Cardioprotective effects of cerebrolysin on the lesion severity and inflammatory factors in a rat model of isoproterenol-induced myocardial injury

Background: Myocardial injury (MI) is an important heart condition and a major cause of morbidity and mortality worldwide. The current study was designed to investigate the cardioprotective effects of cerebrolysin (CLY) on the lesion severity and inflammatory factors in male rats using isoproterenol (ISO)-induced MI model. Methods: MI in rats was induced by injecting ISO (100 mg/kg) subcutaneously (sc) on the first 2 days. Then, CLY (5 ml/kg) was injected intraperitoneally (ip) post-treatment for 7 days. On the 3rd day, creatine phosphokinase (CK-MB) and cardiac troponin I (cTnI) levels in serum and, on the 10th day, the TNF-α and IL6 levels in serum and heart tissue were measured by enzyme-linked immunosorbent assay (ELISA). Finally, the heart of each rat was dissected out and stained for histopathological examination. Results: On the 3rd day, the serum CK-MB and cTnI levels in the ISO and CLY + ISO groups were significantly increased compared with that in the control and CLY + Sal groups. One week after the induction of MI, ISO administration showed a significant increase in the serum level of TNF-α in the ISO group compared with that in the control and CLY + Sal groups. Also, our findings showed only a moderate reduction in inflammatory cell infiltration and extent of edema following CLY treatment in the CLY + ISO group. Also, CLY induced vascular proliferation in the heart tissue. Conclusions: We conclude that the severity of pathological changes induced by ISO in MI (e.g. inflammation and edema) can be limited by CLY treatment. © 2019 Institute of Pharmacology, Polish Academy of Science

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

Abstract Background Hypertension and bronchial asthma are a major issue for people’s health. As of 2014, approximately one billion adults, or ~ 22% of the world population, have had hypertension. As of 2011, 235–330 million people globally have been affected by asthma and approximately 250,000–345,000 people have died each year from the disease. The development of the effective treatment therapies against these diseases is complicated by their comorbidity features. This is often a major problem in diagnosis and their treatment. Hence, in this study the bioinformatical methodology for the analysis of the comorbidity of these two diseases have been developed. As such, the search for candidate genes related to the comorbid conditions of asthma and hypertension can help in elucidating the molecular mechanisms underlying the comorbid condition of these two diseases, and can also be useful for genotyping and identifying new drug targets. Results Using ANDSystem, the reconstruction and analysis of gene networks associated with asthma and hypertension was carried out. The gene network of asthma included 755 genes/proteins and 62,603 interactions, while the gene network of hypertension - 713 genes/proteins and 45,479 interactions. Two hundred and five genes/proteins and 9638 interactions were shared between asthma and hypertension. An approach for ranking genes implicated in the comorbid condition of two diseases was proposed. The approach is based on nine criteria for ranking genes by their importance, including standard methods of gene prioritization (Endeavor, ToppGene) as well as original criteria that take into account the characteristics of an associative gene network and the presence of known polymorphisms in the analysed genes. According to the proposed approach, the genes IL10, TLR4, and CAT had the highest priority in the development of comorbidity of these two diseases. Additionally, it was revealed that the list of top genes is enriched with apoptotic genes and genes involved in biological processes related to the functioning of central nervous system. Conclusions The application of methods of reconstruction and analysis of gene networks is a productive tool for studying the molecular mechanisms of comorbid conditions. The method put forth to rank genes by their importance to the comorbid condition of asthma and hypertension was employed that resulted in prediction of 10 genes, playing the key role in the development of the comorbid condition. The results can be utilised to plan experiments for identification of novel candidate genes along with searching for novel pharmacological targets