Knockdown of lncRNA PVT1 inhibits the proliferation and accelerates the apoptosis of colorectal cancer cells via the miR­761/MAPK1 axis.

Colorectal cancer (CRC) is associated with high morbidity rates. Long non­coding RNAs (lncRNAs) participate in the development of CRC. However, the potential roles of lncRNA plasmacytoma variant translocation 1 (PVT1) in CRC remain unknown. Therefore, the aim of the present study was to investigate the potential roles of PVT1 in CRC. Reverse transcription­quantitative PCR and western blot analyses were conducted to determine the mRNA and protein expression levels. The cellular behaviors were detected using 5­Ethynyl­2'­deoxyuridine, Cell Counting Kit­8 and flow cytometry assays. The interaction between PVT1 and microRNA (miR)­761 or MAPK1 was confirmed using a dual­luciferase reporter assay. Moreover, the Pearson's method was applied for correlation analysis. The results demonstrated that the expression levels of PVT1 and MAPK1 were upregulated, while miR­761 was downregulated in CRC tissues. The expression of PVT1 was positively correlated with MAPK1 and negatively correlated with miR­761. In addition, PVT1 sponged miR­761 to upregulate MAPK1 expression. It was found that the knockdown of PVT1 expression inhibited the proliferation and promoted the apoptosis of CRC cells, which was more potent in cells transfected with miR­761. The regulatory role of small interfering RNA­PVT1 on the expression of apoptosis­related genes was reduced by MAPK1. Collectively, the present results suggested that knockdown of PVT1 may inhibit the progression of CRC by regulating the miR­761/MAPK1 axis, which may provide a promising biomarker for the treatment of CRC.

Dichloroacetate attenuates the stemness of colorectal cancer cells via trigerring ferroptosis through sequestering iron in lysosomes.

Colorectal cancer stem cell (CSC) has been regarded to be the root of colorectal cancer progression. However, there is still no effective therapeutic method targeting colorectal CSC in clinical application. Here, we investigated the effects of dichloroacetate (DCA) on colorectal cancer cell stemness. We showed that DCA could reduce colorectal cancer cell stemness in a dose-dependent manner, which is evident by the decreased expression of stemness markers, tumor cell sphere-formation and cell migration ability. In addition, it was found that DCA trigerred the ferroptosis of colorectal CSC, which is characterized as the upregulation of iron concentration, lipid peroxides, and glutathione level, and decreased cell viability. Mechanistic studies demonstrated that DCA could sequester iron in lysosome and thus trigger ferroptosis, which is necessary for DCA-mediated attenuation on colorectal cancer cell stemness. Taken together, this work suggests that DCA might be a colorectal CSC-killer.

Halitosis and helicobacter pylori infection: A meta-analysis.

BACKGROUND: Halitosis is used to describe any disagreeable odor of expired air regardless of its origin. Numerous trials published have investigated the relation between Helicobacter pylori (H pylori) infection and halitosis, and even some regimes of H pylori eradication have been prescribed to those patients with halitosis in the clinic. We conducted a meta-analysis to define the correlation between H pylori infection and halitosis. OBJECTIVES: To evaluate whether there is a real correlation between H pylori infection and halitosis, and whether H pylori eradication therapy will help relieve halitosis. METHODS: We searched several electronic databases (The Cochrane Library, MEDLINE, EMBASE, PubMed, Web of Science, and Wanfangdata) up to December 2015. Studies published in English and Chinese were considered in this review. After a final set of studies was identified, the list of references reported in the included reports was reviewed to identify additional studies. Screening of titles and abstracts, data extraction and quality assessment was undertaken independently and in duplicate. All analyses were done using Review Manager 5.2 software. RESULTS: A total of 115 articles were identified, 21 of which met the inclusion criteria and presented data that could be used in the analysis. The results showed that the OR of H pylori infection in the stomach between halitosis-positive patients and halitosis-negative patients was 4.03 (95% CI: 1.41-11.50; P = 0.009). The OR of halitosis between H pylori-positive patients and H pylori-negative patients was 2.85 (95% CI: 1.40-5.83; P = 0.004); The RR of halitosis after successful H pylori eradication in those H pylori-infected halitosis-positive patients was 0.17 (95% CI: 0.08-0.39; P <0.0001), compared with those patients without successful H pylori eradication. And the RR of halitosis before successful H pylori eradication therapy was 4.78 (95% CI: 1.45-15.80; P = 0.01), compared with after successful H pylori eradication therapy. CONCLUSIONS: There is clear evidence that H pylori infection correlates with halitosis. H pylori infection might be important in the pathophysiological mechanism of halitosis, and H pylori eradication therapy may be helpful in those patients with refractory halitosis.

Improved autophagic flux is correlated with mTOR activation in the later recovery stage of experimental acute pancreatitis.

BACKGROUND/OBJECTIVES: Lysosomal/autophagic pathway plays important role in the early onset of acute pancreatitis (AP). However, its role in the later recovery phase of AP is unknown. This study aims to investigate the role of lysosomal/autophagic pathway in the self-limited program of AP and elucidate the underlying mechanisms. METHODS: AP was induced in the rat by 3% sodium taurocholate injection in the pancreaticobiliary duct. Serum amylase activity assay, histological examination, and cell death detection were used to assess the time course of AP severity. Meanwhile, the expression of LC3-II, p62 and Lamp-2 was measured to evaluate the status of autophagic flux. S6RP phosphorylation was detected to determine the time course of mTOR activation. Rapamycin was administered to block mTOR activity. RESULTS: AP developed in the rats to the most severe at 24 h but tended to self-restore at 36 and 48 h. The impairment of autophagic flux characterized by the accumulation of LC3-II and p62 and the depletion of Lamp-2 occurred at 24 h after AP induction followed by the restoration over the following 24 h. Furthermore, the phosphorylation of S6RP was increased at 36 and 48 h after AP induction despite the initial inhibition. Rapamycin treatment reduced the level of phospho-S6RP and inhibited the restoration of autophagic homeostasis and pancreatic tissue injury. CONCLUSIONS: Activation of mTOR is correlated with the improvement of autophagic flux and pancreatic injury, suggesting that mTOR activation plays a potential protective role in the later recovery of AP.