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1.
Nanotechnology ; 34(31)2023 May 19.
Article in English | MEDLINE | ID: mdl-37141862

ABSTRACT

Titanium dioxide nanotubes (TNT) are widely researched materials for the photocatalytic generation of free radicals, which are useful in wastewater treatment. We aimed to prepare Mo-doped TNT sheets, covered with a cellulose membrane to avoid TNT surface inactivation by protein adsorption. We studied the susceptibility of serum albumin (SA) bound to different molar ratios of palmitic acid (PA) to denaturation and fibrillation by this system, which is meant to mimic oxidative stress conditions such as non-alcoholic fatty liver disease. The results demonstrated that cellulose membrane-covered TNT successfully oxidized the SA, identified by structural changes to the protein. Increasing the molar ratio of PA to protein-enhanced thiol group oxidation while protecting the protein against structural changes. Finally, we propose that in this photocatalyzed oxidation system, the protein is oxidized by a non-adsorptive mechanism mediated by H2O2. Therefore, we suggest that this system could be used as a sustained oxidation system to oxidize biomolecules as well as potentially in wastewater treatment.


Subject(s)
Hydrogen Peroxide , Nanotubes , Oxidation-Reduction , Oxidative Stress , Nanotubes/chemistry , Titanium/chemistry
2.
Molecules ; 26(24)2021 Dec 17.
Article in English | MEDLINE | ID: mdl-34946740

ABSTRACT

Oxidative stress is the leading player in the onset and development of various diseases. The Keap1-Nrf2 pathway is a pivotal antioxidant system that preserves the cells' redox balance. It decreases inflammation in which the nuclear trans-localization of Nrf2 as a transcription factor promotes various antioxidant responses in cells. Through some other directions and regulatory proteins, this pathway plays a fundamental role in preventing several diseases and reducing their complications. Regulation of the Nrf2 pathway occurs on transcriptional and post-transcriptional levels, and these regulations play a significant role in its activity. There is a subtle correlation between the Nrf2 pathway and the pivotal signaling pathways, including PI3 kinase/AKT/mTOR, NF-κB and HIF-1 factors. This demonstrates its role in the development of various diseases. Curcumin is a yellow polyphenolic compound from Curcuma longa with multiple bioactivities, including antioxidant, anti-inflammatory, anti-tumor, and anti-viral activities. Since hyperglycemia and increased reactive oxygen species (ROS) are the leading causes of common diabetic complications, reducing the generation of ROS can be a fundamental approach to dealing with these complications. Curcumin can be considered a potential treatment option by creating an efficient therapeutic to counteract ROS and reduce its detrimental effects. This review discusses Nrf2 pathway regulation at different levels and its correlation with other important pathways and proteins in the cell involved in the progression of diabetic complications and targeting these pathways by curcumin.


Subject(s)
Antioxidants/therapeutic use , Curcumin/therapeutic use , Diabetes Complications , Hypoxia , Signal Transduction/drug effects , Animals , Diabetes Complications/drug therapy , Diabetes Complications/metabolism , Humans , Hypoxia/drug therapy , Hypoxia/etiology , Hypoxia/metabolism
3.
Biochim Biophys Acta ; 1854(10 Pt A): 1307-16, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26004089

ABSTRACT

In this project, we studied some physicochemical properties of two different globin domains of the polymeric hemoglobin of the brine shrimp Artemia salina and compared them with those of the native molecule. Two domains (AsHbC1D1 and AsHbC1D5) were cloned and expressed in BL21(DE3)pLysS strain of Escherichia coli. The recombinant proteins as well as the native hemoglobin (AfHb) were purified from bacteria and frozen Artemia, respectively by standard chromatographic methods and assessed by SDS-PAGE. The heme environment of these proteins was studied by optical spectroscopy and ligand-binding kinetics (e.g. CO association and O2 binding affinity) were measured for the two recombinant proteins and the native hemoglobin. This indicates that the CO association rate for AsHbC1D1 is higher than that of AsHbC1D5 and AfHb, while the calculated P50 value for AsHbC1D1 is lower than that of AsHbC1D5 and AfHb. The geminate and bimolecular rebinding parameters indicate a significant difference between both domains. Moreover, EPR results showed that the heme pocket in AfHb is in a more closed conformation than the heme pocket in myoglobin. Finally, the reduction potential of -0.13V versus the standard hydrogen electrode was determined for AfHb by direct electrochemical measurements. It is about 0.06V higher than the potential of the single domain AsHbC1D5. This work shows that each domain in the hemoglobin of Artemia has different characteristics of ligand binding.


Subject(s)
Artemia/chemistry , Arthropod Proteins/chemistry , Carbon Monoxide/chemistry , Heme/chemistry , Hemoglobins/chemistry , Oxygen/chemistry , Amino Acid Sequence , Animals , Artemia/metabolism , Arthropod Proteins/genetics , Escherichia coli/genetics , Escherichia coli/metabolism , Gene Expression , Hemoglobins/genetics , Kinetics , Models, Molecular , Molecular Sequence Data , Oxidation-Reduction , Polymerization , Protein Binding , Protein Structure, Secondary , Protein Structure, Tertiary , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Sequence Alignment , Thermodynamics
4.
Sci Rep ; 14(1): 1716, 2024 01 19.
Article in English | MEDLINE | ID: mdl-38242928

ABSTRACT

Bioactive peptide-based drugs have gained exceeding attention as promising treatments for infectious and oxidative-stress-related diseases, are exacerbated by the advent and spread of various multidrug-resistant bacteria and industrial lifestyles. Fish skin mucus has been recognized as a potential source of bioactive peptides, providing the first line of fish defense against invading pathogens which are targeted here to be explored as a new source of biopharmaceutics. Peptide fractions were isolated from the epidermal exudates of Caspian sand goby, Neogobius fluviatilis pallasi, by solid-phase extraction (SPE), ultrafiltration, and reversed-phase chromatography. The resulting fractions were characterized for their antibacterial and antioxidant properties, and results showed that the molecular weight fraction < 5 kDa represented the highest (p < 0.05) bacterial inhibition activity against Staphylococcus aureus and Bacillus subtilis as well as scavenging activity against DPPH and ABTS radicals. Overall, these results introduce the epidermal mucus of Caspian sand goby as a valuable source of bioactive compounds that can be considered new and efficient biopharmaceutics.


Subject(s)
Perciformes , Ultrafiltration , Animals , Chromatography, Reverse-Phase , Epidermis , Antioxidants/chemistry , Peptides/chemistry , Anti-Bacterial Agents/chemistry
5.
Int J Biol Macromol ; 249: 126036, 2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37516225

ABSTRACT

Here we present a novel machine-learning approach to predict protein aggregation propensity (PAP) which is a key factor in the formation of amyloid fibrils based on logistic regression (LR). Amyloid fibrils are associated with various neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD), which are caused by oxidative stress and impaired protein homeostasis. Accordingly, the paper uses a dataset of hexapeptides with known aggregation tendencies and eight physiochemical features to train and test the LR model. Also, it evaluates the performance of the LR model using F-measure and Matthews correlation coefficient (MCC) as metrics and compares it with other existing methods. Moreover, it investigates the effect of combining sequence and feature information in the prediction. In conclusion, the LR model with sequence and feature information achieves high F-measure (0.841) and MCC (0.6692), outperforming other methods and demonstrating its efficiency and reliability for PAP prediction. In addition, the overall performance of the concluded method was higher than the other known servers, for instance, Aggrescan, Metamyl, Foldamyloid, and PASTA 2.0. The LR model can be accessed at: https://github.com/KatherineEshari/Protein-aggregation-prediction.


Subject(s)
Amyloid , Protein Aggregates , Logistic Models , Reproducibility of Results , Machine Learning
6.
Appl Biochem Biotechnol ; 195(5): 3047-3066, 2023 May.
Article in English | MEDLINE | ID: mdl-36508074

ABSTRACT

In this study, the chitin of adult Mediterranean flour moth (Ephestia kuheniella) (Cht) was extracted and then converted to chitosan by deacetylation process to achieve the chitosan derived from E. kuheniella (Chsfm). The new chitosan-based scaffold was produced using the polyvinyl alcohol (PVA) co-electrospinning technique. The degree of deacetylation was obtained using the distillation-titration and Fourier transform infrared spectroscopy. The surface morphology and crystallinity index of Chsfm were observed using scanning electron microscopy and X-ray diffraction analysis, respectively, and compared with the commercial chitosan (Chsc). Thermogravimetric analysis was used to estimate two chitosans' water content and thermal stability. The average molecular mass analysis was performed using viscometry. Moreover, the minimum inhibitory concentration and DPPH assay were used to study the antimicrobial activity and antioxidant potential of the Chsfm, respectively. Accordingly, Chsfm was smoother with fewer pores and flakes than Chsc, and its crystallinity index was higher than Chsc. The water content and thermal stability were lower and similar for Chsfm compared to Chsc. The average molecular mass of Chsfm was ~ 5.8 kDa, making it classified as low molecular weight chitosan. The antimicrobial activity of Chsfm against a representative Gram-negative bacteria; E. coli resulted to be the same as Chsc. However, less effective than Chsc against a representative Gram-positive bacteria is S. aureus. The Chsfm/PVA ratio scaffold was optimized at 30:70 to fabricate a uniform nanofiber scaffold.


Subject(s)
Anti-Infective Agents , Chitosan , Moths , Animals , Chitosan/pharmacology , Chitosan/chemistry , Escherichia coli , Staphylococcus aureus , Anti-Infective Agents/pharmacology , Water/chemistry , Polyvinyl Alcohol/chemistry , Spectroscopy, Fourier Transform Infrared
7.
J Mol Graph Model ; 122: 108495, 2023 07.
Article in English | MEDLINE | ID: mdl-37116337

ABSTRACT

Exploring allosteric inhibition and the discovery of new inhibitor binding sites are important studies in protein regulation mechanisms and drug discovery. Structural and network-based analyses of trajectories resulting from molecular dynamics (MD) simulations have been developed to discover protein dynamics, landscape, functions, and allosteric regions. Here, an experimentally suggested non-competitive inhibitor, xanthene-11v, was considered to explore its allosteric inhibition mechanism in α-glucosidase MAL12. Comparative structural and network analyses were applied to eight 250 ns independent MD simulations, four of which were performed in the free state and four of which were performed in ligand-bound forms. Projected two-dimensional free energy landscapes (FEL) were constructed from the probabilistic distribution of conformations along the first two principal components. The post-simulation analyses of the coordinates, side-chain torsion angles, non-covalent interaction networks, network communities, and their centralities were performed on α-glucosidase conformations and the intermediate sub-states. Important communities of residues have been found that connect the allosteric site to the active site. Some of these residues like Thr307, Arg312, TYR344, ILE345, Phe357, Asp406, Val407, Asp408, and Leu436 are the key messengers in the transition pathway between allosteric and active sites. Evaluating the probability distribution of distances between gate residues including Val407 in one community and Phe158, and Pro65 in another community depicted the closure of this gate due to the inhibitor binding. Six macro states of protein were deduced from the topology of FEL and analysis of conformational preference of free and ligand-bound systems to these macro states shows a combination of lock-and-key, conformational selection, and induced fit mechanisms are effective in ligand binding. All these results reveal structural states, allosteric mechanisms, and key players in the inhibition pathway of α-glucosidase by xanthene-11v.


Subject(s)
Proteins , alpha-Glucosidases , Allosteric Regulation , alpha-Glucosidases/metabolism , Ligands , Molecular Dynamics Simulation , Proteins/chemistry , Proteins/metabolism
8.
Antioxidants (Basel) ; 12(3)2023 Mar 16.
Article in English | MEDLINE | ID: mdl-36978983

ABSTRACT

Oxidative stresses (OSs) are considered a pivotal factor in creating various pathophysiological conditions. Cells have been able to move forward by modulating numerous signaling pathways to moderate the defects of these stresses during their evolution. The company of Kelch-like ECH-associated protein 1 (Keap1) as a molecular sensing element of the oxidative and electrophilic stress and nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) as a master transcriptional regulator of the antioxidant response makes a master cytoprotective antioxidant pathway known as the Keap1/Nrf2 pathway. This pathway is considered a dual-edged sword with beneficial features for both normal and cancer cells by regulating the gene expression of the array of endogenous antioxidant enzymes. Heme oxygenase-1 (HO-1), a critical enzyme in toxic heme removal, is one of the clear state indicators for the duality of this pathway. Therefore, Nrf2/HO-1 axis targeting is known as a novel strategy for cancer treatment. In this review, the molecular mechanism of action of natural antioxidants on lung cancer cells has been investigated by relying on the Nrf2/HO-1 axis.

9.
Daru ; 20(1): 72, 2012 Oct 31.
Article in English | MEDLINE | ID: mdl-23351780

ABSTRACT

BACKGROUND AND PURPOSE OF THE STUDY: H. pylori infection is an important etiologic impetus usually leading to gastric disease and urease enzyme is the most crucial role is to protect the bacteria in the acidic environment of the stomach. Then urease inhibitors would increase sensitivity of the bacteria in acidic medium. METHODS: 137 Iranian traditional medicinal plants were examined against Jack bean urease activity by Berthelot reaction. Each herb was extracted using 50% aqueous methanol. The more effective extracts were further tested and their IC50 values were determined. RESULTS: 37 plants out of the 137 crude extracts revealed strong urease inhibitory activity (more than 70% inhibition against urease activity at 10 mg/ml concentration). Nine of the whole studied plants crude extracts were found as the most effective with IC50 values less than 500 µg/ml including; Rheum ribes, Sambucus ebulus, Pistachia lentiscus, Myrtus communis, Areca catechu, Citrus aurantifolia, Myristica fragrans, Cinnamomum zeylanicum and Nicotiana tabacum. CONCLUSIONS: The most potent urease inhibitory was observed for Sambucus ebulus and Rheum ribes extracts with IC50 values of 57 and 92 µg/ml, respectively.

10.
Sci Rep ; 12(1): 18332, 2022 10 31.
Article in English | MEDLINE | ID: mdl-36316461

ABSTRACT

The relationship between diabetes mellitus (DM) and Alzheimer's disease (AD) is so strong that scientists called it "brain diabetes". According to several studies, the critical factor in this relationship is brain insulin resistance. Due to the rapid global spread of both diseases, overcoming this cross-talk has a significant impact on societies. Long non-coding RNAs (lncRNAs), on the other hand, have a substantial impact on complex diseases due to their ability to influence gene expression via a variety of mechanisms. Consequently, the regulation of lncRNA expression in chronic diseases permits the development of innovative therapeutic techniques. However, developing a new drug requires considerable time and money. Recently repurposing existing drugs has gained popularity due to the use of low-risk compounds, which may result in cost and time savings. in this study, we identified drug repurposing candidates capable of controlling the expression of common lncRNAs in the cross-talk between DM and AD. We also utilized drugs that interfered with this cross-talk. To do this, high degree common lncRNAs were extracted from microRNA-lncRNA bipartite network. The drugs that interact with the specified lncRNAs were then collected from multiple data sources. These drugs, referred to as set D, were classified in to positive (D+) and negative (D-) groups based on their effects on the expression of the interacting lncRNAs. A feature selection algorithm was used to select six important features for D. Using a random forest classifier, these features were capable of classifying D+ and D- with an accuracy of 82.5%. Finally, the same six features were extracted for the most recently Food and Drug Administration (FDA) approved drugs in order to identify those with the highest likelihood of belonging to D+ or D-. The most significant FDA-approved positive drugs, chromium nicotinate and tapentadol, were presented as repurposing candidates, while cefepime and dihydro-alpha-ergocryptine were recommended as significant adverse drugs. Moreover, two natural compounds, curcumin and quercetin, were recommended to prevent this cross-talk. According to the previous studies, less attention has been paid to the role of lncRNAs in this cross-talk. Our research not only did identify important lncRNAs, but it also suggested potential repurposed drugs to control them.


Subject(s)
Alzheimer Disease , Diabetes Mellitus , MicroRNAs , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Pharmaceutical Preparations , MicroRNAs/genetics , Diabetes Mellitus/drug therapy , Diabetes Mellitus/genetics
11.
Front Aging Neurosci ; 14: 955461, 2022.
Article in English | MEDLINE | ID: mdl-36092798

ABSTRACT

Background: Recent research has investigated the connection between Diabetes Mellitus (DM) and Alzheimer's Disease (AD). Insulin resistance plays a crucial role in this interaction. Studies have focused on dysregulated proteins to disrupt this connection. Non-coding RNAs (ncRNAs), on the other hand, play an important role in the development of many diseases. They encode the majority of the human genome and regulate gene expression through a variety of mechanisms. Consequently, identifying significant ncRNAs and utilizing them as biomarkers could facilitate the early detection of this cross-talk. On the other hand, computational-based methods may help to understand the possible relationships between different molecules and conduct future wet laboratory experiments. Materials and methods: In this study, we retrieved Genome-Wide Association Study (GWAS, 2008) results from the United Kingdom Biobank database using the keywords "Alzheimer's" and "Diabetes Mellitus." After excluding low confidence variants, statistical analysis was performed, and adjusted p-values were determined. Using the Linkage Disequilibrium method, 127 significant shared Single Nucleotide Polymorphism (SNP) were chosen and the SNP-SNP interaction network was built. From this network, dense subgraphs were extracted as signatures. By mapping each signature to the reference genome, genes associated with the selected SNPs were retrieved. Then, protein-microRNA (miRNA) and miRNA-long non-coding RNA (lncRNA) bipartite networks were built and significant ncRNAs were extracted. After the validation process, by applying the scoring function, the final protein-miRNA-lncRNA tripartite network was constructed, and significant miRNAs and lncRNAs were identified. Results: Hsa-miR-199a-5p, hsa-miR-199b-5p, hsa-miR-423-5p, and hsa-miR-3184-5p, the four most significant miRNAs, as well as NEAT1, XIST, and KCNQ1OT1, the three most important lncRNAs, and their interacting proteins in the final tripartite network, have been proposed as new candidate biomarkers in the cross-talk between DM and AD. The literature review also validates the obtained ncRNAs. In addition, miRNA/lncRNA pairs; hsa-miR-124-3p/KCNQ1OT1, hsa-miR-124-3p/NEAT1, and hsa-miR-124-3p/XIST, all expressed in the brain, and their interacting proteins in our final network are suggested for future research investigation. Conclusion: This study identified 127 shared SNPs, 7 proteins, 15 miRNAs, and 11 lncRNAs involved in the cross-talk between DM and AD. Different network analysis and scoring function suggested the most significant miRNAs and lncRNAs as potential candidate biomarkers for wet laboratory experiments. Considering these candidate biomarkers may help in the early detection of DM and AD co-occurrence.

12.
Biomedicines ; 10(10)2022 Oct 21.
Article in English | MEDLINE | ID: mdl-36289931

ABSTRACT

Reactive oxygen species (ROS) are identified to control the expression and activity of various essential signaling intermediates involved in cellular proliferation, apoptosis, and differentiation. Indeed, ROS represents a double-edged sword in supporting cell survival and death. Many common pathological processes, including various cancer types and neurodegenerative diseases, are inflammation and oxidative stress triggers, or even initiate them. Keap1-Nrf2 is a master antioxidant pathway in cytoprotective mechanisms through Nrf2 target gene expression. Activation of the Nfr2 pathway benefits cells in the early stages and reduces the level of ROS. In contrast, hyperactivation of Keap1-Nrf2 creates a context that supports the survival of both healthy and cancerous cells, defending them against oxidative stress, chemotherapeutic drugs, and radiotherapy. Considering the dual role of Nrf2 in suppressing or expanding cancer cells, determining its inhibitory/stimulatory position and targeting can represent an impressive role in cancer treatment. This review focused on Nrf2 modulators and their roles in sensitizing breast cancer cells to chemo/radiotherapy agents.

13.
Rev Neurosci ; 33(7): 803-817, 2022 10 26.
Article in English | MEDLINE | ID: mdl-35363449

ABSTRACT

Serum albumin (SA) exists in relatively high concentrations, in close contact with most cells. However, in the adult brain, except for cerebrospinal fluid (CSF), SA concentration is relatively low. It is mainly produced in the liver to serve as the main protein of the blood plasma. In the plasma, it functions as a carrier, chaperon, antioxidant, source of amino acids, osmoregulator, etc. As a carrier, it facilitates the stable presence and transport of the hydrophobic and hydrophilic molecules, including free fatty acids, steroid hormones, medicines, and metal ions. As a chaperon, SA binds to and protects other proteins. As an antioxidant, thanks to a free sulfhydryl group (-SH), albumin is responsible for most antioxidant properties of plasma. These functions qualify SA as a major player in, and a mirror of, overall health status, aging, and neurodegeneration. The low concentration of SA is associated with cognitive deterioration in the elderly and negative prognosis in multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). SA has been shown to be structurally modified in neurological conditions such as Alzheimer's disease (AD). During blood-brain barrier damage albumin enters the brain tissue and could trigger epilepsy and neurodegeneration. SA is able to bind to the precursor agent of the AD, amyloid-beta (Aß), preventing its toxic effects in the periphery, and is being tested for treating this disease. SA therapy may also be effective in brain rejuvenation. In the current review, we will bring forward the prominent properties and roles of SA in neurodegeneration.


Subject(s)
Alzheimer Disease , Serum Albumin, Human , Adult , Aged , Alzheimer Disease/metabolism , Amino Acids , Amyloid beta-Peptides/metabolism , Antioxidants , Fatty Acids, Nonesterified , Hormones , Humans , Serum Albumin , Serum Albumin, Human/metabolism
14.
Materials (Basel) ; 15(24)2022 Dec 08.
Article in English | MEDLINE | ID: mdl-36556567

ABSTRACT

In this study, L-arginine (Arg) modified magnetite (Fe3O4) nanoparticles (RMNPs) were firstly synthesized through a one-step co-precipitation method, and then these aminated nanoparticles (NPs) were, again, coated by pre-oxidized dextran (Dext), in which aldehyde groups (DextCHO) have been introduced on the polymer chain successfully via a strong chemical linkage. Arg, an amino acid, acts as a mediator to link the Dext to a magnetic core. The as-synthesized Arg-modified and Dext-coated arginine modified Fe3O4 NPs were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transformation infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and vibrating sample magnetometer (VSM). Both synthesized samples, XRD pattern and FT-IR spectra proved that the core is magnetite. FT-IR confirmed that the chemical bonds of Arg and Dext both exist in the samples. SEM images showed that the NPs are spherical and have an acceptable distribution size, and the VSM analysis indicated the superparamagnetic behavior of samples. The saturation magnetization was decreased after Dext coating, which confirms successive coating RMNPs with Text. In addition, the TGA analysis demonstrated that the prepared magnetic nanocomposites underwent various weight loss levels, which admitted the modification of magnetic cores with Arg and further coating with Dext.

15.
J Phys Chem B ; 126(8): 1640-1654, 2022 03 03.
Article in English | MEDLINE | ID: mdl-35090112

ABSTRACT

Transthyretin (TTR) aggregation via misfolding of a mutant or wild-type protein leads to systemic or partial amyloidosis (ATTR). Here, we utilized variable biophysical assays to characterize two distinct aggregation pathways for mTTR (a synthesized monomer TTR incapable of association into a tetramer) at pH 4.3 and also pH 7.4 with agitation, referred to as mTTR aggregation and fibrillation, respectively. The findings suggest that early-stage conformational changes termed monomer activation here determine the aggregation pathway, resulting in developing either amorphous aggregates or well-organized fibrils. Less packed partially unfolded monomers consisting of more non-regular secondary structures that were rapidly produced via a mildly acidic condition form amorphous aggregates. Meanwhile, more hydrophobic and packed monomers consisting of rearranged ß sheets and increased helical content developed well-organized fibrils. Conjugating superparamagnetic iron oxide nanoparticles (SPIONs) with leucine and glutamine (L-SPIONs and G-SPIONs in order) via a trimethoxysilane linker provided the chance to study the effect of hydrophobic/hydrophilic surfaces on mTTR aggregation. The results indicated a powerful inhibitory effect of hydrophobic L-SPIONs on both mTTR aggregation and fibrillation. Monomer depletion was introduced as the governing mechanism for inhibiting mTTR aggregation, while a chaperone-like property of L-SPIONs by maintaining an mTTR native structure and adsorbing oligomers suppressed the progression of further fibril formation.


Subject(s)
Amino Acids , Amyloid , Amyloid/chemistry , Magnetic Iron Oxide Nanoparticles , Molecular Chaperones/metabolism , Protein Conformation, beta-Strand , Protein Structure, Secondary
16.
Sci Total Environ ; 810: 152291, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-34902406

ABSTRACT

The health effects of ambient air particulate matter with a diameter of ≤2.5 µm (PM2.5) on the central nervous system are well known and the induced oxidative stress has been shown as their main neuropathologic outcome. Ambient air PM2.5 sampling methods mostly use air sampler systems that collect PM2.5 on filters, which is followed by a PM2.5 extraction approach. Inefficient extraction may lead to compositional bias and unreal interpretation of the results. This study aimed to compare our proposed multi-solvent extraction (MSE) approach for PM2.5 extraction with a conventional aqueous extraction (AqE) method using the analysis of oxidative effects and cytotoxicity in the human neuroblastoma SH-SY5Y cell line. Ambient PM2.5 samples were collected from an urban traffic location in Tehran city, the capital of Iran, using a high-volume sampler. The developed MSE method was proved to have superior advantages over the AqE method including an increased extraction efficiency (as much as 96 against 48% for PMms and PMaq, respectively), and decreased artifacts and compositional biases. Ambient PM2.5, besides PMms and PMaq were analyzed for water-soluble ions, metals, and major elements. Dithiothreitol, ascorbic acid, lipid peroxidation, and cell viability assays on SH-SY5Y cells represented the significantly higher oxidative potential for PMms compared to PMaq. The increased cytotoxicity may occur because of the increased oxidative potential of PMms and possibly is associated with higher efficiency of the MSE over the AqE method for removal of total redox-active PM components.


Subject(s)
Air Pollutants , Air Pollutants/analysis , Air Pollutants/toxicity , Environmental Monitoring , Humans , Iran , Oxidation-Reduction , Oxidative Stress , Particulate Matter/analysis , Particulate Matter/toxicity , Solvents
17.
Neurochem Res ; 35(4): 548-58, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19946744

ABSTRACT

Protein glycation has been implicated to play an important role in the pathogenesis of Alzheimer's disease and other neurological disorders. Glycation induces extensive change in the structure of proteins and leads to the formation of cross beta-structures which are detected by the receptor of AGE. Activation of these receptors by glycated proteins transduces the signaling pathways which contribute to neuronal malfunctions and death. Glycated proteins can induce activation of microglia, which exacerbate the pathology of Alzheimer's disease by causing chronic inflammation. Compounds which can decelerate glycation or prevent the structural change of proteins during glycation should be of therapeutic interest. In this study the effect of nicotine on protein glycation and structural alterations of the glycated protein were investigated. Bovine serum albumin, as a model protein, was glycated by glucose in the presence or absence of nicotine and structural changes in the protein together with the effect of glycated proteins on the activation of microglia via receptor of AGE were studied. Nicotine not only could not prevent glycation, but even increased protein glycation. However, proteins glycated in the presence of nicotine did not form beta-structures. In the absence of this secondary structure glycated proteins cannot bind to the receptor of AGE on microglia. Here we showed that glycated proteins prepared in the presence of nicotine could not activate microglial cells.


Subject(s)
Glucose/metabolism , Microglia/drug effects , Nerve Tissue Proteins/metabolism , Nicotine/pharmacology , Animals , Animals, Newborn , Circular Dichroism , Microglia/cytology , Microglia/metabolism , Nerve Tissue Proteins/chemistry , Protein Structure, Secondary , Rats , Rats, Wistar , Receptor for Advanced Glycation End Products , Receptors, Immunologic/metabolism
18.
Talanta ; 211: 120722, 2020 May 01.
Article in English | MEDLINE | ID: mdl-32070572

ABSTRACT

Herein, an electrochemical label-free biosensor designed for the detection of glycated albumin (GA) using reduced graphene oxide/Au nanoparticles (RGO/AuNPs) modified by anti-GA aptamer. For fast and simple modification of the electrode, the aptamer chain was thiolated. Transition electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) techniques were used to the characterization of synthesized materials. Structural analysis of nanomaterials shows that graphene sheets were synthesized very fine by average thickness of 2.5 nm and Au nanoparticles distributed on the surface of graphene sheets uniformly. Cyclic voltammetry (CV) square wave voltammetry (SWV) and impedance spectroscopy (EIS) were used to electrochemical study of the decorated electrode. Electrochemical studies described the potential of fabricated rGO/AuNPs-aptamer electrode to selectively determine GA properly in buffer solution at the range of 2-10 µg mL-1 by the detection limit of 0.07 µg. mL-1 for GA.

19.
Antioxidants (Basel) ; 9(12)2020 Dec 04.
Article in English | MEDLINE | ID: mdl-33291560

ABSTRACT

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential transcription factor that maintains the cell's redox balance state and reduces inflammation in different adverse stresses. Under the oxidative stress, Nrf2 is separated from Kelch-like ECH-associated protein 1 (Keap1), which is a key sensor of oxidative stress, translocated to the nucleus, interacts with the antioxidant response element (ARE) in the target gene, and then activates the transcriptional pathway to ameliorate the cellular redox condition. Curcumin is a yellow polyphenolic curcuminoid from Curcuma longa (turmeric) that has revealed a broad spectrum of bioactivities, including antioxidant, anti-inflammatory, anti-tumor, and anti-viral activities. Curcumin significantly increases the nuclear expression levels and promotes the biological effects of Nrf2 via the interaction with Cys151 in Keap1, which makes it a marvelous therapeutic candidate against a broad range of oxidative stress-related diseases, including type 2 diabetes (T2D), neurodegenerative diseases (NDs), cardiovascular diseases (CVDs), cancers, viral infections, and more recently SARS-CoV-2. Currently, the multifactorial property of the diseases and lack of adequate medical treatment, especially in viral diseases, result in developing new strategies to finding potential drugs. Curcumin potentially opens up new views as possible Nrf2 activator. However, its low bioavailability that is due to low solubility and low stability in the physiological conditions is a significant challenge in the field of its efficient and effective utilization in medicinal purposes. In this review, we summarized recent studies on the potential effect of curcumin to activate Nrf2 as the design of potential drugs for a viral infection like SARS-Cov2 and acute and chronic inflammation diseases in order to improve the cells' protection.

20.
Int J Biol Macromol ; 122: 359-366, 2019 Feb 01.
Article in English | MEDLINE | ID: mdl-30359660

ABSTRACT

Laccase was immobilized using a combinatorial strategy of cross-linking and entrapping in mesoporous silica to prepare entrapped enzyme species including simply adsorbed, entrapped cross-linked enzyme (E-CLE) and entrapped cross-linked enzyme aggregate (E-CLEA) to explore their potential in phenol removal. Parameters including pH, temperature, time and cross-linker concentration were optimized to achieve an immobilized product with highest laccase specific activity. Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to characterize the immobilization products. The storage and operational stability analysis were also carried out. Accordingly, E-CLEAs showed improved thermal and pH stabilities and activity retention in hydrophobic and hydrophilic solvents. Moreover, based on the resulted half-lives (t1/2) for free and insoluble laccases, the improved storage stability is reported for E-CLEAs at 1.71 and 20.88 days for them, respectively. In addition, the immobilized biocatalyst exhibited good operational stability and reusability through maintaining up to 79% of its initial activity after 20 cycles of successive operations. In conclusion, E-CLEAs have catalytic potential in efficient phenol removal and advantages of the insolubilized form of laccase as E-CLEAs make it an appealing system in applications such as possible treatment of phenol-contaminated wastewater.


Subject(s)
Biocatalysis , Laccase/chemistry , Laccase/metabolism , Phenol/isolation & purification , Phenol/metabolism , Protein Aggregates , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Hydrogen-Ion Concentration , Kinetics , Porosity , Silicon Dioxide/chemistry , Temperature , Trametes/enzymology , Waste Management
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