Efficacy of scopolamine plus propofol in the treatment of recalcitrant psoriasis: A pilot study.

Accumulating evidence suggests that botulinum neurotoxins (BoNTs), which inhibit acetylcholine release, can be used for treating plaque psoriasis. The therapeutic effects of scopolamine occur through antagonism of central muscarinic acetylcholine receptors. Thus, scopolamine has potential for the treatment of psoriasis. We aimed to evaluate the efficacy and safety of scopolamine plus propofol for the treatment of recalcitrant psoriasis. Twelve patients with recalcitrant psoriasis were enrolled. Patients received intravenous injection of scopolamine plus propofol for 5 consecutive days per month for a total of 3 months. Clinical efficacy was evaluated using a Psoriasis Area and Severity Index (PASI) score. Efficacy outcome was ≥75% reduction in PASI score (PASI75) from baseline. Two patients were lost to follow-up. At week 8, two of 10 patients (20%) achieved PASI75, and at week 12, seven of 10 (70%) achieved PASI75. Treatment was well tolerated, with no reported adverse events. Our study revealed the efficacy and safety of scopolamine plus propofol for the treatment of recalcitrant psoriasis. Scopolamine plus propofol therapy may be a new treatment for recalcitrant psoriasis.

Klotho Protein Protects Human Keratinocytes from UVB-Induced Damage Possibly by Reducing Expression and Nuclear Translocation of NF-κB.

BACKGROUND UV-related skin disease such as actinic keratosis is a major concern in public health. In view of the cell injury induced by UVB, Klotho protein it is an ideal therapy to eliminate UVB-induced cell damages and the associated signaling pathways. MATERIAL AND METHODS To gain insights into the potential role of Klotho and the underlying molecular mechanism, we constructed a Klotho-overexpress HaCaT cell line and assessed the protection against UVB insults. The effects of exposure to UVB radiation on the human keratinocyte HaCaT cells, including cell growth, apoptosis, and changes of selected biomarkers, were measured by CCK-8, flow cytometry, Quantitative real-time PCR, and Western blot analysis. RESULTS We found that enhanced NF-κB activity was accompanied by decreased expression of the anti-aging protein Klotho upon UVB stimulation, which was further confirmed with in vivo experiments. Overexpression of Klotho was able to considerably alleviate the UVB-induced damages to cells and reversed the UVB-caused biomarker changes to a great extent, which was comparable to the effects of administration of NF-κB inhibitor PDTC, suggesting the inhibition of nuclear translocation and DNA-binding activity of NF-κB. Furthermore, Klotho overexpression was proved to decrease the nuclear expression of NF-κB as much as the treatment with PDTC, which provides support for the direct regulation of NF-κB by Klotho. CONCLUSIONS Collectively, our work provides new insight into the potential role of Klotho in the context of UVB-induced injuries in human keratinocytes, as well as providing the basis for future study of new therapies against UV-related skin disease.

Potential role of S100A8 in skin rejuvenation with the 1064-nm Q-switched Nd:YAG laser.

The 1064-nm Q-switched Nd:YAG laser is demonstrated to be effective for non-ablative skin rejuvenation, but the molecular mechanism by which dermis responses to laser-induced damage and initiates skin remodeling is still unclear. HaCaT cells and 3T3 skin fibroblasts were irradiated with the 1064-nm Q-switched Nd:YAG laser at the different doses. Then, cells were collected and lysed for PCR and Western blot analysis. Cell viability was detected by Cell Counting Kit-8 (CCK-8) before and after laser irradiation. The expressions of S100A8, advanced glycosylation end product-specific receptor (RAGE) and inflammatory cytokines in two cell lines were markedly upregulated after laser treatments. The PCR, Western blot, and ELISA analysis showed the significant increase of type I and III procollagen in the 3T3 cells treated with the 1064-nm laser. Interestingly, si S100A8 effectively inhibited the expression of cytokines and collagen, while S100A8 treatments significantly increased them. P-p38 and p-p65 levels were also elevated after the 1064-nm laser irradiation, which is positively related with S100A8. Cell viability and reactive oxygen species (ROS) levels were not changed, while the content of superoxidase dismutase (SOD) in two cells was increased after laser irradiation. Our results demonstrated that the overexpression of S100A8 induced by the 1064-nm laser irradiation triggered inflammatory reactions in skin cells. The inflammatory microenvironment and improvement of skin antioxidant capacity contribute to new collagen synthesis in the skin cells. Thus, S100A8 was required for laser-induced new collagen synthesis in skin cells. p38/MAPK and NF-κB signal pathways were involved in S100A8-mediated inflammatory reactions in response to laser irradiation.

Long non-coding RNA RP11-342L8.2, derived from RNA sequencing and validated via RT-qPCR, is upregulated and correlates with disease severity in psoriasis patients.

OBJECTIVE: This study aimed to explore the dysregulated long non-coding RNA (lncRNA) expression profile in psoriatic tissue vs. normal skin tissue via RNA sequencing (RNA-seq), then further sort candidate lncRNAs to be validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), in order to investigate the comprehensive linkage of lncRNA with psoriasis. METHODS: Twenty-five psoriasis patients were consecutively enrolled, with their psoriatic and surrounding normal skin tissues obtained. Ten pairs of psoriatic and normal tissues were proposed to RNA-seq. Then, top 6 differentially expressed lncRNAs (DElncRNA) were sorted as candidate lncRNAs for validation by RT-qPCR in 25 pairs of samples. RESULTS: Principal component analysis (PCA) exhibited that lncRNA profile clearly distinguished psoriatic tissue from normal tissue, so did heatmap. Volcano plot disclosed 412 upregulated and 625 downregulated DElncRNAs in psoriatic tissue vs. normal tissue. Gene Ontology (GO) and Kyoko Encyclopedia of Genes and Genomes (KEGG) enrichment analyses exhibited that these DElncRNAs were mainly enriched in immune, inflammation, or proliferation-related biological processes and pathways such as neutrophil degranulation, regulation of immune response, positive regulation of cell proliferation, and MAPK signaling pathway. By RT-qPCR validation, lncRNAs RP11-22A3.2, RP11-342L8.2, and CTD-2006H14.2 were increased (all P < 0.001), while lncRNAs AP000442.4, CCDC144NL-AS1, and MIR663AHG were decreased (all P < 0.01) in psoriatic tissue vs. normal tissue. Interestingly, psoriatic lncRNA RP11-342L8.2 was also observed to positively correlated with psoriasis area and severity index (PASI) (r = 0.405, P = 0.045). CONCLUSION: Our present study exhibits some evidence for the landscape of lncRNAs implicated in psoriasis.

DDX5 Silencing Suppresses the Migration of Basal cell Carcinoma Cells by Downregulating JAK2/STAT3 Pathway.

Basal cell carcinoma is driven by the aberrant activation of hedgehog signaling. DEAD (Asp-Glu-Ala-Asp) box protein 5 is frequently overexpressed in human cancer cells and associated with the tumor growth and invasion. The purpose of this study was to investigate the role of DEAD (Asp-Glu-Ala-Asp) box protein 5 in the growth, migration, and invasion of basal cell carcinoma. The role of DEAD (Asp-Glu-Ala-Asp) box protein 5 was detected by quantitative real-time polymerase chain reaction, Western blot, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay in basal cell carcinoma cells. The associations between JAK2/STAT3 pathway and DEAD (Asp-Glu-Ala-Asp) box protein 5 were analyzed in basal cell carcinoma cells. Results showed that DEAD (Asp-Glu-Ala-Asp) box protein 5 is overexpressed in basal cell carcinoma cells. DEAD (Asp-Glu-Ala-Asp) box protein 5 knockdown inhibited the migration and invasion of basal cell carcinoma cells. DEAD (Asp-Glu-Ala-Asp) box protein 5 knockdown increased the apoptosis of basal cell carcinoma cells induced by tunicamycin. Results found that DEAD (Asp-Glu-Ala-Asp) box protein 5 knockdown increased JAK2 and STAT3 expression in basal cell carcinoma cells. JAK2 inhibitor decreased STAT3 expression and abolished the inhibitory effects of DEAD (Asp-Glu-Ala-Asp) box protein 5 silencing on migration and invasion in basal cell carcinoma cells. In conclusion, these results indicate that DEAD (Asp-Glu-Ala-Asp) box protein 5 is a potential target for inhibiting basal cell carcinoma cells growth, migration, and invasion by downregulating JAK2/STAT3 pathway.