Influence of methyl donor nutrients as epigenetic regulators in colorectal cancer: A systematic review of observational studies.

BACKGROUND: Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer (CRC). However, whether the influence of methyl donor intake is modified by polymorphisms in such epigenetic regulators is still unclear. AIM: To improve the current understanding of the molecular basis of CRC. METHODS: A literature search in the Medline database, Reference Citation Analysis (https:// www.referencecitationanalysis.com/), and manual reference screening were performed to identify observational studies published from inception to May 2022. RESULTS: A total of fourteen case-control studies and five cohort studies were identified. These studies included information on dietary methyl donors, dietary components that potentially modulate the bioavailability of methyl groups, genetic variants of methyl metabolizing enzymes, and/or markers of CpG island methylator phenotype and/or microsatellite instability, and their possible interactions on CRC risk. CONCLUSION: Several studies have suggested interactions between methylenetetrahydrofolate reductase polymorphisms, methyl donor nutrients (such as folate) and alcohol on CRC risk. Moreover, vitamin B6, niacin, and alcohol may affect CRC risk through not only genetic but also epigenetic regulation. Identification of specific mechanisms in these interactions associated with CRC may assist in developing targeted prevention strategies for individuals at the highest risk of developing CRC.

Continuous monitoring of cell transfection efficiency with micropatterned substrates.

The effect of cell-cell contact on gene transfection is mainly unknown. Usually, transfection is carried out in batch cell cultures without control over cellular interactions, and efficiency analysis relies on complex and expensive protocols commonly involving flow cytometry as the final analytical step. Novel platforms and cell patterning are being studied to control cellular interactions and improve quantification methods. In this study, we report the use of surface patterning of fibronectin for the generation of two types of mesenchymal stromal cell patterns: single-cell patterns without cell-to-cell contact, and small cell-colony patterns. Both scenarios allowed the integration of the full transfection process and the continuous monitoring of thousands of individualized events by fluorescence microscopy. Our results showed that cell-to-cell contact clearly affected the transfection, as single cells presented a maximum transfection peak 6 h earlier and had a 10% higher transfection efficiency than cells with cell-to-cell contact.

Gene-Diet Interactions in Colorectal Cancer: Survey Design, Instruments, Participants and Descriptive Data of a Case-Control Study in the Basque Country.

Epidemiologic studies have revealed inconsistent evidence of gene-diet interaction in relation to colorectal cancer (CRC). The aim of this study was to analyze them in a sample of cases and controls from the population-based bowel cancer screening program of the Osakidetza/Basque Health Service. This study analyzed dietetic, genetic, demographic, socioeconomic factors and lifestyles. In the present manuscript, the survey design, sampling, instruments, measurements and related quality management were presented. Moreover, we analyze differences between cases and controls in some data, especially those related to diet. The participants were 308 cases and 308 age- and sex-matched subjects as controls. Cases were more likely than controls to have overweight/obesity (67.5% vs. 58.1%, p < 0.05), a lower intake of vitamin B2 (0.86 ± 0.23 vs. 0.92 ± 0.23 mg/1000 kcal, p < 0.01) and calcium:phosphorus ratio (0.62 ± 0.12 vs. 0.65 ± 0.13, p < 0.01). A higher proportion of cases than controls did not meet the Nutritional Objectives for saturated fatty acids (85.7% vs. 67.5%, p < 0.001) or cholesterol (35.4% vs. 25.0%, p < 0.01). In conclusion, the present study provides valuable data for analyzing the complexity of gene-diet interaction in relation to CRC. The results presented here suggest that overweight/obesity and a high intake of certain dietary components, especially saturated fatty acids and cholesterol, are more frequent in cases than in controls.

Mitochondrial DNA Reveals the Trace of the Ancient Settlers of a Violently Devastated Late Bronze and Iron Ages Village.

La Hoya (Alava, Basque Country) was one of the most important villages of the Late Bronze and Iron Ages of the north of the Iberian Peninsula, until it was violently devastated around the 4th century and abandoned in the 3rd century B.C. Archaeological evidences suggest that descendants from La Hoya placed their new settlement in a nearby hill, which gave rise to the current village of Laguardia. In this study, we have traced the genetic imprints of the extinct inhabitants of La Hoya through the analysis of maternal lineages. In particular, we have analyzed the mitochondrial DNA (mtDNA) control region of 41 human remains recovered from the archaeological site for comparison with a sample of 51 individuals from the geographically close present-day population of Laguardia, as well as 56 individuals of the general population of the province of Alava, where the archaeological site and Laguardia village are located. MtDNA haplotypes were successfully obtained in 25 out of 41 ancient samples, and 14 different haplotypes were identified. The major mtDNA subhaplogroups observed in La Hoya were H1, H3, J1 and U5, which show a distinctive frequency pattern in the autochthonous populations of the north of the Iberian Peninsula. Approximate Bayesian Computation analysis was performed to test the most likely model for the local demographic history. The results did not sustain a genealogical continuity between Laguardia and La Hoya at the haplotype level, although factors such as sampling effects, recent admixture events, and genetic bottlenecks need to be considered. Likewise, the highly similar subhaplogroup composition detected between La Hoya and Laguardia and Alava populations do not allow us to reject a maternal genetic continuity in the human groups of the area since at least the Iron Age to present times. Broader analyses, based on a larger collection of samples and genetic markers, would be required to study fine-scale population events in these human groups.