Current Pharmaceutical Design - Volume 25, Issue 40, 2019

Objective: One of the most challenging and also the most difficult problems is how to formulate a biological sequence with a vector but considerably keep its sequence order information. Methods: To address such a problem, the approach of Pseudo Amino Acid Components or PseAAC has been developed. Results and Conclusion: It has become increasingly clear via the 10-year recollection that the aforementioned proposal has been indeed very powerful.

Chronic Kidney Disease (CKD) is characterized by the gradual loss of renal mass and functions. It has become a global health problem, with hundreds of millions of people being affected. Both its incidence and prevalence are increasing over time. More than $20,000 are spent on each patient per year. The economic burden on the patients, as well as the society, is heavy and their life quality worsen over time. However, there are still limited effective therapeutic strategies for CKD. Patients mainly rely on dialysis and renal transplantation, which cannot prevent all the complications of CKD. Great efforts are needed in understanding the nature of CKD progression as well as developing effective therapeutic methods, including pharmacological agents. This paper reviews three aspects in the research of CKD that may show great interests to those who devote to bioanalysis, biomedicine and drug development, including important endogenous biomarkers quantification, mechanisms underlying CKD progression and current status of CKD therapy.

Oncolytic viruses, as novel biological anti-tumor agents, provide anti-tumor therapeutic effects by different mechanisms including directly selective tumor cell lysis and secondary systemic anti-tumor immune responses. Some wide-type and genetically engineered oncolytic viruses have been applied in clinical trials. Among them, T-Vec has a significant therapeutic effect on melanoma patients and received the approval of the US Food and Drug Administration (FDA) as the first oncolytic virus to treat cancer in the US. However, the mechanisms of virus interaction with tumor and immune systems have not been clearly elucidated and there are still no “gold standards” for instructions of virotherapy in clinical trials. This Review collected the recent clinical trials data from 2005 to summarize the basic oncolytic viruses biology, describe the application in recent clinical trials, and discuss the challenges in the application of oncolytic viruses in clinical trials.

Bioluminescent Proteins (BLPs) are widely distributed in many living organisms that act as a key role of light emission in bioluminescence. Bioluminescence serves various functions in finding food and protecting the organisms from predators. With the routine biotechnological application of bioluminescence, it is recognized to be essential for many medical, commercial and other general technological advances. Therefore, the prediction and characterization of BLPs are significant and can help to explore more secrets about bioluminescence and promote the development of application of bioluminescence. Since the experimental methods are money and time-consuming for BLPs identification, bioinformatics tools have played important role in fast and accurate prediction of BLPs by combining their sequences information with machine learning methods. In this review, we summarized and compared the application of machine learning methods in the prediction of BLPs from different aspects. We wish that this review will provide insights and inspirations for researches on BLPs.

Coronary artery disease (CAD) is a complex disease caused by the combination of environmental and genetic factors. It is one of the leading causes of death and disability in the world. Much research has been focussed on CAD genetic mechanism. In recent years, genome-wide association study (GWAS) has developed rapidly around the world. Medical researchers around the world have successfully discovered a series of CAD genetic susceptibility genes or susceptible loci using medical research strategies, leading CAD research toward a new stage. This paper briefly summarizes the important progress made by GWAS for CAD in the world in recent years, and then analyzes the challenges faced by GWAS at this stage and the development trend of future research, to promote the transformation of genetic research results into clinical practice and provide guidance for further exploration of the genetic mechanism of CAD.

Background: Nilatinib is an irreversible tyrosine kinase inhibitor, which is used in the treatment of some kinds of cancer. To study the interaction between Neratinib and MAD2L1, a potential tumor target, is of guiding significance for enriching the medicinal value of Neratinib. Method: The binding mechanism between Mitotic arrest deficient 2-like protein 1 (MAD2L1) and Neratinib under simulative physiological conditions was investigated by molecule simulation and multi-spectroscopy approaches. Results: Molecular docking showed the most possible binding mode of Neratinib-MAD2L1 and the potential binding sites and interaction forces of the interaction between MAD2L1 and Neratinib. Fluorescence spectroscopy experiments manifested that Neratinib could interact with MAD2L1 and form a complex by hydrogen bond and van der Waals interaction. These results were consistent with the conclusions obtained from molecular docking. In addition, according to Synchronous fluorescence and three-dimensional fluorescence results, Neratinib might lead to the conformational change of MAD2L1, which may affect the biological functions of MAD2L1. Conclusion: This study indicated that Neratinib could interact with MAD2L1 and lead to the conformational change of MAD2L1. These works provide helpful insights for the further study of biological function of MAD2L1 and novel pharmacological utility of Neratinib.

Background: β thalassemia is a common monogenic genetic disease that is very harmful to human health. The disease arises is due to the deletion of or defects in β-globin, which reduces synthesis of the β-globin chain, resulting in a relatively excess number of α-chains. The formation of inclusion bodies deposited on the cell membrane causes a decrease in the ability of red blood cells to deform and a group of hereditary haemolytic diseases caused by massive destruction in the spleen. Methods: In this work, machine learning algorithms were employed to build a prediction model for inhibitors against K562 based on 117 inhibitors and 190 non-inhibitors. Results: The overall accuracy (ACC) of a 10-fold cross-validation test and an independent set test using Adaboost were 83.1% and 78.0%, respectively, surpassing Bayes Net, Random Forest, Random Tree, C4.5, SVM, KNN and Bagging. Conclusion: This study indicated that Adaboost could be applied to build a learning model in the prediction of inhibitors against K526 cells.

Background: The Matrix Metalloproteinase (MMPs) secreted from macrophages can affect the extracellular matrix remodeling process and improve varicose veins. Aim: The aim of this study was to investigate the MMP-2 and MMP-9 gene expression and activity levels in the differentiated macrophages M2 of subjects with varicose veins, and to evaluate a peptide construct on their catalytic functions. Methods: The macrophages were differentiated from the monocytes using M-CSF. The MMP-2 and MMP-9 gene expression and activity levels were measured by RT-qPCR and Zymography techniques, respectively. A peptide construct (ESLCG) was predicted with bioinformatics tools, and was prepared for the study of enzyme functions as compared to Batimastat. Furthermore, the docking studies were obtained for the evaluation of interactions between peptide construct, Batimastat and enzyme 3D structures. Results: The results showed significant increases in MMP2 and MMP9 gene expression levels (P<0.001 and P<0.004, respectively) and gelatinolytic activities (P<0.001 and P<0.0001, respectively) in the macrophages. In agreement with the inhibitory effects of Batimastat, the peptide construct inhibited the MMP-2 and MMP-9 gelatinolytic activities up to 6.8 and 6.5 folds in the concentration of 150 μM. The docking analyses showed that the Lys187, Arg98, Leu49, Gly189, Leu190, Met97, Tyr53 and Phe57 residues of MMP-2 and the Leu187, His190, Glu402, His401, His405 and His411 residues of MMP-9 are interacted with the atoms of Batimastat and ESLCG peptide. Conclusion: The ESLCG peptide may be applied as an inhibitor of MMP-2 and MMP-9 enzymes in the subjects with varicose veins.

Background/Aims: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. Methods: CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. Results: We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. Conclusion: We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.