Epigenome-wide association study of dietary fatty acid intake.

BACKGROUND: Dietary intake of n-3 polyunsaturated fatty acids (PUFA) may have a protective effect on the development of cardiovascular diseases, diabetes, depression and cancer, while a high intake of n-6 PUFA was often reported to be associated with inflammation-related traits. The effect of PUFAs on health outcomes might be mediated by DNA methylation (DNAm). The aim of our study is to identify the impact of PUFA intake on DNAm in the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort and the Leiden Longevity Study (LLS). RESULTS: DNA methylation levels were measured in whole blood from the population-based KORA FF4 study (N = 1354) and LLS (N = 448), using the Illumina MethylationEPIC BeadChip and Illumina HumanMethylation450 array, respectively. We assessed associations between DNAm and intake of eight and four PUFAs in KORA and LLS, respectively. Where possible, results were meta-analyzed. Below the Bonferroni correction threshold (p < 7.17 × 10-8), we identified two differentially methylated positions (DMPs) associated with PUFA intake in the KORA study. The DMP cg19937480, annotated to gene PRDX1, was positively associated with docosahexaenoic acid (DHA) in model 1 (beta: 2.00 × 10-5, 95%CI: 1.28 × 10-5-2.73 × 10-5, P value: 6.98 × 10-8), while cg05041783, annotated to gene MARK2, was positively associated with docosapentaenoic acid (DPA) in our fully adjusted model (beta: 9.80 × 10-5, 95%CI: 6.25 × 10-5-1.33 × 10-4, P value: 6.75 × 10-8). In the meta-analysis, we identified the CpG site (cg15951061), annotated to gene CDCA7L below Bonferroni correction (1.23 × 10-7) associated with eicosapentaenoic acid (EPA) intake in model 1 (beta: 2.00 × 10-5, 95% CI: 1.27 × 10-5-2.73 × 10-5, P value = 5.99 × 10-8) and we confirmed the association of cg19937480 with DHA in both models 1 and 2 (beta: 2.07 × 10-5, 95% CI: 1.31 × 10-5-2.83 × 10-5, P value = 1.00 × 10-7 and beta: 2.19 × 10-5, 95% CI: 1.41 × 10-5-2.97 × 10-5, P value = 5.91 × 10-8 respectively). CONCLUSIONS: Our study identified three CpG sites associated with PUFA intake. The mechanisms of these sites remain largely unexplored, highlighting the novelty of our findings. Further research is essential to understand the links between CpG site methylation and PUFA outcomes.

Effect of Kangaroo Position on microcirculation of preterm newborns: a controlled randomized clinical trial

Abstract Objective: The objective of this study was to evaluate the effect of Kangaroo Position (KP) in microcirculation (MC) of the flexor muscles of preterm newborns. Method: A controlled clinical trial was conducted in the city of Recife, Brazil, with 26 preterm children randomized in the Kangaroo Group (13) and in the Control Group (13). Assessments of blood flow, temperature, and tissue oxygen saturation (SO2) were made at two different times and in the biceps brachii muscle and hamstrings muscle group: before the KP and after 24 h of KP. In the Control Group, the registrations were performed at the times corresponding to those of the Kangaroo Group. The mean values among the times were analyzed by paired t-test for repeated measures. The clinical trial was recorded in Clinical Trials (NCT03611088). Results: In the Kangaroo Group there was an increase in tissue temperature and blood flow at the time evaluation periods (p < 0.05). In the control group, there was no statistical difference between the recording moments hamstring muscles group, but in the biceps brachii, there was a reduction in mean blood flow (p = 0.023). Conclusion: In conclusion, the KP has effects on the microcirculation of the flexor muscles of preterm newborns.

Effect of Kangaroo Position on microcirculation of preterm newborns: a controlled randomized clinical trial.

OBJECTIVE: The objective of this study was to evaluate the effect of Kangaroo Position (KP) in microcirculation (MC) of the flexor muscles of preterm newborns. METHOD: A controlled clinical trial was conducted in the city of Recife, Brazil, with 26 preterm children randomized in the Kangaroo Group (13) and in the Control Group (13). Assessments of blood flow, temperature, and tissue oxygen saturation (SO2) were made at two different times and in the biceps brachii muscle and hamstrings muscle group: before the KP and after 24 h of KP. In the Control Group, the registrations were performed at the times corresponding to those of the Kangaroo Group. The mean values among the times were analyzed by paired t-test for repeated measures. The clinical trial was recorded in Clinical Trials (NCT03611088). RESULTS: In the Kangaroo Group there was an increase in tissue temperature and blood flow at the time evaluation periods (p < 0.05). In the control group, there was no statistical difference between the recording moments hamstring muscles group, but in the biceps brachii, there was a reduction in mean blood flow (p = 0.023). CONCLUSION: In conclusion, the KP has effects on the microcirculation of the flexor muscles of preterm newborns.

CDK11 Promotes Cytokine-Induced Apoptosis in Pancreatic Beta Cells Independently of Glucose Concentration and Is Regulated by Inflammation in the NOD Mouse Model.

Background: Pancreatic islets are exposed to strong pro-apoptotic stimuli: inflammation and hyperglycemia, during the progression of the autoimmune diabetes (T1D). We found that the Cdk11(Cyclin Dependent Kinase 11) is downregulated by inflammation in the T1D prone NOD (non-obese diabetic) mouse model. The aim of this study is to determine the role of CDK11 in the pathogenesis of T1D and to assess the hierarchical relationship between CDK11 and Cyclin D3 in beta cell viability, since Cyclin D3, a natural ligand for CDK11, promotes beta cell viability and fitness in front of glucose. Methods: We studied T1D pathogenesis in NOD mice hemideficient for CDK11 (N-HTZ), and, in N-HTZ deficient for Cyclin D3 (K11HTZ-D3KO), in comparison to their respective controls (N-WT and K11WT-D3KO). Moreover, we exposed pancreatic islets to either pro-inflammatory cytokines in the presence of increasing glucose concentrations, or Thapsigargin, an Endoplasmic Reticulum (ER)-stress inducing agent, and assessed apoptotic events. The expression of key ER-stress markers (Chop, Atf4 and Bip) was also determined. Results: N-HTZ mice were significantly protected against T1D, and NS-HTZ pancreatic islets exhibited an impaired sensitivity to cytokine-induced apoptosis, regardless of glucose concentration. However, thapsigargin-induced apoptosis was not altered. Furthermore, CDK11 hemideficiency did not attenuate the exacerbation of T1D caused by Cyclin D3 deficiency. Conclusions: This study is the first to report that CDK11 is repressed in T1D as a protection mechanism against inflammation-induced apoptosis and suggests that CDK11 lies upstream Cyclin D3 signaling. We unveil the CDK11/Cyclin D3 tandem as a new potential intervention target in T1D.