👤 Akihiko Nogami

This study aimed to investigate the anti-atherosclerotic properties of tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist, in comparison with semaglutide, a selective GLP-1 receptor agonist. ApoE knockout mice were divided into early diabetes (dosed from 10 to 22 weeks of age), late diabetes (dosed from 18 to 30 weeks of age), and non-diabetic groups after streptozotocin treatment, and each group received semaglutide, tirzepatide, or saline for 12 weeks. In the early diabetes group, both agents significantly suppressed aortic plaque formation compared with control, while modestly improving glycemia and lipid levels. No significant vascular effects were observed in late diabetes or non-diabetic groups. Tirzepatide markedly reduced inflammatory mediators, including Mcp-1, Il-6, I-cam, and Cd68, whereas semaglutide showed partial overlap. Notably, these anti-inflammatory effects were also detected in non-diabetic mice, suggesting vascular protection may involve arterial actions independently of metabolic control. Taken together, our findings demonstrate that tirzepatide exerts anti-atherosclerotic effects comparable to semaglutide, supporting the concept that GIP and GLP-1 signaling can confer vascular benefits. These results highlight the potential clinical relevance of dual incretin receptor agonism for cardiovascular risk reduction, although further studies are required to clarify the specific role of GIP signaling. Show less

Hypothermia is an important cause of death in forensic pathology. For the forensic diagnosis of hypothermia, some reports point out the possibility that hypothermia without diabetes may cause ketoacidosis. In this study, we evaluated the diagnostic value of ketoacidosis in a murine model of hypothermia, using the cold stress at 4 °C for 3 or 5 hrs in genetically diabetic (BKS.Cg-+Lepr Show less

Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases. Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) and near the HEY2 gene (rs9388451). Independent replication confirmed both signals (meta-analyses: rs10428132, P = 1.0 × 10(-68); rs9388451, P = 5.1 × 10(-17)) and identified one additional signal in SCN5A (at 3p21; rs11708996, P = 1.0 × 10(-14)). The cumulative effect of the three loci on disease susceptibility was unexpectedly large (Ptrend = 6.1 × 10(-81)). The association signals at SCN5A-SCN10A demonstrate that genetic polymorphisms modulating cardiac conduction can also influence susceptibility to cardiac arrhythmia. The implication of association with HEY2, supported by new evidence that Hey2 regulates cardiac electrical activity, shows that Brugada syndrome may originate from altered transcriptional programming during cardiac development. Altogether, our findings indicate that common genetic variation can have a strong impact on the predisposition to rare diseases. Show less

Cellular and subcellular morphology reflects the physiological state of a cell. To determine the physiological nature of sake yeast with superior fermentation properties, we quantitatively analyzed the morphology of sake yeast cells by using the CalMorph system. All the sake strains examined here exhibited common morphological traits that are typically observed in the well-characterized whiskey (whi) mutants that show accelerated G(1)/S transition. In agreement with this finding, the sake strain showed less efficient G(0)/G(1) arrest and elevated expression of the G(1) cyclin gene CLN3 throughout the fermentation period. Furthermore, deletion of CLN3 remarkably impaired the fermentation rate in both sake and laboratory strains. Disruption of the SWI6 gene, a transcriptional coactivator responsible for Cln3p-mediated G(1)/S transition, also resulted in a decreased fermentation rate, whereas whi mutants exhibited significant improvement in the fermentation rate, demonstrating positive roles of Cln3p and its downstream signalling pathway in facilitating ethanol fermentation. The combined results indicate that enhanced induction of CLN3 contributes to the high fermentation rate of sake yeast, which are natural whi mutants. Show less