Gene network reveals LASP1, TUBA1C, and S100A6 are likely playing regulatory roles in multiple sclerosis.

Introduction: Multiple sclerosis (MS), a non-contagious and chronic disease of the central nervous system, is an unpredictable and indirectly inherited disease affecting different people in different ways. Using Omics platforms genomics, transcriptomics, proteomics, epigenomics, interactomics, and metabolomics database, it is now possible to construct sound systems biology models to extract full knowledge of the MS and recognize the pathway to uncover the personalized therapeutic tools. Methods: In this study, we used several Bayesian Networks in order to find the transcriptional gene regulation networks that drive MS disease. We used a set of BN algorithms using the R add-on package bnlearn. The BN results underwent further downstream analysis and were validated using a wide range of Cytoscape algorithms, web based computational tools and qPCR amplification of blood samples from 56 MS patients and 44 healthy controls. The results were semantically integrated to improve understanding of the complex molecular architecture underlying MS, distinguishing distinct metabolic pathways and providing a valuable foundation for the discovery of involved genes and possibly new treatments. Results: Results show that the LASP1, TUBA1C, and S100A6 genes were most likely playing a biological role in MS development. Results from qPCR showed a significant increase (P < 0.05) in LASP1 and S100A6 gene expression levels in MS patients compared to that in controls. However, a significant down regulation of TUBA1C gene was observed in the same comparison. Conclusion: This study provides potential diagnostic and therapeutic biomarkers for enhanced understanding of gene regulation underlying MS.

The adsorption of NO2, SO2, and O3 molecules on the Al-doped stanene nanotube: a DFT study.

Adsorption of pollutant gas molecules (NO2, SO2, and O3) on the surface of the Al-doped stanene nanotube was investigated within the first principle calculations of density functional theory (DFT). Adsorption mechanisms were studied by analyzing optimized structures, band structures, projected density of states (PDOS), charge density difference (CDD), molecular orbitals, and band theory. Investigation of charge transfer by Mulliken population showed that NO2 accumulated while SO2 and O3 depleted charge density on the Al-doped nanotube. The differences in band structures before and after adsorption implied that the electronic characteristics of Al-doped nanotube changed dramatically in case of NO2 adsorption, which converted Al-doped nanotube to a semiconductor material. High adsorption energy and the significant overlap between PDOS spectra indicated that the adsorption process was chemisorption for NO2, SO2, and O3 on the doped nanotube with the obtained order of O3 > SO2 > NO2. The results showed that the adsorption of NO2, SO2, and O3 occurred on the Al-doped stanene nanotube, and that all the three gas molecules could be detected by Al-doped stanene nanotube with various detection strengths.

Fabrication of a magnetic nanocarrier for doxorubicin delivery based on hyperbranched polyglycerol and carboxymethyl cellulose: An investigation on the effect of borax cross-linker on pH-sensitivity.

A new core-shell pH-responsive nanocarrier was prepared based on magnetic nanoparticle (MNP) core. Magnetic nanoparticles were first modified with hyperbranched polyglycerol as the first shell. Then the magnetic core was decorated with doxorubicin anticancer drug (DOX) and covered with PEGylated carboxymethylcellulose as the second shell. Borax was used to partially cross-link organic shells in order to evaluate drug loading content and pH-sensitivity. The structure of nanocarrier, organic shell loadings, magnetic responsibility, morphology, size, dispersibility, and drug loading content were investigated by IR, NMR, TG, VSM, XRD, DLS, HR-TEM and UV-Vis analyses. In vitro release investigations demonstrated that the use of borax as cross-linker between organic shells make the nanocarrier highly sensitive to pH so that more that 70% of DOX is released in acidic pH. A reverse pH-sensitivity was observed for the nanocarrier without borax cross-linker. The MTT assay determined that the nanocarrier exhibited excellent biocompatibility toward normal cells (HEK-293) and high toxicity against cancerous cells (HeLa). The nanocarrier also showed high hemocompatibility. Cellular uptake revealed high ability of nanocarrier toward HeLa cells comparable with free DOX. The results also suggested that low concentration of nanocarrier has a great potential for use as contrast agent in magnetic resonance imaging (MRI).

Design, Synthesis, and Docking Studies of Thioimidazolyl Diketoacid Derivatives Targeting HIV-1 Integrase.

BACKGROUND: Integrase enzyme is a validated drug target to discover novel structures as anti-HIV-1 agents. OBJECTIVE: This study aimed at developing a novel series of thioimidazolyl diketoacid derivatives characterizing various substituents at N-1 and 2-thio positions of the central ring as HIV-1integrase inhibitors. METHODS: In this study, eighteen novel thioimidazolyl DKA derivatives were synthesized in a fivestep parallel procedure and tested in vitro for the inhibition of both IN ST reaction and the singlecycle HIV-1 replication in HeLa cell culture. RESULTS: The obtained molecules were evaluated using the enzyme assay, displaying promising integrase inhibitory activity with IC50 values ranging from 0.9 to 7.7 mM. The synthesized compounds were also tested for antiviral activity and cytotoxicity using HeLa cells infected by the single-cycle replicable HIV-1 NL4-3. CONCLUSION: The most potent compound was found to be 18i with EC50 = 19 µM, IC50 = 0.9 µM, and SI = 10.5. Docking studies indicated that the binding mode of the active molecule is well aligned with the known HIV-1integrase inhibitor.

4-(1-Benzyl-1H-benzo[d]imidazol-2-yl)-4-oxo-2-butenoic Acid Derivatives: Design, Synthesis and Anti-HIV-1 Activity.

Acquired immunodeficiency syndrome (AIDS) is still an incurable disease with increasing mortality rate. Despite the development of effective FDA-approved anti-HIV drugs, there are some problems due to the growing of resistant viral strands. Therefore, discovery of novel anti-HIV agents is so needed. Integrase, targeted in highly active antiretroviral therapy (HAART), is a crucial enzyme in viral replication. In this study, new benzimidazolyl diketo acid derivatives were designed according to required features for inhibitors of HIV-1 integrase. Designed compounds were synthesized and evaluated for anti-HIV-1 effects. According to the cell-based biological assay's results, most of the tested compounds demonstrated good anti-HIV-1 activity, ranging from 40-90 µM concentration with no severe cytotoxicity. The most potent compound was 13g with EC50 value of 40 µM and CC50 value of 550 µM. Docking analysis of compound 13g in integrase active site was in good agreement with well-known integrase inhibitors, proposing that anti-HIV-1 potency of compounds may be via integrase inhibition.

Magnetic nanoparticles double wrapped into cross-linked salep/PEGylated carboxymethyl cellulose; a biocompatible nanocarrier for pH-triggered release of doxorubicin.

A magnetic nanocarrier was synthesized in which Fe3O4 nanoparticles were encapsulated into double layers of polysaccharide shells. The first shell, which was composed of cross-linked salep polysaccharide, contained multiple nitrogen atoms in its structure and provided numerous sites for multiple functionalization. A fluorescence dye and doxorubicin, as widely used chemotherapy agent, were easily attached to the first shell and then a second shell of PEGylated carboxymethyl cellulose enveloped the drug loaded carrier to enhance its biocompatibility and regulates the drug release behavior. The results of drug loading and release behavior showed that the resulting nanocarrier can carry large amounts of drug molecules and a remarkable pH-sensitive release was observed in vitro. The hemolysis and coagulation assays proved the biocompatibility of nanocarrier toward red blood cells and the MTT experiments confirmed that the drug loaded nanocarrier is highly toxic for MCF-7 cancer cells while the unloaded nanocarrier was almost nontoxic. Further flow cytometry experiments and confocal microscopy demonstrated that the double layered magnetic nanocarrier can penetrate into the cells and efficiently release the drug molecules into the cell nucleus. Moreover, the results of MRI experiments performed on the nanocarrier showed that it can be serve as a negative MRI contrast agent.

Evaluation of Seizure Frequency Distribution in Epileptic Patients with Normal and Abnormal Electroencephalogram in Al-Zahra Hospital of Isfahan.

BACKGROUND: Epilepsy is a chronic neurological disorder characterized by seizure recurrence in patients. Electroencephalogram (EEG) has a diagnostic and prognostic role in the management of patients. Studies have shown a significant relation between seizure recurrence and abnormal EEG in newly diagnosed epileptic patients, and people with first episode of unprovoked seizure. The aim of this study is to evaluate seizure frequency in chronic epileptic patients on drug therapy based on normal or abnormal EEG. MATERIALS AND METHODS: This prospective cohort study examined seizure recurrence in 59 epileptic patients (50.8% generalized, 49.2% focal) with normal and abnormal EEG. Data were recorded in patient medical file, and patients were followed by telephone call or visiting by neurologist. RESULTS: In this study, 59 patients with a mean age of 29.58 ± 10.37 years were assessed that 42.4% of them were males and 57.6% were females. Seizure frequency in patient with specific abnormal EEG was significantly more than other patients (specific abnormal: 78.9%, nonspecific abnormal: 45.5%, and normal: 31%, P = 0.005). Seizure recurrence in patients on polytherapy was significantly higher than others (polytherapy: 76.9% and monotherapy: 27.3%, P < 0.001). In patient with abnormal imaging seizure, frequency was more than other patients which was nearly significant (P = 0.054). CONCLUSION: Abnormal EEG and number of anticonvulsant drugs have a role in seizure recurrence in epileptic patients.