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Background & Aims: The effort of scientists to control and treat diseases opens new horizons for human society every day. The cloning that has been successful in the case of plants and animals, on the one hand, has fueled enormous challenges and fundamental questions about human cloning, and on the other hand, it has promised to cure many diseases. The goal of cloning therapy is to create stem cells that are similar to the patient's stem cells. The purpose of this will not be the production of a human being, but it is meant to restore life and full health to a person, to be allowed to achieve it. In this context, prominent statements and their opponents and supporters have explained their views. Therapeutic simulation is one of the challenging issues of the contemporary world, but no comprehensive and extensive research has been done on this issue. Cloning, which is another name, comes from the root of clone, which is a Greek word, and its literal meaning is "sprouting and multiplying". Cloning in biological science means "reproduction of a living organism without sexual intercourse" and currently refers to the act of implanting an embryo in the womb that was first produced in a laboratory. The cell is a French word that means that living organisms, despite the differences in shape and characteristics, are all made of small elements called cells, whose structure is almost the same in animals and plants. The meaning of cell in Farsi is "cell" which means a living organism despite the difference in shape and appearance. The process of asexual production of a group of cells, molecules, or living organisms that are all genetically similar is called "simulation" or "cloning". The different uses of this word indicate a common element, which is: the creation and production of a creature similar to the original animal without the involvement of the sexual element. Hence, cloning can be translated into asexual reproduction. Cloning means the steps that are taken to produce several copies of a single gene, and this term is used to mean the physical separation of a single cell and its multiplication in the culture medium to produce a population of those cells. In short, the production of an individual or a group of individuals that are genetically identical to what has been reproduced is called cloning. The most complete form of simulation is somatic cell nuclear transfer through which simulation takes place. By using this technique, the nuclear materials of the human somatic cell or the donor are transferred into an egg that has already been deactivated. Finally, it stimulates the formed egg cell to start its growth and development stages, and as a result, a cloned embryo is obtained. On the other hand, one of the new legal issues is the issue of simulation. This technique is one of the achievements and challenging issues of the contemporary world, but it has also been faced by scholars of jurisprudence, lawyers, and authors of legal texts. Accordingly, this article was conducted with the aim of investigating and analyzing simulation techniques in medical sciences with a legal approach. Methods: This descriptive-analytical study analyzed and described its sayings and ideas with the method of documentary studies. In this method, the simulation process is carried out by splitting the embryo. Explanation that one or more cells are taken from the fertilized embryo and placed in a suitable environment such as the uterus or a laboratory tube. Each of these cells has the ability to turn into a new embryo, the result of which, if placed in a suitable space, is an embryo like the original embryo. This method is the same way that happens in nature, and identical twins or multiple twins are considered to be a manifestation of it. This method has been successfully used on many animals such as sheep, cows, mice and monkeys. Results: The results of the research indicate that the therapeutic simulation of the dual process is carried out by the method of embryo derivation and nuclear transfer, and healthy cells are replaced by defective and unhealthy cells, the purpose of which is the possibility of restoring life and health to a person, on the other hand, techniques Infertility treatment such as in vitro fertilization, sperm injection into the uterus is one of the methods commonly known as assisted reproductive methods. From the point of view of its goals, simulation is classified into two types: human or reproductive (first paragraph) and research or therapeutic (second paragraph). In other words, simulation is done for two purposes: creating a perfect human (human simulation); Creating different organs of the human body (therapeutic simulation). The realization of the second goal is in such a way that every potential cell has the ability to become all the cells of the organs, so the growth can be stopped in the laboratory and only a specific cell, such as the heart, nerve or kidney, etc., can be allowed to grow. gave There are many disagreements and oppositions regarding human cloning due to its negative consequences, but there is no disagreement among scientists regarding therapeutic simulation, and even because of its widespread use and its many and important benefits in medicine, it is welcomed because of the treatment of chronic diseases. Conclusion: In this paper, the simulation technique, which is considered one of the new human achievements, was discussed, and in this regard, the desired approach was expressed from the perspective of the jurists of the Imamiyya school and Iranian law writers. And it is the subject of controversy in the contemporary world, which has entered into the field of writing with the aim of researching, examining, and explaining the jurisprudence and legal ruling of therapeutic simulation technique, and the writer has tried to analyze and describe the material using the library method. The findings of the research indicate that, first, its therapeutic application is to create stem cells that are similar to the patient's stem cells, in this type of simulation, healthy cells are replaced by defective and unhealthy cells; in the continuation of the discussion, we concluded that the simulation phenomenon takes place during the dual process by two methods of embryo derivation and nuclear transfer. In addition, infertility treatment techniques such as in vitro fertilization, sperm injection into the uterus, and other methods are commonly known as assisted reproductive methods. The results of the research show that from the point of view of its goals, simulation is divided into two types of human or reproduction or reproduction (first paragraph) and research or therapeutic (second paragraph) and with the two goals of creating a complete human (human simulation) and creating different organs of the human body (therapeutic simulation) is done that in the legal discussion of this issue, we can pay attention to the following: abortion has a customary meaning and the custom of destroying laboratory embryos is not considered abortion. Also, the analogy of "Mustanbat al-Ala" is not valid in Imami jurisprudence, and the ruling on abortion and the destruction of the fetus outside the womb cannot be considered the same. On the other hand, the similarity of the principle of innocence, if we have doubts about whether something is haram, we rule that it is not haram. The rule of Daraa also stipulates that in case of doubt, punishment cannot be carried out. Therefore, there is no reason to prohibit the destruction of the simulated embryo, and it seems that extracting and using stem cells from it is without problems. [ABSTRACT FROM AUTHOR]

Background and Objectives The expression of Numb as a cell-fate determinant gene leads to inhibition of leukemic cell growth. The high levels of Musashi2 (Msi2) results in down-regulation of Numb in chronic myeloid leukemia cells. In this study we knocked down Msi2 using RNA interference (RNAi) strategy and investigated the effects of this knock down on the expression of Musashi2-Numb axis and genes involved in proliferation and apoptosis. Materials and Methods In this experimental study, synthetic double stranded siRNAs designed to target human Msi2 were transfected to K562 cells using Lipofectamine in duplicate. Changes in the expression levels of Msi-2, Numb, P21, and Bcl-2 genes 48h after transfection were evaluated by realtime PCR. Induction of apoptosis in transfected leukemic cells was determined using Annexin- PI staining and flowcytometry analysis. Data were analyzed by t-test. Results We found that upon Msi2 suppression, the expression levels of the cell-fate determinant Numb showed two-fold increase in K562 cells (p < 0/05). Msi2 down-regulation and subsequent increase in Numb expression levels caused the elevated expression of p21, as a cell cycle regulator (p < 0/05). In addition, Msi2 down-regulation promoted cell apoptosis via the down-regulation of Bcl-2 expression (p < 0/05). We observed that the rates of apoptosis in leukemic increased to 52% and 60%, 24h and 48h after transfection. Conclusions It seems that Msi2 could be an option for targeting leukemic cells and its down-regulation through RNAi strategy may lead to induction of apoptosis in leukemic cells. This approach may open up new opportunities for leukemia therapy. [ABSTRACT FROM AUTHOR]

Background and aims: The most of endurance activity induced changes occur by epigenetic processes which Histone deacetylase 4 transcription factor plays a central role in that. Therefore, the aim of this study was to investigate the effect of endurance activity on slow and fast twitch muscles hdac4 gene expression. Methods: The subjects of this experimental study were 14 rats (231±24 gr) that housed under standard conditions. After familiarization with training protocol, there were randomly assigned into control (n=7) and experimental (n=7) groups. The experimental group performed an endurance program (30 m/min, 50 min, 6 session per week for 14-weeks) on motorized treadmill, and then 48 hours after the end of the last session of training with control group were anesthetized and sacrificed. Then, the EDL and soleus muscles were removed. Real time RTPCR method was used to determine of expression levels of hdac4 gene in EDL and soleus muscles. Finally, t-test was used to compare and evaluate the means of hdac4 gene expression in control and experimental groups. Results: The results showed 14 weeks endurance activity decrease hdac4 gene expression in soleus muscle, so that the rate of expression of this gene in soleus muscle of experimental group was significantly (P=0.0001) less compared to control group, but in EDL muscle in compared with control group there was not seen a significant difference (P=0.76) in hdac4 gene expression in experimental group. Conclusion: The result of this study showed that despite the equal intensity and duration of endurance training, the hdac4 gene expression of fast and slow twitch muscles was different. Decreasing in the rate of hdac4 gene expression in soleus muscle is probably the sign of uncondensed chromatin, which is the begin of genes expression that involves in the endurance activity in slow twitch skeletal muscle. [ABSTRACT FROM AUTHOR]

Objective: Breast cancer is considered a heterogeneous disease, characterized by different biological and phenotypic features which make its diagnosis and treatment challenging. We have sought to investigate the expression levels of key components of the Hedgehog signaling pathway, correlation between the signal transducer Smo, and clinicopathologic features (lymph node metastasis and metastasis stage) in invasive breast carcinoma. Also, we examined the inverse correlation between expression levels of Smo and Claudin-1 (an important gene involved in cell tight junctions). Methods: In this case-control study, we assessed 36 pairs of tumor and adjacent normal tissue specimens obtained from patients with invasive ductal breast carcinoma. The expression levels of key components of Hedgehog signaling (Smo, Gli1 and Ptch), Claudin-1, E-cadherin, and MMP2 were measured by qRT-PCR. The correlations between Smo expression with some clinicopathologic parameters were also analyzed. Results: We found up-regulation of Hedgehog signaling in invasive breast carcinoma samples compared to normal adjacent tissues. Upregulation of the signal transducer Smo correlated with tumor stages and lymph node metastasis of the breast tumors. Interestingly, this correlation was affected by the expression of Her2. A significant correlation existed between expression levels of the signal transducer Smo and Claudin-1, E-cadherin as an epithelial cell marker, and MMP2 as a metastasis-related gene in advanced metastatic tumor samples. Conclusion: Taken together, our study revealed a new layer of molecular complexity which should be considered in the management of patients with invasive breast carcinoma. The results suggested a key role for Hedgehog signaling in invasive breast carcinoma. In terms of the inverse correlation between expression levels of Claudin-1 and Hedgehog signaling, Claudin-1 could serve as a candidate gene in diagnostic studies. Thus, its clinical significance should be further clarified. [ABSTRACT FROM AUTHOR]