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921.
922.
Although estrogen action is indispensable for normal bone growth in both genders, the roles of estrogen receptors (ERs) in
mediating bone growth are not fully understood. The effects of ER inactivation on bone growth are sex and age dependent, and
may differ between the axial and appendicular regions. In this study, the spatial and temporal expression of ERα and β in
the tibial and spinal growth plates of the female and male rats during postnatal development was examined to explore the possible
mechanisms. The level of mRNA was examined and compared with quantitative real-time PCR. The spatial location was determined
by immunohistochemical analysis. The 1-, 4-, 7-, 12- and 16-week age stages correspond to early life, puberty and early adulthood
after puberty, respectively. Gender- and region-specific differences in ERα and β expression were shown in the growth plates.
Mainly nuclear staining of ERα and β immunoreactivity was demonstrated in the spinal and tibial growth plate chondrocytes
for both genders. Moreover, our study indicated significant effect of gender on temporal ERα and β expression and of region
on temporal ERα/ERβ expression ratio. However, spatial differences of region-related ERα and β expression were not observed.
Gender-related spatial changes were detected only at 16 weeks of both spine and limb growth plates. ERα and β immunoreactivity
was detected in the resting, proliferative and prehypertrophic chondrocytes in the early life stage and during puberty. After
puberty, ERα expression was mainly located in the late proliferative and hypertrophic chondrocytes in female, whereas the
expression still extended from the resting to hypertrophic chondrocytes in males. Gender- and region-specific expression patterns
of ERα and β gene might be one possible reason for differences in sex- and region-related body growth phenotypes. Gender,
age and region differences should be taken into consideration when the roles of ERs in the growth plate are investigated. 相似文献
923.
Zhao Y Tan Y Dai J Wang B Li B Guo L Cui J Wang G Li W Cai L 《The Journal of nutritional biochemistry》2012,23(8):1018-1026
Since zinc (Zn) plays an important role in the spermatogenesis and Zn deficiency exacerbated diabetes-induced testicular apoptosis, the present study investigated the effect of Zn deficiency on diabetes-induced testicular Akt-mediated glucose metabolism changes and inflammation. Zn deficiency was induced by chronic treatment of normal and diabetic mice with the Zn chelator N,N,N',N', tetrakis (2-pyridylmethyl) ethylenediaminepentaethylene (TPEN). After diabetes onset induced by streptozotocin, both diabetic and age-matched control mice were given TPEN intraperitoneally for 4 months. Western blotting assay revealed that Akt-mediated glucose metabolism signaling was down-regulated in the diabetic testis and was further decreased in diabetic mice with Zn deficiency, reflected by reduced phosphorylation of both Akt and GSK-3β and increased phosphorylation of glycogen synthase along with a disarrangement of fatty acid metabolism (increased expression of PPAR-α and decreased adenosine-monophosphate-activated protein kinase phosphorylation). Testicular expressions of plasminogen activator inhibitor-1 and intracellular adhesion molecule-1 as inflammatory factors were increased in the TPEN or diabetes-alone group, but not additive in the group of diabetes with Zn deficiency. A mechanistic study showed that Akt negative regulators phosphatase and tensin homology deleted on chromosome 10 (PTEN), protein tyrosine phosphatases 1B and Tribbles 3 all increased in diabetic testis and further increased in the testis of diabetic mice with Zn deficiency. These studies suggest that Zn deficiency significantly exacerbated diabetic down-regulation of Akt expression and function, most likely by up-regulation of Akt negative regulators. Therefore, prevention of Zn deficiency for diabetic patients is important in order to avoid the exacerbation of diabetic inhibition of glucose metabolism in the testis. 相似文献
924.
Zvarec O Polyak SW Tieu W Kuan K Dai H Pedersen DS Morona R Zhang L Booker GW Abell AD 《Bioorganic & medicinal chemistry letters》2012,22(8):2720-2722
Herein we outline the antibacterial activity of amino acid containing thiazolidinediones and rhodanines against Gram-positive bacteria Staphylococcus aureus ATCC 31890, Staphylococcus epidermidis and Bacillus subtilis ATCC 6633. The rhodanine derivatives were generally more active than the analogous thiazolidinediones. Compounds of series 5 showed some selectivity for Bacillus subtilis ATCC 6633, the extent of which is enhanced by the inclusion of a non-polar amino acid at the 5-position of the core thiazolidinediones and rhodanines scaffolds. SAR data of series 8 demonstrated improved activity against the clinically more significant Staphylococci with selectivity over Bacillus subtilis ATCC 6633 induced by introduction of a bulky aryl substituent at the 5-position of the core scaffolds. 相似文献
925.
Dong MX Lu L Li H Wang X Lu H Jiang S Dai QY 《Bioorganic & medicinal chemistry letters》2012,22(9):3284-3286
A series of novel 1,4-disubstituted piperidine/piperazine derivatives were designed, synthesized and evaluated for their in vitro activities against HIV-1 Bal (R5) infection in CEMX174 5.25M7 cells. A majority of these compounds showed potent anti-HIV-1 activities with IC(50) at nanomolar levels. N-(4-Fluoro-benzyl)piperazine analog B07 hydrochloride exhibited potency against HIV-1 activity similar to that of TAK-220 hydrochloride, but it had much better water solubility (25 mg/ml in phosphate sodium buffer at 25 °C) and oral bioavailability (56%) than TAK-220 hydrochloride (a solubility of 2 mg/ml and oral bioavailability of 1.4%). These results suggest that B07 hydrochloride may serve as a better lead for the development of new anti-HIV-1 therapies or microbicides for treatment and prevent of HIV-1 infection. 相似文献
926.
Yan YM Dai HQ Du Y Schneider B Guo H Li DP Zhang LX Fu H Dong XP Cheng YX 《Bioorganic & medicinal chemistry letters》2012,22(12):4179-4181
In this study, we report three novel naturally occurring compounds, blapsins A (1) and B (2), and blapsamide (3) from the ethanol extract of the stink beetle, Blaps japanensis. The structures of these compounds were determined using spectroscopic methods. Compound 3 is a phenolic compound bearing a formamido group in the structure. Functional studies revealed that compounds 1 and 2 potently inhibited 14-3-3 protein-protein interactions (PPIs) with IC(50) values of 9.2 and 10.0 μM as determined by an ELISA assay, and 2.0 and 2.5 μM in an FP assay, respectively. These compounds represent the first example of natural small-molecule 14-3-3 inhibitors. 相似文献
927.
Chen X Mihalic J Fan P Liang L Lindstrom M Wong S Ye Q Fu Y Jaen J Chen JL Dai K Li L 《Bioorganic & medicinal chemistry letters》2012,22(1):363-366
A series of spiropiperidine carbazoles were synthesized and evaluated as MCHR2 antagonists using a FLIPR assay. The pharmacokinetic properties of selected compounds have also been studied. This effort led to the discovery of potent and specific MCHR2 antagonists. Compound 38 demonstrated good pharmacokinetic properties across rat, beagle dog and rhesus monkey and had a favorable selectivity profile against a number of other receptors. These MCHR2 antagonists are considered appropriate tool compounds for study of the function of MCHR2 in vivo. 相似文献
928.
Mihalic JT Fan P Chen X Chen X Fu Y Motani A Liang L Lindstrom M Tang L Chen JL Jaen J Dai K Li L 《Bioorganic & medicinal chemistry letters》2012,22(11):3781-3785
An initial SAR study resulted in the identification of the novel, potent MCHR1 antagonist 2. After further profiling, compound 2 was discovered to be a potent inhibitor of the hERG potassium channel, which prevented its further development. Additional optimization of this structure resulted in the discovery of the potent MCHR1 antagonist 11 with a dramatically reduced hERG liability. The decrease in hERG activity was confirmed by several in vivo preclinical cardiovascular studies examining QT prolongation. This compound demonstrated good selectivity for MCHR1 and possessed good pharmacokinetic properties across preclinical species. Compound 11 was also efficacious in reducing body weight in two in vivo mouse models. This compound was selected for clinical evaluation and was given the code AMG 076. 相似文献
929.
Tang J Dai Y Zhang H Culleton RL Liu Y Zhao S Wang X Guan X Kaneko O Zhu Y 《Parasitology》2012,139(6):709-715
Plasmodium rhoptry neck protein 2 (RON2), which is released from the neck portion of the merozoite rhoptries and interacts with the microneme protein Apical Membrane Antigen 1 (AMA1), plays a crucial role in erythrocyte invasion. In this study, we sequenced the Plasmodium vivax RON2 gene from 19 P. vivax isolates collected in central China in order to establish whether this protein is under positive diversifying selection, which may occur as a result of protective host immune pressure?. In comparison with the P. vivax Sal-1 reference line, we found 10 amino acid substitutions dispersed throughout the open reading frame as well as indels caused by polymorphism in a repeat unit (21-23 repeats of (Q/E/K/N/H)(G/D)G(H/L/Y/P)G) in the second tandem repeat region located at amino acid positions 541-650. A McDonald-Kreitman test with RON2 sequences from the primate malaria parasite Plasmodium knowlesi, detected significant departure from neutrality in the PvRON2 3' region (nucleotide positions 2668-6609). These results suggest that the PvRON2 gene has evolved under positive diversifying selection. 相似文献
930.
During the examination of specimens of Theleporus and Grammothele (Polyporales, Basidiomycota) from tropical China, three new species, Theleporus membranaceus, T. minisporus and Grammothele denticulata, were identified based on both morphological and phylogenetic analyses. They are described and illustrated. T. membranaceus is characterized by its extremely thin basidiocarps (0.12 mm), small pores (7-10 per mm) and ellipsoid to broadly ellipsoid basidiospores. T. minisporus has the smallest basidiospores among the species in the genus. Grammothele denticulata is distinguished in the genus by gray pores, continuous hymenia over dissepiment edge and cylindrical basidiospores with tapering apex. Two annotated identification keys are provided for species thus far accepted in Theleporus and Grammothele. The phylogenetic relationships of Theleporus and Grammothele were inferred based on nITS sequences and are briefly discussed. The molecular evidence showed that Theleporus and Grammothele belong to the core polyporoid clade. 相似文献