Abstract
The present work aims to improve the uses of the carboxymethyl cellulose–polyacrylamide (Na-CMC–PAAm) blend for energy storage, optoelectronic applications, biological control, and plant ...disease management. Nano-sized materials (
α
-Fe
2
O
3
nanoplates (NP), CuO NP, and GO nanosheets (NS), were synthesized and incorporated into the blend. The phase purity and morphologies of the used fillers were studied by XRD and HR-TEM. The interactions and complexation between the nano-fillers and the blend chains were investigated using XRD and FTIR spectra. The chemical composition and surface morphology of the nanocomposites were studied using EDS and FE-SEM analysis. UV-vis-NIR spectra revealed that the blend shows about 95
%
transmittance, reduced by 10–30
%
after doping. The absorption and refractive indices, as well as the optical gaps of the blend, were greatly affected by the doping. The dielectric constant and loss depend on the type of filler and the applied frequency. The maximum ac conductivity of the blend at 303 K and 4.0 MHz is 21.5 × 10
–4
S/m and increased to 23.5 × 10
–4
S/m after doping with CuO NP. The thermal stability, activation energy, stress–strain curves, and tensile strength are dependent on the filler type. All nanocomposite solutions except the blend exhibited a wide range of antifungal properties against pre- and post-harvest phytopathogenic fungi.
Aspergillus niger
among the examined fungi showed high sensitivity to the tested nanocomposite solutions. Furthermore, the CuO/blend nanocomposite had the highest antifungal activity against all tested fungi. Based on that, we suggest the use of CuO/blend and GO/blend nanocomposites to control and combat pre- and post-harvest fungal plant diseases.
A nicotinamide-based derivative was designed as an antiproliferative VEGFR-2 inhibitor with the key pharmacophoric features needed to interact with the VEGFR-2 catalytic pocket. The ability of the ...designed congener ((E)-N-(4-(1-(2-(4-benzamidobenzoyl)hydrazono)ethyl)phenyl)nicotinamide), compound 10, to bind with the VEGFR-2 enzyme was demonstrated by molecular docking studies. Furthermore, six various MD simulations studies established the excellent binding of compound 10 with VEGFR-2 over 100 ns, exhibiting optimum dynamics. MM-GBSA confirmed the proper binding with a total exact binding energy of −38.36 Kcal/Mol. MM-GBSA studies also revealed the crucial amino acids in the binding through the free binding energy decomposition and declared the interactions variation of compound 10 inside VEGFR-2 via the Protein–Ligand Interaction Profiler (PLIP). Being new, its molecular structure was optimized by DFT. The DFT studies also confirmed the binding mode of compound 10 with the VEGFR-2. ADMET (in silico) profiling indicated the examined compound’s acceptable range of drug-likeness. The designed compound was synthesized through the condensation of N-(4-(hydrazinecarbonyl)phenyl)benzamide with N-(4-acetylphenyl)nicotinamide, where the carbonyl group has been replaced by an imine group. The in-vitro studies were consonant with the obtained in silico results as compound 10 prohibited VEGFR-2 with an IC50 value of 51 nM. Compound 10 also showed antiproliferative effects against MCF-7 and HCT 116 cancer cell lines with IC50 values of 8.25 and 6.48 μM, revealing magnificent selectivity indexes of 12.89 and 16.41, respectively.
This book explores the theology and philosophy of the distinguished modern Muslim scholar and theologian Bediuzzaman Said Nursi d.1960. Nursi wrote in both Ottoman Turkish and Arabic and his life and ...thought reflected the transition of modern Turkey from an empire to a secular republic. The contributors to this volume shed new light on two major dimensions of Nursi's thought: theodicy and justice. Classical Muslim theologians debated these two important issues; however, we must consider the modern debate of these issues in the context of the radical political and social transformations of modern Turkey. Nursi explored these matters as they related to the development of state and society and the crisis of Islam in the modern secular nation-state. Nursi is the founder of a 'faith movement' in contemporary Turkey with millions of followers worldwide. In this book, distinguished scholars in Islamic, Middle Eastern, and Turkish Studies explore Nursi's thought on theodicy and justice in comparison with a number of western philosophers, theologians, and men of letters, such as Dante, Merton, Kant, and Moltman. This book presents an invaluable resource for studies in comparative religion, philosophy, and Islamic and Middle Eastern Studies.
Ibrahim M. Abu-Rabi is ECMC Chair Of Islamic Studies, University of Alberta, Edmonton, Canada, and author of 15 books in English on Islamic thought and practice.
Contents: Editor's introduction; Theodicy and the many meanings of Adam and Eve, Barbara Freyer Stowasser; Living life in the light of death: a conversation with Bediuzzaman Said Nursi, Ian Markham; The resurrection of the dead and the final judgment in Said Nursi's thought, Thomas Michel; Proof of the resurrection of the dead: Said Nursi's approach, Sükran Vahide; Death in Nursi's thought, Bilal Kuspinar; La Siyyama: Nursi's treatise on al-Hashr in Mathnawi al-Nuriye, Lucinda Mosher; Resurrection in the writings of Bediuzzaman Said Nursi: comparative reflections with Christian theology, W. Mark Richardson; The resurrection of the dead: Said Nursi and Jürgen Moltmann, Leo D. Lefebure; The problem of animal pain: an introduction to Nursi's approach, Cüneyt M. Simsek; Justice, morality, and modernity: what makes the Risale-i Nur modern?, Dale F. Eickelman; Two epistles of consolation: Al-Shahid al-Thani and Said Nursi on theodicy, Eric Ormsby; 'Landscape and melancholy': Said Nursi, Dante Alighieri and the contexts of modernism, Gareth Jones; Said Nursi's approach to justice and its role for political reforms in the Muslim world, Leonid R. Sykiainen; Reflections on prayer and social justice in the thought of Thomas Merton and Bediuzzaman Said Nursi, David R. Law; God's justice in relation to natural disasters, Thomas Michel; Justice and balance in creation: Said Nursi's analysis, Bilal Kuspinar; Nursi's compassion and Kant's categorical imperative: justice and ethics in building a better world, Ian Kaplow; Index.
GRP78: A cell's response to stress Ibrahim, Ibrahim M.; Abdelmalek, Doaa H.; Elfiky, Abdo A.
Life sciences (1973),
06/2019, Volume:
226
Journal Article
Peer reviewed
Open access
Glucose-Regulated Protein 78 (GRP78) is a chaperone heat shock protein that has been intensely studied in the last two decades. GRP78 is the master of the unfolded protein response (UBR) in the ...Endoplasmic Reticulum (ER) in normal cells. GRP78 force the unfolded proteins to refold or degrade using cellular degradation mechanisms.
Under stress, the overexpression of GRP78 on the cell membrane mediates the vast amount of disordered proteins. Unfortunately, this makes it a tool for pathogens (bacterial, fungal and viral) to enter the cell and to start different pathways leading to pathogenesis. Additionally, GRP78 is overexpressed on the membranes of various cancer cells and increase the aggressiveness of the disease.
The current review summarizes structure, function, and different mechanisms GRP78 mediate in response to normal or stress conditions.
GRP78 targeting and possible inhibition mechanisms are also covered in the present review aiming to prevent the virulence of pathogens and cancer.
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Oxidative stress is an imbalance between free radicals and antioxidants which leads to reactive oxygen species (ROS) production in cells. Reactive oxygen species contains oxygen radicals that easily ...react with other molecules in the biological system. For decades, lead acetate (Pb(C
2
H
3
O2)
2
) is used as an additive for many widely used chemical products such as insecticides, hair dyes, and cosmetics; however, contact with lead acetate may irritate skin, eyes, and mucous membranes.
In the present study, the antioxidant and anti-inflammatory effect of using ferulic acid to inhibit lead acetate-induced toxicity in rats is investigated. Lead acetate was orally given at a dose of 20 mg/kg body weight for 10 days, either alone or with ferulic acid at dose 25 mg/kg. Serum luteinizing hormone (LH), total testosterone, and follicle-stimulating hormone (FSH) levels were measured. Also, reactive oxygen species (ROS), lipid peroxidation (LPO), total antioxidant capacity (TAC), and catalase (CAT) activities were determined. In addition, histopathological changes of testes and kidney were examined. Results showed that administration of lead acetate induced oxidative stress through attenuation of luteinizing hormone, total testosterone, and follicle-stimulating hormone levels in serum. Moreover, the kidney and testes of lead acetate-treated animals exhibited elevation of ROS level, lipid peroxide levels, as well as lysosomal enzyme activity such acid phosphatase and N-acetyl-β-glucosminidase. DNA fragmentation and histological changes were also observed in lead acetate-treated group. In contrast, ferulic acid treatment reduced the deleterious effects induced by lead acetate in both testes and kidney tissues. These results illustrated that ferulic acid has a protective action against toxicity caused by lead acetate in rats. In conclusions, ferulic acid may have future therapeutic relevance in the prevention of lead acetate-induced testicular and renal toxicity in rats.
(
)-
-(3-(1-(2-(4-(2,2,2-Trifluoroacetamido)benzoyl)hydrazono)ethyl)phenyl)nicotinamide (compound
) was designed as an antiangiogenic VEGFR-2 inhibitor with the essential pharmacophoric structural ...properties to interact with the catalytic pocket of VEGFR-2. The designed derivative was synthesized, and its structure was confirmed through Ms, elemental,
H, and
C spectral data. The potentiality of the designed pyridine derivative to bind with and inhibit the vascular endothelial growth factor receptor-2 (VEGFR-2) enzyme was indicated by molecular docking assessments. In addition, six molecular dynamic (MD) experiments proved its correct binding with VEGFR-2 over 100 ns. Additionally, the molecular mechanics energies, combined with the generalized born and surface area (MM-GBSA) analysis, identified the precise binding with optimum energy. To explore the stability and reactivity of the designed pyridine derivative, density functional theory (DFT) calculations, including electrostatic potential maps and total electron density, were carried out. Additionally, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis demonstrated its general likeness and its safety. The designed compound was synthesized to evaluate its effects against VEGFR-2 protein, cancer, and normal cells. The in vitro results were concordant with the in silico results, because the new pyridine derivative (compound
) displayed VEGFR-2 inhibition with an IC
value of 65 nM and displayed potent cytotoxic properties against hepatic (HepG2) and breast (MCF-7) cancer cell lines with IC
values of 21.00 and 26.10 μM, respectively; additionally, it exhibited high selectivity indices against the normal cell lines (W-38) of 1.55 and 1.25, respectively. The obtained results present compound
as a new lead VEGFR-2 inhibitor for further biological investigation and chemical modifications.
A new semisynthetic derivative of the natural alkaloid, theobromine, has been designed as a lead antiangiogenic compound targeting the EGFR protein. The designed compound is an (m-tolyl)acetamide ...theobromine derivative, (T-1-MTA). Molecular Docking studies have shown a great potential for T-1-MTA to bind to EGFR. MD studies (100 ns) verified the proposed binding. By MM-GBSA analysis, the exact binding with optimal energy of T-1-MTA was also identified. Then, DFT calculations were performed to identify the stability, reactivity, electrostatic potential, and total electron density of T-1-MTA. Furthermore, ADMET analysis indicated the T-1-MTA's general likeness and safety. Accordingly, T-1-MTA has been synthesized to be examined in vitro. Intriguingly, T-1-MTA inhibited the EGFR protein with an IC50 value of 22.89 nM and demonstrated cytotoxic activities against the two cancer cell lines, A549, and HCT-116, with IC50 values of 22.49, and 24.97 μM, respectively. Interestingly, T-1-MTA's IC50 against the normal cell lines, WI-38, was very high (55.14 μM) indicating high selectivity degrees of 2.4 and 2.2, respectively. Furthermore, the flow cytometry analysis of A549 treated with T-1-MTA showed significantly increased ratios of early apoptosis (from 0.07% to 21.24%) as well as late apoptosis (from 0.73% to 37.97%).
Fifteen quinazoline derivatives were designed and synthesized as DNA intercalators. The cytotoxicity of the designed members was assessed against HCT-116 and HepG2 cancer cell lines. In addition, the ...topoisomerase II (Topo II) inhibitory effect was assessed. Compound 16 was the most cytotoxic and Topo II inhibitor with low cytotoxicity against Vero cells. Compounds 16, 17, and 18 showed significant DNA binding affinities. Compound 16 showed Topo II catalytic inhibitory effect at a concentration of 10 μM. Further mechanistic investigations revealed the capability of compound 16 to induce apoptosis in HCT-116 cells and arrest the growth at the S and G2/M phases. Also, compound 16 showed a significant increase in the level of BAX (2.18-fold) and a marked decrease in the level of Bcl-2 (1.9-fold) compared to the control cells. In silico studies revealed the ability of the synthesized members to bind to the DNA-Topo II complex.
Based on the pharmacophoric features of EGFR inhibitors, a new semisynthetic theobromine-derived compound was designed to interact with the catalytic pocket of EGFR. Molecular docking against wild ...(EGFRWT; PDB: 4HJO) and mutant (EGFRT790M; PDB: 3W2O) types of EGFR-TK indicated that the designed theobromine derivative had the potential to bind to that pocket as an antiangiogenic inhibitor. The MD and MM-GBSA experiments identified the exact binding with optimum energy and dynamics. Additionally, the DFT calculations studied electrostatic potential, stability, and total electron density of the designed theobromine derivative. Both in silico ADMET and toxicity analyses demonstrated its general likeness and safety. We synthesized the designed theobromine derivative (compound XI) which showed an IC50 value of 17.23 nM for EGFR inhibition besides IC50 values of 21.99 and 22.02 µM for its cytotoxicity against A549 and HCT-116 cell lines, respectively. Interestingly, compound XI expressed a weak cytotoxic potential against the healthy W138 cell line (IC50 = 49.44 µM, 1.6 times safer than erlotinib), exhibiting the high selectivity index of 2.2. Compound XI arrested the growth of A549 at the G2/M stage and increased the incidence of apoptosis.
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