Correlations between indices of dynamic components of ambulatory blood pressure and renal damage in elderly Chinese male with essential hypertension
BLOOD PRESSURE MONITORING
Authors: Leng, Wen-Xiu; Zhang, Meng; Cui, Hua; Zeng, Long-Huan; Hu, Yi-Xin
Abstract
Objective Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is an accurate method to document changes in blood pressure (BP) and is more predictive than office and home BP monitoring for cardiovascular outcomes in elderly people. We aimed to determine the relationship between ABPM indices and renal damage in elderly Chinese male patients with essential hypertension. Methods We investigated 998 Chinese men (mean age of 78.44 +/- 12.02 years) with essential hypertension. Renal function, laboratory testing, and ABPM, including ABP, BP variability, and BP circadian rhythms were investigated. Data were shown according to BP controlling status. The relationships between ABPM indices and renal damage [expressed by urine protein, urine albumin/creatinine ratio (uACR), estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN)] were assessed using multiple regression analysis. Results After adjustments for age, common cardiovascular risk factors, and medications, uACR level was positively associated with 24-h mean systolic blood pressure (SBP), 24-h mean pulse pressure (PP), and 24-h SBP percent time of elevation. eGFR level was negatively associated with the 24-h mean SBP and 24-h mean PP. BUN level was positively correlated with the 24-h mean SBP, 24-h mean PP, and 24-h SBP percent time of elevation, whereas the BUN level was negatively associated with the 24-h DBP SD. Conclusion The ABPM indices associated with renal damage may be regarded as an early predictive marker for renal function impairment in Chinese elderly male patients with hypertension.
Discovery of a dual inhibitor of NQO1 and GSTP1 for treating glioblastoma
JOURNAL OF HEMATOLOGY & ONCOLOGY
Authors: Lei, Kecheng; Gu, Xiaoxia; Alvarado, Alvaro G.; Du, Yuhong; Luo, Shilin; Ahn, Eun Hee; Kang, Seong Su; Ji, Bing; Liu, Xia; Mao, Hui; Fu, Haian; Kornblum, Harley I.; Jin, Lingjing; Li, Hua; Ye, Keqiang
Abstract
Background Glioblastoma (GBM) is a universally lethal tumor with frequently overexpressed or mutated epidermal growth factor receptor (EGFR). NADPH quinone oxidoreductase 1 (NQO1) and glutathione-S-transferase Pi 1 (GSTP1) are commonly upregulated in GBM. NQO1 and GSTP1 decrease the formation of reactive oxygen species (ROS), which mediates the oxidative stress and promotes GBM cell proliferation. Methods High-throughput screen was used for agents selectively active against GBM cells with EGFRvIII mutations. Co-crystal structures were revealed molecular details of target recognition. Pharmacological and gene knockdown/overexpression approaches were used to investigate the oxidative stress in vitro and in vivo. Results We identified a small molecular inhibitor, "MNPC," that binds to both NQO1 and GSTP1 with high affinity and selectivity. MNPC inhibits NQO1 and GSTP1 enzymes and induces apoptosis in GBM, specifically inhibiting the growth of cell lines and primary GBM bearing the EGFRvIII mutation. Co-crystal structures between MNPC and NQO1, and molecular docking of MNPC with GSTP1 reveal that it binds the active sites and acts as a potent dual inhibitor. Inactivation of both NQO1 and GSTP1 with siRNA or MNPC results in imbalanced redox homeostasis, leading to apoptosis and mitigated cancer proliferation in vitro and in vivo. Conclusions Thus, MNPC, a dual inhibitor for both NQO1 and GSTP1, provides a novel lead compound for treating GBM via the exploitation of specific vulnerabilities created by mutant EGFR.
COA
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