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Effects of obesity and weight loss on microRNA expression in the human colorectal mucosa
- Stella Breininger, Laura Sabater, Fiona Malcomson, Sorena Afshar, Jelena Mann, John Mathers
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- Journal:
- Proceedings of the Nutrition Society / Volume 79 / Issue OCE2 / 2020
- Published online by Cambridge University Press:
- 10 June 2020, E140
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Introduction
Colorectal cancer (CRC) is the 3rd most common cancer worldwide. Obesity, and its lifestyle determinants, physical inactivity and poor diet, increase CRC risk. However, the effects of weight loss by bariatric surgery on CRC risk are unclear. Epigenetic mechanisms involving microRNAs that lead to dysregulated gene expression may mediate the effects of obesity and weight loss on CRC risk. We hypothesised that microRNAs are i) aberrantly expressed in obese individuals compared with healthy non-obese individuals and ii) modulated by significant weight loss following bariatric surgery.
MethodsWe used data and samples from the Biomarkers of Colorectal Cancer after Bariatric Surgery (BOCABS) Study. Obese patients listed for bariatric surgery and age- and sex-matched healthy non-obese adults (Controls) were recruited at North Tyneside General Hospital. Rectal mucosal biopsies were collected at baseline and six months post-surgery from obese participants and at baseline only from Controls. Using Next Generation Sequencing and bioinformatics analysis, a panel of 8 microRNAs was selected and validated by quantitative PCR in colorectal mucosal biopsies.
Results and discussionData were available for 20 control participants and for 22 obese participants with matched pre- and post-surgery samples. Next Generation Sequencing revealed that compared with non-obese individuals, obese individuals showed differential expression of 112 microRNAs (p < 0.05). Roux-en-Y gastric bypass, resulted in differential expression of 60 microRNAs, when compared with expression levels at baseline (p < 0.05). A total of 36 microRNAs differed significantly in both i) the obese with non-obese and ii) the pre- and post-surgery comparisons. Validation by quantitative PCR demonstrated that expression of miR-31, miR-215, miR-3196 and miR-4516 was significantly (P < 0.05) higher in obese than in non-obese individuals. Weight loss, (mean 28.5kg) following Roux-en-Y gastric bypass, reduced expression of miR-31, miR-215 and miR-3196 significantly (P < 0.05) to expression levels that were comparable with those in Controls. These differentially expressed microRNAs are implicated in pathways linked with inflammation, obesity and cancer.
ConclusionThe pattern of microRNA expression in macroscopically-normal human colorectal mucosa differed substantially between obese and non-obese individuals. However, six months after Roux-en-Y gastric bypass, the pattern of microRNA expression was similar to that in non-obese Controls. This suggests that surgically-induced weight loss may normalise microRNA expression in the human colorectal mucosa and so reduce CRC risk.
Specific antibody responses against Neospora caninum recombinant rNcGRA7, rNcSAG4, rNcBSR4 and rNcSRS9 proteins are correlated with virulence in mice
- ELENA JIMÉNEZ-RUIZ, GREGORI BECH-SÀBAT, GEMA ÁLVAREZ-GARCÍA, JAVIER REGIDOR-CERRILLO, LAURA HINOJAL-CAMPAÑA, LUIS M. ORTEGA-MORA
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- Journal:
- Parasitology / Volume 140 / Issue 5 / April 2013
- Published online by Cambridge University Press:
- 24 January 2013, pp. 569-579
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The intraspecific diversity of Neospora caninum is a determinant for in vivo parasite virulence and in vitro parasite behaviour. The relationship between isolate virulence and specific antibody responses against key parasite proteins has not been well characterized. The response kinetics and the differences in specific anti-rNcGRA7, -rNcSAG4, -rNcBSR4 and -rNcSRS9 antibody levels were analysed by recombinant protein-based ELISA in groups of mice inoculated with 10 different N. caninum isolates that differ in their virulence. The majority of the virulence parameters analysed correlated with the specific antibody levels against the 4 recombinant proteins. The antibodies developed against the highly immunogenic protein NcGRA7 were significantly higher in mice inoculated with high virulence isolates than in those inoculated with low-to-moderate virulence isolates in both non-pregnant and pregnant mouse models. Moreover, these levels were correlated with the anti-N. caninum IgG1 and IgG2a responses and the in vitro tachyzoite yield at 56 h. The antibodies directed against the bradyzoite-specific proteins were not detected in a non-pregnant mouse model. However, some seropositive mice were found in groups inoculated with high virulence isolates in a pregnant mouse model. NcGRA7 and NcSAG4 are proteins clearly correlated with virulence, and to a lesser extent NcBSR4 and NcSRS9 proteins. Moreover, antibodies to bradyzoite-specific proteins appear to also be related to virulence in mice. Further analyses should be performed in order to verify the usefulness of these proteins as predictive markers for virulence in an experimental bovine model of neosporosis.