New Findings What is the central question of this study? What controls the proliferation and apoptosis in the pathogenesis of psoriasis? What is the main finding and its importance? The pathogenesis psoriasis involves abnormal homeostasis of keratinocytes, with hyperproliferation and decreasing apoptosis. An inhibitor of apoptosis protein family molecule, Livin, is highly expressed in psoriasis vulgaris lesional skin tissue. Expression of Livin was upregulated at transcription and protein levels after stimulation with oncostatin M (OSM). OSM promoted the survival of HaCaT cells in oxidative stress conditions. Expression of Livin and proliferation of HaCaT cells stimulated by OSM was regulated through ERK and STAT3 signalling pathways. This study might provide new insights into targeted therapy for psoriasis. AbstractPsoriasis is an immune‐mediated chronic inflammatory disease. Abnormal homeostasis of keratinocytes, with hyperproliferation and decreasing apoptosis, is involved in the pathogenesis of psoriasis. Here, we report that an inhibitor of apoptosis protein family molecule, Livin, is highly expressed in psoriasis vulgaris lesional skin tissue at transcription and protein levels. Importantly, the expression level of Livin is related to the severity of psoriasis. The aim of the study was to investigate the regulation and functions of Livin in keratinocytes stimulated by the pro‐inflammatory cytokine oncostatin M (OSM). The expression of Livin in HaCaT cells at mRNA and protein levels was measured by real‐time PCR and Western blotting after OSM stimulation. The cell proliferation was measured by a 5‐ethynyl‐2′‐deoxyuridine incorporation assay. Cell death was induced by the exogenous hydrogen peroxide (H2O2) stress model, detected by 7‐amino‐actinomycin D staining and analysed by flow cytometry. Livin was overexpressed by a lentiviral transduction system to validate the roles of OSM and Livin in HaCaT cells. Specific inhibitors of ERK (U0126) and STAT3 (cryptotanshinone) were applied to investigate the signalling pathways involved in the regulation of Livin expression by OSM. The expression of Livin was upregulated after stimulation with OSM. OSM promoted the proliferation and survival of HaCaT cells. The expression of Livin and the proliferation of HaCaT cells induced by OSM were regulated through the ERK and STAT3 signalling pathways. We conclude that OSM promotes HaCaT cell proliferation and survival in conditions of oxidative stress.

Background Activation of keratinocytes (KCs) is the main pathological feature of psoriasis.KCs recruit neutrophils by releasing various antimicrobial peptides and chemokines, which is also related to the expression of KC adhesion molecules. However, the regulatory mechanism governing their expression is still unclear. Livin, an inhibitor of the apoptosis protein family member involved in proliferation and metastasis of tumor cells, is significantly increased in psoriatic lesions.Objectives The aim of this study was to investigate the role of Livin in regulating adhesion molecule expression in KCs and release of chemokines that promote the activation and adhesion of neutrophils. MethodsThe expression of Livin in psoriasis patients, imiquimod mouse model, and the combination of IL-17 alpha, IL-22, IL-1 alpha, OSM, and TNF-a (Mix M5)-treated HaCaT cells were detected by immunofluorescence staining, RT-qPCR, and ELISA. Livinoverexpression and knockdown in HaCaT cells transfected with HIV-1-based lentiviral vectors were used to study the function of Livin using RNA-seq. Moreover, differences in the expression of HaCaT cell adhesion molecules after regulation of Livin expression and activation of neutrophils in the co-culture model were verified. Results Livin was upregulated in the KCs of psoriasis patients, imiquimod mouse model and Mix M5-treated HaCaT cells compared with the control groups. Livin in HaCaT cells might regulate the expression of adhesion molecules in KCs. Conclusion Thus, Livin may be a key effector molecule that regulates the expression of adhesion molecules in KCs and promotes the activation and adhesion of neutrophils.

Background Combined therapy for keloids is currently recommended. Surgery is one of the main options, but the measures to prevent recurrence after excision are still being explored. Objective The randomized controlled study aimed at evaluating the efficacy of excision followed by intralesional low concentrations of 5-fluorouracil (5-FU)(12.5 mg/mL) and betamethasone. Methods Sixty patients were randomly assigned to three groups. Patients in group A had excision followed by 5-FU and betamethasone intralesional injections, group B had 5-FU and betamethasone intralesional injections, and group C had excision followed by radiotherapy. Efficacy parameters were assessed from 8 to 12 months, including improvement on the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Scale (POSAS), as well as side effects and recurrence. Trial registration number: ChiCTR2100046025. Results After 4 months’ treatment, the improvement of the VSS and POSAS scores in group A was not different from that in group C ( P > 0.05) but was superior to that in group B ( P < 0.05); the pain and pruritus of the three groups were relieved more than 50%. After 8 to 12 months’ follow-up, there was no statistical difference in the incidence of side effects and recurrence among the groups ( P > 0.05). Conclusion Excision followed by intralesional low concentrations of 5-FU (12.5mg/mL) with betamethasone is a safe and sustainable treatment for keloid, with no significant difference from excision followed by radiotherapy.