In silico drug repositioning of FDA-approved drugs to predict new inhibitors for alpha-synuclein aggregation

One of the hallmarks of Parkinson's disease (PD), a long-term neurodegenerative syndrome, is the accumulation of alpha-synuclein (α-syn) fibrils. Despite numerous studies and efforts, inhibition of α-syn protein aggregation is still a challenge. To overcome this issue, we propose an in silico pharmacophore-based repositioning strategy, to find a pharmaceutical drug that, in addition to their defined role, can be used to prevent aggregation of the α-syn protein. Ligand-based pharmacophore modeling was developed and the best model was selected with validation parameters including 72 % sensitivity, 98 % specificity and goodness score about 0.7. The optimal model has three groups of hydrogen bond donor (HBD), three groups of hydrogen bond acceptor (HBA), and two aromatic rings (AR). The FDA-Approved reports in the ZINC15 database were screened with the pharmacophore model taken from inhibitor compounds. The model identified 22 hits, as promising candidate drugs for Parkinson's therapy. It is noteworthy that among these, 10 drugs have been reported to inhibition of α-syn aggregation or treat/reduce Parkinson's pathogenesis. This model was used to virtual screen ZINC, NCI databases, and natural products from the pomegranate. The results of this screen were filtered for their inability to cross the blood-brain barrier, poor oral bioavailability, etc. Finally, the selected compounds of two ZINC and NCI databases were combined and structurally clustered. Remained compounds were clustered in 28 different clusters, and the 17 compounds were introduced as final candidates

Tissue Culture of Rubus sp. by Different Methods and Assessment of Genetic Fidelity of Regenerated Plants Using RAPD

Different methods employed in plant tissue culture can provide a valuable source of plants for the horticultural industry and novel germplasm for breeding programs, but the genetic fidelity and lack of somaclonal variation of regenerated plants needs to be verified. In this study, the genetic fidelity of blackberry (Rubus hirtus Waldst. & Kit.) plants regenerated in vitro was assessed with 11 randomly amplified polymorphic DNA (RAPD) markers. Three routes were assessed: callus induction on Yasuda medium with 6-benzyladenine (BA, 8.88 μM), 1-naphthaleneacetic acid (NAA, 10.84 μM) and glycerol (2%, v/v), somatic embryogenesis on Murashige and Skoog (MS) supplemented with 7.57 μM abscisic acid (ABA), and micropropagation from single nodes on MS basal medium containing NAA (0 and 2.86 μM) and BA (0, 4.44, 8.88 and 17.76 μM). MS medium with 2.86 μM NAA and 8.88 or 17,76 μM BA was the most effective medium for axillary shoot multiplication of R. hirtus and Rubus sanctus Schreb. from nodal segments. A total of 618 fragments were successfully generated by RAPD and the maximum of loci was observed in primer 1204-209 that show 10 and 69 bands. Genetic similarity exceeded 86% when regenerated plants were compared to mother plants. Based on the RAPD data profile, almost true-to-type plants were produced by different methods of plant regeneration (direct shoot regeneration, somatic embryogenesis and organogenesis)

A Unified Model of the GABA(A) Receptor Comprising Agonist and Benzodiazepine Binding Sites

We present a full-length α(1)β(2)γ(2) GABA receptor model optimized for agonists and benzodiazepine (BZD) allosteric modulators. We propose binding hypotheses for the agonists GABA, muscimol and THIP and for the allosteric modulator diazepam (DZP). The receptor model is primarily based on the glutamate-gated chloride channel (GluCl) from C. elegans and includes additional structural information from the prokaryotic ligand-gated ion channel ELIC in a few regions. Available mutational data of the binding sites are well explained by the model and the proposed ligand binding poses. We suggest a GABA binding mode similar to the binding mode of glutamate in the GluCl X-ray structure. Key interactions are predicted with residues α(1)R66, β(2)T202, α(1)T129, β(2)E155, β(2)Y205 and the backbone of β(2)S156. Muscimol is predicted to bind similarly, however, with minor differences rationalized with quantum mechanical energy calculations. Muscimol key interactions are predicted to be α(1)R66, β(2)T202, α(1)T129, β(2)E155, β(2)Y205 and β(2)F200. Furthermore, we argue that a water molecule could mediate further interactions between muscimol and the backbone of β(2)S156 and β(2)Y157. DZP is predicted to bind with interactions comparable to those of the agonists in the orthosteric site. The carbonyl group of DZP is predicted to interact with two threonines α(1)T206 and γ(2)T142, similar to the acidic moiety of GABA. The chlorine atom of DZP is placed near the important α(1)H101 and the N-methyl group near α(1)Y159, α(1)T206, and α(1)Y209. We present a binding mode of DZP in which the pending phenyl moiety of DZP is buried in the binding pocket and thus shielded from solvent exposure. Our full length GABA(A) receptor is made available as Model S1

Candiduria; a review article with specific data from Iran

Although, several categories of nosocomial infections are presented during the recent years, urinary tract infections (UTIs) considered as one of the most important systemic infections. The presence of Candida species in the urinary tract system (Candiduria) is seen in only 10-15% of the cases with UTI, however candiduria has been considered as more problematic infection for patients, laboratory workers and physicians. Due to increasing numbers of several predisposing factors, such as antibacterial agents, urinary tract instrumentation, diabetes mellitus, invasive therapies, and prolonged hospital stay, candiduria develops among the hospitalized patients, especially hospitalized in intensive care units (ICUs) and neonatal intensive care units (NICUs). According to the epidemiological studies, Candida albicans is the most common isolated species from candiduric patients. However, during the recent years, due to increasing resistance to antifungal drugs, non-albicans Candida species including, C. glabrata, C. krusei, C. parapsilosis and C. tropicalis have been also implicated. We found that the mean prevalence of candiduria among Iranian patients was lower (16.5%) than worldwide ratio and also males were more frequently affected than females (M:F, 1.2:1). Similar to other countries, C. albicans was most common infectious agent followed by non-albicans Candida species including, C. glabrata, C. tropicalis and C. krusei

Cloud point extraction for the determination of copper in environmental samples by flame atomic absorption spectrometry

A simple cloud point extraction procedure is presented for the preconcentration of copper in various samples. After complexation by 4-hydroxy-2-mercapto-6-propylpyrimidine (PTU), copper ions are quantitatively extracted into the phase rich in Triton X-114 after centrifugation. Methanol acidified with 0.5 mol L-1 HNO3 was added to the surfactant-rich phase prior to its analysis by flame atomic absorption spectrometry (FAAS). Analytical parameters including concentrations for PTU, Triton X-114 and HNO3, bath temperature, centrifugation rate and time were optimized. The influences of the matrix ions on the recoveries of copper ions were investigated. The detection limits (3SDb/m, n=4) of 1.6 ng mL-1 along with enrichment factors of 30 for Cu were achieved. The proposed procedure was applied to the analysis of environmental samples

Synthesis, characteristics, and photocatalytic activity of zinc oxide nanoparticles stabilized on the stone surface for degradation of metronidazole from aqueous solution

Background: The presence of antibiotics such as metronidazole in wastewater even at low concentrations requires searching for a suitable process such as advanced oxidation process (AOP) to reduce the level of pollutants to a standard level in water. Methods: In this study, zinc oxide (ZnO) nanoparticles were synthesized by thermal method using zinc sulfate (ZnSO4) as a precursor, then, stabilized on stone and was used as a catalyst, in order to degrade metronidazole by photocalytic process. Effective factors on the removal efficiency of metronidazole including the initial metronidazole concentration, contact time, pH, and 0.9 gL-1 ZnO stabilized on the stone surface were investigated. Results: The X-ray diffraction (XRD) studies showed that the synthesized nanomaterials have hexagonal Wurtzite structure. Also, scanning electron microscopy (SEM) analysis revealed that the average crystalline size of the synthesized ZnO particles was in the range of 1.9-3.2 nm. The spectra represented a sharp absorption edge at 390 nm for ZnO nanoparticles corresponding to band gap of 3.168 eV. The BET-BJH specific surface area of the synthesized ZnO nanoparticles was 25.504 m2/g. The EDS spectrum of ZnO nanoparticles showed four peaks, which were identified as Zn and O. The maximum removal efficiency was 98.36% for the synthetic solution under a specific condition (pH = 11, reaction time = 90 minutes, ZnO concentration = 0.9 gL-1, and the initial concentration of metronidazole = 10 mgL-1). The photocatalytic degradation was found to follow pseudo-first-order degradation kinetics. Conclusion: Therefore, the ZnO nanoparticles synthesized by thermal decomposition are suitable and effective photocatalytic materials for degradation of pharmaceutical contaminants. Keywords: Zinc oxide, Metronidazole, Ultraviolet rays, Nanoparticle

Magnetic nano-biocomposite CuFe2O4@methylcellulose (MC) prepared as a new nano-photocatalyst for degradation of ciprofloxacin from aqueous solution

Background: Antibiotics such as ciprofloxacin (CIP) are even more important in bacterial resistance, even at low concentrations. The aim of this research was to synthesize CuFe2O4@methylcellulose (MC) as a new nano-photocatalyst for degradation of CIP from aqueous solution. Methods: The nano-photocatalyst (CuFe2O4@MC) was characterized by FESEM, energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and Fourier transform infrared (FTIR), thermogravimetric analysis (TGA), and vibrating sample magnetometer (VSM). Powder XRD and EDS analysis confirmed the formation of pure-phase spinel ferrites. After CuFe2O4@MC characterization, the effective parameters in removal efficiency of CIP such as reaction time, initial antibiotic concentration, pH, photocatalyst loading, and degradation kinetic were investigated and conditions were optimized. Then, CIP degradation experiments were conducted on the real sample in the optimal conditions. The removal of chemical oxygen demand (COD) was determined under optimum conditions. Results: The structural characterization of the magnetic nanobiocomposite showed that it is in nanoscale, ferromagnetic property, and thermal stability. The optimal conditions were obtained at pH = 7, irradiation time (90 minutes), photocatalyst loading (0.2 g), and initial concentration of CIP (3 mg/L). The removal efficiency of CIP in the optimal conditions was obtained as 80.74% and 72.87% from the synthetic and real samples, respectively. The removal of COD was obtained as 68.26% in this process. The evaluation of kinetic linear models showed that the photocatalytic degradation process was fitted by pseudo-first order kinetic model and Langmuir-Hinshelwood. CuFe2O4@MC photocatalyst had a good stability and reusability for the fourth runs. Conclusion: The photocatalytic degradation of CIP from aqueous media with CuFe2O4@MC photocatalyst has a high efficiency, which can be used in the treatment of pharmaceutical wastewaters. Keywords: Spinel, Ciprofloxacin, Methylcellulose, Wastewate

Spectral and thermal data as a proxy for leaf protective energy dissipation under kaolin application in grapevine cultivars

Research ArticleThe dynamic effects of kaolin clay particle film application on the temperature and spectral reflectance of leaves of two autochthonous cultivars (Touriga Nacional (TN, n=32) and Touriga Franca (TF, n=24)) were studied in the Douro wine region. The study was implemented in 2017, in conditions prone to multiple environmental stresses that include excessive light and temperature as well as water shortage. Light reflectance from kaolin-sprayed leaves was higher than the control (leaves without kaolin) on all dates. Kaolin’s protective effect over leaves’ temperatures was low on the 20 days after application and ceased about 60 days after its application. Differences between leaves with and without kaolin were explained by the normalized maximum leaf temperature (T_max_f_N), reflectance at 400 nm, 532 nm, and 737 nm, as assessed through TN data. The wavelengths of 532 nm and 737 nm are associated with plant physiological processes, which support the selection of these variables for assessing kaolin’s effects on leaves. The application of principal component analysis to the TF data, based on these four variables (T_max_f_N and reflectances: 400, 532, 737 nm) selected for TN, explained 83.56% of data variability (considering two principal components), obtaining a clear differentiation between leaves with and without kaolin. The T_max_f_N and the reflectance at 532 nm were the variables with a greater contribution for explaining data variability. The results improve the understanding of the vines’ response to kaolin throughout the grapevine cycle and support decisions about the re-application timinginfo:eu-repo/semantics/publishedVersio