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.
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.
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.
amir ghaffar shahriari; Aminallah Tahmasebi
Abstract
MicroRNAs (miRNAs) are 20-24 nucleotide small RNAs which are processed from nuclear-encoded transcripts. miRNAs control the expression of target transcripts by cleaving or translational inhibition of the target RNAs. Artificial microRNAs (amiRNAs) are modified endogenous miRNA precursors in which the ...
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MicroRNAs (miRNAs) are 20-24 nucleotide small RNAs which are processed from nuclear-encoded transcripts. miRNAs control the expression of target transcripts by cleaving or translational inhibition of the target RNAs. Artificial microRNAs (amiRNAs) are modified endogenous miRNA precursors in which the miRNA: miRNA duplex is replaced with sequences to silence a target gene. amiRNAs are used as new transformation techniques in eukaryotes and have been proven to be more effective in specificity and stability than other RNA-mediated gene silencing methods. amiRNA-based antiviral defense is an effective and new approach to engineer resistance to plant viruses. Here, we summarize the role of miRNAs in resistance to plant viruses.
