Disulfiram ameliorates STING/MITA-dependent inflammation and autoimmunity by targeting RNF115

STING(also known as MITA)is an adaptor protein that mediates cytoplasmic DNA-triggered signaling,and aberrant activation of STING/MITA by cytosolic self-DNA or gain-of-function mutations causes severe inflammation.Here,we show that STING-mediated inflammation and autoimmunity are promoted by RNF115 and alleviated by the RNF115 inhibitor disulfiram(DSF).Knockout of RNF115 or treatment with DSF significantly inhibit systemic inflammation and autoimmune lethality and restore immune cell development in Trex1^(–/–)mice and STING^(N153S/WT) bone marrow chimeric mice.In addition,knockdown or pharmacological inhibition of RNF115 substantially downregulate the expression of IFN-α,IFN-γand proinflammatory cytokines in PBMCs from patients with systemic lupus erythematosus(SLE)who exhibit high concentrations of dsDNA in peripheral blood.Mechanistically,knockout or inhibition of RNF115 impair the oligomerization and Golgi localization of STING in various types of cells transfected with cGAMP and in organs and cells from Trex1^(–/–)mice.Interestingly,knockout of RNF115 inhibits the activation and Golgi localization of STINGN153S as well as the expression of proinflammatory cytokines in myeloid cells but not in endothelial cells or fibroblasts.Taken together,these findings highlight the RNF115-mediated cell type-specific regulation of STING and STINGN153S and provide potential targeted intervention strategies for STING-related autoimmune diseases.

QR code labeling system for Xueteng-related herbs based on DNA barcode

Objective: Xueteng-related herbs include Spatholobi Caulis(Jixueteng in Chinese), Sargentodoxae Caulis(Daxueteng in Chinese), Kadsurae Caulis(Dianjixueteng in Chinese), and other medicinal plant stems that release reddish-brown juices after being cut. However, similarity in phonetic spelling and sound leads to their misuse in clinic or commercial circulation. Accurate labeling is imperative as well as effective for species identification.Methods: In this study, the ITS2 sequences of 76 samples of Xueteng-related herbs were obtained and analyzed to identify them. And then they were converted into QR codes using the open source PHP QR code. Also, a DNA barcode reference library was established according to these sequences and was used to authenticate the 25 samples of Xueteng-related herbs collected from the market.Results: The lengths of the ITS2 sequences of different Xueteng-related herbs ranged from 207 to 235 bp and the GC contents were 57.5%-71.0%. Jixueteng, Daxueteng, and Dianjixueteng were clustered into three clades respectively in the neighbor-joining(NJ) phylogenetic tree, and the efficiency of the BLAST method was 100%. The ITS2 sequences of different Xueteng-related herbs were presented vividly and specifically in QR code. Twenty-two of all 25 commercial samples were consistent with the original labels, whereas three samples marked "Dianjixueteng" were authenticated as "Jixueteng".Conclusion: QR code labeling system based on DNA barcode is an effective labeling system of Xuetengrelated herbs for their circulation regulation.

Study on the hepatocellular carcinoma model with metastasis

Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated death around the world due to advanced clinical stage at diagnosis,high incidence of recurrence and metastasis after surgical treatment.It is in urgent need to create appropriate animal models to explore the mechanism,patterns,risk factors,and therapeutic strategies of HCC metastasis and recurrence.However,most of the established models lack the phenotype of invasion and metastasis in patient,or have unstable phenotype.To establish HCC models with stable metastasis phenotype requires profound understanding in cancer metastasis biology and scientific methodology.Over the past 3 decades,HCC models with stable metastasis have been extensively studied.This paper reviewed the history and development of HCC animal models and cell models,focusing on the screening and maintaining of metastatic potential and phenotype.In-depth studies using these models vastly promote the understanding of cellular and molecular mechanisms and development of therapeutic strategies on HCC metastasis.