Resampling combined with stacking learning for prediction of blood-brain barrier permeability of compounds / 生物医学工程学杂志

It is a significant challenge to improve the blood-brain barrier (BBB) permeability of central nervous system (CNS) drugs in their development. Compared with traditional pharmacokinetic property tests, machine learning techniques have been proven to effectively and cost-effectively predict the BBB permeability of CNS drugs. In this study, we introduce a high-performance BBB permeability prediction model named balanced-stacking-learning based BBB permeability predictor(BSL-B3PP). Firstly, we screen out the feature set that has a strong influence on BBB permeability from the perspective of medicinal chemistry background and machine learning respectively, and summarize the BBB positive(BBB+) quantification intervals. Then, a combination of resampling algorithms and stacking learning(SL) algorithm is used for predicting the BBB permeability of CNS drugs. The BSL-B3PP model is constructed based on a large-scale BBB database (B3DB). Experimental validation shows an area under curve (AUC) of 97.8% and a Matthews correlation coefficient (MCC) of 85.5%. This model demonstrates promising BBB permeability prediction capability, particularly for drugs that cannot penetrate the BBB, which helps reduce CNS drug development costs and accelerate the CNS drug development process.

Protective Effect of Coenzymes Complex Combined with Vitamin E on Liver and Kidney Injury Induced by Neonatal Hyperbilirubinemia / 天津医药

Objective To study the effect of coenzymes complex combined with vitamin E on liver and kidney inju-ry induced by neonatal hyperbilirubinemia. Methods One hundred and fifty full-term neonatals with hyperbilirubinemia were chosen as observation groups, who were divided into mild, moderate and severe groups according bilirubin. Forty five healthy full-term newborns in the same period, who are either healthy or with physiological jaundice, were selected as con-trol group. Serum total bilirubin, gamma-glutamyl transferase (γ-GGT) , Malondialdehyde (MDA) and Cys-C were measured within 24 hours of hospital admission.The observation groups were randomly divided into regular and combined treatment groups. Coenzymes complex combined with vitamin E were given in addition to regular method to combined group while reg-ular group only received regular methods.All above biochemical indexes were tested in the 7th day after medication admin-istration. Results Serum MDA were higher in all observation groups (mild, moderate and severe groups) than in control group (P＜0.05);but the levels ofγ-GGT and Cys-C increased in moderate and severe groups compared with control group (P＜0.05). There were positive correlations (P＜0.05) between levels of serum total bilirubin with MDA,γ-GGT and Cys-C. Positive linear correlation were found between MDA with γ-GGT and Cys-C(P＜0.01). After early intervention,γ-GGT, Cys-C and MDA declined with drop of bilirubin level. This is more prominent and faster in a in combined treatment group than regular group (P＜0.05).Conclusion In hyperbilirubinemia newborns, lipid peroxidation activated by bilirubin may lead to damages of liver and kidney. Coenzymes combined with vitamin E have protective effect to these damages.