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1.
Phys Biol ; 16(6): 066007, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31469100

RESUMO

The glycolytic enzyme pyruvate kinase M2 (PKM2) exists in both catalytically inactive dimeric and active tetrameric forms. In cancer cells, PKM2 dimer predominance contributes to tumor growth by triggering glycolytic reprogramming. However, the mechanism that promotes PKM2 dimer predominance over tetramer in cancer cells remains elusive. Here, we show that pulsatile phosphofructokinase (PFK-1) activity results in PKM2 dimer predominance. Mathematical simulations predict that pulsatile PFK-1 activity prevents the formation of PKM2 tetramer even under high levels of fructose-1,6-bisphosphate (FBP), a PKM2 tetramer-promoting metabolite produced by PFK-1. We experimentally confirm these predictions at the single-molecule level by providing evidence for pulsatile PFK-1 activity-induced synchronized dissociation of PKM2 tetramers and the subsequent accumulation of PKM2 dimers under high levels of FBP in HeLa cells. Moreover, we show that pulsatile PFK-1 activity-induced PKM2 dimer predominance also controls cell proliferation. Thus, our study reveals the significance of pulsatile PFK-1 activity in cancer cell metabolism.

2.
Pathol Res Pract ; 215(3): 594-599, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30691859

RESUMO

Endometrial cancer (EC) is a huge threat to women's health. The aims of this study were to investigate the role of microRNA (miR)-495 in the proliferation and apoptosis of EC cells in vitro. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect the mRNA levels. In addition, dual-luciferase reporter assay was used to verified that PIK3R1 was a target of miR-495. After transfection with miR-495 mimics, Cell Counting Kit 8 (CCK-8) assay was performed to evaluate the cell viability of EC cells. The protein expression of PIK3R1, vascular endothelial growth factor (VEGF), Bcl-2, Bax, caspase 3 after transfection was analyzed using western blotting. Furthermore, cell apoptosis rate of EC cells was evaluated by flow cytometry. These results showed that miR-495 was significantly down-regulated in tumor tissues compared with the adjacent normal tissues, while PIK3R1 was up-regulated. The proliferation of the EC cells that were transfected with miR-495 mimics was markedly inhibited, and apoptosis was significantly promoted. In addition, downregulated expression of PIK3R1, Bcl-2, VEGF expression and upregulated expression of Bax and caspase 3 expression were observed after transfected with miR-495 mimic. Together these findings indicated that miR-495 acts as a tumor suppressor gene by directly targeting PIK3R1 at the post-transcriptional level in EC cells in vitro.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Neoplasias do Endométrio/genética , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor , Humanos
3.
Eur J Pharmacol ; 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30513279

RESUMO

Cervical cancer (CC) is the fourth most frequent malignancy worldwide. MicroRNAs (miRNAs) can function as potential biomarkers or therapeutic targets in multiple cancers including CC. Our present study aimed to investigate the roles and downstream targets of microRNA-20a (miR-20a) in regulating CC proliferation, apoptosis and autophagy. Here, RT-qPCR assay revealed that miR-20a was highly expressed in CC tissues and cells. Functional analysis showed that the inhibition of miR-20a resulted in reduced proliferation, increased apoptosis and downregulated autophagic activity in CC cells. Bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation (RIP) assay manifested that thrombospondin 2 (THBS2) was a target of miR-20a. Also, THBS2 expression was notably reduced in CC tissues and cells, and inversely associated with miR-20a expression in CC tissues. Restoration experiments disclosed that THBS2 knockdown abrogated miR-20a inhibitor-mediated anti-proliferation, pro-apoptosis, and anti-autophagy effects in CC cells. In summary, these data showed that the depletion of miR-20a suppressed proliferation and autophagy and induced apoptosis by targeting THBS2 in CC cells, further elucidating the roles and molecular basis of miR-20a in the development of CC.

4.
Cell Cycle ; 17(16): 1967-1978, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30145936

RESUMO

Systemic sclerosis (SSc) is a multisystemic fibrotic disease characterized by excessive collagen deposition and extracellular matrix synthesis. Though transforming growth factor-ß (TGF-ß) plays a fundamental role in the pathogenesis of SSc, the mechanism by which TGF-ß signaling acts in SSc remains largely unclear. Here, we showed that TGF-ß type II receptor (TGFBR2) was significantly upregulated in both human SSc dermal tissues and primary fibroblasts. In fibroblasts, siRNA-induced knockdown of TGFBR2 resulted in a reduction of p-SMAD2/3 levels and reduced production of type I collagen. Additionally, functional experiments revealed that downregulation of TGFBR2 yielded an anti-growth effect on fibroblasts through inhibiting cell cycle progression. Further studies showed that miR-3606-3p could directly target the 3'-UTR of TGFBR2 and significantly decrease the levels of both TGFBR2 mRNA and protein. Furthermore, SSc dermal tissues and primary fibroblasts contain significantly reduced amounts of miR-3606-3p, and the overexpression of miR-3606-3p in fibroblasts replicates the phenotype of TGFBR2 downregulation. Collectively, our findings demonstrated that increased TGFBR2 could be responsible for the hyperactive TGF-ß signaling observed in SSc. Moreover, we identified a pivotal role for miR-3606-3p in SSc, which acts, at least partly, through the attenuation of TGF-ß signaling via TGFBR2 repression, suggesting that the regulation of miR-3606-3p/TGFBR2 could be a promising therapeutic target that could improve the treatment strategy for fibrosis.

5.
Mol Med Rep ; 18(3): 2841-2849, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30015967

RESUMO

Endometriosis is a common gynecological disease, affecting 6­10% of women of reproductive age. The precise mechanisms underlying the development of endometriosis remain unclear. In the present study, a bioinformatics approach was applied to systematically identify the pathways and genes involved in the development of endometriosis and to discover potential biomarkers. The gene expression profiles of GSE6364, a microarray dataset of endometrial biopsies obtained from women with or without endometriosis, was downloaded from the Gene Expression Omnibus DataSets database that stores original submitter­supplied records (series, samples and platforms), as well as curated datasets. Differentially expressed gene (DEG) analysis was performed with GEO2R. DAVID was used to analyze the gene ontology enrichment of the DEGs. Gene Set Enrichment Analysis (GSEA) was conducted using the GSEA v3.0 software. Protein­protein interactions (PPI) were evaluated with the Search Tool for the Retrieval of Interacting Genes, and PPI network visualization was performed with Cytoscape. In addition, Cell Counting kit­8 and Transwell assays were performed on human endometrial stromal cells (HESCs). A total of 172 DEGs were extracted. Inflammatory response genes were significantly upregulated in the endometriosis tissues and C­X­C motif chemokine receptor 2 (CXCR2), was one of the most up­regulated genes according to DEG analysis. Cell­based experiments confirmed that CXCR2 promoted the proliferation, migration and invasion of HESCs. In conclusion, a bioinformatics approach combined with in vitro experiments in the present study revealed that CXCR2 may be associated with the development of endometriosis and has potential as a biomarker for the diagnosis of endometriosis.


Assuntos
Endometriose/patologia , Receptores de Interleucina-8B/metabolismo , Adulto , Movimento Celular , Proliferação de Células , Células Cultivadas , Biologia Computacional , Endometriose/genética , Endometriose/metabolismo , Endométrio/citologia , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes/genética , Humanos , Pessoa de Meia-Idade , Mapas de Interação de Proteínas/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores de Interleucina-8B/antagonistas & inibidores , Receptores de Interleucina-8B/genética , Células Estromais/citologia , Células Estromais/metabolismo , Adulto Jovem
6.
Pestic Biochem Physiol ; 142: 59-66, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29107248

RESUMO

Insect ryanodine receptors are the main targets of diamide insecticides that have highly selective insecticidal activity but are less toxic to mammals. Therefore, these insecticides are ideal for pest control. Ryanodine receptors (RyRs) play a critical role in Ca2+ signaling in muscle and non-muscle cells. In this study, we cloned the complete cDNA (DcRyR) of the RyR from the citrus whitefly, Dialeurodes citri, a serious pest of citrus orchards in China. The open reading frame of RyR is 15,378bp long and encodes a protein with 5126 amino acids with a computed molecular weight of 579.523kDa. DcRyR shows a high amino acid sequence identity to RyRs from other insects (76%-95%) and low identity to those from nematodes and mammals (44%-52%). DcRyR shares many features of insect and vertebrate RyRs, including a MIR domain, two RIH domains, three SPRY domains, four copies of RyR repeat domain, RIH-associated domain at the N-terminus, two consensus calcium-binding EF-hands and six transmembrane domains at the C-terminus. The expression of DcRyR mRNA was the highest in the nymphs and lowest in eggs; DcRyR mRNA was 1.85-fold higher in the nymphs than in the eggs. Among the tissues, DcRyR mRNA expression was 4.18- and 4.02-fold higher in the adult head and thorax than in the abdomen. DcRyR had three alternative splice sites and the splice variants showed body part-specific expression and were developmentally regulated. These results may help investigate target-based resistance to diamide insecticides in D. citri.


Assuntos
Processamento Alternativo , Hemípteros/genética , Proteínas de Insetos/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Animais , Clonagem Molecular , Hemípteros/química , Hemípteros/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Domínios Proteicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Rianodina/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/química , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo
7.
Oncol Rep ; 38(4): 1977-1984, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28849071

RESUMO

MicroRNAs (miRNAs) are a cluster of short non-coding RNAs playing critical roles in human cancers. miR-187 was recently found to be a novel cancer-related microRNA. However, the expression and function of miR-187 in cervical cancer have not been investigated. In this study, we found that miR-187 level was decreased in cervical cancer tissues and cell lines. Patients with low level of miR-187 had significantly decreased rate of overall survival (OS) and progression-free survival (DFS). miR-187 overexpression inhibited proliferation and promoted apoptosis of cervical cancer cells, whereas miR-187 knockdown promoted proliferation and inhibited apoptosis of cervical cancer cells. Forced expression of miR-187 inhibited the subcutaneous growth of cervical cancer cells in nude mice. Furthermore, FGF9 was found to be the downstream target of miR-187 in cervical cancer cells. Importantly, targeting FGF9 was required for miR-187 exerting its tumor suppressive roles in cervical cancer cells.


Assuntos
Fator 9 de Crescimento de Fibroblastos/metabolismo , MicroRNAs/metabolismo , Neoplasias do Colo do Útero/metabolismo , Animais , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Fator 9 de Crescimento de Fibroblastos/genética , Células HeLa , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , MicroRNAs/biossíntese , MicroRNAs/genética , Prognóstico , Taxa de Sobrevida , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
8.
Tumour Biol ; 35(9): 9179-84, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24927671

RESUMO

Several reports on the association between the BRCC5 gene polymorphism and ovarian cancer risk have been published recently, but the estimates of the risk vary widely. We thus performed a meta-analysis in an effort to determine the association. To identify the eligible studies, we searched the PubMed, Embase, and CNKI databases, and reviewed all original studies retrieved as well as their citations. The risk of ovarian cancer was estimated using odds ratio (OR) and its 95 % confidence interval (CI). Meta-analysis of seven comparisons revealed an obvious rise in the risk of ovarian cancer under the CC vs. GG contrast model (OR = 1.52, 95 % CI = 1.07-2.16, P OR = 0.020). A similar increase was also indicated in the CC vs. GC + GG model (OR = 2.10, 95 % CI = 1.51-2.93, P OR < 0.001). Our meta-analysis indicates that the BRCC5 polymorphism may be a candidate modifier of ovarian cancer risk in Caucasians.


Assuntos
Predisposição Genética para Doença/genética , Neoplasias Ovarianas/genética , Polimorfismo Genético , Rad51 Recombinase/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Razão de Chances , Neoplasias Ovarianas/etnologia , Fatores de Risco
9.
J Huazhong Univ Sci Technolog Med Sci ; 34(2): 207-212, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24710934

RESUMO

Recently, microRNAs (miRNAs) have been shown to be involved in multiple biological pathways that can influence tumor progression and metastasis and they can serve as prognostic biomarkers in many cancers. The present study examined the prognostic significance of miR-215 in cervical cancer. The paraffin-embedded paired cervical scrape samples and tumor tissue samples from 302 patients with stage II cervical cancer were detected for the expression of miR-215 by using qRT-PCR. A miR-215-based classifier was established by using the Cox regression model. The prognostic and predictive accuracy of this classifier was determined in both the internal testing group of 138 patients, and the external independent group of 280 patients. Moreover, cervical cancer HeLa cells overexpressing miR-215 (HeLa-miR-215) were constructed and subcutaneously injected into the nude mice to examine the effect of miR-215 on tumor growth and metastasis in vivo. The results showed that the expression level of miR-215 was significantly higher in cervical cancer tissues than in paired normal tissues (P<0.0001). When patients were classified into high- and low-risk cancer progression groups according to miR-215 level, the 5-year disease-free survival in high- and low-risk groups were 43% (95% CI: 32.1-51.6) and 67% (95% CI: 48.6-77.3) (hazard ratio [HR] 2.02, 95% CI: 1.16-3.52; P=0.013) respectively. Moreover, the expression level of miR-215 was negatively associated with survival rate in patients at TNM stage T3 (HR: 3.317; 95% CI: 1.18-5.14, P=0.017) and TNM stage T4 (HR: 3.48; 95% CI: 1.49-4.45, P=0.008). Tumor volume in nude mice injected with HeLa-miR-215 cells was significantly larger than that in mice injected with control HeLa cells. It was concluded that the expression level of miR-215 is associated with cervical tumor progression and worse survival rate, suggesting that it may serve as a potential prognostic marker to identify patients at higher risk of recurrence.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Idoso , Animais , Intervalo Livre de Doença , Feminino , Células HeLa , Humanos , Masculino , Camundongos , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias do Colo do Útero/patologia
10.
PLoS One ; 8(4): e62380, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23638057

RESUMO

Due to the complexity of biological systems, simulation of biological networks is necessary but sometimes complicated. The classic stochastic simulation algorithm (SSA) by Gillespie and its modified versions are widely used to simulate the stochastic dynamics of biochemical reaction systems. However, it has remained a challenge to implement accurate and efficient simulation algorithms for general reaction schemes in growing cells. Here, we present a modeling and simulation tool, called 'GeneCircuits', which is specifically developed to simulate gene-regulation in exponentially growing bacterial cells (such as E. coli) with overlapping cell cycles. Our tool integrates three specific features of these cells that are not generally included in SSA tools: 1) the time delay between the regulation and synthesis of proteins that is due to transcription and translation processes; 2) cell cycle-dependent periodic changes of gene dosage; and 3) variations in the propensities of chemical reactions that have time-dependent reaction rates as a consequence of volume expansion and cell division. We give three biologically relevant examples to illustrate the use of our simulation tool in quantitative studies of systems biology and synthetic biology.


Assuntos
Divisão Celular/genética , Simulação por Computador , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Cromossomos Bacterianos/genética , Escherichia coli/citologia , Retroalimentação Fisiológica , Dosagem de Genes , Genes Bacterianos/genética , Software , Fatores de Tempo
11.
Mol Med Rep ; 7(2): 425-30, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23229441

RESUMO

Survivin (SVV) is an important member of the inhibitor of apoptosis family. It is overexpressed in a number of cancer types, including human ovarian carcinomas. SVV promotes invasion, metastasis, growth and survival of malignant cells and confers resistance to specific chemotherapeutic drugs. The present study aimed to elucidate the role and possible mechanisms of SVV in cisplatin-resistant ovarian cancer cells (A2780/CP). Using a loss-of-function approach, we investigated the effects of adenovirus-mediated knockdown of SVV by small hairpin RNA (ad5-SVV) on the expression of pro-caspase-3, cleaved caspase-3, proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2) in A2780/CP cells by real-time PCR and western blot analysis. Proliferation was measured by MTT assay, invasive potential by Transwell, and cell apoptosis by FITC-Annexin V and propidium iodide for the functional analysis of A2780/CP cells following infection with ad5-SVV. As a result, knockdown of SVV downregulated the expression of PCNA and MMP-2 and upregulated the expression of pro-caspase-3 and cleaved caspase-3. In addition, knockdown of SVV enhanced cisplatin-induced proliferative activities, induced cell apoptosis and inhibited the invasive potential in A2780/CP cells. The present findings demonstrate that knockdown of SVV contributes to antitumor activity in cisplatin-resistant ovarian cancer cells via the downregulation of PCNA and MMP-2 expression and the upregulation of caspase-3 expression and indicate that SVV is a potential target for therapeutic anticancer drugs.


Assuntos
Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Cisplatino/toxicidade , Proteínas Inibidoras de Apoptose/metabolismo , Antineoplásicos/uso terapêutico , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Cisplatino/uso terapêutico , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Proteínas Inibidoras de Apoptose/genética , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Survivina
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 28(3): 313-7, 2011 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-21644231

RESUMO

OBJECTIVE: To evaluate the association between single nucleotide polymorphisms (SNPs) of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene and susceptibility to cervical cancer. METHODS: One hundred patients and 100 healthy controls from Hubei province were genotyped for 20 polymorphic loci using Sequenom. RESULTS: The frequency of rs11571316 G allele and rs5742909 T allele, which are localized in the promoter region, and rs11571319 A allele, which is downstream of the gene, were significantly higher in patients than in controls. Luciferase assay showed that, as the previously reported rs5742909 T allele, rs11571316 G allele could significantly increase the expression of the reporter gene. CONCLUSION: SNPs in the promoter region of (CTLA4) gene might increase the susceptibility to cervical cancer by increasing (CTLA4) gene expression.


Assuntos
Antígenos CD/genética , Polimorfismo de Nucleotídeo Único , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Alelos , Antígeno CTLA-4 , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Adulto Jovem
13.
Eur J Pharmacol ; 635(1-3): 40-8, 2010 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-20307526

RESUMO

Cellular movement is mainly orchestrated by actin-dependent cytoskeleton in which Rho GTPase Rac1 or vasodilator-stimulated phosphoprotein (VASP) closely collaborates. In the present in vitro study, we investigated the inhibitory effect and underlying molecular mechanism of icariin, a pure extract of the traditional Chinese medicine Herba epimedii, on the invasive and migration properties of human gastric cancer cell line BGC-823. At 50% growth-inhibiting concentration, icariin significantly suppressed tumor cells migration and invasion, which were traceable to down-regulation of Rac1 and VASP. Together with icariin, the selected siRNA targeting Rac1 or VASP reinforced these inhibitory effects. Rac1-siRNA-dependent down-regulation of Rac1 led to a large drop in VASP expression, whereas VASP-siRNA led to a slight fall in Rac1 expression, implying that the amount of Rac1 may influence VASP expression level. Moreover, transfection with Rac1 plasmids pcDNA3-EGFP-Rac1-Q61L led to the enhancement in expression level of both Rac1 and VASP. These results indicate that icariin exerts negative effects on tumor cell invasion and migration via the Rac1-dependent VASP pathway and may be a potential anti-cancer drug.


Assuntos
Moléculas de Adesão Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Flavonoides/farmacologia , Proteínas dos Microfilamentos/metabolismo , Fosfoproteínas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/patologia , Proteínas rac1 de Ligação ao GTP/metabolismo , Moléculas de Adesão Celular/deficiência , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Humanos , Concentração Inibidora 50 , Proteínas dos Microfilamentos/deficiência , Proteínas dos Microfilamentos/genética , Invasividade Neoplásica , Fosfoproteínas/deficiência , Fosfoproteínas/genética , Plasmídeos/genética , RNA Interferente Pequeno/genética , Proteínas rac1 de Ligação ao GTP/deficiência , Proteínas rac1 de Ligação ao GTP/genética
14.
Proc Natl Acad Sci U S A ; 106(3): 847-52, 2009 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-19129487

RESUMO

We studied the robustness of photosynthetic metabolism in the chloroplasts of C(3) plants under drought stress and at high CO(2) concentration conditions by using a method called Minimization of Metabolic Adjustment Dynamic Flux Balance Analysis (M_DFBA). Photosynthetic metabolism in the chloroplasts of C(3) plants applies highly cooperative regulation to minimize the fluctuation of metabolite concentration profiles in the face of transient perturbations. Our work suggests that highly cooperative regulation assures the robustness of the biological system and that there is closer cooperation under perturbation conditions than under normal conditions. This results in minimizing fluctuations in the profiles of metabolite concentrations, which is the key to maintaining a system's function. Our methods help in understanding such phenomena and the mechanisms of robustness for complex metabolic networks in dynamic processes.


Assuntos
Secas , Fotossíntese , Plantas/metabolismo , Biologia de Sistemas/métodos , Dióxido de Carbono/metabolismo , Cloroplastos/metabolismo , Ácidos Glicéricos/metabolismo , Modelos Teóricos
15.
Zhonghua Fu Chan Ke Za Zhi ; 43(8): 619-21, 2008 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-19087500

RESUMO

OBJECTIVE: To explore the effects of quercetin and quercetin in combination with cisplatin on adhesion, migration and invasion of HeLa cells. METHODS: Adhesion, migration and invasion of HeLa cells treated with quercetin and quercetin in combination with cisplatin were measured by adhesion assay, wound healing assay, and transwell chamber method respectively. RESULTS: The results showed that quercetin and quercetin in combination with cisplatin could inhibit adhesion, migration and invasion of HeLa cells. The adhesive ratio, migration rate and the invasiveness were negatively proportional to concentration of quercetin and quercetin in combination with cisplatin. With increasing concentration of quercetin from 20 to 80 micromol/L, the adhesive ratio decreased from (82.2 +/- 1.5)% to (48.4 +/- 1.1)%; the migration rate decreased from (7.26 +/- 0.20) microm/h to (3.78 +/- 0.64) microm/h; the invasiveness decreased from (124.3 +/- 1.5) piece to (90.7 +/- 2.1) piece (P < 0.05). In quercetin and quercetin in combination with 10 micromol/L cisplatin treatment group, with quercetin concentration increasing from 20 to 80 micromol/L, the adhesive ratio decreased from (42.6 +/- 1.2)% to (27.5 +/- 1.7)%, the migration rate decreased from (2.20 +/- 0.33) microm/h to (0.72 +/- 0.19) microm/h and the invasiveness decreased from (78.7 +/- 2.5) piece to (44.0 +/- 4.0) piece (P < 0.05). Compared with the quercetin groups, quercetin in combination with cisplatin groups had significantly higher inhibitory effects (P < 0.05). CONCLUSIONS: Quercetin and quercetin in combination with cisplatin can inhibit adhesion and migration and invasion of HeLa cells. Quercetin can enhance the inhibitory effect of cisplatin on HeLa cell adhesion, migration and invasion.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Cisplatino/farmacologia , Quercetina/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Cisplatino/administração & dosagem , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Células HeLa , Humanos , Invasividade Neoplásica , Estadiamento de Neoplasias , Quercetina/administração & dosagem , Resultado do Tratamento
16.
Artigo em Chinês | MEDLINE | ID: mdl-16866146

RESUMO

OBJECTIVE: To detect the in vitro effect of the traditional Chinese medicine on the tachyzoites of Toxoplasma gondii. METHODS: Supernatant (1.5 ml) of different doses of the traditional Chinese medicine (Changqing capsule) was collected by normal saline immersion and 2.5 x 10(4) Toxoplasma gondii tachyzoites were added in each paste well for 8 hours. Spiramycin, pyrimethamine and azithromycin in different doses were used as controls. Normal saline was used as negative control. Mice were inoculated with drug-treated tachyzoites intraperitoneally or intragastrically. The normal mice were subcultured after 8 days for 3 generations. RESULTS: The incident number of the infected mice was significantly different among groups with different drugs and doses: 2/60, 16/60, 10/60 and 10/60 in the groups of Changqing capsule, spiramycin, pyrimethamine and azithromycin respectively (P < 0.05). No mice were found incident in groups of high and medium dose Changqing capsule while 2 out of 20 found sick in the low dose group (P < 0.05). The subculture observation showed that 2 and 1 mice in the first generation of the low dose Changqing capsule group inoculated intraperitonelly and intragastrically were found infected respectively. 2 mice of the second generation in low dose spiramycin group and 1 mouse of the third generation in low dose pyrimethamine group were also found infected. CONCLUSION: The in vitro killing effect of the Changqing capsule on the tachyzoites of Toxoplasma gondii is better than the current clinical drugs and shows a positive correlation with the dosages.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Toxoplasma/efeitos dos fármacos , Toxoplasmose Animal/tratamento farmacológico , Animais , Cápsulas , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Camundongos , Fitoterapia , Distribuição Aleatória , Toxoplasmose Animal/parasitologia , Resultado do Tratamento
17.
Mol Syst Biol ; 2: 2006.0031, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16760902

RESUMO

To better understand the dynamic regulation of optimality in metabolic networks under perturbed conditions, we reconstruct the energetic-metabolic network in mammalian myocardia using dynamic flux balance analysis (DFBA). Additionally, we modified the optimal objective from the maximization of ATP production to the minimal fluctuation of the profile of metabolite concentration under ischemic conditions, extending the hypothesis of original minimization of metabolic adjustment to create a composite modeling approach called M-DFBA. The simulation results are more consistent with experimental data than are those of the DFBA model, particularly the retentive predominant contribution of fatty acid to oxidative ATP synthesis, the exact mechanism of which has not been elucidated and seems to be unpredictable by the DFBA model. These results suggest that the systemic states of metabolic networks do not always remain optimal, but may become suboptimal when a transient perturbation occurs. This finding supports the relevance of our hypothesis and could contribute to the further exploration of the underlying mechanism of dynamic regulation in metabolic networks.


Assuntos
Metabolismo Energético , Modelos Cardiovasculares , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Simulação por Computador
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