Abstract. Increased deposition of β-amyloid (Aβ) protein is one of the typical characteristics of Alzheimer's disease (AD). Recent evidence has demonstrated that the microRNA let-7 family, which is highly expressed in the central nervous system, participates in the regulation of pathologic processes of AD. In the present study, the effect of let-7a overexpression on Aβ1-40-induced neurotoxicity was evaluated in PC12 and SK-N-SH cells. The results indicated that overexpression of let-7a enhanced the neurotoxicity induced by Aβ1-40 in PC12 and SK-N-SH cells. In addition, the apoptosis induced by Aβ1-40 in PC12 and SK-N-SH cells was increased by let-7a overexpression. Furthermore, Aβ1-40 treatment increased the protein levels of microtubule-associated protein 1A/1B-light chain 3 (LC3) and beclin-1 and increased the LC3 II/I ratio. The mRNA expression levels of beclin-1, autophagy protein 5 (Atg-5) and Atg-7 were also increased by Aβ1-40 treatment in PC12 cells. Let-7a overexpression further upregulated the above autophagy-related markers. Furthermore, the protein level of p62 was increased by Aβ1-40 treatment, and this was further enhanced by let-7a overexpression. Finally, the present results demonstrated that the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was involved in the autophagy regulation by let-7a. In conclusion, the present study demonstrates that the neurotoxicity induced by Aβ1-40 is augmented by let-7a overexpression via regulation of autophagy, and the PI3K/Akt/mTOR signaling pathway also serves a function in this process.

Objective: To investigate the effect of Sulfiredoxin-1 (Srxn1) on astrocyte injury induced by hydrogen peroxide (H 2 O 2 ). Methods: Observing the changes of H 2 O 2 on contents of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) and apoptosis after transfected Srxn1 siRNA into astrocytes. The protein expression of Notch 1, NICD and Hes1, the content of LDH and MDA, the activity of SOD and apoptosis rate of astrocytes after inhibiting or activation of Notch signalling pathway were detected by Western blot, ELISA and flow cytometry, respectively. Results: Knockdown of Srxn1 could promote the secretion of LDH and MDA, decrease the activity of SOD and aggravate apoptosis of astrocytes induced by H 2 O 2 . The results of Western blot, ELISA assay and flow cytometry indicated that activation of the Notch signalling pathway attenuated the effect of Srxn1 on H 2 O 2 -induced oxidative damage and apoptosis of astrocytes. Conclusion: Srxn1 may protect astrocytes from oxidative stress injury induced by H 2 O 2 by activation of Notch signalling pathway.

This study aimed to evaluate survival trends for patients with gastric cancer in northeast China in the most recent three decades and analyze the applicability of the UICC tumor-node-metastasis (TNM) classification 7 th edition for Chinese patients with gastric cancer. A review of all inpatient and outpatient records of patients with gastric cancer was conducted in the first hospital of China Medical University and the Liaoning Cancer Hospital and Institute. All patients who met the inclusion criteria and were seen from January 1980 through December 2009 were included in the study. The primary outcome was 5-year survival, which was analyzed according to decade of diagnosis and TNM classifications. From 1980 through 2009, the 5-year survival rates for patients with gastric cancer (n=2414) increased from 39.1% to 57.3%. Decade of diagnosis was significantly associated with patient survival (p = 0.013), and the 5-year survival rate in the 2000s was remarkably higher than that in the 1980s and 1990s (p = 0.004 and 0.049, respectively). When classified according to the UICC TNM classification of gastric cancer 7 th edition, the prognoses of stage IIIA and stage IIIB patients were not significantly different (p = 0.077). However, if stage T4b and stage N0 patients were classified as stage IIIA, the prognoses of stage IIIA and stage IIIB patients were significantly different (p < 0.001). Hence, there was a significant difference in survival during the three time periods in Northeast China. Classifying stage T4b and stage N0 patients as stage IIIA according to the 7 th edition of UICC gastric cancer TNM classifications better stratified Chinese patients and predicted prognoses.

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BackgroundPrevious studies showed that glutathione S-transferase Pi 1 (GSTP1) is a critical metabolic driver that is heightened specifically in triple negative breast cancer (TNBC) and drives breast cancer pathogenicity. This study focuses on investigating the relationship between the expression of the GSTP1 protein and TNBC metastasis and prognosis in China.ResultsChi-square and Fisher's exact tests showed that tumor size (P=0.023) and clinical stage (P=0.049) were significantly associated with GSTP1 expression. Patients with high GSTP1 expression exhibited an improved survival rate compared with patients with low GSTP1 expression, but the difference was not statistically significant (P=0.437). On multivariate analysis, clinical stage proved to be an independent prognostic factor for survival in breast cancer.Materials and methodsA total of 175 patients with histologically confirmed TNBC, who also underwent radical surgery between January 2008 and November 2011 at the Liaoning Cancer Hospital, were enrolled. Immunohistochemistry was used to detect GSTP1 expression in breast cancer tissue from 175 patients. The correlations between GSTP1 expression and other parameters were evaluated using the Chi-square and Fisher's exact tests. Univariate and multivariate Cox regression analyses were performed to assess independent prognostic factors for survival. Associations of GSTP1 expression with clinical stage and prognosis were analyzed using Kaplan–Meier survival curves.ConclusionsTumors with high GSTP1 protein expression were independently associated with low clinical stages in TNBC patients in China. The expression of the GSTP1 protein may be a novel prognosis marker for TNBC patients in China.