Anaplastic thyroid carcinoma (ATC) responds for the majority of death of thyroid carcinoma and often causes chemotherapy resistance. We investigated the influence of circEIF6 (Hsa_circ_0060060) on the cisplatin-sensitivity in papillary thyroid carcinoma (PTC) and ATC cells, and explored its regulation to downstream molecules miR-144-3p and Transforming Growth Factor α (TGF-α). Differentially expressed circRNAs in PTC were analyzed using the GSE93522 data downloaded. Expressions of circEIF6, miR-144-3p, TGF-α, autophagy-related proteins and apoptosis-related proteins were determined using qRT-PCR or western blot. RNA pull-down assay and dual luciferase report assay were applied to reveal the target relationships. Autophagy marker LC3 and cell proliferation marker ki67 were evaluated by immunofluorescence and immunohistochemistry. Cell viability was evaluated with MTT assay and cell apoptosis was assessed by flow cytometric analysis. CircEIF6, could promote autophagy induced by cisplatin, thus inhibiting cell apoptosis and enhancing the resistance of PTC and ATC cells to cisplatin. Has-miR-144-3p was the target of circEIF6 and was regulated by circEIF6. Besides, circEIF6 promoted autophagy by regulating miR-144-3p/TGF-α axis, enhancing the cisplatin-resistance in PTC and ATC cells. CircEIF6 promoted tumor growth by regulating miR-144-3p/TGF-α and circEIF6 knock-down enhanced cisplatin sensitivity in vivo. CircEIF6 could provide a target for therapy of cisplatin-resistance in thyroid carcinoma.
Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disorder involving the sacroiliac (SI) joints, the spine and often the hips. Biologic therapy has been shown to be efficacious in patients with AS and could improve patients’ quality of life. With the increased use of tumor necrosis factor-ɑ (TNF-ɑ) inhibitors, more paradoxical reactions have been revealed. However, the treatment option for patients with AS is still a challenge when refractory paradoxical palmoplantar pustulosis appeared after the use of TNF-ɑ inhibitors. We reported the case of a 45-year-old male patient with AS treated with adalimumab treatment who developed a refractory paradoxical palmoplantar pustulosis after failure of prior secukinumab treatment. A dramatic improvement was seen in all skin and low back pain after the use of ixekizumab. We conclude that, in TNF-α inhibitors induced refractory paradoxical palmoplantar pustulosis, ixekizumab should be considered as an alternative option to choose from.
Background: Lichen simplex chronicus (LSC) is an acquired chronic dermatosis that is often accompanied by severe paroxysmal pruritus, and its pathogenesis to date is still unclear. Transient receptor potential channel A1 (TRPA1) is a non-selective cation channel. TRPA1 is widely expressed in skin, sensory neurons, and various other tissues, along with various biological functions and activation mechanisms. This study aimed to explore the changes in TRPA1 expression in human LSC and provide evidence for further research on the role of TRPA1 in chronic pruritus.Methods: A total of 21 skin lesion specimens from LSC patients with skin pruritus lasting more than 6 weeks, and 28 normal skin tissue specimens through the skin biopsy from June 2018 to February 2019 were collected. The expression of TRPA1 in these skin tissues was evaluated through western blotting, quantitative reverse transcription PCR (qRT-PCR), and immunohistochemical analysis. The changes of inflammatory mediators, including interleukin (IL)-6, IL-13, endothelin-1 (ET-1), and thymic stromal lymphopoietin (TSLP), as well as substance P, are also analyzed by qRT-PCR. TRPA1 was detected using immunohistochemistry for all skin layers, the basal layer, and around the blood vessels of the dermis.
Results:The expression of TRPA1 in LSC specimens was significantly decreased as compared with that in the normal specimens (P<0.05). Also, TRPA1 protein levels were consistently decreased in LSC specimens (P<0.05). Simultaneously, the mRNA expressions of TRPA1, IL-6, IL-13, ET-1, TSLP, and substance P presented with no significant differences between LSC and normal specimens.Conclusions: TRPA1 expression is proved downregulated in skin lesions of LSC patients with skin pruritus, indicating that TRPA1 serves as a crucial role in the pathogenesis of human LSC.
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