Analysis of serum levels and DNA methylation of fibroblast growth factor 21 using peripheral blood-derived genomes in patients with obesity.

Fibroblast growth factor (FGF) 21, a hormone produced by the liver, improves glucose and lipid metabolism. We recently demonstrated that the FGF21 gene (Fgf21) underwent DNA demethylation in the mouse liver via peroxisome proliferator-activated receptor (PPAR) α during the fetal to lactation periods. Furthermore, we found that the DNA methylation state of Fgf21 was involved in obesity in adult animals. In the present study, we analyzed the DNA methylation state of the FGF21 gene (FGF21) in obese patients using genomic DNA extracted from human monocytes and macrophages and investigated the pathophysiological significance of the FGF21 expression response to pemafibrate (PM), a PPARα ligand. We examined 67 patients with obesity stratified into in- and outpatient cohorts. A positive correlation was observed between serum FGF21 levels and triglyceride (TG) levels before PM administration. However, changes in serum FGF21 levels following PM administration did not correlate with the FGF21 DNA methylation rate, except at one CpG site. The body mass index (BMI) and serum TG levels positively correlated with the FGF21 DNA methylation rate, particularly at different CpG positions. A negative correlation was observed between absolute changes in serum FGF21 levels and the ratio of change in serum TG levels after PM administration. Collectively, these results indicate the potential of FGF21 DNA methylation as a surrogate indicator of BMI and serum TG levels, while absolute changes in serum FGF21 levels after PM administration may offer prognostic insights into the efficacy of reducing serum TG levels through PM administration.

Acquisition and Analysis of Microcirculation Image in Septic Model Rats.

Background: Microcirculation is a vital sign that supplies oxygen and nutrients to maintain normal life activities. Sepsis typically influences the operation of microcirculation, which is recovered by the administration of medicine injection. Objective: Sepsis-induced variation and recovery of microcirculation are quantitatively detected using microcirculation images acquired by a non-contact imaging setup, which might assist the clinical diagnosis and therapy of sepsis. Methods: In this study, a non-contact imaging setup was first used to record images of microcirculation on the back of model rats. Specifically, the model rats were divided into three groups: (i) the sham group as a control group; (ii) the cecum ligation and puncture (CLP) group with sepsis; and (iii) the CLP+thrombomodulin (TM) group with sepsis and the application of TM alfa therapy. Furthermore, considering the sparsity of red blood cells (RBCs), the blood velocity is estimated by robust principal component analysis (RPCA) and U-net, and the blood vessel diameter is estimated by the contrast difference between the blood vessel and tissue. Results and Effectiveness: In the experiments, the continuous degradation of the estimated blood velocity and blood vessel diameter in the CLP group and the recovery after degradation of those in the CLP+TM group were quantitatively observed. The variation tendencies of the estimated blood velocity and blood vessel diameter in each group suggested the effects of sepsis and its corresponding therapy.

Investigation into Effect of Thrombomodulin Alfa for Septic Model Rats based on Microcirculation Image Analysis.

Sepsis is life threatening organ dysfunction caused by microcirculatory dysfunction. With progression of sepsis, the patients are likely to develop septic shock which is associated with multi organ dysfunction. To treat sepsis and septic shock, Thrombomodulin alfa (TM alfa) was developed. Direct observation of the microcirculation may provide new and rich information in terms of the effect of TM alfa on sepsis. Thus we conducted rodent experiments in which we observed the microcirculation with a non-contact optical imaging setup and measured lactate value from collected blood. From the acquired motion pictures, we estimated the blood velocity. As a result, from experiments, the sham rats showed no significant change in both lactate value and the blood velocity during the observation. On the other hand, lactate value of the septic model rats increased and the blood velocity of them decreased. Lactate value of the septic model rats treated with TM alfa decreased after showing an increase while the blood velocity of them increased after showing a decrease. These findings suggest that microcirculatory alteration may be a sign of sepsis as well as septic shock progression and that the TM alfa may be effective for the treatment of sepsis and septic shock.