掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

Existing models of frontotemporal dementia (FTD) may not fully recapitulate the pathophysiology of the disease. To generate more pathophysiologically relevant FTD models, we engineered MAPT knockin mouse lines carrying triple mutations, among which the MAPTP301S;Int10+3;S320F line exhibited robust tau pathology starting before 6 months of age. Severe tau accumulation was predominantly observed in the thalamus, hypothalamus, and amygdala with milder involvement of the cortex and hippocampus, leading to synaptic loss, brain atrophy, and FTD-like behavioral abnormalities. Crossbreeding MAPTP301S;Int10+3;S320F mice with App knockin, AppNL-G-F, mice markedly enhanced tau pathology in the cortex and hippocampus, highlighting the interplay between β-amyloid and tau. These findings establish the mutant mice as valuable models for investigating the mechanisms underlying FTD and other tauopathies, providing a relevant platform for in vivo drug screening.

DOI： 10.1016/j.crmeth.2025.101024

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

BACKGROUND: Through a retrospective analysis of existing FDG PET-MRI images, we recently demonstrated that metformin increases the accumulation of FDG in the intestinal lumen, suggesting that metformin stimulates glucose excretion into the intestine. However, the details of this phenomenon remain unclear. We here investigate the detailed dynamics of intestinal glucose excretion, including the rate of excretion and the metabolism of excreted glucose, in both the presence and absence of metformin. METHODS: We quantified intestinal glucose excretion using newly developed FDG PET-MRI-based bioimaging in individuals with type 2 diabetes, both treated and untreated with metformin. The metabolism of excreted glucose was analyzed through mass spectrometry of fecal samples from mice intravenously injected with 13C-labeled glucose. RESULTS: Continuous FDG PET/MRI image taking reveals that FDG is initially observed in the jejunum, suggesting its involvement in FDG excretion. Metformin-treated individuals excrete a significant amount of glucose (~1.65 g h-1 per body) into the intestinal lumen. In individuals not receiving metformin, a certain amount of glucose (~0.41 g h-1per body) is also excreted into the intestinal lumen, indicating its physiological importance. Intravenous injection of 13C-labeled glucose in mice increases the content of 13C in short-chain fatty acids (SCFAs) extracted from feces, and metformin increased the incorporation of 13C into SCFAs. CONCLUSIONS: A previously unrecognized, substantial flux of glucose from the circulation to the intestinal lumen exists, which likely contributes to the symbiosis between gut microbiota and the host. This flux represents a potential target of metformin's action in humans.

DOI： 10.1038/s43856-025-00755-4

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1038/s42003-024-06223-4

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

This study proposes a new method for radionuclide therapy that involves the use of oligomeric 2,6-diisopropylphenyl azides and a chelator to form stable complexes with metallic radionuclides. The technique works by taking advantage of the endogenous acrolein produced by cancer cells. The azides react with the acrolein to give a diazo derivative that immediately attaches to the nearest organelle, effectively anchoring the radionuclide within the tumor. Preliminary in vivo experiments were conducted on a human lung carcinoma xenograft model, demonstrating the feasibility of this approach for cancer treatment.

DOI： 10.1039/d4cc00048j

PubMed

掲載種別：研究論文（学術雑誌）   国際・国内誌：国際誌  

DOI： 10.1093/braincomms/fcae326

PubMed