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1.
Cell Biol Toxicol ; 39(6): 2631-2645, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36715854

RESUMO

Emerging reports demonstrated that long non-coding RNAs (lncRNAs) play a role in the pathogenesis and metastasis of cancers. However, the biological functions and underlying mechanisms of LncRNA CEBPA-AS1 in acute myeloid leukemia (AML) remain largely elusive. The level of CEBPA-AS1 was examined in AML clinical tissues and cell lines via fluorescence in situ hybridization (FISH) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In vivo and in vitro functional tests were applied to identify the pro-oncogenic role of CEBPA-AS1 in AML development. The overexpressed CEBPA-AS1 was linked to poor survival in AML patients. Moreover, the relationships among CEBPA-AS1, Zinc Finger Protein X-Linked (ZFX), and miR-24-3p were predicted by bioinformatics and validated by RNA immunoprecipitation (RIP) and luciferase reporter assays. Our findings unveiled that transcription factor ZFX particularly interacted with the promoter of CEBPA-AS1 and activated CEBPA-AS1 transcription. Downregulation of CEBPA-AS1 inhibited the proliferation and invasion while promoted apoptosis of AML cells in in vitro, as well as in vivo, xenograft tumor growth was modified. However, overexpression of CEBPA-AS1 observed the opposite effects. Furthermore, CEBPA-AS1 acted as a competitive endogenous RNA (ceRNA) of miR-24-3p to attenuate the repressive effects of miR-24-3p on its downstream target CTBP2. Taken together, this study emphasized the pro-oncogenic role of CEBPA-AS1 in AML and illustrated its connections with the upstream transcription factor ZFX and the downstream regulative axis miR-24-3p/CTBP2, providing important insights to the cancerogenic process in AML.


Assuntos
Leucemia Mieloide Aguda , MicroRNAs , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação para Cima/genética , Linhagem Celular Tumoral , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/genética , Fatores de Transcrição/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Movimento Celular/genética , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Proteínas Correpressoras/genética , Proteínas Correpressoras/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo
2.
World J Surg Oncol ; 21(1): 130, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37046344

RESUMO

BACKGROUND: We aimed to investigate the different metastases and prognoses of neuroblastoma (NB) and determine the risk factors of metastasis. METHOD: Data of 1224 patients with NB were obtained from the Surveillance, Epidemiology and End Results database (2010-2018). Pearson's chi-square test, Kaplan-Meier analysis, multivariable logistic regression and Cox regression analysis were used to determine the factors associated with prognosis. RESULTS: The overall incidence of NB was an age-adjusted rate of 8.2 patients per 1,000,000 children. In total, 1224 patients were included in our study, with 599 patients (48.9%) exhibiting distant metastases. Compared to patients with non-metastatic NB, a greater proportion of patients with metastatic NB were under 1 year, male, had an adrenal primary site, unilateral tumour, a tumour size > 10 cm, neuroblastoma-not otherwise specified (NB-NOS), second malignant neoplasms and were more likely to choose radiotherapy and chemotherapy. Multivariate Cox regression showed that metastasis was an independent risk factor for overall survival (OS) and cancer-specific survival (CSS). The survival rate of non-metastatic patients with NB was better than those with metastasis (OS: hazard ratio (HR): 0.248, P < 0.001; CSS: HR: 0.267, P < 0.001). The bone and liver were the two most common isolated metastatic sites in NB. However, no statistical difference was observed in OS and CSS between the only bone metastasis group, only liver metastasis group and bone metastasis combined with liver metastasis group (all P > 0.05). Additionally, age at diagnosis > 1 year (odds ratio (OR): 3.295, P < 0 .001), grades III-IV (OR: 26.228, P < 0 .001) and 5-10 cm tumours (OR: 1.781, P < 0 .001) increased the risk of bone metastasis of NB. Moreover, no surgical treatment (OR: 2.441, P < 0 .001) increased the risk of liver metastasis of NB. CONCLUSION: Metastatic NB has unique clinicopathological features, with the bone and liver as the most common single metastatic sites of NB. Therefore, more aggressive treatment is recommended for high-risk children with NB displaying distant metastases.


Assuntos
Doenças da Medula Óssea , Neoplasias Ósseas , Neoplasias Hepáticas , Neuroblastoma , Humanos , Masculino , Criança , Prognóstico , Neuroblastoma/terapia , Neuroblastoma/patologia , Fatores de Risco , Neoplasias Hepáticas/secundário , Programa de SEER , Metástase Neoplásica
3.
Environ Res ; 201: 111611, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34217719

RESUMO

Although emerging researches have linked ambient fine particulate matter (PM2.5) to obesity, evidence from high-polluted regions is still lacking. We thus assessed the long-term impacts of PM2.5 on body mass index (BMI) and the risk of the prevalence of overweight/obesity (BMI≥25 kg/m2), by incorporating the well-established Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project comprising 77,609 participants with satellite-based PM2.5 estimates at 1-km spatial resolution. The average of long-term PM2.5 level was 70.4 µg/m3, with the range of 32.1-94.2 µg/m3. Each 10 µg/m3 increment of PM2.5 was associated with 0.421 kg/m2 (95% confidence interval [CI]: 0.402, 0.439) and 13.5% (95% CI: 12.8%, 14.3%) increased BMI and overweight/obesity risk, respectively. Moreover, compared with the lowest quartile of PM2.5 (≤57.5 µg/m3), the relative risk of the prevalence of overweight/obesity from the highest quartile (>85.9 µg/m3) was 1.611 (95% CI: 1.566, 1.657). The exposure-response curve suggested a non-linear relationship between PM2.5 exposure and overweight/obesity. Besides, the association was modified by age, diabetes mellitus, hypertension and dyslipidemia status. Our study provides the evidence for the adverse impacts of long-term PM2.5 on BMI and overweight/obesity in China, and the findings are important for policy development on air quality, especially in severely polluted areas.


Assuntos
Sobrepeso , Material Particulado , Adulto , China/epidemiologia , Humanos , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Material Particulado/toxicidade
4.
Nano Lett ; 15(3): 1609-14, 2015 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-25661863

RESUMO

Rapid construction of flexible circuits has attracted increasing attention according to its important applications in future smart electronic devices. Herein, we introduce a convenient and efficient "writing" approach to fabricate and assemble ultralong functional fibers as fundamental building blocks for flexible electronic devices. We demonstrated that, by a simple hand-writing process, carbon nanotubes (CNTs) can be aligned inside a continuous and uniform polymer fiber with length of more than 50 cm and diameters ranging from 300 nm to several micrometers. The as-prepared continuous fibers exhibit high electrical conductivity as well as superior mechanical flexibility (no obvious conductance increase after 1000 bending cycles to 4 mm diameter). Such functional fibers can be easily configured into designed patterns with high precision according to the easy "writing" process. The easy construction and assembly of functional fiber shown here holds potential for convenient and scalable fabrication of flexible circuits in future smart devices like wearable electronics and three-dimensional (3D) electronic devices.

5.
Biochem Pharmacol ; 222: 116115, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38460910

RESUMO

In recent years, extensive research has been conducted on the pathogenesis of sensorineural hearing loss (SNHL). Apoptosis and necrosis have been identified to play important roles in hearing loss, but they cannot account for all hearing loss. Autophagy, a cellular process responsible for cell self-degradation and reutilization, has emerged as a significant factor contributing to hearing loss, particularly in cases of autophagy deficiency. Autophagy plays a crucial role in maintaining cell health by exerting cytoprotective and metabolically homeostatic effects in organisms. Consequently, modulating autophagy levels can profoundly impact the survival, death, and regeneration of cells in the inner ear, including hair cells (HCs) and spiral ganglion neurons (SGNs). Abnormal mitochondrial autophagy has been demonstrated in animal models of SNHL. These findings indicate the profound significance of comprehending autophagy while suggesting that our perspective on this cellular process holds promise for advancing the treatment of SNHL. Thus, this review aims to clarify the pathogenic mechanisms of SNHL and the role of autophagy in the developmental processes of various cochlear structures, including the greater epithelial ridge (GER), SGNs, and the ribbon synapse. The pathogenic mechanisms of age-related hearing loss (ARHL), also known as presbycusis, and the latest research on autophagy are also discussed. Furthermore, we underscore recent findings on the modulation of autophagy in SNHL induced by ototoxic drugs. Additionally, we suggest further research that might illuminate the complete potential of autophagy in addressing SNHL, ultimately leading to the formulation of pioneering therapeutic strategies and approaches for the treatment of deafness.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva , Animais , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Neurossensorial/metabolismo , Células Ciliadas Auditivas/metabolismo , Perda Auditiva/metabolismo , Modelos Animais de Doenças , Autofagia
6.
J Mol Neurosci ; 74(2): 56, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802701

RESUMO

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that presents a significant global health challenge. To explore drugs targeting key genes in AD, R software was used to analyze the data of single nuclei transcriptome from human cerebral frontal cortex in AD, and the differentially expressed genes (DEGs) were screened. Then the gene ontology (GO) analysis, Kyoto gene and genome encyclopedia (KEGG) pathway enrichment and protein-protein interaction (PPI) network were analyzed. The hub genes were calculated by Cytoscape software. Molecular docking and molecular dynamics simulation were used to evaluate and visualize the binding between candidate drugs and key genes. A total of 564 DEGs were screened, and the hub genes were ISG15, STAT1, MX1, IFIT3, IFIT2, RSAD2, IFIT1, IFI44, IFI44L and DDX58. Enrichment terms mainly included response to virus, IFN-γ signaling pathway and virus infection. Diclofenac had good binding effect with IFI44 and IFI44L. Potential drugs may act on key gene targets and then regulate biological pathways such as virus response and IFN-γ-mediated signal pathway, so as to achieve anti-virus, improve immune balance and reduce inflammatory response, and thus play a role in anti-AD.


Assuntos
Doença de Alzheimer , Simulação de Acoplamento Molecular , Doença de Alzheimer/genética , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Humanos , Transcriptoma , Mapas de Interação de Proteínas , Proteínas Supressoras de Tumor
7.
Cell Signal ; 108: 110732, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37245680

RESUMO

In the cochlea, extracellular ATP (eATP) plays an important role in both physiological and pathological processes, but its role in the hypoxic cochlea remains unclear. The present study aims to investigate the relationship between eATP and hypoxic marginal cells (MCs) in the stria vascularis in cochlea. Combining various methodologies, we found that eATP accelerates cell death and decreases tight junction protein zonula occludens-1 (ZO-1) in hypoxic MCs. Flow cytometry and western blot analyses revealed an increase in apoptosis levels and suppression of autophagy, indicating that eATP causes additional cell death by increasing the apoptosis of hypoxic MCs. Given that autophagy inhibits apoptosis to protect MCs under hypoxia, apoptosis is probably enchanced by suppressing autophagy. Interleukin-33(IL-33)/suppression of tumorigenicity-2(ST-2)/matrix metalloprotein 9(MMP9) pathway activation was also observed during the process. Further experiments involving the use of additional IL-33 protein and an MMP9 inhibitor indicated that this pathway is responsible for the damage to the ZO-1 protein in hypoxic MCs. Our study revealed an adverse effect of eATP on the survival and ZO-1 protein expression of hypoxic MCs, as well as the underlying mechanism.


Assuntos
Interleucina-33 , Metaloproteinase 9 da Matriz , Ratos , Animais , Animais Recém-Nascidos , Metaloproteinase 9 da Matriz/metabolismo , Interleucina-33/metabolismo , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , Cóclea/metabolismo , Morte Celular , Hipóxia/metabolismo , Trifosfato de Adenosina/metabolismo
8.
Int J Biochem Cell Biol ; 149: 106259, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35779841

RESUMO

In the cochlea, various factors, such as noise, aging, and inflammation, induce hypoxia, resulting in the up-regulation of hypoxia inducible factor-1α (HIF-1α). The role of HIF-1α in hypoxic marginal cells (MCs) of the stria vascularis is unknown. This study examined HIF-1α-mediated autophagy in MCs of neonatal rats and its mechanism of action. We found that an increase in HIF-1α expression was associated with autophagy and apoptosis. Treatment with PX478, a specific inhibitor of HIF-1α, decreased the HIF-1α level, and the degree of autophagy decreased in hypoxic and apoptotic MCs. By contrast, treatment with DMOG, an activator of HIF-1α, increased autophagy and decreased apoptosis. Both PX478 and DMOG had no effect on the apoptotic rate after treatment with 3-methyladenine, an inhibitor of autophagy, indicating that HIF-1α promoted autophagy to protect MCs from hypoxia-induced apoptosis. Lastly, we silenced Bnip3(Bcl-2/adenovirus E1B 19-kDa interacting protein) in MCs to identify the mechanism of action. Our results show that the HIF-1α-BNIP3 pathway mediates the anti-apoptotic effects through an increase in autophagy.


Assuntos
Autofagia , Proteínas de Membrana , Animais , Animais Recém-Nascidos , Apoptose , Hipóxia Celular , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas de Membrana/metabolismo , Ratos
9.
Sci Rep ; 12(1): 16909, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207378

RESUMO

Sigmoid colon cancer often has an unsatisfactory prognosis. This study explored the effect of tumor deposits (TDs) on survival, and whether their presence/absence influence individualized treatment. Data of postoperative patients with sigmoid colon cancer were extracted from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) was calculated using the Kaplan-Meier method and prognostic factors were identified using Cox regression analysis and random forest (RF). The nomogram's discrimination performance was evaluated using a concordance index (C-index), integrated discrimination improvement (IDI), calibration curves, and decision-curve analysis. The N1c group showed a worse prognosis than the N0 group. For N1c patients, a combination of surgery and chemotherapy prolonged survival, compared to surgery alone; however, the chemotherapy-surgery combination did not affect the OS of patients younger than 70 years, in stage T1-2, and/or of black race. Multivariable analysis and RF presented Age, T stage, and N stage were the most important predictors for OS. The novel nomogram had superiority to the TNM staging system with improved C-index and IDI, as well as good consistency and higher clinical benefit. TDs are associated with poor survival from sigmoid colon cancer, and considering TDs can inform the formulation of individual treatment regimens. The nomogram shows satisfactory prediction ability for OS.


Assuntos
Neoplasias do Colo Sigmoide , Humanos , Extensão Extranodal , Estadiamento de Neoplasias , Nomogramas , Prognóstico , Programa de SEER , Neoplasias do Colo Sigmoide/tratamento farmacológico , Neoplasias do Colo Sigmoide/cirurgia
10.
Environ Pollut ; 265(Pt A): 114999, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32806418

RESUMO

Overweight and obesity have become a global epidemic and concern, and contributed to at least 4.0 million deaths each year worldwide. However, current evidence regarding the impact of air pollution on body weight status remains inconsistent. We therefore conducted a systematic review and meta-analysis to evaluate the effect of long-term exposure to ambient air pollutants on body weight status in adults. Three databases were searched up to Dec 31, 2019 for articles investigating the association of gaseous (sulfur dioxide, nitrogen dioxide, ozone) and particulate (diameter ≤ 10 µm or ≤ 2.5 µm) air pollutants with body weight status. Random effect models were used to estimate the pooled odds ratios (ORs), regression coefficients (ß) and their 95% confidence intervals (95% CIs) associated with air pollution. Among twelve studies that were eligible in the systematic review, ten were used to estimate the pooled effect size, and most of them were cross-sectional studies. We identified that ambient air pollution had adverse effects on body weight status. For example, elevated PM2.5 and O3 were associated with higher level of body mass index, with the pooled ß (95% CIs) of 0.34 (0.30-0.38) and 0.21 (0.17-0.24) per 10 µg/m3 increment, respectively. In addition, increased NO2, SO2 and O3 were associated with higher risk of having overweight/obesity, with the corresponding pooled OR (95% CI) of 1.13 (1.01-1.26), 1.04 (1.01-1.06) and 1.07 (1.02-1.13) per 10 µg/m3 increment. Overall, air pollution is a potential risk factor for body weight status in adults, and more high-quality studies, especially prospective studies from severely polluted regions, are warranted for comprehensive understanding of its health effects.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/análise , Estudos Transversais , Material Particulado/análise , Estudos Prospectivos
11.
Artigo em Inglês | MEDLINE | ID: mdl-33149748

RESUMO

The study aimed to evaluate the protective effect of Dendrobium officinale flower extraction (DOFE) on alcohol-induced liver injury and its probable mechanisms in mice. The chemical composition of DOFE was performed via UPLC/MS. Male Kunming mice were used to establish alcohol-induced liver injury models by oral gavage of 56% alcohol. Results showed that DOFE dramatically attenuated the increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triacylglycerol (TG). Meanwhile, hematoxylin and eosin and Oil Red O staining showed that DOFE attenuated degeneration, inflammatory infiltration, and lipid droplet accumulation. DOFE was also found to suppress the activity of malonaldehyde (MDA) and enhanced the level of glutathione (GSH) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the liver. The protection of DOFE against oxidative stress was associated with the downregulation of hepatic cytochrome P450 2E1 (CYP2E1) and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase l (NQO1). Additionally, DOFE suppressed inflammation via downregulating Toll-like receptor-4 (TLR-4) and nuclear factor kappa-B P65 (NF-κB P65). Thus, DOFE exhibited a significant protective effect against alcohol-induced liver injury through its antisteatosis, antioxidative, and anti-inflammatory effect.

12.
Cardiovasc Ther ; 35(1): 26-32, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27661060

RESUMO

AIM: To assess the effect of Cytochrome P450 2C9 (CYP2C9) gene polymorphism on pediatric warfarin maintenance dosage requirement. METHODS: A previously developed search strategy was conducted in PubMed, EMBASE, and the Cochrane Library. Eligible studies published prior to January 27, 2016, were identified and compared against strict inclusion/exclusion criteria. Required data were extracted, and researchers were consulted for additional data if needed. Review Manager version 5.2.3 software was used to analyze the relationship between CYP2C9 polymorphisms and warfarin maintenance doses in pediatric patients. Eight articles with a combined total of 507 pediatric patients were included in the meta-analysis. RESULTS: Maintenance warfarin doses in patients with CYP2C9 *1/*2 genotype, CYP2C9 *1/*3 genotype, and CYP2C9 variant carriers which contain at least one variant allele (*2 or *3) were from 15% to 41% lower than doses in patients with the wild-type allele (CYP2C9 *1/*1): All differences were significant with P-values <.05. The Fontan procedure as a medical indication for anticoagulation was also associated with a lower warfarin maintenance dose; however, target INR range was not. CONCLUSIONS: We found that CYP2C9 gene polymorphism (referring to the presence of *1/*2, *1/*3, and variant genotypes in the population in addition to the wild type) was significantly associated with decreased warfarin maintenance dose requirements. Additionally, a specific indication for warfarin, the Fontan procedure, was associated with a lower daily warfarin dose. However, the results of our study require confirmation from more research with larger numbers of pediatric patients.


Assuntos
Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Citocromo P-450 CYP2C9/genética , Polimorfismo Genético , Varfarina/administração & dosagem , Adolescente , Fatores Etários , Anticoagulantes/metabolismo , Anticoagulantes/farmacocinética , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Citocromo P-450 CYP2C9/metabolismo , Cálculos da Dosagem de Medicamento , Feminino , Genótipo , Humanos , Lactente , Coeficiente Internacional Normatizado , Masculino , Farmacogenética , Variantes Farmacogenômicos , Fenótipo , Varfarina/metabolismo , Varfarina/farmacocinética , Adulto Jovem
13.
Oncol Rep ; 37(5): 2663-2671, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28440495

RESUMO

The present study was designed to investigate the relationship among epigenetic changes in Wnt antagonists, histone H4K20me1 and the expression of tumor-suppressor genes in acute leukemia (AL) to better understand the pathogenesis of leukemia. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect messenger RNA (mRNA) expression levels of Wnt antagonists (Wnt5a, HDPR1, DKK1 and DKK3) in patients with AL and in normal controls; pyrophosphate sequencing was performed to detect the methylation status of the Wnt5a promoter; and western blotting was performed to detect the overall expression levels of Wnt5a protein and histone H4K20me1 in patients with acute myeloid leukemia (AML) and in normal controls. The relationship between Wnt5a protein expression and histone H4K20me1 was analyzed. Chromatin immunoprecipitation-qPCR (ChIP-qPCR) was performed to investigate the recruitment of H4K20me1 and SET8 to the Wnt5a promoter and coding regions. Our results demonstrated that the expression levels of Wnt antagonists were generally low in AML, but showed differential expression in acute lymphocytic leukemia (ALL). In most cases of AML, methylation of the Wnt5a promoter was observed and Wnt5a protein expression was low. In some cases of AML, the overall level of H4K20me1 protein was higher than that in normal controls. In addition, Wnt5a expression was positively correlated with H4K20me1 expression and was unrelated to the methylation status of its promoter. Moreover, H4K20me1 and SET8 were enriched in the Wnt5a promoter region and coding region. By contrast, Wnt5a expression was unrelated to H4K20me1 expression in normal controls. Moreover, we observed that the methylation of Wnt antagonists was often found in patients with AL, particularly those with AML, whereas the extent of methylation was variable in ALL patients. Wnt5a expression was positively correlated with the enrichment of H4K20me1 and SET8 at the Wnt5a promoter and coding regions. H4K20me1 increased Wnt5a expression by promoting transcription initiation and elongation.


Assuntos
Metilação de DNA , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteína Wnt-5a/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiocinas , Criança , Epigênese Genética , Feminino , Regulação Leucêmica da Expressão Gênica , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Análise de Sequência de DNA , Proteína Wnt-5a/metabolismo , Adulto Jovem
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(5): 1299-1304, 2016 Oct.
Artigo em Zh | MEDLINE | ID: mdl-27784346

RESUMO

OBJECTIVE: To detect the abnormal methylation of the CPG island in the suppressor gene promoter region of the Wnt signaling pathway in cell strain NB4 of the acute promyelocytic leukemia by using the bisulfite sequcucing PCR(BSP), to screan the hyper-methylated suppressor gene of the Wnt signaling pathway and to evaluatc the potency of BSP in the methylation study. METHODS: The strain NB4 cells of the acute promyelocytic leukemia patients were used as the object, the mononuclear cells from 20 normal persons were used as the controls. The DNA was extracted and processed by bisulfite, the target sequences were amplified with PCR, then the abnormal methylation of the suppressor genes of the Wnt signaling pathway in the NB4 cells was analyzed by BSP, and the advantage and disadvantage of BSP were evaluated by comparison with the Methylation specific PCR and Pyrosequencing. RESULTS: The methylated rate of suppressor genes of the Wnt signaling pathways in the NB4 cells detected by BSP was as follows: the gene WIF1 95.26%, the gene DKK3 86%, the gene SFRP1 81.67%, the gene SFRP2 95.71%, the gene SFRP4 85%, and the gene SFRP5 95%; while the methylations in the control group were respectively as follows: the gene WIF-1 1.5%, the gene DKK3 4.2%, the gene SFRP1 0%, the gene SFRP2 0.9%, the gene SFRP4 2.5%, and the gene SFRP5 1.75%. A more significant methylation happened in the suppressor genes promoter of the Wnt signaling pathway in the NB4 cells as compared with the control group. CONCLUSION: Many hypermethylated suppressor genes are found in the Wnt signaling pathway of the acute promyelocytic leukemia NB4 cells, which may be served as one of the early diagnosis index and therapeutic target of the acute promyelocytic leukemia.


Assuntos
Leucemia Promielocítica Aguda , Via de Sinalização Wnt , Linhagem Celular Tumoral , Metilação de DNA , Genes Supressores , Humanos , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Sulfitos , Proteínas Wnt
16.
Oncol Rep ; 36(6): 3113-3122, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27748863

RESUMO

HOX antisense intergenic RNA (HOTAIR), a long non-coding RNA, plays an important role in the development of many types of cancers. Its function in acute leukemia (AL), however, has not been examined. The present study investigated the role of HOTAIR and its downstream genes in AL, and determined whether it could act as a molecular marker for prediction of leukemia development and prognosis. Real-time quantitative PCR was used to examine the expression of each gene in the HOTAIR signaling pathway in AL patients. The relationship between expression of HOTAIR and downstream genes and AL prognosis was analyzed. Expression of HOTAIR in patients with acute monocytic leukemia (M5) was increased as compared to controls (P<0.05). Compared to patients with low HOTAIR expression, overall survival and event-free survival of patients with high HOTAIR expression was significantly reduced. In addition, the expression of downstream genes in the HOTAIR signaling pathway including EZH2, LSD1, DNMT3A and DNMT3B was significantly increased in AL patients, and showed a significant positive correlation with high expression of HOTAIR (P<0.05). In conclusion, HOTAIR was closely related with a poor prognosis in AL patients. It may be involved in the development of leukemia by mediating methylation of DNA and histones.


Assuntos
Biomarcadores Tumorais/metabolismo , Leucemia Mieloide Aguda/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , RNA Longo não Codificante/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA Metiltransferase 3A , Feminino , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , RNA Longo não Codificante/genética , Transdução de Sinais , Células Tumorais Cultivadas , Adulto Jovem , DNA Metiltransferase 3B
17.
Pest Manag Sci ; 70(3): 510-6, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23966130

RESUMO

BACKGROUND: Essential oil of Pogostemon cablin (Blanco) Benth. has been reported to exhibit strong insecticidal activities, but few studies have focused on the insecticidal activity of its main individual constituent, pogostone (PO). The goal of this research was to investigate the insecticidal activity of PO against two harmful noctuid insects, Spodoptera litura (Fabricius) and Spodoptera exigua (Hübner). RESULTS: In a no-choice assay, PO exhibited strong antifeedant activity against S. litura and S. exigua. PO showed pronounced larvicidal activities, including oral toxicity (LC50 986.88 mg L(-1) and 545.61 mg L(-1) respectively) and contact toxicity (LC50 1041.42 mg L(-1) and 519.48 mg L(-1) respectively) against these two noctuid insects. Additionally, PO treatment significantly increased the larval and pupal developmental period. Furthermore, PO showed moderate ovicidal activities and influenced the emergence and deformity of the moth. However, PO failed to exert a potent effect on adult development. These tested parameters proved to be dose dependent for both insect species. CONCLUSION: PO possesses strong insecticidal activities, especially antifeedant, larvicidal, growth inhibitory and pupicidal activities, against S. litura and S. exigua. PO may partly account for the insecticidal activity of patchouli oil and may be a promising candidate for the control of agricultural insects.


Assuntos
Inseticidas/farmacologia , Lamiaceae/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Spodoptera/efeitos dos fármacos , Animais , Comportamento Alimentar/efeitos dos fármacos , Feminino , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/fisiologia , Masculino , Pupa/efeitos dos fármacos , Pupa/crescimento & desenvolvimento , Pupa/fisiologia , Spodoptera/crescimento & desenvolvimento , Spodoptera/fisiologia
18.
Fitoterapia ; 84: 135-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23160088

RESUMO

Pogostone (PO) is one of the secondary metabolites from Pogostemon cablin (Blanco) Benth. (Lamiaceae), serving as the effective component of the antimicrobial activity. In this study, PO and a series of its analogues were synthesized by the reaction of dehydroacetate and aldehydes in tetrahydrofuran under a nitrogen atmosphere. Their activities against Candida albicans, Gram positive bacteria and Gram negative bacteria were evaluated. The antifungal results demonstrated that PO (MIC ranged from 12 to 97µg/mL against all strains, MFC ranged from 49 to 97µg/mL against all strains) and A3 (MIC ranged from 12 to 49, MFC over 195µg/mL) showed a strong activity against Candida albicans. While A1 (MIC ranged from 49 to 97µg/mL) and A2 (MIC ranged from 24 to 49µg/mL) have only shown effect against Guangzhou clinical isolates, the antibacterial results demonstrated that PO and its analogues showed no effects against the tested bacteria strains. This study suggests that pogostone analogues, with the appropriated structure modification, represented a kind of promising antifungal agents.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Lamiaceae/química , Óleos Voláteis/síntese química , Óleos Voláteis/farmacologia , Animais , Bactérias/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular
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