Remdesivir alleviates skin fibrosis by suppressing TGF-ß1 signaling pathway.

Fibrotic skin diseases, such as keloids, are pathological results of aberrant tissue healing and are characterized by overgrowth of dermal fibroblasts. Remdesivir (RD), an antiviral drug, has been reported to have pharmacological activities in a wide range of fibrotic diseases. However, whether RD function on skin fibrosis remains unclear. Therefore, in our study, we explored the potential effect and mechanisms of RD on skin fibrosis both in vivo and in vitro. As expected, the results demonstrated that RD alleviated BLM-induced skin fibrosis and attenuates the gross weight of keloid tissues in vivo. Further studies suggested that RD suppressed fibroblast activation and autophagy both in vivo and in vitro. In addition, mechanistic research showed that RD attenuated fibroblasts activation by the TGF-ß1/Smad signaling pathway and inhibited fibroblasts autophagy by the PI3K/Akt/mTOR signaling pathway. In summary, our results demonstrate therapeutic potential of RD for skin fibrosis in the future.

Nintedanib ameliorates imiquimod-induced psoriasis in mice by inhibiting NF-κB and VEGFR2 signaling.

Psoriasis is a common chronic skin disorder characterized by keratinocyte hyperproliferation with altered differentiation accompanied by increased inflammation and angiogenesis. Nintedanib is a tyrosine kinase inhibitor that has anti-inflammatory, anti-angiogenesis, and anti-fibrotic effects. In this study, we explored the potential effects and mechanisms of nintedanib on psoriasis in vivo and in vitro. In vivo experiments showed that nintedanib effectively alleviated imiquimod-induced psoriasis-like skin lesions and reduced psoriasis severity index scores. For the mechanism research, we mainly focused on the abnormal phenotype of keratinocyte in the pathogenesis of psoriasis. We used HaCaT cells in the in vitro experiments and the result revealed that nintedanib restored keratinocyte homeostasis by downregulated the expression of proinflammatory factors, inhibited hyperproliferation, promoted apoptosis, maintained normal differentiation via regulating the NF-κB pathway. In addition, nintedanib regulated angiogenesis by inhibiting VEGFR2 activity. In summary, our study indicated that nintedanib is a promising candidate medication for psoriatic treatment.

Lead and other elemental content of normal and Erwinia carotovora infected Amorphallus konjac corms.

Amorphallus konjac corms are important agriculture products in Yichang, Hubei Province, China. The Erwinia carotovora infected Amorphallus konjac corms are processed to food as normal corms. The contents of elements and L: -Proline in the normal and infected Amorphallus konjac corms are analyzed for food safety. Even growing in the almost same soil condition, the contents of Pb, Cd, Mn and L: -Proline in infected corms are significantly higher than those of normal corms (show data as suggestion by peers). Our study suggested that the infected corms are not suitable for food purpose.

[Role of mitogen-activated protein kinase pathway in chloracne].

OBJECTIVE: To investigate the role of mitogen-activated protein kinase (MAPK) signal transduction pathway in chloracne. METHODS: Immunohistochemical technique was used to detect the expression of phosphorylated epidermal growth factor receptor (p-EGFR) and p-MAPK proteins in the epithelium of chloracne group and control group. RESULTS: p-EGFR and p-MAPK was found in all chloracne tissues, whereas no expression of p-EGFR and p-MAPK protein was found in control group. In the skin of chloracne patients, p-EGFR was mainly distributed in the membrane and the cytoplasm, especially in the vicinity of membrane; major positive signal of p-MAPK was in core and serosity. CONCLUSION: EGFR and MAPK phosphorylation is found in chloracne tissues. MAPK signal transduction pathway is one important molecular mechanism of chloracne.

Expression of AhR, CYP1A1, GSTA1, c-fos and TGF-alpha in skin lesions from dioxin-exposed humans with chloracne.

Occupational exposure to certain polychlorinated aromatic hydrocarbons such as dioxins has been suggested to cause chloracne which is a kind of skin disease. The molecular mechanisms of dioxin-mediated chloracne have not been clarified. It is possible that dioxins contribute to the pathogenesis through activation of aryl-hydrocarbon receptor (AhR)-mediated transcription and downstream genes such as CYP1A1, GSTA1 and TGF-alpha. The study on genes was through chloracne lesional skin, which has rarely been reported on previously. The expression levels of key genes, such as AhR, CYP1A1, GSTA1, c-fos and TGF-alpha in human epidermal tissue of chloracne cases and controls were detected by real-time PCR. Compared with controls, AhR, CYP1A1, GSTA1 and c-fos transactivations were significantly induced in the skins of chloracne patients who had long-term exposure to dioxins and dibenzofuranes. The TGF-alpha mRNA content of epidermal tissue was increased, but not significantly compared with controls. The study demonstrates that constitutive activation of the AhR pathway is probably a prerequisite of chloracne pathogenesis. The changes of genes expression may disturb normal proliferation and differentiation of human epidermis cells, and then lead to chloracne.