Search

Abstract: The toxicity of melamine has attracted much attention since the outbreak of nephrolithiasis among children ingesting melamine-contaminated infant formula in China. However, there is little knowledge about the molecular mechanisms underlying the melamine-induced toxicity. In this paper, a ligand–protein docking method (INVDOCK) was applied to predict the toxicity-related target proteins for melamine and its metabolite, cyanuric acid. As a result, 23 and 35 proteins were finally identified as the potential target proteins for melamine and cyanuric acid, respectively. Through an enrichment analysis, it was found that nephrotoxicity and lung toxicity might be the most significant toxicities induced by melamine and cyanuric acid. Four target proteins (glutathione peroxidase 1, beta-hexosaminidase subunit beta, l-lactate dehydrogenase and lysozyme C) may be related to the molecular basis of the nephrotoxicity induced by melamine except for known kidney crystals formation. After mapping all these toxicity-related target proteins onto cellular pathways, it was indicated that the toxicities of melamine and cyanuric acid might also be caused by breaking down redox balance, perturbing the arginine and proline metabolism and damaging the homeostasis of energy production system. To further explore the mechanisms underlying the toxicities of melamine and cyanuric acid, a biological signal cascades network constructed by some of the toxicity-related target proteins was discussed. [Copyright &y& Elsevier]

Background: Prior studies reported that 5 ~ 32% COVID-19 patients were critically ill, a situation that poses great challenge for the management of the patients and ICU resources. We aim to identify independent risk factors to serve as prediction markers for critical illness of SARS-CoV-2 infection., Methods: Fifty-two critical and 200 non-critical SARS-CoV-2 nucleic acid positive patients hospitalized in 15 hospitals outside Wuhan from January 19 to March 6, 2020 were enrolled in this study. Multivariable logistic regression and LASSO logistic regression were performed to identify independent risk factors for critical illness., Results: Age older than 60 years, dyspnea, respiratory rate > 24 breaths per min, leukocytosis > 9.5 × 10 9 /L, neutrophilia > 6.3 × 10 9 /L, lymphopenia < 1.1 × 10 9 /L, neutrophil-to-lymphocyte ratio > 3.53, fibrinogen > 4 g/L, d-dimer > 0.55 μg/mL, blood urea nitrogen > 7.1 mM, elevated aspartate transaminase, elevated alanine aminotransferase, total bilirubin > 21 μM, and Sequential Organ Failure Assessment (SOFA) score ≥ 2 were identified as risk factors for critical illness. LASSO logistic regression identified the best combination of risk factors as SOFA score, age, dyspnea, and leukocytosis. The Area Under the Receiver-Operator Curve values for the risk factors in predicting critical illness were 0.921 for SOFA score, 0.776 for age, 0.764 for dyspnea, 0.658 for leukocytosis, and 0.960 for the combination of the four risk factors., Conclusions: Our findings advocate the use of risk factors SOFA score ≥ 2, age > 60, dyspnea and leukocytosis > 9.5 × 10 9 /L on admission, alone or in combination, to determine the optimal management of the patients and health care resources.