Inflammasomes are multi-protein platforms that are assembled in response to microbial and danger signals to activate proinflammatory caspase-1 for production of active form of IL-1β and induction of pyroptotic cell death. Where and how an inflammasome is assembled in cells has remained controversial. While the endoplasmic reticulum, mitochondria and Golgi apparatus have been reported to be associated with inflammasome assembly, none of these sites seems to match the morphology, number and size of activated inflammasomes that are microscopically observable as one single perinuclear micrometer-sized punctum in each cell. Recently, emerging evidence shows that NLRP3 and pyrin inflammasomes are assembled, activated and locally regulated at the centrosome, the major microtubule organizing center in mammalian cells, elegantly accounting for the singularity, size and perinuclear location of activated inflammasomes. These new exciting findings reveal the previously unappreciated importance of the centrosome in controlling inflammasome assembly and activation as well as inflammasome-related diseases.

Snail is a denoted transcriptional repressor that plays key roles in epithelial-mesenchymal transition (EMT) and metastasis. Lately, a plethora of genes can be induced by stable expression of Snail in multiple cell lines. However, the biological roles of these upregulated genes are largely elusive. Here, we report identification of a gene encoding the key GlcNAc sulfation enzyme CHST2 is induced by Snail in multiple breast cancer cells. Biologically, CHST2 depletion results in inhibition of breast cancer cell migration and metastasis, while overexpression of CHST2 promotes cell migration and lung metastasis in nude mice. In addition, the expression level of MECA79 antigen is elevated and blocking the cell surface MECA79 antigen with specific antibodies can override cell migration mediated by CHST2 upregulation. Moreover, the sulfation inhibitor sodium chlorate effectively inhibits the cell migration induced by CHST2. Collectively, these data provide novel insights into the biology of Snail/CHST2/MECA79 axis in breast cancer progression and metastasis as well as potential therapeutic strategy for the diagnosis and treatment of breast cancer metastasis.

Abnormal levels of some peripheral cytokines have been reported in children patients with tic disorders (TDs), but none of these cytokines can be a biomarker for this disease. Our aim was to systemically profile differentially expressed cytokines (DECs) in the blood of TD patients, examine their associations with TD development, and identify from them potential biomarkers for the prediction and management of the risk for TDs. In this study, a cytokine array capable of measuring 105 cytokines was used to screen for DECs in the plasma from 53 comorbidity-free and drug-naïve TD patients and 37 age-matched healthy controls. DECs were verified by ELISA and their associations with TD development were evaluated by binary logistic regression analysis. Elevation of a set of cytokines was observed in TD patients compared with controls, including previously uncharacterized cytokines in tic disorders, CCL5, Serpin E1, Thrombospondin-1, MIF, PDGF-AA, and PDGF-AB/BB. Further analysis of DECs revealed a significant association of elevated CCL5 with TD development (p = 0.005) and a significant ROC curve for CCL5 as a risk factor [AUC, 0.801 (95% CI: 0.707–0.895), p < 0.0001].ConclusionThis study identifies associations of a set of circulating cytokines, particularly CCL5 with TD development, and provides evidence that high blood CCL5 has potential to be a risk factor for TD development.Clinical Trial Registrationidentifier ChiCTR-2000029616.

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