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1.
Anal Biochem ; 631: 114355, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34461080

RESUMO

This study aimed to develop an LC-MS/MS method for determining sildenafil and its metabolites N-desmethylsildenafil and N1,N4-desmethylsildenafil in human plasma and applying it to a pharmacokinetic study of sildenafil in healthy volunteers. Sildenafil-d8 was used as the internal standard. Plasma samples were pretreated via protein precipitation with acetonitrile. The extractives were then separated on an ACQUITY UPLC BEH C18 (50-mm × 2.1-mm, 1.7-µm) column using gradient elution. The aqueous and organic mobile phases were ammonium formate 2 mM supplemented with 0.1% formic acid in water and acetonitrile, respectively, and the flow rate was 0.3 mL/min. An electrospray ionization source was applied, and multiple reaction monitoring was operated in the positive mode with selective channels at m/z 475.30 â†’ 100.10, 461.20 â†’ 283.30, 483.30 â†’ 108.10, and 449.00 â†’ 283.00 for sildenafil, sildenafil-d8, N-desmethylsildenafil, and N1,N4-desmethylsildenafil, respectively. The linear calibration curves of sildenafil and its metabolites spanned 1.0-1000 ng/mL. The lower limit of quantification was 1.0 ng/mL. The extractive recovery of analytes from the biological matrix was more than 90% and the matrix effect complied with relevant provisions. The intra- and inter-day precisions of sildenafil and its metabolite were <10%. The intra- and inter-day accuracy of sildenafil, N-desmethylsildenafil, and N1,N4-desmethylsildenafil was more than 99%. The method is highly sensitive and selective, and it was successfully applied to the bioequivalence studies of 100-mg sildenafil citrate tablets in 40 healthy Chinese volunteers.


Assuntos
Cromatografia Líquida/métodos , Citrato de Sildenafila/sangue , Citrato de Sildenafila/farmacocinética , Espectrometria de Massas em Tandem/métodos , Administração Oral , Adolescente , Adulto , Análise Química do Sangue/métodos , Calibragem , Estabilidade de Medicamentos , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Citrato de Sildenafila/administração & dosagem , Citrato de Sildenafila/metabolismo , Equivalência Terapêutica , Adulto Jovem
2.
Zhonghua Nan Ke Xue ; 26(1): 3-16, 2020 Jan.
Artigo em Zh | MEDLINE | ID: mdl-33345471

RESUMO

Reproductive health is a key aim of the population health strategy, and male reproductive health constitutes an important part of reproductive health. This article systematically analyzes the applications to and grants from the National Natural Science Foundation of China (NSFC) and some related scientific problems in the field of male reproductive health in the past 30 years. It also discusses the development of the basic researches on male reproductive health in China and the facilitating role of NSFC in this field.


Assuntos
Pesquisa Biomédica/tendências , Saúde Reprodutiva , China , Fundações , Humanos , Masculino
3.
Tumour Biol ; 37(1): 239-51, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26198045

RESUMO

MicroRNAs (miRNAs) are a class of noncoding RNAs and function as key regulators of gene expression at the post-transcriptional level. In this study, we found that miR-495 reduces cell growth, induces apoptosis and suppresses the migration of endometrial cancer by directly inhibiting FOXC1 expression. Further analysis revealed that FOXC1 promotes growth and migration and functions as an oncogene in vitro. FOXC1 overexpression reversed the cellular responses mediated by miR-495 in endometrial cancer cells. We also found that miR-495 suppresses the growth of endometrial cancer in vivo. Altogether, these results indicate that miR-495 acts as a tumour suppressor gene by targeting FOXC1 at the post-transcriptional level in endometrial cancer.


Assuntos
Neoplasias do Endométrio/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Oncogenes , Proteínas Supressoras de Tumor/metabolismo , Regiões 3' não Traduzidas , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Regulação para Baixo , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Genes Reporter , Proteínas de Fluorescência Verde/metabolismo , Humanos , Camundongos , Camundongos Nus , Reação em Cadeia da Polimerase em Tempo Real
4.
Sci Rep ; 13(1): 743, 2023 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639415

RESUMO

It is of great significance to find new effective drugs for an adjuvant therapy targeting lung cancer to improve the survival rate and prognosis of patients with the disease. Previous studies have confirmed that certain Chinese herbal extracts have clear anti-tumor effects, and in our preliminary study, betulinaldehyde was screened for its potential anti-tumor effects. The current study thus aimed to confirm the anti-tumor effect of betulinaldehyde, using in vitro experiments to explore its underlying molecular mechanism. It was found that betulinaldehyde treatment significantly inhibited the viability, proliferation, and migration of A549 cells in a dose-dependent manner. In addition, betulinaldehyde inhibited the activation of Akt, MAPK, and STAT3 signaling pathways in A549 cells in a time-dependent manner. More importantly, betulinaldehyde also decreased the expression level of SQSTM1 protein, increased the expression level of LC3 II, and increased the autophagy flux in A549 cells. The pretreatment of A549 cells with the autophagy inhibitor, 3-methyladenine, could partially negate the anti-tumor effects of betulinaldehyde. These findings suggest that betulinaldehyde could significantly inhibit the oncological activity of A549 cells by regulating the intracellular autophagy level, making it a potentially effective option for the adjuvant therapy used to treat lung cancer in the future.


Assuntos
Aldeídos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Células A549 , Apoptose , Autofagia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Pulmonares/patologia , Transdução de Sinais , Aldeídos/farmacologia
6.
Zhonghua Yan Ke Za Zhi ; 48(2): 164-9, 2012 Feb.
Artigo em Zh | MEDLINE | ID: mdl-22490954

RESUMO

OBJECTIVE: To analyze the role of National Natural Science Foundation of China (NSFC) on the development of the discipline of Ophthalmology from 1986 to 2010. METHODS: Data on the total number of projects and funding of NSFC allocated to Ophthalmology, as well as papers published, awards, personnel training, subject construction were collected, and the role of NSFC on other sources of funding was evaluated. RESULTS: From 1986 to 2010, NSFC supported a total of 593 scientific research projects of Ophthalmology, funding a total amount of 152.44 million Yuan, among which were 371 free application projects, 156 Young Scientist Funds, 9 Key Programs, 5 National Science Fund for Distinguished Young Scholars, 3 Major international (regional) joint research programs, 1 Science Fund for Creative Research Group and 48 other projects. Over the past 25 years, the number of NSFC projects received by Ophthalmology has been an overall upward trend in the share in the Department of Life (Health) Sciences. Take the projects (186 of 292, 63.7%) as examples completed between 2002 and 2010, a total 262 papers were published in Science Citation Index (SCI) included journals and 442 papers were published in Chinese journals. Meanwhile, 8 Second prizes of National Science and Technology Progress Award and 1 State Technological Invention Award were received. As of 2010, the training of a total of more than 40 postdoctoral, more than 400 doctoral students and more than 600 graduate students have been completed. 5 national key disciplines and 1 national key laboratory have been built. Moreover, 2 "973" programs from Ministry of Science and Technology and 1 project of special fund in the public interest from Ministry of Public Health were obtained. 2 scholars were among the list of Yangtze Fund Scholars granted by Ministry of Education. CONCLUSIONS: Over the past 25 years, a full range of continuous funding from NSFC has led to fruitful results and a strong impetus to the progress of discipline of Ophthalmology.


Assuntos
Apoio Financeiro , Fundações , Oftalmologia , China , Organização do Financiamento
7.
Clin Pharmacol Drug Dev ; 11(3): 341-347, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34472200

RESUMO

We designed a study to compare the newly developed 5-mg flunarizine hydrochloride capsules (test) to that of its marketed counterpart (5-mg; reference) among healthy adult Chinese volunteers. We performed an open-label, single-center study that consisted of 2 randomized, crossover trials, including a fasting trial and a fed trial. In each part of the study, the subjects were randomly assigned to either receive the test or reference products (5-mg flunarizine) in a 1:1 ratio. Subjects then received the alternative products, following a 14-day washout period. Concentrations of plasma flunarizine were analyzed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters (noncompartmental model) were evaluated using the WinNonlin software. The analysis of variance and Food and Drug Administration bioequivalence statistical criterion of 90% confidence interval for 80% to 125% range (set at P ≤ .05) of geometric means ratios of test: reference product for peak plasma concentration, area under the plasma concentration-time curve (AUC) from time 0 to time t, and AUC from time 0 to infinity were determined. Tolerability was evaluated during the entire study period. Overall, 23 volunteers completed the fasting study, while 40 volunteers completed the fed study. The test formulation was found to be bioequivalent to the marketed formulation, as the 90% confidence interval for the ratio of geometric means of peak plasma concentration (fasting: 87.61%-101.67%; fed: 87.38%-104.06%), AUC from time 0 to time t (fasting: 89.44%-99.92%; fed: 92.65%-98.28%), and AUC from time 0 to infinity (fasting: 95.02%-104.33%; fed: 90.41%-96.96%) were within equivalence limits (80-125%) under both the fasting and fed conditions. When flunarizine was given alongside high-fat meals, time to maximum concentration was delayed ≈3.5 hours compared to fasting conditions. Meantime, high-fat meals increased its exposure by nearly 50%. Furthermore, there were no serious adverse events found among the subjects. This study confirmed that test and reference flunarizine hydrochloride capsules were bioequivalent under fasting and postprandial conditions.


Assuntos
Flunarizina , Adulto , Área Sob a Curva , Estudos Cross-Over , Meia-Vida , Voluntários Saudáveis , Humanos , Comprimidos , Equivalência Terapêutica
8.
Huan Jing Ke Xue ; 41(4): 1950-1959, 2020 Apr 08.
Artigo em Zh | MEDLINE | ID: mdl-32608704

RESUMO

Dissolved carbon (DC) is the most active carbon fraction in soils. Vegetation restoration and reconstruction accelerate the carbon cycle in arid desert regions. Studying the DC distribution in soil profiles of artificial shelterbelt under saline irrigation can provide theoretical support and decision-making basis for artificial shelterbelt management, development, and utilization in arid desert areas. In this study, we took the artificial shelterbelts drip-irrigated with five different mineralization and one shifting sandy land (CK) along the Taklimakan Desert Highway as sampling plots, analyzed and discussed the vertical distribution characteristics of soil dissolved organic carbon (SDOC) and dissolved inorganic carbon (SDIC) in the 0-1 m profiles, and further analyzed their relationships among different factors. The results showed that SDOC and SDIC of CK and shelterbelts under 2.82 g·L-1 irrigation showed an "I" type distribution with a linear function relationship. The SDOC and SDIC of four other treatments showed a "Γ" type distribution with power function relationships. The fluctuation ability and contribution degree of SDOC and SDIC of different treatments in the surface layer were higher than those in the lower layers, and the fluctuation and contribution intensity of SDOC were higher than those of SDIC. Except for 2.82 g·L-1 treatment, the average SDOC contents of other treatments were 2-4 times those of SDIC. The average SDOC content of 2.82 g·L-1 treatment was lower than CK; other treatments were 3-5 times that of CK; and the average SDIC content of all treatments increased 15.0%-57.9% than CK. For the 0-5 cm layer, SDOC content increased with the irrigation water mineralization except the 2.82 g·L-1 treatment, but SDIC content firstly increased and then decreased with increasing mineralization, and that for the 4.82 g·L-1 treatment was highest. The SDOC and SDIC were positively correlated with EC, SOC, irrigation water mineralization, SIC, and soil moisture, for which they both showed a weak positive correlation with soil moisture; they were negatively correlated with soil depth. The SDOC and SDIC showed a weak negative correlation and a weak positive correlation with pH, respectively. In summary, the mineralization of irrigation water has an important impact on the vertical distribution of SDOC and SDIC, and their distribution also has close relationships with EC, SOC, SIC, soil moisture, and soil depth, which is of great significance for plantations in extremely drought deserts.

9.
Zhonghua Yu Fang Yi Xue Za Zhi ; 43(7): 607-10, 2009 Jul.
Artigo em Zh | MEDLINE | ID: mdl-19954073

RESUMO

OBJECTIVE: To observe the alterations of saliva nitrate and nitrite level in patients with oral candidiasis. METHODS: Parotid saliva and whole saliva were collected from 33 patients and 34 healthy volunteers. Concentrations of nitrate and nitrite in saliva were determined by high-performance liquid chromatography. Follow-up observation was performed on 10 patients after treatment. The data were statistically analyzed with independent-samples t test or paired-samples t test at alpha = 0.05. RESULTS: There was significant increase of the concentrations and secretion rate of parotid saliva nitrate in patient group as compared with controls: (49.70 +/- 0.50) vs (21.51 +/- 0.60) mg/L (t = 2.692, P = 0.009) and (27.71 +/- 0.50) vs (12.55 +/- 0.60) microg/min (t = 2.554, P = 0.013), respectively. Significantly increased concentrations and secretion rate of nitrate and nitrite [nitrate: (6.46 +/- 0.94) vs (1.11 +/- 0.70) mg/L (t = 3.792, P = 0.000); nitrite: (8.48 +/- 0.58) vs (3.39 +/- 0.53) mg/L (t = 2.888, P = 0.005); nitrate secretion rate: (10.57 +/- 0.91) vs (2.10 +/- 0.74) microg/min (t = 3.464, P= 0.001); nitrite secretion rate: (13.91 +/- 0.55) vs (6.42 +/- 0.58) microg/min (t = 2.397, P = 0.020)] were revealed in whole saliva of patients group. Significantly decreased nitrate and nitrite levels were also observed in patients after treatment, especially the changes of parotid saliva nitrate secretion rate [(37.50 +/- 0.50) vs (14.34 +/- 0.64) microg/min (t = 3.142, P = 0.012)], whole saliva nitrate [(14.29 +/- 1.01) vs (2.59 +/- 1.03) mg/L (t = 3.475, P = 0.007)] and whole saliva nitrate secretion rate [(25.97 +/- 0.93) vs (4.12 +/- 1.00) microg/min (t = 3.922, P = 0.003)]. CONCLUSION: The present study revealed the significant increase of salivary nitrate and nitrite level in patients with oral candidiasis is considered to be associated with the host defense reaction.


Assuntos
Candidíase Bucal/metabolismo , Nitratos/metabolismo , Nitritos/metabolismo , Saliva/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Exp Ther Med ; 17(4): 2945-2952, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30936964

RESUMO

Diabetic retinopathy (DR) is a chronic and progressive complication of diabetes mellitus. DR impairs sight due to neuronal and vascular dysfunction in the retina. It is critical to investigate the pathogenesis of DR to develop effective treatment. In the present study, a streptozotocin (STZ)-induced diabetic rat model was constructed and the expression of microRNA (miR)-204-5p and vascular endothelial growth factor (VEGF) were determined. Immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were employed to detect the effects of miR-204-5p on the expression of microtubule-associated protein 1 light chain 3 (LC3B). RT-qPCR analysis demonstrated that miR-204-5p and VEGF were significantly upregulated in the retina tissue of diabetic rats compared with the control group (P<0.01). Immunohistochemistry and western blotting revealed that the protein expression levels of LC3B-II and the ratio of LC3B-II/LC3B-I were significantly suppressed in the diabetes group compared with the control (P<0.01). In retinal tissues, anti-miR-204-5p treatment significantly enhanced the protein expression levels of LC3B-II and the ratio of LC3B-II/LC3B-I and these levels were significantly reduced in response to miR-204-5p mimic treatment compared with the negative miR control (P<0.01). In rat retinal endothelial cells isolated from diabetic rats, anti-miR-204-5p treatment increased the number of autophagic vacuoles, and significantly promoted LC3B-II expression and the LC3B-II/LC3B-I ratio compared with the negative control (P<0.01). The results of the present study revealed that miR-204-5p downregulated the expression of LC3B-II to inhibit autophagy in DR. Therefore, miR-204-5p may be considered as a novel effective therapeutic target during the development of DR.

11.
J Ovarian Res ; 12(1): 118, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783885

RESUMO

Ovarian cancer (OC) is a type of gynaecological malignancy with high mortality in females. Serous ovarian cancer (SOC) is a distinct subtype of OC with poor early diagnosis. Given the limitations of traditional therapies, such as chemotherapy, targeted treatment is therefore a promising therapy to improve the survival rate of SOC patients. Cyclophilin A (CYPA) is a member of Cyclophilin family and thought to participates in multiple cellular processes such as cell transduction and immune modulation. Recently, various of studies indicated that CYPA has critical impact on cancer progression. CYPA could regulate cell proliferation, invasion, and chemoresistance of multiple types of cancers. However, it is still unclear whether it could affect ovarian cancer. In this study, we demonstrated that CYPA was highly expressed in SOC tissues compared with adjacent tissues. Further, CYPA was significantly associated with clinical stage and lymphnode metastasis of SOC patients. Additionally, data indicated that knockdown of CYPA by its shRNA dramatically reduces migration and invasion capacity of SOC cells in vitro and blocks tumor metastasis in vivo. Our study investigates the involvement of CYPA in the progression and metastasis of SOC, and therefore provides CYPA as a promising therapeutic target for SOC treatment.


Assuntos
Ciclofilina A/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Neoplasias Ovarianas/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Ciclofilina A/genética , Cistadenocarcinoma Seroso/patologia , Progressão da Doença , Feminino , Humanos , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , RNA Interferente Pequeno/genética
12.
Oncol Lett ; 18(4): 3792-3802, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31579409

RESUMO

The present study focused on exploring the inhibitory mechanism of microRNA (miR)-23a in endometrial cancer. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to investigate miR-23a expression in endometrial tissues and endometrial cancer cells. A colony formation assay using crystal violet staining was performed to compare cell proliferation, while wound-healing and Transwell assays were performed to compare cell migration and invasion. Subsequently, bioinformatics and a luciferase reporter gene assay were used to investigate the effect of miR-23a on sine oculis homeobox homolog 1 (SIX1) expression, and the biological function of SIX1 was analyzed. Additionally, a nude mouse tumorigenicity assay was performed to test the inhibitory effect of miR-23a and Taxol® therapy in endometrial cancer. Finally, immunohistochemistry and RT-qPCR were used to explore the association between miR-23a and SIX1 expression in endometrial cancer tissues. miR-23a was underexpressed in endometrial cancer tissues compared with in para-carcinoma tissues, and the overexpression of miR-23a inhibited proliferation and invasion of endometrial cancer cells. Furthermore, SIX1 was demonstrated to be a downstream target of miR-23a, and miR-23a reduced SIX1 expression. Additionally, SIX1 inversely promoted cell proliferation, migration and invasion. In addition, the effects of reduced cell proliferation and increased cell invasion following miR-23a overexpression could be reversed by adding SIX1 to in vitro culture. Furthermore, the inhibitory effect of miR-23a and Taxol therapy, which reduced SIX1 expression in endometrial cancer, was demonstrated in vivo. Finally, a negative association between miR-23a and SIX1 expression was demonstrated in endometrial cancer tissues. The results of the present study revealed that miR-23a may inhibit endometrial cancer development by targeting SIX1.

13.
Zhonghua Yan Ke Za Zhi ; 44(9): 839-44, 2008 Sep.
Artigo em Zh | MEDLINE | ID: mdl-19175165

RESUMO

OBJECTIVE: To understand the status of basic research work in the field of ophthalmology by analyzing the projects funded by the National Natural Science Foundation of China (NSFC) from the year of 1986 to 2007, and offer as a reference to the ophthalmologists and researchers. METHODS: NSFC supported ophthalmology projects in the 22 year's period were collected from the database of NSFC. The field of funded projects, the research team and their achievements were analyzed. RESULTS: There were 228 applicants from 47 home institutions were funded in the field of ophthalmology during the past 22 years, 323 projects funded with 66.74 million Yuan in total, in which 165 projects were fulfilled before the end of 2006. The applied and funded projects mainly focus on six different kinds of research area related to retinal diseases, corneal diseases, glaucoma, optic nerve diseases, myopia and cataract, and 70% of them were basic research in nature. As a brief achievement of 165 fulfilled projects, more than 610 papers were published in domestic journals, over 140 papers were published in Science Citation Index journals, more than 600 people were trained, and over 20 scientific awards were obtained. CONCLUSION: The number of funded projects and achievement of fulfilled projects in the discipline of ophthalmology gradually increased over the past two decades, the research fields were concentrated in certain diseases. NSFC has played an important role in promoting the development of ophthalmology research and bringing up specialists in China. However, clinical research, continuously research, transforming from basic research to clinic applications and multidisciplinary cross studies should be strengthened.


Assuntos
Fundações , Oftalmologia/economia , China
15.
Am J Transl Res ; 9(3): 1127-1138, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28386339

RESUMO

Cisplatin (CDDP) resistance becomes a large obstacle of the beneficial therapy for patients with ovarian cancer. MicroRNAs (miRNAs) act as post-transcriptional regulators of multiple genes' expression and have been reported to be involved in multi-drug resistance. The purpose of this study was to determine the roles and molecular mechanism of miR-490-3p in the CDDP resistance in ovarian cancer. We found that miR-490-3p was downregulated in CDDP-resistant OVCAR3/CDDP and SKOV3/CDDP cells, which was due to the hypermethylation of miR-490-3p promoter. Functional studies demonstrated that miR-490-3p increased the cell response to CDDP in OVCAR3, SKOV3 and CDDP-resistant cells, while miR-490-3p inhibition resulted in opposite effects. Luciferase assay, real-time PCR and Western blot as well as immunohistochemistry validated that ABCC2 was a direct target of miR-490-3p and miR-490-3p downregulated ABCC2 expression via binding to its 3'UTR. Importantly, silencing of ABCC2 alleviated CDDP resistance induced by miR-490-3p inhibition, while ABCC2 overexpression restored CDDP resistance inhibited by miR-490-3p. In vivo study showed that miR-490-3p enhanced the cytotoxicity of CDDP. Finally, we found that miR-490-3p was downregulated in CDDP-resistant ovarian cancer tissues, while ABCC2 was upregulated. In conclusion, our data indicate that miR-490-3p enhances CDDP sensitivity of ovarian cancer cells through downregulating ABCC2 expression, and suggest that delivery of miR-490-3p might be a potential therapeutic strategy for patients with CDP-resistant ovarian cancer.

16.
Am J Transl Res ; 9(8): 3541-3557, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28861147

RESUMO

OBJECT: MicroRNAs (miRNAs) play key roles in progression of cervical cancer. In the present study, we investigated the role of miR-214 in the process of migration, invasion and drug sensitivity to cisplatin in cervical cancer. METHODS: We detected the differential expression of miR-214 in 19 cases cervical cancer tissues and normal tissues as well as 4 cervical cancer cells and one normal cervical cells by Real-time PCR. Then, wound healing assay, transwell invasion assay and MTT were used to detect the effects of migration, invasion and sensitivity to cisplatin of cervical cancer when miR-214 was overexpressed. Western blot, immunofluorescence and Flow Cytometry were used to detect the mechanism of migration, invasion and sensitivity to cisplatin. Next, bioinformatics analysis was used to find the target of miR-214. Through the luciferase reporter assay, Real-time PCR and western blot, we confirmed the binding relationship of miR-214 and FOXM1. In cervical cancer tissues, the expression of FOXM1 was detected by western blot and Immunohistochemistry. We also knocked down FOXM1 in cervical cancer cells, wound healing assay, transwell invasion assay and MTT were performed to detect the migration, invasion and sensitivity to cisplatin abilities of FOXM1. Western blot and Flow Cytometry were used to detect the mechanism of migration, invasion and sensitivity to cisplatin by FOXM1. Finally, we performed rescue expriments to confirm the function relationship between miR-214 and FOXM1. RESULTS: 1. Our results showed that miR-214 was frequently downregulated in tumor tissues and cancer cells especially in CIN III and cervical cancer stages. 2. Overexpression of miR-214 significantly inhibited migration and invasion of cervical cancer cells and prompted the sensitivity to cisplatin. 3. FOXM1 was identified as a target of miR-214 and down-regulated by miR-214. 4. Knocking down FOXM1 could inhibited migration and invasion of cervical cancer cells and prompted the sensitivity to cisplatin. 5. FOXM1 was upregulated in tumor tissues. 6. The mechanism of migration, invasion and sensitivity to cisplatin were the resluts of changes of EMT and apoptosis. 7. The restoration of FOXM1 expression can counteract the effect of miR-214 on cell migration, invasion and sensitivity to cisplatin of cervical cancer cells. CONCLUSIONS: These findings indicate that miR-214 acts as a tumor suppressor during the process of migration, invasion and drug sensitivity through targeting FOXM1, suggesting miR-214 as a potential new diagnostic and therapeutic target for the treatment of cervical cancer.

18.
FEBS J ; 280(16): 3768-79, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23731275

RESUMO

MicroRNAs (miRNAs) are post-transcriptional inhibitor regulators of gene expression that act by directly binding complementary mRNA and are key determinants of cancer initiation and progression. In this study, we revealed a role for the tumor-suppressor miRNA miR-503 in endometrioid endometrial cancer (EEC) cells. The miR-503 expression level gradually decreases across normal endometrial tissues, endometrial tissues with complex atypical hyperplasia, and EEC tissues. A relatively high level of miR-503 in EEC tissues indicates a longer survival time in EEC patients. The expression of a cell cycle-associated oncogene encoding cyclin D1 (CCND1) was inversely correlated with miR-503 expression in EEC tissues and cell lines. CCND1 has a binding sequence of miR-503 within its 3' untranslated region, and was confirmed to be a direct target of miR-503 by the fluorescent reporter assays. Increasing the miR-503 level in EEC cells suppressed cell viability, colon formation activity and cell-cycle progression, and the inhibited oncogenic phenotypes induced by miR-503 were alleviated by ectopic expression of CCND1 without the untranslated region sequence. Furthermore, in vivo studies also suggested a suppressive effect of miR-503 on EEC cell-derived xenografts. miR-503 increased in cell cycle-arrested EEC cells, and was restored to a normal level in EEC cells after cell cycle re-entry, while CCND1 displayed the opposite expression pattern. Collectively, this study suggested that miR-503 plays a tumor-suppressor role by targeting CCND1. Abnormal suppression of miR-503 leads to an increase in the CCND1 level, which may promote carcinogenesis and progression of EEC.


Assuntos
Carcinoma Endometrioide/metabolismo , Ciclo Celular , Ciclina D1/antagonistas & inibidores , Neoplasias do Endométrio/metabolismo , Endométrio/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Idoso , Animais , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/prevenção & controle , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/genética , Ciclina D1/metabolismo , Hiperplasia Endometrial/metabolismo , Hiperplasia Endometrial/patologia , Hiperplasia Endometrial/prevenção & controle , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/prevenção & controle , Endométrio/patologia , Feminino , Técnicas de Transferência de Genes , Genes Reporter , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Zhonghua Liu Xing Bing Xue Za Zhi ; 33(1): 32-6, 2012 Jan.
Artigo em Zh | MEDLINE | ID: mdl-22575106

RESUMO

OBJECTIVE: This study was operated to investigate the association between urinary albumin-to-creatinine ratio (UACR) and physical situations as hypertension and prehypertension among women. METHODS: Blood pressure, height, weight and waist circumference were measured and factors such as cigarette smoking, alcohol intake, family history of hypertension, were investigated. Blood glucose and lipid, serum uric acid, urinary albumin and urinary creatinine were tested on 1796 women aged ≥ 30 years living in the Jinchang district of Suzhou. Associations between UACR and hypertension as well as prehypertension were analyzed, by using ordinal multinomial logistic regression models. RESULTS: The mean levels of UACR were 15.54 (7.67, 32.53), 9.01 (5.45, 18.06), 7.13 (4.60, 12.50) mg/g and the rates of higher UACR were 27.57%, 13.42%, 9.61% in hypertensive, pre-hypertensive and normotensive subjects, respectively, with significant differences noticed among the three groups (P < 0.05). The average systolic blood pressure/diastolic blood pressure appeared to be 125.3/80.9, 128.8/82.7, 130.8/84.0 and 135.1/85.9 mm Hg for participants with UACR in the first, second, third and fourth quartile, respectively. The risks of prehypertension or hypertension increased with increasing UACR levels. Dose-response relationship was seen between UACR and risks of prehypertension or hypertension. Multivariable adjusted odds ratios (95%CI) of prehypertension or hypertension in the upper quartiles of UACR were 1.32 (1.02, 1.70), 1.72 (1.32, 2.24), and 2.37 (1.80, 3.11), respectively, when compared with the lowest quartile. CONCLUSION: Elevated UACR was associated with both hypertension and prehypertension among women.


Assuntos
Albuminúria/complicações , Creatinina/urina , Pré-Hipertensão/urina , Adulto , Feminino , Humanos , Pessoa de Meia-Idade
20.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 46(10): 616-20, 2011 Oct.
Artigo em Zh | MEDLINE | ID: mdl-22321633

RESUMO

OBJECTIVE: To investigate the effect of National Natural Science Foundation of China (NSFC) on the progress of dental research from 1986 to 2010. METHODS: The data regarding the NSFC allocated to dental and craniofacial research from 1986 to 2010 were collected. Total expenses and numbers of the majority of programs and the situation of completed program finished in recent 7 years were provided. RESULTS: From 1986 to 2010, a total of 922 projects and 204 401 thousands Chinese Yuan supported by NSFC were allocated to dental research. The detailed allocations were as follows: general program (564), young scientists fund (258), regional fund (40), key program (11), national science fund for distinguished young scholars (5), major international (regional) joint research program (1), others (43). The grants of talent training increased dramatically. Taking the projects (307) completed between 2003 and 2009 for example, 307 papers were published in Science Citation Index (SCI) included journals and 1049 papers were published on Chinese journals. By the time of completion of the projects, 39 post-doctoral students, 590 students for PhD degree and 670 students for Master degree had been trained. CONCLUSIONS: Over the past 25 years, the continuous increase of NSF on dental research has led to substantial achievement, resulting in great progress of dental oral-cranio-facial research.


Assuntos
Economia em Odontologia , Apoio Financeiro , Fundações , Medicina Bucal , Apoio à Pesquisa como Assunto , China , Organização do Financiamento , Fundações/economia , Medicina Bucal/economia , Apoio à Pesquisa como Assunto/economia , Estudos Retrospectivos
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