Despite the long history of use of steroid ointments for oral mucositis, the analgesic mechanism has not been fully elucidated. In this study, we examined the effects of triamcinolone acetonide (Tmc) on oral ulcerative mucositis-induced pain in conscious rats by our proprietary assay system. Based on evaluations of the physical properties and retention periods in the oral mucosa of human volunteers and rats, we selected TRAFUL^® ointment as a long-lasting base. In oral ulcerative mucositis model rats, TRAFUL^® with Tmc suppressed cyclooxygenase-dependent inflammatory responses with upregulations of glucocorticoid receptor-induced anti-inflammatory genes and inhibited spontaneous nociceptive behavior. When an ointment with a shorter residual period was used, the effects of Tmc were not elicited or were induced to a lesser extent. Importantly, TRAFUL^® with Tmc also improved oral ulcerative mucositis-induced mechanical allodynia, which has been reported to be independent of cyclooxygenase. Ca²⁺ imaging in dissociated trigeminal ganglion neurons showed that long-term preincubation with Tmc inhibited the hypertonic stimulation-induced Ca²⁺ response. These results suggest that the representative steroid Tmc suppresses oral ulcerative mucositis-induced pain by general anti-inflammatory actions and inhibits mechanical sensitivity in peripheral nerves. For drug delivery, long-lasting ointments such as TRAFUL^® are needed to sufficiently induce the therapeutic effects.

Presently, people are not only exposed to sunlight but also to a large amount of blue light from personal computers and smartphones. This blue light has various effects on the living body. However, its effect on the induction of skin cancer is unknown. In this study, we investigated the induction of skin cancer by long-term blue light irradiation. Hairless mice were irradiated with blue light (LED; peak emission 479 nm) every day for one year, and a control was irradiated with white light (LED), green light (LED; peak emission 538 nm), and red light (LED; peak emission 629 nm) for one year, respectively. Skin cancer was induced only in the mice exposed to blue light. Long-term blue light irradiation also increased the migration of neutrophils and macrophages involved in carcinogenesis in the skin. In neutrophils, an increased expression of citH3 and PAD4 was observed, suggesting the possibility of NETosis. Conversely, in macrophages, inflammatory macrophages (type 1 macrophages) increased and anti-inflammatory macrophages (type 2 macrophages) decreased due to continuous blue light irradiation. These findings suggest that long-term continuous irradiation with blue light induces neutrophil NETosis and an increase in type 1 macrophages, resulting in skin cancer.

Humans are persistently exposed to massive amounts of blue light via sunlight, computers, smartphones, and similar devices. Although the positive and negative effects of blue light on living organisms have been reported, its impact on learning and memory remains unknown. Herein, we examined the effects of widespread blue light exposure on the learning and memory abilities of blue light-exposed mice. Ten-week-old male ICR mice were divided into five groups (five mice/group) and irradiated with blue light from a light-emitting diode daily for 6 months. After 6 months of blue light irradiation, mice exhibited a decline in memory and learning abilities, assessed using the Morris water maze and step-through passive avoidance paradigms. Blue light-irradiated mice exhibited a decreased expression of the clock gene brain and muscle arnt-like 1 (Bmal1). The number of microglia and levels of M1 macrophage CC-chemokine receptor 7 and inducible nitric oxide synthase were increased, accompanied by a decrease in M2 macrophage arginase-1 levels. Levels of angiopoietin-like protein 2 and inflammatory cytokines interleukin-6, tumor necrosis factor-α, and interleukin-1β were elevated. Our findings suggest that long-term blue light exposure could reduce Bmal1 expression, activate the M1 macrophage/Angptl2/inflammatory cytokine pathway, induce neurodegeneration, and lead to a decline in memory.

Background: Lactic acid bacteria consumption serves several health benefits to humans. However, their effect on natural skin aging is still unclear. Methods: This study examined the effects of skin naturalization (particularly skin drying) by administering a spore-bearing lactic acid bacteria (Bacillus coagulans) in mice for 2 years. Results: B. coagulans administration improved the natural skin of mice and significantly increased proportions of the genera Bacteroides and Muribaculum, among other intestinal bacteria. As metabolites, increases in nicotinic acid, putrescin, and pantothenic acid levels and a decrease in choline levels were observed. Increased hyaluronic acid, interleukin-10, and M2 macrophage levels indicate aging-related molecules in the skin. Intestinal permeability was also suppressed. Thus, these changes together improved natural skin aging. Conclusions: This study revealed that B. coagulans administration improved the natural skin aging in mice. This enhancement might be induced by the interaction of alterations in intestinal flora, metabolites, or inflammatory substances.

TFEB, a basic helix-loop-helix transcription factor, is a master regulator of autophagy, lysosome biogenesis and lipid catabolism. Compared to posttranslational regulation of TFEB, the regulation of TFEB mRNA stability remains relatively uncharacterized. In this study, we identified the mRNA-binding protein THOC4 as a novel regulator of TFEB. In mammalian cells, siRNA-mediated knockdown of THOC4 decreased the level of TFEB protein to a greater extent than other bHLH transcription factors. THOC4 bound to TFEB mRNA and stabilized it after transcription by maintaining poly(A) tail length. We further found that this mode of regulation was conserved in Caenorhabditiselegans and was essential for TFEB-mediated lipid breakdown, which becomes over-represented during prolonged starvation. Taken together, our findings reveal the presence of an additional layer of TFEB regulation by THOC4 and provide novel insights into the function of TFEB in mediating autophagy and lipid metabolism.

Humans are exposed to significant amounts of blue light from computers and smartphones. However, the effects of blue light on ulcerative colitis remain unclear. In this study, we assessed blue-light-irradiation-induced alterations in colonic symptoms using a dextran sodium sulfate (DSS)-induced ulcerative colitis model mice. Both male and female institute of cancer research (ICR) mice were administered DSS (5%) ad libitum for 5 days while irradiated with 40 kJ/m² blue light daily. Additionally, tranexamic acid (TA) was administered daily throughout the study. Male mice treated with DSS/blue light exhibited exacerbated colitis compared to those treated with DSS alone. In contrast, female mice treated with DSS/blue light exhibited enhanced symptoms compared to those treated with DSS alone. Additionally, in male mice exposed to blue light, the clock/brain and muscle Arndt-like 1 (Bma1)/noradrenaline/macrophage or beta2-adrenergic receptor (β2-AR) pathways were activated. In female mice, the Bmal1/acetylcholine/macrophage/nicotinic acetylcholine receptor alpha 7 (α7nAChR) pathway was activated. These findings highlight sex differences in the effects of blue light on DSS-induced ulcerative colitis. Moreover, the worsening of symptoms in males was ameliorated through TA administration.