Dysregulation of inflammatory cytokines in keratinocytes promote the pathogenesis of the skin inflammation, such as allergic contact dermatitis (ACD). High-mobility group box 1 protein (HMGB1) has been implicated in the promotion of skin inflammation upon its extracellular release as a damage-associated molecular pattern molecule. However, whether and how HMGB1 in keratinocytes contributes to ACD and other skin disorders remain elusive. In this study, we generated conditional knockout mice in which theHmgb1gene is specifically deleted in keratinocytes, and examined its role in ACD models. Interestingly, the mutant mice showed exacerbated skin inflammation, accompanied by increased ear thickening in 2,4-dinitrofluorobenezene-induced ACDs. The mRNA expression of interleukin-24 (IL-24), a cytokine known to critically contribute to ACD pathogenesis, was elevated in skin lesions of the mutant mice. As with constitutively expressed, IL-4–inducedIl24mRNA, expression was also augmented in theHmgb1-deficient keratinocytes, which would account for the exacerbation of ACD in the mutant mice. Mechanistically, we observed an increased binding of trimethyl histone H3 (lys4) (H3K4me3), a hallmark of transcriptionally active genes, to the promoter region of theIl24gene in thehmgb1-deficient cells. Thus, the nuclear HMGB1 is a critical “gate keeper” in that the dermal homeostasis is contingent to its function in chromatin remodeling. Our study revealed a facet of nuclear HMGB1, namely its antiinflammatory function in keratinocytes for the skin homeostasis.
In response to new findings and comments from the members and the public, the Dysphagia Diet Committee of the Medical Review Committee of the Japanese Society of Dysphagia Rehabilitation, which was established in April 2010, has discussed and made regular improvements to the Japanese Dysphagia Diet of 2013 (JDD2013) [1,2] since its creation eight years ago. As a result, the JDD2013 was revised and "the Japanese Dysphagia Diet of 2021 by the Japanese Society of Dysphagia Rehabilitation" was drawn up. In the future, the Board of Directors will discuss how to deal with additional opinions and the necessity of reviewing the classification.This article is a translation of "the Japanese Dysphagia Diet of 2021 by the Japanese Society of Dysphagia Rehabilitation [3]" published in Japanese in August 2021. I. Overview and General Remarks NameThe name of the classification is the Japanese Dysphagia Diet of 2021 of the Japanese Society of Dysphagia Rehabilitation (JDD2021). The JDD2021 describes the classification of meals and the classification of thickened liquid and is referred to as the JDD2021 (meal) and the JDD2021 (thickened liquid), respectively. To simplify this, we created a quick reference table for the JDD2021 (meal) and the JDD2021 (thickened liquid); however, this explanation should be read carefully before use (refer to Table 1 and 2). Purpose of establishmentIn Japan, since there was no unified stage of dysphagia diet, such as the National Dysphagia Diet (2002) [4] in the United States, many names and stages of dysphagia diet were used inconsistently in each region and facility. Moreover, the lack of consensus and standard classification contributed to the delay in the listing of medical fees.These factors are disadvantages for patients with dysphagia and people involved in the care of such patients, for example, those involved in the transfer of dysphagia patients from acute hospitals to convalescent hospitals, or from hospitals to facilities or homes. Therefore, the JDD2013 shows the graded classification of meals and thickened liquids that are
High mobility group box-1 (HMGB1) is a ubiquitously expressed nonhistone nuclear protein which acts as a danger signal on extracellular release. Extracellular HMGB1 induces inflammation, migration, proliferation, angiogenesis, and activation of various cells. It is reported that HMGB1 contributes to the development of various kinds of malignant tumors, including hematologic malignancies, through fulfillment of tumor energy metabolism, inhibition of antitumor immunity and promotion of angiogenesis. In addition, HMGB1 overexpression is associated with poorer prognosis in patients with various types of solid malignancies. In this study, to investigate the roles of HMGB1 in cutaneous T-cell lymphoma (CTCL), we examined HMGB1 expression in blood and lesional skin of CTCL patients. Serum HMGB1 levels were significantly higher in patients with CTCL than those in healthy controls. Importantly, serum HMGB1 levels in patients with CTCL positively correlated with serum soluble interleukin 2 receptor and thymus and activation-regulated chemokine levels, both of which are disease severity markers of CTCL. HMGB1 mRNA levels in lesional skin of CTCL were also significantly higher than those in healthy controls. When classified with types of skin lesions, HMGB1 expression levels in both blood and lesional skin were significantly higher in patients with erythrodermic CTCL compared to those in healthy controls. Immunohistochemical staining revealed that HMGB1 was ubiquitously expressed in the nucleus of all cells. In lesional skin of CTCL, HMGB1 is relatively highly concentrated in the cytosol of keratinocytes and dermal perivascular infiltrates. Our results suggest that enhanced HMGB1 expression is associated with development of erythrodermic CTCL.
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