Green synthesis of silver nanoparticles using a combination of Urtica dioica and Scrophularia striata plant extracts and evaluation of their antifungal effects against dermatophytes

       Infection of the skin is caused by various microbial agents such as fungi. Given the alarming spread of microbial resistance, a new therapeutic approach to combat antibiotic-resistant microbes such as nanoparticles seems necessary. The objective of this study was the investigation of properties of silver nanoparticles synthesized by a mixed extract of Scrophularia striata and Urtica dioica and to evaluate their biological activity against skin infectious fungi. ultra violet (UV) spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Energy-Dispersive X-ray (EDAX) and scanning electron microscopy (SEM) were used for characterizing the synthesized nanoparticles. Antimicrobial activity of the nanoparticles was then evaluated against three dermatophytes namely Microsporum canis, Trichophyton rubrum and Candida albicans by measuring the growth disc diameter method. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were also determined using microdilution technique. The maximum absorption peak of the nanoparticles was observed at 450 nm, which is in the range of absorption for silver nanoparticles. X-ray diffraction also confirmed the presence of nano silver crystals. The electron microscopy imaging showed that the nanoparticles were spherical in shape and have an average size of 40±5 nm. MIC value for biosynthesized nanoparticles were 31, 15 and 7 ppm for T. rubrum, M. canis and C. albicans, respectively. It is suggested that the silver nanoparticles synthesized by using a combination of U. dioica and S. striata extracts could be used as potent antifungal agents against the skin-deep pathogenic fungi

Metformin accelerates myelin recovery and ameliorates behavioral deficits in the animal model of multiple sclerosis via adjustment of AMPK/Nrf2/mTOR signaling and maintenance of endogenous oligodendrogenesis during brain self-repairing period

BACKGROUND: Multiple sclerosis (MS) is a devastating autoimmune disorder characterized by oligodendrocytes (OLGs) loss and demyelination. In this study, we have examined the effects of metformin (MET) on the oligodendrogenesis, redox signaling, apoptosis, and glial responses during a self-repairing period (1-week) in the animal model of MS. METHODS: For induction of demyelination, C57BL/6 J mice were fed a 0.2% cuprizone (CPZ) for 5 weeks. Thereafter, CPZ was removed for 1-week and molecular and behavioral changes were monitored in the presence or absence of MET (50 mg/kg body weight/day). RESULTS: MET remarkably increased the localization of precursor OLGs (NG2+/O4+ cells) and subsequently the renewal of mature OLGs (MOG+ cells) in the corpus callosum via AMPK/mammalian target of rapamycin (mTOR) pathway. Moreover, we observed a significant elevation in the antioxidant responses, especially in mature OLGs (MOG+/nuclear factor erythroid 2-related factor 2 (Nrf2+) cells) after MET intervention. MET also reduced brain apoptosis markers and lessened motor dysfunction in the open-field test. While MET was unable to decrease active astrogliosis (GFAP mRNA), it reduced microgliosis by down-regulation of Mac-3 mRNA a marker of pro-inflammatory microglia/macrophages. Molecular modeling studies, likewise, confirmed that MET exerts its effects via direct interaction with AMPK. CONCLUSIONS: Altogether, our study reveals that MET effectively induces lesion reduction and elevated molecular processes that support myelin recovery via direct activation of AMPK and indirect regulation of AMPK/Nrf2/mTOR pathway in OLGs. These findings facilitate the development of new therapeutic strategies based on AMPK activation for MS in the near future. KEYWORDS: AMPK; Cuprizone; Multiple sclerosis; Nrf2; mTO

Evaluation of Sesquiterpenes from Ferula assa-foetida on inflamatory parameters and study of biding modes using computational methods

introduction: Ferula assafoetida is a source of sesquiterpenes [1]. According to an investigation, phenolic compounds at physiological concentration can inhibit inflammatory enzymes [2]. These enzymes digest the extracellular matrix and provide the conditions for activation and migration and proliferation of endothelial cells. Reported studies on medicinal plants for their inhibitory effect on MMP are very limited. Methods and Results: Acetone extract of plant was prepared and Sesquiterpenes were purified using HPLC preparative analyses and their structures were elucidated. After culturing the cell at confluence, cells were isolated and the supernatant was removed. The pure substances were applied on cell lines U87MG and Wehi activities. Besides the structure has been docked in the active site of metalloproteinase, and significant interactions were determined.Subsequently, ligand-protein complexes were subjected to molecular dynamics simulation in water and thermodynamic properties were calculated. In the phytochemistry field galbanic acid, mogoltadone, kellerin, polyanthin and polyanthininwere produced from F. assafoetida. The results of celluar toxicity study shows that IC50 of Galbanic acid, Mogoltadone and Polyanthin in Wehi cell line were 925.2703, 721.86, and 680.3 µg/ml in U87MG cell line were 952.193, 752.352, 678.742. Galbanic acid, mogoltadone, kellerin, polyanthin and polyanthininwere solated from F. assafoetida. The results of celluar toxicity study show that IC50 of Galbanic acid, Mogoltadone and Polyanthin in Wehi cell line were 925.2703, 721.86, and 680.3 µg/ml in U87MG cell line were 952.193, 752.352, 678.742 Conclusion: Investigation revealed that the coumarins have inhibitory effects on the content and activity of MMP 2.9 and showed anti-angiogenetic effect. So, they can be potentially effective in the treatment of cancer. Interactive and competitive binding between MMP-9 and Galbanic acid were studied with FT-IR, UV-Vis and fluorescence methods and MMP-9 structure was changed in these interactions

Determination of Arsenic in Drinking Water Samples by Electrothermal Atomic Absorption Spectrometry after Preconcentration Using the Biomass of Aspergillus niger Loaded on Activated Charcoal

A simple, fast, and sensitive method for determination of total arsenic in drinking water sample by ETAAS after solid phase preconcentration has been developed. The dead biomass of A. niger loaded on activated charcoal has been applied as bioadsorbent for preconcentration step. The effects of parameters such as pH, type and concentration of eluent, biosorption time, sample volume, and effect of interfering ions have also been studied. Under the optimum condition, the enrichment factor of 10 for the analyte has been obtained. The accuracy of the method has been investigated by the recovery of spiked standards and the recovery percents between 99 and 102% have been achieved. Total amount of arsenic was determined by reducing As (V) to As (III) with potassium iodide (KI) and ascorbic acid in HCl solution. Under the optimum conditions, for 400 mL of drinking water samples, the detection limit (3σ) and linear range were achieved 1 ng/mL and 5–100 ng/mL, respectively. The relative standard deviation for ten determinations of a spiked sample with concentration of 10 ng/mL As was 3.2%

A coupling of homology modeling with multiple molecular dynamics simulation for identifying representative conformation of GPCR structures: a case study on human bombesin receptor subtype-3

<p>In this study, a computational pipeline was therefore devised to overcome homology modeling (HM) bottlenecks. The coupling of HM with molecular dynamics (MD) simulation is useful in that it tackles the sampling deficiency of dynamics simulations by providing good-quality initial guesses for the native structure. Indeed, HM also relaxes the severe requirement of force fields to explore the huge conformational space of protein structures. In this study, the interaction between the human bombesin receptor subtype-3 and MK-5046 was investigated integrating HM, molecular docking, and MD simulations. To improve conformational sampling in typical MD simulations of GPCRs, as in other biomolecules, multiple trajectories with different initial conditions can be employed rather than a single long trajectory. Multiple MD simulations of human bombesin receptor subtype-3 with different initial atomic velocities are applied to sample conformations in the vicinity of the structure generated by HM. The backbone atom conformational space distribution of replicates is analyzed employing principal components analysis. As a result, the averages of structural and dynamic properties over the twenty-one trajectories differ significantly from those obtained from individual trajectories.</p

Gastric cancer biomarkers; A systems biology approach

Gastric cancer is one of the most fatal cancers in the world. Many efforts in recent years have attempted to find effective proteins in gastric cancer. By using a comprehensive list of proteins involved in gastric cancer, scientists were able to retrieve interaction information. The study of protein-protein interaction networks through systems biology based analysis provides appropriate strategies to discover candidate proteins and key biological pathways.In this study, we investigated dominant functional themes and centrality parameters including betweenness as well as the degree of each topological clusters and expressionally active sub-networks in the resulted network. The results of functional analysis on gene sets showed that neurotrophin signaling pathway, cell cycle and nucleotide excision possess the strongest enrichment signals. According to the computed centrality parameters, HNF4A, TAF1 and TP53 manifested as the most significant nodes in the interaction network of the engaged proteins in gastric cancer. This study also demonstrates pathways and proteins that are applicable as diagnostic markers and therapeutic targets for future attempts to overcome gastric cancer. Keywords: Gastric cancer, Systems biology, Neurotrophin signaling pathway, HNF4A, TAF1, TP5

Critical effects on binding of epidermal growth factor produced by amino acid substitutions

<p>Epidermal growth factor (EGF) plays important roles in multiple biological processes, such as the regulation of cell growth, proliferation, and differentiation. EGF exerts their pharmacologic effects via receptor-mediated mechanism associated with high affinity to epidermal growth factor receptor (EGFR) on the cell surface. Overexpression of EGFR has been reported and implicated in the pathogenesis of many human cancers. The current study addresses the effects of mutations on binding properties of EGF to EGFR. Two mutant structures with three point mutations of conserved residues, Ile23, Arg41 and Leu47, which have been found to be important for the receptor binding, were built using homology modeling. The “wild type” (WT) and the mutant structures, after structural validations, were subjected to molecular dynamics simulations (MDSs). The primary aim of MDS was to investigate the possible impact of mutations on the protein structure and function. Analysis of root mean square deviation (RMSD), other time dependent structural properties and their averages provided some insights into the possible structural characteristics of the mutant and the WT forms of the EGF. RMSD analysis showed that WT EGF was more stable than the mutant structures. The docking analysis revealed that the binding energy of mutant EGFs to EGFR is lower than WT. Combination of the used computational approaches provides a way in understanding the impact of deleterious mutations in altering the EGF and EGFR interactions.</p

Synthesis, characterization and comparative DNA interaction studies of new copper(II) and nickel(II) complexes containing mesalamine drug using molecular modeling and multispectroscopic methods

<div><p>Complexes of copper(II) and nickel(II) containing the drug mesalamine (5-ASA) have been synthesized and characterized by FT-IR, mass and UV–vis spectra, elemental analysis, and theoretical methods. The binding interactions between mesalamine and its Cu(II) and Ni(II) complexes with calf thymus DNA (ct-DNA) were investigated using absorption, fluorescence emission and circular dichroism (CD) spectroscopies, and viscosity measurements. Absorption spectra of 5-ASA, Cu(II) and Ni(II) complexes showed hypochromism. The calculated binding constants (<i>K</i>_b) obtained from UV–vis absorption studies were 1.27 × 10³, 1.6 × 10³, and 1.2 × 10⁴ M⁻¹ for 5-ASA, Cu(II) and Ni(II) complexes, respectively. The compounds induced detectable changes in the CD spectra of ct-DNA (B → A structural transition, B → C structural transition and stabilization of the right-handed B form, for mesalamine, Cu(II) and Ni(II) complexes, respectively). The competitive binding experiments with Hoechst 33258 indicated that 5-ASA and copper complex could interact as groove binders. Furthermore, Ni complex had no effect on the fluorescence intensity and peak position of MB-DNA system. Finally, the results obtained from experimental and molecular modeling showed that complexes bind to DNA via minor-groove binding.</p></div

Chemometrics-assisted multi-instrumental techniques for investigation of interactions of dapagliflozin with normal and glycated human serum albumin: application to exploiting second-order advantage for determination of glycated human serum albumin as a biomarker for controlling diabetes

In this paper, we have collected useful information about interactions of dapagliflozin (DPA) with normal human serum albumin (HSA) and glycated HSA (GHSA) by using spectroscopic and electrochemical methods. Instrumental data were analyzed by graphical and conventional methods and then, the data were mathematically modeled and simultaneously analyzed by multivariate curve resolution-alternating least squares (MCR-ALS). Hard-modeling algorithm of the data helped us to obtain qualitative and quantitative information to cast a deep look at the interactions of the DPA with HSA and GHSA. The results of MCR-BANDS showed that the MCR-ALS gave us unambiguous and reliable results. Afterwards, molecular docking techniques were used to investigate binding of the DPA with HSA and GHSA to obtain new information and to complete the previous findings. The DPA was bound with HSA and GHSA with different binding strengths. Fortunately, the results were compatible and confirmed each other. Finally, according to the results of interaction and binding of the DPA with HSA and GHSA, a second-order calibration model was developed with aim of exploiting second-order advantage for determination of the GHSA in the presence of HSA as uncalibrated interference. The developed method had a good performance for determination of the GHSA in both of synthetic and real samples.Fil: Mohamady, Asma. Kermanshah University Of Medical Sciences; IránFil: Shahlaei, Mohsen. Kermanshah University Of Medical Sciences; IránFil: Akbari, Vali. Kermanshah University Of Medical Sciences; IránFil: Goicoechea, Hector Casimiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Desarrollo Analítico y Quimiometría; ArgentinaFil: Jalalvand, Ali R.. Kermanshah University Of Medical Sciences; Irá

A comprehensive physicochemical, in vitro and molecular characterization of letrozole incorporated chitosan-lipid nanocomplex

Purpose: The aim of this study is to show a new mesomicroscopic insight into Letrozole (LTZ) loaded nanocomplexes and their ex vivo characteristics as a drug delivery system. Methods: The LTZ loaded hybrid chitosan-based carrier was fabricated using a modified ionic crosslinking technique and characterized in more detail. To understand the mechanism of LTZ action encapsulated in the hybrid polymer-lipid carrier, all-atom molecular dynamics simulations were also used. Results: The physicochemical properties of the carrier demonstrated the uniform morphology, but different drug loading ratios. In vitro cytotoxic activity of the optimized carrier demonstrated IC 50 of 67.85 ± 0.55 nM against breast cancer cell line. The ex vivo study showed the positive effect of nanocomplex on LTZ permeability 7–10 fold greater than the free drug. The molecular dynamic study also confirmed the prsence of hydrophobic peak of lipids at a distance of 5 Å from the center of mass of LTZ which proved drug entrapment in the core of nanocomplex. Conclusions: The hybrid nanoparticle increased the cytotoxicity and tissue permeability of LTZ for oral delivery. This study also confirmed the atomic mesostructures and interaction of LTZ in the core of hybrid polymer-lipid nanoparticles. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.research council of Kermanshah University of Medical Sciences [96372