Development Cabinet Formalized

Alzheimer's disease (AD) is a kind of brain disease that arises due to the aggregation and fibrillation of amyloid β-peptides (Aβ). The peptide Aβ17-42 forms U-shape protofilaments of amyloid mature fibrils by cross-β strands, detected in brain cells of individuals with AD. Targeting the structure of Aβ17-42 and destabilizing its β-strands by natural compounds could be effective in the treatment of AD patients. Therefore, the interaction features of monomeric U-shape Aβ17-42 with natural flavonoids including myricetin, morin and flavone at different mole ratios were comprehensively studied to recognize the mechanism of Aβ monomer instability using molecular dynamics (MD) simulations. We found that all flavonoids have tendency to interact and destabilize Aβ peptide structure with mole ratio-dependent effects. The interaction free energies of myricetin (with 6 OHs) and morin (with 5 OHs) were more negative compared to flavone, although the total binding energies of all flavonoids are favorable and negative. Myricetin, morin and flavone penetrated into the core of the Aβ17-42 and formed self-clusters of Aβ17-42-flavonoid complexes. Analysis of Aβ17-42-flavonoids interactions identified that the hydrophobic interactions related to SASA-dependent energy are weak in all complexes. However, the intermolecular H-bonds are a main binding factor for shifting U-shape rod-like state of Aβ17-42 to globular-like disordered state. Myricetin and morin polyphenols form H-bonds with both peptide's carbonyl and amine groups whereas flavone makes H-bonds only with amine substitution. As a result, polyphenols are more efficient in destabilizing β-sheet structures of peptide. Accordingly, the natural polyphenolic flavonoids are useful in forming stable Aβ17-42-flavonoid clusters to inhibit Aβ17-42 aggregation and these compounds could be an effective candidate for therapeutically targeting U-shape protofilaments' monomer in amyloid mature fibrils

Application of Chitosan Hydrogels in Traumatic Spinal Cord Injury; A Therapeutic Approach Based on the Anti-inflammatory and Antioxidant Properties of Selenium Nanoparticles

Abstract Purpose: The pathophysiological progression of traumatic spinal cord injury (SCI) includes primary and secondary injury. Secondary injury causes the destruction of the spinal cord tissue and neurological disorders. After primary mechanical damage, inflammation is the most important factor inducing astrogliosis and scar formation. The activation of inflammatory cells in the area of ​​damage causes the production of free radicals, all of which damage cell membranes. A significant level of oxygen free radical production is involved in the pathology of SCI; Therefore, limiting secondary damage is very important in the clinical treatment of acute traumatic spinal cord injury. Materials and Methods: In this review article, the articles indexed in various databases were used. The collection of articles was evaluated without time constraints using keywords inducing traumatic spinal cord injury (SCI), inflammation, oxidative stress, chitosan, selenium nanoparticles. Results: Inflammation and oxygen free radicals play a key role in secondary damage after SCI. Therefore, as a new therapeutic approach, the use of - hydrogels based on chitosan has been considered in SCI. The biocompatibility and biological properties of chitosan have made it considered as a suitable material for nerve regeneration. Conclusion: The use of reactive oxygen species scavengers, including metal nanoparticles, can control inflammation and oxidative stress in spinal cord injuries. Selenium nanoparticles treatment may reduce secondary damage in SCI by using its anti-inflammatory and antioxidant properties. Therefore, the use of selenium nanoparticles in the chitosan hydrogel bed can control the degeneration and functional improvement of the nerve tissue of the spinal cord

Intracellular ROS Protection Efficiency and Free Radical-Scavenging Activity of Curcumin

Curcumin has many pharmaceutical applications, many of which arise from its potent antioxidant properties. The present research examined the antioxidant activities of curcumin in polar solvents by a comparative study using ESR, reduction of ferric iron in aqueous medium and intracellular ROS/toxicity assays. ESR data indicated that the steric hindrance among adjacent big size groups within a galvinoxyl molecule limited the curcumin to scavenge galvinoxyl radicals effectively, while curcumin showed a powerful capacity for scavenging intracellular smaller oxidative molecules such as H2O2, HO•, ROO•. Cell viability and ROS assays demonstrated that curcumin was able to penetrate into the polar medium inside the cells and to protect them against the highly toxic and lethal effects of cumene hydroperoxide. Curcumin also showed good electron-transfer capability, with greater activity than trolox in aqueous solution. Curcumin can readily transfer electron or easily donate H-atom from two phenolic sites to scavenge free radicals. The excellent electron transfer capability of curcumin is because of its unique structure and different functional groups, including a β-diketone and several π electrons that have the capacity to conjugate between two phenyl rings. Therfore, since curcumin is inherently a lipophilic compound, because of its superb intracellular ROS scavenging activity, it can be used as an effective antioxidant for ROS protection within the polar cytoplasm

Customer Experience of Electronic Services in Information Technology Organizations Based on Digital Developments

Purpose: Customer experience management is one of the most important activities for managers who are trying to grow and develop to achieve a favorable competitive position. The purpose of this study is to evaluate the dimensions of customer experience in the process of using electronic services in information technology organizations (Hamrah-e-Aval). Method: The method of this study is quantitative. In this regard, a questionnaire was designed and distributed among the statistical population by the available sampling method. The data analysis method is structural equation modeling and the software used is SPSS25 and SMART PLS 3.0. Findings: Findings show that awareness is the first step in managing customer experience. The second step deals with the active organizational actor. The third step, or evaluation, is based on service characteristics and service arrangements. The fourth step (buying decision). Purchasing and the resulting experience is the fifth step. Step 6 (Use) is a function of activities including delivery and use. The seventh step is to repeat the purchase, complain or not react to the use of the product (service). Finally, the customer's secondary response is the last step of the customer experience model. Conclusion: Based on the findings of the present study, information interface can play a decisive role in shaping customer experiences. Therefore, it is suggested that in the active businesses in the information and communication technology industry, by studying the media and customer information tools, the most optimal and effective tools should be selected and used

Development of a new sequential block finding strategy for detection of conserved sequences in riboswitches

Introduction: Some non-coding RNAs have an important role in the regulation of gene expression and consequently cellular function. Riboswitches are examples of these regulatory RNAs. Riboswitches are classified into various families according to sequential and structural similarities. Methods: In this study, a block finder algorithm for identification of frequently appearing sequential blocks in five families of riboswitches from Rfam 12.0 database, without the use of alignment methods, was developed. Results: The developed program identified 21 frequently appearing blocks in five families of riboswitches. Conclusion: Comparison of the results of the proposed algorithm with those of sequential alignment methods revealed that our method can recognize most of the patterns present in conserved areas of individual riboswitch families and determine them as specific blocks, implying potential of the developed program as a platform for further studies and developments

Preparation and Administration of a Controlled-Release Delivery System of Chitosan Hydrogel loaded with Methadone and Piroxicam in Experimental Defect of Tibial in Rats; Histopathological Evaluation

Purpose: In this study, a controlled release drug delivery system loaded with piroxicam and methadone was synthesized and used subcutaneously in rat with experimental tibial defect and healing were assessed histopathologically. Materials and Methods: For this purpose 100 adult female rats were were randomly divided into five equal groups; group control, chitosan group, piroxicam group, methadone group, and piroxicam-methadone group. The morphological structure of the synthesized drug systems was studied by scanning electron microscope. In addition, the structure of the hydrogels was investigated by fourier transform infrared spectroscopy and while releasing the hydrogels gelation time, the release of piroxicam and methadone from the hydrogels were evaluated in vitro.   Results: Histological results of the 3rd day of the study showed the lowest extent and severity of inflammation in the chitosan, piroxicam, and piroxicam-methadone groups, while on the 7th day, tissue inflammation and the extent of bleeding was lower in the piroxicam, methadone, and piroxicam-methadone groups than in the other groups. Evaluation of new bone formation on day 21 showed that the chitosan, piroxicam, and methadone groups had better repair than the other groups. Conclusion: It seems that in the control group that did not receive any treatment intervention, following the experimental bone defect, the highest inflammatory response was observed in histological examination and finally the weakest bone repair. On the other hand, the presence of piroxicam, methadone and chitosan in the piroxicam-methadone group (all of which have anti-inflammatory effects) also seems to have a negative effect on repair

Spectroscopic, thermodynamic and molecular docking studies of bovine serum albumin interaction with ascorbyl palmitate food additive

Introduction: Ascorbyl palmitate (AP) is an example of natural secondary food antioxidant, which has been used for oxidative rancidity prevention in food industry. In this study, the interaction of AP with bovine serum albumin (BSA) was investigated. Methods: The mechanism of BSA interaction with AP was investigated using spectroscopic methods (UV-Vis, fluorescence). The thermodynamic parameters including enthalpy change (ΔH), entropy change (ΔS), and Gibb’s free energy (ΔG) were calculated using Van’t Hoff equation at different temperatures. Results: The experimental results showed that UV-Vis absorption spectra of BSA decreased upon increasing AP concentration, indicating that the AP can bind to BSA. Formation of the AP-BSA complex was approved by quenching of fluorescence and the quenching mechanism was found to be resultant from dynamic procedure. The positive values of both ΔH and ΔS showed that hydrophobic forces were the major binding forces. The negative value of ΔG demonstrated that AP interacts with BSA spontaneously. Molecular docking results confirmed that AP binds to BSA through hydrophobic forces. Conclusion: The attained results showed that AP can bind to BSA and effectively distributed into the bloodstream

Classification of seed members of five riboswitch families as short sequences based on the features extracted by Block Location-Based Feature Extraction (BLBFE) method

Introduction: Riboswitches are short regulatory elements generally found in the untranslated regions of prokaryotes’ mRNAs and classified into several families. Due to the binding possibility between riboswitches and antibiotics, their usage as engineered regulatory elements and also their evolutionary contribution, the need for bioinformatics tools of riboswitch detection is increasing. We have previously introduced an alignment independent algorithm for the identification of frequent sequential blocks in the families of riboswitches. Herein, we report the application of block location-based feature extraction strategy (BLBFE), which uses the locations of detected blocks on riboswitch sequences as features for classification of seed sequences. Besides, mono- and dinucleotide frequencies, k-mer, DAC, DCC, DACC, PC-PseDNC-General and SC-PseDNC-General methods as some feature extraction strategies were investigated. Methods: The classifiers of the Decision tree, KNN, LDA, and Naïve Bayes, as well as k-fold cross-validation, were employed for all methods of feature extraction to compare their performances based on the criteria of accuracy, sensitivity, specificity, and f-score performance measures. Results: The outcome of the study showed that the BLBFE strategy classified the riboswitches indicating 87.65% average correct classification rate (CCR). Moreover, the performance of the proposed feature extraction method was confirmed with average values of 94.31%, 85.01%, 95.45% and 85.38% for accuracy, sensitivity, specificity, and f-score, respectively. Conclusion: Our result approved the performance of the BLBFE strategy in the classification and discrimination of the riboswitch groups showing remarkable higher values of CCR, accuracy, sensitivity, specificity and f-score relative to previously studied feature extraction methods

Proton-Coupled Electron-Transfer Mechanism for the Radical Scavenging Activity of Cardiovascular Drug Dipyridamole

Dipyridamole (DIP) is a well-known pharmaceutical drug used as a coronary vasodilator and anti-platelet agent in clinics for treating several cardiovascular diseases. Primarily, the therapeutic effects of the drug are attributed to its antioxidant potency. In this research, we aim to declare the unknown antioxidant mechanism of DIP as well as its potent chain-breaking antioxidant activity in polar aqueous medium inside the cells, using different experimental methods and theoretical quantum calculations. Data demonstrated the higher antioxidant capacity of DIP against ROS and free radicals in polar cell's interior. DIP is capable of generating long living and noninvasive DIP• radicals in oxidant condition that leads to an effective “chain-breaking antioxidant” activity. Quantum computational data indicated that DIP antioxidant has more favorable ionization potential than trolox which means DIP has higher antioxidant activity. Also, data showed that the direct hydrogen-transfer is not a favorable process to construct DIP• because of high barrier energy, though electron-transfer process can more easily to produce DIP•+ with the lowest barrier energy. Altogether, the electron donating potency of DIP to reduce ferric ion, having the low anodic oxidation peak potential, producing long lived stable DIP• radicals and protecting myoblast cells from oxidation, proposed the excellent “chain-breaking antioxidant” potency via electron-transfer mechanism of this vasodilator DIP drug in polar aqueous medium