Ali Javadmanesh; Atefe Paknafs; Marjan Azghandi
Abstract
Rotavirus infections impose a significant global health burden, particularly affecting infants and young children and causing severe gastroenteritis. To combat this viral pathogen, there is a growing interest in exploring the therapeutic potential of lactoferrins derived from different farm animal milk ...
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Rotavirus infections impose a significant global health burden, particularly affecting infants and young children and causing severe gastroenteritis. To combat this viral pathogen, there is a growing interest in exploring the therapeutic potential of lactoferrins derived from different farm animal milk as antiviral agents. This study employed molecular simulation techniques to investigate the intricate binding mechanisms between different animal milk lactoferrins and rotavirus, providing insights into their molecular interactions. These animals included cow, sheep, camel, goat, horse, buffalo, in addition to humans. Molecular dynamics simulation techniques were employed using Gromacs software to simulate the interaction between animal milk lactoferrins and rotavirus. Precise computational models and simulations were conducted to investigate the binding mechanisms and identify critical amino acid residues involved. Our findings indicate that cow lactoferrin exhibits superior interaction with rotavirus compared to other lactoferrin sources. We identified specific binding sites and crucial amino acid residues responsible for these interactions. These results provide insights into the molecular determinants governing the strong binding affinity and specificity of lactoferrins towards rotavirus. This study provided valuable insights for the design of targeted antiviral strategies against rotavirus infections. Animal milk lactoferrins, particularly cow lactoferrin, demonstrated a promising potential as an antiviral agent against retroviruses. These findings enhanced our understanding of the molecular mechanisms underlying lactoferrin-mediated antiviral activity, paving the way for future experimental and clinical investigations in this field and supporting the development of efficient antiviral therapeutics against rotavirus.
Khadijeh Haghighat; Fariba Mahmoudi; Homayoun Khazali
Abstract
Stress is one of the most prevalent mental health disorders. Chrysin, a phytochemical compound, is known for its anti-stress effects; however, the molecular mechanisms underlying its anxiolytic properties are not well understood. The present study aimed to investigate the effects of chrysin on the gene ...
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Stress is one of the most prevalent mental health disorders. Chrysin, a phytochemical compound, is known for its anti-stress effects; however, the molecular mechanisms underlying its anxiolytic properties are not well understood. The present study aimed to investigate the effects of chrysin on the gene expression of hypothalamic phoenixin and nesfatin-1 in a rat model of acute restraint stress. In the study, twenty male Wistar rats weighing 200 ± 10 g were split up into four groups (n=5). A cannula was surgically implanted into the third cerebral ventricle. Following a one-week recovery period, the rats were exposed to a two-hour acute restraint stress protocol. While the control and stress groups received saline, two additional experimental groups subjected to stress were administered either 20 µg or 40 µg of chrysin via the third cerebral ventricle. Hypothalamic samples were removed. Then, RNA was extracted. In the next step, cDNA was synthesized. Finally, relative gene expression was assessed by a real-time polymerase chain reaction (PCR). The findings revealed a significant upregulation of nesfatin-1 mRNA in the stressed rat relative to the control group. The mRNA level of nesfatin-1 in the chrysin-treated group was significantly reduced compared to the stressed group. Furthermore, the stressed rats showed a significant decrease in mRNA levels of phoenixin in comparison to the control group. There was no significant increase in the mRNA level of phoenixin between the stressed group and the group receiving chrysin. In conclusion, downregulation of the hypothalamic nesfatin may be involved in mediating the anti-anxiety effects of chrysin.
Roohallah Yousefi
Abstract
The HIV integrase enzyme, comprising its N-terminal (NTD), central (CD), and C-terminal (CTD) domains, plays a crucial role in the integration of the HIV genome into host DNA and in the viral life cycle. It accomplishes this by recognizing and binding viral DNA, maintaining structural integrity, and ...
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The HIV integrase enzyme, comprising its N-terminal (NTD), central (CD), and C-terminal (CTD) domains, plays a crucial role in the integration of the HIV genome into host DNA and in the viral life cycle. It accomplishes this by recognizing and binding viral DNA, maintaining structural integrity, and catalyzing integration into the host genome. The CTD domain contains the catalytic core, which includes the DDE motif, essential for cleavage and joining reactions, and interacts with LEDGF/p75 to enhance the specificity and efficiency of integration. Inhibitors that block integrase improve HIV treatment and reduce resistance. We utilized molecular docking methods to investigate the catalytic core of HIV integrase and its interactions with inhibitory ligands. The physicochemical properties and pharmacokinetics of the compounds under investigation were calculated using the SwissADME webtool database. Except for compounds with high molecular weight, the remaining compounds exhibit high gastrointestinal absorption, allowing for easy entry into the bloodstream. However, they often have low dermal absorption, which limits their effectiveness for dermal delivery. Compounds with CID numbers 74071, 24800940, and 133081875 demonstrate high dermal absorption. The compound with CID number 91899501 is the only exception, as the other compounds studied bind to a specific site composed of several amino acids. These amino acids, including Gln62, Leu63, Asp64, Val77, His114, Thr115, Asp116, Gly140, Ile141, and Glu152, are crucial for the effective binding of compounds to the enzyme. Understanding the binding sites of integrase strand transfer inhibitors (INSTIs) is crucial for assessing the efficacy of antiretroviral therapy against HIV. The active site of integrase contains the key amino acids D64, D116, and E152, which are targeted by most of the INSTIs studied. Our study aims to enhance the effectiveness of INSTIs and prevent the development of resistant viruses.
Shima Amirsadri; Seyed Morteza Babamir; Shahyar Arab
Abstract
The protein’s motifs (called super secondary structures) are dense three-dimensional structures of proteins consisting of several secondary structures in a specific geometric arrangement. The prediction of motifs is a matter of concern and has been studied. The previous studies dealt with motif ...
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The protein’s motifs (called super secondary structures) are dense three-dimensional structures of proteins consisting of several secondary structures in a specific geometric arrangement. The prediction of motifs is a matter of concern and has been studied. The previous studies dealt with motif prediction based on the polypeptide chain; however, the prediction of motifs based on the secondary structures leads to more accurate prediction. This study aims to address such a prediction. First, several secondary structures are constructed and then, based on the energy level and using a metaheuristic (evolutionary) algorithm called Imperialist Competitive Algorithm. (ICA) The protein’s motifs are predicted. The advantage of our approach over existing approaches is that secondary structural data as input to our algorithm leads to a more accurate prediction that is closer to the real protein third than previous algorithms. We applied our method to predict super secondaries of the enzyme β−LACTAMASE, whose specification was obtained from the PDB file in Yasara. This enzyme is produced by bacteria and provides multi-resistance to antibiotics β−LACTAMA. Then we evaluated our prediction using Root-Mean-Square Deviation (RMSD). It shows the average distance between the two proteins structurally having the same alignment. Having determined the structural alignment of the two proteins, we determined the similarity of their 3D structures using RMSD. If the RMSD between two structures is less than 2, it denotes they are very similar. Accordingly, we used RMSD to show how much similarity exists between the motif obtained by our proposed algorithm for β−LACTAMASE and its native structure.
Ali Javadmanesh; Amir Rashid Lamir; Mitra Riasi; Mehrdad Movahed Nasab; Nazila Dardmeh; Helia Khayyami; Kasra Khayami; Elnaz Karbaschian
Abstract
The growth and development of skeletal muscle tissue is largely regulated by myostatin during tissue development in embryos. This tissue may overgrow if myostatin expression is deficient. Gene expression may be regulated in a particular way by oligonucleotide antisense molecules. It has been demonstrated ...
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The growth and development of skeletal muscle tissue is largely regulated by myostatin during tissue development in embryos. This tissue may overgrow if myostatin expression is deficient. Gene expression may be regulated in a particular way by oligonucleotide antisense molecules. It has been demonstrated that a new DNA-based oligonucleotide can downregulate myostatin expression in a rat model. The purpose of this work was to evaluate the impact of a DNAi-based myostatin inhibitor on the visceral fat and leg muscle weights of Wistar rats undergoing strength training. Three groups of male rats, with an average weight of 203g ± 10.5, were chosen at four weeks of age. These cohorts comprised: 1) DNAi group had resistance training in addition to receiving 10 mg/kg of rat body weight of DNAi. 2) Resistance exercise and saline injection group. Group for injection of saline. Then, weight measurements for the carcass, heart, liver, left kidney, right kidney, spleen, visceral fat, twin muscles, soleus muscle, and left leg were made for each group. Histological assessment of the soleus muscle section was performed. One-way ANOVA was then used to examine the results, and means were compared using Tukey’s test. As the data show, the proposed molecule did not significantly contribute to an increase in body weight, in contrast to previous assumptions. Nonetheless, the twin muscles' relative and absolute weights increased significantly with visceral fat decreased with DNAi injection (P<0.05). Although weekly body weight increase and the final weights were not affected by DNAi injection, this could be explained by the loss of fat tissue during the experiment. This molecule is promising in increasing muscle tissue growth; however, further prolonged experiments and evaluating myostatin gene expression are recommended in future experiments.
