Effects of enriched environment on the expression of ß-amyloid and transport-related proteins LRP1 and RAGE in chronic sleep-deprived mice.

Sleep plays an important role in the learning process and memory consolidation, and sleep deprivation (SD) leads to inadequate memory consolidation and plays an important role in brain development and plasticity. SD increases ß-amyloid levels while impairing cognitive function. We explored the effect of enriched environment (EE) on ß-amyloid and transporter protein LRP1 and receptor for advanced glycosylation end-products (RAGE) expression in chronic sleep deprived mice. We randomly divided mice into four groups (n = 10), the standard environment group (Ctrl group), the sleep deprivation group (SD group), the enriched environment intervention group (EE group), and the sleep deprivation plus environmental enrichment intervention group (SD + EE group). A modified multi-platform SD model was used to sleep deprive the mice for 19 h per day. Five hours of EE intervention was performed daily in the EE group and the SD + EE group, respectively. The behavioral measurements of mice were performed by Y-maze method and new object recognition; the expression levels of Aß1-42, LRP1, and RAGE in prefrontal cortex and hippocampus of mice were measured by immunofluorescence; the expression levels of LRP1 and RAGE in prefrontal cortex and hippocampus were detected by Western blot. The results showed that EE could effectively ameliorate the effects of SD on cognitive impairment, reduce SD induced Aß deposition, and decrease the expression of RAGE, while increase the expression of LRP1.

Author Correction: Impact of low lethal concentrations of buprofezin on biological traits and expression profile of chitin synthase 1 gene (CHS1) in melon aphid, Aphis gossypii.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Impact of low lethal concentrations of buprofezin on biological traits and expression profile of chitin synthase 1 gene (CHS1) in melon aphid, Aphis gossypii.

Buprofezin, a chitin synthesis inhibitor that can be used for the control of hemipteran pests, especially melon aphid, Aphis gossypii. The impact of low lethal concentrations of buprofezin on the biological parameters and expression profile of CHS1 gene were estimated for two successive generations of A. gossypii. The present result shows that the LC15 and LC30 of buprofezin significantly decreased the fecundity and longevity of both generations. Exposure of F0 individuals to both concentrations delay the developmental period in F1. Furthermore, the survival rate, intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (R0) were reduced significantly in progeny generation at both concentrations. However, the reduction in gross reproductive rate (GRR) was observed only at LC30. Although, the mean generation time (T) prolonged substantially at LC30. Additionally, expression of the CHS1 gene was significantly increased in F0 adults. Significant increase in the relative abundance of CHS1 mRNA transcript was also observed at the juvenile and adult stages of F1 generation following exposure to LC15 and LC30. Therefore, our results show that buprofezin could affect the biological traits by diminishing the chitin contents owing to the inhibition of chitin synthase activity in the succeeding generation of melon aphid.

AMP-activated protein kinase α1 serves a carcinogenic role via regulation of vascular endothelial growth factor expression in patients with non-small cell lung cancer.

AMP-activated protein kinase α1 (AMPK α1) is involved in the tumorigenesis of various cancer types. However, the role of AMPK α1 in non-small cell lung cancer (NSCLC) remains unclear. In the present study, 99 NSCLC tumor tissues and paired normal tissues were obtained. The expression levels of AMPK α1 were significantly upregulated in NSCLC tumor tissues compared with those in adjacent non-tumor lung tissues. The patients were further divided into two groups according to their expression levels of AMPK α1 in tumor tissues. The results outlined that overexpression of AMPK α1 was associated with poor prognosis. In addition, vascular endothelial growth factor (VEGF) expression levels were associated with malignant progression in patients with NSCLC. Patients with NSCLC that overexpressed AMPK α1 and VEGF had the worst outcomes. Moreover, AMPK α1 may positively regulate VEGF expression. These results suggest that AMPK α1 serves a carcinogenic role at least in part through the regulation of VEGF expression, and thus represents a potential treatment target in patients with NSCLC.

Mono-2-ethyhexyl phthalate advancing the progression of prostate cancer through activating the hedgehog pathway in LNCaP cells.

Hedgehog (Hh) pathway plays a critical role in the progression of prostate cancer (PCa), the most commonly diagnosed non-cutaneous cancer in male adults. Studies showed that di-n-butyl phthalate (DBP) could interference with the Hh pathway. Di-2-ethylhexyl phthalate (DEHP), the congener of DBP, is the major plasticizer used in plastic materials that are inevitably exposed by patients with PCa. The aim of this in vitro study was to investigate whether mono-2-ethyhexyl phthalate (MEHP, the active metabolite of DEHP) could activate the Hh pathway of LNCaP cells. Results showed that the expression of the critical gene of Hh pathway PTCH and androgen-regulated gene KLK3 was significantly decreased on 3, 6 and 9 days with Hh pathway inhibitor cyclopamine's treatment. MEHP notably up-regulated the expression of PTCH with a dose-response relationship in the presence of cyclopamine, which indicate that MEHP might target on the downstream components of Hh pathway and advance the progression of PCa through activating the Hh pathway.

Method for location of puncture point guided by digital mammography image.

The main purpose of this study was to develop a method that can optimize the algorithm for puncture point calculation, and therefore improve the accuracy of X-ray guided breast biopsy. The proposed method is: first, select two guiding points; then, use the guiding points to construct X-ray cone-beams, so the joining section of the cone-beams can be used to determine the puncture target point. The method was verified by a phantom emulation, in which the calculated target-points were all found within the central part of the target lesion, and far away from the boarder of the lesion (change the x-ray tube angle by 15° would only cause a slight deviation no more than 1.4 mm), the accuracy is enough to fulfill the needs of biopsy operation. This study also found out that, the shorter the distance between the guiding point and the center of the lesion's project, the nearer the calculated biopsy-point will be to the actual lesion center.

MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN.

BACKGROUND: MicroRNAs (miRNAs) can function as either oncogenes or tumor suppressor genes via regulation of cell proliferation and/or apoptosis. MiR-221 and miR-222 were discovered to induce cell growth and cell cycle progression via direct targeting of p27 and p57 in various human malignancies. However, the roles of miR-221 and miR-222 have not been reported in human gastric cancer. In this study, we examined the impact of miR-221 and miR-222 on human gastric cancer cells, and identified target genes for miR-221 and miR-222 that might mediate their biology. METHODS: The human gastric cancer cell line SGC7901 was transfected with AS-miR-221/222 or transduced with pMSCV-miR-221/222 to knockdown or restore expression of miR-221 and miR-222, respectively. The effects of miR-221 and miR-222 were then assessed by cell viability, cell cycle analysis, apoptosis, transwell, and clonogenic assay. Potential target genes were identified by Western blot and luciferase reporter assay. RESULTS: Upregulation of miR-221 and miR-222 induced the malignant phenotype of SGC7901 cells, whereas knockdown of miR-221 and miR-222 reversed this phenotype via induction of PTEN expression. In addition, knockdonwn of miR-221 and miR-222 inhibited cell growth and invasion and increased the radiosensitivity of SGC7901 cells. Notably, the seed sequence of miR-221 and miR-222 matched the 3'UTR of PTEN, and introducing a PTEN cDNA without the 3'UTR into SGC7901 cells abrogated the miR-221 and miR-222-induced malignant phenotype. PTEN-3'UTR luciferase reporter assay confirmed PTEN as a direct target of miR-221 and miR-222. CONCLUSION: These results demonstrate that miR-221 and miR-222 regulate radiosensitivity, and cell growth and invasion of SGC7901 cells, possibly via direct modulation of PTEN expression. Our study suggests that inhibition of miR-221 and miR-222 might form a novel therapeutic strategy for human gastric cancer.

Curcumin synergistically augments bcr/abl phosphorothioate antisense oligonucleotides to inhibit growth of chronic myelogenous leukemia cells.

AIM: To investigate the growth inhibition effect of the combination of bcr/abl phosphorothioate antisense oligonucleotides (PS-ASODN) and curcumin (cur), and the possible mechanisms of cur on the chronic myelogenous leukemia cell line K562. METHODS: The K562 cell line was used as a P210( bcr/abl )-positive cell model in vitro and was exposed to different concentrations of PS-ASODN (0-20 micromol/L), cur (0-20 micromol/L), or a combination of both. Growth inhibition and apoptosis of K562 cells were assessed by MTT assay and AO/EB fluorescent staining, respectively. The expression levels of P210( bcr/abl ), NF-kappaB and heat shock protein 90 (Hsp90) were assessed by Western blot. RESULTS: Exposure to cur (5-20 micromol/L) and PSASODN (5-20 micromol/L) resulted in a synergistic inhibitory effect on cell growth. Growth inhibition was associated with the inhibition of the proliferation and induction of apoptosis. Western blot analysis showed that the drugs synergistically downregulated the level of P210( bcr/abl ) and NF-kappaB. Cur downregulated Hsp90, whereas no synergism was observed when cur was combined with PS-ASODN. CONCLUSION: PS-ASODN and cur exhibited a synergistic inhibitory effect on the cell growth of K562. The synergistic growth inhibition was mediated through different mechanisms that involved the inhibition of P210( bcr/abl ).

Down-regulation of p210(bcr/abl) by curcumin involves disrupting molecular chaperone functions of Hsp90.

AIM: To investigate the effects of curcumin (Cur) on p210(bcr/abl) level in K562 cells, and the relationship between these effects and the molecular chaperone functions of heat shock protein 90 (Hsp90). METHODS: Flow cytometry and Western blot were used to examine the abundance of p210(bcr/abl), Hsp90, p23, Hsp70, and p60(Hop) in K562 cells treated with Cur. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the bcr-abl mRNA level in K562 cells treated with Cur. After co-immunoprecipitation of p210(bcr/abl) and its molecular chaperones, the immunoprecipitate was then subjected to Western blot analysis with anti-Hsp90, anti-Hsp70, anti-p23, and anti- p60(Hop)mAb. RESULTS: An exposure of K562 cells to Cur produced time-dependent down-regulation of p210(bcr/abl), the inhibition rate of p210(bcr/abl) in K562 cells determined by flow cytometry after treatment with Cur 27.2 micromol/L for 1 h, 6 h, 12 h and 24 h was 31.2%, 63.7%, 81.3% and 94.5%, respectively. In contrast, Cur had almost no influence on bcr-abl mRNA level. Treatment with Cur for 24 h reduced the association of p210(bcr/abl) with Hsp90/p23 complex, while increasing the association of p210(bcr/abl) with Hsp70/ p60(Hop) complex; however, the total protein abundance of Hsp90, p23, and p60(Hop) in K562 cells had no apparent change, while Hsp70 increased greatly. CONCLUSION: Down-regulation of p210(bcr/abl) by Cur involves dissociating the binding of p210(bcr/abl) with Hsp90/p23 complex. In contrast, the association of p210(bcr/abl) with Hsp70/ p60(Hop) complex increased.