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1.
Molecules ; 28(9)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37175205

RESUMO

Glioblastoma (GBM) is the most aggressive brain tumor, with high mortality. Timosaponin AIII (TIA), a steroidal saponin isolated from the medicinal plant Anemarrhena asphodeloides Bge., has been shown to possess anticancer properties in various cancer types. However, the effect of TIA on GBM is unknown. In this study, we reveal that TIA not only inhibited U87MG in vitro cell growth but also in vivo tumor development. Moreover, we found that the cause of TIA-induced cell growth suppression was apoptosis. When seeking to uncover antitumor mechanisms of TIA, we found that TIA diminished the expression of cGMP-specific phosphodiesterase 5(PDE5) while elevating the levels of guanylate cyclases (sGCß), cellular cGMP, and phosphorylation of VASPser239. Following the knockdown of PDE5, PDE5 inhibitor tadalafil and cGMP analog 8-Bro-cGMP both inhibited cell growth and inactivated ß-catenin; we reason that TIA elicited an antitumor effect by suppressing PDE5, leading to the activation of the cGMP signaling pathway, which, in turn, impeded ß-catenin expression. As ß-catenin is key for cell growth and survival in GBM, this study suggests that TIA elicits its anti-tumorigenic effect by interfering with ß-catenin function through the activation of a PDE5/cGMP functional axis.


Assuntos
Glioblastoma , beta Catenina , Humanos , beta Catenina/metabolismo , Glioblastoma/tratamento farmacológico , Esteroides/farmacologia , Apoptose , Transdução de Sinais , GMP Cíclico/metabolismo
2.
Infect Dis Poverty ; 10(1): 29, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731213

RESUMO

BACKGROUND: In China, an indigenously developed electronic medication monitor (EMM) was designed and used in 138 counties from three provinces. Previous studies showed positive results on accuracy, effectiveness, acceptability, and feasibility, but also found some ineffective implementations. In this paper, we assessed the effect of implementation of EMMs on treatment outcomes. METHODS: The longitudinal ecological method was used at the county level with aggregate secondary programmatic data. All the notified TB cases in 138 counties were involved in this study from April 2017 to June 2019, and rifampicin-resistant cases were excluded. We fitted a multilevel model to assess the relative change in the quarterly treatment success rate with increasing quarterly EMM coverage rate, in which a mixed effects maximum likelihood regression using random intercept model was applied, by adjusting for seasonal trends, population size, sociodemographic and clinical characteristics, and clustering within counties. RESULTS: Among all 69 678 notified TB cases, the treatment success rate was slightly increased from 93.5% [95% confidence interval (CI): 93.0-94.0] in second quarter of 2018 to 94.9% (95% CI: 94.4-95.4) in second quarter of 2019 after implementing EMMs. There was a statistically significant effect between quarterly EMM coverage and treatment success rate after adjusting for potential confounders (P = 0.0036), increasing 10% of EMM coverage rate will lead to 0.2% treatment success rate augment. Besides, an increase of 10% of elderly or bacteriologically confirmed TB will lead to a decrease of 0.4% and 0.9% of the treatment success rate. CONCLUSIONS: Under programmatic settings, we found a statistically significant effect between increasing coverage of EMM and treatment success rate at the county level. More prospective studies are needed to confirm the effect of using EMM on TB treatment outcomes. We suggest performing operational research on EMMs that provides real-time data under programmatic conditions in the future.


Assuntos
Antituberculosos/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Tuberculose Pulmonar/tratamento farmacológico , Idoso , China , Eletrônica , Feminino , Humanos , Estudos Longitudinais , Adesão à Medicação/psicologia , Sistemas de Alerta , Resultado do Tratamento
3.
Technol Cancer Res Treat ; 18: 1533033819851833, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31570091

RESUMO

OBJECTIVE: To investigate the role of miR-26a-5p in cell proliferation and doxorubicin sensitivity in hepatocellular carcinoma. METHODS: We evaluated miR-26a-5p expression in hepatocellular carcinoma tissues and cell lines by reverse transcription polymerase chain reaction. Cell Counting Kit-8 was used to examine cell proliferation. Relationship between miR-26a-5p and aurora kinase A was evaluated by luciferase report system. Western blot was used to detect expression of aurora kinase A. RESULTS: In this study, we observed miR-26a-5p was downregulated in hepatocellular carcinoma tissues and cell lines. Gain-of-function experiments showed that proliferation rate of hepatocellular carcinoma cells decreased under condition of miR-26a-5p mimics. We found miR-26a-5p mimics could enhance doxorubicin sensitivity of hepatocellular carcinoma cells. Further study showed that aurora kinase A was target gene of miR-26a-5p. Suppression of aurora kinase A could lead to lower cell proliferation and higher doxorubicin sensitivity of hepatocellular carcinoma cells. CONCLUSION: Our study found that miR-26a-5p could inhibit cell proliferation and enhance doxorubicin sensitivity in hepatocellular carcinoma cells by targeting aurora kinase A.


Assuntos
Aurora Quinase A/genética , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , MicroRNAs/genética , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Oncol Rep ; 41(3): 1649-1657, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30592290

RESUMO

The present study investigated the expression and potential influence of SHC SH2 domain­binding protein 1 (SHCBP1) in gastric cancer (GC) cells. SHCBP1 is closely related to cell proliferation and cell cycle progression, but its role in GC remains unclear. The TCGA database revealed that SHCBP1 is highly expressed in GC tissues. Furthermore, SHCBP1 was revealed to be highly expressed in GC cell lines MGC­803 and SGC­7901 cells, and downregulation of SHCBP1 significantly inhibited GC cell proliferation. Furthermore, SHCBP1 expression promoted cell cycle progression and inhibition of apoptosis. Since the CDK4, cyclin D1 and caspase family proteins play important roles in cell cycle and apoptosis regulation, it was examined whether there was an association between SHCBP1 and these signaling pathways in GC. Our results revealed that SHCBP1 promoted cell cycle progression by regulating the CDK4­cyclin D1 cascade and suppressed caspase­3, caspase PARP­dependent apoptotic pathways. Cell invasion and metastasis experiments also revealed that SHCBP1 promoted tumor growth and invasiveness. These tumor­promoting functions of SHCBP1 may provide a potential molecular basis for the diagnosis and targeted therapy of GC.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas Adaptadoras da Sinalização Shc/metabolismo , Neoplasias Gástricas/patologia , Apoptose , Biomarcadores Tumorais/genética , Caspase 3/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , RNA Interferente Pequeno/metabolismo , Proteínas Adaptadoras da Sinalização Shc/genética , Transdução de Sinais , Estômago/patologia , Neoplasias Gástricas/diagnóstico
5.
Mol Cell Biochem ; 390(1-2): 215-23, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24526523

RESUMO

Spinal cord injury (SCI) results in a loss of normal motor and sensory function, leading to severe disability and reduced quality of life. The aim of this work was to investigate the effect of receptor for advanced glycation end products (RAGE) deficiency on the function recovery in a mouse model of SCI. Mice received a mid-thoracic spinal contusion injury. Upregulation of RAGE protein expression in spinal cord tissue was evident at 12 h after SCI and continued at 2 and 5 days. Furthermore, we showed that locomotor recovery was improved and lesion pathology was reduced after SCI in RAGE-deficient mice. RAGE deficiency in mice attenuated apoptosis after SCI through inhibiting p53/Bax/caspase-3 pathway. RAGE deficiency in mice inhibited inflammation after SCI, marked by reduced myeloperoxidase activity, NFκB nuclear translocation, and TNF-α, IL-1ß, and IL-6 mRNA and protein levels. RAGE deficiency in mice exposed to SCI suppressed the upregulation of inducible nitric oxide synthase (iNOS) and gp91-phox and attenuated oxidative and nitrosative stresses, marked by reduced formation of malondialdehyde, reactive oxygen species, peroxynitrite (OONO(-)), and 3-nitrotyrosine. RAGE deficiency in mice exposed to SCI attenuated glial scar at the injury site, marked by decreased expression of glial fibrillary acidic protein. These data indicate that the RAGE plays an important role in the development of SCI and might provide a therapeutic target to promote recovery from SCI.


Assuntos
Regulação da Expressão Gênica/genética , Inflamação/genética , Estresse Oxidativo/genética , Receptores Imunológicos/biossíntese , Traumatismos da Medula Espinal/genética , Animais , Caspase 3/metabolismo , Modelos Animais de Doenças , Humanos , Inflamação/patologia , Interleucina-6/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Espécies Reativas de Oxigênio/metabolismo , Receptor para Produtos Finais de Glicação Avançada , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/patologia
6.
Beijing Da Xue Xue Bao Yi Xue Ban ; 42(3): 299-303, 2010 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-20559405

RESUMO

OBJECTIVE: To develop an adherence rating score (ARS) system specific for tuberculosis (TB) patients. METHODS: A cross-sectional survey of 124 TB patients was conducted to figure out risk factors for adherence to treatment. The step-wise logistic regression models were used for selecting adherence-related variables. ARS was developed based on the weighting scores of the parameters of all the predicted variables in the logistic model. The reliability and responsibility of ARS was evaluated by using external data from an open label randomized controlled trial on 574 TB patients. The patients were grouped as adherence group (247 patients) and non-adherence group (327 patients) based on the predicted ARS. And the non-adherence group was randomized divided into a trail group (146 patients) and a control group (181 patients). The intervention for the trail group was custom health educational material aimed to reduce ARS, while the intervention for control groups was general TB education material, which was routinely used in the current local TB control settings. The cumulative non-adherence rates of the three groups were compared with each other after six-month follow-up period of treatment. RESULTS: The ARS system had 7 items which covered the following domains: disease status, psychology, patients' KAP (knowledge, attitude, and practice), regularly life-style and social supports. The score of ARS was 2.38+/-0.18 (mean+/-SD) for adherence patients, and 4.69 +/-0.20 (mean+/-SD) for non-adherence patients (t=8.52, P<0.01). In the randomized controlled trial, the six months cumulative non-adherence rates ware 24.7% for the trail group and it was 41.4% for the control group(P<0.01); while the six months cumulative non-adherence rates were not statistical significant difference between trail group and adherence group (P>0.05). CONCLUSION: The ARS system was reliability and validity for evaluating the adherence of TB treatment in the stop TB settings in China.


Assuntos
Antituberculosos/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Cooperação do Paciente/estatística & dados numéricos , Educação de Pacientes como Assunto/métodos , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Idoso , China , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e Questionários , Adulto Jovem
7.
BMC Public Health ; 10: 267, 2010 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-20492672

RESUMO

BACKGROUND: More than 1 million tuberculosis (TB) patients are receiving the standard anti-TB treatment provided by China National Tuberculosis Prevention and Control Scheme (CNTS) in China every year. Adverse reactions (ADRs) induced by anti-TB drugs could both do harm to patients and lead to anti-TB treatment failure. The ADACS aimed to explore ADRs' incidences, prognoses, economical and public health impacts for TB patients and TB control, and build a DNA bank of TB patients. METHODS/DESIGN: Multiple study designs were adopted. Firstly, a prospective cohort with 4488 sputum smears positive pulmonary tuberculosis patients was established. Patients were followed up for 6-9 months in 52 counties of four regions. Those suspected ADRs should be checked and confirmed by Chinese State Food and Drug Administration (SFDA). Secondly, if the suspected ADR was anti-TB drug induced liver injury (ATLI), a nested case-control study would be performed which comprised choosing a matched control and doing a plus questionnaire inquiry. Thirdly, health economical data of ADRs would be collected to analyze financial burdens brought by ADRs and cost-effectiveness of ADRs' treatments. Fourthly, a drop of intravenous blood for each patient was taken and saved in FTA card for DNA banking and genotyping. Finally, the demographic, clinical, environmental, administrative and genetic data would be merged for the comprehensive analysis. DISCUSSION: ADACS will give an overview of anti-TB drugs induced ADRs' incidences, risk factors, treatments, prognoses, and clinical, economical and public health impacts for TB patients applying CNTS regimen in China, and provide suggestions for individualized health care and TB control policy.


Assuntos
Antituberculosos/efeitos adversos , Programas Nacionais de Saúde , Projetos de Pesquisa , Tuberculose/tratamento farmacológico , Adulto , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , China , Estudos de Coortes , Feminino , Humanos , Masculino , Manejo de Espécimes , Escarro/microbiologia , Inquéritos e Questionários
8.
Zhonghua Liu Xing Bing Xue Za Zhi ; 30(5): 502-6, 2009 May.
Artigo em Chinês | MEDLINE | ID: mdl-19799150

RESUMO

OBJECTIVE: To investigate the distribution of glutathione-S-transferase M1 (GSTM1) and T1 (GSTT1) genes polymorphisms in Chinese population and smear-positive pulmonary tuberculosis cases of Jilin province. METHODS: Articles about GSTM1 and GSTT1 genes polymorphisms published before 2009 in China were searched. The study population was obtained from fourteen counties (or districts) of Jilin province, which included all cases from November, 2007 to May, 2008, totally 1120. The genotypes of GSTM1 and GSTT1 were detected by multiplex PCR technique. RESULTS: The frequencies of GSTM1 and GSTT1 'null' genotypes and combination M1-T1 'null' genotype acquired from systematic review were 54.2%, 46.8% and 26.2%, respectively, in Chinese Hans they were 53.4%, 44.9% and 25.5%, and in our research they are 57.2%, 20.4% and 13.7%, respectively. No significant differences between the frequencies of males and females as well as among that of different age groups were observed (P > 0.05). The frequency of GSTM1 'null' genotype in our research is slightly higher than that in systematic review (P = 0.016) , and the frequencies of GSTT1 'null' genotype and combination M1-T1 'null' genotype and are significantly lower than those in systematic review (both P < 0.001). CONCLUSION: The frequencies of GSTM1 and GSTT1 'null' genotypes were different among ethnic. The statistical difference between systematic review and our research may due to our large sample size and mostly Southern people in previous studies.


Assuntos
Glutationa Transferase/genética , Polimorfismo Genético , Tuberculose/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Criança , China/epidemiologia , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Tuberculose/enzimologia , Tuberculose/epidemiologia , Adulto Jovem
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