Paeonol Ameliorates Chronic Itch and Spinal Astrocytic Activation via CXCR3 in an Experimental Dry Skin Model in Mice

Paeonol is a bioactive phenol presents mainly in Paeonia suffruticosa Andr. (Paeoniaceae), Paeonia lactiflora Pall., and Dioscorea japonica Thunb. (Dioscoreaceae), harboring various pharmacological activities including anti-inflammatory, antioxidant, immune regulatory activity and reverse chemoresistance. Recent reports revealed paeonol exhibited good effects on chronic dermatitis, such as atopic dermatitis (AD) and psoriasis. However, whether paeonol is effective for dry skin disease and its mechanism of action still remain unclear. In this study, we analysed the effects of paeonol on a mouse model of dry skin treated with acetone-ether-water (AEW), which showed impressive activities in reducing scratching behavior and skin inflammation. To elucidate the underlying molecular targets for the anti-pruritic ability of paeonol, we screened the expression of possible chemokine pathways in the spinal cord. The expression of CXCR3 was significantly alleviated by paeonol, which increased greatly in the spinal neurons of AEW mice. In addition, treatment of paeonol significantly inhibited AEW-induced expression of astrocyte activity-dependent genes including Tlr4, Lcn2 and Hspb1 et al. The inhibitory effects of paeonol on scratching behavior and astrocytic activation in the spinal cord induced by AEW were abolished when CXCR3 was antagonized or genetically ablated. Taken together, our results indicated that paeonol can ameliorate AEW-induced inflammatory response and itching behavior, and reduce the expression of spinal astrocyte activity-dependent genes induced by AEW, which are driven by CXCR3.

Keratin 17 Is Required for Lipid Metabolism in Keratinocytes and Benefits Epidermal Permeability Barrier Homeostasis

The epidermal barrier refers to the stratum corneum, the uppermost layer of the skin, and constitutes the first line of defense against invasion by potentially harmful pathogens, diminishes trans-epidermal water loss, and plays a crucial role in the maintenance of skin homeostasis. Keratin 17 (K17) is a type I epithelial keratin with multiple functions, including in skin inflammation, epithelial cell growth, protein synthesis, and tumorigenesis. However, the relationship between K17 and the skin barrier has yet to be systematically investigated. In this study, we found that acute disruption of the epidermal permeability barrier led to a rapid increase in epidermal K17 expression in vivo. Krt17 gene deficiency in mice resulted in decreased expression of lipid metabolism-related enzymes and antimicrobial peptides, while also delaying epidermal permeability barrier recovery after acute disruption. Adenovirus-mediated overexpression of K17 enhanced, whereas siRNA-mediated knockdown of Krt17 inhibited, the expression of fatty acid synthase (FASN) and that of the transcription factors SREBP-1 and PPARγ in vitro. We further confirmed that K17 can facilitate the nuclear transportation of SREBP-1 and PPARγ and promote lipid synthesis in keratinocytes. This study demonstrated that K17 contributes to the restoration of the epidermal permeability barrier via stabilizing lipid metabolism in keratinocytes.

Effect of the cure time on the Mechanical Properties of Silicone Rubber used as Socket Liners

This work is focused on the upper part of the prosthesis which is called a socket, it is in contact connect with the amputated part. The shear force between skin and socket, local pressure, sweating, and bacteria generation, all lead to skin inflammation and a bad smell. Consequently, the prosthesis became uncomfortable for a patient. To address this issue silicone rubber liners is proposed to use because it can absorb moisture, stress distribution, and anti-bacterial. The curing time and temperature are important factors for determining crosslink density, from the results obtained, can be noticed that, the cross-link density can greatly affect the silicone rubber properties, it can have a direct effect on the tensile strength, modulus of elasticity, percentage of elongation as well as the water absorption, and the cure time (15 min.) shoes the best resalt. As a result, using it making the prosthesis more comfortable and acceptable to the patient. In this paper, the effect of cure time on physical properties was studied.

M-CSF-Stimulated CD11b+ Myeloid Cells Induce Alopecia Areata in C3H/HeJ Mice

Alopecia areata (AA) is a T cell-mediated autoimmune skin disease with clinical features of hair loss and skin inflammation. It is unclear whether other immune cells except T lymphocytes are also involved in the development of AA. Here, our results reveal that dermal injection of either CD11b+ myeloid cells isolated from AA-affected skin or non-AA splenocyte-derived CD11b+ cells treated with macrophage colony-stimulating factor (M-CSF) induces AA in C3H/HeJ mice. The functional similarity of these cells in induction of AA seems to be due to a higher expression of M-CSF in AA affected skin. To explore the mechanism by which dermal injection of CD11b+ cells induce AA, we co-culture either AA derived skin cells or M-CSF-stimulated CD11b+ cells with naïve splenocytes. The results of splenocyte proliferation assay and immunoglobulin release in conditioned medium show a significant increase of splenocyte proliferation and IgG level in conditioned medium under both conditions as compared to controls. Most activated splenocytes induced by M-CSF-stimulated myeloid cells are B lymphocytes. B cell activation are further confirmed in AA-affected skin and skin draining lymph nodes of AA mice. In conclusion, in this study, we have provided evidence that M-CSF stimulated CD11b+ cells are able to induce AA in C3H/HeJ mice through a possible mechanism by activating B lymphocytes. This finding may provide insight for understanding the pathogenesis of AA.

The lncRNA H19/miR-766-3p/S1PR3 Axis Contributes to the Hyperproliferation of Keratinocytes and Skin Inflammation in Psoriasis via the AKT/mTOR Pathway

Background. The pathogenesis of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are well studied in psoriasis. However, little is known about how specific lncRNAs and miRNAs affect the mechanism of psoriasis development and which pathways are involved. Objectives. To explore the role of the lncRNA H19/miR-766-3p/S1PR3 axis in psoriasis. Methods. miRNA and lncRNA microarrays were performed using IL-22-induced HaCaT cells and psoriatic lesions, respectively. Fluorescence in situ hybridization and quantitative reverse-transcriptase polymerase chain reaction were used to detect the expression of miR-766-3p and lncRNA H19. Luciferase reporter assays were used to identify miR-766-3p/lncRNA H19 and miR-766-3p/S1PR3 combinations. CCK-8 and ELISA were performed to evaluate the proliferation of keratinocytes and the secretion of pro-inflammatory cytokines. Western blot analysis was used to detect the expression of S1PR3 and its downstream effector proteins. Results. MiR-766-3p was upregulated in both HaCaT cells treated with the psoriasis-related cytokine pool (IL-17A, IL-22, IL-1 alpha, oncostatin M, and TNF-alpha) and tissues. Overexpression of miR-766-3p promoted keratinocyte proliferation and IL-17A and IL-22 secretion. LncRNA H19 and S1PR3 were demonstrably combined with miR-766-3p by luciferase reporter assay. lncRNA H19 repressed proliferation and inflammation, which were reduced by the miR-766-3p. AKT/mTOR pathway effected proliferation and inflammation by the lncRNA H19/miR-766-3p/S1PR3 axis. Conclusions. We established that downregulation of lncRNA H19 promoted the proliferation of keratinocytes and skin inflammation by up-regulating miR-766-3p expression levels and inhibiting activation of S1PR3 through the AKT/mTOR pathway in psoriasis.

The role of gut microbiome in inflammatory skin disorders: a systematic review

The close relationship between the intestine and the skin has been widely stated, seen from gastrointestinal (GI) disorders often accompanied by skin manifestations. Exactly how the gut microbiome is related to skin inflammation and influences the pathophysiology mechanism of skin disorders are still unclear. Many studies have shown a two-way relationship between gut and skin associated with GI health and skin homeostasis and allostasis. This systematic review aimed to explore the associations between the gut microbiome with inflammatory skin disorders, such as acne, psoriasis, atopic dermatitis, and urticaria, and to discover the advanced concept of this relationship. Methods: The literature search was limited to any articles published up to December 2020 using PubMed and EBSCOHost. The review followed the PRISMA guidelines for conducting a systematic review. Result: Of the 319 articles screened based on title and abstract, 111 articles underwent full-text screening. Of these, 23 articles met our inclusion criteria, comprising 13 AD, three psoriasis, four acne vulgaris, and four chronic urticaria articles. Discussion: Acne vulgaris, atopic dermatitis, psoriasis, and chronic urticaria are inflammation skin disorders that were studied recently to ascertain the relationship of these disorders with dysbiosis of the GI microbiome. All acne vulgaris, psoriasis, and chronic urticaria studies stated the association of gut microbiome with skin manifestations. However, the results in atopic dermatitis are still conflicting. Most of the articles agree that Bifidobacterium plays an essential role as anti-inflammation bacteria, and Proteobacteria and Enterobacteria impact inflammation in inflammatory skin disorder.