RESUMEN
There is evidence that BRCA1, particularly cytoplasmic BRCA1, plays a significant role in initiating apoptosis through various mechanisms. Maintaining the stability of BRCA1 in cancer cells may be a promising therapeutic strategy for breast cancer, especially in cases of triple-negative breast cancer (TNBC) lacking appropriate therapeutic targets. Previously, it was reported that cathepsin S (CTSS) interacts with the BRCT domain of BRCA1, leading to ubiquitin-mediated degradation. We further investigated the critical role of BRCA1 phosphorylation at Ser1387, which is mediated by ionizing radiation (IR)-induced activation of ATM. This phosphorylation event was identified as a key factor in CTSS-mediated ubiquitin degradation of BRCA1. The functional inhibition of CTSS, using small molecules or a knockdown system, sensitized TNBC cells when exposed to IR by restoring the stability of cytoplasmic BRCA1. The increase in cytoplasmic BRCA1 led to the degradation of anti-apoptotic BCL2, which was responsible for the radiosensitization effect observed with CTSS inhibition. These results suggest that inhibiting CTSS may be an effective strategy for radiosensitization in TNBC cells through BCL2 degradation that is mediated by inhibition of CTSS-induced BRCA1 degradation.
RESUMEN
Ribes diacanthum Pall (RDP) is a member of the Saxifragaceae family. The plant is traditionally used in Mongolia for the treatment of various ailments associated with kidney and bladder's diseases, cystitis, kidney stone, and edema. This study was aimed to investigate antioxidant activities of different solvent extracts of whole Pall plants, based on ferric-reducing antioxidant potential (FRAP), 2,2'-azinobis(3-ethybenzothiazoline-6-sulfonic acid) (ABTS· +) radical scavenging activity, 1,1-diphenyl-2-picrydrazyl (DPPH·), and hydroxyl (·OH) radical scavenging activities. Additionally, total flavonoids and phenolic contents (TPC) were also determined. The ethyl acetate extract of RDP (EARDP) had a remarkable radical scavenging capacity with an IC50 value of 0.1482 mg/mL. In addition, EARDP was shown to be higher in total phenolic and flavonoid contents than the methanol extract of RDP (MRDP). Moreover, the EARDP had the predominant antioxidant capacity, DPPH, hydroxyl, and ABTS radical scavenging activities and ferric reducing power. These results suggest a potential for R. diacanthum Pall extract as a functional medicinal material against free-radical-associated oxidative damage.
RESUMEN
BACKGROUND AND OBJECTIVES: In patients with neurocardiogenic syncope or presyncope, symptoms developed unpredictably and intermittently. The purpose of this study was to determine whether there was any significant difference in the recurrence rate of symptoms during the follow-up period between patients with many episodes of symptoms and those with fewer episodes of symptoms before diagnosis, as well as to assess the clinical significance of previous episodes of symptoms during treatment. SUBJECTS AND METHODS: A total of 100 patients with neurocardiogenic syncope or presyncope were divided in two groups (high episode group, n=54; low episode group, n=46) according to the frequency of symptoms before the head-up tilt test. We retrospectively analyzed the recurrence of symptoms using telephone interviews and medical record reviews. RESULTS: The clinical characteristics were not significantly different between the two groups. However, the recurrence rate was significantly lower in the high episode group than in the low episode group (5.6% vs. 19.6%, p=0.001). In the high episode group, patients treated with medication showed higher recurrence of symptoms than those without medication. In the lower episode group, a similar result was observed. CONCLUSION: The frequency of previous symptoms at the diagnosis of neurocardiogenic syncope or presyncope did not predict the occurrence of symptoms during the follow-up period. Therefore, to continue drug treatment based on the frequency of symptoms in patients with neurocardiogenic syncope or presyncope may not be the best option.
RESUMEN
BACKGROUND: The N-terminal fragment of pro Brain Natriuretic Peptide (NT-pro BNP) is a neuro-hormone synthesized in the cardiac ventricles in response to increased wall tension. The purpose of this study was to assess the correlation between the NT-pro BNP levels and the New York Heart Association function class (NYHA Fc) of dyspnea and echocardiographic findings for the patients who visited our cardiology departments. METHODS: From October, 2002 to April, 2003, serum NT-pro BNP levels were measured in 348 patients who visited the Samsung Medical Center and the Jong Koo Lee Heart Clinic. RESULTS: The NT-pro BNP levels were increased with the progression of NYHA Fc of dyspnea (p < 0.001 by ANOVA), the increase in the systolic left ventricular internal dimension (p < 0.05), and the decrease in the ejection fraction (p < 0.01). For the NYHA Fc I patients, the NT-pro BNP levels were positively correlated with age (0 < 0.001) and left atrial size (p < 0.001). For the patients with ischemic heart disease, the NT-pro BNP levels were also positively correlated with the NYHA Fc (p < 0.001 by ANOVA). The NT-pro BNP levels were increased with the increase in the systolic (p < 0.001) and diastolic pressure (p = 0.017), the left ventricular internal dimension as well as the decrease in the ejection fraction (p < 0.001). The area under the receiver operating characteristic (ROC) curve for the NT-pro BNP levels was 0.994 (95% confidence interval, 0.979-0.999), and the most reliable cut-off level for the NT-pro BNP was 293.6 pg/mL. CONCLUSION: The NT-pro BNP levels were positively correlated with the NYHA Fc of dyspnea and the systolic dysfunction for the patients who visited our cardiology departments. A 300 pg/mL value for the NT-pro BNP cut-off point appears to be a sensitive level to differentiate dyspnea originating from an ailing heart or not for the patients who visited our cardiology departments.
