Dopaminérgicos/metabolismo , Transtornos Parkinsonianos/metabolismo , Substância Negra/metabolismo , Fatores de Transcrição/metabolismo , Animais , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína Beclina-1/genética , Sobrevivência Celular/fisiologia , Neurônios Dopaminérgicos/patologia , Masculino , Células PC12 , Transtornos Parkinsonianos/patologia , Distribuição Aleatória , Ratos , Ratos Endogâmicos Lew , Rotenona , Substância Negra/patologia , Tirosina 3-Mono-Oxigenase/metabolismo , alfa-Sinucleína/metabolismo
6.
Exp Neurol ; 271: 112-21, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26001614

RESUMO

Tumor necrosis factor-α (TNF) is increasingly implicated as a critical pro-inflammatory cytokine involved in chronic inflammation and neurodegeneration of Parkinson's disease (PD). However, the cellular and molecular events that lead to dopaminergic neuron degeneration are not fully understood. In this study, we demonstrated that microglia-released and recombinant TNF disrupted α-synuclein (α-SYN) degradation and caused its accumulation in PC12 cells and midbrain neurons. At subtoxic doses, recombinant TNF was found to increase the number of LC3 puncta dots and LC3II protein level, associated with the increases of P62 protein level. Inhibition of lysosomal degradation with Bafilomycin A1 pretreatment abrogated the TNF-induced elevation in LC3II protein level whereas autophagy inhibitor 3-methyladenine did not affect it. Moreover, TNF led to a marked increase in the number of yellow LC3 dots with a marginal elevation in red-only dots in RFP-GFP-tandem fluorescent LC3 (tf-LC3) transfected PC12 cells, implying the impairment in autophagic flux. Furthermore, TNF treatment reduced lysosomal acidification, as LysoTracker Red fluorescence and LysoSensor fluorescence shift from blue to yellow was markedly decreased in TNF-treated PC12 cells. Co-treatment with mammalian target of rapamycin kinase complex 1 (mTORC1) inhibitor PP242, which activated transcription factor EB (TFEB) signaling and lysosome biogenesis, partially rescued the accumulation of α-SYN in PC12 cells and midbrain neurons. Taken together, our results demonstrated that at subtoxic levels, TNF was able to impair autophagic flux and result in α-SYN accumulation by compromising lysosomal acidification in dopaminergic cells. This may represent a novel mechanism for TNF-induced dopaminergic neuron degeneration in PD.


Assuntos
Autofagia/fisiologia , Neurônios Dopaminérgicos/metabolismo , Lisossomos/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , alfa-Sinucleína/metabolismo , Animais , Autofagia/efeitos dos fármacos , Sobrevivência Celular , Células Cultivadas , Neurônios Dopaminérgicos/efeitos dos fármacos , Embrião de Mamíferos , Feminino , Concentração de Íons de Hidrogênio , Indóis/farmacologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Lisossomos/efeitos dos fármacos , Mesencéfalo/citologia , Células PC12 , Gravidez , Purinas/farmacologia , Ratos , Ratos Sprague-Dawley , Sincalida/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , alfa-Sinucleína/genética
7.
Biochem Biophys Res Commun ; 455(3-4): 353-7, 2014 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-25446097

RESUMO

It has been demonstrated that acid sensing ionic channels (ASICs) are present in the central and peripheral nervous system of mammals, including the retina. However, it remains unclear whether the zebrafish retina also expresses ASICs. In the present study, the expression and distribution of zasic1 were examined in the retina of zebrafish. Both zasic1 mRNA and protein expressions were detected in the adult zebrafish retina. A wide distribution of ASIC1 in zebrafish retina was confirmed using whole mount in situ hybridization and immunohistochemistry study. Acidosis-induced currents in the isolated retinal ganglion cells (RGCs) were also recorded using whole cell patch clamping. Moreover, blockade of ASICs channel significantly reduced the locomotion of larval zebrafish in response to light exposure. In sum, our data demonstrate the presence of ASIC1 and its possible functional relevance in the retina of zebrafish.


Assuntos
Canais Iônicos Sensíveis a Ácido/fisiologia , Retina/metabolismo , Proteínas de Peixe-Zebra/fisiologia , Peixe-Zebra/genética , Canais Iônicos Sensíveis a Ácido/genética , Animais , Regulação da Expressão Gênica no Desenvolvimento , Imuno-Histoquímica , Hibridização In Situ , Larva , Luz , Microscopia de Fluorescência , Atividade Motora , Técnicas de Patch-Clamp , RNA Mensageiro/metabolismo , Células Ganglionares da Retina/citologia , Peixe-Zebra/fisiologia , Proteínas de Peixe-Zebra/genética
8.
PLoS One ; 8(8): e70472, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23936437

RESUMO

BACKGROUND: Neuroinflammation plays an important role in the pathogenesis of Parkinson's disease (PD), inducing and accelerating dopaminergic (DA) neuron loss. Autophagy, a critical mechanism for clearing misfolded or aggregated proteins such as α-synuclein (α-SYN), may affect DA neuron survival in the midbrain. However, whether autophagy contributes to neuroinflammation-induced toxicity in DA neurons remains unknown. RESULTS: Intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) into young (3-month-old) and aged (16-month-old) male C57BL/6J mice was observed to cause persistent neuroinflammation that was associated with a delayed and progressive loss of DA neurons and accumulation of α-SYN in the midbrain. The autophagic substrate-p62 (SQSTM1) persistently increased, whereas LC3-II and HDAC6 exhibited early increases followed by a decline. In vitro studies further demonstrated that TNF-α induced cell death in PC12 cells. Moreover, a sublethal dose of TNF-α (50 ng/ml) increased the expression of LC3-II, p62, and α-SYN, implying that TNF-α triggered autophagic impairment in cells. CONCLUSION: Neuroinflammation may cause autophagic impairment, which could in turn result in DA neuron degeneration in midbrain.


Assuntos
Autofagia , Neurônios Dopaminérgicos/patologia , Inflamação/patologia , Mesencéfalo/patologia , Animais , Autofagia/efeitos dos fármacos , Contagem de Células , Neurônios Dopaminérgicos/metabolismo , Inflamação/induzido quimicamente , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células PC12 , Doença de Parkinson/patologia , Ratos , Fator de Necrose Tumoral alfa/farmacologia , alfa-Sinucleína/metabolismo
9.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(4): 510-5, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23841274

RESUMO

OBJECTIVE: To observe the effects of ginseng and Ligustrazine drug containing serum on the proliferation, vitality, and extracellular-signal-responsive kinase (ERK) pathway in neural stem cells undergoing in vitro oxygen-glucose deprivation/reoxygenation culture. METHODS: The cultured neural stem cells were randomly divided into 5 groups, i.e., the normal control group (Group A), the oxygen-glucose deprivation/reoxygenation group (Group B), the oxygen-glucose deprivation/reoxygenation +ginseng serum group (Group C), the oxygen-glucose deprivation/reoxygenation + Ligustrazine serum group (Group D), and oxygen-glucose deprivation/reoxygenation +ginseng and Ligustrazine drug serum group (Group E).The protein expression levels of ERK and phosphorylated ERK (p-ERK) were observed using immunoblotting. The proliferation of neural stem cells was observed using 5-bromodeoxyuridine (BrdU) incorporation assay. The vitality of neural stem cells was detected using methyl thiazolyl tetrazolium (MTT) colorimetry. RESULTS: The p-ERK level increased transiently at 10 min and 30 min after reoxygenation, but it decreased to the normal level at 4 h, 6 h, and 1 day, respectively. Compared with Group B, the p-ERK level at 6 h after reoxygenation could be elevated in Group C, D, and E. The proliferation and the vitality of neural stem cells at 1 day after reoxygenation could be enhanced. Furthermore, the effects of combination of ginseng and Ligusticum were better than those of using ginseng or Ligusticum alone. CONCLUSIONS: Combination of ginseng and Ligusticum could promote the proliferation and vitality of rats' neural stem cells undergoing oxygen-glucose deprivation/reoxygenation culture through ERK signal pathway. Its effects was better than that of using ginseng or Ligusticum alone.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Ligusticum/química , Masculino , Células-Tronco Neurais/citologia , Panax/química , Fosforilação , Pirazinas/farmacologia , Ratos , Ratos Sprague-Dawley
10.
Zhonghua Gan Zang Bing Za Zhi ; 20(10): 769-73, 2012 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-23207339

RESUMO

OBJECTIVE: To investigate the in vivo functional roles of the La autoantigen (La), the human homologue of the 33-kDa vesicle-associated membrane protein-associated protein (hVAP-33), and the subunit gamma of the human eukaryotic initiation factors 2B (eIF2Bgamma) as co-infection factors supporting chronic infection with hepatitis C virus (HCV). METHODS: Small interfering (si)RNAs were designed against the HCV internal ribosome entry site (IRES) and transfected into Huh7 cells chronically infected with the HCV pseudovirus (designated as Huh7-HCV cells). The IRES siRNA producing the most effective silencing was selected for further analysis by fluorescence quantitative polymerase chain reaction (qPCR). siRNAs designed against La, hVAP-33, and eIF2Bgamma and the IRES-specific siRNA were then transfected, respectively or in various combinations, into the Huh7-HCV cell line for 48 h. The delta CT values were calculated and used to compare the HCV inhibitive efficacies of the siRNAs in isolation or in combination. Western blotting analysis was used to compare the quantity of core protein expression in each group. RESULTS: The four gene-specific siRNAs, in isolation or in combination, caused inhibition of HCV replication and gene and protein expressions to varying degrees. The combination of La + IRES siRNAs produced the strongest inhibition of HCV core antigen expression. The combinations of hVAP-33 + IRES siRNAs and eIF2Bgamma + IRES siRNAs produced stronger inhibitions of HCV replication and gene and protein expressions than either hVAP-33 siRNA or eIF2Bgamma siRNA alone. CONCLUSION: La, hVAP-33, and eIF2Bgamma act as co-infection factors of HCV chronic infection in vivo. HCV replication and gene and protein expression can be inhibited significantly by RNA interference of these co-infection factors and/or HCV IRES.


Assuntos
Autoantígenos/genética , Fator de Iniciação 2B em Eucariotos/genética , Hepacivirus/fisiologia , RNA Interferente Pequeno , Ribonucleoproteínas/genética , Proteínas de Transporte Vesicular/genética , Linhagem Celular , Hepacivirus/imunologia , Humanos , RNA Interferente Pequeno/genética , Replicação Viral
11.
World J Microbiol Biotechnol ; 28(3): 1155-62, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22805836

RESUMO

Two 1-aminocyclopropane-1-carboxylate deaminase-producing bacterial strains (DP24 and XG32) were isolated from surface-sterilized tomato roots and rizhospere soil. The strains were identified as Pseudomonas fluorescens biovar. IV (XG2) and Erwinia herbicola (DP24) by physiological and biochemical tests, and 16S rRNA gene analysis. Both strains showed positive plant growth-promoting activity when inoculated into cucumber (Cucumis sativus), tomato (Lycopersicon esculentum), pepper (Capsicum annuum) and rapeseed (Brassica napus L.). Colonization ability and behavior of these two strains were determined by treating mutant strains with rifampicin and fluorescence in situ hybridization (FISH) assay with rRNA targeted probes, respectively. Both strains were endophytic colonizers of pepper plants. The behavior of the two strains was not identical. Strain XG32 only colonized the root and reached the max level of 27.7 × 10(7) c.f.u./g (fresh weight), after 12 days postinoculation, while strain DP24 was able to colonize the roots, stems and leaves. The max level was reached at 40.87 × 10(7) c.f.u./g (fresh weight) in the roots, 17 × 10(7) c.f.u./g in the stems after 7 days postinoculation and 44.84 × 10(7) c.f.u./g in the leaves after 12 days postinoculation.


Assuntos
Carbono-Carbono Liases/biossíntese , Carbono-Carbono Liases/genética , Erwinia/enzimologia , Erwinia/isolamento & purificação , Pseudomonas fluorescens/enzimologia , Pseudomonas fluorescens/isolamento & purificação , Carga Bacteriana , Técnicas de Tipagem Bacteriana , Brassica napus/crescimento & desenvolvimento , Capsicum/crescimento & desenvolvimento , Análise por Conglomerados , Cucumis sativus/crescimento & desenvolvimento , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Endófitos/classificação , Endófitos/enzimologia , Endófitos/genética , Endófitos/isolamento & purificação , Erwinia/classificação , Erwinia/genética , Lycopersicon esculentum/crescimento & desenvolvimento , Lycopersicon esculentum/microbiologia , Dados de Sequência Molecular , Filogenia , Raízes de Plantas/microbiologia , Pseudomonas fluorescens/classificação , Pseudomonas fluorescens/genética , RNA Ribossômico 16S/genética , Rizosfera , Análise de Sequência de DNA , Microbiologia do Solo
12.
Nat Prod Commun ; 6(8): 1131-2, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21922917

RESUMO

Two compounds, apigenin-8-C-beta-D-glucopyranoside and 2-(hydroxymethylthio)ethanol, were extracted from the fermentation products of a strain of endophytic fungus, Colletotrichum sp. NTB-2, isolated from the leafstalk of Ginkgo biloba. The structures of the two compounds were determined on the basis of extensive spectroscopic analysis, including 1D and 2D NMR spectral data. The compounds wereobtained from microorganisms for the first time.


Assuntos
Álcoois/química , Apigenina/química , Colletotrichum/química , Ginkgo biloba/microbiologia , Glicosídeos/química , Piranos/química , Compostos de Sulfidrila/química , Estrutura Molecular
13.
Zhong Xi Yi Jie He Xue Bao ; 8(5): 427-31, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20456840

RESUMO

OBJECTIVE: To explore the main characteristics of syndromes in traditional Chinese medicine (TCM) in post-stroke depression (PSD) and to provide basis for treatments with TCM herbs. METHODS: According to diagnostic criteria of PSD, stroke patients and depression patients from Department of Neurology, First Affiliated Hospital, Anhui University of Traditional Chinese Medicine were assigned into cerebral stroke group (150 cases), depression group (151 cases) and PSD group (123 cases). Neuropsychological assessments and imaging and biochemical analyses were conducted. TCM syndrome differentiation for these diseases was performed. We also determined the characteristics of TCM syndromes of PSD, relative risk of the syndromes and their correlations with ages as well. RESULTS: Scores of qi stagnation and blood stasis, liver qi depression, and transformation of fire due to qi stagnation in PSD group were significant higher than those in cerebral stroke group (P<0.05, P<0.01). In cerebral stroke group, majority of the patients displayed one syndrome, while in PSD and depression groups, the patients had three or more syndromes. Of these syndromes, the incidence rate of syndrome of liver qi depression complicated with transformation of fire due to qi stagnation or flaring of fire due to yin deficiency was high. The syndrome of liver qi depression occurred much more frequently in PSD group and depression group than in cerebral stroke group (P<0.05, P<0.01). The logistic regression analysis showed that the syndrome of qi stagnation and blood stasis had high relative risk to PSD. The syndrome of deficiency of heart and spleen was positively correlated with age in cerebral stroke group. CONCLUSION: The main TCM syndromes of PSD and depression are qi stagnation and blood stasis, liver qi depression, and transformation of fire due to qi stagnation. The syndrome of deficiency of heart and spleen is closely related to age among the stroke patients. The syndrome of qi stagnation and blood stasis serves as an independent risk factor for PSD. The more complicated the syndromes are, the more serious depression becomes.


Assuntos
Depressão/diagnóstico , Medicina Tradicional Chinesa/métodos , Acidente Vascular Cerebral/diagnóstico , Idoso , Depressão/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações
14.
Zhonghua Gan Zang Bing Za Zhi ; 14(1): 11-4, 2006 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-16420757

RESUMO

OBJECTIVE: To determine the advantage of U1 small nuclear RNA as a ribozyme vector (U1-Rz) to inhibit HCV replication in vivo. METHODS: The 3rd stem-loop was substituted by HCV core specific ribozyme to construct an U1-Rz eucaryotic expression plasmid. Then it was co-transfected with pCMV/T7-NCRC Delta-luc into Huh7 cell line mediated by lipofectin. The cell lysis supernatant was subjected to Western blot and lumenometer to determine the luciferase levels. RESULTS: A U1 snRNA chimeric ribozyme was constructed successfully. Both Rz and U1-Rz inhibited luciferase expression in Huh7 by 48.64% and 87.46%, respectively. CONCLUSION: Rz has more efficacy in cells when using U1 snRNA delivery system. U1 can be an efficient vector for HCV specific ribozyme.


Assuntos
Hepacivirus/fisiologia , RNA Catalítico/genética , RNA Nuclear Pequeno/genética , Replicação Viral/genética , Sequência de Bases , Terapia Genética , Vetores Genéticos , Humanos , Dados de Sequência Molecular
15.
Zhonghua Gan Zang Bing Za Zhi ; 12(12): 749-51, 2004 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-15619345

RESUMO

OBJECTIVE: To study the cleavage activity on the HCV RNA of a chimeric recombinant of HCV specific ribozyme and U1 small nuclear RNA, which compartmentalizes within the nucleolus. METHODS: The third stem-loop sequence of human U1 snRNA (position 95-116) within pBSIISK+ U1 was substituted by hammerhead ribozyme against HCV RNA by PCR and cloning methods, and the constructed plasmid was named pBSIISK+ (U1-Rz). Then the whole gene fragment of the chimeric ribozyme was cloned into a pGEM-T vector under the control of T7 promoter, and the constructed plasmid was named pGEM- (U1-Rz). The pGEM- (U1-Rz) and pGEM-Rz (containing the same ribozyme sequence as that in U1-Rz) transcripts as enzyme were transcribed in vitro. Also the (32)P-labeled pCMV/T7-NCRC luc (containing the gene sequence of the whole 5'-NCR and part core of HCV RNA) transcripts as target-RNAs were transcribed in vitro. The enzymes were incubated with the target RNAs under different conditions and autoradiographed after denaturing gel-electrophoresis. RESULTS: The sequencing result showed that the construction of U1 snRNA chimeric ribozyme was correct. Compared with the ribozyme alone, both of them were active at 37 degree C and with Mg2+ (10 mmol/L) and TrisCl (10 mmol/L, pH7.9), and there was no remarkable difference between them. The cleavage activity of the chimeric ribozyme increased with the prolongation of reaction time and increment of enzyme concentration. CONCLUSION: Both ribozyme and U1 snRNA chimeric ribozyme exhibited specifically catalytic activity against HCV RNA in vitro. There was no remarkable difference between their cleavage efficiencies.


Assuntos
Hepacivirus/genética , RNA Catalítico/genética , RNA Nuclear Pequeno/genética , RNA Nuclear Pequeno/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Quimera/genética , Terapia Genética , Hepatite C/terapia , RNA Catalítico/metabolismo , RNA Viral/genética
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