Objective To explore the mechanism underlying the induction of systemic lupus erythematosus (SLE) by estrogen, hydralazine and ultraviolet irradiation. Methods Peripheral blood mononuclear cells (PBMCs) were harvested from 10 patients with SLE and 9 normal human controls, and cultured with or without the intervention with estrogen, hydralazine or ultraviolet irradiation. The DNA methyltransferase-1 (DNMT1) activity of PBMCs was quantified by using DNMT activity/inhibition assay kit. Results No statistical difference was observed in DNMT1 activity between patients with SLE and normal controls (0.36 ± 0.24 vs 0.46 ± 0.17, P ＞ 0.05). A significant decrease was noted in DNMT1 activity in PBMCs from patients with SLE after intervention with estrogen (0.32 ± 0.18 vs 0.46 ± 0.17, t = 1.725, P ＜ 0.05), hydralazine (0.33 ±0.13 vs 0.46 ± 0.17, t = 1.739, P ＜ 0.05) and ultraviolet irradiation (0.30 ± 0.14 vs 0.46 ± 0.17, t = 1.739,P ＜ 0.05 ) compared with that from normal human controls. The treatment with hydralazine also induced an attenuation of DNMT1 activity in PBMCs from normal human controls (0.38 ± 0.12 vs 0.46 ± 0.17, P＜ 0.05).Conclusion Estrogen, hydralazine and ultraviolet irradiation can inhibit the DNMT1 activity of SLE patients,indicating that they may induce the initiation of SLE by altering the activity of DNMT1.

New Delhi metallo-β-lactamase-1 (NDM-1) is capable of hydrolyzing nearly all β-lactam antibiotics, posing an emerging threat to public health. There are currently less effective treatment options for treating NDM-1 positive “superbug”, and no promising NDM-1 inhibitors were used in clinical practice. In this study, structure–activity relationship based on thiosemicarbazone derivatives was systematically characterized and their potential activities combined with meropenem (MEM) were evaluated. Compounds 19bg and 19bh exhibited excellent activity against 10 NDM-positive isolate clinical isolates in reversing MEM resistance. Further studies demonstrated compounds 19bg and 19bh were uncompetitive NDM-1 inhibitors with Ki = 0.63 and 0.44 μmol/L, respectively. Molecular docking speculated that compounds 19bg and 19bh were most likely to bind in the allosteric pocket which would affect the catalytic effect of NDM-1 on the substrate meropenem. Toxicity evaluation experiment showed that no hemolysis activities even at concentrations of 1000 mg/mL against red blood cells. In vivo experimental results showed combination of MEM and compound 19bh was markedly effective in treating infections caused by NDM-1 positive strain and prolonging the survival time of sepsis mice. Our finding showed that compound 19bh might be a promising lead in developing new inhibitor to treat NDM-1 producing superbug.