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PURPOSE: To explore the esophageal cancer (EC) incidence and mortality trends and risk factors in China during 2005-2015. MATERIALS AND METHODS: The data were stratified by area (urban, rural), gender (male, female), and age groups (0 ~, 5 ~, , 85 ~). The age-standardized incidence rate (ASIR) and mortality rate (ASMR), age-specific incidence and mortality were calculated to describe the trends, which were analyzed by Joinpoint software, negative binomial regression model, and age-period-cohort model. RESULTS: Trends in EC ASIR decreased markedly during 2010-2015 (APC=-6.14%, P<0.05), and the average annual percent change (AAPC) value was -8.07% (95% confidence interval (CI): -9.98~-6.12) for rural areas during 2005-2015. The ASMR was on a fast-downward trend after 2011 (APC=-6.67%, P<0.05), with AAPC values of -1.34% (95% CI: -2.56~-0.19) for males, -3.39% (95% CI: -5.65, -1.07) for females, and -9.67% (95% CI: -10.56~-8.77) for rural areas during 2005-2015. The age-specific incidence and mortality increased with age. The risk of EC for males was 3.1675 times higher than females (P<0.001), and for urban areas, it was 0.58 times larger than rural (P<0.001). The age and period effects presented an increasing trend, with a decreasing trend for the cohort effects in incidence and mortality risk. Later birth cohorts presented lower risks than previous birth cohorts. CONCLUSION: ASIR and ASMR in China are higher in males than females, and higher in rural than urban areas, which have decreased during 2005-2015, especially in rural areas. The incidence increased with age up to the peak age group of 75. Area, gender, and age were independent risk factors for EC incidence.
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Colorectal cancer is the main leading cause of death from cancer worldwide. Protective effects of vitamin B1 on colorectal cancer have been observed in some epidemiological studies. A systematic review and meta-analysis of observational studies evaluated the association of intake of vitamin B1 with the incidence of colorectal cancer. Relevant studies were identified in MEDLINE via PubMed (published up to September 2020). We extracted data from articles on vitamin B1 and used a multivariable-adjusted odds ratio (OR) and a random-effects model for analysis. We found seven articles meeting the inclusion criteria (1 of cohort studies and 6 case-control studies) and a total of 6,184 colorectal cancer cases were included in this meta-analysis. The multivariable-adjusted OR for pooled studies for the association of roughly the same high dose level versus the lowest vitamin B1 intake and the risk of colorectal cancer was 0.76 (95% confidence interval ([95%CI]: 0.65, 0.89). This meta-analysis studied the relationship between vitamin B1 and colorectal cancer. We found vitamin B1 intake was inversely associated with the risk of colorectal cancer. However, further research and large sample studies need to be conducted to better validate the result.
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Neoplasias Colorretais , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Humanos , Incidência , Estado Nutricional , Estudos Observacionais como Assunto , Fatores de Risco , TiaminaRESUMO
PURPOSE: This study aimed to analyze incidence and mortality trends and risk factors of colorectal cancer (CRC) in China during 2005-2015. MATERIALS AND METHODS: Patient cases were extracted from the Chinese Cancer Registry Annual Report. Joinpoint regression and Poisson regression were applied to analyze incidence and mortality trends and risk factors of CRC. Age-period-cohort model was used to evaluate the age, period and cohort effects on CRC. RESULTS: The standardized incidence and mortality rate of CRC in China showed a decreasing trend during 2005-2015. The incidence in men (APC=-1.22%, P<0.05) decreased from 2005 to 2015 and decreased in women (APC =-3.55%, P<0.05) from 2005 to 2013, then increased during 2013-2015 (APC =18.77%, P<0.05). The incidence and mortality in urban areas were higher than those in rural (The incidence in urban: APC =-0.97%, P<0.05; rural: APC =1.94%, P<0.05; the mortality in urban: APC =-0.67%, P<0.05; rural: APC =0.29%). For age-specific rates, the incidence begins to increase significantly at 40-45 age group and reached a peak at 75; the mortality increased significantly at 45-50. The age effect increased with age in general. The 1920 birth cohort had the highest risk of colorectal cancer incidence and death. Poisson regression showed region, gender and age were independent risk factors of CRC. CONCLUSION: The age-adjusted standardized incidence rate (ASIR) and age-adjusted standardized mortality rate (ASMR) of CRC in China during 2005-2015 were decreasing. A great concern on men, rural areas and people aged over 75 should be aroused to prevent colorectal cancer.
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A superior electrochemical biosensor was designed for the determination of UO22+ in aqueous solution by integration of DNAzyme and DNA-modified gold nanoparticle (DNA-AuNP) network structure. Key features of this method include UO22+ inducing the cleavage of the DNAzyme and signal amplification of DNA-AuNP network structure. In this electrochemical method, the DNA-AuNP network structure can be effectively modified on the surface of gold electrode and then employed as an ideal signal amplification unit to generate amplified electrochemical response by inserting a large amount of electrochemically active indicator methylene blue (MB). In the presence of UO22+, the specific sites on DNA-AuNP network structure can be cleaved by UO22+, releasing the DNA-AuNP network structure with detectable reduction of electrochemical response intensity. The electrochemical response intensity is related to the concentration of UO22+. The logarithm of electrochemical response intensity and UO22+ concentration showed a wide linear range of 10~100 pM, and the detection limit reached 8.1 pM (S/N = 3). This method is successfully used for determination of UO22+ in water samples. Graphical abstract Fabricated DNAzyme network structure for enhanced electrical signal. Numerical experiments show that the current signal decreases as the concentration of UO22+ increases. It can be seen that the biosensors could be used to detect UO22+ in aqueous solution effectively.
Assuntos
Técnicas Biossensoriais/métodos , DNA Catalítico/química , Técnicas Eletroquímicas/métodos , Nanopartículas Metálicas/química , Compostos de Urânio/análise , Poluentes Químicos da Água/análise , Água Potável/análise , Ouro/química , Ácidos Nucleicos Imobilizados/química , Limite de Detecção , Azul de Metileno/química , Reprodutibilidade dos Testes , Rios/química , Compostos de Urânio/química , Poluentes Químicos da Água/químicaRESUMO
Pregnant women are a unique group undergoing profound structural modifications in uterus, breast, adipose tissue and extracellular fluids. Amino acid metabolic stress is a unique physical process that occurs during pregnancy. Metals constitute a fundamental part of the maternal body and have a universal effect on amino acid metabolism. However, the exact interaction between metals and amino acid metabolism during pregnancy is unknown. The aim of the present study was to determine the correlations of metals with amino acid metabolic intermediates in the urine of 232 healthy pregnant women in their first, second and third trimesters during normal pregnancy. Sixteen metals in the urine of 232 healthy pregnant women in their first, second and third trimesters were quantified using inductively coupled plasma mass spectrometry (ICP-MS). An ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometer (UPLC-QTOFMS)-based metabolomics approach was conducted to detect intermediate products involved in amino acid metabolism during the entire pregnancy period. A panel regression model was established to investigate the relationship between urine metals and amino acid metabolism. Seven metals-cadmium, cobalt, copper, cesium, manganese, thallium and vanadium-showed significant association with amino acid metabolic intermediates, including 2-oxoarginine, 3-indoleacetonitrile, indole, indole-5,6-quinone, N2-succinyl-l-glutamic acid 5-semialdehyde, N-methyltryptamine and N-succinyl-l,l-2,6-diaminopimelate, in the healthy pregnant women. These findings indicated that exposure to cadmium, cobalt, copper, cesium, manganese, thallium and vanadium significantly affected the metabolic status of tryptophan, arginine, proline, tyrosine and lysine metabolism in the maternal body during normal pregnancy.
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TNKS1BP1 is a member of the poly(ADP-ribose) polymerase (PARP) superfamily. Our previous studies have demonstrated that TNKS1BP1 plays an important role in DNA damage response. But whether and how TNKS1BP1 associates with cancer is still not clear. Here, we found that TNKS1BP1 was upregulated in human lung adenocarcinoma (LAC) tissues, and was associated with poor overall survival (OS) in LAC patients. Dysregulation of TNKS1BP1 affected the sensitivity of A549 cells to several DNA damage agents including cisplatin, bleomycin, and ionizing radiation. Mechanically, overexpression of TNKS1BP1 increased the accumulation of S phase cells, which was accompanied by a decrease in M phase cells. More importantly, we found TNKS1BP1 regulated genome stability, mainly through affecting the homologous recombination pathway of DNA double-strand breaks by inhibiting the RAD51 foci formation. Overall, our study indicates that, in LAC, aberrant expressions of TNKS1BP1 are common events, and overexpression of TNKS1BP1 might affect outcomes of cancer patients to chemotherapy and radiotherapy.
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Adenocarcinoma/metabolismo , Neoplasias Pulmonares/metabolismo , Reparo de DNA por Recombinação , Proteína 1 de Ligação a Repetições Teloméricas/metabolismo , Regulação para Cima , Células A549 , Adenocarcinoma/genética , Adenocarcinoma de Pulmão , Bleomicina/farmacologia , Proliferação de Células , Sobrevivência Celular , Cisplatino/farmacologia , Quebras de DNA de Cadeia Dupla , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Prognóstico , Análise de SobrevidaRESUMO
Indoor air quality has great impact on the human health. An increasing number of studies have shown that printers could release particulate matters and pose adverse effects on indoor air quality. In this study, a thorough investigation was designed to assess the aerosol printer particle total number concentration (TNC) and size distribution in normal office environment, one copy center, and a clean chamber. Particle analyzers, SMPS, OPS, and CPC3007 were used to monitor the total printing process. In normal office environment, 37 laser printers out of all surveyed 55 printers were classified as high particle emitters. Comparing to laser printers, 5 inkjet printers showed no particle emission. Particle emission level in a copy center increased slightly with TNC elevating to about 2 times of the aerosol background. Simulating test in a clean chamber indicated that printer-emitted particles were dominated by particles in nanoscale (diameter of particle, D(p) < 100 nm). These particles in a sealed clean chamber attenuated so slowly that it still held at high level with the concentration of 1.5 x 10(4) particles/cm3 after printing for 2.5 hours. Our present results demonstrate that printers indeed release particulates which keeping at a high concentration level in the indoor environment. Special care should be taken to this kind of widely applied machines and effective controls of particle emission at printing processes are necessary.
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Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Nanopartículas/análise , Impressão , Exposição Ocupacional/análise , Tamanho da Partícula , Material Particulado/análiseRESUMO
Accurate mitotic regulation is as important as intrinsic DNA repair for maintaining genomic stability. It is believed that these two cellular mechanisms are interconnected with DNA damage. DNA-PKcs is a critical component of the non-homologous end-joining pathway of DNA double-stranded break repair, and it was recently discovered to be involved in mitotic processing. However, the underlying mechanism of DNA-PKcs action in mitotic control is unknown. Here, we demonstrated that depletion of DNA-PKcs led to the dysregulation of mitotic progression in response to DNA damage, which eventually resulted in multiple failures, including failure to segregate sister chromatids and failure to complete cytokinesis, with daughter cells becoming fused again. The depletion of DNA-PKcs resulted in a notable failure of cytokinesis, with a high incidence of multinucleated cells. There were also cytoplasmic bridges containing DNA that continuously connected the daughter cells after DNA damage was induced. Phosphorylated DNA-PKcs (T2609) colocalizes with PLK1 throughout mitosis, including at the centrosomes from prophase to anaphase and at the kinetochores from prometaphase to metaphase, with accumulation at the midbody during cytokinesis. Importantly, DNA-PKcs was found to associate with PLK1 in the mitotic phase, and the depletion of DNA-PKcs resulted in the overexpression of PLK1 due to increased protein stability. However, deficiency in DNA-PKcs attenuated the recruitment of phosphorylated PLK1 to the midbody but not to the kinetochores and centrosomes. Our results demonstrate the functional association of DNA-PKcs with PLK1, especially in chromosomal segregation and cytokinesis control.
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Proteínas de Ciclo Celular/metabolismo , Segregação de Cromossomos , Citocinese , Proteína Quinase Ativada por DNA/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Domínio Catalítico , Ciclo Celular , Proteínas de Ciclo Celular/genética , Centrossomo/metabolismo , Dano ao DNA , Reparo do DNA , Proteína Quinase Ativada por DNA/genética , Citometria de Fluxo , Células HeLa , Humanos , Immunoblotting , Cinetocoros/metabolismo , Microscopia Confocal , Mitose , Fosforilação , Ligação Proteica , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Interferência de RNA , Imagem com Lapso de Tempo/métodos , Quinase 1 Polo-LikeRESUMO
Phosphorylated H2AX is considered to be a biomarker for DNA double-strand breaks (DSB), but recent evidence suggests that γH2AX does not always indicate the presence of DSB. Here we demonstrate the bimodal dynamic of H2AX phosphorylation induced by ionizing radiation, with the second peak appearing when G2/M arrest is induced. An increased level of γH2AX occurred in mitotic cells, and this increase was attenuated by DNA-PKcs inactivation or Chk2 depletion, but not by ATM inhibition. The phosphorylation-mimic CHK2-T68D abrogated the attenuation of mitotic γH2AX induced by DNA-PKcs inactivation. Thus, the DNA-PKcs/CHK2 pathway mediates the mitotic phosphorylation of H2AX in the absence of DNA damage.
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Quinase do Ponto de Checagem 2/metabolismo , Dano ao DNA , DNA/metabolismo , Histonas/metabolismo , Mitose/efeitos da radiação , Oligopeptídeos/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , DNA/efeitos da radiação , Quebras de DNA de Cadeia Dupla , Células HeLa , Histonas/genética , Humanos , Fosforilação , Radiação Ionizante , Transdução de SinaisRESUMO
The essential function of eIF4E-binding protein 1 (4E-BP1) in translation initiation has been well established; however, the role of 4E-BP1 in normal cell cycle progression is coming to attention. Here, we revealed the role of 4E-BP1 on mitotic regulation and chromosomal DNA dynamics during mitosis. First, we have observed the co-localization of the phosphorylated 4E-BP1 at T37/46 with Polo-like kinase 1 (PLK1) at the centrosomes during. Depression of 4E-BP1 by small interfering RNA in HepG2 or HeLa cells resulted in an increased outcome of polyploidy and aberrant mitosis, including chromosomal DNA misaligned and multi-polar spindles or multiple centrosomes. We observed that 4E-BP1 interacted with PLK1 directly in vitro and in vivo in mitotic cells, and the C-terminal aa 77-118 of 4E-BP1 mediates its interaction with PLK1. PLK1 can phosphorylate 4E-BP1 in vitro. Furthermore, the depletion of 4E-BP1 sensitized HepG2 and HeLa cells to the microtubule disruption agent paclitaxel. These results demonstrate that 4E-BP1, beyond its role in translation regulation, can function as a regulator of mitosis via interacting with PLK1, and possibly plays a role in genomic stability maintaining.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Instabilidade Genômica , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Fuso Acromático/metabolismo , Centrossomo/efeitos dos fármacos , Centrossomo/metabolismo , Cromossomos Humanos/metabolismo , DNA de Neoplasias/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Instabilidade Genômica/efeitos dos fármacos , Células HeLa , Células Hep G2 , Humanos , Mitose/efeitos dos fármacos , Paclitaxel/farmacologia , Fosforilação/efeitos dos fármacos , Poliploidia , Ligação Proteica/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Fuso Acromático/efeitos dos fármacos , Quinase 1 Polo-LikeRESUMO
OBJECTIVE: To discover the characteristic changes of metabolic profiles in C57 mice with cyclophosphamide induced blood deficiency and the effect of Siwutang. METHOD: An integrated metabonomic study using high-resolution 1H nuclear magnetic resonance (NMR) spectroscopy has been applied to investigate the metabolic profiles of serum, aqueous and lipidic extracts of thoracic gland, spleen, bone marrow obtained from control, model group (intraperitoneal injection of cyclophosphamide at a dose of 250 mg x kg(-1)) and Siwutang treated model group. The NMR spectra were integrated in segments of 0.04 ppm and then analyzed by principal component analysis (PCA) using SIMCA-P software to visualize the similarities and differences in metabolic profiles between these groups. RESULT: PCA result showed conspicuous difference in the metabolic profiles between groups. Compared with the control group, the model group contained lower concentration of lactate, 3-hydroxybutyrate, choline, glucose, and higher concentration of VLDL/LDL, leucine/isoleucine in serum. Lower concentration of taurine choline, Fbeta:RCH2CH2CO, Epi-coprostanol and lactate were found in both in thoracic gland extracts and spleen extracts. And in spleen extracts, we also found the lower concentration of 3-HB. In the extracts of bone marrow, the lower concentration of lactate, choline, glucosee were observed. When they were dosed with Siwutang 10 g x kg(-1) x d(-1) for 7 days, the effects above-mentioned were reversed. CONCLUSION: The injury established by injecting CTX is a kind of proper model to develop further metabonomics researches. The damage of mitochondria, disorder of energy metabolism and osmoregulation are observed in cyclophosphamide caused blood deficiency model by NMR-based-metabonomics method, and the Siwutang can improve these effects.
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Anemia/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Espectroscopia de Ressonância Magnética/métodos , Medicina Tradicional Chinesa , Metabolômica , Anemia/metabolismo , Animais , Ciclofosfamida/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Paeonia , Análise de Componente PrincipalRESUMO
In the present study, an ultra performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC/Q-TOFMS) based on chemical profiling approach to evaluate chemical constitution between mixed decoction and co-decoction of monkshood-pinellia combination of the eighteen incompatible medications (Shi Ba Fan) was proposed. Two different kinds of decoctions, namely monkshood-pinellia co-decoction: water extract of the two herbs together, and monkshood-pinellia mixed decoction: water extract of each individual herbs mixed together, were prepared. Batches of these two kinds of decoction samples were subjected to UPLC/Q-TOFMS analysis, the datasets were processed with MassLynx 4.1 to holistically compare the difference between these two kinds of decoction samples. The most changed components during decocting were analyzed. Using the proposed approach, global chemical difference was found between co-decoction and mixed decoction, mesaconitine, aconitine and hypaconitine were identified as the most changed components (changed most significantly) during decocting. Result shows significant difference between two kinds of decoction samples, and the significant differences are probably related to the incompatibility of monkshood and pinellia.
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Aconitina/análogos & derivados , Aconitina/análise , Aconitum/química , Incompatibilidade de Medicamentos , Pinellia/química , Cromatografia Líquida de Alta Pressão/métodos , Combinação de Medicamentos , Análise Multivariada , Raízes de Plantas/química , Tubérculos/química , Plantas Medicinais/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
OBJECTIVE: To study the micronucleus rate and chromosome aberration of mouse embryo liver induced by formaldehyde. METHODS: The pregnant mice (been pregnant for 13 days) were divided into 5 groups randomly: Formaldehyde was given as intraperitoneal injection (0.00, 0.20, 2.00, 20.00 mg/kg) for exposure group and Cyclophosphamide (30 mg/kg) for positive control group. When the 14th days (i.e After exposed in formaldehyde 18 hours), escapes the cervical vertebra cervical killed off pregnant mouse, peels on both sides of the uterus, takes an embryo respectively each side, beheads and emits the circumference blood, takes out the embryo liver, performs micronucleus experiment and chromosome aberration experiment by use of embryo liver, validate embryo liver blood micronucleus rate and the chromosome distortion factor. RESULTS: The micronucleus rate and chromosome aberration (mainly for chromosome breakage, polyploid) rate of embryonic liver showed significant differences in formaldehyde exposure group (2.00, 20.00 mg/kg) compared with the control group (P < 0.01). CONCLUSION: The micronucleus rate and chromosome aberration of mouse embryos liver induced by formaldehyde.
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Aberrações Cromossômicas/efeitos dos fármacos , Formaldeído/toxicidade , Fígado/efeitos dos fármacos , Testes para Micronúcleos , Animais , Embrião de Mamíferos , Feminino , Fígado/metabolismo , Masculino , Camundongos , Gravidez , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
HYPOTHESIS: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor (NOS), may play an important role in endothelium dysfunction. Probucol, a potent antioxidant drug, may improve endothelium function via reduction of NOS inhibitor level. The present study examined whether the decreased level of ADMA by probucol is related to enhancement of protein arginine methyltransferase I (PRMT I) expression and reduction of dimethylarginine dimethylaminohydrolase (DDAH) activity. METHODS: Endothelial cells were cultured and used for all these studies. ADMA concentration and DDAH activity were determined by HPLC. Expression of PRMT I and eNOS were characterized by western blot. RESULTS: Pretreatment with oxidized-low density lipoprotein (ox-LDL) (10, 30 or 100 microg/ml) or lysophosphatidylcholine (LPC) (1.0, 2.5 or 5.0 microg/ml) for 12, 24 or 48 h markedly increased the activity of lactate dehydrogenase (LDH) in cultured endothelial cell. Incubation ofendothelial cells with ox-LDL (100 microg/ml) or LPC (5.0 microg/ml) for 48 h significantly increased the expression of PRMT I, and levels of MDA and ADMA, and decreased the concentration of nitrite/nitrate, the expression of eNOS and the activity of DDAH. Probucol significantly decreased the level of ADMA, concomitantly with reduction of PRMT I expression and elevation of DDAH activity and up-regulation of eNOS expression. CONCLUSION: In summary, the present results suggest that the protective effect of probucol on endothelium is related to reduction of ADMA concentration by inhibition of PRMT I expression and enhancement of DDAH activity.
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Amidoidrolases/metabolismo , Antioxidantes/farmacologia , Arginina/análogos & derivados , Probucol/farmacologia , Proteína-Arginina N-Metiltransferases/metabolismo , Arginina/metabolismo , Linhagem Celular , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Lipoproteínas LDL/farmacologia , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismoRESUMO
The purpose of this study was to test whether the insulin sensitivity, lipid metabolism and the susceptibility of the heart to ischemia/reperfusion injury are modulated by the chronic estrogen status. Rats were ovariectomized (OVX), not ovariectomized (sham) or ovariectomized and treated with subcutaneous 17 -estradiol (30 mug/kg/day, OVX+E2) (n=14-17 per group). Within 3 months after operation, body weight, the serum levels of estrogen, glucose, insulin, total cholesterol (T-chol), HDL-chol, LDL-cholesterol (LDL-chol), triglycerides (TG) and lipoprotein a (Lp(a)) were monitored. Three months after operation, hearts of partial rats (n=6-8 per group) were isolated and allowed an initial 20-min stabilization period, and then cardiac function was recorded and creatine kinase (CK) release in the coronary effluent was measured after 4 h of hypothermic ischemia in isolated rat hearts. The experimental results showed that from 2 weeks after ovariectomy to the end of the study, body weights of OVX were significantly higher compared with the other two groups (p<0.05). On weeks 5 and 9, insulin level of OVX was significantly higher than that of the other two groups (p<0.05), whereas it was not different among the three groups on weeks 12 and 13 (p>0.05). Blood glucose on week 13 was significantly higher in OVX (p<0.05). Consequently, Insulin Sensitivity Index (ISI) of OVX was lower than that of the other two groups on weeks 5 and 9 (p<0.05), but not on weeks 12 and 13. Serum values for T-chol, HDL-chol and LDL-chol were not significantly different among the three groups within the observing period. On week 13, TG level in ovariectomized group was significantly lower than in the sham- and E2-treated groups (p<0.05). Compared with sham, Lp(a) level was slight increased in OVX rats (p<0.05), while it was further increased in E2-treated rats (p<0.05). Cardiac function (left ventricular pressure (LVP) and +/-dp/dtmax) of hearts removed from OVX rats was depressed, and CK release was markedly increased (p<0.05). However, treatment with E2 significantly improved cardiac function, as shown by increasing left ventricular pressure,+dp/dtmax and -dp/dtmax, and decreased CK release. In conclusion, chronic E2 treatment has some beneficial effects on cardiovascular disease (CVD), which come from the results of improvement of insulin sensitivity and post-ischemia cardiac function. However, the mechanism did not include changes in lipids and lipoproteins. The change in Lp(a) level shows that estrogen does not confer cardiovascular protection and may increase the risk of stroke.
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Estradiol/uso terapêutico , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos , Isquemia Miocárdica/terapia , Ovariectomia , Animais , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Creatina Quinase/metabolismo , Feminino , Lipídeos/sangue , Isquemia Miocárdica/complicações , Ratos , Ratos Sprague-DawleyRESUMO
Previous investigations have indicated that rutaecarpine activates the vanilloid receptor to evoke calcitonin gene-related peptide (CGRP) release. CGRP has been shown to alleviate cardiac anaphylactic injury. In the present study, the effect of rutaecarpine on cardiac anaphylaxis was examined. Challenge of presensitized guinea-pig hearts with a specific antigen caused marked decreases in coronary flow (CF), left ventricular pressure (LVP) and its derivatives (+/- dp/dt(max)), an increase in heart rate, and prolongation of the P-R interval. Rutaecarpine (0.3 or 1 microM) markedly increased the content of calcitonin gene-related peptide (CGRP) in the coronary effluent and decreased the content of tumor necrosis factor-alpha (TNF-alpha) in myocardial tissues concomitantly with a significant improvement of cardiac function and alleviation of the extension of the P-R interval. Rutaecarpine at the concentration of 1 microM also inhibited the sinus tachycardia. The protective effects of rutaecarpine on cardiac anaphylaxis were abolished by CGRP (8-37), a selective CGRP receptor antagonist. These results suggest that the protective effects of rutaecarpine on cardiac anaphylactic injury are related to inhibition of TNF-alpha production by stimulation of CGRP release.
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Alcaloides/farmacologia , Anafilaxia/prevenção & controle , Cardiotônicos/farmacologia , Evodia , Coração/efeitos dos fármacos , Fitoterapia , Alcaloides/administração & dosagem , Alcaloides/uso terapêutico , Anafilaxia/fisiopatologia , Animais , Pressão Sanguínea , Cardiotônicos/administração & dosagem , Cardiotônicos/uso terapêutico , Vasos Coronários/fisiopatologia , Feminino , Cobaias , Coração/fisiopatologia , Frequência Cardíaca , Alcaloides Indólicos , Masculino , Miocárdio/metabolismo , Quinazolinas , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Previous investigations have indicated that the pharmacological activities of evodiamine, a major alkaloidal component of the dried, unripe fruit of Evodia rutaecarpa Bentham (Rutaceae), are associated with the stimulation of calcitonin gene-related peptide (CGRP) release and that CGRP protects the myocardium against ischemia-reperfusion injury. In the present study, we have examined whether evodiamine protects against myocardial ischemia-reperfusion injury in rats and whether the protective effects of evodiamine are related to the activation of capsaicin-sensitive sensory nerves. Rats were pretreated with evodiamine 10 min before the experiment, and then the left main coronary artery of rat hearts was subjected to 60 min occlusion followed by 180 min reperfusion. Infarct size, the activity of serum creatine kinase, serum concentrations of TNF-alpha and plasma concentrations of CGRP were measured. Pretreatment with evodiamine (30 or 60 microg/kg, i.v.) markedly increased the content of CGRP in plasma concomitantly with a significant reduction in infarct size, the activity of serum creatine kinase, and TNF-alpha level, and the effects of evodiamine were completely abolished by capsazepine (5.0 mg/kg, s.c.), a competitive vanilloid receptor antagonist. These results suggest that evodiamine exerts a protection against myocardial ischemia-reperfusion injury in rats and that the protective effects of evodiamine are related to stimulation of CGRP release via activation of vanilloid receptors.
Assuntos
Capsaicina/análogos & derivados , Cardiotônicos/farmacologia , Evodia , Miocárdio/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Quinazolinas/farmacologia , Animais , Peptídeo Relacionado com Gene de Calcitonina/sangue , Cardiotônicos/administração & dosagem , Cardiotônicos/uso terapêutico , Creatina Quinase/sangue , Infusões Intravenosas , Masculino , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Quinazolinas/administração & dosagem , Quinazolinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Previous investigations have indicated that the pharmacological effects of evodiamine, a major alkaloidal component of the dried, unripe fruit of Evodia rutaecarpa Bentham (Rutaceae), are associated with stimulation of calcitonin gene-related peptide (CGRP) release and CGRP prevents cardiac anaphylactic injury. In the present study, the protective effects of evodiamine on cardiac anaphylaxis were examined. Presensitized guinea-pig hearts challenged with specific antigen (bovine serum albumin) caused a marked decrease in coronary flow, left ventricular pressure and its derivatives (+/-dp/dt(max)), an increase in heart rate, and prolongation of P-R interval. Evodiamine (0.3 microM or 1 microM) markedly increased the content of CGRP in the coronary effluent concomitantly with a significant improvement of cardiac function and alleviation of the extension of P-R interval. Evodiamine at the concentration of 1 microM also inhibited the sinus tachycardia. The protective effect of evodiamine on cardiac anaphylaxis was abolished by CGRP(8-37), the selective CGRP receptor antagonist. These results suggest that evodiamine possesses a protective effect of cardiac anaphylactic injury and that the effect of evodiamine is related to stimulation of CGRP release.