Evaluation of serum nitric oxide synthase levels in patients with coronary slow flow based on corrected TIMI frame count.

Introduction: The coronary slow flow phenomenon (CSFP) finding in angiography is characterized by the delayed filling of the terminal vessels without significant epicardial coronary disease. The endothelium performs a vital role in cardiovascular homeostasis by releasing vasoactive substances. Endothelial cells produce nitric oxide (NO) as one of these essential compounds.

Improvement of binding pose prediction of the MR1 covalent ligands by inclusion of simple pharmacophore constraints and structural waters in the docking process.

Unlabelled: The major histocompatibility complex (MHC) class I-related molecule, MR1, is a key component of the immune system, presenting antigens to T-cell receptors (TCRs) and modulating the immune response against various antigens. MR1 possesses a compact ligand-binding pocket despite its ability to interact with ligands that can have either agonistic or antagonistic effects on the immune system. Agonistic ligands can stimulate the immune response, while antagonistic ligands do not elicit an immune response.

Docetaxel encapsulation in nanoscale assembly micelles of folate-PEG-docetaxel conjugates for targeted fighting against metastatic breast cancer in vitro and in vivo.

Due to the high frequency and mortality of breast cancer, developing efficient targeted drug delivery systems for frightening against this malignancy is among cancer research priorities. The aim of this study was to synthesize a targeted micellar formulation of docetaxel (DTX) using DTX, folic acid (FA) and polyethylene glycol (PEG) conjugates as building blocks. In the current study, two therapeutic polymers consisting of FA-PEG-DTX and PEG-DTX conjugates were synthesized and implemented to form folate-targeted and non-targeted micelles.

Corrigendum to "Evaluation of the Correlation between Serum Concentrations of Asymmetric Dimethylarginine and Corrected TIMI Frame Count in Patients with Slow Coronary Flow".

[This corrects the article DOI: 10.1155/2020/4592190.].

Evaluation of the performance of various machine learning methods on the discrimination of the active compounds.

Machine learning (ML) method performances, including deep learning (DL) on a diverse set with or without feature selection (FS), were evaluated. The superior performance of DL on small sets has not been approved previously. On the other hand, the available sets for the newly identified targets usually are limited in terms of size.

Bioinformatics analysis of the genes involved in the extension of prostate cancer to adjacent lymph nodes by supervised and unsupervised machine learning methods: The role of SPAG1 and PLEKHF2.

The present study aimed to identify the genes associated with the involvement of adjunct lymph nodes of patients with prostate cancer (PCa) and to provide valuable information for the identification of potential diagnostic biomarkers and pathological genes in PCa metastasis. The most important candidate genes were identified through several machine learning approaches including K-means clustering, neural network, Naïve Bayesian classifications and PCA with or without downsampling. In total, 21 genes associated with lymph nodes involvement were identified.

A Random Forest Model to Predict the Activity of a Large Set of Soluble Epoxide Hydrolase Inhibitors Solely Based on a Set of Simple Fragmental Descriptors.

Background: The Soluble Epoxide Hydrolase (sEH) is a ubiquitously expressed enzyme in various tissues. The inhibition of the sEH has shown promising results to treat hypertension, alleviate pain and inflammation.

Objective: In this study, the power of machine learning has been employed to develop a predictive QSAR model for a large set of sEH inhibitors.

Identification of Non-Zinc Binding Inhibitors of MMP-2 Through Virtual Screening and Subsequent Rescoring.

MMP-2 belongs to a large family of proteases called matrix metalloproteinases (MMPs) that degrades type IV collagen, the main structural component of basement membranes and gelatin. The main pathologic role of MMP-2 overexpression is to contribute to the development of cancer through the progression of metastasis and angiogenesis. A structure-based virtual screening was employed to find new inhibitors with possible selectivity for MMP-2.

Correlation between Virtual Screening Performance and Binding Site Descriptors of Protein Targets.

Rescoring is a simple approach that theoretically could improve the original docking results. In this study AutoDock Vina was used as a docked engine and three other scoring functions besides the original scoring function, Vina, as well as their combinations as consensus scoring functions were employed to explore the effect of rescoring on virtual screenings that had been done on diverse targets. Rescoring by DrugScore produces the most number of cases with significant changes in screening power.

An integrated structure- and pharmacophore-based MMP-12 virtual screening.

MMP-12 belongs to a large family of proteases called matrix metalloproteinases (MMPs) that degrades elastin. The main pathologic role of MMP-12 overexpression was suggested to be associated with pathogenesis mechanism of inflammatory respiratory diseases and atherosclerosis. An integrated ligand- and structure-based virtual screening was employed in hope of finding inhibitors with new scaffolds and selectivity for MMP-12.

Ezqsar: An R Package for Developing QSAR Models Directly From Structures.

Background: Quantitative Structure Activity Relationship (QSAR) is a difficult computational chemistry approach for beginner scientists and a time consuming one for even more experienced researchers.

Method And Materials: Ezqsar which is introduced here addresses both the issues. It considers important steps to have a reliable QSAR model.

Homology Modeling of 5-alpha-Reductase 2 Using Available Experimental Data.

5-Alpha-reductase 2 is an interesting pharmaceutical target for the treatment of several diseases, including prostate cancer, benign prostatic hyperplasia, male pattern baldness, acne, and hirsutism. One of the main approaches in computer aided drug design is structure-based drug discovery. However, the experimental 3D structure of 5-alpha-reductase 2 is not available at present.

Virtual Screening on MMP-13 Led to Discovering New Inhibitors Including a Non-Zinc Binding and a Micro Molar One: A Successful Example of Receptor Selection According to Cross-Docking Results for a Flexible Enzyme.

Aim And Objective: MMP-13 belongs to a large family of proteases called matrix metalloproteinases (MMPs) that degrades type II collagen, the main structural protein of articular cartilage. The main pathologic role of MMP-13 over expression is to contribute to the development of osteoarthritis.

Methods: To find new inhibitors with possible selectivity for MMP-13 a structure based virtual screening was employed.

Qualitative Estimation of Drug Entrapment Efficiency in Polymeric Nano - Micelles Using Dissipative Particle Dynamics (DPD).

Background: Dissipative particle dynamics (DPD) is a simulation method that has one of its applications in the field of pharmaceutical science and drug delivery.

Objective: DPD is employed to study morphology and some other characteristics of polymeric nanomicelles. Two systems were considered in this study: system A which includes curcumin, Polycaprolactone (PCL), Polyethylene glycol (PEG) and water beads and system B which includes paclitaxel, Polylactic acid (PLA), PEG and water beads.

Docking and QSAR Studies of 1,4-Dihydropyridine Derivatives as Anti- Cancer Agent.

Background: The multidrug resistance (MDR) of cancer cells has become a great barrier to the success of chemotherapy.

Objective: In this study, quantitative structure activity relationship (QSAR) modeling was applied to 46 1,4-dihydropyridine structures (DHPs), and some selected compounds were docked.

Methods: QSAR was used to generate models and predict the MDR inhibitory activity for a series of 1,4-dihydropyridines (DHP).

Developing a CoMSIA Model for Inhibition of COX-2 by Resveratrol Derivatives.

Design of selective cyclooxygenase-2 (COX-2) inhibitors is still a challenging task because of active site similarities between COX isoenzymes. To help with this issue, we tried to generate a 3D-QSAR (3 dimensional quantitative structure activity relationships) model that might reflect the essential features of COX-2 active sites. Compounds in a series of resveratrol derivatives inhibitors with reported biological activity against COX-2 were used to construct a predictive comparative molecular similarity indices (CoMSIA) model.

CrossDocker: a tool for performing cross-docking using Autodock Vina.

Background: Cross-docking is an approach to find the best holo structures among multiple structures available for a target protein.

Results: CrossDocker significantly decreases the time needed for setting parameters and inputs for performing multiple dockings, data collection and subsequent analysis.

Conclusion: CrossDocker was written in Python language and is available as executable binary for Windows operating system.

Optimal control therapy and vaccination for special HIV-1 model with delay.

In this paper, we consider a four dimensional model of the human immunodeficiency virus-1 (HIV-1) with delay, which is an extension of some three dimensional models. We approach the treatment problem by adding two controllers to the system for inhibiting viral production. The optimal controller [Formula: see text] is considered for vaccine and [Formula: see text] for the drug.

Considering Rotatability of Hydroxyl Groups for the Active Site Residues of MMP-13 in Retrospective Virtual Screening Campaigns.

Considering different orientation of hydroxyl and thiol groups of receptor residues such as Thr, Tyr, Ser and Cys is an option available on Glide docking software. This is an attempt that can provide more realistic ligand-receptor interactions. Matrix metalloproteinase 13 (MMP-13) is a suggested target for several diseases including osteoarthritis and cancer.

Application of DPD in the design of polymeric nano-micelles as drug carriers.

Developing new drug carrier systems are of a great importance in the treatment approach for a wide range of diseases. The simulation techniques can be valuable for decreasing the time and cost of developing novel drug carriers. Among the simulation methods there are a vast number of studies using dissipative particle dynamics (DPD) method for the prediction of different aspects of polymeric nano-micelles for encapsulating drugs.

A Cross-Docking Study on Matrix Metalloproteinase Family.

Background: Matrix metalloproteinases (MMPs) contribute to various physiological and pathophysiological processes. An imbalance in MMP activity causes pathological conditions including inflammatory diseases, cancer, and cardiovascular diseases. Each MMP member has many 3D structures available; therefore, selecting one structure for virtual screening becomes challenging.

Receptor-based 3D-QSAR approach to find selectivity features of flexible similar binding sites: case study on MMP-12/MMP-13.

Design of selective matrix metalloproteinases (MMPs) inhibitors is still a challenging task because of binding pocket similarities and flexibility among MMPs family. To overcome this issue we try to generate a (three-dimensional quantitative structure activity relationship) 3D-QSAR model that might reflect, at least in part, the differential properties of MMP-12 and MMP-13 active sites compared to each other. The different alignment rules were applied for CoMFA/CoMSIA model development.

Evaluation of 11 scoring functions performance on matrix metalloproteinases.

Matrix metalloproteinases (MMPs) have distinctive roles in various physiological and pathological processes such as inflammatory diseases and cancer. This study explored the performance of eleven scoring functions (D-Score, G-Score, ChemScore, F-Score, PMF-Score, PoseScore, RankScore, DSX, and X-Score and scoring functions of AutoDock4.1 and AutoDockVina).

A Predictive HQSAR Model for a Series of Tricycle Core Containing MMP-12 Inhibitors with Dibenzofuran Ring.

MMP-12 is a member of matrix metalloproteinases (MMPs) family involved in pathogenesis of some inflammatory based diseases. Design of selective matrix MMPs inhibitors is still challenging because of binding pocket similarities among MMPs family. We tried to generate a HQSAR (hologram quantitative structure activity relationship) model for a series of MMP-12 inhibitors.

Evaluation of the effect of pentoxifylline on erythropoietin-resistant anemia in hemodialysis patients.

Use of recombinant human erythropoietin (rh-Epo) improves hemoglobin (Hgb) in 90-95% of the cases of anemia of chronic kidney disease (CKD). However, it is known that pro-inflammatory cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-alfa (TNF-α) and interleukin-1 (IL-1) suppress erythropoiesis, resulting in inadequate response to rh-Epo. Pentoxifylline has been shown to have modulatory effects on the immune system.