The gastrointestinal (GI) tract serves as a dynamic chemosensory interface that integrates signals from dietary phytochemicals and microbiota-derived metabolites to regulate host physiology. Beyond digestion and absorption, specialized epithelial and enteroendocrine cells detect luminal compounds via receptors such as taste (sweet, bitter), olfactory, and transient receptor potential (TRP) channels. Phytochemicals — including terpenoids, glycosides, flavonoids, and volatile compounds — activate these receptors to modulate gut hormone secretion, appetite, energy balance, and immune function. Similarly, microbiota-derived metabolites such as short-chain fatty acids, bile acids, and tryptophan derivatives act through G protein-coupled and nuclear receptors to coordinate metabolic, immune, and neuroendocrine processes. Together, these receptor-mediated pathways form a complex communication network linking diet, microbes, and host signaling systems, influencing metabolic health and disease. Future research integrating multi-omics and advanced imaging is expected to clarify these molecular interactions and support the development of precision nutrition strategies targeting gut chemosensory systems for the prevention and treatment of obesity, diabetes, and related disorders.

Trace amine–associated receptor 1 (TAAR1) is highly expressed in rat parotid acinar cells; however, its role in exocrine Ca2+ signaling remains unclear. We herein demonstrated that the selective TAAR1 agonist RO5256390 induced rapid and transient increases in intracellular Ca2+ levels that were completely abolished by the TAAR1 antagonist EPPTB, confirming receptor specificity. Pharmacological dissection revealed dual contributions from extracellular Ca2+ influx via L‐type, T‐type, and receptor‐operated channels and Ca2+ release from intracellular stores mediated by phospholipase C, inositol trisphosphate receptors, and ryanodine receptors. Inhibition of adenylyl cyclase or protein kinase A (PKA) nearly abolished the Ca2+ response, and displacement of PKA from AKAPs using the cell‐permeable AKAP‐displacing peptide st‐Ht31 produced a comparable suppression, underscoring the requirement for microdomain‐restricted PKA activity. Exchange protein directly activated by cAMP 2 (Epac 2) and downstream calmodulin‐dependent protein kinase II were also indispensable, whereas Epac 1 was dispensable. The present study identified a TAAR1‐centered, 3’,5’‐cyclic adenosine monophosphate microdomain network that co‐ordinates Ca2+ entry and release, thereby providing novel targets for the modulation of salivary secretion.

Radiological and nuclear accidents require reliable biomarkers for rapid detection of radiation exposure and dose estimation. While conventional biodosimetry has focused on nuclear DNA damage in lymphocytes, mitochondrial DNA (mtDNA) may provide an additional index because of its high copy number and limited repair capacity. Previous studies using Epstein–Barr virus-transformed lymphocytes and HeLa-FUCCI cells demonstrated radiation-induced changes in mtDNA copy number (mtDNAcn), suggesting compensatory replication as a characteristic response, but in vivo evidence has been limited. In this study, we analyzed peripheral blood from C57BL/6N male mice (8 weeks old) exposed to 0, 0.05, 0.2, 0.5, or 2 Gy of X-rays. MtDNAcn and intact copy ratio, defined as the proportion of undamaged copies, were quantified at 1 day and 1 week post-irradiation. We found that mtDNAcn was significantly increased only in the 2 Gy group at both 1 day and 1 week, whereas the intact copy ratio was significantly decreased in the 0.5 Gy and 2 Gy groups at 1 day but returned to baseline by 1 week. These findings indicate that peripheral blood-derived mtDNA indices are promising biomarkers for radiation biodosimetry, and that intact copy ratio may be particularly useful for detecting low-dose exposure.

The health benefits of apple polyphenols are well-documented. Phlorizin (Pz), an apple-derived polyphenol, is a known inhibitor of sodium-glucose cotransporters (SGLTs); however, the effects of other apple constituents on SGLTs remain unclear. In this study, we examined the inhibitory effects of an unripe apple polyphenol extract, ApplePhenon® (AP), and its constituents—including Pz, phloretin, procyanidins B1 and B2, chlorogenic acid, gallic acid, catechin, epicatechin, epigallocatechin gallate, and quercetin—on SGLTs using the Ussing chamber in mouse small intestinal mucosa. AP exhibited noncompetitive inhibition of glucose-induced short-circuit current (Isc), reflecting electrogenic Na+ transport via SGLTs (apparent Ki = 22.23 ± 3.06 μg·mL−1). A similar inhibitory effect was observed in the case of Pz (Ki = 1.88 ± 0.32 μg·mL−1), phloretin (Ki = 18.82 ± 3.52 μg·mL−1), and quercetin (Ki = 220.9 ± 3.52 μg·mL−1) but not in other components. Based on the total Pz content of 6.2%, 86.0% of the inhibitory effect can be attributed to Pz. Although Pz is known to inhibit SGLT1 competitively, AP and its constituents, including Pz, phloretin, and quercetin, showed noncompetitive inhibition in this study. These findings warrant further investigation into the mechanisms underlying SGLT inhibition by AP.