سوسك زرد آرد (Tenebrio molitor) به‌عنوان يكي از مهم‌ترين گونه‌هاي حشرات خوراكي، در سال‌هاي اخير به دليل ارزش غذايي بالا، قابليت پرورش آسان، بازده توليد مناسب و سازگاري با شرايط محيطي، توجه بسياري از پژوهشگران و صنايع غذايي را به خود جلب كرده است. دماي پرورش يكي از عوامل كليدي تعيين‌كننده موفقيت اقتصادي اين فعاليت مي‌باشد.   پژوهش حاضر با   هدف بررسي چهار تيمار دمايي (??، ??، ?? و ?? درجه سانتي‌گراد) و سه تكرار انجام گرديد. لاروها با جيره پايه سبوس گندم و قطعات هويج تغذيه شدند. پارامترهاي زيستي (مدت زمان دوره لاروي و شفيرگي، نرخ بقا و دگرديسي، وزن و طول بدن)، پارامترهاي تغذيه‌اي (مصرف غذا، نرخ رشد نسبي، بازده تبديل غذا) و پروفايل ارزش غذايي (پروتئين، چربي، فيبر، خاكستر و انرژي) به‌طور هفتگي اندازه‌گيري و محاسبه شدند. داده‌ها با استفاده از نرم‌افزار    و آزمون‌هاي آماري سطح معني‌داري ??/? مورد تحليل قرار گرفتند. تغيير دما تأثير معني‌داري بر تركيبات شيميايي بدن لاروها (پروتئين، چربي، فيبر و خاكستر) نداشت   (p > 0.05) و ميزان اين تركيبات نسبتا پايدار باقي ماند كه نشان مي‌دهند تركيبات شيميايي بيشتر تحت تأثير كيفيت بستر غذايي قرار دارند تا دما. در مقابل، شاخص‌هاي زيستي و تغذيه‌اي به شدت تحت تأثير دما بودند(p < 0.05). با افزايش دما، طول دوره لاروي و شفيرگي به‌طور معني‌داري كاهش يافت.   بيشترين نرخ رشد نسبي و اندازه نهايي لاروها در دماي ?? درجه مشاهده شد. اما بالاترين نرخ بقا (????) و موفقيت در دگرديسي مربوط به دماهاي ?? و ?? درجه بود كه در دماي ?? درجه به ترتيب به ??/??? و ??/??? كاهش يافت.   مصرف غذا و غذاي جذب‌شده با افزايش دما به‌طور معني‌داري افزايش، اما كارايي تبديل غذاي خورده‌شده (ECI) و هضم‌شده (ECD) كاهش يافت . در نتيجه بايستي گفت كه اگرچه دماهاي بالاتر (?? و ?? درجه) منجر به تسريع رشد و كوتاه‌تر شدن چرخه توليد مي‌شوند، اما اين مزيت با كاهش نرخ بقا و كارايي تبديل غذا همراه است. با در نظر گرفتن توأم تمامي فاكتورها، محدوده دمايي ?? تا ?? درجه سانتي‌گراد به‌عنوان دماي بهينه براي پرورش لارو T. molitor   پيشنهاد مي‌گردد. در اين محدوده، تعادل مناسبي بين سرعت رشد، نرخ بقاي بالا و كارايي قابل قبول سيستم برقرار مي‌شود.

 Abstract

 Quercetin and thymoquinone are important plant chemical compounds that have various antioxidant, anti-inflammatory and anti-cancer effects by inhibiting different signaling pathways and epigenetic changes. MiRNA are also a group of small non-coding RNAs that, by targeting different genes and affecting signaling pathways, play an important role in regulating gene expression and controlling breast cancer symptoms, and are used as biomarkers for diagnosis, prognosis, and treatment. The aim of this research is to investigate the simultaneous effect of quercetin and thymoquinone on the expression of TSG6, ANO9 genes and their targeting microarrays in MCF-7 breast cancer cells. In this study, MCF-7 cells were cultured and propagated and then treated with different concentrations of quercetin and thymoquinone. After RNA and microarray extraction from cells and cDNA synthesis, using bioinformatics sites including TargetScan, miRBase and miRDB, target microarrays of studied genes were predicted. Also, by using the mentioned sites and the miRNet site, R and Cytoscape software, the best microarrays targeting these genes were predicted for future research. qRT-PCR method was used to quantitatively investigate the expression of genes and microarrays. The results showed that the treatment of MCF-7 cells simultaneously with thymoquinone and quercetin decreases TSG6 gene expression. When the concentration of quercetin or thymoquinone was kept constant, by increasing the concentration of the other substance, the gene expression approached the control group. It is possible that the reduction of TSG6 expression only at the concentration of 35 ?M thymoquinone and 50 ?M quercetin can be affected by hsa-miR-23a-3p, and at other concentrations, it is probably due to the involvement of other pathways and factors. It was also found that with the increase in the concentration of quercetin, the expression of the ANO9 gene decreased significantly at the concentration of 20 ?M thymoquinone, but at the concentration of 35 ?M, the expression of the gene was closer to the control group and also positive. Examining the effect of these two substances on the expression of has-miR-6789-3p, the target of this gene, revealed that increasing the concentration of thymoquinone and quercetin increased the expression, and low concentrations of these two substances decreased the expression of this microarray. It is possible that this microarray targets the ANO9 gene at the concentration of 20 ?M thymoquinone and 50 ?M quercetin. The data showed that the expression of has-miR-154-3p increased with

     Breast cancer is one of the most common types of cancer in women, influenced by various factors including growth factors, cytokines, and extracellular matrix (ECM) components. These factors can induce changes in cellular pathways, leading to increased growth and proliferation of cancer cells. MicroRNAs (miRNAs) are short RNA molecules involved in gene regulation and cellular function. In breast cancer, alterations in miRNA expression can play a significant role in the initiation and progression of the disease. Their roles include regulating the expression of key genes, modulating cellular pathways, influencing treatment resistance, and affecting tumor size and composition. Investigating the role of miRNAs in cellular processes and their expression patterns can enhance our understanding of breast cancer and aid in the development of effective therapeutic strategies. Hypoxia, or oxygen deficiency, is a crucial feature of the tumor microenvironment that can impact tumor growth, progression, and response to treatment. Cobalt chloride II (CoCl2) serves as an artificial hypoxia model in cellular and cancer research. In this study, the effect of CoCl2-induced hypoxia on the expression of genes such as TSG6, IDO1, and TEX10, as well as their targeted miRNAs in breast cancer cells, was examined. Using bioinformatics tools such as Targetscan, miRDB, and miRBase, the binding sites, scoring, and overlap of hsa-miR-23a-3p, hsa-miR-6728-3p, and hsa-miR-576-3p were analyzed, identifying them as target miRNAs for TSG6, IDO1, and TEX10, respectively. In the experimental phase, MCF7 breast cancer cells were treated with CoCl2 at concentrations of 75, 150, and 200 ?M for 24 hours. Following treatment, RNA and miRNA were extracted, and cDNA was synthesized. Gene and miRNA expression changes were then assessed using Real-time PCR. Data analysis revealed that TSG6 expression increased at 75 and 150 ?M concentrations, with a significant increase observed only at 75 ?M compared to the control, suggesting that some gene responses may be concentration-dependent. The expression of miR-23a-3p, the target miRNA for TSG6, decreased at all concentrations, with a significant reduction observed only at 150 ?M. Additionally, hsa-miR-6728-3p and hsa-miR-576-3p also showed reduced expression at all concentrations, with significant decreases at 150 and 200 ?M for hsa-miR-6728-3p and at 150 ?M for hsa-miR-576-3p. It is worth noting that the genes targeted by these miRNAs, IDO1 and TEX10, were excluded due to unsatisfactory results and non-specific bands. In conclusion, the study demonstrates that CoCl2-induced hypoxia can have varied effects on gene and miRNA expression in breast cancer cells. These findings could contribute to a deeper understanding of cellular processes in breast cancer and aid in the development of more effective treatment approaches.   

   Breast cancer is the most common malignancy in women, which can arise due to various factors including hormonal, genetic, and environmental changes. In this cancer, disruptions in signaling pathways or deficiencies in DNA repair pathways can lead to tumor growth and progression. Understanding the molecular biology of breast cancer assists in diagnosis, personalized treatment, and development of therapeutic strategies. One of the characteristics of most solid tumors is hypoxia. In general, cells respond to hypoxic conditions with different cellular and molecular reactions, which help to regulate metabolism, energy production and cells under hypoxic conditions. MicroRNAs (miRNAs) are small non-coding RNA molecules that play crucial roles in biological mechanisms such as apoptosis, cellular differentiation, proliferation, and responses to stressors including hypoxia. Under hypoxic conditions, certain miRNAs can function as either repressors or activators of gene expression. In laboratory studies. cobalt chloride (CoCl2) is used to induce hypoxic conditions in cells. we investigated the effect of hypoxia induced by cobalt chloride (II) on the expression of ANO9, SIRT1, and PLK4 genes as well as their target miRNAs in MCF7 breast cancer cells. Initially, using various bioinformatics tools such as TargetScan, miRDB, and miRBase, target miRNAs for the receptor genes of interest were evaluated based on scoring, binding site suitability, and overlap with other software. Ultimately, hsa-miR-6789-3p, hsa-miR-154-3p, and hsa-miR-3065-5p were selected as the target miRNAs for the ANO9, SIRT1, and PLK4 genes, respectively. Additionally, the MCF7 breast cancer cell line was cultured under appropriate conditions, after which treated with cobalt chloride (II) at concentrations of 75, 150 and 200 µM. After RNA and miRNA extraction, cDNA was synthesized from the samples. Finally, Real-time PCR was used to examine changes in the expression of the genes and their target miRNAs. Subsequently, the results were analyzed using the Livak method and GraphPad Prism software. The findings revealed that the expression of the ANO9 gene significantly increased at all three concentrations, with the most pronounced increase observed at 150 µM cobalt chloride (II) compared to 75 and 200 µM concentrations. Conversely, the expression of hsa-miR-6789-3p, the target miRNA for the ANO9 gene, decreased with increasing concentrations of cobalt chloride (II). Analysis of SIRT1 gene expression showed a significant initial increase with cobalt chloride (II) concentrations rising from 75 to 150 µM, followed by a relative decrease at 150 µM and a significant reduction at 200 micromolar. In contrast, the expression of hsa-miR-154-3p revealed a significant increase at both 150 and 200 µM concentrations. Additionally, hsa-miR-3065-5p decreased with increasing concentrations of cobalt chloride (II). Notably, the expression of the PLK4 gene, the target gene for hsa-miR-3065-5p, was excluded due to a lack of specificity in binding and suboptimal results.   

   Sulfonamides and their derivatives are classical carbonic anhydrase inhibitors (CAIs) currently employed in clinical settings. Much research is centered around enhancing the efficacy of sulfonamide derivatives as potent CAIs. Nevertheless, numerous sulfonamide compounds exhibit no  ecific inhibition of all CA isoforms, leading to reduced drug efficacy and the occurrence of undesirable side effects due to off-target inhibition. Consequently, non-classical CAIs, such as inhibitors that contain carboxylic acid groups, have been employed to selectively target specific isozymes, minimizing adverse effects. In this study, we investigated the interaction between sulfonamide/carboxylic acid derivatives as novel non-classical inhibitors and the hCA II by using various spectroscopic and docking methods. The kinetic data demonstrates that compounds 1 and 2 share a similar inhibitory strength against hCA II, effectively inhibiting its esterase activity through a noncompetitive mechanism with Ki values at low micromolar levels. Fluorescence measurements indicated that the synthesized compounds suppressed the inherent fluorescence of hCA II via a static quenching process, with each compound showing a single binding site within the hCA II structure. A thermodynamic analysis highlights the significance of van der Waals interactions and hydrogen bonds in the binding of these compounds to hCA II. Docking results showed that both compound 1 and compound 2 effectively obstruct the entrance to hCA II's active site, with no significant differences in their binding conformations. While compounds 1 and 2 exhibit CA inhibitory potency lower than that of sulfonamide compounds, this study offers valuable insights that could pave the way for the development of a promising scaffold for designing new CA inhibitors.

   Abstract    Colorectal carcinoma (CRC) is one of the most common cancers and one of the main causes of cancer death in the world. Colon cancer begins at the colon (the end of the digestive system) and usually affects the elderly, although it can occur at any age. Inhibitors of histone deacetylases (HDACis) such as sodium butyrate inhibit the growth and induce apoptosis in CRC. On the other hand, the concentration of oxygen in the tissue is one of the most important factors in determining the behavior and function of the tissues. Oxygen deficiency or hypoxia can induce some factors in the development of cancer. Cobalt II chloride induces hypoxia by stimulating Hif1-? expression. Despite the previous studies in the field of investigating the effect of sodium butyrate and cobalt chloride II on the cellular and molecular characteristics of colorectal cancer cells, but no study has been conducted on the simultaneous effect of these two compounds and as a result of inhibition of histone deacetylase enzyme and hypoxia on colorectal cancer cells. Therefore, this study is designed to investigate their simultaneous effect on cellular and molecular characteristics of a rat colon cancer cell line called CT-26. CT-26 cells line was cultured in suitable laboratory conditions and 10% fetal bovine serum (FBS). This study aims to investigate the effect of different concentrations of cobalt II chloride, sodium butyrate and a mixture of both on survival, proliferation, apoptosis, cell cycle, antioxidant capacity, cell migration and expression of Hif-1a, Hdac1, Casp-3, C-met, Oct-4 and lncRNA-H19 genes. Then were prepared in CT-26 cell line at different time. The results of the MTT assay showed that in the period of 24, 48 and 72 hours, the percentage of cell viability decreases depending on the time. Also, with NBT assay, it was found that the amount of ROS production increased in all three treatments and with the passage of time, the ROS accumulation graph decreased significantly. The evaluation of cell migration test with different concentrations of both compounds and a mixture of them showed that cells migration increased in cobalt chloride II treatment within 24 hours. But after 48 hours, it decreased to an insignificant amount. While the cell treatment with sodium butyrate and the mixture concentrations in both 24 and 48 hours led to a decrease in cell migration. In order to investigate the cell cycle using flow cytometry technique, they were treated with cobalt II chloride and sodium butyrate and a combination of both. Treatment of cells with cobalt chloride led to accumulation of cells in G2/M phase of cell cycle. While the treatment of cells with 0.1 and 0.2 millimolar sodium butyrate respectively led to the accumulation of cells in the G2/M and G0/G1 phases of the cell cycle. In the mixed treatment, the population of cells was often stopped in the G2/M phase. The results obtained from the analysis of gene expression by real-time PCR method with cobalt chloride II treatment compared to the control group, no significant expression changes were observed in the expression of genes (Oct-4, c-Met, Casp-3, Hdac1, Hif1-?, lncRNA H19). However, in the treatment group with sodium butyrate, the expression of c-Met gene increased by 7.81% and the expression of Hdac1 gene decreased by -4.99%. Also, in mixed treatment, the Hdac1 gene expression decreased by -22.62% and a significant increase of 1.67% was reported in Oct-4 gene.   In this study, it was reported that the treatment of CT-26 cells with cobalt chloride II, sodium butyrate and mixed treatment with specific concentrations, it leads to reduction or stoppage of cell growth, reduction of cell migration and changes in gene expression. Keywords

SOX2, HIF-1a, HDAC1, and c-MET genes. And lncRNA-H19 and Casp-3 were prepared in MCF-7 cell line at different time intervals and cultured in optimal laboratory conditions. The results of the MTT test showed that increasing the concentration in the treatment with cobalt II chloride, sodium butyrate, and the combination of these two together, significantly decreases the survival of MCF-7 cells. Also, using the NBT test, it was proved that the amount of ROS accumulated in the cell increased with the increase in concentration in all three treatments. While, with the passage of time, the graph of ROS accumulation decreased significantly. Evaluation of migration was done with different concentrations of both compounds and a mixture of them. The results showed that the treatment with cobalt II chloride increased the migration of cells compared to the control group. In the treatment group with sodium butyrate, a decrease in migration was observed compared to the control group. In addition, in the mixed treatment of both compounds, a decrease in migration was observed compared to the control group. In order to investigate the cell cycle using flow cytometry technique, they were treated with cobalt II chloride and sodium butyrate and a combination of both. The results showed that cobalt chloride II led to the aggregation of cells in the G2/M phase, the cells treated with sodium butyrate aggregated in the G2/M phase and the group treated with a higher concentration of sodium butyrate aggregated in the G0/G1 phase. In the combined treatment of both compounds, the population of cells was often arrested in the G2/M phase. Also, the effect of treatment with sodium butyrate cobalt chloride II and a mixture of both compounds was measured by Real-time PCR technique to investigate the expression of, HIF-1?, HDAC, c-MET and lncRNA-H19 genes. In the treatment with cobalt II chloride, the expression level of c-MET and HDAC genes decreased, and the expression of HIF-1? and H19 genes increased compared to the control group. In the treatment with sodium butyrate, the expression of HDAC gene decreased and the expression of HIF-1?, H19, c-MET genes increased compared to the control group. In the treatment group with a mixture of two compounds, the expression of HDAC and c-MET genes decreased and HIF-1? and H19

      طب سنتي يكي از علوم تجربي است كه با ظهور و پيدايش علوم مدرن همچنان اهميت و جايگاه خود را مانند گذشته حفظ كرده است. طب سنتي كه در گذشته حاصل كسب تجارب در زمينه­ي استفاده از روش­هاي درماني مختلف بوده است امروزه به صورت آكادميك و سازمان يافته شده تدريس و مورد بهره برداري قرار مي­گيرد. طب سنتي بنابر تعريف ارائه شده توسط سازمان بهداشت جهاني عبارت است از مجموعه­اي از مهارت­ها، دانش و روش­هاي مبتني بر تجربه كه به منظور پيشگيري، كاهش و درمان انواع بيماري­ها مورد استفاده قرار مي­گيرد. كتاب الصيدنه في الطب (داروشناسي در پزشكي) آخرين اثر ابوريحان بيروني است كه به صورت تنها نسخه­ي اصلاح نشده به زبان عربي به ما رسيده ‌است. اين اثر گرانبها منبعي در داروشناسي سده‌هاي ميانه­ي خاورزمين است كه در آن بيش از هزار دارو با منشا گياهي، حيواني و معدني با اشاره به نام‌هاي آن‌ها به بسياري از زبان‌ها و گويش‌ها توصيف شده‌ است. در صيدنه اثري از مدح و اهدا نامه معمول ديده نمي‌شود و از هدف‌هاي نوشتن آن نيز مستقيما سخني نرفته ‌است. بيروني با درك اهميت زياد اين مسئله، حدود ???? نام گياه، حيوان، ماده­ي معدني و فراورده‌هاي آن‌ها را به زبان‌هاي عربي، يوناني، سرياني، هندي، فارسي، خوارزمي، سغدي، تركي و جز اين‌ها گرد آورده و توضيح داده ‌است و بدين ترتيب گام جديدي در راه تنظيم و ترتيب اصطلاحات دارويي زمان خود برداشته ‌است. با توجه به اين كه تا كنون يك بررسي جامع در خصوص اين كتاب انجام نشده است اين پژوهش انجام شد و اميدواريم كه در آينده بتوانيم اطلاعات موجود در اين كتاب ارزشمند را استخراج و در صورت امكان به صورت يك پايگاه داده­ي مناسب درآوريم.    واژگان كليدي: طب سنتي، الصيدنه في الطب، پايگاه داده.       طب سنتي يكي از علوم تجربي است كه با ظهور و پيدايش علوم مدرن همچنان اهميت و جايگاه خود را مانند گذشته حفظ كرده است. طب سنتي كه در گذشته حاصل كسب تجارب در زمينه­ي استفاده از روش­هاي درماني مختلف بوده است امروزه به صورت آكادميك و سازمان يافته شده تدريس و مورد بهره برداري قرار مي­گيرد. طب سنتي بنابر تعريف ارائه شده توسط سازمان بهداشت جهاني عبارت است از مجموعه­اي از مهارت­ها، دانش و روش­هاي مبتني بر تجربه كه به منظور پيشگيري، كاهش و درمان انواع بيماري­ها مورد استفاده قرار مي­گيرد. كتاب الصيدنه في الطب (داروشناسي در پزشكي) آخرين اثر ابوريحان بيروني است كه به صورت تنها نسخه­ي اصلاح نشده به زبان عربي به ما رسيده ‌است. اين اثر گرانبها منبعي در داروشناسي سده‌هاي ميانه­ي خاورزمين است كه در آن بيش از هزار دارو با منشا گياهي، حيواني و معدني با اشاره به نام‌هاي آن‌ها به بسياري از زبان‌ها و گويش‌ها توصيف شده‌ است. در صيدنه اثري از مدح و اهدا نامه معمول ديده نمي‌شود و از هدف‌هاي نوشتن آن نيز مستقيما سخني نرفته ‌است. بيروني با درك اهميت زياد اين مسئله، حدود ???? نام گياه، حيوان، ماده­ي معدني و فراورده‌هاي آن‌ها را به زبان‌هاي عربي، يوناني، سرياني، هندي، فارسي، خوارزمي، سغدي، تركي و جز اين‌ها گرد آورده و توضيح داده ‌است و بدين ترتيب گام جديدي در راه تنظيم و ترتيب اصطلاحات دارويي زمان خود برداشته ‌است. با توجه به اين كه تا كنون يك بررسي جامع در خصوص اين كتاب انجام نشده است اين پژوهش انجام شد و اميدواريم كه در آينده بتوانيم اطلاعات موجود در اين كتاب ارزشمند را استخراج و در صورت امكان به صورت يك پايگاه داده­ي مناسب درآوريم.    واژگان كليدي: طب سنتي، الصيدنه في الطب، پايگاه داده.   

  Nowadays, the use of mesenchymal stem cells (MSCs) as a suitable therapeutic method to treat many disorders is increasing and becoming a popular research topic. due to their unique feature in migration, proliferation, differentiation, and immune-modulatory activities These cells have become one of the most used stem cells in recent decades. One of the reasons for the well-received of these cells is their ability to treat immune disorders and repair damaged tissues. In vitro Treating cells with various chemical compounds that seem to be able to amplify the unique feature of mesenchymal stem cells can be a useful approach for the furtherance of medical science. Epigenetics and hypoxia induction play a significant role in guiding mesenchymal stem cells. The purpose of this research is to investigate the effect of sodium butyrate as a compound that causes epigenetic changes (histone deacetylase inhibitor), cobalt II chloride as a hypoxia inducing compound, and also the mixture of these two compounds on the ability to survive, proliferation, migration and immune regulatory effect of mesenchymal stem cells with the In vitro conditions. many studies have been done on the effect of these compounds on other different cells. But so far, no study has been done as this study was conducted on the effect of these two compounds and their mixture on human mesenchymal stem cells. In this study, the effects of different concentrations of sodium butyrate, cobalt II chloride, and the mixture of these two compounds on the survival, proliferation, and production of reactive oxygen species (ROS) of MSCs were measured respectively by MTT, trypan blue, and NBT tests. Further, the effect of these compounds on the cell cycle, cell migration, and the expression of the studied genes were also investigated respectively by flow cytometry, wound healing, and RT-PCR tests. It was observed that sodium butyrate, cobalt II chloride, and the mixture of the two compounds reduce cell survival and increase the level of ROS in mesenchymal stem cells. It was also observed that sodium butyrate stops the cell cycle in the G0/G1 and G2/M phases, cobalt II chloride stops it in the G0/G1 phase and the mixture of the two substances stops the cell cycle in the G2/M and G0/G1 phases. In the following, it was observed that cobalt II chloride has an increasing effect on the migration ability of mesenchymal stem cells, but sodium butyrate and the mixture of these two compounds do not have such an effect. Due to the multiple effects that these compounds have on MSCs. The effect of these compounds was investigated at the molecular level and the expression of TLR3, H19, HIF1?, c-MET, HDAC1, and SOX2 genes was measured under the influence of optimal concentrations of these substances. It was seen that the treatment of mesenchymal stem cells with cobalt (II) chloride increases the expression of TLR3 and H19 genes and decreases the expression of c-MET gene. Also, in the treatment of these cells with sodium butyrate, it was seen that this substance increases the expression of TLR3, H19 and HIF1? genes and decreases the expression of c-MET gene. In the following of this study, it was seen that the treatment of these cells with a mixture of two substances increases the expression of TLR3 and H19 genes and decreases the expression of the c-MET and HIF1? genes. In total, this study shows that all three compounds increase the immune-modulatory property of MSCs, and cobalt (II) chloride plays a significant role in enhancing the migration ability of mesenchymal stem cells.

   In the tumor microenvironment, differences in cancer cells' access to nutrients and oxygen modify cellular metabolism. Hypoxic cancer cells turn to glycolytic metabolism to survive and proliferate, producing large amounts of lactate that must be tra  orted out of the cell. During a metabolic symbiosis, oxidative cancer cells import the excess lactate and use it as a preferred fuel instead of glucose. Lactate tra  ort is facilitated by monocarboxylate membrane tra  orters (MCTs) belonging to the solute carrier gene family-16, which is a proton-dependent process and plays a role in intracellular pH regulation. The export of lactate from the cell is mainly facilitated by MCT4, while MCT1 mediates its intracellular uptake. Overexpression of these tra  orters has been shown to be associated with a variety of malignancies, including breast, gastric, lymphoma, brain, lung, skin, and soft tissue cancers, and targeting them could be a potential treatment for some types of cancer. In this study, we used various virtual screening techniques including pharmacophore modeling, molecular docking and molecular dynamics simulation to identify effective and potential drug candidates against human MCT1. The atomic coordinates of the protein in outward-open conformation were downloaded from the protein data bank with the code 6LYY, and a library of chemical compounds including 12 million molecules purchasable from the ZINC database and 4683 FDA-approved drugs was created. After performing the preparation steps, molecular docking calculations were performed based on a consensus approach using AutoDock Vina, Molegro, and DOCK programs. Ligands with high binding energy were analyzed in successive steps, and their interaction with key residues of the protein active site was investigated. Finally, seven ligands that showed promising results were selected for the molecular dynamics simulation study. For each protein-ligand complex in the membrane bilayer, calculations of protein backbone RMSD, ligand RMSD, RMSF, and interaction analyses were performed. The results showed that Olmesartan, an angiotensin II receptor inhibitor, can have an inhibitory effect on human MCT1 with a strong and stable binding and pave the way to inhibit this tra  orter. Since this study is based solely on computational tools, further evaluation in experimental conditions is necessary to confirm its effectiveness.

Mesenchymal stem cells are cells with special abilities such as pluripotency, high proliferative power, self-renewal, differentiation, escape from the immune system, etc. and are obtained from many sources and at all ages. The increasing applications of these cells in various fields such as cell therapy, personalized medicine, regenerative medicine and drug delivery show the high potential of these cells for clinical use. Due to the high importance of mesenchymal stem cells, it is very important to identify factors and conditions affecting their characteristics. Examining the interaction and effects of nanomaterials on these cells is of particular importance due to the high potential of both fields and the need for research and studies in this field. Nanotechnologies are developing rapidly due to the unique and key properties of nanomaterials. Manganese dioxide nanoparticles are considered one of the most attractive nanoparticles in research due to their excellent physicochemical properties, electrochemical stability, high surface area and abundance of resources, nanozyme activity, etc. These nanoparticles are used to eliminate the hypoxic conditions of the cancer microenvironment, increase the contrast in imaging methods such as MRI, drug delivery, etc. Therefore, investigating the effect of manganese dioxide nanoparticles on the characteristics and functions of MSC cells creates an attractive research field. In addition, by making surface changes in MnO2 nanoparticles, its properties and functions can be improved. There are several strategies to improve the performance and properties of nanoparticles. Surface modification by connecting different agents is one of the appropriate strategies to improve the performance and properties of nanoparticles. Amino acids are suitable candidates for coating nanoparticles due to having different functional groups and multiple roles in organisms. Also, there are not enough studies on the effect of chirality of surface agents on the properties of nanoparticles. In this research, MnO2 nanoparticles were synthesized by hydrothermal method and then functionalized by right-rounded and left-rounded forms of alanine. Then, to ensure the accuracy of the synthesis and binding of alanine forms, FT-IR, UV-VIS, DLS, zeta potential, EDX and SEM analyzes were performed, which indicated the proper synthesis of MnO2 and the binding of L and D forms of alanine to these nanoparticles. hTER-MSC cells were obtained from Ferdowsi University (Dr. Ahmadreza Bahrami's laboratory). Then, with the help of MTT, LDH, trypan blue, NBT, PI-flow cytometry tests, wound healing in the laboratory and gene expression investigation, the effect of these nanoparticles on survival, cytotoxicity, proliferation, pro/antioxidant, cell cycle arrest and gene expression, respectively Involved in these characteristics and fundamentality, immune regulation and lncRNA of MSC cells were investigated.

Mesenchymal stem cells (MSCs) have important properties such as, self-renewal, multipotent differentiation, migration, proliferation, differentiation and immune regulation. The use of natural compounds in the treatment of various diseases, including cancer, is very important. Among these compounds, we can mention flavonoids, which are abundantly found in fruits and vegetables. Considering the characteristics and capabilities of MSC cells in cell therapy, as well as the importance of using herbal compounds and new methods in the treatment of diseases, the purpose of this study is to investigate the effect of quercetin and cobalt (II) chloride on cell lines. To carry out this study, human mesenchymal stem cell lines were prepared and cultured in appropriate laboratory conditions. In order to investigate the effect of different concentrations of quercetin and cobalt chloride (II) on the survival of mesenchymal stem cells, MTT test is used in different time intervals. After that cells were treated with appropriate concentration of these compounds and the effect of this treatment on cell cycle and cell migration was evaluated. Also, the simultaneous effect of quercetin and cobalt chloride (II) on the expression of genes (Sox2, H19, Cas-3, c-Met, GAPDH, TLR3 and HIF-a) is investigated. The results showed that quercetin in high concentrations leads to an increase the number of cells by inducing the proliferation of mesenchymal stem cells. Also, the results of the NBT test indicated that quercetin causes free oxygen radicals in MSC cells in a time-dependent manner. This substance in concentrations induces cell migration. Also, the results of Real-time PCR analysis showed that the concentration of 80 µM of this substance causes the expression of TLR3 gene. During the treatment with cobalt chloride, the results showed that the concentration of 800 ?M significantly decreased the survival and proliferation of cells. For this purpose, in order to investigate the effects of this substance on the cell cycle, migration and gene expression, lower concentrations were used, and the flow cytometry results indicate the inhibitory effect of this substance on the cell cycle and stop cell proliferation. Also, the results of Real-time PCR analysis showed that at a concentration of 150 µM, this substance induces the expression of TLR3 and HIF-a genes. Quercetin without changing the basic characteristics of cells is known as a useful substance to enhance the proliferation and maintain the integrity of stem cells.   

سرطان پستان شايع ترين نوع سرطان و دومين عامل مرگ و مير در زنان است. عوامل موثر بر سرطان پستان شامل عوامل محيطي و ژنتيكي مي باشد. براي درمان اين بيماري از روش جراحي، پرتو درماني وشيمي درماني استفاده مي شود.   اما هركدام از اين روش ها با عوارض و محدوديت هايي نظير سركوب سيستم ايمني كارديوميوپاتي و افزايش احتمال ابتلا به سرطان اندومتر، مقاومت دارويي و عود مجدد بيماري مواجه هستند، به همين دليل امروزه به دنبال روش هاي درماني جايگزين هستند كه استفاده از تركيبات گياهي و فيتوكميكال از جمله روش هاي موثر در درمان سرطان است كه به تنهايي يا به صورت تركيبي با روش هاي درماني قديمي تر يعني شيمي درماني و پرتودرماني استفاده مي شود. ميوه ي انگور حاوي تركيبات فيتوكميكال است و با توجه به اينكه ميزان غلظت تركيبات فنولي و خاصيت آنتي اكسيداني هسته ي انگور نسبت به ديگر اجزاي انگور بيشتر است، از عصاره ي هسته ي انگور (GSE) در اين پژوهش استفاده شد. همچنين پژوهش هاي پيشين حاكي از آن بود كه انگور شاهاني ملاير نسبت به انگور عسگري تاثير ضدسرطاني بيشتري دارد، بنابراين در اين پژوهش از هسته ي انگور شاهاني ملاير استفاده شد. در اين مطالعه عصاره گيري هسته ي انگور به كمك اتانول انجام گرفت. سپس سلول هاي MCF-7 در پليت 96 خانه كشت داده شد و با غلظت 10، 25، 50 و 100 ميكروگرم بر ميلي ليتر از GSE به مدت 24، 48 و 72 ساعت مورد تيمار قرار گرفت و در ادامه با روش تريپان بلو و تست MTT تاثير اين غلظت ها بر تكثير رده ي سلولي MCF-7 سنجيده شد. براي بررسي سيكل سلولي از روش فلوسايتومتري استفاده شد و در نهايت به كمك روش Real-Time PCR، تاثير غلظت هاي 50 و 100 ميكروگرم بر ميلي ليتر بر بيان ژن P53 مورد ارزيابي قرار گرفت. تجزيه و تحليل داده ها نيزبه كمك نرم افزار SPSS، tseuQllec، LinReg PCR، REST 2009 sofware انجام گرفت. نتايج حاصل از اين پژوهش نشان داد كه غلظت هاي 50 و 100 ميكرو گرم بر ميلي ليتر GSE بيشترين تاثير را بر تكثير رده ي سلولي MCF-7 دارد، همچنين GSE شاهاني ملاير به صورت وابسته به زمان و غلظت، سبب توقف سيكل سلولي در فاز G0/G1 و القاي آپوپتوز به كمك افزايش بيان P53 مي شود و غلظت 100 ميكروگرم بر ميلي ليتر GSE بيشترين تاثير را در القاي آپوپتوز به همراه دارد.

Abstract Diabetes is a multifactorial, chronic and progressive metabolic disorder characterized by chronic elevation of blood sugar caused by defects in carbohydrate, fat and protein metabolism. Aspirin, also known as acetylsalicylic acid (ASA), is a drug used to reduce pain, fever or inflammation. Aspirin is used long-term to help prevent more heart attacks, ischemic strokes, and blood clots in people at risk. Due to the fact that no study has been conducted on the effect of aspirin on diabetes and its related pathways, the present study aims to investigate the effect of aspirin on the expression of genes involved in the development of pancreatic beta cells and the regulation of transmission. Glucose was measured in pancreatic and liver tissues of alloxan-induced diabetes rats. The present study was conducted on 24 adult male Wistar rats. These animals were divided into 3 groups of 8 including control (non-diabetic), alloxan-treated diabetic rats, and aspirin-treated diabetic rats. In order to investigate the effect of aspirin, changes in weight, blood sugar and expression of candidate genes including Ins1/2, Insr, Glut1, Glut2, Pdx1, and Tnfa were performed in liver and pancreas. The results of the present study showed that the administration of aspirin caused a decrease in blood sugar and weight in the treatment groups compared to the diabetic group. In addition, the relative expression of genes in the liver tissue has decreased in the comparison of the group receiving aspirin and the diabetic group, and this decrease in expression has occurred in a significant way in all genes. In the pancreatic tissue, comparing the diabetic group with the aspirin receiving group, the expression changes related to Pdx1and Ins1/2 are increased and the changes shown are significant. Also, the expression changes related to Insr and Tnfa decreased, although the decrease shown is not significant. In general, it was shown that the administration of aspirin can have an effect on various cell pathways and signaling involved in diabetes, in addition to affecting weight and blood sugar. In fact, the administration of aspirin has increased insulin expression by reducing inflammatory factors and positive effects on pancreatic tissue. Also, the administration of aspirin reduced insulin resistance caused by the Insr gene and modulated the expression of Glut genes. Key words: diabetes, aspirin, gene expression, pancreas, liver   

Abstract    Today, infertility is considered one of the most important problems in men, in such a way that clinical and epidemiological evidence has confirmed the increase in infertility in men. Several factors such as ionizing rays, magnetic fields, smoking, and some drugs lead to an increase in infertility in men. On the other hand, due to the effectiveness of some herbal medicines and chemical compounds in increasing male fertility, extensive research has been done to discover biologically active substances that can overcome the problem of male infertility. Also, due to the wide applications of stem cells, especially spermatogonial sperm cells (SSCs), and the use of natural substances, it has provided new hope for the treatment of many human diseases, especially infertility and maintaining fertility in men. vitamin C, due to the glutathione enzyme dependent on dehydroascorbic acid reductase, keeps the amount of vitamin C in the testicular tissue at a high level, in increasing the activity of sperm movement, increasing the quality Semen and fertility of rats play an important role, also Eugenol is a phenolic compound derived from clove extract, which has antioxidant, anti-inflammatory, and anti-cancer effects, Few studies have been done on the effect of these two compounds on SSCs. Therefore, this study was designed with the aim of studying the effect of vitamin C and eugenol treatment on fertility and the expression of genes involved in self-renewal (Plzf, Sox2) and differentiation (Dazl) of spermatogenic stem cells in rats. For this purpose, after treating the animals, their testicular tissue was separated. The expression patterns of different molecular markers in the testis were investigated using RT-PCR methods and histomorphological analyses of the testis tissue and the counting of its spermatogonia, spermatocytes, and spermatids.The results of this study showed an increase in the number of spermatogonial, spermatocytes, and spermatids cells in testicular tissue. In addition, it was found that the genes involved in self-renewal (Plzf, Sox2) and differentiation (Dazl) are expressed at the transcript level. Also, this study indicated that the use of eugenol alone had a greater effect than its treatment with other compounds, in addition, it was determined that vitamin C in the body according to the environmental conditions of the cell and the presence of free transition metals such as copper and iron. In addition to its antioxidant properties, it can also have a pro-oxidant effect.Overal, this study has presented a new perspective on the effect of natural substances and antioxidants on the expression pattern of molecular markers in SSCs and the increase in the number of sperm progenitor cells in rat testicular tissue.  Keywords: Treatment, Vitamin C, Eugenol, Self-renewality, Differentiation, Spermatogonial stem cells, Rat, Fertility  

   Natural products, including herbal formulas and extracts, have been used to treat human diseases for thousands of years, serving as valuable resources for treating diabetes. This study aimed to investigate the simultaneous effect of eugenol and ascorbic acid on the expression of genes involved in the regulation and tra  ort of glucose in diabetic rats treated with alloxan. To carry out this study, first after preparing the rats, keeping them and adapting them to the environmental conditions, the target groups were made diabetic by injecting 180 mg/kg body weight of the chemical substance alloxan and after making sure that they had diabetes; treatment with gavage of 10 mg/kg of body weight of eugenol and injection of 100 mg/kg of body weight of ascorbic acid to the target groups continued for 45 days. In the next step, the rats were anaesthetized, and after dissection, their liver and pancreas tissues were separated. After quick freezing with liquid nitrogen, they were placed in a -80 degree refrigerator. In the continuation of the work, RNA was isolated from all liver and pancreas tissues and cDNA synthesis was performed for all treatment and control samples. Then the expression of genes in pancreatic and liver tissue was checked using the Real-time PCR method. The results showed that the expression of Ins1/2, InsR, Glut2, and Pdx1 genes in the pancreatic tissue of treated rats increased significantly (P ? 0.05) compared to the diabetic control group, and the expression of Tnf? gene in the pancreatic tissue compared to the control group Diabetic showed a significant decrease in expression. In addition, in the liver tissue of the treated group, the expression of Glut1 and Glut2 genes significantly decreased compared to the diabetic and non-diabetic control groups, the expression of Tnf? gene compared to the diabetic control group without significant change, and increased compared to the non-diabetic control group, the expression of InsR gene showed no significant change compared to the diabetic control group and a significant decrease compared to the non-diabetic control group. Therefore, investigating the simultaneous effect of eugenol and ascorbic acid on the expression of genes involved in the regulation and tra  ort of glucose in diabetic rats showed that these natural products have an effect on blood sugar levels and also the antidiabetic capacity of the samples Treated with these products compared to tissue samples of diabetic control, they showed a significant increase in expression and a decrease in expression compared to non-diabetic control. Keywords: eugenol, ascorbic acid, rats, diabetes, glucose tra  ort

  In pharmacy, drug delivery is an essential part of drug production. Nanotechnology has emerged as a new approach to drug delivery. Radiopharmaceuticals, or radiopharmaceuticals, are a group of drug compounds that contain radioactive isotopes. In this research, magnetite nanoparticles with solution of iron (III) and iron (II) were prepared by precipitation method and then the surface of these nanoparticles was modified using thioglycolic acid at 37 ° C in aqueous medium. Then, 67 functionalized particles were labeled with gallium chloride solution. The results of TEM imaging showed that the average size of nanoparticles is 20 nm, which is a suitable size for biological applications. The stability of labeled nanoparticles was investigated using thin layer chromatography in normal saline medium and the results showed that 98% of labeled nanoparticles are stable. After determining the structure and characteristics of these nanoparticles, these modified particles were injected into rats and the type of adsorption and excretion in this biological structure was investigated. The complete circulation of these nanoparticles in the body began with entry into the liver and excretion through the kidneys and urinary system. The results showed that the prepared nanoparticles are fully compatible and stable, which makes it a suitable option for clinical diagnostic methods. Comparison of the results showed that the surface modification of nanoparticles completely changes their absorption and excretion behavior because of the new surface activating agent, namely thioglycolic, which has been used in this study.

During the last half century, the earth's surface has undergone many changes due to human activities through deforestation and urban development. The rate of biodiversity destruction is on the rise due to increasing human domination on natural ecosystems, and this fact becomes alarming when the degradation of human activities is exceeding existing efforts to conserve biodiversity. Human encroachments may impede habitat use by reducing mobility and communication. Bats, as bird mammals, are the second largest order after rodents. This group has a wide variety due to its flight power and echolocation. The use of habitat utility models in order to identify the preferred habitat as well as identify the connection routes of protected areas has become a reliable approach that if combined with field data and use of applied models can create important and reliable results that can be used as a tool for managers. The aim of this study was to investigate the distribution model as well as the   habitat patch connectivity of Rhinopoma microphyllum. 11 habitat variables including maximum temperature of the hottest month, seasonal temperature, isotherm, average daily temperature range, vegetation density, distance from surface water sources, altitude, annual rainfall, surface moisture, surface roughness and vegetation roughness near points beside the presence of species were used for modeling. Modeling was performed using the maximum entropy algorithm in MaxEnt software. In order to use the maximum number of points entered in the modeling process, the model was performed with 10 replications and cross-validation method was used to evaluate the model. Then, circuits cape theory by All-To-One method was used to identify connection paths in the study area. Since it is to identify the connection paths of habitat spots, habitat patches were identified using the TSS threshold and the their relationship was established. Based on the results of Jack Knife analysis, vegetation variables, then climatic variables, and finally topographic variables have an effect on species distribution. By applying the threshold limit on the desired habitat of the species, 30 habitat patches were identified, whose area varies from 221.04 square km as the smallest patch to 219416.78 square km as the largest spot, and covers 15.9 percent of the country area totally. The total length of the corridors was calculated 8338.32 km. Most of the connection paths in this study passed through open and low altitude areas and almost no connection path passed through desert areas to connect habitat patches. The largest habitat patch for the species includes the southern, southwestern and western parts as a continuous habitat, and there is no connection corridor in this large habitat patch.   

Over the past three decades, the increase in the number of people with diabetes has made it one of the most important challenges to all nations. The global prevalence of diabetes mellitus is increasing rapidly following lifestyle changes. Type2 diabetes mellitus is a complex multifactorial disease characterized by the interaction between multiple genetic loci and various environmental factors. Differences in the risk of developing type2 diabetes between different ethnic groups indicate the influence of genetic predisposition to developing it. The OPRM1 gene encodes the mu-opioid receptor, which is the major target for both endogenous and exogenous opioids in the pain relief process. Several studies examining the association between type2 diabetes and the 6q24-q27 region have suggested a role for the OPRM1 gene, based on its chromosomal location, in the risk of developing the disease. Another research suggests that the mu-opioid receptor may modulate genes involved in glucose metabolism, leading to lower plasma glucose levels. The most common single nucleotide polymorphism (  ) in the coding region of the human OPRM1 gene is the A118G variant, which results from the replacement of adenine with a guanine. This variant has been reported to alter both endogenous ligand (?-endorphin) binding and receptor signalling following this binding. The aim of this study was to investigate the association of A118G polymorphism in the OPRM1 gene with type2 diabetes mellitus because according to the above, the study of the gene polymorphisms can provide a new strategy for the prognosis of the disease and improvement of treatment strategies. In this study, 207 diabetic and 201 non-diabetic individuals (as controls) were selected and blood samples were taken from these individuals. Blood samples were used to extract DNA. The extracted DNA was used for PCR reaction to analyze for polymorphism using primers pre-designed by Primer1 online software, and then the PCR product was used for sequencing studies. Finally, the results of sequencing were analyzed to examine the presence of the    in different individuals. Sequencing results showed the presence of the corresponding polymorphism in the diabetic samples, while it was not found in control samples. Therefore, given the role of the OPRM1 gene in glucose metabolism, the presence of this polymorphism may be related to the risk of developing type2 diabetes; However, definitive results require further research.   

  reast cancer is recognized as the most common cancer worldwide amongwomen, regardless of age and race, and in various physical, psychological, economic, and social aspects, it can cause problems for the individuals, their family, society, and the health system. Therefore, finding new treatment targets, especially in aggressive and treatment-resistant subtypes of breast cancer, is significant. Hypoxia is an important regularizer biological parameter in cancer progression which leads to some resistance mechanisms to treatment. Nowadays, the use of various medicinal herbs has received much attention in the treatment of breast cancer due to their extensive therapeutic properties and minimal side effects. Thymoquinone (TQ) is considered as a bioactive compound in the black seed with vast remedial attributes in breast cancer treatment. In the recent study, to check the simultaneous effect of TQ and hypoxia caused by cobalt II chloride on MCF-7 cell line, first, the cells were cultured under appropriate conditions until they reached the optimal confluency. Then they were treated with 500 ng/ml TQ and 100 ?M cobalt II chloride for 24 hours. Finally, the expression of Sox2, Cdk4, c-Met, and Dnmt1 genes at the mRNA level was investigated by real-time PCR. The results of real-time PCR data analysis by Levak method with considering the meaningful level of FC?1.5 showed that the group treated with TQ and cobalt II chloride simultaneously compared to the control group (treated with only cobalt II chloride), the expression of all studied genes were decreased over a period of 24 hours, which considering a meaningful level greater than or equal to 1.5, these decreases are significant for Cdk4, c-Met, and Dnmt1 genes but not for Sox2

  owadays, finding new treatment methods for woundhealing with maximum efficiency and minimum side effects is important. In physiological condition, duo to wound, inflammation, and the secretion of various cytokines, cells especially fibroblast cells emigrate and proliferate to repair damaged tissue. By the use of different compounds, we can increase the rate of wound healing and repair of damaged tissue. Thymoquinone (TQ), a bioactive compound in the black seed, has extensive healing properties, especially in wound healing. In this study, to evaluate the simultaneous effect of TQ and cobalt chloride (II) on fibroblast cells, fibroblast cells were cultured in a suitable condition. Then they are treated with TQ (500 ng/ml concentration) and cobalt chloride for 24 hours. Finally, the expression of genes (Sox2, Cdk4, c-Met, Dnmt1) was analyzed in the transcription level by using a real-time PCR technique. Data analysis of real-time PCR showed that expressions of Cdk4 and c-Met genes in the treatment group increased to reach to 1.26 and 1.86 respectively in comparison with control groups during the 24 hours. Due to the significance level of 1.5, the increase in expression of c-Met gene was significant but the increase in expression of Cdk4 gene was not significant. During the mentioned period, the expression of Sox2 and Dnmt1 genes in the treated group with cobalt chloride and TQ decreased to get to -1.28 and -1.32, respectively in comparison with the control group that both of them was not significant. The results of the present study showed that the simultaneous treatment of fibroblast cells with TQ and cobalt chloride may increase the migration of these cells at the wound site by the effect on cell migration genes that result in wound healing

  Arginine is a semi-essential amino acid, which participates in many metabolic pathways, such as nitric oxide, creatine and urea synthesis. The availability of arginine is determined by a series of plasma membrane carries called cationic amino acid tra  orters (CATs), which are overexpressed in many types of cancers including Acute myeloid leukemia (AML) that is one of the most common cancers in adults and children; therefore, these tra  orters have been considered as a putative target in therapeutic and medicinal goals. In the present research, the mechanism of L-arginine tra  ort through CAT1 and hotspot amino acids in the tra  ortation was investigated using molecular dynamic simulation techniques. For this purpose, prokaryotic CAT1 (p-CAT) with PDB ID 6F34 was received from Protein Data Bank (PDB). Since eukaryotic CAT1 (e-CAT) has not yet solved, the e-CAT structure was modeled using MODELLER 9.20 based on p-CAT as template. After that, because the CAT proteins are membrane tra  orters, the proteins were inserted in the suitable membranes using CHARMM-GUI server. Then, molecular dynamics simulation was performed for 300 nanosecond (ns) for each system. In the next stage, L-arginine (L-Arg) was docked against both the equilibrated system using AutoDock VINA, and molecular dynamics simulation was run for 600 ns for each system. In order to calculate total free binding energy of L-Arg, MM-  A approach was carried out on both p-CAT and e-CAT trajectories. To determine the contribution of each amino acid residue to the binding energy, the per-residue energy analysis was performed. In the p-CAT/Arg complex, Ile40, Thr43, Asp111, Glu115, Lys191, Phe230, Ile234 and Asp237 had the greatest contribution toward the binding to L-Arg and were formed stable hydrogen bonds with it. The residues Ser44, Glu185, Asp270, Cys271, Ser350, Ser354 and Arg360 were found to be the highest contributing residues that interact with L-Arg in e-CAT/Arg complex. In order to evaluate the tra  ortation processes through CAT tra  orters and also to study more precisely the role of hot spot amino acids during tra  ort, the umbrella sampling method was employed. Hydrogen bond analyses revealed that in p-CAT, the residues Asp237, Glu115, Ser321, Glu245, Lys19 are the most involving residues in interaction with L-Arg during tra  ortation. In e-CAT, the residues Asp270, Glu185, Ser22, Asp20 and Arg27 are the most involving residues in interaction with L-Arg during tra  ortation. To investigate the effects of membrane lipids on the structures of p-CAT and e-CAT, membrane analyzes such as lipid-protein interaction, MSD, SCD, density and membrane thickness were performed for both systems. The results showed that protein loops had reduced flexibility due to interaction with lipids. Further, in eukaryotic membrane, due to the ordering effect of cholestrol, the SCD value and membrane thickness are higher than prokaryotic membrane.Key words: L-Arginine, CAT1 protein, molecular dynamics simulation, umbrella sampling

   Abstract Introduction: The accumulation of genetic and epigenetic changes in the epithelial cells of the intestinal wall converts them into malignant adenocarcinoma cells. In colorectal cancer, epigenetic changes such as DNA methylation in CpG islands occur to a large extent. Epigenetic studies on a number of genes have shown that methylation of the promoter region of the gene in colorectal cancer causes the expression of these genes to be silenced. Colorectal and healthy subjects are discussed..   Materials and Methods: In this study, we measured methylation rate for ITGA4 gene promoter region in 50 tumoral and adjacent normal tissue in CRC patients also 50 tumoral and normal stools by qMSP. In this teqnique, was used from TaqMan prob and primers for ITGA4 and ALU-C4 gene (for normalize of early DNA) and bisulfited DNA as templet. The level of methylated DNA (the percentage of methylated reference , PMR) was calculated for all samples using the following formula: [(ITGA4/ALU-C4)sample / (ITGA4/ALU-C4)positive control]x100. All data were statistically analyzed using    v 24.0 software. Findings :The results of this study showed that there was a significant difference between the mean PMR between the tumor and normal tissue samples of patients with colorectal cancer as well as between the stool samples of patients and healthy individuals (PValue <0.001) The median PMR for ITGA4 gene was 36.8 in tumor tissue and 10 in normal tissue samples. The mean PMR in tumor stool samples was 2.54 and in normal stool samples 0.01 Was . Sensitivity and specificity in tissue samples were 63% and 63%, respectively, and in fecal samples were 57% and 100%, respectively. Results: These results indicated significant difference in PMR mean between tumoral and normal tissue specimens of CRC patients and also between stool specimens of case and control groups. PMR mean in tumoral tissue samples was 18.95 and in normal tissue samples was 0.77. PMR mean mean in tumoral stool samples was 8.7 and in normal stool samples was 0.6. Sensitivity and specificity in tissue samples was 86% and 91.8% respectively. Also Sensitivity and specificity in stool samples was 82% and 91.8% respectively. Conclusion:DNA methylation of the ITGA4 promoter region in stool samples using MethLight PCR has the sensitivity and specificity as a noninvasive method for the detection of colorectal cancer. This study is the first report in Iran to investigate the methylation of ITGA4 gene in stool specimens in colorectal cancer. Therefore, it is suggested to use this gene as a biomarker of a diagnostic panel.

  Gastric cancer is aninvasive disease and one of the causes of mortality resulting from cancer inthe world, which is due to the accumulation of environmental factors and genetic changes. Despite the advent of food preservation technologies, accessto fresh fruits and vegetables, and better anticipation, gastric cancer is still known as the third cause of mortality in the world. The traditional receptors in the gastric cancer cells and also the relationship betweenapproaches to treating gastric cancer include surgery, radiotherapy, andchemotherapy, showing drug resistance and disease recurrence after a period,which these drawbacks have caused new treatment approaches. Drug repositioningwith the aim of using discovered drugs for new applications is a treatment estrogen and carcinogenesis, an anti-estrogenic drug, called tamoxifen,strategy to reduce time and costs. Regarding the expression of estrogen was used as an inhibitor of estrogen receptors in this experiment. In this study,a change in CT  1 gene expression was measured as one of the important genesThe cancer cells multiplied after culturing under appropriate conditions andof Wnt / beta-catenin signaling pathway in the gastric cancer cell line MKN-45.was selected as an appropriate dose over a period of 48 hours. Then, one groupthen, using the Tripan Blue test, the concentration of 100 micromolar tamoxifenof cells was considered as treatment group and the other group as control one. gene expression in the samples was investigated by real-time method usingRNA was extracted from the control and treatment cells and used to preparecDNA. The resulting cDNA was amplified by PCR and then the change of CT  1 expression of the CT  1 gene under treatment with 100 ?M of tamoxifen.specific gene primers. The results of real-time showed a decrease in the

    Climate change is one of the most important threats to biodiversity. During recent years, much attention has been focused on declining amphibians. Alien species including hunting fish, and global warming are the important factors of decline amphibians. One of the consequences of global warming is the early droughts of the ponds. On the other hand, amphibian densities in ponds are also affected by changes in water levels. In this study, the interaction effects of three factors including temperature, water level and density were investigated on snout-vent length (SVL), SVL at metamorphosis, time at metamorphosis, percentage of metamorphosis, cannibalism and survival of larvae of Pelophylax bedriagae which was previously known as Pelophylax ridibundus, carried out within 10 months. We designed a 2×2×3 factorial experiment, crossing two levels of temperature ( high =22.5 and low=18.5 ), two levels of density (low, n =5 and high, n =25) and three level of water (low: 300 cc, high 1400 cc, and decreasing 150 cc of water, Once a week). Results of experiment showed the highest survival rate in was observed in the low density / low water / low temperature with 73.33% ±5.77 and the lowest survival rate was observed in the high density / low water / low temperature with 13.31 % ±2.54. The highest hatching percentage was observed in the low temperature×   decreasing water level × low density (93.3 mm±11.54) and the lowest hatching percentage was observed in high temperature× high water level × low density (56.6 mm±15.27). Results of ANOVA showed that three temperature, density, and water level had not significant independent effects on the hatching but   interaction of three factors included temperature, water level and density had a significant effect on the hatching (P=0.05). The highest size at metamorphosis (SVL) was observed in high temperature × decreasing water level × high density (16.21 mm±1.89) and the lowest was observed in low temperature× decreasing water level × high density (10.33 mm±8.95(.Results of ANOVA showed that   temperature had significant independent effects on the size at metamorphosis (SVL)   ut water level and density had not significant independent effects on the size at metamorphosis (SVL). Interaction of three factors included temperature, water level and density had a significant effect on the size at metamorphosis (P=0.008).. Interaction of three factors included temperature, water level and density had a significant effect on the percentage of metamorphosis (P=0.05).  

Parkinson'sdisease is a neurodegenerative disease characterized by genetic and environmentalfactors that contribute to the disease. miRNAs are ribonucleotide sequences that control the expression of somegenes at the post-transcriptional level. In Parkinson's disease, miRNAsinvolved in the recovery or progression of the disease. Thetarget the genes of the various pathways involved in the disease that arevalidate the interaction between the desired predicted gene and hsa-miR-361-5p.   According to past studies,aim of this study was to predict the target genes of hsa-miR-361-5p and towith neurodegenerative diseases and subsequently in the cellular model of thesehsa-miR-361-5p has a decreasing expression pattern in the blood of patientsdiseases.   After selecting miRNAs formirwalk, genes involved in Parkinson's disease and their transcripts targetedthis study, using validated bioinformatics databases including Targetscan,to hsa-miR-361-5p , Predicted and identified. Then, one of these mRNAs that hadthe target gene of choice was shown to express the inhibitory role of miRNAs onthe opposite expression pattern to hsa-miR-361-5p was selected as the gene ofinterest. Finally, the binding and interaction of this miRNA with the 3?UTR ofgene expression in HEK293T cell line using luciferase reporter gene assay.

  AbstractCancer stem cells are the main cause of cancer, so resistance to chemotherapy drugs is attributed to this tumor cell. The main reason for the drug resistance of tumor cells is the inactivation and division of cancer stem cells into a tumor tissue. This cell population that is distributed unevenly in the tumor tissue, such as stem cells, is self-destructive and is responsible for the survival of the tumor and the differences in its genetic and metabolic characteristics. These cells were initially identified in 1997 by Dick and colleagues in chronic myeloid leukemia and then in a variety of cancers, including breast cancer and gastric cancer. Stomach stem cells are a potent candidate for the formation of gastric cancer. Gastric cancer is a multifactorial disease caused by interactions between genetic and environmental factors at the gastric mucosal surface. In cancer stem cells, one or more diversions have been observed in different pathways of signaling. For a better study of signal pathways in stem cells Cancer should separate them from non-cellular cells.Many studies have focused on the effects of selective estrogen receptor modulators, such as tamoxifen, as a good drug for the prevention and treatment of cancer. Therefore, in this study, we examined the effects of treatment of gastric cancer stem cells from the MKN-45 cell line on Wnt1 gene expression.In this study, we isolated gastric cancer stem cells from MKN-45 cell line by spherical formation, and the survival rate of gastric cancer stem cells under the influence of tamoxifen drug at concentrations of 100, 200, 400, 600, and 800 ?m after the passage 48 hours was evaluated by Trypan Blue test. Finally, the cells were treated with tamoxifen at a concentration of 100 ?M.The expression of Wnt1 gene expression under tamoxifen treatment revealed a reduction in the expression of this gene. Further evaluation of gastric cancer stem cells suggests that these cells undergo tamoxifen treatment, losing their tumorigenicity and colony formation.

  Endometriosis occurs in 6% to 10% of women of reproductiveage,1 is associated with chronic pelvic pain andinfertility, and represents a huge socioeconomic burden.2The defining feature of the condition is the presence ofendometrial tissue outside the uterine cavity, typically onthe peritoneal wall3 or the surface of the ovary

  CancerStem Cells (CSCs) are the source of many cancers, including gastric cancer.These cells are characterized by self-renewal, tumorigenicity, and resistanceto treatment. The results of the studies indicate the key role of the Wntsignaling pathway in controlling cancer stem cells and drug resistance   that created by these cells, which is reasonof most studies today focus on these cells. Also, tamoxifen is a non-steroidalanti-estrogenic drug that has been shown to have antitumoural effects. According to this information, we examined theeffect of certain concentrations of tamoxifen on the expression of CT  IP1in cancer stem cells derived from the MKN-45 cell line of gastric cancer as atherapeutic potential

AbsrtractHuman mesenchymal stem cells (MSCs) are increasingly being considered in cell-based therapeutic strategies for regeneration of various tissues. MSCs derived from different tissues, with unique feature, are one of the most useful raw materials in cell therapy and tissue engineering. Despite the MSC inherent migration ability to the site of injury, inflammation or tumor, the in vivo and in vitro migration efficiency of the cultured MSCs is still not satisfactory. As a result, scientists are always looking for ways to improve MSC functions. In addition to the use of cytokines and chemicals to increase the expression of molecules involved in migration process, the use of medicinal plants in the biological domain has been considered. One of the herbaceous species used is black seed and its active compound, Thymoquinone (TQ). Despite numerous studies on the therapeutic applications of TQ, its effect on MSC migration has remain to be clarified. Thus, this study aimed to evaluate the effect of TQ on mice bone marrow-derived MSC migration and examining its effects on the expression of specific genes involved in migration. To do this research, MSCs were isolated from the mice femurs and tibias bone marrow. In order to investigate the effect of different TQ concentrations (0, 75, 150, 250, 500 ng/ml) on MSC migration in serum free DMEM/F12 medium, wound healing assay was performed. Cell migration was investigated 24 and 48 hours after treatment. After determination of the optimal TQ concentration and sufficient time to repair the cellular scratch in wound healing assay, MSCs were treated with TQ (250 ng/ml) for 48h. To check the expression level of genes involved in MSC migration (c-Met and Ccr1), RNA extraction and cDNA synthesis from the control and treated cells were performed and the expression of candidate genes was evaluated using Real-time PCR.   The results of the wound healing assay indicated a significant (P<0.05) increase in the percent gap closure of treated cells with 250 ng/ml TQ at 48h, compared to the control cells. Also, the gene expression analysis demonstrated a significant increase (3/8 fold) in c-Met gene expression and a non-significant change (1/1 fold) in Ccr1 gene expression in TQ-treated cells compared to the control cells. Altogether, this study indicated that TQ increases the migration potential of MSCs in vitro. Therefore, the results of this study provide a good prospect for using TQ to improve the MSC migration in cell therapy. However, further studies are needed to investigate the TQ effect on the expression of other essential and important MSC migratory genes and also the in vivo migration potency of the treated cells.  Keywords: Mouse, Mesenchymal stem cell, Thymoquinone, Migration, Gene expression, Wound healing assay.

    Identification of the core gene regulatory network involved in conversion of PC12 cell line into neuron-likecells by staurosporine.

Abstract Nowadays, stem cells, particularly mesenchymal stem cells (MSCs), and the use of natural ingredients have provided new hopes for treating many human diseases.   MSCs are one of the most applicable cells for cell therapy because they are easily isolated from adult tissues and have unlimited proliferation potential. In addition, these cells have the most significant effect on immune system due to their immunomodulatory properties. Eugenol is a natural and versatile vegetable molecule, which has a wide variety of applications in different fields. Eugenol is an extract clove-derived phenolic compound which has anti-oxidant, anti-microbial, anti-inflammatory, anti-cancer, anti-mutagenicity, anti-spasmodic, anti-fungal, anti-seizure, anti-fever and analgesic activity. Despite extensive studies on the biological and pharmacological effects of Eugenol, there is no report on its effects on MSCs functions and properties, especially on their immunomodulatory properties. Therefore, the aim of this study was to investigate the effects of Eugenol on the expression of genes involved in the immunomodulatory ability of mouse bone marrow-derived MSCs (BM-MSCs).In this study, MSCs were isolated from mouse (NMRI) femur and tibia, then cultured in medium with 15% FBS. In order to confirm the identity of MSCs, we employed differentiation assays into osteoblasts and adipocytes. Then, the effect of different concentrations of Eugenol on the viability of MSCs was evaluated by MTT assay at 24, 48, and 72h. After determining the IC50 value and concentration which about 90% of MSCs were alive, MSCs were treated with Eugenol. We extracted RNA from the Eugenol-treated and control (without treatment) MSCs. DNase I treated RNAs were used to synthese cDNAs. The expression level of target genes (Tlr3, Tlr4, Ccl2, and Ccl3) in the samples was measured by real-time PCR method.MSCs were isolated from mouse bone marrow and their identity was confirmed by differentiation into adipocytes and osteoblasts. The IC50 values of Eugenol on MSCs were 400 ?g/ml at 24 and 48h and 200 ?g/ml at 72h after treatment. Furthermore, MTT assay results showed that about 90% of MSCs were alive at concentrations less than or equal to 12.5 ?g/ml at 24h after treatment. Therefore, the concentration 10 ?g/ml was used to determine the effect of Eugenol on the expression of target genes at transcript level in BM-MSCs. The results of the quantitative gene expression analysis by real-time PCR indicated that Tlr3, Tlr4, Ccl2, and Ccl3 genes upregulated 1.5 -, 1.8-, 1.3 -, 2.2 -fold, respectively, in Eugenol treated-MSCs compaired to untreated controls In general, according to the results of this study, Eugenol-treated MSCs show increased expression of Tlr3, Tlr4, Ccl2, and Ccl3. Therefore, it can be concluded that Eugenol influences the immunomodulatory properties of MSCs by overexpression of this genes. Furthermore, the results of this study can provide a situation for further studies in the field, which may finally improve and increase the therapeutic potential of MSCs for research and clinicla applications.           

  AbstractMesenchymal stem cells (MSCs) have receved considerable attentio   in the last 15 years. These cells provide a new hope for treatment of many diseases, therefore, scientists try to find efficient protocols to maintain and enhance MSCs behavior and function in vitro using natural and chemical component. Eugenol is the most important component in Caryophillium aromaticus that has several effects such as anti-cancer, anti-inflammatory, anti-inflammation, anti-mutation, anti-oxidant, anti-virus, anti-fungal, anti-microbial and anti-bloat. However, the effects of Eugenol are well known, its effect on MSCs has not been studied yet. Due to the therapeutic advantages of Eugenol and also the importance of proliferation and migration of MSC in new treatment protocols, the aim of this study was to investigate the effect of Eugenol on the proliferation and migration of MSCs derived from mice bone marrow in vitro.In this study, bone marrow MSCs were isolated from 4 to 8 week old NMRI mice. The identity of MSCs was evaluated by differentiation assays into adipocytes and osteoblasts. To investigation the effect of Eugenol on MSCs migration and proliferation, wound healing and MTT assays were used and the IC50 values was determined at 24h, 48h and 72h after treatment. In continue, to examine the effect of Eugenol on MSCs proliferation and migration, the expression of Rex1, Sox2, Vla4, Cxcr4 genes was evaluated by Real-time PCR.

  AbstractGastric cancer is the second most common cancer and cancer-related death in the world. The uncontrollable cell proliferation and metastasis is the problem most cancers, including gastric cancer. the effective factors in Uncontrolled cell proliferation and metastasis can be noted to distinct population and rare of Starter Cancer cells (in various cancers) that called cancer stem cells , cause tumor   growth, local invasion and metastasis to distant tissues at each malignant tumor. PlGF is a placental growth factor that Its role is well known in angiogenesis, metastasis and invasion to lymph node and in various studies have shown that reduced expression of these genes decreased metastasis, angiogenesis and Offensive power in malignant tumor. Hence it appears that PlGF gene expression in marker gene expression may play a role in cancer stem cell that this topic Was evaluated the first time in this study. In this study, first AGS cells as to human gastric carcinoma were treated with various concentrations of Scrambled siRNA and PlGF-siRNA and was evaluated In conditions in vitro and using the method trypan blue cytotoxicity. Gene expression of PlGF, SOX2, OCT3 / 4, CD44 was evaluated   with quantitative measurement method Real-time RT-PCR . After securing the PlGF gene effects on gene expression of SOX2, OCT3 / 4, CD44, via spheroid colony formation technique, cancer stem cells were isolated from other cells of two cell lines AGS and MKN45 for the first time without the use of growth factors.Isolation of cancer stem cells with a certain concentration of SIRNA was treated against PlGF gene and gene expression of PlGF, SOX2, OCT3 / 4, CD44, PCNA and Caspase was evaluated with PCR RT-Real-time quantitative assay and as well as the inhibitory effect of PlGF gene was investigated on the strength of angiogenesis, migration, metastasis, cell proliferation, apoptosis and differentiation ability of gastric cancer cells. As a result of this investigation was determined which Scrambled siRNA had no effect on the survival of AGS cells, but PlGF-siRNA reduced the survival of AGS cells. Real-time PCR RT results indicated expression of SOX2 and decreased expression PlGF, CD44 and OCT3 / 4. In addition, checkrein of PLGF gene increased SOX2 expression and decreased expression of PlGF, PCNA, OCT3 / 4, CD44 at isolated stem cells from both cell lines of AGS and MKN45. As well as angiogenesis, invasion, metastasis, cell proliferation and differentiation ability of these cells was reduced compared to the cancer stem cells but the checkrein of PLGF gene has no effect on apoptosis of gastric cancer stem cells.Keywords: gastric cancer, cancer stem cells, PlGF,SOX2,OCT3/4,CD44