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Background: Eosinophilic inflammation is a hallmark of refractory chronic rhinosinusitis (CRS) and considered a major therapeutic target. Autophagy deficiency in myeloid cells plays a causal role in eosinophilic CRS (ECRS) via macrophage IL‐1β overproduction, thereby suggesting autophagy regulation as a potential therapeutic modality. Trehalose is a disaccharide sugar with known pro‐autophagy activity and effective in alleviating diverse inflammatory diseases. We sought to investigate the therapeutic potential of autophagy‐enhancing agent, trehalose, or related sugar compounds, and the underlying mechanism focusing on macrophage IL‐1β production in ECRS pathogenesis. Methods: We investigated the therapeutic effects of trehalose and saccharin on macrophage IL‐1β production and eosinophilia in the mouse model of ECRS with myeloid cell‐specific autophagy‐related gene 7 (Atg7) deletion. The mechanisms underlying their anti‐inflammatory effects were assessed using specific inhibitor, genetic knockdown or knockout, and overexpression of cognate receptors. Results: Unexpectedly, trehalose significantly attenuated eosinophilia and disease pathogenesis in ECRS mice caused by autophagy deficiency in myeloid cells. This autophagy‐independent effect was associated with reduced macrophage IL‐1β expression. Various sugars recapitulated the anti‐inflammatory effect of trehalose, and saccharin was particularly effective amongst other sugars. The mechanistic study revealed an involvement of sweet taste receptor (STR), especially T1R3, in alleviating macrophage IL‐1β production and eosinophilia in CRS, which was supported by genetic depletion of T1R3 or overexpression of T1R2/T1R3 in macrophages and treatment with the T1R3 antagonist gurmarin. Conclusion: Our results revealed a previously unappreciated anti‐inflammatory effect of STR agonists, particularly trehalose and saccharin, and may provide an alternative strategy to autophagy modulation in the ECRS treatment. [ABSTRACT FROM AUTHOR]

Drawing on various studies, we provide a holistic view incorporating different nested cultural contexts, organizational shame, and health outcomes. We introduce the concept of organizational shame and explain its two key domains: conformity and status/competition. Then, we comprehensively review prior studies on cultural approaches to shame and propose our cultural variance model of organizational shame. Our model illustrates an equilibrium, exhibiting dominant and stable patterns of shame domains formed by reinforcing relationships among three key nested contextual layers: individuals (workers), organizations (firms), and the labor market. We apply our model to discuss general and occupational implications and outline future research directions. Thus, we hope to conceptualize organizational shame within the dynamic contexts of organizations and cultures. [ABSTRACT FROM AUTHOR]

Despite the high potency of bilirubin as an endogenous anti-inflammatory compound, its clinical translation has been hampered because of its insolubility in water. Bilirubin-based nanoparticles that may overcome this critical issue are presented. A polyethylene glycol compound (PEG) was covalently attached to bilirubin, yielding PEGylated bilirubin (PEG-BR). The PEG-BR self-assembled into nanoscale particles with a size of approximately 110 nm, termed bilirubin nanoparticles (BRNPs). BRNPs are highly efficient hydrogen peroxide scavengers, thereby protecting cells from H2O2-induced cytotoxicity. In a murine model of ulcerative colitis, intravenous injection of BRNPs showed preferential accumulation of nanoparticles at the sites of inflammation and significantly inhibited the progression of acute inflammation in the colon. Taken together, BRNPs show potential for use as a therapeutic nanomedicine in various inflammatory diseases. [ABSTRACT FROM AUTHOR]

Drawing on various studies, we provide a holistic view incorporating different nested cultural contexts, organizational shame, and health outcomes. We introduce the concept of organizational shame and explain its two key domains: conformity and status/competition. Then, we comprehensively review prior studies on cultural approaches to shame and propose our cultural variance model of organizational shame. Our model illustrates an equilibrium, exhibiting dominant and stable patterns of shame domains formed by reinforcing relationships among three key nested contextual layers: individuals (workers), organizations (firms), and the labor market. We apply our model to discuss general and occupational implications and outline future research directions. Thus, we hope to conceptualize organizational shame within the dynamic contexts of organizations and cultures. [ABSTRACT FROM AUTHOR]