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 ...
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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 were including cow , sheep , camel , goat , horse , buffalo in addition to human . 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 binding affinity and specificity of lactoferrins towards rotavirus. This study offers 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.
Ali Javadmanesh; Mitra Riasi
Abstract
TGF-β group member myostatin (MSTN) inhibits the growth and differentiation of skeletal muscle. It is unknown that how total inhibition of MSTN restricts the hyperproliferation of muscle cells, though. This study aimed to determine the differentially expressed genes and biological pathways associated ...
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TGF-β group member myostatin (MSTN) inhibits the growth and differentiation of skeletal muscle. It is unknown that how total inhibition of MSTN restricts the hyperproliferation of muscle cells, though. This study aimed to determine the differentially expressed genes and biological pathways associated with myostatin in mouse C2C12 myogenic cells and skeletal muscle tissue utilizing high throughput mRNA expression data. In both tissue and cell line, two experimental groups were compared including wild-type vs. MSTN-Knockout. Transcriptome data were extracted from GEO and analyzed using the LIMMA package in R environment, and GEO2R. Significant differentially expressed genes were considered as False discovery rate < 0.05 with log fold change > |0.5|. Lastly, the possible biological pathways were examined with KEGG database and the protein-protein interaction (PPI) network was created using Cytoscape software. To find key genes in the PPI network, a topological analysis was conducted using the Network analyzer tool in Cytoscape software. The total number of differentially expressed genes was 14549 for C2C12 cell line and 45267 for mouse skeletal muscle tissue; among them 235 and 1425 transcripts were significant. The comparison between these two DEG lists showed that 49 genes were common between myogenic C2C12 cell and skeletal muscle tissue. Additionally, three biological pathways between the C2C12 cell line and the skeletal muscle tissue were in common and they were associated to the decrease of MSTN gene expression including: hypertrophic cardiomyopathy, Axon guidance, and dilated cardiomyopathy. These pathways were all related to muscle tissue. Despite the large number of DEGs, only 49 were in common in tissue and cell line; this could indicate that comparing a tissue with its relevant cell line at transcriptome level might not be precise enough to draw a solid conclusion. This is due to the nature of cell heterogeneity of most tissues including skeletal muscle.
Ali Javadmanesh; Amir Rashid Lamir; Mitra Riasi; مهرداد موحد نسب; نازیلا دردمه; Elnaz Karbaschian; Kasra Kayyami; Helia Khayyami
Abstract
The growth and development of skeletal muscle tissue is largely regulated by myostatin during the tissue development in embryos. This tissue may overgrow if there is a deficiency in myostatin expression. Gene expression may be regulated in a particular way by oligonucleotide antisense molecules. It has ...
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The growth and development of skeletal muscle tissue is largely regulated by myostatin during the tissue development in embryos. This tissue may overgrow if there is a deficiency in myostatin expression. Gene expression may be regulated in a particular way by oligonucleotide antisense molecules. It has been demonstrated that a new DNA-based oligonucleotide can down-regulate myostatin expression in a rat model. The purpose of this work was to evaluate the impact of a DNAi-based myostatin inhibitor on the vesceral 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 on 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 muscle's relative and absolute weights increased significantly with and visceral fat decreased with DNAi injection (P<0.05). Although weekly body weight increase and the final weights were not affected by DNAi injection, it could be explained by loosing fat tissue during experiment. This molecule is promising in increasing muscle tissue grow however further prolonged experiments and evaluating myostatin gene expression is recommended in future experiments.
Fahime Mohammadi; Mojtaba Tahmoorespour; Ali Javadmanesh
Abstract
The formation of muscle myofibrils as well as the growth and hypertrophy of the muscle are controlled by various genes. Bioinformatics tools could also be used to integrate and analyze heterogeneous data sets. In this study, the DEGs, gene network, GO and biological pathways have been investigated by ...
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The formation of muscle myofibrils as well as the growth and hypertrophy of the muscle are controlled by various genes. Bioinformatics tools could also be used to integrate and analyze heterogeneous data sets. In this study, the DEGs, gene network, GO and biological pathways have been investigated by incorporating the data obtained by expression array and RNA-Seq, related to the muscle tissue transcriptome of Texel sheep respectively before and after birth. The microarray expression profile was extracted from the GEO database, and the RNA-Seq expression profile was extracted from the ArrayExpress database. DEGs were identified with limma and sva software packages in R environment and a gene network was drawn with STRING, an application in Cytoscape software. The clustering and gene ontology were done with CytoCluster and ClueGO applications. The results showed a significant difference between the juvenile and 70-day embryonic stages the expression of 103 genes, between the adult and juvenile stages the expression of 28 genes and between the adult and 70-day embryonic stages the expression of 62 genes. By constructing the gene network between these DEGs, a total of 37 selected genes were identified. The results revealed the function of these genes in cell proliferation, protein synthesis, formation and organization of myofibrils, muscle contraction, and lipid metabolism. By integrating the expression data, this study provided a general view of the differences in transcriptomes in the muscle tissue of sheep. Also, the selected genes such as BUB1, RFC2, KIAA0101, RAD51, CKS2, and UQCRB were identified for the first time being reported as effective genes for myogenesis.
Mitra Riasi; Elnaz Karbaschian; Ali Javadmanesh
Abstract
DNA-based approaches can now be utilized as low-risk methods to change gene expression. It appears that this approach has the ability to partially replace RNA-based approaches for altering gene expression, which in the majority of cases leads to immunological responses in patients. When utilized as a ...
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DNA-based approaches can now be utilized as low-risk methods to change gene expression. It appears that this approach has the ability to partially replace RNA-based approaches for altering gene expression, which in the majority of cases leads to immunological responses in patients. When utilized as a technique to silence target gene expression, DNA interference (DNAi) is a single-stranded DNA created to complement the upstream region of a gene. This DNAi molecule is stabilized using a variety of chemical changes, including phosphorothioates, methylphosphonate setC, etc. Several studies of the efficient application of DNA-based methods both in eukaryotic cell lines and the therapy of various disorders, such as Duchenne muscular dystrophy, cancer, etc., have been mentioned. Understanding the DNAi process, its transfer carriers, stabilization techniques, and their limitations is crucial for advancing these applications and predicting the future of DNAi both in basic science and the treatment of disorders brought on by abnormal gene expression. The main purpose of this review is introducing benefits of using DNAi in gene silencing. this review has discussed about different applications of DNAi in drug discovery and treatment, criteria of designing DNAi, possible modifications, introducing different types of carriers and limitations of DNAi administration.
Jawad Kadhim Sallal Al-Jorani; Mohammadreza Nassiry; Ali Javadmanesh
Abstract
Today, ostrich breeding has been widely developed in Iran and other countries due to the ability of this animal to produce quality meat, leather, and oil. However, one of the main problems in breeding them is sex determination using aggressive techniques with low accuracy. This study aimed to determine ...
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Today, ostrich breeding has been widely developed in Iran and other countries due to the ability of this animal to produce quality meat, leather, and oil. However, one of the main problems in breeding them is sex determination using aggressive techniques with low accuracy. This study aimed to determine the sex of immature ostriches using specific primers in a multiplex PCR reaction. This study considered 20 specimens of unspecified immature and six specimens (three adult males and females) of known-sex African ostriches as controls. SS and OSFES primers were used to amplify part of the female-specific sequence and 18S primer was used as a control in a PCR reaction. The presence of SS and OSFES bands in gel electrophoresis indicated the amplification of the desired parts related to the female sex and the absence of these bands indicates the male sex of the species. In total, out of 20 African ostriches studied, 50% of them belonged to females and 50% of them belonged to males. Later, with the growth of immature individuals, the results of this experiment were confirmed. In this study, it was found that the use of feather samples for DNA extraction and multiplex PCR is a suitable, accurate, and cost-effective method in identifying and determining the sex of young ostrich and leads to more real and reliable results, avoiding stress in birds.
Mitra Riasi; Sina Mozaffari Jovin; Ali Javadmanesh
Abstract
Myostatin (MSTN) is primarily expressed in skeletal muscle tissue and acts as a negative regulator of skeletal muscle growth by inhibiting differentiation and proliferation of myoblasts. Inhibition of MSTN expression could result in muscular hypertrophy. An effective therapeutic approach based on specific ...
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Myostatin (MSTN) is primarily expressed in skeletal muscle tissue and acts as a negative regulator of skeletal muscle growth by inhibiting differentiation and proliferation of myoblasts. Inhibition of MSTN expression could result in muscular hypertrophy. An effective therapeutic approach based on specific silencing of a target gene is provided by RNA interference. The distribution of biologically active small interfering RNAs (siRNAs) inside the target cells/ tissue, is a significant problem due to the limited stability and delivery of siRNAs. Strategies depending on vector delivery have also a limited clinical utility due to safety concerns. Thus direct application of active siRNAs in vivo is the preferred strategy. We described the efficiency of intramuscular and intraperitoneal injections of MSTN-siRNA conjugated with cholesterol into the skeletal muscle of mice. The designed siRNA molecule was complementary to the exon II of the mouse MSTN gene. Mice were injected with a weekly dose of 10 μg/kg conjucated siRNA-cholesterol intraperitoneally or intramuscularly. Our findings suggested that within a few weeks of application, siRNA-treated mice showed a significant increase in muscle mass and suppressed MSTN gene expression. Even though both types of injections increased muscle weight, intramuscular siRNA injections suppressed the MSTN gene more effectively, whereas intraperitoneal RNA injections had a more significant impact on total body weight. The cholesterol-conjugated siRNA platform discussed here may hold promise for treating several skeletal muscle-related diseases, such as atrophic muscle disease, muscular dystrophy, and type II diabetes.
