[Retracted] Rotenone restrains colon cancer cell viability, motility and epithelial­mesenchymal transition and tumorigenesis in nude mice via the PI3K/AKT pathway.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the immunofluorescence staining data shown in Fig. 3C, and the migration and invasion assay data shown in Figs. 4C and 4D were strikingly similar to data appearing in different form in other research articles written by different authors at different research institutes that had either already been published, or were submitted for publication at around the same time, one of which has been retracted. In addition, the western blotting data shown for the E­cadherin and AKT protein bands in Fig. 5 were strikingly similar, albeit the bands had been flipped vertically. Owing to the fact that contentious data in the above article had already been submitted for publication elsewhere prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 44: 700­708, 2020; DOI: 10.3892/ijmm.2020.4637].

Evaluation of the competence of an artificial intelligence-assisted colonoscopy system in clinical practice: A post hoc analysis.

Background: Artificial intelligence-assisted colonoscopy (AIAC) has been proposed and validated in recent years, but the effectiveness of clinic application remains unclear since it was only validated in some clinical trials rather than normal conditions. In addition, previous clinical trials were mostly concerned with colorectal polyp identification, while fewer studies are focusing on adenoma identification and polyps size measurement. In this study, we validated the effectiveness of AIAC in the clinical environment and further investigated its capacity for adenoma identification and polyps size measurement. Methods: The information of 174 continued patients who went for coloscopy in Chongqing Rongchang District People's hospital with detected colon polyps was retrospectively collected, and their coloscopy images were divided into three validation datasets, polyps dataset, polyps/adenomas dataset (all containing narrow band image, NBI images), and polyp size measurement dataset (images with biopsy forceps and polyps) to assess the competence of the artificial intelligence system, and compare its diagnostic ability with endoscopists with different experiences. Results: A total of 174 patients were included, and the sensitivity of the colorectal polyp recognition model was 99.40%, the accuracy of the colorectal adenoma diagnostic model was 93.06%, which was higher than that of endoscopists, and the mean absolute error of the polyp size measurement model was 0.62 mm and the mean relative error was 10.89%, which was lower than that of endoscopists. Conclusion: Artificial intelligence-assisted model demonstrated higher competence compared with endoscopists and stable diagnosis ability in clinical use.

FOXQ1-mediated SIRT1 upregulation enhances stemness and radio-resistance of colorectal cancer cells and restores intestinal microbiota function by promoting ß-catenin nuclear translocation.

BACKGROUND: Resistance of colorectal cancer (CRC) cells to radiotherapy considerably contributes to poor clinical outcomes of CRC patients. Microarray profiling in this study revealed the differentially expressed forkhead box Q1 (FOXQ1) in CRC, and thus we aimed to illustrate the role of FOXQ1 in CRC by modulating stemness and radio-resistance of CRC cells. METHODS: CRC and adjacent normal tissues were collected from CRC patients, and the correlation between FOXQ1 expression and CRC prognosis was analyzed. Subsequently, we determined the expression of FOXQ1, sirtuin 1 (SIRT1) and ß-catenin in CRC tissues and cell lines. The binding affinity between FOXQ1 and SIRT1 and that between SIRT1 and ß-catenin were validated with luciferase reporter gene, Co-IP and ChIP assays. Following a metagenomics analysis of CRC intestinal microbiota, the effects of the FOXQ1/SIRT1/ß-catenin axis on CRC stem cell phenotypes and radio-resistance was evaluated in vitro and in vivo through manipulation of gene expression. Besides, mouse feces were collected to examine changes in intestinal microbiota. RESULTS: FOXQ1 was highly expressed in CRC tissues and cells and positively correlated with poor prognosis of CRC patients. FOXQ1 overexpression contributed to resistance of CRC cells to radiation. Knockdown of FOXQ1 inhibited the stemness of CRC cells and reversed their radio-resistance. FOXQ1 enhanced the transcriptional expression of SIRT1, and SIRT1 enhanced the expression and nuclear translocation of ß-catenin. Knockdown of FOXQ1 repressed SIRT1 expression, thus reducing the stemness and radio-resistance of CRC cells. Moreover, FOXQ1 knockdown suppressed CRC xenograft formation in xenograft-bearing nude mice through inhibiting SIRT1 and ß-catenin to reduce the content of pathological bacteria that were up-regulated in CRC. CONCLUSION: FOXQ1-mediated SIRT1 upregulation augments expression and nuclear translocation of ß-catenin and benefits CRC-related intestinal pathological bacterial, thereby enhancing the stemness and radio-resistance of CRC cells.

Short-Chain Fatty Acid Decreases the Expression of CEBPB to Inhibit miR-145-Mediated DUSP6 and Thus Further Suppresses Intestinal Inflammation.

Intestinal inflammation is a common disease which can further lead to inflammatory bowel disease and even intestinal cancer. The increasing focus has come to the role of short-chain fatty acid (SCFA) in various bowel diseases. Hence, this study was designed to explore the specific role of SCFA in intestinal inflammation. In vivo and in vitro models of intestinal inflammation were constructed by lipopolysaccharide (LPS) injection in mice and LPS treatment on intestinal epithelial cells. A possible regulatory mechanism involving SCFA, CCAAT enhancer-binding protein beta (CEBPB), microRNA-145 (miR-145), and dual-specificity phosphatase 6 (DUSP6) in intestinal inflammation was verified by ChIP assay and dual-luciferase reporter gene assay. To evaluate the effects of SCFA on LPS-treated intestinal epithelial cells, the expression of relevant genes and inflammatory factors (IL-6, TNF-α, and IL-1ß) were determined. Last, the role of SCFA in vivo was explored through the scoring of disease activity index (DAI) and observation of colonic histology of LPS-treated mice. SCFA decreased the CEBPB expression in mouse colon tissues and small intestine epithelial cells induced by LPS. Furthermore, CEBPB could bind to the miR-145 promoter to inhibit its expression, thereby promoting the expression of DUSP6. In addition, SCFA improved the DAI, colonic histology, and the expression of serum inflammatory factors in LPS-treated mice and cells, noting that SCFA alleviated intestinal inflammation in vitro and in vivo. To sum up, SCFA inhibited DUSP6 by upregulating miR-145 through CEBPB repression and thus prevented the development of intestinal inflammation.

Efficacy of faecal microbiota transplantation on ulcerative colitis and its effect on gastrointestinal motility and immune function.

OBJECTIVE: To investigate the efficacy of faecal microbiota transplantation (FMT) in the treatment of ulcerative colitis (UC) and its effect on gastrointestinal motility (GM) and immune function. METHODS: A retrospective cohort study was conducted on 47 UC patients. The patients were divided into an observation group (n=17, treated with FMT) and a control group (n=30, treated with conventional treatment) according to the treatment regimen. In the observation group, FMT was used to treat colonic lesions by transplanting colonic bacteria fluid from healthy people. Clinical efficacy, immune function, level of inflammatory factors and gastrointestinal function of the two groups were observed before and after treatment. RESULTS: The total response rates of observation group was 94.12%, which was higher than that of control group (70.00%; P<0.05). After treatment, the contents of CD3+, CD4+ T cells and CD4+/CD8+ ratio were increased, while the content of CD8+ T cells was decreased in both groups compared with those before treatment (all P<0.05); and the contents of CD3+, CD4+ T cells and CD4+/CD8+ ratio in the observation group were higher than those in the control group, while CD8+ T cells showed an opposite trend (P<0.05). The levels of immunoglobulin A, immunoglobulin G and immunoglobulin M as well as interleukin-6, C-reactive protein, tumor necrosis factor-α and motilin were lower than those before treatment in both groups (all P<0.05), and the decreases in the observation group were more significant than those in the control group (all P<0.001). After treatment, cholecystokinin and vasoactive peptide were higher than those before treatment in both groups (all P<0.05), and the increased degree in the observation group was more obvious than that in the control group (all P<0.001). CONCLUSION: FMT has significant clinical efficacy in the treatment of UC, which may be related to the improvement of immune function, alleviation of inflammatory response and promotion of GM recovery.

Rotenone restrains colon cancer cell viability, motility and epithelial­mesenchymal transition and tumorigenesis in nude mice via the PI3K/AKT pathway.

Rotenone, a natural hydrophobic pesticide, has been reported to display anticancer activity in a variety of cancer cells. However, the mechanism of rotenone on colon cancer (CC) cell migration, invasion and metastasis is still unknown. In the present study, the cytotoxicity of rotenone on CC cells were detected by the Cell Counting Kit­8 assay and confirmed by clone formation assay. The effects of rotenone on CC cell invasion and migration activity were determined in vitro by Transwell invasion and wound healing assays, respectively. In addition, to reveal whether rotenone affected the epithelial­mesenchymal­transition (EMT) process, reverse transcription­quantitative PCR, western blotting and immunofluorescence assays were used to detect the expression of EMT markers. The expression levels of the key markers of the PI3K/AKT pathway after rotenone treatment alone or in combination with a PI3K/AKT signaling activator in CC were also detected by western blotting. Finally, the in vivo antitumor effects of rotenone were evaluated in a subcutaneous xenotransplant tumor model treated with an intraperitoneal injection of rotenone. The results of the present study demonstrated that rotenone treatment induced CC cell cytotoxicity and greater effects were observed with increasing concentrations and inhibited cell proliferation compared with untreated cells. In vitro cell function assays revealed that rotenone inhibited CC cell migration, invasion and EMT compared with untreated cells. Mechanically, the phosphorylation levels of AKT and mTOR were downregulated in rotenone­treated CC cells compared with untreated cells. Additionally, AKT and mTOR phosphorylation levels were increased by the PI3K/AKT signaling activator insulin­like growth factor 1 (IGF­1), which was reversed by rotenone treatment. The cell function assays confirmed that the IGF­1­activated cell proliferation, migration and invasion were decreased by rotenone treatment. These results indicated that rotenone affected CC cell proliferation and metastatic capabilities by inhibiting the PI3K/AKT/mTOR signaling pathway. In addition, rotenone inhibited tumor growth and metastatic capability of CC, which was confirmed in a xenograft mouse model. In conclusion, the present study revealed that rotenone inhibited CC cell viability, motility, EMT and metastasis in vitro and in vivo by inhibiting the PI3K/AKT/mTOR signaling pathway.