Perceptions of diabetes management among adolescents with type 1 diabetes and their caregivers: development and validation of the Japanese version of the diabetes family responsibility questionnaire.

The shift in diabetes management responsibility is critical for adolescents with type 1 diabetes (T1D). Currently, in Japan, there is insufficient progress in the development of scales for evaluating diabetes management responsibility. We developed the Japanese version of the Diabetes Family Responsibility Questionnaire (DFRQ), a scale to evaluate diabetes management responsibility, and verified its reliability and validity. We recruited 12-18-year-old adolescents with T1D and their caregivers. The DFRQ questionnaires (DFRQ-A for adolescents and DFRQ-C for caregivers) were distributed. The responses of 31 pairs were analyzed (adolescents: 9 males, 22 females; mean age: 14.8 ± 1.5 years). The median total DFRQ scores of adolescents (30.0) and caregivers (32.0) were not significantly different (p = 0.269). The internal consistencies (Cronbach's α) were 0.784 and 0.687 for DFRQ-A and DFRQ-C, respectively. DFRQ-A scores and adolescent age demonstrated a weak statistically significant negative correlation (r = - 0.397, p = 0.027), whereas DFRQ-C scores and adolescent age demonstrated a weak negative correlation not statistically significant (r = - 0.311, p = 0.089). Both scores were significantly negatively correlated with self-efficacy for diabetes self-management scores (r = - 0.390, p = 0.030; r = - 0.478, p = 0.006, respectively). Furthermore, a significantly moderate positive correlation was found between these scores (r = 0.624, p < 0.001). We confirmed the reliability and validity of the Japanese version of DFRQ. DFRQ is expected to be used as a dyadic scale to evaluate the status of diabetes management responsibility and its transition during adolescence in Japan.

Enhancement of bone formation ex vivo and in vivo by a helioxanthin-derivative.

To effectively treat serious bone defects using bone-regenerative medicine, a small chemical compound that potently induces bone formation must be developed. We previously reported on the osteogenic effect of 4-(4-methoxyphenyl)pyrido[40,30:4,5]thieno[2,3-b]pyridine-2-carboxamide (TH), a helioxanthin-derivative, in vitro. Here, we report on TH's osteogenic effects ex vivo and in vivo. TH-induced new bone formation in both calvarial and metatarsal organ cultures. A novel monitoring system of osteoblastic differentiation using MC3T3-E1 cells revealed that TH was released from alpha-TCP bone cement and this release continued for more than one month. Lastly, the implantation of the alpha-TCP carrier containing TH into defects in mouse skull resulted in increased new bone areas within the defects after 4 weeks. A TH-containing scaffold may help establish a more efficient bone regeneration system.

The peroxisome proliferator-activated receptor gamma/retinoid X receptor alpha heterodimer targets the histone modification enzyme PR-Set7/Setd8 gene and regulates adipogenesis through a positive feedback loop.

Control of cell differentiation occurs through transcriptional mechanisms and through epigenetic modification. Using a chromatin immunoprecipitation-on-chip approach, we performed a genome-wide search for target genes of peroxisome proliferator-activated receptor gamma (PPAR gamma) and its partner protein retinoid X receptor alpha during adipogenesis. We show that these two receptors target several genes that encode histone lysine methyltransferase SET domain proteins. The histone H4 Lys 20 (H4K20) monomethyltransferase PR-Set7/Setd8 gene is upregulated by PPAR gamma during adipogenesis, and the knockdown of PR-Set7/Setd8 suppressed adipogenesis. Intriguingly, monomethylated H4K20 (H4K20me1) levels are robustly increased toward the end of differentiation. PR-Set7/Setd8 positively regulates the expression of PPAR gamma and its targets through H4K20 monomethylation. Furthermore, the activation of PPAR gamma transcriptional activity leads to the induction of H4K20me1 modification of PPAR gamma and its targets and thereby promotes adipogenesis. We also show that PPAR gamma targets PPAR gamma2 and promotes its gene expression through H4K20 monomethylation. Our results connect transcriptional regulation and epigenetic chromatin modulation through H4K20 monomethylation during adipogenesis through a feedback loop.