Psoriasis is a prevalent, chronic inflammatory skin disease that arises from rapid and excessive growth of keratinocytes induced by abnormal inflammatory responses.Metformin is the first-line drug in type 2 diabetes and has been proven to possess significant anti-inflammatory effects in various diseases. In the present study, we examined the role of metformin in nuclear factor kappa B (NF-κB)-mediated inflammatory responses in HaCaT cells, a cell line for the keratinocyte. Our results demonstrated that metformin significantly decreased the mRNA and protein levels of tumour necrosis factor-α (TNFα), interleukin (IL)-6, IL-8, and IL-1β induced by TNFα. Immunofluorescence staining and western blot analysis showed that metformin inhibited the nuclear localization of p65, a subunit of nuclear factor NF-κB. In addition, metformin suppressed the transcription activity of NF-κB by inhibiting the degradation of IκBα. The inhibitory effect of metformin on NF-κB signalling is comparable with a specific IKKβ inhibitor BI605906. Collectively, our data suggest that metformin may be a potential therapeutic agent in inflammatory skin diseases like psoriasis.

Rab23 was a member of Ras-related small GTPase family, which played a key role in the regulation of Shh signaling pathway. However, the function and regulatory mechanism of Rab23 in cutaneous squamous cell carcinoma was unknown. In this study, we found that the expression level of Rab23 was higher in moderately to poorly tumor differentiation tissue and non-exposed positions, and no statistically significant difference showed in Rab23 expression according to trauma/chronic disease, location on lips/ears, tumor size, gender, or age. Interestingly, we found that Rab23 RNAi suppressed cell invasion and Rab23 overexpression promoted cell invasion depended on GTP-bound form of Rab23. Inhibition of Rac1 activity or Rac1 silencing with siRNA fragment attenuated Rab23 promoted cells migration and invasion. Notably, we confirmed that Rab23 was co-localized with integrin β1 in cell membrane of Rab23 WT and Rab23 Q68L stable expression cells and Rab23 efficiently coprecipitated with integrin β1 and Tiam1 in a GTP-dependent manner. Further, integrin β1 siRNA interrupted the coprecipitation between Rab23 and Tiam1 and attenuated Rab23 promoted cells migration and invasion. Taken together, our results indicated that Rab23 promotes squamous cell carcinoma cells migration and invasion by regulating Integrin β1/Tiam1/Rac1 pathway.

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Lymphomatoid papulosis (LyP) type E is a recently described variant characterized by the occurrence of large necrotic eschar-like lesions displaying microscopically angioinvasive and angiodestructive infiltrates of CD30+ lymphocytes, frequently coexpressing CD8.Rare cases of LyP type E with a CD56+ immunophenotype have been described. Herein, we describe a 36-year-old woman with LyP type E, characterized by purpura-like lesions on her left ankle. Initially, she presented with left ankle swelling, petechiae and ecchymosis, and rapidly developing necrotic papules, all of which resolved spontaneously over a period of a few months without intentional therapy. Biopsy revealed CD30 and CD56 positive atypical cell infiltrates with marked angiocentricity and angiodestruction. Awareness of this rare LyP variant and its correct recognition, even if the clinical presentation is unusual, is important to avoid aggressive treatment.

Background: 5-aminolevulinic acid photodynamic therapy (PDT) for genital warts is effective, safe, and can prevent recurrence. It is believed that PDT can induce immune responses, but the mechanism is not completely understood. Objectives: The objectives of this article are to confirm the effect of PDT for genital warts on local immunity and to investigate the recruitment and significance of immune cells in tissues. Methods: Local immune changes in T lymphocytes (CD3+, CD4+, CD8+), plasmacytoid dendritic cells (pDCs) (CD123+), and myeloid dendritic cells (CD1a+) after PDT in patients were evaluated by immunohistochemistry staining. Changes in mRNA levels of IFN-γ, IFN-α, IFN-ß, interferon-stimulated gene 15 kDa (ISG-15), Mx2, Toll-like receptor 9 (TLR9), and interferon regulatory factor 7 (IRF7) were analyzed by real-time quantitative polymerase chain reaction. Results: At 4 hours after PDT, CD4+ increased, accompanied by increased levels of mRNA expression of IFN-γ, but CD4+ and mRNA expression levels of IFN-γ were decreased at 24 hours after PDT. CD123+ pDCs showed an increasing trend. CD1a+ LCs in the epidermis gradually decreased, and DCs in the epidermis gradually increased. CD3+ infiltrated and migrated to the superficial dermis, but CD8+ did not change significantly after PDT. The mRNA expression levels of IFN-α, IFN-ß, ISG-15, Mx2, TLR9, and IRF7 showed an increasing trend after PDT. As compared with the patients without significantly increased IFN-α and IFN-ß after PDT sessions, patients with significant increases needed fewer sessions of PDT for remission. Conclusions: PDT for genital warts can activate T lymphocyte-mediated, DC-related, and pDC-related immunity. The clinical efficacy of PDT for genital warts may be related to the increased levels of IFN-α and IFN-ß after treatment.