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951.
Dong-Il Kang Jee-Young Lee Woonghee Kim Ki-Woong Jeong Soyoung Shin Jiyoung Yang Eujin Park Young Kee Chae Yangmee Kim 《Molecules and cells》2010,29(6):595-602
With the aid of receptor-oriented pharmacophore-based in silico screening, we established three pharmacophore maps explaining the binding model of hPNMT and a known inhibitor, SK&F 29661
(Martin et al., 2001). The compound library was searched using these maps. Nineteen selected candidate inhibitors of hPNMT
were screened using STD-NMR and fluorescence experiments. An enzymatic activity assay based on HPLC was additionally performed.
Consequently, three potential hPNMT inhibitors were identified, specifically, 4-oxo-1,4-dihydroquinoline-3,7-dicarboxylic
acid, 4-(benzo[d][1,3]dioxol-5-ylamino)-4-oxobutanoic acid, and 1,4-diaminonaphthalene-2,6-disulfonic acid. These novel inhibitors
were retrieved using Map II comprising one hydrogen bond acceptor, one hydrogen bond donor, one lipophilic feature, and shape
constraints, including a hydrogen bond between Lys57 of hPNMT and a hydrogen bond donor of the inhibitor, and stacked hydrophobic
interactions between the side-chain of Phe182 and an aromatic region of the inhibitor. Water-mediated interactions between
Asn267 and Asn39 of hPNMT and the amide or amine group of three potent inhibitors were additional important features for hPNMT
activity. The binding model presented here may be applied to identify inhibitors with higher potency. Moreover, our novel
compounds are valuable candidates for further lead optimization of PNMT inhibitors. 相似文献
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Age-related hearing impairment (ARHI) is becoming a more significant issue as geriatric population increases. Sarcopenia in older people is known to have a diverse health problem in various circumstances in recent studies. We assessed whether the decrease in muscle mass is related to ARHI. We used the 2010 data of the Korea National Health and Nutrition Examination Survey (KNHANES) to examine the associations between sarcopenia and ARHI. A total number of participants was 1,622 including 746 males and 876 females aged 60 years or older. Muscle mass was assessed as an appendicular skeletal muscle mass, and hearing loss was defined as the pure-tone averages (PTA) of test frequencies 0.5, 1, 2, 4 kHz at a threshold of 40 dB or higher in worse hearing side of the ear. Among 1,622 participants, 298 men and 256 women had hearing loss. Appendicular muscle mass (ASM), expressed as kg, was categorized in tertiles. In female population, after adjusting for age, smoking, drinking, amount of exercise, total body fat, education level, income level, and tinnitus, the odds ratio (OR) for hearing loss was 1.57 (95% confidence interval (CI) = 0.92–2.68) in the middle tertile and 1.79 (1.03–3.08) in the lowest tertile, compared with the highest tertile. P for trend in this model was 0.036. Controlling further for hypertension, diabetes mellitus, chronic kidney disease, and three types of noise exposure did not change the association. Larger muscle mass is associated with lower prevalence of hearing loss in elderly Korean females. 相似文献
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957.
Young Seok Park Young Joo Jeon Hyun Seok Kim Kyu Young Chae Seung-Hun Oh In Bo Han Hyun Sook Kim Won-Chan Kim Ok-Joon Kim Tae Gon Kim Joong-Uhn Choi Dong-Seok Kim Nam Keun Kim 《PloS one》2012,7(10)
We conducted a case-control study to investigate whether vascular endothelial growth factor (VEGF −2578, −1154, −634, and 936) and kinase insert domain containing receptor (KDR −604, 1192, and 1719) polymorphisms are associated with moyamoya disease. Korean patients with moyamoya disease (n = 107, mean age, 20.9±15.9 years; 66.4% female) and 243 healthy control subjects (mean age, 23.0±16.1 years; 56.8% female) were included. The subjects were divided into pediatric and adult groups. Among the 64 surgical patients, we evaluated collateral vessel formation after 2 years and divided patients into good (collateral grade A) or poor (collateral grade B and C) groups. The frequencies and distributions of four VEGF (−2578, −1154, −634, and 936) and KDR (−604, 1192, and 1719) polymorphisms were assessed from patients with moyamoya disease and compared to the control group. No differences were observed in VEGF −2578, −1154, −634, and 936 or KDR −604, 1192, and 1719 polymorphisms between the control group and moyamoya disease group. However, we found the −634CC genotype occurred less frequently in the pediatric moyamoya group (p = 0.040) whereas the KDR −604C/1192A/1719T haplotype increased the risk of pediatric moyamoya (p = 0.024). Patients with the CC genotype of VEGF −634 had better collateral vessel formation after surgery. Our results suggest that the VEGF −634G allele is associated with pediatric moyamoya disease and poor collateral vessel formation. 相似文献
958.
Hak-Jae Kim Kyeong-Hun Park Dong-Hwi Kim Han-Jung Chae Gi-Ho Sung Young-Ock Kim 《Saudi Journal of Biological Sciences》2018,25(6):1135-1139
Recent research has confirmed that Panax ginseng (P. ginseng) has effect on cultured osteoblast of the mouse. In this study we aim to validate the usefulness of tibia quantification by correlating micro-computed tomographic (microCT) images with histology analysis in the aged male rats. A total of thirty – old male WISTAR rats were used and divided into ten 8?weeks rats and ten 112?weeks aged rats with vehicle and ten 112?weeks aged rats with P. ginseng (300?mg/kg/day). Daily oral administration of P. ginseng lasted for 8?weeks. Bone histomorphometric parameters and the trabecular bone microarchitectural properties of tibia were determined by microCT scan. MicroCT analysis showed significantly lower bone mineral density (BMD) and trabecular bone number in the aged group. Ginseng prevented total BMD decrease in the tibia induced by natural aging, which was accompanied by a significant decrease in skeletal remodeling. Furthermore, the aged group with ginseng was found to have a significantly higher osteoblast. In the blood biochemistry results, serum phosphorus, calcium, osteocalcin, T3, and T4 remained unchanged. The present study indicated that P. ginseng might be a potential alternative medicine for the prevention and treatment of natural aging-induced osteoporosis in human. 相似文献
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960.
Mi-Young Chae Juyoung Yoon Anthony W. Czarnik 《Journal of molecular recognition : JMR》1996,9(4):297-303
Pb(II) ion serves as a quencher of anthracene fluorescence both intermolecularly and in intracomplex systems reported to date. The advantages of intensimetric analyses showing increasing signal require the design of mechanistically novel fluorescent chemosensors capable of yielding enhanced fluorescence upon chelation of inherently quenching metals. We synthesized both 2- and 9-derivatives of anthracene bearing the N-methylthiohydroxamate ligand, which is capable of quenching fluorescence in the uncomplexed form and which shows some selectivity for Pb(II). Complexation of the 2-derivative to Pb(II) results in rapid metal ion-catalyzed hydrolysis, rendering this compound useless as a sensor with real-time response. However, complexation of the 9-derivative with Pb(II) results in a 13-fold fluorescence increase, reversible upon dissociation of the metal ion. While blood lead analysis is a major potential application for fluorescent chemosensors, the present compound is insufficiently selective for this use. 相似文献