Rutin-coated zinc oxide nanoparticles: a promising antivirulence formulation against pathogenic bacteria.

The use of engineered nanoparticles against pathogenic bacteria has gained attention. In this study, zinc oxide nanoparticles conjugated with rutin were synthesized and their antivirulence properties against Pseudomonas aeruginosa and Staphylococcus aureus. The physicochemical characteristics of ZnO-Rutin NPs were investigated using SEM, FT-IR, XRD, DLS, EDS, and zeta potential analyses. Antimicrobial properties were evaluated by well diffusion, microdilution, growth curve, and hemolytic activity assays. The expression of quorum sensing (QS) genes including the lasI and rhlI in P. aeruginosa and agrA in S. aureus was assessed using real-time PCR. Swimming, swarming, twitching, and pyocyanin production by P. aeruginosa were evaluated. The NPs were amorphous, 14-100 nm in diameter, surface charge of -34.3 mV, and an average hydrodynamic size of 161.7 nm. Regarding the antibacterial activity, ZnO-Rutin NPs were more potent than ZnO NPs and rutin, and stronger inhibitory effects were observed on S. aureus than on P. aeruginosa. ZnO-Rutin NPs inhibited the hemolytic activity of P. aeruginosa and S. aureus by 93.4 and 92.2%, respectively, which was more efficient than bare ZnO NPs and rutin. ZnO-Rutin NPs reduced the expression of the lasI and rhlI in P. aeruginosa by 0.17-0.43 and 0.37-0.70 folds, respectively while the expression of the agrA gene in S. aureus was decreased by 0.46-0.56 folds. Furthermore, ZnO-Rutin NPs significantly reduced the swimming and twitching motility and pyocyanin production of P. aeruginosa. This study demonstrates the antivirulence features of ZnO-Rutin NPs against pathogenic bacteria which can be associated with their QS inhibitory effects.

Diclofenac-loaded PLGA nanoparticles downregulate LasI/R quorum sensing genes in pathogenic P. aeruginosa isolates.

Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible polymer that can gradually and consistently release drugs in a controlled manner. In this study, diclofenac sodium-loaded PLGA nanoparticles (DS-PLGA NPs) were produced by solvent evaporation technique and characterized using SEM, DLS, and zeta potential analyses. The antibacterial and antivirulence potential of DS-PLGA NPs against P. aeruginosa strains were examined using broth microdilution, crystal violet staining, hemolysis, and twitching quantification assays. Furthermore, the expression of the quorum sensing (QS) genes, lasI and lasR in P. aeruginosa strains after treatment with 1/2 MIC of DS-PLGA NPs was assessed using real-time PCR. SEM imaging of the synthesized NPs exhibited that the NPs have a spherical structure with a size range of 60-150 nm. The zeta potential of the NPs was - 15.2 mV, while the size of the particles in the aquatic environment was in a range of 111.5-153.8 nm. The MIC of prepared NPs against various strains of P. aeruginosa ranged from 4.5 to 9 mg/mL. Moreover, exposure of bacteria to sub-MIC of DS-PLGA NPs significantly down-regulated the expression of the lasI and lasR genes to 0.51- and 0.75-fold, respectively. Further, prepared NPs efficiently reduced the biofilm formation of P. aeruginosa strains by 9-27%, compared with the controls. Besides, DS-PLGA NPs showed considerable attenuation in bacterial hemolytic activity by 32-88% and twitching motility by 0-32.3%, compared with untreated cells. Overall, the present work exhibited the anti-QS activity of DS-PLGA NPs, which could be a safe and useful approach for treating P. aeruginosa infections.

Effect of samarium oxide nanoparticles on virulence factors and motility of multi-drug resistant Pseudomonas aeruginosa.

Biofilm formation and quorum sensing (QS) dependent virulence factors are considered the major causes of the emergence of drug resistance, therapeutic failure and development of Pseudomonas aeruginosa infections. This study aimed to investigate the effects of samarium oxide nanoparticles (Sm2O3NPs) on biofilm, virulence factors, and motility of multidrug-resistant P. aeruginosa. Sm2O3NPs were synthesized using curcumin and characterized by Transmission Electron Microscopy, X-ray diffractometer, Field Emission Scanning Electron Microscopy, and Energy-dispersive X-ray spectroscopy. Minimum inhibitory concentration (MIC) was determined using broth microdilution method. The antibiofilm potential of Sm2O3NPs was also evaluated by crystal violet staining and light microscopy examination. Then, the effect of sub-MICs concentrations of Sm2O3NPs on the proteolytic and hemolytic activities of P. aeruginosa was investigated. Finally, the effect of Sm2O3NPs on various types of motility including swarming, swimming, and twitching was studied. Our results showed that Sm2O3NPs significantly inhibited biofilm formation of P. aeruginosa by 49-61%. Additionally, sub-MICs concentrations of Sm2O3NPs effectively decreased virulence factors including pyocyanin (33-55%), protease (24-45%), and hemolytic activity (22-41%). Moreover, swarming, swimming, and twitching motility remarkably was reduced after exposure to the NPs. The findings of this work showed that Sm2O3NPs have a high potential in inhibiting QS-dependent virulence of P. aeruginosa, which could be considered for antibacterial chemotherapy after further characterization.

Ibuprofen involves with the reduced expression of pelD and pelF in pathogenic Pseudomonas aeruginosa strains.

Biofilm formation is an important factor in disease development by Pseudomonas aeruginosa. Similar to many bacterial species, biofilm formation in P. aeruginosa is regulated by the bacterial quorum sensing system. The pel genes are responsible for the synthesis of a glucose-rich polysaccharide that is associated with biofilm initiation and maturation. The antibiofilm potential of ibuprofen has been reported; however, the effect of the drug on the expression of the genes involved with biofilm formation has rarely been described. In this work, the effect of ibuprofen on the biofilm formation and expression of pelD and pelF genes among pathogenic P. aeruginosa strains was investigated. Multiple drug-resistant P. aeruginosa strains were treated with ibuprofen at ½ MIC concentration and their biofilm formation and expression of pelD and pelF genes was determined using the crystal violet and real-time PCR assays, respectively. The results showed that the ibuprofen at 1024 µg/mL significantly reduced biofilm formation of P. aeruginosa strains by 52-77%, compared with the controls. In addition, treating the bacteria with ibuprofen decreased the expression of pelD and pelF genes to 0.56 and 0.69 folds, respectively. We hypothesized that the attenuation of the pel genes could be associated with the reduction of bacterial QS autoinducers, which in turn reduced cellular c-di-GMP level. This work suggests that ibuprofen is a potent antibiofilm drug that could be used to enhance bacterial susceptibility to antimicrobials through the inhibition of biofilm formation.

Does ibuprofen affect the expression of alginate genes in pathogenic Pseudomonas aeruginosa strains?

Conversion to mucoid form is a crucial step in the pathogenesis of P. aeruginosa in burns and cystic fibrosis (CF) patients. Alginate is considered the major component of biofilm and is highly associated with the formation of mucoid biofilm in this species. Nonsteroid anti-inflammatory drugs (NSAIDs), including ibuprofen, have shown promising antibacterial and antibiofilm potential for bacterial pathogens. In this study, we aimed to evaluate the effect of ibuprofen on the expression of alginate synthetase (alg8), GDP-mannose dehydrogenase (algD), and alginate lyase (algL) genes in multiple drug-resistant (MDR) P. aeruginosa strains. The biofilm formation potential and the expression of alg8, algD, and algL among the bacteria treated with ibuprofen (at sub-inhibitory concentration) were investigated using the crystal violet staining and real-time PCR assays, respectively. The minimum inhibitory concentration of ibuprofen for the studied strains was determined 1024-2048 µg/mL. We observed that ibuprofen was able to reduce bacterial biofilm by 51-77%. Also, the expression of alg8, algD, and algL decreased by 32, 52, and 48%, respectively. The reduction of the genes responsible for alginate synthesis indicates promising antivirulece potential of ibuprofen to combat P. aeruginosa infection, especially in burns and CF patients. Our findings suggest that ibuprofen could be used to reduce the pathogenicity of P. aeruginosa that could be used in combination with antibiotics to treat drug-resistant infections.

Quantitative Characterization of the Chemical Space Governed by Human Carbonic Anhydrases and selenium-containing derivatives of solfonamides

Abstract Due to the fact that different isoforms of carbonic anhydrase play distinct physiological roles, their diseases/disorders involvement are different as well. Involvement in major disorders such as glaucoma, epilepsy, Alzheimer's disease, obesity and cancers, have turned carbonic anhydrase into a popular case study in the field of rational drug design. Since carbonic anhydrases are highly similar with regard to their structures, selective inhibition of different isoforms has been a significant challenge. By applying a proteochemometrics approach, herein the chemical interaction space governed by acyl selenoureido benzensulfonamides and human carbonic anhydrases is explored. To assess the validity, robustness and predictivity power of the proteochemometrics model, a diverse set of validation methods was used. The final model is shown to provide valuable structural information that can be considered for new selective inhibitors design. Using the supplied information and to show the applicability of the constructed model, new compounds were designed. Monitoring of selectivity ratios of new designs shows very promising results with regard to their selectivity for a specific isoform of carbonic anhydrase.

Reinforcing our defense or weakening the enemy? A comparative overview of defensive and offensive strategies developed to confront COVID-19.

Developing effective strategies to confront coronavirus disease 2019 (COVID-19) has become one of the greatest concerns of the scientific community. In addition to the vast number of global mortalities due to COVID-19, since its outbreak, almost every aspect of human lives has changed one way or another. In the present review, various defensive and offensive strategies developed to confront COVID-19 are illustrated. The Administration of immune-boosting micronutrients/agents, as well as the inhibition of the activity of incompetent gatekeepers, including some host cell receptors (e.g. ACE2) and proteases (e.g. TMPRSS2), are some efficient defensive strategies. Antibody/phage therapies and specifically vaccines also play a prominent role in the enhancement of host defense against COVID-19. Nanotechnology, however, can considerably weaken the virulence of SARS-CoV-2, utilizing fake cellular locks (compounds mimicking cell receptors) to block the viral keys (spike proteins). Generally, two strategies are developed to interfere with the binding of spike proteins to the host cell receptors, either utilizing fake cellular locks to block the viral keys or utilizing fake viral keys to block the cellular locks. Due to their evolutionary conserved nature, viral enzymes, including 3CLpro, PLpro, RdRp, and helicase are highly potential targets for drug repurposing strategy. Thus, various steps of viral replication/transcription can effectively be blocked by their inhibition, leading to the elimination of SARS-CoV-2. Moreover, RNA decoy and CRISPR technologies likely offer the best offensive strategies after viral entry into the host cells, inhibiting the viral replication/assembly in the infected cells and substantially reducing the quantity of viral progeny.

A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin.

The widespread antigenic changes lead to the emergence of a new type of coronavirus (CoV) called as severe acute respiratory syndrome (SARS)-CoV-2 that is immunologically different from the previous circulating species. Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. Hence, in this review, we presented an overview on the interaction of ACE-2 and furin with SP. As several kinds of CoVs, from various genera, have at their S1/S2 binding site a preserved site, we further surveyed the role of furin cleavage site (FCS) on the life cycle of the CoV. Furthermore, we discussed that the small molecular inhibitors can limit the interaction of ACE-2 and furin with SP and can be used as potential therapeutic platforms to combat the spreading CoV epidemic. Finally, some ongoing challenges and future prospects for the development of potential drugs to promote targeting specific activities of the CoV were reviewed. In conclusion, this review may pave the way for providing useful information about different compounds involved in improving the effectiveness of CoV vaccine or drugs with minimum toxicity against human health.Communicated by Ramaswamy H. Sarma.

Nanoporous iron oxide nanoparticle: hydrothermal fabrication, human serum albumin interaction and potential antibacterial effects.

Nanoporous iron oxide (Fe3O4) nanoparticles (NIONPs) have been widely used as promising agents in biomedical applications. Herein, the NIONPs were synthesized by one-step hydrothermal method and well-characterized by FESEM and TEM investigations. Afterwards, their interaction with human serum albumin (HSA) was studied using a wide range of biophysical approaches, including intrinsic and extrinsic fluorescence, far and near UV-CD, and UV-Vis spectroscopic methods as well as molecular docking investigation. Furthermore, the antibacterial effect of NIONPs was examined on the standard strains of the following pathogenic bacteria, Staphylococcus aureus (ATCC 25923), Klebsiella penumoniae (ATCC 33883), Enterococcus faecalis (ATCC 29212) and Pseudomonas aeruginosa (ATCC 27853). The results showed the feasible fabrication of spherical-shaped NIONPs with an average diameter of around 100 nm. Intrinsic fluorescence spectroscopy data depicted that NIONPs formed a complex with HSA by a KSV value of 0.092 (µg/ml)-1. Extrinsic fluorescence, near UV-CD and UV-vis spectroscopic methods revealed that NIONPs induced some changes on the quaternary structure of HSA, whereas Tm measurement and far UV-CD spectroscopy showed some slight changes on the secondary structure of HSA even in the presence of high concentration of NIONPs. Molecular docking study disclosed that Fe3O4 nanoclusters with varying morphologies and dimensions could interact with different residues on the surface of HSA molecules. In addition, antibacterial assays exhibited a significant inhibition on both Gram-positive and Gram-negative pathogenic bacteria. In conclusion, these NPs can be used as promising antibacterial agents.Communicated by Ramaswamy H. Sarma.

Inhibitory Potential of Acroptilon repens against Key Enzymes involved in Alzheimer and Diabetes, Phytochemical Profile, Radical Scavenging, and Antibacterial Activity.

Background: This study was devoted to assessing the inhibitory potential of acetone, methanol, and ethanol extracts of Acroptilon repens against disease-associated enzymes, as well as their antioxidant/antibacterial activity and phytochemical composition. Methods: Comparative assessment using various antioxidant evaluation methods, including ferric reducing antioxidant power, scavenging ability on 2,2-diphenyl-1-picrylhydrazyl radical and hydrogen peroxide, and reducing power, indicated that the acetone extract presented the highest antioxidant activity, due to its highest total antioxidant content. Results: The total phenolic content and total flavonoids content of these extracts were 3.44 ± 0.32 mg GAE/g DW and 2.09 ± 0.2 mg QE/g DW, respectively. The hydrodistillation essential oil from A. repens was analyzed by gas chromatography-mass spectroscopy, and 17 compounds were identified. All extracts showed good inhibitory activities against disease-related enzyme acetylcholinesterase and α-amylase, with the lowest IC50 for acetonic extract. Extracts of A. repens exhibited inhibiting activities against the Gram-positive bacteria, with the most effect of acetone extract. Conclusion: Our findings suggest A. repens as a promising source of natural antioxidant, antimicrobial, anti-cholinesterase and anti-amylase agents for the management of oxidative damage, and pharmaceutical, food, and cosmeceutical purposes.

Characteristics, dynamics and mechanisms of actions of some major stress-induced biomacromolecules; addressing Artemia as an excellent biological model.

Stress tolerance is one of the most prominent and interesting topics in biology since many macro- and micro-adaptations have evolved in resistant organisms that are worth studying. When it comes to confronting various environmental stressors, the extremophile Artemia is unrivaled in the animal kingdom. In the present review, the evolved molecular and cellular basis of stress tolerance in resistant biological systems are described, focusing on Artemia cyst as an excellent biological model. The main purpose of the review is to discuss how the structure and physicochemical characteristics of protective factors such as late embryogenesis abundant proteins (LEAPs), small heat shock proteins (sHSPs) and trehalose are related to their functions and by which mechanisms, they exert their functions. In addition, some metabolic depressors in Artemia encysted embryos are also mentioned, indirectly playing important roles in stress tolerance. Importantly, a great deal of attention is given to the LEAPs, exhibiting distinctive folding behaviors and mechanisms of actions. For instance, molecular shield function, chaperone-like activity, moonlighting property, sponging and snorkeling capabilities of the LEAPs are delineated here. Moreover, the molecular interplay between some of these factors is mentioned, leading to their synergistic effects. Interestingly, Artemia life cycle adapts to environmental conditions. Diapause is the defense mode of this life cycle, safeguarding Artemia encysted embryos against various environmental stressors. Communicated by Ramaswamy H. Sarma.

Exploring the Interaction of Cobalt Oxide Nanoparticles with Albumin, Leukemia Cancer Cells and Pathogenic Bacteria by Multispectroscopic, Docking, Cellular and Antibacterial Approaches.

AIM: The interaction of NPs with biological systems may reveal useful details about their pharmacodynamic, anticancer and antibacterial effects. METHODS: Herein, the interaction of as-synthesized Co3O4 NPs with HSA was explored by different kinds of fluorescence and CD spectroscopic methods, as well as molecular docking studies. Also, the anticancer effect of Co3O4 NPs against leukemia K562 cells was investigated by MTT, LDH, caspase, real-time PCR, ROS, cell cycle, and apoptosis assays. Afterwards, the antibacterial effects of Co3O4 NPs against three pathogenic bacteria were disclosed by antibacterial assays. RESULTS: Different characterization methods such as TEM, DLS, zeta potential and XRD studies proved that fabricated Co3O4 NPs by sol-gel method have a diameter of around 50 nm, hydrodynamic radius of 177 nm with a charge distribution of -33.04 mV and a well-defined crystalline phase. Intrinsic, extrinsic, and synchronous fluorescence as well as CD studies, respectively, showed that the HSA undergoes some fluorescence quenching, minor conformational changes, microenvironmental changes as well as no structural changes in the secondary structure, after interaction with Co3O4 NPs. Molecular docking results also verified that the spherical clusters with a dimension of 1.5 nm exhibit the most binding energy with HSA molecules. Anticancer assays demonstrated that Co3O4 NPs can selectively lead to the reduction of K562 cell viability through the cell membrane damage, activation of caspase-9, -8 and -3, elevation of Bax/Bcl-2 mRNA ratio, ROS production, cell cycle arrest, and apoptosis. Finally, antibacterial assays disclosed that Co3O4 NPs can stimulate a promising antibacterial effect against pathogenic bacteria. CONCLUSION: In general, these observations can provide useful information for the early stages of nanomaterial applications in therapeutic platforms.

Nanozyme-based sensing platforms for detection of toxic mercury ions: An alternative approach to conventional methods.

Mercury (Hg) is known as a poisonous heavy metal which stimulates a wide range of adverse effects on the human health. Therefore, development of some feasible, practical and highly sensitive platforms would be desirable in determination of Hg2+ level as low as nmol L-1 or pmol L-1. Different approaches such as ICP-MS, AAS/AES, and nanomaterial-based nanobiosensors have been manipulated for determination of Hg2+ level. However, these approaches suffer from expensive instruments and complicated sample preparation. Recently, nanozymes have been assembled to address some disadvantages of conventional methods in the detection of Hg2+. Along with the outstanding progress in nanotechnology and computational approaches, pronounced improvement has been attained in the field of nanozymes, recently. To accentuate these progresses, this review presents an overview on the different reports of Hg2+-induced toxicity on the different tissues followed by various conventional approaches validated for the determination of Hg2+ level. Afterwards, different types of nanozymes like AuNPs, PtNPs for quantitative detection of Hg2+ were surveyed. Finally, the current challenges and the future directions were explored to alleviate the limitation of nanozyme-based platforms with potential engineering in detection of heavy metals, namely Hg2+. The current overview can provide outstanding information to develop nano-based platforms for improvement of LOD and LOQ of analytical methods in sensitive detection of Hg2+ and other heavy metals.

The interaction of silica nanoparticles with catalase and human mesenchymal stem cells: biophysical, theoretical and cellular studies.

AIM: Nanoparticles (NPs) have been receiving potential interests in protein delivery and cell therapy. As a matter of fact, NPs may be used as great candidates in promoting cell therapy by catalase (CAT) delivery into high oxidative stress tissues. However, for using NPs like SiO2 as carriers, the interaction of NPs with proteins and mesenchymal stem cells (MSCs) should be explored in advance. METHODS: In the present study, the interaction of SiO2 NPs with CAT and human MSCs (hMSCs) was explored by various spectroscopic methods (fluorescence, circular dichroism (CD), UV-visible), molecular docking and dynamics studies, and cellular (MTT, cellular morphology, cellular uptake, lactate dehydrogenase, ROS, caspase-3, flow cytometry) assays. RESULTS: Fluorescence study displayed that both dynamic and static quenching mechanisms and hydrophobic interactions are involved in the spontaneous interaction of SiO2 NPs with CAT. CD spectra indicated that native structure of CAT remains stable after interaction with SiO2 NPs. UV-visible study also revealed that the kinetic parameters of CAT such as Km, Vmax, Kcat, and enzyme efficiency were not changed after the addition of SiO2 NPs. Molecular docking and dynamics studies showed that Si and SiO2 clusters interact with hydrophobic residues of CAT and SiO2 cluster causes minor changes in the CAT structure at a total simulation time of 200 ps. Cellular assays depicted that SiO2 NPs induce significant cell mortality, change in cellular morphology, cellular internalization, ROS elevation, and apoptosis in hMSCs at higher concentration than 100 µg/mL (170 µM). CONCLUSION: The current results suggest that low concentrations of SiO2 NPs induce no substantial change or mortality against CAT and hMSCs, and potentially useful carriers in CAT delivery to hMSC.

The effect of aluminum oxide on red blood cell integrity and hemoglobin structure at nanoscale.

Herein, we explored the interaction of Al2O3 NPs with RBCs and Hb to determine the effect of Al2O3 NPs on hemolytic activity and Hb denaturation. The percentage of hemolysis of extracts and direct contact assays triggered by Al2O3 NPs was calculated by determining supernatant Hb concentration at 540 nm. Far-UV CD and Trp/ANS/acrylamide fluorescence spectroscopic methods were used to determine the structural changes of Hb upon interaction with Al2O3 NPs. Theoretical studies were carried out to display the residues involved in the binding site of Hb with Al2O3 nanocluster as well as the structural changes of Hb after interaction. The results showed that the percentage of hemolysis of extract and direct contact assays induced by Al2O3 NPs were 1.16 and 0.46, respectively. Fluorescence spectroscopy revealed that Al2O3 NPs alter the quaternary structure of the protein; however, CD spectroscopy indicated that the secondary structure of Hb remains almost unchanged. Theoretical study displayed that Al2O3 nanocluster interacts with different residues of protein, and Hb tends to be destabilized at the binding site with nanocluster. This study may be significant in exploring the toxicity profile of Al2O3 NPs for their in vivo implementations.

New insights into the selective inhibition of the ß-carbonic anhydrases of pathogenic bacteria Burkholderia pseudomallei and Francisella tularensis: a proteochemometrics study.

Nowadays, antibiotic resistance has turned into one of the most important worldwide health problems. Biological end point of critical enzymes induced by potent inhibitors is recently being considered as a highly effective and popular strategy to defeat antibiotic-resistant pathogens. For instance, the simple but critical ß-carbonic anhydrase has recently been in the center of attention for anti-pathogen drug discoveries. However, no ß-carbonic anhydrase selective inhibitor has yet been developed. Available ß-carbonic anhydrase inhibitors are also highly potent with regard to human carbonic anhydrases, leading to severe inevitable side effects in case of usage. Therefore, developing novel inhibitors with high selectivity against pathogenic ß-carbonic anhydrases is of great essence. Herein, for the first time, we have conducted a proteochemometric study to explore the structural and the chemical aspects of the interactions governed by bacterial ß-carbonic anhydrases and their inhibitors. We have found valuable information which can lead to designing novel inhibitors with better selectivity for bacterial ß-carbonic anhydrases.

Biophysical, molecular dynamics and cellular studies on the interaction of nickel oxide nanoparticles with tau proteins and neuron-like cells.

Nickel oxide nanoparticles (NiO NPs) have been used in the biological and medical sciences. However, their toxic effects against biological systems such as nervous system have not been well studied. Therefore, the adverse effect of NiO NPs on tau structure was investigated by fluorescence and CD spectroscopic methods as well as TEM study. Also, molecular dynamic study was run to extend the experimental data. Cytotoxic activity of NiO NPs against SH-SY5Y cell was determined by trypan blue exclusion, cell morphology, ROS, and apoptosis assays. ANS, Nile red, ThT assays and electron micrograph investigation revealed that NiO NPs can increase the hydrophobic portions of tau and induce the formation of amorphous tau aggregates. Far and near CD spectroscopic methods revealed that NiO NPs can change the secondary and tertiary structure of tau, respectively. Theoretical studies depicted that NiO NPs lead to folding of tau structure. In the cellular view, NiO NPs induced significant mortality and morphological effects against SH-SY5Y cells. NiO NPs also provided a significant impact on generating intracellular ROS and apoptosis induction. This study determined that NiO NPs could mediate the induction of some undesired effects on the nervous system.

Probing the chemical interaction space governed by 4-aminosubstituted benzenesulfonamides and carbonic anhydrase isoforms.

Isoform diversity, critical physiological roles and involvement in major diseases/disorders such as glaucoma, epilepsy, Alzheimer's disease, obesity, and cancers have made carbonic anhydrase (CA), one of the most interesting case studies in the field of computer aided drug design. Since applying non-selective inhibitors can result in major side effects, there have been considerable efforts so far to achieve selective inhibitors for different isoforms of CA. Using proteochemometrics approach, the chemical interaction space governed by a group of 4-amino-substituted benzenesulfonamides and human CAs has been explored in the present study. Several validation methods have been utilized to assess the validity, robustness and predictivity power of the proposed proteochemometric model. Our model has offered major structural information that can be applied to design new selective inhibitors for distinct isoforms of CA. To prove the applicability of the proposed model, new compounds have been designed based on the offered discriminative structural features.

An inter-subunit disulfide bond of artemin acts as a redox switch for its chaperone-like activity.

Encysted embryos of Artemia are among the most stress-resistant eukaryotes partly due to the massive amount of a cysteine-rich protein termed artemin. High number of cysteine residues in artemin and their intramolecular spatial positions motivated us to investigate the role of the cysteine residues in the chaperone-like activity of artemin. According to the result of Ellman's assay, there are nine free thiols (seven buried and two exposed) and one disulfide bond per monomer of artemin. Subsequent theoretical analysis of the predicted 3D structure of artemin confirmed the data obtained by the spectroscopic study. Native and reduced/modified forms of artemin were also compared with respect to their efficiency in chaperoning activity, tertiary structure, and stability. Since the alkylation and reduction of artemin diminished its chaperone activity, it appears that its chaperoning potential depends on the formation of intermolecular disulfide bond and the presence of cysteine residues. Comparative fluorescence studies on the structure and stability of the native and reduced protein revealed some differences between them. Due to the redox-dependent functional switching of artemin from the less to more active form, it can be finally suggested as a redox-dependent chaperone.

Probing the interaction of zero valent iron nanoparticles with blood system by biophysical, docking, cellular, and molecular studies.

Human exposure to nanoparticles (NPs) is inevitable as NPs become more widely applied and, as a result, nanotoxicology study is now gaining attention. Herein, the interaction of zero valent iron NPs (ZVFe-NPs) with human hemoglobin (Hb) was evaluated using a variety of techniques including fluorescence spectroscopy, far circular dichroism (CD) spectroscopy as well as docking study. Also, the cytotoxicity of ZVFe-NPs on the human lymphocyte cell line as a model of blood system cell line was investigated by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), acridine orange/ethidium bromide (AO/EB) staining, flow cytometry, and real-time PCR assays. Fluorescence studies revealed that ZVFe-NPs bind to Hb via hydrogen bonds and induced conformational changes of Hb in a static denaturation mechanism. CD experiment showed that Hb retained its native structure in the presence of ZVFe-NP. Molecular docking study also demonstrated that polar residues of Hb provide convenient medium to establish hydrogen bonds with water molecules on ZVFe-NP surface. Likewise, it was also revealed that ZVFe-NPs impaired the viability of lymphocyte cells through apoptotic pathway. For NPs to move into the clinical area, it is crucial that nanotoxicology research provide pivotal information about the adverse effect of NPs against biological systems.