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1.
J Exp Clin Cancer Res ; 38(1): 337, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383001

RESUMO

BACKGROUND: Metabolic rewiring is a common feature of many cancer types, including prostate cancer (PCa). Alterations in master genes lead to mitochondrial metabolic rewiring and provide an appealing target to inhibit cancer progression and improve survival. Phospholipase C (PLC)ε is a regulator of tumor generation and progression. However, its role in mitochondrial metabolism remains unclear. METHODS: The GEO, The Cancer Genome Atlas, and the GTEx databases were used to determine Twist1 mRNA levels in tumors and their non-tumor counterparts. Fifty-five PCa and 48 benign prostatic hypertrophy tissue samples were tested for the presence of PLCε and Twist1 immunohistochemically. An association between PLCε and Twist1 was determined by Pearson's correlation analysis. PLCε was knocked down with a lentiviral short hairpin RNA. Mitochondrial activity was assessed by measuring the oxygen consumption rate. Western blotting analyses were used to measure levels of PPARß, Twist1, phosphorylated (p)-Twist1, p-MEK, p-ERK, p-P38, and p-c-Jun N-terminal kinase (JNK). Cells were treated with inhibitors of MEK, JNK, and P38 MAPK, and an agonist and inhibitor of peroxisome proliferator activated receptor (PPAR) ß, to evaluate which signaling pathways were involved in PLCε-mediated Twist1 expression. The stability of Twist1 was determined after blocking protein synthesis with cycloheximide. Reporter assays utilized E-cadherin or N-cadherin luciferase reporters under depletion of PLCε or Twist1. Transwell assays assessed cell migration. Finally, a nude mouse tumor xenograft assay was conducted to verify the role of PLCε in tumor formation. RESULTS: Our findings revealed that the expression of PLCε was positively associated with Twist1 in clinical PCa samples. PLCε knockdown promoted mitochondrial oxidative metabolism in PCa cells. Mechanistically, PLCε increased phosphorylation of Twist1 and stabilized the Twist1 protein through MAPK signaling. The transcriptional activity of Twist1, and the Twist1-mediated epithelial-to-mesenchymal transition, cell migration, and transcription regulation, were suppressed by PLCε knockdown and by blocking PPARß nuclear translocation. The tumor xenograft assay demonstrated that PLCε depletion diminished PCa cell tumorigenesis. CONCLUSIONS: These findings reveal an undiscovered physiological role for PLCε in the suppression of mitochondrial oxidative metabolism that has significant implications for understanding PCa occurrence and migration.

2.
Med Sci Monit ; 25: 4438-4449, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31201297

RESUMO

BACKGROUND Primary therapy for patients with advanced prostate cancer (PCa) consists of androgen deprivation therapy targeting the androgen receptor (AR) axis. However, most tumors progress to castration-resistant prostate cancer (CRPC) within 18-24 months. The purpose of the present study was to investigate the mechanisms through which PCa acquires drug resistance after long-term treatment with AR antagonists. MATERIAL AND METHODS Online database analysis and bioinformatics analysis were performed to identify signaling activated during anti-androgen treatment. MTT assay was used to detect cell viability. RT-qPCR was performed to examine the mRNA expression of the indicated genes. Colony formation assay was performed to observe cell proliferation. Transwell assay was conducted to demonstrate invasive ability. Protein levels were determined by Western blot analysis and immunofluorescence assays. RESULTS An online database search and bioinformatics analysis indicated that bone morphogenetic protein (BMP)-6/SMAD signaling was activated in enzalutamide-resistant LNCaP cells. Furthermore, this signaling interaction was experimentally verified in bicalutamide- and enzalutamide-resistant LNCaP cells, which may be regulated by phospholipase C (PLC)ε and induced cell proliferation and invasion. Of note, a positive correlation was observed between PLCε and BMP-6 in CRPC tissue samples, which may promote bone metastasis and suggests a poor prognosis. CONCLUSIONS The present results suggest that targeting of PLCε/BMP-6/SMAD signaling may increase the sensitivity of CRPC to AR antagonists and inhibit tumor progression.

3.
Int J Oncol ; 54(6): 2054-2068, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31081050

RESUMO

The failure of androgen deprivation therapy in prostate cancer treatment mainly results from drug resistance to androgen receptor antagonists. Although an aberrant caveolin­1 (Cav­1) expression has been reported in multiple tumor cell lines, it is unknown whether it is responsible for the progression of castration­resistant prostate cancer (CRPC). Thus, the aim of the present study was to determine whether Cav­1 can be used as a key molecule for the prevention and treatment of CRPC, and to explore its mechanism of action in CRPC. For this purpose, tissue and serum samples from patients with primary prostate cancer and CRPC were analyzed using immunohistochemistry and enzyme­linked immunosorbent assay, which revealed that Cav­1 was overexpressed in CRPC. Furthermore, Kaplan­Meier survival analysis and univariate Cox proportional hazards regression analysis demonstrated that Cav­1 expression in tumors was an independent risk factor for the occurrence of CRPC and was associated with a shorter recurrence­free survival time in patients with CRPC. Receiver operating characteristic curves suggested that serum Cav­1 could be used as a diagnostic biomarker for CRPC (area under the curve, 0.876) using a cut­off value of 0.68 ng/ml (with a sensitivity of 82.1% and specificity of 80%). In addition, it was determined that Cav­1 induced the invasion and migration of CRPC cells by the activation of the H­Ras/phosphoinositide­specific phospholipase Cε signaling cascade in the cell membrane caveolae. Importantly, simvastatin was able to augment the anticancer effects of androgen receptor antagonists by downregulating the expression of Cav­1. Collectively, the findings of this study provide evidence that Cav­1 is a promising predictive biomarker for CRPC and that lowering cholesterol levels with simvastatin or interfering with the expression of Cav­1 may prove to be a useful strategy with which to prevent and/or treat CRPC.


Assuntos
Antagonistas de Receptores de Andrógenos/farmacologia , Caveolina 1/genética , Caveolina 1/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias de Próstata Resistentes à Castração/metabolismo , Sinvastatina/farmacologia , Adulto , Idoso , Caveolina 1/sangue , Linhagem Celular Tumoral , Movimento Celular , Colesterol/sangue , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Estudos Retrospectivos , Análise de Sobrevida , Regulação para Cima/efeitos dos fármacos
4.
Sci Rep ; 9(1): 6400, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30996288

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

5.
Braz J Med Biol Res ; 52(3): e8055, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30916219

RESUMO

This study aimed to investigate the clinical characteristics, prognosis, and factors for survival of patients who underwent early-start peritoneal dialysis (PD) within 24 h after catheter insertion three years after PD. This study was conducted from January 1, 2013 to December 31, 2017. All adult patients who were diagnosed with end-stage renal disease (ESRD) and underwent PD for the first time within 24 h after catheter insertion in our hospital were included. All patients with PD were followed-up until they withdrew from PD, switching to hemodialysis, were transferred to other medical centers, underwent renal transplantation, died or were lost to follow-up, or continued to undergo dialysis until the end of the study period. The follow-up observation lasted three years. The number of eligible patients was 110, and switching to hemodialysis and death were the main reasons for patients to withdraw from PD. The 1-, 2-, and 3-year technical survival rates of patients were 89.1, 79.1, and 79.1% respectively, while the 1-, 2- and 3-year survival rates were 90, 81.8, and 81.8%, respectively. The Charlson comorbidity index, age, hemoglobin, serum albumin, diabetic nephropathy, chronic glomerulonephritis, and hypertensive renal damage were independent risk factors that affected the prognosis of PD patients. Under the condition of ensuring the quality of the PD catheter insertion, early-start PD within 24 h after catheter insertion is a safe treatment approach for ESRD patients.


Assuntos
Cateterismo/métodos , Cateteres de Demora , Falência Renal Crônica/terapia , Diálise Peritoneal/métodos , Adulto , Fatores Etários , Índice de Massa Corporal , Cateterismo/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Diálise Peritoneal/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo
6.
Oncol Rep ; 41(5): 2689-2702, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30864728

RESUMO

Castration­resistant prostate cancer (CRPC) is a major challenge in the treatment of prostate cancer (PCa). Phospholipase Cε (PLCε), an oncogene, has been found to be involved in the carcinogenesis, tumor proliferation and migration of several types of cancer. The effects, however, of PLCε on CRPC remains unclear. In the present study, the expression of PLCε and glioma­associated homolog (Gli)­1/Gli­2 in benign prostatic hyperplasia (BPH), PCa and CRPC tissues and cells was investigated, and the correlations between PLCε and Gli­1/Gli­2 in CRPC tissues and cell lines were further explored. In addition, the effect of PLCε on cell proliferation and invasion was assessed in CRPC cell lines, and the sensitivity of EN­R and 22RV1 cells to enzalutamide following the downregulation of PLCε expression was determined using lentivirus­mediated shPLCε and/or treatment with specific Gli inhibitor GANT61. It was found that the PLCε expression was excessively upregulated in the majority of CRPC tissues, and PLCε positivity was linked to poor progression­free survival (PFS) and overall survival (OS) in patients with PCa. Furthermore, PLCε knockdown significantly suppressed CRPC cell proliferation and invasion. Of note, it was found that PLCε knockdown increased the sensitivity of CRPC cells to enzalutamide in vitro by suppressing androgen receptor (AR) activities via the non­canonical Hedgehog/Gli­2 and p­STAT3 signaling pathways. PLCε knockdown was shown to increase the sensitivity of CRPC cell xenografts to enzalutamide in vivo. Finally, the combination of PLCε knockdown with GANT61 significantly sensitized CRPC cells to enzalutamide. Collectively, the results of the present study suggest that PLCε is a potential therapeutic target for CRPC.


Assuntos
Feniltioidantoína/análogos & derivados , Fosfoinositídeo Fosfolipase C/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Técnicas de Silenciamento de Genes , Humanos , Imunoglobulina G/farmacologia , Imunoglobulina G/uso terapêutico , Masculino , Melfalan/farmacologia , Melfalan/uso terapêutico , Camundongos , Camundongos Nus , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/metabolismo , Feniltioidantoína/farmacologia , Feniltioidantoína/uso terapêutico , Fosfoinositídeo Fosfolipase C/genética , Prognóstico , Intervalo Livre de Progressão , Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Piridinas/farmacologia , Piridinas/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Análise de Sobrevida , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína GLI1 em Dedos de Zinco/antagonistas & inibidores , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína Gli2 com Dedos de Zinco/antagonistas & inibidores , Proteína Gli2 com Dedos de Zinco/metabolismo
7.
Arch Microbiol ; 201(6): 807-816, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30874825

RESUMO

Rice blast, caused by Magnaporthe oryzae, is a serious threat to global rice production. In recent years, many pathogenicity genes of M. oryzae have been identified, although most of their functions remain unknown. In this study, we report the synergistic deletion of RGS1 and COS1 that may reduce the pathogenicity of M. oryzae. The investigation involved comparing ΔMorgs1, ΔMocos1, and ΔMorgs1/ΔMocos1 mutants. The ΔMorgs1/ΔMocos1 mutant showed a weak reduction in vegetative growth, and the colonies displayed fewer and smoother aerial hyphae. The ΔMorgs1/ΔMocos1 mutant exhibited delayed appressorium-like structure formation and 'low pathogenicity' on detached rice seedling leaves when compared with ΔMocos1. Moreover, the melanin content of the single and double mutants was remarkably lower than that of the WT type. Thus, our results indicate that the synergy between RGS1 and COS1 may be crucial in the pathogenicity of M. oryzae.


Assuntos
Proteínas Fúngicas/genética , Deleção de Genes , Magnaporthe/genética , Magnaporthe/patogenicidade , Oryza/microbiologia , Doenças das Plantas/microbiologia , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Hifas/genética , Hifas/crescimento & desenvolvimento , Hifas/metabolismo , Hifas/patogenicidade , Magnaporthe/crescimento & desenvolvimento , Magnaporthe/metabolismo , Plântula/microbiologia , Esporos Fúngicos/genética , Esporos Fúngicos/crescimento & desenvolvimento , Esporos Fúngicos/metabolismo , Esporos Fúngicos/patogenicidade , Virulência
8.
J Cell Physiol ; 2019 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-30684266

RESUMO

Most prostate cancers (Pcas) develop into castration-resistant prostate cancer (CRPC) after receiving androgen deprivation therapy (ADT). The expression levels of PLCε and wnt3a are increased in Pca and regulate androgen receptor (AR) activity. However, the biological function and mechanisms of PLCε and wnt3a in CRPC remain unknown. In this study, we found that the expression levels of PLCε, wnt3a, and AR were significantly increased in CRPC tissues as well as bicalutamide-resistant-LNCaP and enzalutamide-resistant-LNCaP cells. In addition, PLCε knockdown partly restored the sensitivity of drug-resistant cells to bicalutamide and enzalutamide by inhibiting the activity of the wnt3a/ß-catenin/AR signaling axis. Interestingly, the resistance of LNCaP cells docetaxel is related to PLCε but not the wnt3a/ß-catenin pathway. We also found that the combination of PLCε knockdown and enzalutamide treatment synergistically suppressed cell proliferation, tumor growth, and bone metastasis using in vitro and in vivo experiments. Our study revealed that PLCε is involved in the progression of drug-resistance in CRPC and could be a new target for the treatment of CRPC.

9.
Urology ; 127: 61-67, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30528714

RESUMO

OBJECTIVE: To investigate how hepatocyte cell adhesion molecule (hepaCAM) regulates cancer energy metabolism through hypoxia-inducible factor (HIF-1α) in renal cell carcinoma (RCC). MATERIALS AND METHODS: The expression of hepaCAM and HIF-1α in RCC tissue samples was examined by immunohistochemistry. Glucose consumption and lactate production assays were used to detect metabolic activity in RCC cell lines. P65 and IκB kinase (IKKß) mRNA and protein expression were detected using quantitative real-time polymerase chain reaction and western blotting, respectively. Nuclear translocation of P65 was observed by immunofluorescence staining after re-expressing hepaCAM. The luciferase reporter assay was applied to validate the transcriptional activity of HIF-1α. RESULTS: HIF-1α expression was elevated and hepaCAM suppressed in RCC compared with adjacent normal tissues. Furthermore, hepaCAM re-expression significantly decreased glycolytic metabolism in RCC cell lines, and reduced HIF-1α, IKKß, and P65 expression. The expression of HIF-1α, GLUT1, LDHA, and PKM2 were further reduced with combined hepaCAM overexpression and treatment with the NF-κB inhibitor BAY11-7082, compared to hepaCAM overexpression alone. Additionally, hepaCAM decreased the transcriptional activity of HIF-1α and blocked P65 nuclear translocation by the NF-κB pathway. CONCLUSION: Our data suggest that hepaCAM suppresses the Warburg effect via the HIF-1α/NF-κB pathway in RCC, which is a facilitating factor in hepaCAM-reduced tumorigenesis.


Assuntos
Carcinogênese/genética , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Renais/genética , Proteínas/genética , Análise de Variância , Biópsia por Agulha , Carcinoma de Células Renais/patologia , Divisão Celular/genética , Proliferação de Células/genética , Humanos , Quinase I-kappa B/genética , Imuno-Histoquímica , Neoplasias Renais/patologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Transdução de Sinais/genética , Células Tumorais Cultivadas
10.
Braz. j. med. biol. res ; 52(3): e8055, 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-989464

RESUMO

This study aimed to investigate the clinical characteristics, prognosis, and factors for survival of patients who underwent early-start peritoneal dialysis (PD) within 24 h after catheter insertion three years after PD. This study was conducted from January 1, 2013 to December 31, 2017. All adult patients who were diagnosed with end-stage renal disease (ESRD) and underwent PD for the first time within 24 h after catheter insertion in our hospital were included. All patients with PD were followed-up until they withdrew from PD, switching to hemodialysis, were transferred to other medical centers, underwent renal transplantation, died or were lost to follow-up, or continued to undergo dialysis until the end of the study period. The follow-up observation lasted three years. The number of eligible patients was 110, and switching to hemodialysis and death were the main reasons for patients to withdraw from PD. The 1-, 2-, and 3-year technical survival rates of patients were 89.1, 79.1, and 79.1% respectively, while the 1-, 2- and 3-year survival rates were 90, 81.8, and 81.8%, respectively. The Charlson comorbidity index, age, hemoglobin, serum albumin, diabetic nephropathy, chronic glomerulonephritis, and hypertensive renal damage were independent risk factors that affected the prognosis of PD patients. Under the condition of ensuring the quality of the PD catheter insertion, early-start PD within 24 h after catheter insertion is a safe treatment approach for ESRD patients.

11.
Cancer Cell Int ; 18: 98, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30008615

RESUMO

Background: We aimed to figure out the molecular network of PVT1 and EZH2 on hepatocellular carcinoma (HCC) cells growth. We also explored the interaction between PVT1, EZH2, MDM2 and P53. Methods: Microarray analysis was performed to screen for abnormally expressed genes in HCC tissues and PVT1 was identified as one gene significantly upregulated in HCC. CCK-8 assay, colony formation assay, and flow cytometry detected cell vitality, proliferation and apoptosis, respectively. RIP and RNA pull-down assays were employed to examine the connection between PVT1 and EZH2. The effect of PVT1 on the stability of EZH2 protein and the impact of EZH2 on MDM2 were detected by ELISA. Co-immunoprecipitation assay was used to evaluate the relationship between MDM2 and EZH2. Western blot detected the expression of EZH2, MDM2 and P53. Results: Up-regulated PVT1 was detected in HCC. Knockdown of PVT1 inhibited HCC cell propagation and promoted apoptotic cells. PVT1 could improve EZH2 protein stability by binding to EZH2 protein but have no significant impact on EZH2 mRNA expression. EZH2 protein stabilized MDM2 protein expression by binding to MDM2 protein. PVT1 enhanced the protein expression of EZH2 and MDM2 as well as inhibited P53 protein expression. Conclusions: PVT1 promoted HCC cell propagation and inhibited apoptotic cells by recruiting EZH2, stabilizing MDM2 protein expression and restraining P53 expression.

12.
Free Radic Biol Med ; 124: 484-492, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-29723666

RESUMO

Contamination of soil and water by waste from abandoned uranium mines has led to chronic exposures to metal mixtures in Native American communities. Our previous work demonstrated that community exposures to mine waste increase the likelihood of developing cardiovascular disease, as well as the likelihood of developing multiple chronic diseases including diabetes, hypertension and kidney disease. Exposure to various environmental metals is associated with elevated oxidative stress, which is considered a contributor to these and other chronic disease states. The purpose of the current research was to assess potential associations between exposure to uranium and arsenic and evidence for increased oxidative stress as measured by urinary F2 -isoprostanes in pregnant women enrolled in the Navajo Birth Cohort Study. The current study also included an analysis of zinc as a potential mediator of oxidative stress in the study population. Urinary arsenic and uranium, serum zinc and urinary F2 -isoprostanes were measured for each study participant at enrollment. Study participants were pregnant women with median age of 26.8; 18.9% were enrolled in the 1st trimester, 44.7% were enrolled in the 2nd trimester, and 36.4% were enrolled in the 3rd trimester. Median urinary metal levels were 5.5 and 0.016 µg/g creatinine for arsenic and uranium, respectively. Multivariable regression analysis indicated a significant association between arsenic exposure and the lipid peroxidation product 8-iso-prostaglandin F2α, controlling for zinc and trimester. No associations were detected with uranium despite evidence that levels were in the Navajo Birth Cohort samples were 2.3 times the median reported for women in the National Health and Nutrition Examination Survey (2011-12). Zinc was not found to have any causal mediation of the effects of the other metals on oxidative stress. The current work is consistent with other studies that have detected an association between arsenic and elevated oxidative stress. In contrast to arsenic, uranium did not appear to increase oxidative stress response in this study population. These findings are relevant to assessing the potential human impact of chronic exposure to mixed metal waste from abandoned uranium mines.

13.
Int J Oncol ; 53(1): 99-112, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29658567

RESUMO

Castration-resistant prostate cancer (CRPC) continues to be a major challenge in the treatment of prostate cancer (PCa). The expression of hepatocyte cell adhesion molecule (HepaCAM), a novel tumor suppressor, is frequently downregulated or lost in PCa. Overactivated Notch signaling is involved in the development and progression of PCa, including CRPC. In this study, we found that the activities of Notch signaling were elevated, while HepaCAM expression was decreased in CRPC tissues compared with matched primary prostate cancer (PPC) tissues. In addition, HepaCAM negativity was found to be associated with a worse progression­free survival (PFS). Furthermore, the overexpression of HepaCAM induced by transfection with a HepaCAM overexpression vector (Ad­HepaCAM) exerted antitumor effects by decreasing the proliferation, and suppressing the invasion and migration of bicalutamide­resistant (Bica­R) cells and enzalutamide­resistant (Enza­R) cells. Importantly, we found that the antitumor effects of HepaCAM on the resistant cells were associated with the downregulation of Notch signaling. Moreover, we revealed that PF­3084014 (a γ­secretase inhibitor) re­sensitized Enza­R cells to enzalutamide, and sequential dual­resistant (E+D­R) cells to docetaxel. Additionally, the findings of this study demonstrated that the use of PF­3084014 alone exerted potent antitumor effect on the resistant cells in vitro. On the whole, this study indicates that HepaCAM potentially represents a therapeutic target and PF­3084014 may prove to a promising agent for use in the treatment of refractory PCa.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Proteínas/genética , Tetra-Hidronaftalenos/administração & dosagem , Valina/análogos & derivados , Adulto , Idoso , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Intervalo Livre de Doença , Docetaxel , Humanos , Masculino , Pessoa de Meia-Idade , Feniltioidantoína/administração & dosagem , Feniltioidantoína/efeitos adversos , Feniltioidantoína/análogos & derivados , Próstata/efeitos dos fármacos , Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Notch/antagonistas & inibidores , Receptores Notch/genética , Transdução de Sinais/efeitos dos fármacos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Valina/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Molecules ; 22(9)2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28872608

RESUMO

A new type of blue emitter, N²-Indolyl-1,2,3-triazoles (NITs), with the λmax ranging from 420-480 nm and the Stokes shift from 89-143 nm, were synthesized through the coupling reaction of indoles with triazole derivatives. The influence of different substitution patterns on the optical properties (efficiency, excitation, and emission wavelengths) of the NITs was investigated. In addition, one palladium complex were synthesized by using NITs as the ligands, which, however, exhibited no fluorescent activity, but did show the enhanced co-planarity. Lastly, two bio-active molecule derivatives were explored for the potential use of these novel dyes in related chemical and biological applications.


Assuntos
Complexos de Coordenação/química , Corantes Fluorescentes/química , Indóis/química , Paládio/química , Triazóis/química , Complexos de Coordenação/síntese química , Fluorescência , Corantes Fluorescentes/síntese química , Indóis/síntese química , Ligantes , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Triazóis/síntese química
15.
Sci Rep ; 7(1): 11569, 2017 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-28912531

RESUMO

Aberrant expression of microRNAs hae been shown to be closely associated with glioblastoma cell proliferation, apoptosis and drug resistance. However, mechanisms underlying the role of mcroRNAs in glioblastoma cell growth and apoptosis are not fully understood. In this study, we report that miR-503 is overexpressed in glioblastoma tissue compared with normal human brain tissue. Mechanistically, miR-503 can be induced by TGF-â1 at the transcriptional level by binding the smad2/3 binding elements in the promoter. Ectopic overexpression of miR-503 promotes cell growth and inhibits apoptosis by targeting PDCD4. In contrast, inhibition of miR-503 reduces cell growth. Furthermore, miR-503 inhibitor augments the growth inhibitory effect of temozolomide in glioblastoma cells. These results establish miR-503 as a promising molecular target for glioblastoma therapy.

16.
Mol Med Rep ; 16(3): 3673-3679, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28713956

RESUMO

MDG­1, a water­soluble polysaccharide extracted from Ophiopogon japonicus, has been reported to serve a role in antimyocardial ischemia by protecting cardiomyocytes from hypoxia/reoxygenation­induced damage. However, it remains unknown whether MDG­1 protects human umbilical vein endothelial cells (HUVECs) against oxidative stress­induced damage. In the present study, HUVECs were treated with hydrogen peroxide (H2O2) to establish an oxidative stress­induced cell injury model. Treatment of HUVECs with different concentrations of H2O2 significantly attenuated cell viability and increased cell apoptosis in a time and dose­dependent manner. Pretreatment with MDG­1 markedly reduced H2O2­induced cell death, ROS generation and inflammatory factor secretion. In addition, pretreatment with MDG­1 decreased the expression levels of proapoptotic proteins BCL2 associated X (Bax) and caspase­3, while it increased the expression levels of the antiapoptotic protein BCL2 apoptosis regulator (Bcl­2), compared with H2O2 treatment alone. Taken together, the present data suggest that MDG­1 protected HUVECs against H2O2­induced apoptosis and inflammation through inhibition of Bax/Bcl­2 protein ratio, caspase­3 expression, and inflammatory factor secretion. This study provides a potential application for MDG­1 in the treatment of cardiovascular disease.


Assuntos
Apoptose/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/patologia , Peróxido de Hidrogênio/toxicidade , Inflamação/patologia , Polissacarídeos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Citoproteção/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos
17.
Hu Li Za Zhi ; 64(3): 56-64, 2017 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-28580559

RESUMO

BACKGROUND: The unauthorized releasing of confidential patient information is a serious problem worldwide. Nurses, the healthcare professionals who are in most frequent contact with patients, have access to a significant amount of confidential patient information and play a key role in protecting patient privacy. However, currently, there is no proper tool to measure the level to which clinical nurses protect the privacy of their patients in China. PURPOSE: To translate the patient privacy scale (PPS) into Chinese and to test the reliability and validity of this Chinese version. METHODS: The original scale was developed by Özturk, Bahcecik, and Özçelik (2014) to identify whether nurses protect or violate patient privacy in the workplace. This study used the "back translation" method to translate the scale. A total of 616 nurses in two tertiary hospitals in the Western region of China were enrolled to test the internal consistency, test-retest reliability, and construct validity of the translated scale. RESULTS: The Cronbach's coefficients of the total scale and its 5 factors ranged from .84 to .94; the split half reliability was .91; the test-retest reliability was .82; and the content validity index was .95. Explanatory factor analysis revealed that the 5 factors explained 64.98% of the total variance. CONCLUSIONS: The Chinese version of the PPS is reliable and valid, and may be used to reliably assess the behaviors of nurses with regard to protecting the privacy of their patients. The scale may also be used to evaluate the effects of training on patient privacy protection.


Assuntos
Privacidade , Tradução , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
18.
IEEE J Biomed Health Inform ; 21(2): 515-526, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28055928

RESUMO

For hospitals where decisions regarding acceptable rates of elective admissions are made in advance based on expected available bed capacity and emergency requests, accurate predictions of inpatient bed capacity are especially useful for capacity reservation purposes. As given, the remaining unoccupied beds at the end of each day, bed capacity of the next day can be obtained by examining the forecasts of the number of discharged patients during the next day. The features of fluctuations in daily discharges like trend, seasonal cycles, special-day effects, and autocorrelation complicate decision optimizing, while time-series models can capture these features well. This research compares three models: a model combining seasonal regression and ARIMA, a multiplicative seasonal ARIMA (MSARIMA) model, and a combinatorial model based on MSARIMA and weighted Markov Chain models in generating forecasts of daily discharges. The models are applied to three years of discharge data of an entire hospital. Several performance measures like the direction of the symmetry value, normalized mean squared error, and mean absolute percentage error are utilized to capture the under- and overprediction in model selection. The findings indicate that daily discharges can be forecast by using the proposed models. A number of important practical implications are discussed, such as the use of accurate forecasts in discharge planning, admission scheduling, and capacity reservation.


Assuntos
Ocupação de Leitos/estatística & dados numéricos , Previsões/métodos , Modelos Estatísticos , Alta do Paciente/estatística & dados numéricos , Número de Leitos em Hospital , Humanos , Cadeias de Markov , Análise de Regressão , Fatores de Tempo
19.
Mar Pollut Bull ; 111(1-2): 143-152, 2016 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-27456239

RESUMO

Stable isotopes (δ(15)N, δ(18)O) can serve as tracers for sources of nitrogen in the receiving environment. Hong Kong discharges ~3×10(6)m(3)d(-1) of treated wastewater into the ocean from 68 facilities implementing preliminary to tertiary treatment. We sampled treated sewage from 18 plants across 5 treatment types and examined receiving seawater from northeast Hong Kong. We analyzed nitrate and nitrite (NO3(-)+NO2(-), hereafter NOx) ammonium (NH4(+)), phosphate (PO4(+)) concentrations and δ(15)NNOx, δ(18)ONOx. Sewage effluents contained high mean nutrient concentrations (NO3(-)=260µmolL(-1), NH4(+)=1400µmolL(-1), PO4(+)=50µmolL(-1)) with some indication of nitrogen removal in advanced treatment types. Mean δ(15)NNOx of sewage effluents from all plants and treatment types (12‰) was higher than natural sources and varied spatially and seasonally. There was no overall effect of sewage treatment type on δ(15)NNOx. A mass balance model indicated that sewage (>68%) remains a dominant source of nitrate pollution in seawater in Tolo Harbor.


Assuntos
Monitoramento Ambiental , Isótopos de Nitrogênio , Águas Residuárias , Poluentes Químicos da Água , Hong Kong , Nitratos , Água do Mar
20.
Mol Med ; 21(1): 969-978, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26736179

RESUMO

Effects of ARA290 on glucose homeostasis were studied in type 2 diabetic Goto-Kakizaki (GK) rats. In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity. Glucose-stimulated insulin secretion was increased in islets from ARA290-treated rats. Additionally, in response to glucose, carbachol and KCl, islet cytoplasmic free Ca2+ concentrations, [Ca2+]i, were higher and the frequency of [Ca2+]i oscillations enhanced compared with placebo. ARA290 also improved stimulus-secretion coupling for glucose in GK rat islets, as shown by an improved glucose oxidation rate, ATP production and acutely enhanced glucose-stimulated insulin secretion. ARA290 also exerted an effect distal to the ATP-sensitive potassium (KATP) channel on the insulin exocytotic pathway, since the insulin response was improved following islet depolarization by KCl when KATP channels were kept open by diazoxide. Finally, inhibition of protein kinase A completely abolished effects of ARA290 on insulin secretion. In conclusion, ARA290 improved glucose tolerance without affecting hematocrit in diabetic GK rats. This effect appears to be due to improved γ-cell glucose metabolism and [Ca2+]i handling, and thereby enhanced glucose-induced insulin release.

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