Discovery of Potent Kappa Opioid Receptor Agonists Derived from Akuammicine.

Akuammicine (), an alkaloid isolated from , is an agonist of the kappa opioid receptor (κOR). To establish structure-activity relationships (SARs) for this structurally unique κOR ligand, a collection of semisynthetic derivatives was synthesized. Evaluating these derivatives for their ability to activate the κOR and mu opioid receptor (μOR) revealed key SAR trends and identified derivatives with enhanced κOR potency.

The effects of short-time air pollution, SO2, and ozone on biochemical, histo-pathological, oxidative stress, and carcinogenesis related genes expressions in the liver of the rats.

Objective Of The Research: Air pollution is a universal issue and has significant deleterious effects on both human health and also environment. The important indicators of air pollution include ozone (O3), particulate matter (PM), nitrogen dioxide (NO2), and sulfur dioxide (SO2). This research aims to investigate the impacts of ambient air pollution (AAP), SO2, and O3 on oxidative stress parameters, liver tissue histopathology, and expression of some carcinogenesis-related genes in the hepatic tissue of rats.

Come for the atmosphere, stay for the interactions: Deciphering small molecule partitioning into biomolecular condensates.

Optimizing pharmacokinetic properties remains challenging but is generally guided by a set of structural rules. However, no such rule set exists for intracellular distribution. Kilgore et al.

Identifying the main barriers for participation in a population-based colorectal cancer screening programme in East Azerbaijan, Iran.

Background: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. However, CRC is considered as one of the most preventable cancers by which the mortality rates reduce about 60% through implementing the screening programmes. The present study aimed to evaluate the main barriers of CRC screening in a defined population.

Identifying SARS-CoV-2 main protease inhibitors by applying the computer screening of a large database of molecules.

The outbreak of coronavirus disease 2019 (COVID-19) at the end of 2019 affected global health. Its infection agent was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Wearing a mask, maintaining social distance, and vaccination are effective ways to prevent infection of SARS-CoV-2, but none of them help infected people.

Optimization of Frizzled-8 Receptor Inhibition Activity of Carbamazepine: Designing New Anti-Cancer Agent.

Background: Frizzled-8 (FZD8) receptor is a therapeutic target for cancer treatment and recent research has shown that carbamazepine (CBZ) can inhibit this receptor.

Objective: In this work, it has been tried to optimize CBZ to enhance its binding capacity to the N6W binding site of FZD8 by using structure-based drug design methods.

Methods: CBZ and its 83 derivatives were docked to the N6W binding site of FZD8.

Mucosa-Associated in Colorectal Cancer Patients and Control Subjects: Variations in the Prevalence and Attributing Features.

Accumulating evidence indicates that specific strains of mucosa-associated () can influence the development of colorectal carcinoma. This study aimed to investigate the prevalence and characterization of mucosa-associated obtained from the colorectal cancer (CRC) patients and control group. At two referral university-affiliated hospitals in northwest Iran, 100 patients, 50 with CRC and 50 without, were studied over the course of a year.

Escherichia coli and Colorectal Cancer: Unfolding the Enigmatic Relationship.

Colorectal cancer (CRC) is one of the deadliest cancers in the world. Specific strains of intestinal Escherichia coli (E. coli) may influence the initiation and development of CRC by exploiting virulence factors and inflammatory pathways.

Efficacy of Sovodak in the Management of Patients Co-infected with HIV/HCV.

Sofosbuvir (SOF) and daclatasvir (DOC) are suggested for the treatment of hepatitis C virus (HCV) in patients with concomitant HCV and human immunodeficiency virus (HIV). In 2016, Sovodak tablet a combination of SOF and DOC was introduced. In the present study we assessed the effectiveness of SOF in the treatment of HCV in patients co-infected with HIV.

Development linear and non-linear QSAR models for predicting AXL kinase inhibitory activity of N-[4-(quinolin-4-yloxy)phenyl]benzenesulfonamides.

In this research, we used CoMFA, LSSVM and FFANN for creating QSAR models for predicting AXL Kinase inhibitory activity of N-[4-(Quinolin-4-yloxy)phenyl]benzenesulfonamides. A CoMFA model with three components was developed and CoMFA contour maps were interpreted to extract chemical features that influence the inhibitory activity of these molecules. for train and test set of CoMFA model were 0.

CpG Islands Methylation Analysis of CDH11, EphA5, and HS3ST2 Genes in Gastric Adenocarcinoma Patients.

Purpose: Gastric cancer is an aggressive disease which is the fourth prevalent malignancy in the world. Beside the genetic factors, epigenetic alterations such as promoter CpG island hyper methylation are involved in the emergence of gastric cancer. Herein, we investigated the methylation status of CDH11, EphA5, and HS3ST2 genes in patients with and without gastric adenocarcinoma for the first time.

Evaluation of the Methylation of MIR129-2 Gene in Gastric Cancer.

Background: Genetic and epigenetic changes have strong role in the development of gastric cancer. The mutation of the MIR129-2 gene is one of the major causes in many cancers, especially gastric cancer. The aim of this study was to investigate the methylation changes of the MIR129-2 gene in tumor and normal tissue of patients with gastric cancer.

Turmeric and chicory seed have beneficial effects on obesity markers and lipid profile in non-alcoholic fatty liver disease (NAFLD).

In an attempt to investigate new strategies aimed at reducing risk factors of non-alcoholic fatty liver disease (NAFLD), effects of turmeric (Curcuma longa L.) and chicory seed (Cichorium intybus L.) supplementation was evaluated in these patients.

Design of new CD38 inhibitors based on CoMFA modelling and molecular docking analysis of 4‑amino-8-quinoline carboxamides and 2,4-diamino-8-quinazoline carboxamides.

In this study, based on molecular docking analysis and comparative molecular field analysis (CoMFA) modelling of a series of 71 CD38 inhibitors including 4‑amino-8-quinoline carboxamides and 2,4-diamino-8-quinazoline carboxamides, new CD38 inhibitors were designed. The interactions of the molecules with the greatest and the lowest activities with the nicotinamide mononucleotide (NMN) binding site were investigated by molecular docking analysis. A CoMFA model with four partial least squares regression (PLSR) components was developed to predict the CD38 inhibitory activity of the molecules.

The in silico identification of potent anti-cancer agents by targeting the ATP binding site of the N-domain of HSP90.

To identify new HSP90 inhibitors, the ATP binding site of the N-domain of HSP90 was targeted by molecular docking of a library of 23,129,083 compounds (from the ZINC database) to the ATP binding site of the N-domain of HSP90. Structure-based virtual screen (SBVS) was performed using idock software on the istar web platform. Based on idock binding energies, 40 molecules were considered as HSP90 inhibitors.

Towards the In-silico Design of New HSP90 Inhibitors: Molecular Docking and 3D-QSAR CoMFA Studies of Tetrahydropyrido [4, 3-d] Pyrimidine Derivatives as HSP90 Inhibitors.

Background: HSP90 is necessary for the conformational maturation of proteins, proteins disaggregation, folding newly synthesized peptides and the refolding of denatured proteins. The inhibition of HSP90 leads to proteasomal degradations of client proteins that finally kill cancer cells.

Methods: In this research, molecular docking and comparative molecular field analysis (CoMFA) were used to investigate the interactions of tetrahydropyrido[4,3-d]pyrimidine derivatives with the N-terminal domain binding site of the HSP90 and predicting their inhibitory activities.

Expression Level of miR-34a in Tumor Tissue from Patients with Esophageal Squamous Cell Carcinoma.

Background: miR-34a has been shown to be involved in P53 regulation. In this study, we aimed to evaluate the expression level of miR-34a in esophageal cancer and compare it with that of the normal marginal tissues.

Methods: Tumor and marginal tissues were obtained from 50 patients with esophageal cancer.

Predictive and Descriptive CoMFA Models: The Effect of Variable Selection.

Unlabelled: Aims & Scope: In this research, 8 variable selection approaches were used to investigate the effect of variable selection on the predictive power and stability of CoMFA models.

Materials & Methods: Three data sets including 36 EPAC antagonists, 79 CD38 inhibitors and 57 ATAD2 bromodomain inhibitors were modelled by CoMFA. First of all, for all three data sets, CoMFA models with all CoMFA descriptors were created then by applying each variable selection method a new CoMFA model was developed so for each data set, 9 CoMFA models were built.

Congenital Hypertrophy of Retinal Pigment Epithelium for Diagnosis of Familial Adenomatous Polyposis - the First FAP registry in Iran.

Objective: Familial adenomatous polyposis (FAP), an autosomal dominant inherited disorder is characterized by the presence of multiple adenomatous colorectal polyps, which can develop into cancer during early adulthood. Therefore, early diagnosis is essential. Most FAP patients have several extracolonic manifestations, including congenital hypertrophy of the retinal pigment epithelium (CHRPE).

The identification of new ATAD2 bromodomain inhibitors: the application of combined ligand and structure-based virtual screening.

Ligand-based virtual screening (LBVS) and structure-based virtual screening (SBVS) approaches were used to identify new inhibitors for ATAD2 bromodomain. The LBVS approach was used to search 23,129,083 clean compounds to identify compounds similar to an active compound with reported pIC equal to 7.2.

Association between proto-oncogene mutations and clinicopathologic characteristics and overall survival in colorectal cancer in East Azerbaijan, Iran.

Background: Colorectal cancer (CRC) is the third-most common cancer in Iran. The increasing incidence of CRC in the past three decades has made it a major public health burden in the country. This study aimed to determine any relationship of specific mutations in CRCs with clinicopathologic aspects and outcome of patients.

Molecular docking and CoMFA studies of thiazoloquin(az)olin(on)es as CD38 inhibitors: determination of inhibitory mechanism, pharmacophore interactions, and design of new inhibitors.

In this research, molecular docking and 3D-QSAR studies were carried out on a series of 79 thiazoloquin(az)olin(on)es as CD38 inhibitors. Based on docking results, four interactions including hydrogen bonding with main chain of GLU-226 (H-M-GLU-226), Van der Waals interactions with side chain of TRP-125 (V-S-TRP-125), TRP-189 (V-S-TRP-189), and THR-221 (V-S-THR-221) were considered as pharmacological interactions. Active conformation of each ligand was extracted from docking studies and was used for carrying out 3D-QSAR modeling.

The Relation between Left Coronary Dominancy and AtheroscleroticInvolvement of Left Anterior Descending Artery Origin.

Introduction: Limited information is available regarding the relationship between coronary vessel dominance and atherosclerotic involvement. Rheological factors have been implicated in the pathogenesis of coronary lesions. More than 90% of the coronary blood flow enters the left coronary if it is the dominant artery.

Pseudoaneurysm of the portal vein as a rare source of gastrointestinal bleeding in pregnancy: a case report.

A 28-year-old, 32 week pregnant primigravida woman with a past history of increased blood pressure presented with RUQ pain as well as sudden onset of hematemesis. This case illustrates the occurrence of a rare complication (rupture of portal vein pseudoaneurysm inside the biliary system), appearing as upper gastrointestinal bleeding in a pregnant woman. The cause of the rupture is presumably pregnancy-related.

Investigation of retention behavior of polychlorinated biphenyl congeners on 18 different HRGC columns using molecular surface average local ionization energy descriptors.

In this paper, based on the general interaction properties function (GIPF) family descriptors computed at the B3LYP/6-31G* level in Gaussian98 software, a significant quantitative structure-retention relationship (QSRR) models for the high resolution gas chromatographic relative retention time (HRGC-RRT) of all PCB congeners on 18 different HRGC capillary columns were constructed by using multiple linear regression (MLR) analysis, following the guidelines for development and validation of QSRR models. By means of the elimination selection stepwise regression algorithms, the molecular surface average local ionization energy was selected as one-parameter univariate linear regression to develop a QSRR model for prediction of GC-RRT of PCBs on each stationary phase. The accuracy of all developed models was confirmed using different types of internal and external procedures.