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1.
Front Neurol ; 9: 949, 2018.
Article in English | MEDLINE | ID: mdl-30483211

ABSTRACT

Background: Evidence has shown that the greater the accumulation of risk factors for stroke, the greater the risk of stroke. Early intervention in the accumulation of risk factors for stroke can effectively reduce the incidence of stroke. The study aimed to investigate the distribution of the number of certain risk factors for stroke (hypertension, hyperlipidemia, overweight and obesity, and diabetes) and to explore the cause of the accumulation of certain stroke risk factors. Methods: A total of 4,052 participants aged 40 years or older were selected by the multistage stratified cluster sampling method in Dehui City in Jilin province, China. Descriptive data analyses were conducted. Multiple regression analyses were used to explore the adjusted association between the accumulation of key stroke risk factors and subjects' lifestyle and demographic characteristics. Results: Overall, 84.1% of the participants in this study had one or more of the four certain risk factors for stroke. The odds ratios (ORs) and 95% confidence intervals (CIs) of having ≥1, ≥2, and ≥3 key stroke risk factors were 1.627 (1.258, 2.103), 1.446 (1.209, 1.728), and 1.394 (1.164, 1.670), respectively, for males compared to females. Similarly, the ORs and 95% CIs of having ≥1, ≥2, and ≥3 key stroke risk factors were 1.227 (1.009, 1.492), 1.256 (1.096, 1.442), and 1.450 (1.262, 1.667), respectively, for partially salty diets compared to normal diets. Compared to people who did not exercise regularly, the ORs and 95% CIs of having ≥1, ≥2, and ≥3 key stroke risk factors were 0.693 (0.544, 0.883), 0.800 (0.679, 0.944), and 0.775 (0.659, 0.913), respectively, for people who regularly exercised. Compared to people who without a family history of cerebrovascular diseases, the ORs and 95% CIs were 1.418 (1.162, 1.732), 1.327 (1.154, 1.525), and 1.209 (1.050, 1.393), for people who with it. Conclusions: Male, partially salty diets, and family history of cerebrovascular diseases were risk factors for the accumulation of certain stroke risk factors while regular physical exercise was a protective factor.

2.
Eur J Med Chem ; 94: 298-305, 2015 Apr 13.
Article in English | MEDLINE | ID: mdl-25771108

ABSTRACT

Acetohydroxyacid synthase (AHAS) catalyzes the first essential biosynthetic step of branched-chain amino acids and is a biologically safe target against Mycobacterium tuberculosis (MTB). In our previous research, we used virtual screening to identify some novel AHAS inhibitors as potent antituberculosis agents. In this study, we synthesized twenty-four additional quinazolinone benzoates and explored their antitubercular activity. Five of these compounds displayed significant MTB-AHAS inhibition and their IC50 values were determined to be in the range of 6.50 µM-12.08 µM. Importantly, these compounds also exhibited strong in vitro activity (MICs in the range of 2.5-10 mg/L) and intracellular activity against clinically isolated extensively drug-resistant strains of M. tuberculosis. Taken together, these results indicated that the quinazolinone benzoate compounds should be regarded as promising lead compounds for the development of potent antituberculosis drugs with a novel mode of action.


Subject(s)
Acetolactate Synthase/antagonists & inhibitors , Antitubercular Agents/pharmacology , Benzoates/pharmacology , Enzyme Inhibitors/pharmacology , Mycobacterium tuberculosis/drug effects , Quinazolinones/pharmacology , Acetolactate Synthase/metabolism , Antitubercular Agents/chemical synthesis , Antitubercular Agents/chemistry , Benzoates/chemical synthesis , Benzoates/chemistry , Crystallography, X-Ray , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Microbial Sensitivity Tests , Models, Molecular , Molecular Structure , Quinazolinones/chemical synthesis , Quinazolinones/chemistry , Structure-Activity Relationship
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