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1.
Mol Ther Oncolytics ; 23: 220-230, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34729397

RESUMO

The progression of breast cancer is closely related to obstructive sleep apnea-hypopnea syndrome (OSAHS). Low concentrations of cannabinoids promote tumor proliferation. However, the role of cannabinoid receptors (CBs) in chronic intermittent hypoxia (CIH)-induced breast cancer has not been reported. The migration and invasion of breast cancer cell lines (MCF-7 and T47D) were measured by scratch assay and transwell assay. Gene and protein expressions were analyzed by qPCR and western blotting. Tumor xenograft mice model were established to evaluate the function of CBs. We observed that chronic hypoxia (CH) and CIH increased CBs expression and promoted migration and invasion in breast cancer. Mice grafted with MCF-7 exhibited obvious tumor growth, angiogenesis, and lung metastasis in CIH compared with CH and control. In addition, CIH induced CBs expression, which subsequently activated insulin-like growth factor-1 receptor (IGF-1R)/AKT/glycogen synthase kinase-3ß (GSK-3ß) axis. Knockdown of CBs alleviated CIH-induced migration and invasion of breast cancer in vitro. Furthermore, CIH exaggerated the malignancy of breast cancer and silencing of CBs suppressed tumor growth and metastasis in vivo. Our study contributed to understanding the role of CIH in breast cancer development modulation.

2.
Aging (Albany NY) ; 12(5): 4082-4092, 2020 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-32112550

RESUMO

Although observational studies have reported a positive association between obstructive sleep apnea syndrome (OSAS) and breast cancer (BC) risk, causality remains inconclusive. We aim to explore whether OSAS is associated with etiology of BC by conducting a two-sample Mendelian randomization (MR) study in a Chinese population and Asian population from the Breast Cancer Association Consortium (BCAC). We found a detrimental causal effect of OSAS on BC risk in the primary analysis of our samples (IVW OR, 2.47 for BC risk per log-odds increment in OSAS risk, 95% CI = 1.86-3.27; P = 3.6×10-10). This was very similar to results of the direct observational case-control study between OSAS and BC risk (OR = 2.80; 95% CI = 2.24-3.50; P =1.4×10-19). Replication in the Asian population of the BCAC study also supported our results (IVW OR, 1.33 for BC risk per log-odds increment in OSAS risk, 95% CI = 1.13-1.56; P = 0.0006). Sensitivity analyses confirmed the robustness of our findings. We provide novel evidence that genetically determined higher risk of OSAS has a causal effect on higher risk of BC. Further studies focused on the mechanisms of the relationship between OSAS and breast carcinogenesis are needed.


Assuntos
Neoplasias da Mama/genética , Genótipo , Polimorfismo de Nucleotídeo Único , Apneia Obstrutiva do Sono/genética , Alelos , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Feminino , Loci Gênicos , Humanos , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Risco
3.
Int J Mol Med ; 40(1): 137-145, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28560446

RESUMO

This study aimed to explore the underlying marker genes associated with hypertension by bioinformatics analyses. A gene expression profile (GSE54015) was downloaded. The differentially expressed genes (DEGs) between the normotensive female (NF) and hypertensive female (HF), and between the normotensive male (NM) and hypertensive male (HM) groups were analyzed. Gene Ontology (GO) and pathway enrichment analyses were performed, followed by protein-protein interaction (PPI) network construction. The transcription factors (TFs), and the common DEGs between the HF and HM groups were then analyzed. In total, 411 DEGs were identified between the HF and NF groups, and 418 DEGs were identified between the HM and NM groups. The upregulated DEGs in the HF and HM groups were enriched in 9 GO terms, including oxidation reduction, such as cytochrome P450, family 4, subfamily b, polypeptide 1 (Cyp4b1) and cytochrome P450, family 4, subfamily a, polypeptide 31 Cyp4a31). The downregulated DEGs were mainly enriched in GO terms related to hormone metabolic processes. In the PPI network, cytochrome P450, family 2, subfamily e, polypeptide 1 (Cyp2e1) had the highest degree in all 3 analysis methods in the HF group. Additionally, 4 TFs were indentified from the 2 groups of data, including sterol regulatory element binding transcription factor 1 (Srebf1), estrogen receptor 1 (Esr1), retinoid X receptor gamma (Rxrg) and peroxisome proliferator-activated receptor gamma (Pparg). The intersection genes were mainly enriched in GO terms related to the extracellular region. On the whole, our data indicate that the DEGs, Cyp4b1, Cyp4a31 and Loxl2, and the TFs, Esr1, Pparg and Rxrg, are associated with the progression of hypertension, and may thus serve as potential therapeutic targets in this disease.


Assuntos
Regulação da Expressão Gênica , Ontologia Genética , Hipertensão/genética , Animais , Biologia Computacional , Feminino , Marcadores Genéticos , Hipertensão/metabolismo , Masculino , Camundongos
4.
Chin Med J (Engl) ; 125(13): 2250-4, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22882843

RESUMO

BACKGROUND: Early loading statin therapy before percutaneous coronary intervention (PCI) is associated with reduced mortality and periprocedural myocardial injury. The aim of this study was to study the effect of rosuvastatin loading therapy before PCI in female patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). METHODS: Consecutive 117 female patients with NSTEACS were randomly assigned to either the group of rosuvastatin loading before PCI (20 mg 12 hours before angioplasty procedure, with a further 10 mg dose 2 hours before procedure, the loading dose group, n = 59) or the no rosuvastatin treatment group before PCI (control group, n = 58). Periprocedural myocardial injury, periprocedural changes of high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-a in serum and the incidence of major adverse cardiac events (MACE) 3 months and 6 months later were assessed. RESULTS: The incidence of periprocedural myocardial injury was higher in control group than loading dose group (CKMB: 10.17% vs. 25.86%, P = 0.027; Troponin I: 11.86% vs. 29.31%, P = 0.019). MACE occurred in 1.69% of patients in loading dose group and 12.07% of those in control group 3 months after procedure (P = 0.026), 3.39% vs. 17.24% at 6 months (P = 0.014). The levels of hs-CRP, IL-1, IL-6, and TNF-a in serum were not significantly different between the two groups before PCI, but after PCI they were significantly higher in control group. CONCLUSIONS: High-dose rosuvastatin loading before PCI significantly reduced periprocedural myocardial injury and periprocedural inflammation cytokines release and improved 3-month and 6-month clinical outcomes in female patients with NSTEACS who underwent PCI.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Fluorbenzenos/uso terapêutico , Intervenção Coronária Percutânea/métodos , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Síndrome Coronariana Aguda/metabolismo , Idoso , Proteína C-Reativa/metabolismo , Relação Dose-Resposta a Droga , Feminino , Fluorbenzenos/administração & dosagem , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Pirimidinas/administração & dosagem , Rosuvastatina Cálcica , Sulfonamidas/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismo
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 27(9): 761-4, 2006 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-17299959

RESUMO

OBJECTIVE: To study the relationship between serum iron(SI) and essential hypertension (EHT) based on population-based samples. METHODS: Using clustering multistage sampling method, all the people above 18 years old in the target population were investigated. Blood pressure was measured and the questionnaire was used to find out related factors. Five milliliters fast vein blood were drawn and the serum were used for testing on serum iron (SI) and other elements such as blood sugar, cholesterol (CHOL), triglyceride (TG), high density lipoprotein(HDL-C), low density lipoprotein (LDL-C), serum sodium, serum potassium, serum calcium etc. A case control study was carried out with EHT patients from the selected population as case group, and the other healthy peoples as controls. Database was created by Fox Pro and SPSS 10.0 was used for statistical analysis. RESULTS: The concentrations of SI, with (17.75 +/- 7.66) micromol/ L in EHT group and (17.23 +/- 7.83) micromol/L in control group, showed statistical difference (P < 0.05) between the two groups. The concentrations of SI also showed statistical difference (P < 0.05) between the high DBP and normal group with the average level as (17.84 +/- 7.58) micromol/L in high DBP group and (17.26 +/- 7.85) micromol/L in normal group. Data from monovariate analysis showed that the increase of SI was a risk factor for EHT, DBP and SBP. By multivariate analysis for EHT, while SI still existed in the model (OR = 1.296, 95% CI: 1.057-1.590), but for SBP the results almost remained the same (OR = 1.285, 95% CI:1.102-1.498). CONCLUSION: Data from the results showed that SI was probably a risk factor for EHT.


Assuntos
Hipertensão/sangue , Ferro/sangue , Estudos de Casos e Controles , China/epidemiologia , Humanos , Hipertensão/epidemiologia , Fatores de Risco
7.
Zhonghua Liu Xing Bing Xue Za Zhi ; 24(7): 547-50, 2003 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-12975004

RESUMO

OBJECTIVE: To investigate the prevalence state of essential hypertension in the countryside of Zhangwu county, Liaoning province to confirm whether this county is the high prevalence region of essential hypertension. METHODS: Five thousand, two hundred and eight 15-year olds or older were sampled by means of whole population random sampling. Blood pressure was measured and the related risk factors were investigated with the uniform questionnaire. SPSS 10.0 of statistical software was used for data analysis. RESULTS: The standardized prevalence rate of hypertension was 35.0% at this region, 40.0% in male, 32.0% in female. The prevalence rates of hypertension were increased with the increasing of the age in both males and females. There were significant statistically differences in the prevalence rates of hypertension between the different age groups, different countrysides and different villages. The standardized prevalence rate of hypertension were 43.0% the highest and 29.0% lowest respectively in the countryside, with prevalence rates, were 59.4% highest and 26.9% lowest respectively in the village. In all the patients with hypertension, 72.0% having hypertension II, III. CONCLUSION: The countryside of Zhangwu county was a high prevalence region of essential hypertension which was unusual in our country. The reason of this status was still unknown which called for further study.


Assuntos
Hipertensão/epidemiologia , Adolescente , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Hipertensão/etiologia , Hipertensão/prevenção & controle , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , População Rural , Estudos de Amostragem , Inquéritos e Questionários
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