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Alopecia areata (AA) is an autoimmune inflammatory disease characterized by non‐scarring hair loss due to an immune response that targets hair follicles. The current treatment approach for AA involves the use of immunosuppressants and immunomodulators to reduce cytokine levels around affected hair follicles. Sodium‐glucose cotransporter 2 (SGLT2) inhibitors have emerged as potential anti‐inflammatory agents with diverse beneficial effects in various medical conditions. This study investigates the role of beta‐hydroxybutyrate (BHB), a ketone body produced during SGLT2 inhibition, in the pathogenesis of AA. Serum BHB levels were found to be significantly elevated in patients with AA compared with healthy controls, with higher levels correlating with severity of hair loss. BHB treatment increased inflammatory cytokine production in outer root sheath (ORS) cells, mimicking the inflammatory conditions seen in AA. The results suggest that elevated BHB levels may exacerbate the inflammatory immune response in AA patients and may be associated with chronic hair loss and resistance to treatment. Serum BHB levels may serve as a potential marker of poor prognosis in patients with severe AA. Further research is needed to elucidate the precise role of BHB in the pathogenesis of AA and its implications for disease management. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is a T‐cell‐mediated autoimmune disease that causes chronic, relapsing hair loss; however, its precise pathogenesis remains to be elucidated. Recent studies have provided compelling evidence of crosstalk between inflammasomes and mitophagy—a process that contributes to the removal of damaged mitochondria. Our previous studies showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome is important for eliciting and progressing inflammation in AA. In this study, we detected mitochondrial DNA damage in AA‐affected scalp tissues and IFNγ and poly(I:C) treated outer root sheath (ORS) cells. In addition, IFNγ and poly(I:C) treatment increased mitochondrial reactive oxygen species (ROS) levels in ORS cells. Moreover, we showed that mitophagy induction alleviates IFNγ and poly(I:C)‐induced NLRP3 inflammasome activation in ORS cells. Lastly, PTEN‐induced kinase 1 (PINK1) knockdown increased NLRP3 inflammasome activation, indicating that PINK1‐mediated mitophagy plays a critical role in NLRP3 inflammasome activation in ORS cells. This study supports previous studies showing that oxidative stress disrupts immune privilege status and promotes autoimmunity in AA. The results emphasize the significance of crosstalk between mitophagy and inflammasomes in the pathogenesis of AA. Finally, mitophagy factors regulating mitochondrial dysfunction and inhibiting inflammasome activation could be novel therapeutic targets for AA. [ABSTRACT FROM AUTHOR]

Keywords: acne; IGF-1; lipogenesis; sebocytes; YAP EN acne IGF-1 lipogenesis sebocytes YAP 996 998 3 07/14/23 20230701 NES 230701 Acne is a chronic inflammatory disorder of the pilosebaceous unit. From these results, we determined that IGF-1 increased YAP activity in sebocytes and YAP inhibition attenuated IGF-1-induced lipid production by preventing IGFR-mTOR signalling pathway. To investigate the mechanism of YAP inhibition on IGF-1-induced lipogenesis, we evaluated the protein expression of important transcription factors related to lipid production. [Extracted from the article]

We conducted large‐scale screening test on drugs that were already approved for other diseases to find pigmentation‐modulating agents. Among drugs with potential for pigmentation control, we selected sorafenib and further investigated the effect on pigmentation using HM3KO melanoma cells. As a result of treating melanoma cells with sorafenib, pigmentation was promoted in terms of melanin content and tyrosinase activity. Sorafenib increased mRNA and protein levels of pigmentation‐related genes such as MITF, tyrosinase and TRP1. To uncover the action mechanism, we investigated the effect of sorafenib on the intracellular signalling pathways. Sorafenib reduced phosphorylation of AKT and ERK, suggesting that sorafenib induces pigmentation through inhibition of the AKT and ERK pathways. In addition, sorafenib significantly increased the level of active β‐catenin, together with activation of β‐catenin signalling. Mechanistic study revealed that sorafenib decreased phosphorylation of serine 9 (S9) of GSK3β, while it increased phosphorylation of tyrosine 216 (Y216) of GSK3β. These results suggest that sorafenib activates the β‐catenin signalling through the regulation of GSK3β phosphorylation, thereby affecting the pigmentation process. [ABSTRACT FROM AUTHOR]