RESUMO
Levels of hydrogen sulfide (H2S), a gaseous signaling molecule, are reduced in the serum of individuals who smoke. We hypothesized that tobacco smoke influenced smooth muscle relaxation by decreasing H2S levels and this effect could also influence expression of cystathionine γ-lyase (CSE) and sulfonylurea receptor-2 (SUR-2). The aim of this study was to explore the effect of tobacco smoke on H2S-mediated rat thoracic aorta relaxation and its possible mechanism. Thirty-two Sprague-Dawley rats were divided into four groups: control (C) group, short-term smoker (SS) group, mid-term smoker (MS) group, and long-term smoker (LS) group. H2S concentrations in serum, action of H2S on rat aortic vascular relaxation, and expression of CSE and SUR-2 in thoracic aortic smooth muscle were measured. Although there was no significant difference in H2S between the C and the SS groups, concentration of H2S was significantly reduced in both the LS and MS groups compared to control (P<0.01). Furthermore, H2S was significantly lower in the LS than in the MS group (P<0.05). Rat aortic vascular relaxation was lower in all three treatment groups compared to the control, with the most significant decrease observed in the LS group (P<0.05 compared to the MS group). Expression of CSE and SUR-2 was reduced in the LS and MS groups compared to control (P<0.05), with the lowest levels observed in the LS group (P<0.05). Therefore, tobacco smoke reduced expression of CSE and SUR-2 in rat thoracic aorta, which may inhibit H2S production and vascular dilation.
Assuntos
Aorta Torácica/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Sulfeto de Hidrogênio , Poluição por Fumaça de Tabaco , Animais , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
PURPOSE: To study the feasibility and clinical value of dynamic contrast-enhanced (DCE) computed tomography (CT) for early evaluation of targeted therapy efficacy in non-small cell lung cancer (NSCLC). METHODS: We measured tumor diameter, peak height (PH), time to peak (TP), tumor mass-aortic peak height ratio (M/A), and blood perfusion (BP) in 20 patients with advanced NSCLC using DCE-CT before and 7 days after treatment. Therapy efficacy was assessed with conventional CT 4-6 weeks post-treatment. RESULTS: Patients were grouped into those with partial response (PR), stable disease (SD), and progressive disease (PD) according to the therapy efficacy assessment at 4-6 weeks post-treatment. The PR group primary tumor diameter (P = 0.0007) and BP (P = 0.0225) were reduced at 7 days post-treatment; the SD group DCE-CT value changes were not significant. The PD group M/A (P = 0.0443) and BP (P = 0.0268) were increased 7 days post-treatment. The BP decrease group had significantly longer progression-free survival than the BP increase group (median, 54 vs. 6 weeks). CONCLUSION: DCE-CT can evaluate targeted therapy efficacy at 7 days post-treatment. Decreased primary tumor diameter and BP indicate tumor sensitivity to therapy; increased BP with unchanged tumor diameter suggests the tumor is not sensitive to therapy. Reduced BP suggests treatment effectiveness.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Tomografia Computadorizada Espiral/métodos , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Meios de Contraste , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Prognóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
To understand the effects of disease-resistant maize varieties and new cropping systems on the population of Curvularia lunata, 52 isolates of C. lunata were collected in China from 2011 to 2013. The isolates were analyzed in terms of phylogenetic relationships, morphology, and pathogenicity. Phylogenetic analysis showed that the 52 isolates clustered into 2 distinct clusters with further subdivisions, suggesting the emergence of new genetic divergence within C. lunata. Results of morphology and pathogenicity analyses demonstrated that there were significant differences among these isolates: 27 isolates were classified as fast growing, 5 as slow growing, and 20 as moderate growing. Three isolates had white-colored colonies, 13 had yellowish green-colored colonies, and the remaining isolates had dark green-colored colonies. Furthermore, conidiation rates were assessed: 30 isolates were characterized as having low conidiation rates, 15 as having medium conidiation rates, and the remaining 7 isolates as having high conidiation rates. Eleven of the isolates appeared to be strongly pathogenic against maize, 15 isolates proved to be weakly pathogenic against maize, and the remaining isolates were regarded to be moderately pathogenic. Interestingly, correlation analysis demonstrated a negative correlation between the growth rate and the pathogenicity of the isolates, while a positive correlation was observed between the conidiation rate and the pathogenicity. No correlation was observed between the colony color and the pathogenicity of the isolates.
Assuntos
Ascomicetos/genética , Ascomicetos/patogenicidade , Doenças das Plantas/microbiologia , Zea mays/microbiologia , China , Filogenia , VirulênciaRESUMO
Dilated cardiomyopathy (DCM) is a myocardial disease with a high mortality rate. Approximately 40 genes have been found to be associated with DCM to date. Non-familial DCM can also be caused by gene mutations, suggesting that genetic factors were involved in the pathogenesis of DCM; therefore genetic testing is beneficial for the early diagnosis of DCM, which can facilitate the implementation of preventive measures by and within patient's families. Here, we investigated the underlying genetic mutations involved in the cause of patients with DCM. This prospective study included 240 patients with idiopathic DCM and 240 healthy volunteers. Subject clinical data were collected and polymerase chain reaction amplification was carried out on subject DNA for three candidate genes tropomyosin (TPM1), cardiac troponin T type-2 (TNNT2), and nuclear lamina protein A/C. Single nucleotide polymorphism (SNP) loci were detected in the TPM1 (rs1071646) and TNNT2 (rs3729547) genes, respectively. The genotype distributions and allele frequencies were found to satisfy Hardy-Weinberg equilibrium, which indicated that the group was representative. Statistically significant differences were found between the variant frequencies in the two SNP loci between the Kazakh patients with idiopathic DCM (IDCM) and healthy volunteers. A significant difference in the genotype distributions (P = 0.000) and allele frequencies (P = 0.000) of SNP rs1071646, and another significant difference in the genotype distributions (P = 0.000) and allele frequencies (P = 0.039) of SNP rs3729547 between Kazakhs with IDCM and Kazakh controls. These results suggest that the TPM1 (rs1071646) and TNNT2 (rs3729547) gene variants might represent risk factors for patients with DCM in the Kazakh population.
Assuntos
Cardiomiopatia Dilatada/genética , Tropomiosina/genética , Troponina T/genética , Adulto , Sequência de Bases , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Sarcômeros/genética , Análise de Sequência de DNARESUMO
We investigated the effects of cadmium on lung cell DNA in immature mice. The mice were randomly divided into four groups: control group, low-dose group (1/100 LD(50)), middle-dose group (1/50 LD(50)), and high-dose group (1/25 LD(50)); they were supplied with cadmium chloride or control water for 40 days. Lung cells collected from sacrificed mice were used to evaluate the extent of DNA damage by comet assay. The ratio of tailing cells, DNA tail length, DNA comet length, DNA tail moment, DNA olive tail moment, and percentage of DNA in the comet tail were measured. The rate of tailing lung cells exposed to cadmium increased significantly; the low-concentration group had significantly (P < 0.05) higher rates, and the middle- and high-concentration groups had higher (P < 0.01) rates compared to the control. DNA tail length, DNA comet length, DNA tail moment, and DNA olive tail moment all increased with the increase in cadmium doses, but compared with those of the control group, no significant differences in low-dose group were found (P > 0.05), and the differences in middle- and high-dose groups were all highly significant (P < 0.01). The degree of DNA damage also increased with the increase of the cadmium concentrations. We conclude that cadmium significantly increases DNA damage in lung cells of immature mice in a dose-dependent manner.
Assuntos
Cloreto de Cádmio/toxicidade , Dano ao DNA , Água Potável/efeitos adversos , Pulmão/patologia , Poluentes Químicos da Água/toxicidade , Animais , Ensaio Cometa , Feminino , Dose Letal Mediana , Pulmão/efeitos dos fármacos , Masculino , CamundongosRESUMO
Evidence is accumulating that chronic inflammation has an important role in prostate cancer. Two common polymorphisms in the prostaglandin-endoperoxide synthase 2 (PTGS2) gene, rs20417 and rs689470, have been found to alter the risk for prostate cancer, but the various studies are not in agreement. To derive a more precise estimation of this association, all available studies were considered in a meta-analysis, with 10,700 patients and 13,021 controls for rs20417 and 4087 patients and 3761 controls for rs689470. We used odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) to determine the precision of the estimate. When all groups were pooled, we did not detect a significant association of rs20417 polymorphism with prostate cancer risk. Similarly, no associations were found in the subgroup analysis. However, we found that rs689470 was significantly associated with a trend towards increased prostate cancer risk when using both additive (OR = 2.15, 95%CI = 1.04-4.44, P = 0.04) and recessive models (OR = 2.07, 95%CI = 1.07-4.03, P = 0.03) to analyze the data. In subgroup analyses stratified by ethnicity, there was no evidence that rs689470 has a significant association with prostate cancer in Caucasians. Based on our meta-analysis, rs689470 polymorphism is significantly associated with prostate cancer risk in the overall population. Nevertheless, we suggest that further studies should be made to confirm these findings.