Table S3. Subgroup analysis of methylation levels of CpG sites in C3 promoter between CAD and controls by smoking status. Table S4. Subgroup analysis of methylation levels of CpG sites in C3 promoter between CAD and controls by EH status. Table S5. Subgroup analysis of methylation levels of CpG sites in C3 promoter between CAD and controls by DM status. (ZIP 34.7 kb)
Human Atg4 homologs are cysteine proteases, which play key roles in the macroautophagy/autophagy process by cleaving Atg8 homologs for conjugation to lipid membranes and for deconjugation of Atg8 homologs from membranes. Expression of ATG4B is significantly increased in colorectal cancer cells compared to normal cells, suggesting that ATG4B may be important for cancer biology. Inhibition of ATG4B may reduce the autophagy activity, thereby sensitizing cancer cells to therapeutic agents. Thus, developing specific and potent ATG4B inhibitors for research as well as for potential therapeutic uses is highly needed. In this study, we integrated in silico screening and in vitro assays to discover a potent ATG4B inhibitor, named S130, from a noncommercial library. This chemical binds to ATG4B with strong affinity and specifically suppresses the activity of ATG4B but not other proteases. S130 did not cause the impairment of autophagosome fusion, nor did it result in the dysfunction of lysosomes. Instead, S130 might attenuate the delipidation of LC3-II on the autolysosomes to suppress the recycling of LC3-I, which normally occurs after LC3-II cleavage by ATG4B. Intriguingly, S130 induced cell death, which was accompanied with autophagy stress and could be further exacerbated by nutrient deprivation. Such cytotoxicity could be partially reversed by enhancing ATG4B activity. Finally, we found that S130 was distributed in tumor tissues in vivo and was also effective in arresting the growth of colorectal cancer cells. Thus, this study indicates that ATG4B is a potential anticancer target and S130 might be a novel small-molecule candidate for future cancer therapy.
Abstract T-helper (Th) 17 and Th22 cells are critical for the pathogenic process of Kawasaki Disease (KD). A total of 43 children with freshly diagnosed KD and 20 healthy controls (HC) were quantified for the numbers of Th17, Th22 and Th1 cells by flow cytometry. The concentrations of serum IL-17, IL-22, IL-6, IFN-γ and TNF-α were examined by ELISA. Compared to those in the HC, significantly increased numbers of Th17 and Th22 cells, but not Th1 cells, and higher levels of serum IL-17 and IL-22, but not IFN-γ, were found in KD patients. Stratification analysis indicated the numbers of both Th17 and Th22 cells and the concentrations of serum IL-17 and IL-22 in KD patients with coronary artery lesions (CAL) were significantly greater than that in those with noncoronary artery lesions (NCAL). Treatment with the intravenous immunoglobulin (IVIG) therapy significantly decreased numbers of Th22 and Th17 cells as well as the serum concentrations of IL-22 and IL-17 in KD patients. The concentrations of serum IL-22 and IL-17 were correlated positively with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values as well as N-terminal pro-brain natriuretic peptide (NT-proBNP) in those patients respectively. Conclusion : Our study provided direct evidence that Th22 and Th17 cells might contribute to the pathogenesis of KD.
Objective To study the effect of the wall-broken spore power of Aurantii Fructus Immaturus on the intestinal transit and acute toxicity test in mice.Methods The effect of the wall-broken spore power of Aurantii Fructus Immaturus on the intestinal transit was evaluated by the small intestinal carbon transit rate,which toxicity was detected by maximum dosage test.Results The clinical equivalent dose of the wall-broken spore power of Aurantii Fructus Immaturus showed a prominent promotion effect on intestinal transit.Half dose of the wall-broken spore power worked equally to its cut crude drugs.And no acute toxicity in mice occurred.Conclusion The wall-broken spore power of Aurantii Furctus Immaturus exhibits a beneficial effect on intestinal transit with no acute toxicity.
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