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1.
Org Lett ; 22(3): 814-817, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31933372

RESUMO

Indole and phthalide are privileged heterocyclic scaffolds in numerous natural products and bioactive molecules. The synthesis and biological evaluation of the compounds combining these two scaffolds have rarely been reported. Herein, we repot the first palladium-catalyzed ligand-free double cyclization reactions that enable efficient synthesis of 3-(1'-indolyl)-phthalides (42 examples, up to 96% yield) under mild conditions. Notably, only 1.0 mol % of catalyst loading is used, suggesting high efficiency. Late-stage elaborations give highly functionalized analogues.

2.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(5): 480-484, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31721493

RESUMO

OBJECTIVE: This study aimed to evaluate the stress distribution of the mandibular first molar with different thicknesses and heights of the axial wall restored by the endocrown with two marginal designs and thus provide a theoretical basis for selecting clinical preparation through the finite-element method. METHODS: Two marginal endocrowns of the mandibular first molar with different axial-wall thicknesses (t=1, 2, 3 mm) and heights (h=2, 3, 4 mm) were established. Group A was the butt-joint design, whereas group B was the shoulder-surrounded design. After applying vertical and oblique loads , the size and distribution of the maximum principal stress and equivalent stress of residual tooth tissue were recorded. RESULTS: The maximum principal stress and equivalent stress distribution of residual tooth tissue were similar among different models. Group A showed a lower maximum principal stress and equivalent stress than group B at the same thickness and height under vertical load. Meanwhile, under oblique load, the maximum principal stress values of groups A and B decreased with increased thickness at constant height. Group A showed lower equivalent stress than group B at the same thickness and height of 2 and 3 mm. However, when the height was 4 mm, the trend was reversed. CONCLUSIONS: In mastication, when bearing the vertical force, the retention of the butt-joint marginal endocrown preferred to the shoulder-surrounded one. Given the higher axial wall of the shoulder-surrounded marginal endocrown, it showed better ability to bear the oblique force than the butt-joint one.


Assuntos
Coroas , Dente Molar , Análise do Estresse Dentário , Análise de Elementos Finitos , Mastigação
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(2): 234-240, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-31106546

RESUMO

OBJECTIVE: To screen the genes with significant changes in DNA methylation level in active tuberculosis patients, we used the methylation chips and expanded the sample size to verify candidate genes. METHODS: ① This study enrolled 9 cases of active tuberculosis patients, 3 cases of latent tuberculosis patients and 3 cases of healthy controls whose age and gender were all matched. Genome DNA was extracted from peripheral blood mononuclear cell in blood samples collected from these candidates, and bisulfite conversion treatment was then conducted. After hybridization with the Illumina HD 450K Infinium Mehtylation BeadChip, the results were compared between patients group and control group, and GO and KEGG pathway analyses were performed to evaluate the function of differentially expressed genes. ② We further enrolled 60 cases of active tuberculosis patients and 60 cases of health controls (age-and gender-matched), DNA was extracted from their peripheral blood and also followed bisulfite conversion treatment. Pyrosequencing method was used to detect the methylation levels of candidate genes (IFNGR2, PTPN6, CRK1, ATP6V0B, WIF1, DKK1 and SFRP1) screened by gene chip. RESULTS: Compared with healthy controls, the fragments in the patients that showed low methylation change accounted for the vast majority. Most of the methylation differential fragments (DMRs) were located in the main body region, followed by the upstream region of transcription initiation site, and the lowest DMRs distribution area was 3´UTR area. GO and Pathway analysis showed that the functions of the differentially methylated regions related genes are mainly enriched in the biological processes of the regulation of leukocyte differentiation, apoptosis, cytokine regulation and inflammatory response which are closely related to tuberculosis. There were 32 CpG sites involved in the verified 7 tuberculosis related genes, and 16 CpG locus showed significant difference (P<0.05), they were distributed in 6 genes: PTPN6, WIF1, CRK1, SFRP1, DKK1 and IFNGR2.Of these genes with significant difference, PTPN6 genes showed hypermethylation status and WIF1, CRK1, SFRP1, DKK1 and IFNGR2 genes exhibited demethylation status in the patients group compared to the health controls. SFRP1 and CRK-1 mRNA up-regulated in the patients group compared with health controls. CONCLUSION: In the course of MTB infection, the methylation status of genomic DNA is altered, and most of the differentially methylated regions (DMRs) are showed status of demethylation. The expressions ofSFRP1and CRK-1gene up-regulate in tuberculosis infection.


Assuntos
Metilação de DNA , Tuberculose Latente/genética , Análise de Sequência com Séries de Oligonucleotídeos , Tuberculose/genética , Ilhas de CpG , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Leucócitos Mononucleares , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas c-crk/genética
5.
Clin Lab ; 65(5)2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31115239

RESUMO

BACKGROUND: Accumulating evidence has revealed that inflammation might play an important role in the genesis and development of cancer. High levels of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ration (PLR) are parameters of systemic inflammation which have been identified to be associated with poor prognosis in PCa. Bone is one of the most common sites of metastasis from prostate cancer; however, there are few studies concerning the correlation of NLR, PLR, and bone metastases in PCa. The aim of this study was to evaluate the performance of neutrophil to lymphocyte ratio (NLR) or platelet to lymphocyte (PLR) in diagnosis of bone metastasis of prostate cancer (PCa). METHODS: Data of 74 PCa patients without metastases, 51 PCa patients with bone metastases, and 43 patients with benign prostatic hypertrophy (BPH) were retrospectively reviewed. The difference of patients' clinical and laboratory characteristics of the three groups was comparatively studied. ROC analysis was used to evaluate the benefit of adding NLR or PLR to prostate specific antigen (PSA) in prediction of bone metastases. Depending on this cutoff value, patients were divided into high-NLR or low-NLR group, high-PLR or low-PLR group. RESULTS: There were significant differences in NLR and PLR between groups with bone metastases and without bone metastases (p = 0.044; p = 0.030), while there was no significant difference between NLR and PLR of the patients with localized prostate cancer and BPH (p = 0.462; p = 0.102). NLR and PLR were correlated with PSA level in the patients with prostate cancer (p = 0.006, r = 0.247; p = 0.025, r = 0.200). The distribution of PSA showed significant differences between the high-NLR and low-NLR group, as well as between the high-PLR and low-PLR group. By applying the ROC curve method, the AUC values of PSA with NLR or PLR were 0.725 and 0.838 (0.763 - 0.913), respectively. Although PSA + PLR had the largest area, there was no statistical significance between PSA + PLR and PSA (p = 0.6992). CONCLUSIONS: NLR and PLR significantly increase in PCa patients with bone metastases and are valuable in the diagnosis of bone metastases in PCa patients.


Assuntos
Neoplasias Ósseas/sangue , Contagem de Leucócitos , Contagem de Plaquetas , Neoplasias da Próstata/sangue , Idoso , Plaquetas , Neoplasias Ósseas/patologia , Humanos , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Prognóstico , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/secundário , Estudos Retrospectivos , Sensibilidade e Especificidade
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(5): 731-736, 2018 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30378335

RESUMO

OBJECTIVE: To screen and identify the gene of DNA methylation in patients with active tuberculosis. METHODS: ① This study enrolled 9 cases of active tuberculosis patients (including 3 newly diagnosed tuberculosis patients and 6 cases of retreatment of active tuberculosis patients), 3 cases of latent tuberculosis patients and 3 cases of healthy controls. Genome DNA was extracted from Peripheral Blood Mononuclear Cell and following bisulfite conversion treatment. After hybridization with the Illumina HD 450K Infinium Mehtylation BeadChip, the results were compared between patients group and control group, GO and Pathway analysis were performed to evaluate the function of differentially expressed genes; ② We further enrolled 60 cases of active tuberculosis patients and 60 cases of health controls (their age and gender were matched). By using pyrosequencing method to detect the methylation levels of candidate genes (TLR1, TLR2, TLR4) screened by gene chip. RESULTS: ① Compared with healthy controls, we found that most of them were showed demethylation status. GO and Pathway analysis showed that the functions of the differentially methylated regions related genes were mainly enriched in the biological processes of the regulation of leukocyte apoptosis, cytokine regulation and inflammatory response which were closely related to tuberculosis. ②There were 10 CpG sites involved in the verified tuberculosis related genes (TLR1, TLR2, TLR4), the CpG sites of TLR1 gene showed the hypermethylation status (P<0.001), the CpG sites of TLR4 gene showed demethylation status (P=0.012). CONCLUSION: The present study demonstrated that in the course of MTB infection, the methylation status of genomic DNA was altered, and most of the Differentially Methylated Regions (DMRs) were showed status of demethylation. TLR1 gene and TLR4 gene may play an important role in the occurrence and development of tuberculosis.


Assuntos
Metilação de DNA , Tuberculose/genética , Estudos de Casos e Controles , Ilhas de CpG , Humanos , Leucócitos Mononucleares , Análise de Sequência com Séries de Oligonucleotídeos , Receptor 1 Toll-Like/genética , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética
7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(6): 920-925, 2016 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-28598125

RESUMO

OBJECTIVES: To determine the correlation between gene polymorphisms in Wnt signal pathway and susceptibility of Chinese Tibetan people to tuberculosis. METHODS: A total of 488 active tuberculosis patients and 454 healthy subjects(control) were enrolled in this case-control study.Five single nucleotide polymorphisms (SNPs) in Wnt signal pathway (rs4135385 in CTNNB1 gene,rs11001553 in DKK1 gene,rs56900803 in WIF1 gene,rs7832767 in SFRP1 gene and rs11079571 in AXIN2 gene) were genotyped using MassARRAY method.The genotype and allele distributions of these loci were determined using SPSS19.0 and SNP stats software.Significant SNPs were measured in the co-dominant,dominant and recessive genetic models.The polymorphism distributions of Chinese Tibetans were compared with those of Chinese Han populations. RESULTS: The genotype distributions of all SNPs coincided with the Hardy-Weinberg equilibrium in the 2 groups.The frequencies of genotype and allele of rs7832767 in SFRP1 gene were significantly different (P=0.004,0.002,respectively) between the Tibetan patients with tuberculosis and the Tibetan healthy controls.Compared with C allele carriers,those carrying T allele of rs7832767 showed increased risk of tuberculosis [odds ratio (OR)=1.260,95% confidence interval (CI):1.086-1.471,P=0.002].The co-dominant,dominant and recessive models of this locus were also associated with higher risk of tuberculosis.No significant differences in genotype and allele distributions were observed for the other four SNP loci (P all>0.05).The distribution of rs4135385 in CTNNB1 gene in the Chinese Tibetan population differed from the Han population (P=0.035 for genotype,0.021 for allele).There were no obvious differences in genotype and allele distributions for the other four SNPs between the Tibetan and Han populations (P all >0.05). CONCLUSIONS: SFRP1 gene polymorphism in Wnt signal pathway is associated with tuberculosis susceptibility in Chinese Tibetan population.The distribution of CTNNB1 gene polymorphism differs between Chinese Tibetan and Han populations.


Assuntos
Polimorfismo de Nucleotídeo Único , Tuberculose/genética , Via de Sinalização Wnt/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Proteína Axina/genética , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas Repressoras/genética , Tibet , beta Catenina/genética
8.
Chem Biol Interact ; 203(1): 309-13, 2013 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-22944069

RESUMO

Lithium is one of the most widely used mood-stabilizing agents for the treatment of bipolar disorder. Lithium is also a potent inhibitor of glycogen synthase kinase-3ß (GSK3ß) activity, which is linked to Alzheimer's disease (AD). In experiments with cultured HEK293T cells, we show here that GSK3ß stabilizes synaptic acetylcholinesterase (AChE-S), a critical component of AD development. Cells treated with lithium exhibited rapid proteasomal degradation of AChE-S. Furthermore treatment of the cells with MG132, an inhibitor of the 26S proteasome, prevented the destabilizing effect of lithium on AChE-S. Taken together, these findings suggest that regulation of AChE-S protein stability may be an important biological target of lithium therapy.


Assuntos
Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Lítio/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/enzimologia , Substituição de Aminoácidos , Animais , Inibidores Enzimáticos/farmacologia , Estabilidade Enzimática/efeitos dos fármacos , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Quinase 3 da Glicogênio Sintase/genética , Glicogênio Sintase Quinase 3 beta , Células HEK293 , Humanos , Leupeptinas/farmacologia , Mutagênese Sítio-Dirigida , Células PC12 , Ratos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
9.
Physiol Plant ; 145(3): 384-94, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22380525

RESUMO

The 'stage albinism line of winter wheat' FA85 exhibits a severe block in chlorophyll (Chl) biosynthesis with prolonged low-temperature treatment. The correlations between leaf color and low temperature provide more comprehensive understanding of low temperature as an environmental signal that regulate the metabolic changes in the entire Chl-synthesizing pathway. In this study, we investigated differences in Chl biosynthesis between leaves of Aibian1 and FA85 by measuring their Chl precursors and heme content, transcripts for key genes of Chl biosynthesis and key enzyme activities. With prolonged low-temperature treatment, the Chl content gradually decreased, but Chl precursors, including protoporphyrin IX, Mg-protoporphyrin IX and protochlorophyllide (Pchlide), simultaneously accumulated. Parallel to the decline in Chl content, the protoporphyrin IX distribution toward Chl synthesis was less than that in heme synthesis in the leaves of FA85. Corresponding to the change of protoporphyrin IX distribution, the relative changes in magnesium chelatase (EC 6.6.1.1) and ferrochelatase (EC 4.99.1.1) activities in the leaves of FA85 also indirectly reflected channeling of the metabolic flow into heme rather than Chl. A drastic loss in the transcripts for Pchlide oxidoreductase (EC 1.3.1.33) and Chl synthase (EC 2.5.1.62) accounted for a decrease in the metabolic flux and the re-direction of metabolites. The high-level accumulations of Chl precursors and traces of Chl in the leaves of FA85 suggest that a severe block between the steps from Pchlide to Chl formation during Chl biosynthesis is partially derived from the transcriptional downregulation of Pchlide oxidoreductase and Chl synthase.


Assuntos
Temperatura Baixa , Protoclorifilida/biossíntese , Protoporfirinas/biossíntese , Triticum/metabolismo , Cor , Ativação Enzimática , Ferroquelatase/genética , Ferroquelatase/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Liases/genética , Liases/metabolismo , Oxirredutases/genética , Oxirredutases/metabolismo , Fenótipo , Folhas de Planta/enzimologia , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Protoclorifilida/genética , Protoporfirinas/genética , RNA de Plantas/genética , Especificidade da Espécie , Fatores de Tempo , Transcrição Genética , Triticum/enzimologia , Triticum/genética
10.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 12): o3307, 2011 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-22199808

RESUMO

The asymmetric unit of the title compound, C(26)H(28)BrN, contains two independent mol-ecules in which the carbazole rings are almost planar, with r.m.s. deviations of 0.0212 (1) and 0.0229 (1) Å. The dihedral angles between the carbazole ring system and the pendent benzene ring are 60.5 (1) and 56.3 (1)° in the two mol-ecules. In the crystal, mol-ecules are linked into chains along the b axis by C-H⋯π inter-actions.

11.
Cell Mol Life Sci ; 66(13): 2181-93, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19468687

RESUMO

Recently, acetylcholinesterase (AChE) has been studied as an important apoptosis regulator. We previously showed that cellular calcium mobilization upregulated AChE expression by modulating promoter activity and mRNA stability. In this study, we have identified a potential Smad3/4 binding element, TGCCAGACA, located within the -601 to -571 bp fragment of the AChE promoter, as an important calcium response motif. Smad2/3 and Smad4 were shown to bind this element. Overexpression of human Smad3 increased AChE transcription activity in a dose-dependent manner in HeLa cells, whereas dominant-negative Smad3 blocked this activation. Upon A23187 and thapsigargin treatment, nuclear Smad3 accumulation was observed, an effect that was blocked by the intracellular Ca(2+) chelator BAPTA-AM. Calcium-induced AChE transcriptional activation was significantly blocked when the nuclear localization signal of Smad3 was destroyed. Taken together, our data suggest Smad3 can regulate AChE transcriptional activation following calcium-induced nuclear accumulation.


Assuntos
Acetilcolinesterase/genética , Apoptose/fisiologia , Sinalização do Cálcio/fisiologia , Núcleo Celular/metabolismo , Regulação Enzimológica da Expressão Gênica , Proteína Smad3/metabolismo , Transcrição Genética , Acetilcolinesterase/metabolismo , Animais , Cálcio/metabolismo , Inibidores Enzimáticos/metabolismo , Células HeLa , Humanos , Regiões Promotoras Genéticas , Proteína Smad2/metabolismo , Proteína Smad3/genética , Proteína Smad4/metabolismo , Tapsigargina/metabolismo
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