Terpenoids from the barks of Magnolia maudiae (Dunn) Figlar.

A new germacrenolide (1) and fourteen known terpenoids (2-15) were isolated from the barks of Magnolia maudiae (Dunn) Figlar (Magnoliaceae). The structure of (7αH,11ßH)-2α,8α-dihydroxy-4α,5ß-epoxy-germacr-1(10)-en-6α,12-olide (1) was elucidated by physical and spectroscopic data analysis, including 1D, 2D NMR and HR-ESI-MS. Lyratol F (9) was isolated from Magnolia for the first time. The structures of known compounds were established by comparing their spectroscopic data with those in literatures.

Inhibition control impairments in adolescent smokers: electrophysiological evidence from a Go/NoGo study.

Smoking during adolescence may promote nicotine dependence later on in life. Therefore, it is extremely important to study the neural mechanisms of adolescent smokers. As inhibition control is emphasized in several contemporary theoretical models of addiction, in the current study, we focused on the electrophysiological evidence of inhibition control deficits in adolescent smokers. By using relatively homogenous groups of adolescent smokers (n = 18) and matched nonsmokers (n = 18), we employed event-related potentials (ERP) to investigate the N200 and P300 amplitude and latency differences during a Go/NoGo task between the adolescent smokers and nonsmokers. Relative to nonsmokers, more NoGo response errors, reduced NoGo P300 amplitude, and longer P300 latency were observed in adolescent smokers. Correlation analysis revealed that the NoGo P300 amplitudes were significantly correlated with NoGo errors in both adolescent smokers and nonsmokers. Our findings provided direct electrophysiological evidence for inhibitory control impairments in adolescent smokers. It is hoped that our results may enhance understanding of the pathology of inhibitory control in adolescent smokers.

Polymorphism of rs2767485 in Leptin Receptor Gene is Associated With the Occurrence of Adolescent Idiopathic Scoliosis.

STUDY DESIGN: A genetic association study of leptin receptor (LEPR) gene with adolescent idiopathic scoliosis (AIS) in the Chinese Han population. OBJECTIVE: To determine whether LEPR gene polymorphisms are associated with the predisposition and/or disease severity of AIS. SUMMARY OF BACKGROUND DATA: Patients with AIS were reported to have lower body mass index (BMI), abnormal leptin bioavailability, and systemic lower bone mass, which implied that leptin/LEPR signaling pathway may be implicated in the etiology of AIS. Previous association study of the polymorphisms in leptin gene did not show significant differences between AIS cases and controls. However, no study has been done to investigate the relationship between genetic polymorphisms of the LEPR gene and susceptibility to AIS. METHODS: 570 patients with AIS aged 10 to 18 years were enrolled, and 570 age-matched healthy subjects were recruited as controls. 6 single nucleotide polymorphisms (SNPs) (rs1137101, rs1137100, rs4655555, rs2767485, rs1751492, and rs8179183) of LEPR gene were selected. The polymorphisms were genotyped using the polymerase chain reaction (PCR)-based Invader assay. Case-control study was performed to define the contribution of the 6 SNPs to predisposition of AIS. 1-way analysis of variance (ANOVA) test was used to compare the mean Cobb angles and BMI among patients with different genotypes in case-only analyses. Statistical significance was set at P < 0.05. RESULTS: Both the genotype and allele frequencies of SNP rs2767485 were significantly different between the patient with AIS and the control groups. No significant difference of allele frequency was noted in other 5 SNPs between the patients with AIS and the normal controls. Both the mean maximum Cobb angles and BMI of different genotype AIS groups were similar to each other for all the 6 SNPs (P > 0.05). CONCLUSION: Polymorphism of rs2767485 in LEPR gene is associated with the occurrence of AIS, suggesting LEPR is a predisposition gene.

[Correlation between the shifting of medulla oblongata and cerebellum and syrinx resolution after posterior fossa decompression in Chiari malformation].

OBJECTIVES: To evaluate the changes of the position of medulla oblongata and cerebellum following posterior fossa decompression (PFD), and to investigate their influences on the prognosis of the syringomyelia in adolescents with Chiari malformation (CM). METHODS: A retrospective review was performed on all CM patients between September 2006 and September 2011. A subset of 46 patients, including 25 male and 21 female patients, was finally enrolled according to the inclusion criteria. The initial age and duration of follow-up averaged 13.9 years (range, 10-17 years) and 13 months (range, 6-52 months), respectively. On mid-sagittal MRI, the following parameters were evaluated pre- and postoperatively (follow-up ≥ 6 months): the longitudinal and transverse position of bulbopontine sulcus, the fourth ventricle vertex, the lower extreme of cerebella tonsil, the cervico-medullary angle, the maximal syrinx/cord(S/C) ratio and the syrinx length. Changes in these parameters were analysed using the paired samples t test, and for these reaching statistical significances, an additional bivariate correlation analysis was performed to investigate their relation with syrinx resolution. RESULTS: At the latest follow-up, upward shifting of the bulbopontine sulcus was observed in 31 patients(67.4%), with upward shifting of the lower extreme of cerebella tonsil presenting in 35 patients(76.0%). The maximal S/C ratio and the syrinx length were significantly improved postoperatively (t = 7.114 and 7.816, P = 0.000).Significant resolution of the syrinx was demonstrated in 40 patients(86.9%), and more specifically, the average improvement rates of the maximal S/C ratio and the syrinx length were 32% ± 30%and 43% ± 33%, respectively. In addition, the bivariate correlation analysis revealed that syrinx resolution was significantly correlated with the upward shifting of the bulbopontine sulcus (r = 0.332, P = 0.027) and lower extreme of cerebella (r = 0.298, P = 0.044) . CONCLUSION: The upward shifting of the bulbopontine sulcus and the lower extreme of cerebella tonsil might be implicated in the mechanisms of postoperative syrinx resolution.

Cell cycle phenotype-based optimization of G2-abrogating peptides yields CBP501 with a unique mechanism of action at the G2 checkpoint.

Cell cycle G(2) checkpoint abrogation is an attractive strategy for sensitizing cancer cells to DNA-damaging anticancer agent without increasing adverse effects on normal cells. However, there is no single proven molecular target for this therapeutic approach. High-throughput screening for molecules inhibiting CHK1, a kinase that is essential for the G(2) checkpoint, has not yet yielded therapeutic G(2) checkpoint inhibitors, and the tumor suppressor phenotypes of ATM and CHK2 suggest they may not be ideal targets. Here, we optimized two G(2) checkpoint-abrogating peptides, TAT-S216 and TAT-S216A, based on their ability to reduce G(2) phase accumulation of DNA-damaged cells without affecting M phase accumulation of cells treated with a microtubule-disrupting compound. This approach yielded a peptide CBP501, which has a unique, focused activity against molecules that phosphorylate Ser(216) of CDC25C, including MAPKAP-K2, C-Tak1, and CHK1. CBP501 is >100-fold more potent than TAT-S216A and retains its selectivity for cancer cells. CBP501 is unusually stable, enters cells rapidly, and increases the cytotoxicity of DNA-damaging anticancer drugs against cancer cells without increasing adverse effects. These findings highlight the potency of CBP501 as a G(2)-abrogating drug candidate. This report also shows the usefulness of the cell cycle phenotype-based protocol for identifying G(2) checkpoint-abrogating compounds as well as the potential of peptide-based compounds as focused multitarget inhibitors.

Butyrolactone I reversibly alters nuclear configuration, periooplasmic microtubules and development of porcine oocytes.

In the present study, we investigated the effects of specific cdc2 kinase inhibitor, butyrolactone I (BL I) on the prevention of germinal vesicle breakdown, changes of microtubular structures, and development of porcine oocytes after removal of the drug. In Experiment 1, cumulus-oocyte complexes (COCs) were cultured (44 h) in NCSU-23 medium containing different concentrations of BL I. The percentages of oocytes remaining at GV stage were 0, 0, 32, 80, and 84% (P<0.05), and the maturation rates were 86, 63, 30, 0, and 0% (P<0.05) for oocytes treated with 0, 10, 20, 40, and 80 microM of BL I, respectively. When oocytes were released from BL I incubation (Experiment 2) and cultured for an additional 44 h, 79, 84, and 83% of oocytes resumed meiosis, but only 52, 38 and 17% of oocytes reached normal metaphase II (MII) stage in the groups treated with 20, 40 and 80 microM BL I, respectively. In Experiments 3-5, reversibility and development of oocytes and embryos were evaluated after removal of the inhibitor. A reduced duration of BL I incubation (22 h) at 20 microM increased the percentage of oocytes remaining at the GV stage compared to the control group (85% versus 9%, P<0.05). Blastocyst rates were lower in treatment groups than in the control (44 h) group (0-14% versus 24%; P<0.05). However, all developing blastocysts possessed similar cell numbers, regardless of the drug-treated or non-treated controls. Taken together, treatment with 20-80 microM of BL I effectively prevented the resumption of meiosis and polymerization of periooplasmic microtubules. Furthermore, reversibility of the oocytes after reduced duration of BL I treatment was satisfactory.