RESUMEN
Despite continuous progress in therapy, melanoma is one of the most aggressive and malignant human tumors, often relapsing and metastasizing to almost all organs. Cold atmospheric plasma (CAP) is a novel anticancer tool that utilizes abundant reactive oxygen and nitrogen species (RONS) being deposited on the target cells and tissues. CAP-induced differential effects between non-cancerous and cancer cells were comparatively examined. Melanoma and non-cancerous skin fibroblast cells (counterparts; both cell types were isolated from the same patient) were used for plasma-cell interactions. The production of intracellular RONS, such as nitric oxide (NO), hydroxyl radical (â¢OH), and hydrogen peroxide (H2O2), increased remarkably only in melanoma cancer cells. It was observed that cancer cells morphed from spread to round cell shapes after plasma exposure, suggesting that they were more affected than non-cancerous cells in the same plasma condition. Immediately after both cell types were treated with plasma, there were no differences in the amount of extracellular H2O2 production, while Hanks' balanced salt solution-containing cancer cells had lower concentrations of H2O2 than that of non-cancerous cells at 1 h after treatment. The melanoma cells seemed to respond to CAP treatment with a greater rise in RONS and a higher consumption rate of H2O2 than homologous non-cancerous cells. These results suggest that differential sensitivities of non-cancerous skin and melanoma cells to CAP-induced RONS can enable the applicability of CAP in anticancer therapy.
Asunto(s)
Melanoma , Gases em Plasma , Humanos , Gases em Plasma/farmacología , Oxígeno , Nitrógeno , Peróxido de Hidrógeno/metabolismo , Recurrencia Local de Neoplasia , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Homologous recombination (HR) plays a critical role in facilitating replication fork progression when the polymerase complex encounters a blocking DNA lesion, and it also serves as the primary mechanism for error-free DNA repair of double-stranded breaks. DNA repair protein RAD51 homolog 1 (RAD51) plays a central role in HR. However, the role of RAD51 during porcine early embryo development is unknown. In the present study, we examined whether RAD51 is involved in the regulation of early embryonic development of porcine parthenotes. We found that inhibition of RAD51 delayed cleavage and ceased development before the blastocyst stage. Disrupting RAD51 activity with RNAi or an inhibitor induces sustained DNA damage, as demonstrated by the formation of distinct γH2AX foci in nuclei of four-cell embryos. Inhibiting RAD51 triggers a DNA damage checkpoint by activating the ataxia telangiectasia mutated (ATM)-p53-p21 pathway. Furthermore, RAD51 inhibition caused apoptosis, reactive oxygen species accumulation, abnormal mitochondrial distribution and decreased pluripotent gene expression in blastocysts. Thus, our results indicate that RAD51 is required for proper porcine parthenogenetic activation (PA) embryo development.
Asunto(s)
Blastocisto/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Recombinasa Rad51/antagonistas & inhibidores , Animales , Apoptosis/efectos de los fármacos , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Blastocisto/metabolismo , Reparación del ADN/efectos de los fármacos , Femenino , Embarazo , Recombinasa Rad51/metabolismo , Transducción de Señal/efectos de los fármacos , Porcinos , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Objectives: Growth hormone (GH) therapy's capacity to increase height velocity and height at the end of the study in children with idiopathic short stature (ISS) is controversial. We aimed to investigate the height standard deviation score (SDS) and height velocity of patients with ISS in Korea who received GH treatment. Methods: We retrospectively reviewed and performed linear mixed model and survival analyses on data from 12 tertiary hospitals in Korea, including subjects diagnosed with ISS from January 2009 to September 2019, treated with GH therapy for more than 6 months, and who were at a pre-pubertal state at the time of diagnosis. Results: We included 578 children (330 boys and 248 girls). The mean daily dose of GH in this study was 0.051 mg/kg, which was lower than the approved dose in Korea of 0.062 - 0.067 mg/kg. Height SDS was higher in patients who started treatment before the age of 6 years. The probability of reaching the target SDS (-1 SDS) from the beginning of treatment to 2-3 years after its start was higher in children starting treatment before the age of 6 years. The hazard ratio to reach the target SDS (-1 SDS) when using automatic pen or electronic devices was 1.727 times higher than that when using the needle and syringe device. Conclusion: ISS patients should start GH treatment at an early age, and even lower-than-recommended drug doses may be effective. The selection of automatic pen or electronic device can have a positive effect on reaching the target height SDS.
Asunto(s)
Trastornos del Crecimiento , Hormona de Crecimiento Humana , Estatura , Niño , Femenino , Trastornos del Crecimiento/tratamiento farmacológico , Hormona del Crecimiento/farmacología , Humanos , Masculino , Estudios RetrospectivosRESUMEN
OBJECTIVES: The association between smoking and obesity is a significant public health concern. Both are preventable risk factors of cardiovascular disease and a range of other conditions. However, despite numerous previous studies, no consensus has emerged regarding the effect of smoking on obesity. We therefore carried out a novel study evaluating the relationship between smoking and obesity. METHODS: A total of 5,254 subjects aged 19 years or older drawn from the 2010-2013 Korea National Health and Nutrition Examination Survey were included in this cross-sectional study. Smoking was examined both in terms of smoking status and the quantity of cigarettes smoked by current smokers. Multiple logistic regression analysis was used to assess the association between smoking and obesity. Overall obesity was defined as a body mass index (BMI) ≥25 kg/m2, and central obesity was defined as a waist circumference ≥90 cm for males and ≥85 cm for females. We adjusted for the possible confounding effects of age, sex, physical activity, alcohol consumption, and the presence of hypertension or diabetes. RESULTS: A statistically significant difference in central obesity according to smoking status was identified. Current smokers were more likely to be centrally obese than never-smokers (adjusted odds ratio,1.30; 95% confidence interval, 1.02 to 1.67). However, no significant association was found between smoking and obesity defined by BMI. Moreover, among current smokers, no statistically significant association was found between the daily amount of smoking and obesity or central obesity. CONCLUSIONS: Smoking was positively associated with central obesity. Current smokers should be acquainted that they may be more prone to central obesity.