Budesonide and Poractant Alfa prevent bronchopulmonary dysplasia via triggering SIRT1 signaling pathway.

OBJECTIVE: This study aimed to evaluate effect of budesonide combining Poractant Alfa on preventing bronchopulmonary dysplasia (BPD). PATIENTS AND METHODS: A total of 120 preterm infants were involved. pH value, partial pressure of oxygen (PO2), and blood gas analysis were evaluated. Peripheral blood was collected and mononuclear cells were isolated. Reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) were detected with laser confocal. Sirtuin 1 (SIRT1) in PBMCs was detected using immunofluorescence. SIRT1 and small ubiquitin-like modifier (SUMO)-specific protease 1 (SENP1) were detected with Western blot. RESULTS: Compared with group B, pH value and PO2 were improved significantly in group C and D (p<0.01). Compared with group B, oxygen inhalation duration, rate of having a respirator assisted ventilation, and using pulmonary surfactant (PS) again, and BPD incidence were significantly decreased in other groups (p<0.05). BPD incidence in group D was less than group C (χ2=4.00, p<0.05). Compared with control group, ROS level of neonatal respiratory distress syndrome (NRDS) group was significantly increased, SENP1 was increased, and SIRT1 was decreased in SIRT1 group. Compared with NRDS, when budesonide combined with Poractant Alfa, ROS decreased, SENP1 decreased, SIRT1 nuclear pulp shuttling rate reduced, nuclear SIRT1 increased (p<0.01). Compared with control, ROS level of NRDS group was significantly increased, SENP1 increased, and SIRT1 in nucleus decreased (p<0.05). Compared with NRDS group, when treated with budesonide and Poractant Alfa, ROS levels decreased, SENP1 decreased, nuclear SIRT1 increased (p<0.01). CONCLUSIONS: Budesonide combining Poractant Alfa can prevent BPD in preterm infants by activating the SIRT1 signaling pathway.

[Three dimensional quantitative structure activity relationship of P450(17) alpha inhibitors of 17-substituted steroids].

AIM: To develop a three dimensional quantitative structure activity relationship (3D-QSAR) model and gain further insights into the requirements for potential P450(17) alpha inhibitors. METHODS AND RESULTS: A predictive 3D pharmacophore model was established based on comparative molecular field analysis (CoMFA). The correlation between the activities and structures was significant with cross-validated value (R2cv), non-cross-validated value (R2) and standard error of estimate (SEE) of 0.538, 0.799 and 0.257, respectively. According to this model, the predicted inhibition activities of three compounds synthesized in our laboratory were compatible to actual activities. CONCLUSION: This model would contribute to the understanding of the interaction between the inhibitors and P450(17) alpha and rational design of novel lead molecules.

[Studies on the anticonvulsive activity of pyrazolidinones].

The anticonvulsive activity of three kinds of pyrazolidinones: 5-benzyl-substituted-3-pyrazolidinones; 5-benzyl-1-alkyl substituted and 1-alkyl substituted-3-pyrazolidinones were studied. Fourteen substitutes of these three kinds of pyrazolidinones were found to be potent anticonvulsants. In doses less than TD50, they were found to be able to protect mice and rats from seizures produced by maximal electroshock seizure (MES), such action appeared rapidly and lasted for a short period. II-f was shown to be the most potent anti-MES agent among these three kinds of pyrazolidinones. It also showed therapeutic effect in treating experimental epilepsy produced by intrahippocampal injection of zinc sulfate in rabbits and audiogenic seizures in rats. The third kind of pyrazolidinones also showed anti-metrazol induced seizures in mice.

[QSAR studies on the anticonvulsant activity of 5-substitutedphenyl-1-hydro- and 1-propyl-3-pyrazolidinones].

The chemical structure and anticonvulsant activity relationship of some 5-substituted phenyl-3-pyrazolidinone derivatives were studied. Six pairs (1-hydro and 1-propyl substituted) of compounds were designed and synthesized according to the Topliss improved method, and a compound with the highest anticonvulsant activity was found, i.e. 5-(4-fluorophenyl)-1-propyl-3-pyrazolidinone, ED50 14.7 mg/kg (MES Test). QSAR analysis showed that the hydrophobic constant sigma pi greatly influenced their anticonvulsant activity, and the steric parameter (B4) and electronic parameter (I x 10(2] of the substitutions on the phenyl ring can improve the correlation coefficient (r). Smaller steric volume and more powerful electron withdrawing effect of the substitution on the 5-phenyl ring increased the anticonvulsant activity.