Eighteen-year trends in the management of patients with diabetes in the Shiga Diabetes Clinical Survey: overall trends and differences by age group.

Aim: To examine the trends in the management of patients with diabetes over an 18-year period in Japan. Participants and methods: We recorded the height, body mass, laboratory data, diabetes treatment, and screening status of diabetic complications from the data collected during the Shiga Diabetes Clinical Survey, which has been performed every 6 years since 2000. We then evaluated the management of patients with diabetes in Shiga Prefecture. The study included 17,870, 18,398, 24,243, and 26,624 participants in each of the 4 years of measurements. Results: The mean age and body mass index (BMI) of the participants gradually increased. The percentage of patients with BMI of ≥ 25 kg/m2 was higher in younger patients. Glycemic control significantly improved over 18 years (hemoglobin A1c: 7.3% ± 1.4% in 2000 to 7.1% ± 1.1% in 2018, P for trend < 0.001). The mean hemoglobin A1c levels were higher in younger patients than in elderly patients and increased from 2012 to 2018 in patients aged ≥ 65 years. The proportion of participants who underwent screening for albuminuria and diabetic retinopathy increased. The mean blood pressure and low-density lipoprotein cholesterol concentration decreased. Conclusions: Glycemic control has been maintained at an acceptable level since the previous survey. Although glycemic control has become less strict in elderly patients with diabetes, glycemic control is poorer in younger patients than in elderly patients. Obesity is an increasingly important problem, particularly in younger patients. The frequency of screening for diabetic complications and the control of blood pressure should be improved. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-022-00573-2.

Colorectal Cancer-Derived CAT1-Positive Extracellular Vesicles Alter Nitric Oxide Metabolism in Endothelial Cells and Promote Angiogenesis.

Accumulating scientific evidences strongly support the importance of cancer-derived extracellular vesicles (EV) in organization of tumor microenvironment and metastatic niches, which are also considered as ideal tools for cancer liquid biopsy. To uncover the full scope of proteomic information packaged within EVs secreted directly from human colorectal cancer, we cultured surgically resected viable tissues and obtained tissue-exudative EVs (Te-EV). Our quantitative profiling of 6,307 Te-EV proteins and 8,565 tissue proteins from primary colorectal cancer and adjacent normal mucosa (n = 17) allowed identification of a specific cargo in colorectal cancer-derived Te-EVs, high-affinity cationic amino acid transporter 1 (CAT1, P = 5.0 × 10-3, fold change = 6.2), in addition to discovery of a new class of EV markers, VPS family proteins. The EV sandwich ELISA confirmed escalation of the EV-CAT1 level in plasma from patients with colorectal cancer compared with healthy donors (n = 119, P = 3.8 × 10-7). Further metabolomic analysis revealed that CAT1-overexpressed EVs drastically enhanced vascular endothelial cell growth and tubule formation via upregulation of arginine transport and downstream NO metabolic pathway. These findings demonstrate the potency of CAT1 as an EV-based biomarker for colorectal cancer and its functional significance on tumor angiogenesis. IMPLICATIONS: This study provides a proteome-wide compositional dataset for viable colorectal cancer tissue-derived EVs and especially emphasizes importance of EV-CAT1 as a key regulator of angiogenesis.

Quantitative analyses of the metaphase-to-anaphase transition reveal differential kinetic regulation for securin and cyclin B1.

Separation of sister chromatids is a drastic and irreversible step in the cell cycle. The key biochemistry behind this event is the proteolysis mediated by the ubiquitin ligase called the anaphase promoting complex, or APC/C. Securin and cyclin B1 are the two established substrates for APC/C whose degradation releases separase and inactivates cyclin B1-dependent kinase 1 (cdk1), respectively, at the metaphase-to-anaphase transition. In this study, we have combined biochemical quantifications with mathematical simulations to characterize the kinetic regulation of securin and cyclin B1, in the cytoplasmic and chromosomal compartments, and found that they are differentially distributed and degraded with different rates. Modeling their interaction with separase predicted that activation timing of separase well coincides with the decline of securin-separase concentration in the cytoplasm. Notably, it also coincides with the peak of cyclin B1-separase level on chromosomes, which appeared crucial to coordinate the timing for separase activation and cdk1 inhibition. We have also conducted phosphoproteomic analysis and identified Ki67 as a chromosomal cdk1 substrate whose dephosphorylation is facilitated by cyclin B1-separase interaction in anaphase.