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    The Psoriasis Glycome: Differential Expression of Cholesterol Particle Glycans and IgA Glycans Linked to Disease Severity. The Journal of investigative dermatology 10.1016/j.jid.2022.03.030
    Associations between TERT promoter mutations and survival in superficial spreading and nodular melanomas in a large prospective patient cohort. The Journal of investigative dermatology Survival outcomes in melanoma, and their association with mutations in the telomerase reverse transcriptase (TERT) promoter, remain uncertain. In addition, few studies have examined whether these associations are affected by a nearby common germline polymorphism, or vary based on melanoma histopathological subtype. We analyzed 408 primary tumors from a prospective melanoma cohort for somatic TERT and TERT mutations, the germline polymorphism rs2853669, and BRAF and NRAS mutations. We tested the associations between these variants and clinicopathologic factors and survival outcomes. TERT was associated with thicker tumors, ulceration, mitoses (>0/mm), nodular histotype and CNS involvement. In a multivariable model controlling for AJCC stage, TERT was an independent predictor of shorter recurrence-free survival (RFS) (HR=2.58, p=0.001), and overall survival (HR=2.47, p=0.029). Patients with the germline variant and TERT mutant melanomas had significantly shorter RFS than those patients lacking either or both sequence variants (p<0.04). The impact of the germline variant appeared to be more pronounced in superficial spreading compared to nodular melanoma. No associations were found between survival and TERT, BRAF or NRAS mutations. These findings strongly suggest that TERT mutation is a biomarker of aggressive primary melanomas, an effect that may be modulated by rs2853669. 10.1016/j.jid.2022.03.031
    miR-10a, miR-30c, and miR-451a encapsulated in small extracellular vesicles are pro-senescence factors in human dermal fibroblasts. The Journal of investigative dermatology Although small extracellular vesicles (sEV) have been reported to play an important role in cellular senescence and aging, little is known about the potential role and function of microRNAs (miRNAs) contained within the sEV. To determine senescence-associated factors secreted from sEV of human dermal fibroblasts (HDF), we isolated and characterized sEV from non-senescent vs. senescent HDF. Small RNA sequencing analysis identified many enriched miRNAs in sEV of senescent HDF, as shown by the upregulation of miR-10a, miR-30c, and miR-451a, and downregulation of miR-128, miR-184, miR-200c, and miR-125a. Overexpression of miR-10a, miR-30c, and miR-451a induced an aging phenotype in HDF, whereas inhibition of these miRNAs reduced senescent-like phenotypes in senescent HDF. Moreover, treatment with sEV or sEV-containing conditioned medium promoted cellular senescence in HDF, whereas sEV depletion abrogated pro-senescence effects of the senescent HDF secretome. Interestingly, pro-senescence sEV miRNAs were found to have an essential role in regulating reactive oxygen species production and mitophagy activation. Taken together, our results revealed miR-10a, miR-30c, and miR-451a as pro-senescence factors that are differentially expressed in sEV of senescent HDF, demonstrating the essential role of sEV miRNAs in the biological processes of aging. 10.1016/j.jid.2022.03.032
    A distinct immature low-density neutrophil population characterizes acute generalized pustular psoriasis. The Journal of investigative dermatology 10.1016/j.jid.2022.04.011
    Chrna5 is overexpressed in psoriasis patients and promotes psoriasis-like inflammation in mouse models. The Journal of investigative dermatology It is well known that psoriasis is closely related to smoking, and the cholinergic receptor nicotinic subunit alpha-5 (Chrna5) plays an important role in smoking-related diseases. However, studies on the relationship between Chrna5 and psoriasis are limited. This study aimed to examine the role of Chrna5 in psoriasis development and pathogenesis. Analysis in psoriatic tissues and imiquimod (IMQ)-induced mouse models showed that Chrna5 was highly expressed in psoriatic lesional skin. To further verify the function of Chrna5, we constructed Chrna5-knockout mice and induced the psoriasis model. We found that Chrna5 knockout significantly reduced the severity of psoriasis and could regulate inflammation via the mitogen-activated protein kinase kinase kinase 1 (MEKK1)/c-Jun NH(2)-terminal kinase (JNK)-MAPK/NF-κB pathway. The single-cell sequencing results revealed that after Chrna5 knockout, the keratinocyte subpopulation was significantly reduced and the related Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway was downregulated, further indicating the importance of Chrna5 in psoriasis. Human keratinocytes were analyzed, and silencing Chrna5 inhibited keratinocyte proliferation and migration. In summary, Chrna5 played important roles in the development and pathogenesis of psoriasis, and targeting Chrna5 may be an effective strategy for the treatment of psoriasis. 10.1016/j.jid.2022.04.014