A Mediterranean Diet Mix Has Chemopreventive Effects in a Murine Model of Colorectal Cancer Modulating Apoptosis and the Gut Microbiota.

Objectives: Unhealthy dietary patterns have been associated with colorectal cancer (CRC) onset while Mediterranean Diet (MD) has been proposed for CRC prevention. This study evaluated the effect of a Mediterranean Diet Mix (MD-MIX) on colonic tumors development in A/J mice fed a low-fat (LFD) or a high-fat western diet (HFWD), and injected with the procarcinogen azoxymethane (AOM). Materials and Methods: Forty A/J male mice were randomly assigned into four feeding arms (10 mice/arm; LFD, LFD-MD-MIX, HFWD, HFWD-MD-MIX) to be treated with AOM. Ten mice were exposed to the diets alone (Healthy LFD and Healthy HFWD) to be used as control. Tumor incidence and multiplicity were evaluated at sacrifice. Mucosal fatty acid content and urinary phenolic compounds were assayed by mass spectrometry. Apoptosis was evaluated by TUNEL assay and gene expression markers. Cell proliferation was evaluated by Ki67 immunohistochemistry. Microbiota composition was assessed at different time points by 16S RNA sequencing. Results: A tumor incidence of 100% was obtained in AOM-treated mice. The MD-MIX supplementation was able to reduce the number of colonic lesions in both LFD and HFWD-fed mice and to induce apoptosis, in particular in the LFD-MD-MIX arm. Moreover, a preventive effect on low-grade dysplasia and macroscopical lesions (>1 mm) development was found in HFWD-fed mice together with a regulation of the AOM-driven intestinal dysbiosis. Conclusions: MD-MIX was able to counteract CRC development in mice under different dietary backgrounds through the regulation of apoptosis and gut microbiota.

miR-155 Is Downregulated in Familial Adenomatous Polyposis and Modulates WNT Signaling by Targeting AXIN1 and TCF4.

Adenomatous Polyposis Coli (APC) gene mutations are responsible for the onset of familial adenomatous polyposis (FAP) and sporadic colorectal cancer and have been associated with miRNAs dysregulation. The capacity of miR-155, a cancer-related miRNA, to target components of the WNT/ß-CATENIN pathway suggests that APC gene mutations, controlling miRNAs expression, may critically regulate WNT/ß-CATENIN signaling. To this end, APC gene target sequencing was performed on colonic adenomatous polyps and paired normal mucosa clinical specimens from FAP patients (n = 9) to elucidate the role of miR-155-5p in APC-mutant setting. The expression of selected miRNAs and WNT/ß-CATENIN signaling components was characterized in FAP patients and non-FAP control subjects (n = 5). miR-155-5p expression and functional effects on WNT cascade, cell survival, growth, and apoptosis were investigated in different colorectal cancer cell lines. A somatic second hit in the APC gene was found in adenomatous polyps from 6 of 9 FAP patients. Heterozygous APC gene mutations in FAP patients were associated with altered expression of candidate miRNAs and increased levels of AXIN1 and AXIN2 mRNAs. miR-155-5p was downregulated in FAP patients and in the APC and ß-CATENIN-mutant colorectal cancer cell lines, and critically regulates WNT/ß-CATENIN cascade by targeting both AXIN1 and TCF4. Importantly, miR-155-5p may sustain long-term WNT/ß-CATENIN activation in colorectal cancer cells upon WNT3A stimulation. IMPLICATIONS: This study supports a key role of miR-155-5p in modulating WNT/ß-CATENIN signaling in colorectal cancer and unravels a new mechanism for AXIN1 regulation which represents a potential therapeutic target in specific tumor subtypes.

Body piercing and tattoos: a survey on young adults' knowledge of the risks and practices in body art.

BACKGROUND: The practice of tattooing and piercing has expanded in western society. In order to verify young adults' knowledge of the risk and practices related to body art, an investigation was conducted among freshmen of the University of Bari in the region of Apulia, Italy. METHODS: The study was carried out in the Academic Year 2009-2010 through an anonymous self-administered written questionnaire distributed to 1.656 freshmen enrolled in 17 Degree Courses. RESULTS: Of the 1.598 students included in the analysis, 78.3% believe it is risky to undergo piercing/tattoo practices. AIDS was indicated as a possible infection by 60.3% of freshmen, hepatitis C by 38.2%, tetanus by 34.3% and hepatitis B by 33.7% of the sample. 28.1% of freshmen were not aware that there are also non-infectious complications. 29% of the sample had at least one piercing or tattoo (this percentage does not include earlobe piercing in women). Of those with body art, the decision to undergo body art was made autonomously in 57.9% of the participants. 56.3% of freshmen undergoing body art had taken less than a month to decide. With regard to the reasons that led the sample to undergo body art, 28.4% were unable to explain it, 23.8% answered to improve their aesthetic aspect, 18.4% to distinguish themselves from others, 12.3% for fashion; 17.1% for other reasons. 25.4% of the sample declared that they had a piercing (79.8% female vs 20.2% male; ratio M/F 1:4.0). The average age for a first piercing was 15.3 years (range 10-27; SD ± 2.9). 9.6% of the sample declared that they have a tattoo (69.9% female vs 30.1% male; ratio M/F 1:2.3). The average age for a first tattoo was 17.5 years (range 10-26, SD ± 2.4). CONCLUSIONS: Most of the freshmen knew about AIDS-related risks but not other potential risks. Body art is fairly common among young adults (especially women). The decision is often not shared with the family and is undertaken mostly without a specific reason or for the improvement of aesthetic aspect. Information about freshmen's knowledge, attitudes and practices could help in effective planning of health promotion strategies.