Aberrant expression of interleukin-17A in mast cells contributes to the pathogenesis of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) significantly diminishes the quality of life for patients. Delayed diagnosis represents a significant challenge in effectively managing HS. OBJECTIVES: To identify and characterize the key mediator in HS. METHODS: Bioinformatic transcriptomic analysis was applied to identify potential candidates contributing to the disease process of HS. Skin samples from 40 patients with HS, four with psoriasis and 29 with normal skin were included. The expression of interleukin (IL)-17A was evaluated and compared among samples of normal skin, psoriatic skin and skin from different stages of HS by immunohistochemistry or dual-colour immunofluorescence. In vitro experiments and RNA sequencing analysis were also conducted to validate the expression of IL-17A and its pathogenic effect in HS. RESULTS: Transcriptomic database analyses identified IL-17 signalling as a potential contributor to HS. In HS, the predominant IL-17A+ cell population was identified as mast cells. IL-17A+ mast-cell density was significantly elevated in HS, especially in samples with advanced Hurley stages, compared with normal skin and psoriasis samples. The close contact between IL-17A+ mast cells and IL-17 receptor A (IL-17RA)-expressing keratinocytes was demonstrated, along with the significant effects of IL-17A on keratinocyte cell proliferation and HS pathogenic gene expression. Treatment with biologics (brodalumab or adalimumab) reduced the severity of the disease and the number of IL-17A+ mast cells in affected tissues. CONCLUSIONS: The presence of high-density IL-17A+ mast cells may serve as a valuable pathological marker for diagnosing HS. Moreover, developing therapeutic drugs targeting IL-17A+ mast cells may provide a new approach to treating HS.

The Complete Mitochondrial Genome and Phylogenetic Analysis of Rhagastis binoculata (Matsumura, 1909) (Lepidoptera: Sphingidae).

The mitochondrial genome (mitogenome) Rhagastis binoculata (Matsumura, 1909), an endemic moth species in Taiwan, was sequenced and analyzed. The complete circular mitogenome of R. binoculata is 15,303 bp and contains 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and an AT-rich control region. The mitogenome has an overall nucleotide composition of 41.2% A, 11.9% C, 7.5% G, and 39.4% T, with an AT content of 80.6%. Of the protein-coding genes (PCGs), 12 start with ATG, ATT, and ATC, and COX1 starts with a "CGA" codon. All of the stop codons are "TAA, TAG, or T". Our phylogenetic analysis of 21 species of Sphingidae insects suggests that R. binoculata is clustered with Rhagastis mongoliana, which belongs to the subfamily Macroglossinae.

Piperlongumine-inhibited TRIM14 signaling sensitizes glioblastoma cells to temozolomide treatment.

AIMS: Glioblastoma multiforme (GBM) is the most aggressive and mortal primary glioma in adults. Temozolomide (TMZ) is a first-line clinical chemotherapeutic drug. However, TMZ resistance causes treatment failure in patients. Thus, exploring effective adjuvant drugs for GBM is crucial. Piperlongumine (PL), a bioactive alkaloid isolated from long pepper, possesses promising anticancer abilities. However, PL-mediated cytotoxic mechanisms in GBM are still unclear. We attempted to identify PL-regulated networks in suppressing GBM malignancy. MAIN METHODS AND KEY FINDINGS: PL treatment significantly induced more apoptotic death in several GBM cell lines than in normal astrocytes. Decreased cell invasion, colony generation, and sphere formation, and enhanced TMZ cytotoxicity were found in PL-treated cells. Through RNA sequencing, PL-mediated transcriptomic profiles were established. By intersecting PL-downregulated genes, higher expressing genes in The Cancer Genome Atlas (TCGA) tumor tissues, and risk genes in three different GBM databases, tripartite motif-containing 14 (TRIM14) was selected. Higher TRIM14 expression was correlated with poor patient survival, and it existed in tumor samples, in mesenchymal type of GBM patients, and in GBM cells. PL significantly reduced TRIM14 expression through activating the p38/MAPK pathway. Overexpression or knockdown of TRIM14 influenced cell growth, PL-inhibited cell viability, invasion, colony generation, and sphere formation. Finally, using a gene set enrichment analysis, genes positively correlated with TRIM14 levels were enriched in epithelial-to-mesenchymal transition signaling. TRIM14 overexpression attenuated PL-regulated mesenchymal transition signaling. SIGNIFICANCE: PL inhibited TRIM14 signaling through activating the p38/MAPK pathway to inhibit GBM malignancy. Our findings may provide better insights and directions for future GBM therapies.