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991.
Ha YM Park YJ Lee JY Park D Choi YJ Lee EK Kim JM Kim JA Park JY Lee HJ Moon HR Chung HY 《Biochimie》2012,94(2):533-540
Herein we describe the design, synthesis and biological activities of 2-(substituted phenyl)thiazolidine-4-carboxylic acid derivatives as novel tyrosinase inhibitors. The target compounds 2a–2j were designed and synthesized from the structural characteristics of N-phenylthiourea, tyrosinase inhibitor and tyrosine, and l-DOPA, the natural substrates of tyrosinase. Among them, (2R/S,4R)-2-(2,4-dimethoxyphenyl)thiazolidine-4-carboxylic acid (2g) caused the greatest inhibition 66.47% at 20 μM of l-DOPA oxidase activity of mushroom tyrosinase. Kinetic analysis of tyrosinase inhibition revealed that 2g is a competitive inhibitor. We predicted the tertiary structure of tyrosinase, and simulated the docking of mushroom tyrosinase with 2g. These results suggest that the binding affinity of 2g with tyrosinase is high. Also, 2g effectively inhibited tyrosinase activity and reduced melanin levels in B16 cells treated with α-MSH. These data strongly suggest that 2g can suppress the production of melanin via the inhibition of tyrosinase activity. 相似文献
992.
Guillain-Barré syndrome (GBS) is an inflammatory disorder that may implicate proinflammatory cytokines such as tumor necrosis
factor alpha (TNF-alpha) in its pathogenesis. The association between TNF-alpha 308 G/A polymorphism and GBS largely remains
unknown. The aim of this study was to investigate the association between TNF-alpha 308 G/A polymorphism and GBS in Chinese
Han patients. TNF-alpha 308 G/A polymorphism in 150 GBS patients and 150 healthy controls were studied using polymerase chain
reaction–restriction fragment length polymorphism (PCR–RFLP) assay. Patients with GBS had a significantly higher frequency
of TNF-alpha 308AA genotype [odds ratio (OR) = 3.79, 95% confidence interval (CI) = 1.03, 13.94; P = 0.04] than controls. When stratified by the GBS subtype, there was a significantly higher frequency of TNF-alpha 308AA
genotype in patients with AMAN (OR = 6.05, 95% CI = 1.45, 25.31; P = 0.01) and AMSAN (OR = 5.56, 95% CI = 1.18, 26.23; P = 0.03) than controls. There was no significant difference in the distribution of each genotype between patients with AIDP
and the control group. These data indicated that TNF-alpha 308AA genotype was associated with a higher risk of GBS in Chinese
population, especially to AMAN and AMSAN. 相似文献
993.
Some studies have shown that IL-18 was associated with aetiology and progression of asthma. However, the association between
single-nucleotide polymorphisms −607C/A (rs1946518) and −137G/C (rs187238) located in the IL-18 gene promoter and asthma risk
was still controversial and ambiguous. To derive a more precise effect on the association between these polymorphisms and
asthma risk, we performed a meta-analysis based on the currently available evidence of the literature. A total of 5 studies
with 1411 cases and 1525 controls for −607C/A polymorphism and 5 studies with 1883 cases and 6645 controls for −137G/C polymorphism
were identified to perform a meta-analysis, up to October 2010. Summary ORs and corresponding 95% CIs for IL-18 polymorphisms
and asthma were estimated using fixed- and random-effects models when appropriate. Heterogeneity and publication bias were
evaluated. We found that individuals carrying AC/CC genotype of −607C/A polymorphism were associated with an increased asthma
risk in recessive model (OR = 1.278; 95% CI, 1.073–1.522). However, no significant association was observed between −137G/C
polymorphism and asthma risk under different contrast models. There was no evidence of publication bias. The present meta-analysis
suggested that IL-18 −607C/A polymorphism in promoter region was associated with asthma risk. 相似文献
994.
To replicating the associations of type 2 diabetes (T2D) and six novel reported variants in Han Chinese lean individuals of
first episode T2D, a total of six high risk single nucleotide polymorphisms (SNPs) from the BCL11A, DUSP9, IRS1, CENTD2, ADRA2A, and CDKAL1 genes were examined. Candidate six SNPs were genotyped in 761 T2D patients and 433 control subjects, and associations between
the six SNPs and Body Mass Index (BMI), Fasting Plasma Glucose (FPG) and Two Hours Oral Glucose Tolerance Test (2hOGTT) were
also investigated. CDKAL1 provided the strongest evidence for replication, where rs7754840 was associated with T2D (odds ratio = 1.54, per copy of
the risk C allele, P = 8.10 × 10−7). SNP rs5945326 at DUSP9 showed modest significance (odds ratio = 0.81, per copy of the protective G allele, P = 0.02). After adjusting the confounders of age, gender and BMI, the above results remain significant for both rs7754840
(P < 1.0 × 10−4) and rs5945326 (P = 0.043) respectively. After correcting for multiple testing, however, only the association between T2D and rs7754840 at
CDKAL1 (P < 1×10−4) remains significant. In addition, the risk C allele of CDKAL1 rs7754840 was significantly associated with increased FPG levels (P = 3.8 × 10−4). The association between genetic variant in CDKAL1 gene was detected in the Han Chinese lean individuals. The correlation between rs7754840-C allele and increased FPG levels
is consistent with the potential function of CDKAL1 gene in pancreatic islets. 相似文献
995.
Li JM Yao ZF Zou YZ Ge JB Guan AL Wu J Mi SL Liang YY Ma Z 《Molecular biology reports》2012,39(1):5-12
In animal models of clinical entities causative of severe right and left ventricular (LV) pressure overload hypertrophy, increased
density of the cellular microtubule network, through viscous loading of active myofilaments, causes contractile dysfunction
that is normalized by microtubule depolymerization. In this study, 86 male mice were divided into seven groups. The transverse
ascending aorta constriction (TAC) in six groups were performed in order to make heart failure model. Mice in each group were
injected with G-CSF or/and telmisartan subcutaneously at different time respectively. Results showed that reduction in left
ventricular volume and improved function persisted at 2 week, but recurrent dilatation at 4 weeks was associated with a loss
of functional improvement. Compared with PBS group, the expression of VEGF protein and HIF-1 mRNA were significantly higher
in mice injected with G-CSF or/and telmisartan (P < 0.05). The expression of p53 mRNA, myocardial fibrosis and mortality were significantly lower in mice injected with G-CSF
or/and telmisartan (P < 0.05). It could be concluded that G-CSF can delay the progression of pressure overload induced ventricular reconstruction
and heart failure in mice. 相似文献
996.
Tsai MS Yang YL Wang AH Wang LS Lu DC Liou CH Hsieh LY Wu CJ Cheng MF Shi ZY Lo HJ 《Mycopathologia》2012,174(2):121-130
A total of 35 Trichosporon isolates were collected from the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) project from 1999 to 2006, and their identifications as well as drug susceptibilities were determined. The most frequently isolated species was T. asahii (62.9%), and the most common clinical sample that yielded Trichosporon isolates was urine (37.1%). The etiology of all seven invasive trichosporonosis was T. asahii. For the 22 T. asahii isolates, the MIC(50) and MIC(90) for amphotericin B were 0.25 and 1 μg/mL, respectively. Those for fluconazole were 2 and 4 μg/mL, respectively, and for voriconazole 0.031 and 0.063 μg/mL, respectively. When the intraclass correlation coefficients (ICCs) and agreements were calculated, we found that the MICs of fluconazole obtained from different methods were similar and the inter-method discrepancies were low. Nevertheless, no unanimous MIC of amphotericin B and voriconazole was obtained among different methods. 相似文献
997.
Tang Z Yuan S Hu Y Zhang H Wu W Zeng Z Yang J Yun J Xu R Huang P 《Journal of bioenergetics and biomembranes》2012,44(1):117-125
It has long been observed that many cancer cells exhibit increased aerobic glycolysis and rely more on this pathway to generate
ATP and metabolic intermediates for cell proliferation. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key enzyme in
glycolysis and has been known as a housekeeping molecule. In the present study, we found that GAPDH expression was significantly
up-regulated in human colorectal carcinoma tissues compared to the adjacent normal tissues, and also increased in colon cancer
cell lines compared to the non-tumor colon mucosa cells in culture. The expression of GAPDH was further elevated in the liver
metastatic tissues compared to the original colon cancer tissue of the same patients, suggesting that high expression of GAPDH
might play an important role in colon cancer development and metastasis. Importantly, we found that 3-bromopyruvate propyl
ester (3-BrOP) preferentially inhibited GAPDH and exhibited potent activity in inducing colon cancer cell death by causing
severe depletion of ATP. 3-BrOP at low concentrations (1–10 μM) inhibited GAPDH and a much higher concentration (300 μM) was
required to inhibit hexokinase-2. The cytotoxic effect of 3-BrOP was associated with its inhibition of GAPDH, and colon cancer
cells with loss of p53 were more sensitive to this compound. Our study suggests that GAPDH may be a potential target for colon
cancer therapy. 相似文献
998.
In order to study functional gene expression in Streptomyces coelicolor, a mini-transposon encoding the apramycin resistance gene aac(3)IV within its inverted repeat (IR) boundaries was constructed based on IS204, which was previously identified in the genome of Nocardia asteroides YP21. The mini-transposon and IS204 transposase gene were then put on a kanamycin-resistant conjugative plasmid pDZY101 that can only replicate in Escherichia coli. After mating with S. coelicolor A3(2) M145, resistant colonies arose efficiently on both apramycin and kanamycin plates. Plasmid rescue indicated that entire plasmids were inserted into the M145 genome with cleavage at an inverted repeat junction formed by the right inverted repeat (IRR) and the last 18 bp of the transposase gene, while the left inverted repeat (IRL) was untouched. Southern blot analysis of the mutants using an aac(3)IV gene probe showed that transposition of plasmid pDZY101 was genetically stable, with a single-copy insertion within the S. coelicolor M145 genome. Several mutagenesis libraries of S. coelicolor M145 were constructed using plasmid pDZY101 derivatives and the transposon insertion site was determined. The correlation between novel mutant phenotypes and previously uncharacterized genes was established and these transposon locations were widely scattered around the genome. 相似文献
999.
Yoo BK Yanda MK No YR Yun CC 《American journal of physiology. Gastrointestinal and liver physiology》2012,303(2):G180-G188
The Caco-2 cell line represents absorptive polarized intestinal epithelial cells that express multiple forms of Na(+)/H(+) exchanger (NHE) in their plasma membranes. Caco-2 cells express the major apical NHE isoform NHE3, but low NHE3 expression together with inefficient transfection often hamper intended studies. In this study, we examined whether SK-CO15 cells could be used to study NHE3 regulation. SK-CO15 cells grown on Transwell inserts developed polarized epithelial cells with microvilli. The transfection efficiency of SK-CO15 cells was markedly higher compared with Caco-2 cells, an advantage in gene transfer and knockout. SK-CO15 cells expressed NHE1, NHE2, and NHE3. NHE3 expression was significantly greater in these cells than Caco-2, and NHE3 comprised more than half of total NHE activity. Apical expression of NHE3 in SK-CO15 cells was confirmed by confocal immunofluorescence and surface biotinylation. NHE regulatory factors NHERF1 and NHERF2, which are important for regulation of NHE3 activity, were expressed in these cells. Stimulatory response of NHE3 in SK-CO15 cells was assessed by dexamethasone and lysophosphatidic acid (LPA). Treatment with dexamethasone for 24-48 h increased NHE3 expression and activity. Similarly to Caco-2 cells, SK-CO15 cells lacked the expression of the LPA receptor LPA(5,) but exogenous expression of LPA(5) resulted in acute stimulation of NHE3. Forskolin acutely inhibited NHE3 activity in SK-CO15 cells, further attesting the validity of these cells. We conclude that SK-CO15 cells with the amenity for transfection and high endogenous NHE3 expression are a new and better cell model for NHE3 regulatory investigation than widely used Caco-2 cells. 相似文献
1000.
Hae‐June Lee Yeung Bae Jin Tae‐Hong Kim Jeong‐Ki Pack Nam Kim Hyung‐Do Choi Jae‐Seon Lee Yun‐Sil Lee 《Bioelectromagnetics》2012,33(4):356-364
Wireless mobile phones and other telecommunication devices are used extensively in daily life. We therefore examined the effects of combined exposure to radiofrequency electromagnetic fields (RF‐EMF) on rat testicular function, specifically with respect to sensitive processes such as spermatogenesis. Male rats were exposed to single code division multiple access (CDMA) and wideband code division multiple access (WCDMA) RF signals for 12 weeks. The RF exposure schedule comprised 45 min/day, 5 days/week for a total of 12 weeks. The whole‐body average specific absorption rate (SAR) of CDMA and WCDMA was 2.0 W/kg each or 4.0 W/kg in total. We then investigated the correlates of testicular function such as sperm count in the cauda epididymis, testosterone concentration in the blood serum, malondialdehyde concentrations in the testes and epididymis, frequency of spermatogenesis stages, and appearance of apoptotic cells in the testes. We also immunoblotted for p53, bcl2, GADD45, cyclin G, and HSP70 in the testes of sham‐ and combined RF‐exposed animals. Based on the results, we concluded that simultaneous exposure to CDMA and WCDMA RF‐EMFs at 4.0 W/kg SAR did not have any observable adverse effects on rat spermatogenesis. Bioelectromagnetics 33:356–364, 2012. © 2011 Wiley Periodicals, Inc. 相似文献