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1.
Gene ; 710: 316-323, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31200086

RESUMO

AIM: To investigate the correlation between the polymorphism of estrogen receptor ß gene (ESR2) rs3020450 and cancer susceptibility, and explore the epidemiological significance and the effect of ESR2 expression levels on the prognosis of ovarian cancer. METHODS: Based on meta-analysis the association between ESR2 rs3020450 polymorphism and cancer susceptibility was estimated and a case-control design was used to verify this result in ovarian cancer. The epidemiological effect of ESR2 rs3020450 polymorphism was assessed by attributable risk percentage (ARP) and population attributable risk percentage (PARP). Kaplan Meier plotters were used to evaluate overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients and GEPIA for the differential expression of ESR2 levels in ovarian cancer and adjacent normal tissues. RESULTS: The pooled analysis indicated no significant correlation between the ESR2 rs3020450 polymorphism and the cancer susceptibility. In the stratified analysis by cancer types, significantly decreased risk was found in ovarian cancer (AG vs GG: OR = 0.73, 95%CI: 0.53-0.97, P = 0.03). Unconditional logistic regression results of case-control study in ovarian cancer observed significant differences in all comparisons (AG vs GG: OR = 0.81, 95%CI: 0.62-0.98, P = 0.04; AA vs GG: OR = 0.63, 95%CI: 0.42-0.92, P = 0.01 and AG + AA vs GG: OR = 0.73, 95%CI: 0.53-0.96, P < 0.001). Based on meta-analysis and case-control pooled results, ARP and PARP were evaluated respectively in allele (21.95% and7.97%), heterozygote (36.99% and 12.11%) and dominant model (36.84% and 12.97%) of rs3020450 polymorphism in ovarian cancer. The expression levels of ESR2 in normal tissues was significantly higher than that in cancer tissues (OV, Median, 4.7:0.21), and significant correlations were observed between high ESR2 expression levels and long OS (HR = 0.80, 95%CI: 0.70-0.92, P = 0.002) and PFS (HR = 0.767, 95%Cl: 0.67-0.88, P < 0.001). CONCLUSION: Our results indicated that ESR2 rs3020450 polymorphism was associated with ovarian cancer risk from epidemiological perspective, and high ESR2 expression levels was associated with long survival in patients with ovarian cancer.


Assuntos
Regulação para Baixo , Receptor beta de Estrogênio/genética , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Metanálise como Assunto , Pessoa de Meia-Idade , Prognóstico
2.
BMC Public Health ; 19(1): 281, 2019 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-30849990

RESUMO

BACKGROUND: Few studies in China have examined personal ultraviolet radiation (UVR) exposure using polysulfone dosimetry. METHODS: In this study, 93 mother and adolescent child pairs (N = 186) from two locations in China, one rural (higher latitude) and one urban (lower latitude), completed 3 days of personal UVR dosimetry and a sun/clothing diary, as part of a larger pilot study. RESULTS: The average daily ambient UVR in each location as measured by dosimetry was 20.24 Minimal Erythemal Doses (MED) in the rural location and 20.53 MED in the urban location. Rural mothers had more average daily time outdoors than urban mothers (5.5 h, compared with 1.5 h, in urban mothers) and a much higher daily average personal UVR exposure (4.50 MED, compared with 0.78 MED in urban mothers). Amongst adolescents, rural males had the highest average daily personal UVR exposure, followed by rural females, urban females and urban males (average 2.16, 1.05, 0.81, and 0.48 MED, respectively). CONCLUSIONS: Although based on small numbers, our findings show the importance of geographic location, age, work/school responsibilities, and sex of the adolescents in determining personal UVR exposure in China. These results suggest that latitude of residence may not be a good proxy for personal UVR exposure in all circumstances.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Exposição à Radiação/estatística & dados numéricos , Raios Ultravioleta , Adolescente , Criança , China , Estudos de Coortes , Feminino , Humanos , Masculino , Mães , Projetos Piloto , Radiometria , População Rural
3.
Front Oncol ; 8: 252, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30062087

RESUMO

Background: Numerous studies have demonstrated the presence of microRNA-124 abnormalities involving gene expression, methylation, and single nucleotide polymorphism (SNP) in multiple and diverse cancers, but the prognostic value of these abnormalities in cancer remains inconclusive. Objective: The aim of this study is to determine the prognostic value of miR-124 in cancer. Methods: We scrutinized the electronic databases and estimate the association between miR-124 expression, methylation and single nucleotide polymorphisms (SNPs), and prognosis in cancers. The pooled hazard ratios with 95% confidence intervals (CIs) for overall survival (OS), and disease-free survival/recurrence-free survival (RFS)/progression-free survival (PFS) were calculated to estimate the effects of miR-124 expression, methylation, and SNPs on cancer prognosis. The Quality in Prognosis Studies and Newcastle-Ottawa Scale were utilized to assess the quality of included studies. Results: A total of 20 studies involving 3,574 participants were analyzed in evidence synthesis. Our findings showed that the low expression of miR-124 was significantly associated with poor OS (HR = 2.37, 95% CI: 1.91-2.94, P = 0.00; HR = 3.10, 95% CI: 2.04-4.70, P = 0.00) and PFS/RFS (HR = 2.21, 95% CI: 1.50-3.26, P = 0.00; HR = 2.12, 95% CI: 1.20-3.74, P = 0.00). The hyper-methylation of miR-124 was associated with poor OS (HR = 2.09, 95% CI: 1.48-2.95, P = 0.00) and PFS (HR = 3.70, 95% CI: 1.72-7.97, P = 0.00) (Table 3). The patients carrying with Allele C of miR-124 rs5315649 had a worse OS (HR = 1.50, 95% CI: 1.09-2.07, P = 0.00) and PFS (HR = 1.67, 95% CI: 1.20-2.33, P = 0.00) than the carriers with Allele G. Conclusion: The low expression and hyper-methylation of miR-124 was strongly associated with poor prognosis, and genetic variations of miR-124 rs531564 affected prognosis in cancer patients.

4.
Nutr Today ; 53(3): 104-114, 2018 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29930434

RESUMO

This article reports the study design, methodological issues and early results of a pilot study testing methods for collecting nutrition, physical activity, and ultraviolet (UV) radiation exposure data in a groundbreaking study in China. Epidemiological studies suggest that exposures across the entire life course, including in utero, early childhood, and adolescence, may be important in the etiology of adult cancers and other chronic diseases. The Chinese Children and Families Cohort Study intends to follow-up subjects from the 1993 to 1995 Community Intervention Program of folic acid supplementation for the prevention of neural tube defects. This cohort is unique in that only folic acid exposure during pregnancy varies between groups as other supplements were not available, and there were nutrient deficiencies in the populations. Prior to launching a large-scale follow-up effort, a pilot study was conducted to assess the feasibility of recontacting original study participants to collect extensive diet, physical activity, and UV radiation exposure data in this population. The pilot study included 92 mothers and 184 adolescent children aged 14 to 17 years from 1 urban and 1 rural Community Intervention Program site. Subjects completed a Food Frequency Questionnaire, a 3-day food record, a physical activity questionnaire, a 3-day sun exposure diary together with 3 days of personal UV dosimetry, and 7 days of pedometry measurements and provided blood, saliva, and toenail samples. Grip strength and body composition measurements were taken, and ambient solar UV radiation was monitored in both study sites. While most of the assessments were successful, future studies would likely require different dietary intake instruments. The purpose of this report is to describe the study design and methodological issues emerging from this pilot work relevant for the follow-up of this large birth cohort.

5.
Life Sci ; 203: 92-98, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29679701

RESUMO

AIMS: PMNs (polymorphonuclear neutrophil) play important roles in early stage of inflammation induced ARDS (Acute Respiratory Distress Syndrome). Both HBP (Heparin-Binding Protein) released from active PMNs and ß2 integrins on the surface of PMNs are involved in vascular leakage. The role and relationship of HBP and ß2 integrins on ARDS still requires study. MATERIALS AND METHODS: We established ARDS model using C57BL/6 mice with cecal ligation and puncture and eliminating HBP and ß2 integrin with respective antibodies. The mice were also challenged with HBP endotracheal instillation. Histopathology score, lung wet/dry ratio, bronchoalveolar lavage fluid protein, plasma HBP and ß2 integrin on PMNs from all groups were measured. ß2 integrin and HBP were analyzed after incubated PMNs with streptococcal and pretreat with anti-CD18, anti-HBP, 1-phosphatidylinositol 3-kinase (PI3K) inhibitor and p38 mitogen-activated protein kinase (MAPK) inhibitor. KEY FINDINGS: All lung injury indicatrix accompanied with HBP and ß2 integrin elevated in CLP group, and HBP and ß2 integrin were in correlation with each other and both were in correlation with the severity of lung injury. Endotracheal instillation HBP induced lung injury in CLP mice. Inhibiting both HBP and integrin ameliorated lung injury. HBP release was suppressed by inhibiting integrin and PI3K pathway, while integrin level did not decrease after eliminating HBP. SIGNIFICANCE: Both HBP and ß2 integrin play important roles in ARDS. HBP released from PMNs is ß2 integrin-PI3K signaling pathway dependent process revealing potential novel therapeutic targets for ARDS treatment.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas Sanguíneas/metabolismo , Antígenos CD18/metabolismo , Proteínas de Transporte/metabolismo , Modelos Animais de Doenças , Ligadura/efeitos adversos , Neutrófilos/patologia , Edema Pulmonar/patologia , Síndrome do Desconforto Respiratório do Adulto/patologia , Animais , Líquido da Lavagem Broncoalveolar , Ceco/cirurgia , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Edema Pulmonar/etiologia , Edema Pulmonar/metabolismo , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/metabolismo , Transdução de Sinais
6.
Lancet Respir Med ; 6(6): 421-430, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29650407

RESUMO

BACKGROUND: Because of the rapid change in economic development and lifestyle in China, and the ageing population, concerns have grown that chronic obstructive pulmonary disease (COPD) could become epidemic. An up-to-date nationwide estimation of COPD prevalence in China is needed. METHODS: We did a cross-sectional survey of a nationally representative sample of individuals from mainland China aged 40 years or older. The primary outcome was COPD, defined according to the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) lung function criteria. FINDINGS: Between Dec 29, 2014, and Dec 31, 2015, 66 752 adults were recruited to the study population. The estimated standardised prevalence of COPD was 13·6% (95% CI 12·0-15·2). The prevalence of COPD differed significantly between men and women (19·0%, 95% CI 16·9-21·2 vs 8·1%, 6·8-9·3; p<0·0001), mainly because of a significant difference in smoking status between men and women (current smokers 58·2% vs 4·0%). The prevalence of COPD differed by geographic region, with the highest prevalence in southwest China (20·2%, 95% CI 14·7-25·8) and the lowest in central China (10·2%, 8·2-12·2). Among adults with COPD, 56·4% (95% CI 53·7-59·2) had mild disease (GOLD stage I), 36·3% (34·3-38·3) had moderate disease (GOLD stage II), 6·5% (5·5-7·4) had severe disease (GOLD stage III), and 0·9% (0·6-1·1) had very severe disease (GOLD stage IV). INTERPRETATION: In a large, nationally representative sample of adults aged 40 years or older, the estimated overall prevalence of COPD in China in 2014-15 was 13·6%, indicating that this disease has become a major public-health problem. Strategies aimed at prevention and treatment of COPD are needed urgently. FUNDING: Chinese Central Government, the Ministry of Science and Technology of The People's Republic of China, and the National Natural Science Foundation of China.

7.
Nat Prod Res ; 32(20): 2468-2475, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29298500

RESUMO

One new sesqui-neolignan compound, namely, sesqui-illisimonan A (1), one new neolignan, illisimonan A (2), and one new phenylpropanoid compound, illisimoid A (3) were isolated from the fruits of Illicium simonsii Maxim. The structures and absolute configurations of these compounds were determined by extensive spectroscopic, including NMR, circular dichroism and calculated electronic circular dichroism methods. The antioxidant activities of compounds 1-3 were also evaluated. Vitamin E was selected as the positive control (IC50 = 49.73 ± 0.88 µM). Compounds 1 and 2 exhibited in vitro antioxidant activity with an IC50 value of 55.76 ± 1.30 and 59.36 ± 0.50 µM, respectively. However, the compound 3 didn't show obvious antioxidant activity.


Assuntos
Antioxidantes/farmacologia , Illicium/química , Lignanas/farmacologia , Fenilpropionatos/farmacologia , Antioxidantes/isolamento & purificação , China , Dicroísmo Circular , Frutas/química , Lignanas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Fenilpropionatos/isolamento & purificação
8.
Oncotarget ; 8(43): 75350-75360, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-29088870

RESUMO

Previous studies showed that microRNA-214 (miR-214) may act as a prognostic biomarker of cancer. However, the available evidence is controversial. This study summarizes evidence and evaluates the prognostic role of miR-214 in various cancers. We carried out a systematic literature review and assessed the quality of included studies based on Oxford Centre for Evidence-based Medicine Criteria and Newcastle-Ottawa Scale (NOS). Pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for overall survival (OS) and disease free survival/progressive free survival/recurrence free survival (DFS/PFS/RFS) were calculated to measure the effective value of miR-214 expression on prognosis. Thirteen studies were included in pooled analysis. We found that miR-214 was significantly correlated with OS (HR=2.21, 95%CI: 1.33-3.68, P=0.00), no significant difference was found with DFS/PFS/RFS (HR=1.73, 95%CI: 0.78-3.83, P=0.18) in various carcinomas. In subgroup analysis, higher expression of miR-214 was significantly associated with poor OS in Asians (HR=2.27, 95%CI: 1.09-4.73, P=0.00) and Caucasians (HR=2.04, 95%CI: 1.47-3.30, P=0.00). On the contrary, high miR-214 expression significantly predicted favorable DFS/PFS/RFS (HR=0.50, 95%CI: 0.31-0.82, P=0.00) in hepatocellular carcinoma (HCC) group. Our data indicates that high miR-214 could be a promising biomarker for prognosis prediction of cancer. However, further clinical studies are needed for the current insufficient relevant data.

9.
Oncotarget ; 8(44): 77999-78010, 2017 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-29100442

RESUMO

Background: The prognostic significance of MicroRNA-148/152 (miR-148/152) family expression in various cancers has been investigated by many studies with inconsistent results. To address this issue, we performed a meta-analysis to clarify this relationship. Materials and Methods: Eligible studies were recruited by a systematic literature search and assessed the quality of included studies based on Quality In Prognosis Studies (QUIPS) and Newcastle-Ottawa Scale (NOS). Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and disease free survival/progressive free survival/recurrence free survival (DFS/PFS/RFS) were calculated to estimate the effects of miR-148/152 family expression on prognosis. Results: A final total of 23 articles (26 studies) were considered in evidence synthesis. A significant association was observed between low miR-148a level and poor OS in patients (HR = 1.59, 95% CI: 1.14 - 2.20, P = 0.00), especially with digestive tract cancer (DTC) (HR = 1.29, 95% CI: 1.03-1.63, P = 0.03), and another significant association was observed between low miR-148b level and poor OS in patients (HR=2.09, 95% CI: 1.70-2.56, P = 0.00), especially with (hepatocellular carcinoma) HCC (HR = 1.97, 95% Cl: 1.52-2.56, P = 0.00) and non-small cell lung cancer (NSCLC) (HR = 2.29, 95% Cl: 1.64-3.18, P = 0.00). The significant correlation between miR-152 and DFS/RFS was found in our research (HR = 3.49, 95% Cl: 1.13-10.08, P = 0.03). Conclusions: Our findings suggest that low miR-148/152 family expression is significantly associated with poor prognosis and may be a feasible prognostic biomarker in some cancers, especially in HCC and NSCLC.

10.
Zhongguo Zhong Yao Za Zhi ; 42(1): 135-139, 2017 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-28945038

RESUMO

A new neolignan, (-)-(7R,8S,7'E)-3',4-dihydroxy-3-methoxy-8,4'-oxyneoligna-7'-ene-7,9,9'-triol(1), and seven known compounds, 9-(tetrahydropyran-2-yl)-nona-trans,trans-2,8-diene-4,6-diyn-1-ol (2), 9-(tetrahydropyran-2-yl)-trans-non-8-ene-4,6-diyn-1-ol (3), lobetyol (4), lobetyolin (5),dehydrodieoniferyl alcohol (6), 5-hydroxymethylfurfural (7), and 4, 4'-dihydroxy-3, 3'-dimethoxy-trans-stilbene (8), were isolated from the H2O extract of Codonopsis pilosula. The structures of 1-8 were elucidated by spectroscopic methods including NMR, HR-ESI-MS, and CD. In addition, compounds 2 and 3 were isolated from the genus Codonopsis for the first time.


Assuntos
Codonopsis/química , Lignanas/isolamento & purificação , Lignanas/química , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
11.
World J Gastroenterol ; 22(43): 9515-9524, 2016 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-27920472

RESUMO

AIM: To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid (CB) receptors, WIN55-212-2 (WIN55), in mice with experimental colitis, so as to supply experimental evidence for its clinical use in future. METHODS: We established the colitis model in C57BL/6 mice by replacing the animals' water supply with 4% dextran sulfate sodium (DSS) for 7 consecutive days. A colitis scoring system was used to evaluate the severity of colon local lesion. The plasma levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the myeloperoxidase (MPO) activity in colon tissue were measured. The expressions of cannabinoid receptors, claudin-1 protein, p38 mitogen-activated protein kinase (p38MAPK) and its phosphorylated form (p-p38) in colon tissue were determined by immunohistochemistry and Western blot. In addition, the effect of SB203580 (SB), an inhibitor of p38, was investigated in parallel experiments, and the data were compared with those from intervention groups of WIN55 and SB alone or used together. RESULTS: The results demonstrated that WIN55 or SB treatment alone or together improved the pathological changes in mice with DSS colitis, decreased the plasma levels of TNF-α, and IL-6, and MPO activity in colon. The enhanced expression of claudin-1 and the inhibited expression of p-p38 in colon tissues were found in the WIN55-treated group. Besides, the expression of CB1 and CB2 receptors was enhanced in the colon after the induction of DSS colitis, but reduced when p38MAPK was inhibited. CONCLUSION: These results confirmed the anti-inflammatory effect and protective role of WIN55 on the mice with experimental colitis, and revealed that this agent exercises its action at least partially by inhibiting p38MAPK. Furthermore, the results showed that SB203580, affected the expression of CB1 and CB2 receptors in the mouse colon, suggesting a close linkage and cross-talk between the p38MAPK signaling pathway and the endogenous CB system.


Assuntos
Anti-Inflamatórios/farmacologia , Benzoxazinas/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Colite/prevenção & controle , Colo/efeitos dos fármacos , Morfolinas/farmacologia , Naftalenos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Colite/induzido quimicamente , Colite/enzimologia , Colite/patologia , Colo/enzimologia , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Feminino , Imidazóis/farmacologia , Interleucina-6/sangue , Masculino , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Piridinas/farmacologia , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/agonistas , Receptor CB2 de Canabinoide/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
Medicine (Baltimore) ; 95(37): e4773, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27631228

RESUMO

BACKGROUND: Mounting evidence showed that microRNAs may be useful as prognostic biomarkers of cancer. Therefore, we summarize the predictive role of microRNA-218 (miR-218) for survival in patients with various cancers. METHODS: We performed a systematic literature review and assessed the quality of included studies based on Meta-analysis of Observational Studies in Epidemiology group (MOOSE). Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated to assess the correlation between miR-218 expression and prognosis of different cancers. RESULTS: We identified 10 studies for pooled analyses. For overall survival, a lower expression levels of miR-218 significantly predicted poorer survival, with the pooled HR of 2.61 (95% CI: 2.11-3.22, P < 0.001). For disease-free survival/progressive-free survival/recurrence-free survival (DFS/PFS/RFS), a lower expression level of miR-218 significantly predicted worse DFS/PFS/RFS in various carcinomas, with the pooled HR of 2.73 (95% CI: 2.08-3.58, P < 0.001). Similarly, subgroup analysis by detection method, ethnicity and cancer subtype analysis suggested that lower expression of miR-218 correlated with. CONCLUSION: Our data demonstrated that lower miR-218 expression is significantly associated with poorer overall survival (OS) and DFS/PFS/RFS and may be a novel prognostic biomarker in some cancer types.


Assuntos
MicroRNAs/metabolismo , Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Humanos , Neoplasias/diagnóstico , Prognóstico
13.
Oncotarget ; 7(16): 22368-84, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-26993779

RESUMO

The aim of this study is to provide a precise quantification for the association between miR-149 T > C (rs2292832) and miR-27a A > G (rs895819) and the risk of cancer. We conducted a systematic literature review and evaluated the quality of included studies based on Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to assess the strengths of the associations. We identified 40 studies for pooled analyses. Overall, the results demonstrated that the rs2292832 polymorphism was subtly decrease the risk of breast cancer (CT + CC vs TT: OR = 0.83, 95% CI: 0.70-0.98, P = 0.03; CC vs CT + TT: OR = 0.80, 95% CI: 0.68-0.93, P = 0.00), and the rs895819 polymorphism wasassociated with significantly increased cancer risk in the Asian population (AG + GG vs AA: OR = 1.24, 95% CI: 1.03-1.50, P = 0.02) and in colorectal cancer subgroup (GG vs AA: OR = 1.45, 95% CI: 1.10-1.92, P = 0.00; AG + GG vs AA: OR = 1.35, 95% CI: 1.15-1.58, P = 0.00; GG vs AG + AA: OR = 1.36, 95% CI: 1.04-1.77, P = 0.02). In addition, a subtly decreased risk was observed in the Caucasian population and in breast cancer subgroup. In conclusion, the rs2292832 polymorphism was significantly associated with increased breast cancer risk, and the rs895819 polymorphism contributes to the susceptibility of colorectal and breast cancer.


Assuntos
Predisposição Genética para Doença/genética , MicroRNAs/genética , Neoplasias/genética , Genótipo , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores de Risco
14.
Arch Med Res ; 46(6): 439-47, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26254701

RESUMO

BACKGROUND AND AIMS: This study aims to investigate the effects of cannabinoid (CB)1 and CB2 receptor ligands on intestinal motor function and muscular electrophysiological activity in rodent gastrointestinal (GI) tract. METHODS: Lipopolysaccharide (LPS) was used to induce intestinal hypomotility. The effect of selective CB1 and CB2 agonists and antagonists on contractility of the muscle strips from rat jejunum was measured using organ bath, and the membrane potential of the jejunal smooth muscle cells was recorded with intracellular microelectrodes. The single cell patch clamp technique was applied to record delayed rectifying potassium currents (IKV) and spontaneous transient outward currents (STOC). RESULTS: LPS significantly reduced contractility of the smooth muscle strips (p <0.010) and caused hyperpolarization of membrane potential of the smooth muscle cells (p <0.010). This LPS-induced effect was reversed by AM251 and AM630, selective CB1 and CB2 antagonists, respectively, which promoted contractions of smooth muscle strips and triggered cell depolarization (p <0.010). LPS-induced changes were further enhanced in the presence of CB agonists, HU210 and WIN55 (p <0.050 or p <0.010). No effect of HU210 or AM251 on IKV and STOC has been observed. This ex vivo study suggests that CB1 and CB2 receptors are involved in intestinal motor function in normal and LPS-induced pathological states and the regulation of the membrane potential of smooth muscle cells is very likely one of the effective mechanisms. CONCLUSIONS: This is one of the first reports on neuronal regulation of intestinal motility through CB-dependent pathways with potential application in the treatment of inflammatory and functional GI disorders.


Assuntos
Canabinoides/química , Eletrofisiologia/métodos , Motilidade Gastrointestinal/fisiologia , Lipopolissacarídeos/química , Células Musculares/química , Receptor CB2 de Canabinoide/química , Animais , Masculino , Ratos
15.
Hepatobiliary Pancreat Dis Int ; 14(1): 101-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25655298

RESUMO

BACKGROUND: The mitogen-activated protein kinases (MAPKs) signaling pathway is involved in inflammatory process. However, the mechanism is not clear. The present study was to investigate the role of p38 MAPK in acute pancreatitis in mice. METHODS: Mice were divided into 4 groups: saline control; acute pancreatitis induced with repeated injections of cerulein; control plus p38 MAPK inhibitor SB203580; and acute pancreatitis plus SB203580. The pancreatic histology, pancreatic enzymes, cytokines, myeloperoxidase activity, p38 MAPK and heat shock protein (HSP) 60 and 70 were evaluated. RESULTS: Repeated injections of cerulein resulted in acute pancreatitis in mice, accompanying with the activation of p38 MAPK and overexpression of HSP60 and HSP70 in the pancreatic tissues. Treatment with SB203580 significantly inhibited the activation of p38 MAPK, and furthermore, inhibited the expression of HSP60 and HSP70 in the pancreas, the inflammatory cytokines in the serum, and myeloperoxidase activity in the lung. CONCLUSION: The p38 MAPK signaling pathway is involved in the regulation of inflammatory response and the expression of HSP60 and HSP70 in acute pancreatitis.


Assuntos
Anti-Inflamatórios/farmacologia , Imidazóis/farmacologia , Pâncreas/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Doença Aguda , Animais , Biomarcadores/sangue , Ceruletídeo , Chaperonina 60/metabolismo , Modelos Animais de Doenças , Proteínas de Choque Térmico HSP70/metabolismo , Mediadores da Inflamação/sangue , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/metabolismo , Pâncreas/enzimologia , Pâncreas/imunologia , Pancreatite/induzido quimicamente , Pancreatite/enzimologia , Pancreatite/imunologia , Pancreatite/prevenção & controle , Peroxidase/metabolismo , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
16.
PLoS One ; 8(7): e67427, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23844009

RESUMO

INTRODUCTION: Intestinal inflammatory responses play a critical role in the pathogenesis of postoperative ileus (POI). As cannabinoid receptor-1 (CB1) is involved in inhibiting gastrointestinal (GI) motility and anti-inflammation, we aimed to explore its contribution to POI. METHODS: Experimental POI was induced in adult female CB1-deficient (CB1-/-) mice and wild-type littermates (C57BL/6N) by standardized small bowel manipulation. Twenty-four hours after surgery, GI transit was assessed by charcoal transport. FITC avidin, F4/80, and myeloperoxidase immunohistochemistry techniques were used to evaluate the inflammatory response in the muscularis of ileum and colon. Expressions of p38MAPK and its phosphorylated form (pp38) in the intestine were determined. Plasma levels of proinflammatory cytokines and chemokines were measured by ELISA as well. RESULTS: POI was characterized by decreased GI transit (p<0.01) and accompanied by a marked intestinal and systematic inflammatory response in wild-type and CB1-/- mice. Increased numbers of inflammatory cells, including macrophages, neutrophils, and mast cells were observed in the muscularis of ileum and colon (p<0.01, or p<0.05). Plasma levels of interleukin-6 (IL-6), cytokine-induced neutrophil chemoattractant-1 (CINC-1/KC), and monocyte chemoattractant protein-1 (MCP-1) were elevated (p<0.01, or p<0.05). Expression of p38 and pp38 increased in the intestine (p<0.01, or p<0.05). CB1-/- mice showed an increased inflammatory response during POI, especially the systemic inflammatory markers, such as IL-6, KC, CINC1, and pp38 expression were increased as compared to those in WT mice (p<0.05). CONCLUSIONS: Intestinal motility was inhibited during POI. In this condition, inhibition of motility did not seem to be altered by the absence of CB1 receptors, however, an increased inflammatory response was observed in CB1-/- mice. Hence, CB1 receptor activation rather than inhibition may reduce the inflammatory response in POI, which has a remote potential to relate into reduced inhibition of intestinal motility during POI.


Assuntos
Íleus/genética , Complicações Pós-Operatórias/genética , Receptor CB1 de Canabinoide/deficiência , Animais , Quimiocina CCL2/sangue , Colo/metabolismo , Colo/patologia , Modelos Animais de Doenças , Feminino , Motilidade Gastrointestinal/genética , Íleo/metabolismo , Íleo/patologia , Íleus/metabolismo , Interleucina-6/sangue , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Knockout , Músculo Liso/metabolismo , Músculo Liso/patologia , Complicações Pós-Operatórias/metabolismo , Período Pós-Operatório , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/metabolismo , Fator de Necrose Tumoral alfa/sangue , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Phytother Res ; 27(10): 1564-71, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23339028

RESUMO

Although Berberine (BER) is popular in treating gastrointestinal (GI) disorders, its mechanisms are not clear yet. In order to investigate the effects and possible mechanism of BER on GI motility in rodents, we first explored GI motility by recording the myoelectrical activity of jejunum and colon in rats, and upper GI transit with a charcoal marker in mice. Then, the plasma levels of gastrin, motilin, somatostatin and glucagon-like-peptide-1 (Glp-1) were measured by ELISA or radioimmunoassay (RIA). Furthermore, endogenous opioid-peptides (ß-endorphin, dynorphin-A, met-enkephalin) were detected by RIA after treatment with BER. Our results showed that BER concentration-dependently inhibited myoelectrical activity and GI transit, which can be antagonized by opioid-receptor antagonists to different extents. The elevated somatostatin and Glp-1, and decreased gastrin and motilin in plasma, which were caused by BER application, also could be antagonized by the opioid-receptor antagonists. Additionally, plasma level of ß-endorphin, but not dynorphin-A and met-enkephalin, was increased by applying BER. Taken together, these studies show that BER plays inhibiting roles on GI motility and up-regulating roles on somatostatin, Glp-1 and down-regulating roles on gastrin, motilin. The pharmacological mechanisms of BER on GI motility and plasma levels of GI hormones were discovered to be closely related to endogenous opioid system.


Assuntos
Berberina/farmacologia , Hormônios Gastrointestinais/fisiologia , Motilidade Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Peptídeos Opioides/fisiologia , Animais , Colo/efeitos dos fármacos , Colo/fisiologia , Dinorfinas/fisiologia , Encefalina Metionina/fisiologia , Gastrinas/fisiologia , Trato Gastrointestinal/fisiologia , Trânsito Gastrointestinal/efeitos dos fármacos , Trânsito Gastrointestinal/fisiologia , Peptídeo 1 Semelhante ao Glucagon/fisiologia , Jejuno/efeitos dos fármacos , Jejuno/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Motilina/fisiologia , Ratos , Ratos Sprague-Dawley , Somatostatina/fisiologia , beta-Endorfina/fisiologia
18.
Pancreas ; 42(1): 123-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22850623

RESUMO

OBJECTIVES: The anti-inflammatory effects of O-1602 and cannabidiol (CBD), the ligands of G protein-coupled receptor 55 (GPR55), on experimental acute pancreatitis (AP) were investigated. METHODS: Acute pancreatitis was induced in C57BL mice by intraperitoneal injection of 50 µg/kg cerulein hourly, with a total of 6 times. Drugs (O-1602, 10 mg/kg, or CBD, 0.5 mg/kg) were given by intraperitoneal injection 2 times at 30 minutes before the first injection and immediately before the fifth cerulein injection. At 3 hours after the last injection, the blood, the lungs, and the pancreas were harvested for the pancreatic enzyme activity, myeloperoxidase activity, and pro-inflammatory cytokines measurement; and the expressions of GPR55 mRNA and protein in the pancreas were detected. RESULTS: Cannabidiol or O-1602 treatment significantly improved the pathological changes of mice with AP and decreased the enzyme activities, IL-6 and tumor necrosis factor α; levels, and the myeloperoxidase activities in plasma and in the organ tissues. G protein-coupled receptor 55 mRNA and protein expressed in the pancreatic tissue, and the expressions were decreased in the mice with AP, and either CBD or O-1602 attenuated these changes to a certain extent. CONCLUSION: Cannabidiol and O-1602 showed anti-inflammatory effects in mice with AP and improved the expression of GPR55 in the pancreatic tissue as well.


Assuntos
Anti-Inflamatórios/farmacologia , Canabidiol/análogos & derivados , Ceruletídeo , Pâncreas/efeitos dos fármacos , Pancreatite/prevenção & controle , Doença Aguda , Amilases/sangue , Animais , Anti-Inflamatórios/administração & dosagem , Western Blotting , Canabidiol/administração & dosagem , Canabidiol/farmacologia , Modelos Animais de Doenças , Imuno-Histoquímica , Mediadores da Inflamação/sangue , Injeções Intraperitoneais , Interleucina-6/sangue , Lipase/sangue , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatite/sangue , Pancreatite/induzido quimicamente , Pancreatite/patologia , Peroxidase/sangue , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Canabinoides/efeitos dos fármacos , Receptores de Canabinoides/genética , Receptores de Canabinoides/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue
19.
PLoS One ; 7(12): e52921, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23285225

RESUMO

Acute pancreatitis (AP), especially severe acute pancreatitis often causes extra-pancreatic complications, such as acute gastrointestinal mucosal lesion (AGML) which is accompanied by a considerably high mortality, yet the pathogenesis of AP-induced AGML is still not fully understood. In this report, we investigated the alterations of serum components and gastric endocrine and exocrine functions in rats with experimental acute pancreatitis, and studied the possible contributions of these alterations in the pathogenesis of AGML. In addition, we explored the intervention effects of cannabinoid receptor agonist HU210 and antagonist AM251 on isolated and serum-perfused rat stomach. Our results showed that the AGML occurred after 5 h of AP replication, and the body homeostasis was disturbed in AP rat, with increased levels of pancreatic enzymes, lipopolysaccharide (LPS), proinflammtory cytokines and chemokines in the blood, and an imbalance of the gastric secretion function. Perfusing the isolated rat stomach with the AP rat serum caused morphological changes in the stomach, accompanied with a significant increment of pepsin and [H+] release, and increased gastrin and decreased somatostatin secretion. HU210 reversed the AP-serum-induced rat pathological alterations, including the reversal of transformation of the gastric morphology to certain degree. The results from this study prove that the inflammatory responses and the imbalance of the gastric secretion during the development of AP are responsible for the pathogenesis of AGML, and suggest the therapeutic potential of HU210 for AGML associated with acute pancreatitis.


Assuntos
Citoproteção , Dronabinol/análogos & derivados , Pancreatite/sangue , Soro/fisiologia , Estômago/efeitos dos fármacos , Doença Aguda , Animais , Antieméticos/farmacologia , Antieméticos/uso terapêutico , Canabinoides/agonistas , Canabinoides/antagonistas & inibidores , Canabinoides/farmacologia , Células Cultivadas , Modelos Animais de Doenças , Dronabinol/farmacologia , Dronabinol/uso terapêutico , Lipopolissacarídeos/farmacologia , Masculino , Técnicas de Cultura de Órgãos , Pancreatite/patologia , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Sprague-Dawley , Estômago/citologia , Estômago/patologia
20.
Wei Sheng Yan Jiu ; 40(6): 738-40, 2011 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-22279669

RESUMO

OBJECTIVE: To explore the acute toxicity and genotoxicity of inlet and outlet water of a sewage treatment plant in Zhengzhou to provide scientific basis for the safety of sewage reuse. METHODS: Inlet water, secondary and tertiary processed outlet water were collected from the sewage treatment plant. Acute toxicity and genotoxicity of the inlet and outlet water were detected by luminescent bacteria toxicity test and Vicia faba root tip cell micronucleus test, respectively. RESULTS: The luminosity inhibition rates of luminescent bacteria by inlet water, secondary and tertiary processed outlet water were (33.96 +/- 7.51)%, (14.32 +/- 7.36)% and (7.24 +/- 5.58)%, and the micronucleus rates were (12.67 +/- 2.08) per thousand, (6.33 +/- 1.53) per thousand and (2.67 +/- 0.58) per thousand, respectively. The pollution levels of these three samples were heavy, mild and scarce, respectively. The inhibition rates of luminescent bacteria by the secondary and tertiary processed water were significantly lower than that of inlet water (F = 12.159, P = 0.008). A similar result was observed for micronucleus rate (F = 56.850, P < 0.001). CONCLUSION: The acute toxicity and genotoxicity of processed water were decreased greatly. However, some potential ecological risks of the processed water still existed for environment.


Assuntos
Testes para Micronúcleos/métodos , Mutagênicos/toxicidade , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/toxicidade , Bactérias/metabolismo , China , Cidades , Medições Luminescentes , Raízes de Plantas , Esgotos , Testes de Toxicidade Aguda , Vicia faba/efeitos dos fármacos , Vicia faba/genética
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