Search

Gene is a factor encoding genetic information and the basic unit of inheritance. Gene expression is a phenomenon consisting of two complex stages of transcription and translation. In this study, the yeast cell of Saccharomyces cerevisiae evolution is investigated due to the importance of the gene expression phenomenon. To clarify the accuracy of the obtained results, we have used experimental data on the Saccharomyces cerevisiae yeast cell from the gene bank. We are using chaos theory to study gene expression due to the nonlinear dynamics of the phenomenon. The obtained results predict that, by increasing the rate of degradation in the messenger arena to 0.03, we have reached the threshold value for the gene expression phenomenon. Also, we have recognized that increased transcription is associated with an increased mRNA degradation rate. The optimal values of transcription delay rate (18.2 min) and protein degradation rate (0.03) were obtained. There was a good agreement between the experimental and theoretical results.

Background & Aims: Cancer is one of the most important issues in the world which affects public health as an important problem. Cancer is the third cause of death in Iran with an annual occurrence of 51,000 new cases [1]. Previous studies demonstrated the considerable increasing trends in the mortality of gastrointestinal cancer in Iran, especially for Gastric cancer and colorectal cancer [2]. In general, incidence rates of these two cancers are high in Eastern Europe, Eastern Asia, and South America and the lowest rates are in North America, and most parts of Africa [3]. The most critical factors that increases the risk of gastrointestinal cancer are aging, inappropriate diet, biological factors, and infectious diseases which contribute to the cancer occurrence [4]. Colon cancer is studied to be one of the most critical digestive diseases and is the second leading cause of cancer deaths [5]. Gastric cancer is important cancer in the world and the prevalence of gastric cancer is raised with aging in both men and women [6]. Colon cancer is a disorder in which malignant cells form in the large intestinal tissues [7]. On the other hand, in gastric cancer the malignant cells form in the lining layer of the stomach caused it. The risk of gastric cancer is high in Iran, and unlike in Western countries it is not under the control, thus it is on a dramatically increasing trend in Iran [8]. Secondary metabolites and phenolic compounds of plants can play an important role in reducing the side effects of chemotherapy drugs and have some positive effects on cancer cells, as well as in the expression of apoptotic pathway genes [9]. Colutea persica was used in traditional medicine as an anti-inflammatory agent in gastrointestinal problems [10]. The aim of this study was to investigate the cytotoxic effects of aqueous and hydroalcoholic extracts of Colutea persica on gastric cancer (AGS), colon cancer (HT-29), and normal fibroblast (SKM) cell lines. Methods: Fresh Colutea persica leaves were collected from the Delfard region of Kerman province in 1399. Dried leaves of Colutea persica were ground into a fine powder by the electronic grinder. At the next step, the ground powder was extracted using ethanol by the maceration. Then, it was placed on a shaker at room temperature. After that, the collective extracted was filtered using a filter membrane. The solvent extracted was evaporated in the rotary evaporator. Finally, to completely remove the solvent, the extract was placed in an oven, and the hydroalcoholic extract was maintained at -20 °C until use. In order to measure the total flavonoid content (TFC) of the extracts the aluminum chloride complex-forming assay was applied. In this method, quercetin was applied as the standard which flavonoid content was distinguished based on the quercetin equivalent. Briefly, Colutea persica extract was added to the aluminum chloride hexahydrate and mixed with potassium acetate and distilled water. After 30 minutes, the absorbance of the reaction was checked using a UV-Vis spectrophotometer at 415 nm. The blank sample was made by replacing aluminum chloride with deionized water. Before measuring, all of the solutions were filtered by using Whatmann filter papers (number 41). Total flavonoid content in Colutea persica extract was measured using the standard calibration curve which is achieved from different concentrations of the standard reference. The total phenolic content (TPC) of organic crude extracts was calculated using the FolinCiocalteu reagent method. In this method, gallic acid was used as a reference standard (20-100 μg/mL) for plotting the calibration curve. 0.5 mL of the Colutea persica extract was added to 1.5 mL of Folin-Ciocalteu solution. Then, it was diluted (1:10) with deionized water and added to the sodium carbonate solution. The absorbance was recorded after one hour at 765 nm by using a UV-Vis spectrophotometer. Finally, the total phenolic content was calculated based on gallic acid equivalents (mgGAE/g). All the experiments were done in triplicate. Cytotoxic effects of 5, 10, 25, 50, 100 μg/ml concentrations of aqueous and hydroalcoholic extracts were evaluated on the cells for 24 hours using MTT assay. The apoptosis induction was monitored using flowcytometry by annexin-V FITC/PI doublestaining. Cells were seeded and after 24 h they were incubated with a 1.25 mg/ml concentration of the extract and for each treated cell line, one control cell was considered. The annexin V/PI assay was performed to confirm the cytotoxic activity of the plant extracts against AGS and HT-29 cell lines. Total RNA was isolated from cells using RNX-plus TM Reagent before and after treatment. Total RNA was reverse transcribed to cDNA using M-MuLV-RT and random hexamers. The cDNA was assayed by real-time PCR using primers for BAX and BCL-2 genes. Data were analyzed using SPSS software, one way ANOVA, Tukey test at p ≤0.05... Results: The MTT assay revealed the cytotoxicity against both two cell lines (HT29 and AGS) in comparison to the HT29 and AGS normal cell line (SKM). The expression level of BAX gene increased and BCL2 gene decreased in AGS cell line after treatment by plant extract. (p<0.05). The total phenolic content was expressed in terms of milligram gallic acid equivalent per gram dry weight of plant extract. The total phenolic content of hydroalcoholic and aqueous extracts of Colutea persica were 5.02±.05 and 5.85.±0.08 mgGAE/g respectively. Conclusion: In conclusion, our findings show that Colutea. persica has anti-cancer effects in vitro against AGS and HT-29 cancer cell lines. Induction of apoptosis by using plant extract was achieved by down-regulation of BCL2 and up-regulation of BAX. Finally, the current study suggests that Colutea. persica may have cancer-fighting properties and could be a promising new candidate in this field. Besides, the molecular target of Colutea. persica and its mechanism are unknown, and the author intends to use animal models and bioinformatics methods to discover the active ingredients of Colutea. persica. [ABSTRACT FROM AUTHOR]

Background: After breast cancer, cervix neoplasm is the most common disease among young women. Nowadays, natural substances are used in the treatment of diseases, because of the known side effects of the chemical drugs. Dunaliella is a green alga that lives in the saltwater lakes of Iran and is abundant in antioxidant substances. This paper aimed to study the effect of Dunaliella extract on the expression of the anti-apoptotic BCL-2 gene in Hela cell line. Expression of this gene is increased during cancer. It is expected that gene expression will be reduced if the alga extract is effective. Methods: Hela was prepared from the Center for Genetic and Biological Reserves of Iran and cultured. After culture, cells were divided into two treatment and control groups. Different concentrations of algae extract were applied to the treatment group for 48 hours. Then its toxicity was measured using MTT assay and IC50 was determined. RNA was extracted from cells of two groups, to determine the relative amount of gene expression at a concentration of IC50. Then Real-time PCR was used. Results: The result of Real-time PCR showed that the relative expression of BCL-2, in treatment group cells that were affected by algae extract, was four times lower than the control group. Since the P-value is less than 0.05 (Pvalue = 0), this decrease is significant. Conclusion: After 48 hours, at a concentration of IC50 of algae extract, the relative expression of BCL-2 was four times lower than control group. [ABSTRACT FROM AUTHOR]

Background and Aim MicroRNAs (miRNAs) are a class of small non-coding RNAs (17-25 nucleotides) that have been studied in many diseases. miRNAs studies in different cancers have shown that miRNAs may be considered oncogene or tumor suppressor. So far, many studies have shown that miR-17-5p and miR-93-5p are important regulatory molecules in some biological processes, such as cell proliferation, associated with cancer formation. This study aimed to investigate and compare the tissue and plasma expression levels of miR-17-5p and miR-93-5p in patients with ductal carcinoma breast cancer with the normal control group. Methods & Materials The total RNA (including miRNA) was extracted from breast and plasma tissue samples of cancerous and normal samples. The RNA concentration and purity were confirmed using optical absorbance measurements. cDNA was synthesized, and the expression levels of miR-17-5p and miR-93-5p were assessed semi-quantitatively by SYBR Green-based real-time RT-PCR assay in plasma and breast tissues of ductal carcinoma breast cancer compared with the control normal samples with SNORD47 as internal normalizer. Data were statistically evaluated using GraphPad Prism 8.0.2. Ethical Considerations This study was approved by the Ethics Committee of the institute (IRAN 52d/4922, 6.10.2016). All study individuals signed a consent form to use their clinical samples and personal data under the physician’s supervision. Results The expression level of miR-17-5p showed significantly higher expression in tissues and plasma of the cancer group compared with the control group (P<0.0001). It was also significantly associated with tumor stage and lymph node, and ER (estrogen receptor) and PR (progesterone receptor) status (P<0.0001). While decreased expression of miR-93-5p in plasma and tumor tissues was shown to be significantly associated with tumor stage and lymph node involvement (P<0.0001). Conclusion The data revealed that high expression of miR-17-5p and low expression of miR-93-5p in both plasma and breast tumor might be associated with poor prognosis in breast cancer. However, miR-17-5p, due to the greater change in expression and ease of plasma detection, may serve as a possible non-invasive biomarker for breast cancer’s poor prognosis. Further follow-up studies are required to confirm this finding. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer, which is one of the most common cancers with high mortality in women, has always been the focus of researchers, and every day, scientists are trying to identify mechanisms, genes, and medicines related to this disease. Nowadays, bioinformatics methods are used to identify and repurpose drugs for the treatment of diseases, especially cancer. Material & Methods: In this study, bioinformatics and biological network analysis were used to identify candidate drugs for breast cancer treatment. In this regard, analysis of the protein interaction network and drug-gene network were employed. The needed data were collected from the GEO database with the access code GSE54002. For the selected data set, genes with significant expression changes between two groups of healthy people and people with breast cancer cases were selected and considered primary genes. Thereafter, the protein-protein interaction network was constructed using the STRING database, and a significant gene module was obtained from the network. Following that, gene ontology studies and biological pathways were conducted. Next, the drug-gene network was constructed to identify drugs that target module genes and were introduced as essential drugs for the treatment of breast cancer. Cytoscape software and STRING and OncoDB databases were used to reconstruct and analyze the networks. Results: After analyzing the protein-protein interaction network and the drug-gene network, three important drugs that target the genes of the modules were identified and introduced as candidate drugs for the treatment of breast cancer. These drugs were RG1530, R-406, and GW441756x. Discussion & Conclusion: The obtained results demonstrated that the introduced drugs (RG-1530, R-406, and GW441756x) can be effective in the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: The use of functionalized metal nanoparticles against cancer cells has gained assiduous attention. This study aimed to assess the inhibitory activity of iron oxide nanoparticles coated with glucose and conjugated with coumarin (Fe3O4@GluCoumarin) on breast cancer cell line, as well as the expression of the caspase-8 and caspase-9 genes. Material & Methods: The physical and chemical properties of nanoparticles were evaluated using FT-IR, XRD, EDS-map, and electron microscope imaging. The toxicity of the synthesized nanoparticles was determined using the MTT assay, and the 50% inhibitory dose (IC50) was calculated. Moreover, the effect of nanoparticles on apoptosis induction was investigated by measuring the expression level of the caspase 8 and 9 genes and flow cytometry analysis. Statistical analyses were performed in SPSS software. One-way analysis of variance (ANOVA) was employed to assess significant differences between nanoparticle-treated and control groups. A p-value of less than 0.05 was regarded as statistically significant. Results: The synthesis of Fe3O4@Glu-Coumarin nanoparticles was confirmed by physicochemical tests, including FT-IR, XRD, EDS-mapping, and electron microscope imaging. The nanoparticles had dimensions of 25 to 50 nm and contained Fe, O, and C elements. The treatment of MCF-7 cells with nanoparticles caused a significant decrease in the survival of cancer cells, and the IC50 was 93μg/ml. The exposure of cells to the nanoparticles caused a marked increase in the expression of caspases 8 and 9 by 2.6 and 2.9 folds, respectively, compared to the control group. In addition, the frequency of apoptotic cells after treatment with the nanoparticles increased from 2.21% to 84%.. Discussion & Conclusion: The results of this study pointed out that Fe3O4@GluCoumarin increased the expression of the caspases 8 and 9 genes in breast cancer cells and, as a result, can activate the intrinsic and extrinsic apoptotic pathways, thereby inhibiting the proliferation of cancer cells. [ABSTRACT FROM AUTHOR]

Background and Aim: Enterotoxigenic Escherichia coli (ETEC) is one of the most common bacterial causes of diarrhea deaths among children and travelers in developing countries. The ETEC colonization factors, such as CFA/I and CS2 play an important role in the development of the disease. In this study, to produce the CFaE fusion recombinant protein, the tip subunits CFA/I(CfaE) and sub structural unit of CS2 (CotD) from ETEC, were used. Since mucosal immune responses to CFs can prevent disease, the aim of this study was to develop a chimeric antigen for developing the effective vaccine. Materials and Methods: In order to amplify the cfae-cotd gene, a dual gene construct consisting of cfae and cotd, the PCR reaction was performed by designed primers. The propagated gene was cloned in the expression vector pET28a. Following the induction of a recombinant gene construct with IPTG, the recombinant protein was expressed and purified by Ni-NTA chromatography column and confirmed by western blotting by Anti-Histag. Ethical Considerations: This study with research ethics code IR.IAU.SRB.REC.1397.066 has been approved by research ethics committee at Islamic Azad University, Science and Research Branch of Tehran, Iran. Findings: Cloning accuracy was confirmed by PCR and enzyme digestion reaction. The presence of the band in the SDS-PAGE 10% gel in the 68 kDa region, the expression of the recombinant protein, and the presence of the band on the nitrocellulose paper in the Western blotting test confirmed the production of recombinant protein. Conclusion: Optimization of codon and expression in heterologous hosts is a useful method for the production of recombinant proteins. The production of ETEC antigens as a candidate for vaccination against this bacterium is also prominent. [ABSTRACT FROM AUTHOR]

Introduction: Consuming a high-fat diet causes obesity, which is one of the hallmarks of metabolic syndrome. The present study aimed to assess the effect of aerobic training and capsaicin supplementation on the expression of lipogenic genes SREBP-1c and FASN in the liver tissue of obese rats Material & Methods: For this experimental research, 40 eight-week-old male Wistar rats weighing 181.5±2.3 grams were selected as samples. Thereafter, eight rats were fed a normal diet (ND), and 32 rats were fed a high-fat diet (HFD) and randomly assigned to five groups: normal diet, high-fat diet, high-fat diet-training, high-fat dietcapsaicin, and high-fat diet-training-capsaicin. The exercise groups performed an incremental aerobic exercise program (15-25 m/min, 30-60 min/day, five days/week) on a treadmill for eight weeks. Capsaicin (4 mg/kg/day) was taken orally by gavage once a day. Results: Induction of obesity was associated with increased expression of SREBP-1C (P=0.001) and FASN (P=0.001). It was also revealed that aerobic exercise with capsaicin supplementation significantly decreased SREBP-1C and FASN gene expression in the experimental groups compared to the obese group. Finally, this reduction trend was significant in the combined group compared to the supplement group. Discussion & Conclusion: It is possible that the use of capsaicin, along with aerobic physical activity, is an effective strategy to neutralize the markers of hepatic lipogenesis. [ABSTRACT FROM AUTHOR]

Introduction: Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults. The aim of this study is to investigate the effects of the buforin II gene on the expression of lncRNAs PVT1, EGOT and LINC00312 in ACHN kidney cancer cells. Material & Methods: Recombinant plasmid pcDNA3.1(+) containing buforin II gene and empty plasmid pcDNA3.1(+) were introduced into E.coli strain TOP10 by heat shock method and then purified. Then both mentioned plasmids were introduced into ACHN cells by lipofection method and screening was done by neomycin antibiotic. Finally, real time RT-PCR reaction was performed in order to investigate the expression change of EGOT, PVT1 and LINC00312 lncRNAs. Results: After lipofection, the transfected cells grew in the culture medium containing neomycin antibiotic. The real time RT-PCR reaction showed that the expression of buforin II gene in ACHN kidney cancer cells caused a significant increase in the expression of lncRNAs EGOT (P=0.0033) and LINC00312 (P=0.0272) and a significant decrease in the expression of PVT1 (P=0.0278). Discussion & Conclusion: Considering that the presence of buforin II gene causes a significant change in the expression of lncRNAs EGOT, PVT1 and LINC00312, it is possible that it can activate cell pathways including apoptosis. [ABSTRACT FROM AUTHOR]

Introduction and Objective: Alpha-lipoic acid (α-LA) synthesized enzymatically in the mitochondrion from octanoic acid. Endogenous levels of α-lipoic acid have been reported in the micro molar range. Alpha-lipoic acid can easily pass through biological membranes due to its high lipophilicity and is converted into dihydro lipoic acid (DHLA) in cells. Alpha-lipoic acid and DHLA have been described as an ideal antioxidant couple, due to their very high protection ability against oxidative stress through multiple pathways. Alpha-lipoic acid and DHLA have metal chelating activity, acts as a coenzyme in glucose metabolism, and can produce other antioxidants such as ascorbate, vitamin E, and glutathione (GST). Alpha-lipoic acid has anti-inflammatory properties and its supplementation to broiler diets improves the expression of inflammation-related genes in the spleen. On the other hand, trivalent chromium has been recognized as an essential trace element for humans and other animals, which is part of the glucose tolerance factor (GTF). Chromium is essential for the metabolism of carbohydrates, proteins and lipids. Chromium may be present in the diet in the form of inorganic compounds or organic complexes. After absorption, chromium circulates in a free state and binds to transferrin or other plasma proteins (protein β-globulin). Trivalent chromium seems to play a role in the structure and expression of genetic information in animals. Chromium binding to nucleic acids is stronger than other metal ions. Chromium protects RNA against thermal denaturation. It is also clear that chromium is concentrated in the cell nucleus. By binding to chromatin, chromium participates in gene expression and increases the start sites and thus increases RNA synthesis. This increase is due to the induction of protein bound to the nucleus and the activation of nuclear chromatin, as a result, chromium effects gene function. Chromium supplementation has shown a positive effect on immune response of broiler chickens. The aim of this research was to investigate the simultaneous effect of dietary chromium propionate and alpha-lipoic acid supplementation on the expression of cytokines interleukin 1, 2, 4, and 10, as well as IFN-γ, TNF, and TGF β4 genes in the spleen tissue of broiler chickens. Material and Methods: For this purpose, an experiment was performed with 144 Ross 308 broiler chicks in complete randomized design (CRD) with a 3×2 factorial arrangement of treatments including six treatments, 3 replicates and 8 chickens in each replicate. There were 6 dietary treatments: three doses of chromium propionate (0, 750 and 1500 μg / kg) combined with two levels of alpha-lipoic acid (0 and 300 mg/kg) supplemented to the basal diets. At the end of the experimental period (42 days old), two chickens from each pen were randomly selected and killed. The sample was taken from the spleen and immediately frozen in liquid nitrogen and then stored at -80°C. The quantity and purity of the extracted RNA was checked using a Nanodrop device. In order to confirm the specific amplification of the desired genes in this study using primers, the PCR reaction was first performed. The expression of cytokine profile genes were quantified by quantitative real time PCR. In this way, 28S was used as a house-keeping gene to normalize the gene expression data. To analyze the obtained data, the method of difference in threshold degree changes (ΔΔCT) was used. The method of investigating gene expression changes in this research was the 2-ΔΔCT method (comparative threshold) and the ratio of gene expression (28s). Results: The results of electrophoresis confirmed the expression of genes in the spleen cells of broiler chickens and they appeared as one band on 2% agarose gel. Electrophoresis of polymerase chain reaction products showed fragments of 86, 51, 82, and 88bp for interleukin 1, 2, 4, and 10, respectively. No bands were formed on agarose gel for IFN-γ, TNF and TGF β4 genes. The results showed that alpha-lipoic acid at the level of 300 mg/kg significantly decreased interleukin 1 gene expression than the control group (0 mg/kg). Also, supplementing the basal diet with the chromium propionate at the level of 1500 μg/kg significantly increased interleukin 1 and 4 genes expression compared to the control group and the chromium propionate at the level of 750 μg/kg. While the addition of alpha lipoic acid and chromium propionate had no effect on the expression of interleukin 2 and 10 genes. Conclusion: Adding 300 mg/kg alpha lipoic acid to the diet can improve the immune response by reducing the expression of IL 1 gene in broilers. In addition, the addition of high amounts of chromium propionate (1500 μg) leads to a decrease in immunity (by increasing the expression of IL 1 and 4 genes). While the addition of chromium propionate up to the level of 750 μg/kg does not affect safety. Considering the results, it is recommended to add alpha lipoic acid at the level of 300 mg to the broiler diet. Addition of chromium propionate up to the level of 750 μg is fine if it has beneficial effects on yield and production characteristics. [ABSTRACT FROM AUTHOR]

Introduction and Objective: Cold stress is one of the most important factors limiting the early cultivation of most crops, including corn. Cold causes oxidative stress through the production of reactive oxygen species (ROS) in plants. This study was conducted in order to investigate the expression pattern of some genes involved in the response to cold stress (catalase, superoxide dismutase and metallothionein) in corn plants. Material and Methods: This experiment was conducted as a factorial in the form of a randomized complete block design with four replications and with three varieties of corn singlecross 260, singlecross 302 and doublecross 370. Planting was done in pots with a capacity of 4 kg of soil. qPCR technique was used to check gene expression pattern. Results: The results of the analysis of the gene expression pattern showed that among the examined cultivars, singlecross 260 had the highest expression of catalase and superoxide dismutase genes, and singlecross 302 had the lowest expression of these genes. Examining the metallothionein gene expression pattern also showed that the expression level of this gene is the lowest in singlecross 260 and the highest in singlecross 302. The high expression of metallothionein gene in singlecross 302 is probably due to the occurrence of oxidative stress due to cold stress, accumulation of hydrogen peroxide and low expression of catalase gene. Also, growth indices including germination percentage, germination speed, leaf surface and chlorophyll a and b showed a good correlation with the expression level of catalase and superoxide dismutase genes. Conclusion: Singlecross 260 and Singlecross 302 had the highest and lowest levels of expression of superoxide dismutase and catalase genes, germination percentage, germination speed, leaf area and chlorophyll, respectively. The activity of antioxidant genes such as catalase and superoxide dismutase prevent the reduction of chlorophyll and damage to the plant's photosynthetic apparatus. [ABSTRACT FROM AUTHOR]

Background and Objectives: Leukemia is a cancer type in the world. One of the most accurate methods for detection and prediction of Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia is to use DNA and genetic information of people. Microarray technology is a tool to study the expression of thousands of genes in shortest possible time. Analyzing the microarray datasets may not be possible without the statistical analysis and machine learning techniques. In this paper، microarray data sets and machine learning techniques are used for the diagnosis of leukemia. Materials and Methods:The data used in this descriptive study are the expression of 7129 genes of 72 patients with leukemia which have been achieved by the microarray technology. Then، the diagnosis of AML and ALL was performed using the microarray data based on anisotropic radial basis function with the gain ratio and information gain. Results:The proposed method using information gain with the selection of 230 important genes and using gain ratio with the selection of 86 important genes was able to detect AML and ALL with accuracy of 97.06%، whereas non-parametric kernel classification method based on the radial basis function has the accuracy of 35.29٪ with 7129 genes. Conclusions:The results of this study showed that the gene expression data and proposed method with gain ratio method are able to detect leukemia with high accuracy. Therefore، it seems that proposed method can help to accurately diagnose leukemia for a better decision making about the diagnosis of diseases and treatment of patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: Nowadays, cell therapy is one of the most important and promising strategies in the treatment of diseases. Unique capabilities of stem cells caused them to be used in both research and treatment as a valuable resource in basic science and medical researches. The use of stem cells has been limited due to the related ethical problems. One of the major concerns of scientists to develop and use more of this science is finding alternative methods for producing these cells. Creating induced pluripotent stem cells (IPSCs) is one of the most important methods in achieving this goal. In this regard, various methods are developing that have the ability to change the gene expression and protein profiles, which results in a change in cells morphology and function in the direction of returning to a undifferentiated status and creating stem cells. These methods include nuclear transfer, use of cell extracts and synthetic molecules, mandatory expression of specific genes, and changes in the levels of cytoplasmic. In this review article, it has been tried to review the methods in the field of the induced pluripotent stem cells production. Literature search was performed through various combinations of keywords regarding induced pluripotent stem cells, Dedifferentiation methods, and IPSCs generation methods. Papers included in our review cover the period between 2002 to 2015.At the end of the review process, 68 articles were used in our final manuscript. In the present study, we review various methods in the IPS cells generation. [ABSTRACT FROM AUTHOR]

Introduction and Objective Rivers serve as crucial sources of freshwater on Earth, and precise prediction of river flows plays a vital role in effective water resource management. To address this need, researchers have proposed various models. These models can be categorized into two types: (1) hydrological/hydraulic physically based models and (2) data-driven models. The cited papers provide evidence of the significance of employing data-driven models for hydrological issues, particularly in predicting river discharge.Materials and Methods In this study, the researchers utilized a gene expression programming model (GEP) and support vector machine (SVM) to predict the discharge of the Ferizi River. The dataset used in the study covered a period of ten years (2011-2020) and consisted of daily Ferizi river discharge readings obtained from the Moushang hydrometry station. The study area had an average altitude of 2171 meters above sea level, with a longitude range of 58° 49' 30" to 59° 4' 30" E and a latitude range of 36° 20' 1" to 36° 32' 1". For the prediction models, daily river discharge data from 1 to 5 days ahead were utilized as input variables for both the GEP and SVM models. To ensure data homogeneity and address any deficiencies, the researchers employed the run test and calculated the correlation coefficient between neighboring stations. Subsequently, the dataset was randomly divided into two groups: 80% for model training and 20% for model testing, as well as evaluating the modeling error. The performance of the models was assessed during the training and validation stages using various evaluation metrics, including root mean square error (RMSE), coefficient of correlation (R), bias, Kling Gupta (KGE), and Nash–Sutcliffe model efficiency (NSE). Additionally, in order to estimate the inflow to the Ferizi River using the SVM model, three common types of kernel functions in hydrology were examined, namely linear kernel, polynomial, and radial basis functions.Results and Discussion Among the different functions considered, the radial basis function was selected due to its lower error compared to other functions when applied to the variables. The best input model, Model No. 5, incorporated previous flow variables with a delay of five time steps. In the training phase, both the GEP and SVM models exhibited the highest performance in forecasting the daily flow of Moshang station. The performance of the applied models suggests that SVM (RSME = 1.15, R = 0.985, NSE = 0.85, and KGE = 0.79) demonstrates higher precision in the validation stage for river discharge prediction compared to GEP (RSME = 1.65, R = 0.964, NSE = 0.78, and KGE = 0.69).Conclusion and Suggestions This study has demonstrated that the utilization of soft computing techniques, such as SVM and GEP, is a powerful tool in predicting river flow. These techniques are capable of establishing a favorable relationship between input and output parameters, enabling accurate simulation of average and maximum daily flow.

Introduction: Based on current knowledge, it has been proven that many edible ingredients in addition to meeting the needs of creatures, in terms of energy and protein, contain compounds that affect cellular actions and intracellular signaling pathways and can temporarily or permanently change the function of the cell. The use of molecular biology tools and genetic research defines the mechanisms through which gene expression is affected by food, and conversely, these genes also affect the absorption of food, metabolism, and excretion. From the point of view of nutrigenomics, dietary nutrients are signals that are received by sensitive cell systems and can affect the expression of genes and proteins and the production of metabolites. Nutritional manipulations and strategies are key tools to influence ruminant production. Fatty acids act on the nucleus by binding to and regulating the activity of specific nuclear receptors or transcription factors, thus playing a central role in regulating the expression of genes involved in fatty acid uptake by muscle cells. Interactions between diet nutrients and the expression of genes involved in lipid metabolism have many possibilities regarding the deposition of fatty acids in the tissue. The study of gene expression has enabled clarification of the mode of fatty acid metabolism in muscle and the accumulation of intramuscular fat or marbling and the role of the genes that promote fatty acid oxidation and mitochondrial respiration in the liver muscle and adipose tissue. Polyunsaturated fatty acids with multiple double bonds (PUFA) and monounsaturated fatty acids with one double bond (MUFA) have received much attention in the last decade, and their health benefits are increasingly evident. Therefore, this study investigated the effect of using calcium salts of fish oil, olive oil, and saturated fat on the expression of some genes related to fat metabolism in Lori Bakhtiari×Romanov fattening lambs. Materials and methods: This study was carried out at the educational research station of the Department of Animal Science of the College of Agriculture and Natural Resources, University of Tehran. 49 male lambs aged four to five months with an average initial weight of 29.97 ± 0.88 kg were divided into seven groups of seven lambs in a completely randomized design. The experiment consisted of seven treatments with a basic diet as follows: 1) Basic diet without fat powder (control), 2 and 3) Basic diet with calcium salt of fish oil (rich in omega3 fatty acids) in the amount of 2% dry matter of the diet for 90 and 45 days, respectively, 4 and 5) Basic diet with calcium salt of olive oil (rich in omega-9 fatty acids) at the rate of 2% dry matter of the diet for 90 and 45 days, respectively, 6 and 7) Basic diet with saturated fat powder in the amount of 2% dry matter of the diet for 90 and 45 days, respectively. Rations were adjusted based on the NRC Sheep and Goat and using the fifth version of CNCPS (The Cornell Net Carbohydrate and Protein System) software so that they are the same in terms of energy and protein. Twenty-eight lambs were slaughtered and a liver sample was taken for nutrigenomics studies. Total RNA was extracted from liver tissue samples using the RNA extraction kit produced by Dena Bio Asia Company (Mashhad) and according to the protocol provided with the kit. The expression of four main genes involved in lipid metabolism in liver tissue was investigated to provide comprehensive information on the effects of omega3, omega-9 fatty acids, and saturated fat at the molecular level. Results and discussion: The results showed that feeding with calcium salts of fish oil, olive oil, and saturated fat, both in the whole 90 days or the last 45 days of the fattening period, had no significant effect on the expression of FADS1 and FADS2 genes in liver tissue compared to the control group. However, the use of calcium salts of fish and olive oils in periods of 90 and 45 days significantly increased the hepatic mRNA expression of the CPT1 gene (P=0.001) and ACOX1 gene mRNA expression in liver tissue compared to control and saturated fat treatments (P=0.002). The CPT1 enzyme is responsible for a mitochondrial transport system and plays a key role in controlling the oxidation of long-chain fatty acids and stimulating mitochondrial β-oxidation. Conclusions: The results of this study showed that diet supplementation with calcium salts of fish and olive unsaturated fatty acids, regardless of the period of consumption, increased the expression of genes involved in the lipolysis of liver tissue fats of lambs. [ABSTRACT FROM AUTHOR]

Introduction: A total dissolved solid (TDS) is an important indicator for water quality assessment. Since the composition of mineral salts and discharge affects the TDS of water, it is important to understand the relationship of mineral salts composition with TDS. Materials and Methods: In this study, methods of artificial neural networks with Levenberg-Marquardt training algorithm, adaptive neuro fuzzy inference system based on Subtractive Clustering and Gene expression programming were used to model water quality properties of Zarrineh River Basin at upstream of Boukan dam, to be developed in total dissolved solids prediction. ANN and ANFIS programs code were written using MATLAB programming language. Here, the ANN with one hidden layer was used and the hidden nodes’ number was determined using trial and error. Different activation functions (logarithm sigmoid, tangent sigmoid and linear) were tried for the hidden and output nodes and the GeneXpro Tools 4.0 were used to obtain the equation of the best models. Therefore, water quality data from two hydrometer stations, namely Anyan and Safakhaneh hydrometer stations were used during the statistical period of 18 years (1389-1372). In this research, for selecting input variables to the data driven models the stepwise regression method was used. In the application, 75% of data set were used for training and the remaining, 25% of data set were used for testing, randomly. In this paper, three statistical evaluation criteria, correlation coefficient (R), the root mean square error (RMSE) and mean absolute error (MAE), were used to assess model’s performances. Results and Discussion: By applying stepwise method, the first significant (at 95% level) variable entered to the model was the HCO3. The second variable that entered to the model was Ca. The third and fourth ones were Na and Q respectively. Mg was finally entered to the model. The optimal ANN architecture used in this study consists of an input layer with five inputs, one hidden and output layer with three and two neurons for Anyan and Safakhaneh hydrometer stations, respectively. Similar ANN, ANFIS-SC5 model had the best performance. It is clear that the ANFIS with 0/4 and 0/7 radii value has the highest R and the lowest RMSE for Anyan and Safakhaneh hydrometer stations, respectively. Various GEP models have been developed using the input combinations similar ANN and ANFIS models. Comparing the GEP5 estimations with the measured data for the test stage demonstrates a high generalization capacity of the model, with relatively low error and high correlation. From the scatter plots it is obviously seen that the GEP5 predictions are closer to the corresponding measured TDS than other models. As seen from the best straight line equations (assume the equation as y=ax) in the scatter plots that the a coefficient for GEP5 is closer to 1 than other models. In addition to previous operation, Gene expression programming offered mathematical relationships in the stations of Anyan and Safakhane with the correlation coefficients, respectively 0.962 , 0.971 and with Root-mean-square errors, respectively 12.82 , 29.08 in order to predict dissolved solids (TDS) in the rivers located at upstream of the dam. The obtained results showed the efficiency of the applied models in simulating the nonlinear behavior of TDS variations in terms of performance indices. Overall, the GEP model outperformed the other models. For all of applied models, the best result was obtained by application of input combination (5) including HCO3, Ca, Na, Q and Mg. The results are also tested by using t test for verifying the robustness of the models at 95% significance level. Comparison results indicated that the poorest model in TDS simulation was ANN especially in test period. The observed relationship between residuals and model computed TDS values shows complete independence and random distribution. It is further supported by the respective correlations for GEP5 models (R2 = 0.0011 for Anyan station and R2 = 0.0123 for safakhaneh station) which are negligible small. Plots of the residuals versus model computed values can be more informative regarding model fitting to a data set. If the residuals appear to behave randomly it suggests that the model fits the data well. On the other hand, if non- random distribution is evident in the residuals, the model does not fit the data adequately. On the base of these results, we propose GEP, ANFIS-SC and ANN methods as effective tools for the computation of total dissolved solids in river water, respectively. Conclusion: It can be concluded that the ANN, ANFIS-GP, ANFIS-SC and GEP models can be considered as promising tools for forecasting TDS values, based on water quality parameters. It is notable from the results that the prediction accuracy of all applied models increases by increasing the number of input combinations. With attention to the aim of current research that is presenting the feasibility of artificial intelligence techniques for modeling TDS values, it is notable that the results presented in this paper are for research purpose and applying the abstained results for real-world needs some complicated steps and building artificial intelligences methods, based on complete data and parameters maybe affected the TDS values.

Background: After recognition of sequences of different genomes, the next logical step is the discovery of their function and regulation. To classify genes in the laboratory, factors such as the behavior of genes, gene expression control and protein interactions have been reviewed. It is expected that genes with similar regulation mechanisms have the same expression patterns. Methods: In this paper, we introduce a special way of clustering, called biclustering, for microarray data obtained from multiple sclerosis (MS) patients. From a biological perspective, gene regulatory modules consist of genes that have similar behaviors at different points of time under several conditions. By identifying these modules, the recognition of the regulatory mechanisms that are the common causes of genes behaviors might be conceivable. Findings: We used a modified format of iterative signature algorithm (ISA) to extract co-expressed gene profiles from microarray data. The combination of K-nearest neighbor (KNN) algorithm and ISA provides a helpful algorithm which results in an outstanding and optimum way to obtain similar genes in microarray data. Conclusion: The algorithm was performed on a synthetic as well as a real database (MS patients' data), and showed a pronounced difference between the extracted modules in contrast to ISA. Although we showed our method's efficiency over synthetic and MS data, it will be usable for any other kinds of data. In other words, our method is based on a series of logical and statistical methods rather than data-based methods. [ABSTRACT FROM AUTHOR]

Introduction: Recurrent Pregnancy Loss and Recurrent Implantation Failure are major limiting factors in the establishment of pregnancy. Recurrent Pregnancy loss is defined as the failure of two or more clinically recognized pregnancies. A considerable proportion of infertile couples undergoing IVF treatment experiencing recurrent implantation failure (RIF) fail repeatedly to implant following at least three IVF cycles. MicroRNAs (miRNAs) can serve as reliable non-invasive diagnostic and prognostic biomarkers for pregnancy-related complications. Therefore, this study aimed to quantify miR-23a-3p expression level in the plasma of patients with idiopathic recurrent pregnancy loss (iRPL) and recurrent implantation failure compared to healthy subjects to evaluate its potential diagnostic value in iRPL and RIF patients. Material & Methods: This study is a cross-sectional descriptive study. A total of 120 plasma samples were obtained from 40 women with a history of at least two consecutive iRPL, 40 women with RIF, and 40 healthy women without a history of miscarriage to evaluate the expression level of the circulating miR-23a-3p by quantitative real-time polymerase chain reaction (qPCR) technique. All participants were recruited from Assisted Reproductive Technology (ART) and Stem Cell Research Center, Tabriz, Iran, September 2019-March 2020. Statistical analysis was performed using SPSS (version 22). Diagnostic efficiency of the circulating miRNAs was determined by Receiver Operatig Characteristic curve analysis using Graphpad Prism version 9.1.1. Findings: Our results showed that the miR-23a-3p expression level in plasma of iRPL patients was lower than those in healthy controls but without a statistically significant difference (P=0.113). We also found that miR-23a-3p plasma level in patients with RIF tended to be lower compared to healthy participants; however, it was not statistically significant (P=0.974). Discussion & Conclusion: The current study provides evidence indicating that downregulation of miR-23a-3p may be associated with iRPL and RIF. Therefore, further research is needed, such as using different geographic regions, large sample sizes, and other techniques (microarray). [ABSTRACT FROM AUTHOR]

Introduction: The increasing prevalence of obesity has affected millions of people across the globe, leading to various diseases, such as prediabetes, diabetes, cardiovascular diseases, cancer, and muscle disorders. One of the therapeutic interventions in the prevention of diabetes is the use of herbal supplements, such as green coffee and its phenolic compounds, including chlorogenic acid, due to its antioxidant, anti-inflammatory, and insulin-sensitive properties. Therefore, the present study aimed to investigate the effect of green coffee and chlorogenic acid on glycogen content in the muscles of prediabetic mice. Material & Methods: A total of 20 male C57BL/6 mice were randomly assigned to two groups: normal diet mice (5 mice) and high-fat diet mice (15 mice), which were fed for 12 weeks. After the induction of prediabetes by Fasting blood sugar (FBS) and Glucose tolerance test (GTT) tests, this group was divided into three subgroups: prediabetes mice (5 cases), prediabetes mice with diabetes with green coffee consumption (Prediabetes - Green Coffee, 5 cases) and prediabetes with chlorogenic acid consumption (Prediabetes - Chlorogenic Acid, 5 cases) which were treated for 10 weeks. In the end, the mice were sacrificed, and the relative level of expression of genes involved in the glycogen content of the Gastrocnemius muscle, including PI3K, AKT, GSK3, GYS1, as well as the LRRC8A gene, was measured through the Real-Time PCR technique. The data were analyzed using the one-way analysis of variance test by GraphPad Prism software (version 8). Findings: The results pointed to a significant increase in the blood glucose level in the HFD group (129.9±5.4 mg/dL) compared to ND (95±3.3 mg/dL) and a significant decrease in the PD-GC group (103.5±8.16 mg/dL) and PD-CA (99±8 mg/dL) compared to the PD group (129.5±9.4 mg/dL) (P<0.001). The periodic acid-Schiff (PAS) staining technique demonstrated a significant decrease in the level of glycogen content in the rats of the PD group compared to the ND group. While in the treatment groups, a significant increase was observed in muscle glycogen accumulation compared to the PD group (P<0.001). The expression level of PI3K, AKT, LRRC8A, and GYS1 genes decreased, and GSK3 significantly increased in the PD group compared to the ND group (P<0.001), indicating a disturbance in the signaling pathway of glycogen content in the PD group. Nonetheless, in the treated groups, a significant increase was observed in the expression level of PI3K, AKT, LRRC8A, and GYS1 genes compared to the PD group (P<0.001). Discussion & Conclusion: Considering the complications caused by prediabetes disease, in addition to early diagnosis of prediabetes, it seems to control weight and increase insulin sensitivity, the consumption of green coffee and chlorogenic acid can improve the prediabetic condition caused by the signaling pathway of glycogen synthesis in the muscle tissue of prediabetic rats. [ABSTRACT FROM AUTHOR]

Introduction: Assisted reproductive techniques and Preimplantation Genetic Test (PGT) are performed to detect aneuploidy to achieve a euploid baby's birth in infertile or lowfertility couples. miRNAs are single-stranded, non-coding RNA molecules and essential regulators of gene expression in various biological and physiological processes. The present study aimed to investigate some miRNAs damaged in the culture media of human embryos (as diagnostic biomarkers) and their relationship with the degree of aneuploidy of the embryo and assisted reproductive methods. Material & Methods: The PGT cycles derived sperm intracytoplasmic injection (April 2021 to June 2021) were evaluated using fluorescence in situ hybridization (FISH). Following that, the culture medium of three euploids and three aneuploid embryos with an X sex chromosome (Turner) was collected and the expression of has-miR-199a-5p, has-miR-199b-3p has-miR-379-5p, has-miR-483-5p, has-miR-99a-5p, and has-miR432-5p were investigated using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Findings: In the culture medium of euploid embryos, a significant increase was observed in the expression of three miRNAs, including hsa-miR-379-5p, hsa-miR-199a-5p, hsamiR-199b-3p. Moreover, a decrease was detected in the expression of three miRNAs, including hsa-miR-432-5p, hsa -miR-483-5p, and hsa-miR-99a-5p, with a significant difference (P<0.0001). The expression of these miRNAs in the culture medium of Turner embryos with the model was the opposite. Discussion & Conclusion: In examining the expression level of miRNAs investigated in this project, the increase in the expression of three miRNAs and the decrease in the expression of three other miRNAs in euploid embryos demonstrated the opposite expression pattern of the same miRNAs in Turner embryos. These results can be considered promising for using non-invasive methods instead of fetal biopsy in the diagnostic studies of the number of sex chromosomes. [ABSTRACT FROM AUTHOR]

Objective Rosmarinic acid (RA), an anticancer, antiallergic, and antimicrobial agent, is a secondary metabolite in many plants of the family Lamiaceae including M. officinalis L. The application of nanoparticles (NPs) as a novel elicitor for the biosynthesis of bioactive compounds shown that the NPs could affect the secondary metabolites in plants by eliciting the expression of biosynthetic pathway genes. The present paper aimed to assess the effect of Magnetic Iron Oxide Nanoparticles (MIONPs) in comparison with their dissolved counterpart. Materials and methods Foliar application of different concentrations: including 5, 10, 25, and 50 mg/L Fe of ferric chloride and MIONPs on the plant leaves was performed. The relative mRNA levels of TAT, RAS, and HPPR were evaluated with quantitative real-time PCR (qRT-PCR) and compared between treated and untreated samples. Results This study showed the positive effects of ferric chloride and MIONPs on the expression of genes involved in the biosynthesis pathway of RA. The highest expression level of TAT, HPPR, and RAS genes was observed in plants treated with MIONPs at the concentration of 25 mg/L and the expression of genes decreased as the concentration increased to 50 mg/L. However, the genes expression was still higher compared to the control plant. Conclusions The results showed that the exposure of plants to ferric chloride and magnetic iron oxide nanoparticles led to an increase in the expression of the genes under study compared to control samples. However, the application of nano-scale iron particles had more effect than ferric chloride on the expression levels. An increase in the expression of genes involved in the biosynthesis pathway of RA through treatment with MIONPs provides an opportunity for induction of synthesis and accumulation of RA. Therefore, we hope to be able to enhance the production of RA in M. officinalis L. by using these NPs.

Increasing the growth and immune system of beluga sturgeon (Huso huso) which is a valuable species is an important aim for aquaculture so The purpose of this study was to investigate the effect of pectin and L. plantarum on growth performance and growth genes of juvenile beluga sturgeon (Huso huso). Triplicate groups of beluga juveniles each (15 ± 3 g) were placed in 9 oval tanks (400) and fed with the 107 cfu g-1, 108 cfu g-1 , pectin (1%), pectin (2%), 107 cfu g-1 and 1% pectin, 107 cfu g-1 and 2% pectin, 108 cfu g-1 and 1% pectin, 108 cfu g-1 and 2% pectin and control group. The trial lasted 8 weeks. At the end of experiment biometery was done and brain and liver tissue were separataed. Results showed that although pectin and L. plantarum could enhance growth factors separately, the highest FW, GW and SGR was observed in fish fed 108 cfu g-1 and 2% pectin which had significant differences with others treatments and control (P<0.05). Also the highest genes expression was in this treatment and the lowest in control. In general, pectin and L. plantarum could significantly affect growth performance in juvenile blugae. [ABSTRACT FROM AUTHOR]

Introduction: Cancer is a complex disease in which gene expression changes. This study was conducted with the aim of investigating the effects of MT1JP lncRNA in controlling lung cancer cells. Material & Methods: TC-1 [JHU-1] cells were transfected with pcDNA3.1(+)- MT1JP, Plko.1-EGFP-PURO-siRNA and empty plasmids, and the expression of MT1JP gene and siRNA fragment was confirmed by RT-PCR reaction. The role of MT1JP in migration was investigated by scratch assay and apoptosis by flow cytometry. The expression change of candidate genes involved in apoptosis and cell proliferation (Bim, AKT, Bax and Bcl-2) was evaluated by q-PCR reaction. Findings: The results showed that the expression of Bim gene showed a significant increase in the presence of high expression of MT1JP, while the expression of Bim gene decreased significantly with silencing of MT1JP by siRNA. The expression of Bax and Bcl-2 genes showed a significant increase and decrease, respectively, in the presence of high expression of MT1JP. In the cells transfected with pcDNA3.1(+)- MT1JP, the AKT gene showed a decrease in expression, and on the other hand, in the cells transfected with siRNA, the AKT gene had a significant increase in expression (p < 0.05). Also, the scratch assay results showed that MT1JP lncRNA has an inhibitory role on cell migration. Flow cytometry data showed that transfection by pCDNA3.1(+)-MT1JP could increase cell apoptosis levels. Discussion & Conclusion: The present study showed that lncRNA MT1JP inhibits cell proliferation and migration and at the same time increases apoptosis of TC-1 [JHU-1] cells. This study may help improve our understanding of lung cancer; however further studies are needed. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease is a common progressive neurogenerative disease that leads to dementia and destruction of brain cells, especially in areas related to learning and memory such as the hippocampus. The role of the Arc gene in synaptic flexibility and memory consolidation has been proven and its expression is strongly influenced by neuronal activity. The aim of this study was to investigate the effect of Lactobacillus fermentum on the expression of Arc (effective in synaptic flexibility and memory consolidation) and CREB (effective in stabilizing synaptic changes during learning) genes, involved in the memory of Alzheimer's rats. Material & Methods: In this study that was conducted in 2019, 30 male Wistar rats were divided into 5 groups (control, Alzheimer and 3 groups as treatment). In the treatment groups, simultaneously with induction of Alzheimer by stereotaxic method with streptozotocin, supernatant of Lactobacillus fermentum PTCC 1744 in MRS broth with doses of 108, 107, and 106 cfu/ml was injected intraperitoneally for 21 days. After RNA extraction from hippocampus samples, cDNA was synthesized and the expression of the genes was evaluated by real-time PCR and LinReg PCR software. Findings: The data showed an increase in gene expression of Arc and CREB in the treatment groups with a dose of 106 cfu/ml compared to the Alzheimer's group and the difference was significant (P <0.001). Discussion & Conclusion: Extracellular compounds of L. fermentum may inhibit the progression of neuronal lesions due to their antioxidant and anti-inflammatory effects and may be effective in improving Alzheimer's. [ABSTRACT FROM AUTHOR]

Background & Aims: Diabetic cardiomyopathy (DCM) is a functional, metabolic, and morphological deterioration of the myocardium caused by changes in glucose homeostasis caused by diabetes. miRs play a significant role in the occurrence of DCM. Reducing the overexpression of miR373 gene has a potential role in the appearance of this disease. Therefore, the purpose of this research was to compare the effect of six weeks of aerobic and resistance training on the expression of miR373 gene in mice with diabetic cardiomyopathy and male Wistar rats. Methods: This research had a developmental goal, from the point of view of the experimental method and from the point of view of the laboratory execution method, with a post-test design. 36 healthy male Wistar rats with an average weight of 200 ± 20 grams and an age of 8 weeks were purchased from Pasteur Institute in Tehran. To induce diabetes, 50 mg/kg of streptozotocin (STZ) was injected intraperitoneally in a single dose to 27 rats. To confirm the validity of diabetes induction, glucose ≥ 200 mg/dl or hema index ≥ 3.5 were considered. According to research, diabetic cardiomyopathy occurs two months after the induction of diabetes. To confirm the occurrence of diabetic cardiomyopathy in the form of a pilot project, 3 heads of healthy rats (before the start of the research) and 3 heads of diabetic rats (after two months of becoming diabetic) were dissected and samples of myocardial tissue were taken. Rats with cardiomyopathy were randomly classified into four groups of 6 vertices (control, sham exercise, resistance exercise and aerobic exercise). A healthy group of 6 vertices was also considered for comparison with other groups. After two weeks of familiarization with the environment and learning to exercise, aerobic (running on a treadmill) and resistance (walking on an ascending ladder) training protocols were implemented for six weeks. 48 hours after the last training session (along with 12 hours of fasting), all rats were anesthetized using ketamine and xylazine and dissected and sampled from the left ventricular tissue. Real Time PCR was used to evaluate the expression of miR373 genes. For the statistical analysis of the data, ANOVA and T-correlated tests were used at the significance level of P ≤ 0.05. Results: Both exercise protocols led to a significant (P ≤ 0.05) decrease in fasting blood glucose (FBS) and insulin resistance index (HOMA-IR%). VO2peak (P: 0.1) of the aerobic group and 1RM (P: 0.73) of the resistance group increased significantly. The miR-373 gene expression level decreased in the control and sham diabetic groups compared to the healthy group, but increased in both exercise groups. But this increase was not significant (P > 0.05). It was also shown that resistance training had more significant changes on FBS and HOMA-IR indices compared to aerobic training (P = 0.001). Finally, aerobic and resistance training led to a significant increase in Vpeak (T = -4.9, P = 0.004) and 1RM (T = -7.68, P = 0.001). Conclusion: Aerobic and resistance training improved the aerobic capacity and strength of the training groups, respectively. In addition, both exercises led to the improvement of diabetic complications (increased the expression level of miR-373), but aerobic exercise caused a better improvement of diabetic cardiomyopathy complications. [ABSTRACT FROM AUTHOR]

Background & Aims: Diabetes mellitus is one of the most common chronic diseases in the world (1). Diabetes and hyperglycemia caused by diabetes lead to disorders in various organs such as lungs, heart, muscles, kidneys, etc. (9, 10). One of the main complications of diabetes is diabetic cardiomyopathy; Diabetic cardiomyopathy is the result of diabetes-induced changes in the structure and function of the heart. Diabetic cardiomyopathy occurs as a result of impaired glucose and lipid metabolism associated with diabetes, which leads to increased oxidative stress and activation of multiple inflammatory pathways that mediate cellular and extracellular damage, pathological remodeling of the heart, and diastolic and systolic dysfunction. Preclinical studies in animal models of diabetes have identified several intracellular pathways involved in the pathogenesis of diabetic cardiomyopathy and potential cardioprotective strategies for disease prevention and treatment, including anti-fibrotic agents, anti-inflammatory agents, and antioxidants (11). Cellular energy homeostasis is a fundamental process that governs the overall health of the cell and is critical for cell survival. Central to this is the control of ATP production and utilization, which is regulated by a myriad of enzymatic reactions controlling cellular metabolism (12). Adenosine monophosphateactivated protein kinase (AMPK) is an energy sensor with aberrant expression in various diseases, including diabetes (12). There is considerable evidence that AMPK is reduced in cardiac tissues of animals and humans with type 2 diabetes or metabolic syndrome compared with non-diabetic controls, and that AMPK stimulation (physiological or pharmacological) can ameliorate diabetesrelated cardiovascular complications (14). Considering the role of AMPK in energy metabolism in the heart, as well as the effects of diabetes and exercise on the gene and protein expression of this energy sensor, measuring the changes of this gene can improve our knowledge about the effect of different adaptations caused by different exercises, as well as the effect of lack of exercise. With the aim of investigating the effect of maintaining these adaptations after training (22, 23). However, so far, no research has been done that specifically compares the effect of two common training methods, continuous and intermittent training, followed by no training on cardiac AMPK gene expression in diabetic rats, which shows the necessity of the current research. According to the mentioned information, the present study was conducted with the aim of comparing the effect of a detraining period followed by aerobic and HIIT exercises on cardiac AMPK gene expression in alloxan-treated diabetic rats. Methods: In this experimental research, 48 male Wistar rats (age: 10-weeks; weigh: 220±20 grams) were randomly divided into six groups (n=8). One group was considered as a healthy control and the rest of the rats were made diabetic using a single dose of 90 mg/kg of alloxan. One group was considered as diabetic control; and the rats were divided into two groups of high-intensity interval training (HIIT) and continuous moderate aerobic training (MICT). After 12 weeks of training, half of the rats in each group were sacrificed; and the rats were sacrificed after 2 weeks of no training. MICT program was performed for 5 sessions per week with a gradual increase in speed (18-26 m/min) and time (10-55 minutes). HIIT program also included 5 30-minute sessions per week in the form of running on a treadmill with one-minute repetitions and 2-minute active rest between each interval. For statistical analysis, one-way analysis of variance and Tukey's post hoc test were used and the significance level (P ≤ 0.05) was considered. Results: The results showed that the induction of diabetes decreased the cardiac AMPK gene expression compared to the healthy control group (P < 0.001), also the results showed that after 12 weeks of training, there was a significant increase in the cardiac AMPK gene expression in the training groups compared to the control group. Diabetes control was observed (P < 0.001), but no significant difference was observed between the two exercise groups (P > 0.05). Also, the results showed that after 2 weeks of non-training, there was a slight decrease in cardiac AMPK gene expression compared to the training groups, and these changes were not significant (P > 0.05). Conclution: The results of the present study showed that induction of diabetes with alloxan decreased cardiac AMPK gene expression, which was related to hyperglycemia caused by induction of diabetes with alloxan injection. Previous research has also shown that a single dose of alloxan injection with 90 mg/kg body weight of rats induces diabetes (24-26). According to the findings of the present study, 12 weeks of continuous aerobic exercise and HIIT both significantly increased cardiac AMPK gene expression in diabetic rats, but no significant difference was observed between the two types of exercise. Based on the research conducted in animal models, exercise increases cardiac AMPK values, which are consistent with the results of the present study (30, 31). However, comparing the effects of continuous and HIIT exercises, the results of these two studies were different from our findings; In their research comparing the effect of moderate intensity continuous training and HIIT training on AMPK of skeletal and cardiac muscle, Wen et al. reported that the effects of HIIT training on increasing oxidative capacity and AMPK are more obvious (30); The results of Su et al.'s research showed better effects of continuous training on AMPK and PGC-1α gene expression in the HIIT group than continuous aerobic training (30). As shown in various animal models and patient studies, physical exercise is known to be cardioprotective and can partially compensate for cardiac damage. At the cellular level, exercise counteracts heart disease-related changes in these cellular pathways and can improve heart function (32). AMPK activation leads to the regulation of metabolism, protein transport, transcription factors and/or activators, kinases, and other enzymes and non-enzymatic proteins. AMPK increases substrate uptake and utilization in the heart, enhances mitochondrial biogenesis, and modulates the activity of specific proteins and transcription factors to exert cardioprotective functions (33). Therefore, exercise training can moderate the effects of diabetes on the heart by increasing cardiac AMPK. AMPK also plays an important role in reducing oxidative stress, regulating autophagy and anti-apoptosis of cardiomyocytes (29, 34). Exercise activates signaling molecules and transcriptional networks to promote physiological adaptations such as mitochondrial biogenesis (35). It has been reported that after swimming exercises in rats, the levels of activated AMPK showed a decrease in cardiac fibrosis due to the inhibition of NADPH oxidase (36). This finding has been confirmed as decreased AMPK activity by beta-adrenergic activation exacerbates cardiac fibrosis (37). These changes are important because exercise activates AMPK and thus may be able to inhibit pathological hypertrophy and cardiac fibrosis (38). Other findings of our research showed that 2 weeks of detraining after exercise decreased AMPK in both exercise groups, but this decrease was not statistically significant. In line with the findings of the current research, Cao et al also reported in their research that after the training period, a significant increase in AMPK level was observed, but after stopping training for 10 days, the AMPK level started to decrease, but the changes were not significant 40). Based on the results, it can be said that any two methods of continuous aerobic exercise and HIIT increase the expression of the AMPK gene; Also, after two weeks ofdetraining, cardiac AMPK gene expression is still high in diabetic rats. However, more research is needed to investigate the longer-term effects of non-exercise on AMPK gene expression and mechanisms related to non-exercise on diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Introduction: The increasing trend of cancer morbidity and mortality is a major human health concern, indicating the necessity for the design and introduction of novel anticancer compounds. The use of nanotechnology products is a new approach to cancer treatment. Therefore, the current study was performed to synthesize Titanium Dioxide nanoparticles (NPs) functionalized with glutamine and conjugated to Thiosemicarbazide (TiO2@Gln-TSC) to inhibit the proliferation of liver cancer cells line (HepG2) and evaluate the effect of TiO2@Gln-TSC NPs on the expression of apoptotic genes. Material & Methods: TiO2@Gln-TSC NPs were synthesized by a chemical method and characterized by Fourier-transform infrared spectroscopy (FT-IR), Energy-dispersive X-ray spectroscopy (EDS), Scanning electron microscopy (SEM), and Transmission electron microscopy (TEM). The cytotoxicity of the Titanium Dioxide nanoparticles was evaluated by the MTT assay, and relative gene expression was studied by Real Time PCR method. Findings: The results showed that the synthesized Titanium Dioxide nanoparticles were spherical with a size range of 59 to 82 nm. The particles had a considerable anti-proliferative effect on liver cancer cells line with IC50 of 80 µg/mL. The treatment of the cancer cell line with TiO2@Gln-TSC NPs significantly increased the expression of the CASP3, BAX, and BCL2 by 2.8, 2.7, and 1.3 folds, respectively, which indicated the activation of apoptotic pathways in the treated cells. Discussion & Conclusion: The results showed that the TiO2@Gln-TSC NPs could inhibit the proliferation of liver cancer cells line and by triggering the apoptosis pathway. [ABSTRACT FROM AUTHOR]

Introduction: According to previous reports, treatment of infertile women who are candidates for in vitro fertilization (IVF), about 15% of the oocytes remains immature. Therefore, finding an efficient approach to make these types of oocytes usable in the clinic, especially in women with limited oocytes, is necessary. One of these approaches is the laboratory culture of immature oocytes in such a way that the expression of genes involved in cytoplasmic maturation increases. Methods: Forty-eight infertile women candidates for IVF donated their immature oocytes at the time of oocyte retrieval. The obtained immature oocytes were randomly divided into two groups: the control group without in-Vitro culture and the intervention group in the form of 24-hour culture. The total oocytes of both groups (ninety-five immature oocytes) were pooled separately and analyzed by quantitative polymerase chain reaction (q-PCR). Results: The level of expression of MT-ATP6 and BMP15 genes in the intervention group has a significant increase compared to the control group, with a fold change of 7.867± 3.12 and 6.327 ± 0.78, respectively (P<0.001). Furthermore, according to the morphological changes, 54% of the immature oocytes in the intervention group had resumed meiosis. Conclusion: Increasing the expression of two cytoplasmic maturation genes, MT-ATP6 and BMP15 can cause the resumption of meiosis in immature oocytes. Therefore, this strategy can be promising in women with low eggs. [ABSTRACT FROM AUTHOR]

Background: and Aim Acinetobacter baumannii causes various nosocomial infections and has a high antibiotic resistance. Probiotics can produce metabolites with antimicrobial properties. This study aims to evaluate the antimicrobial ability of probiotics against nosocomial pathogens by inhibiting the ompA gene expression effective in biofilm formation in Acinetobacter baumannii. Methods & Materials: The antimicrobial properties of probiotics against nosocomial pathogens were evaluated phenotypically. The polymerase chain reaction (PCR) technique was used to identify the ompA gene in Acinetobacter baumannii. After treatment with Bacillus licheniformis supernatant, the ompA gene expression was compared before and after treatment with real-time PCR technique. Ethical Considerations This study was approved by the ethics committee of Islamic Azad University, Qom branch (Code: IR.IAU.QOM.REC.1398.004). Results: Among the study probiotics, Bacillus licheniformis supernatant had the best antimicrobial properties against nosocomial isolates of Acinetobacter baumannii A52, Acinetobacter baumannii ATCC19606, Kelebsiella pneumonia ATCC70063, and Pseudomonas aeruginosa PAO1. Bacillus licheniformis supernatant also significantly reduced the biofilm formation and ompA gene expression in Acinetobacter baumannii. Conclusion: Bacillus licheniformis can produce substances with antimicrobial and antibiofilm properties. It can be used for controlling the causative agents of nosocomial infections. [ABSTRACT FROM AUTHOR]

Introduction: The bacterium Burkholderia Pseudomallei is the cause of melioidosis disease. BLF1 plays an important role in the pathogenesis and infection of B. Pseudomallei. STxB has an adjuvant and carrier role and can be produced by mixing vaccine-candidate antigens with this adjuvant to produce a suitable vaccine. This study aimed to construct and evaluate the immunogenicity of trimethyl chitosan nanoparticles containing BLF1-stxB protein by subcutaneous injection. Material & Methods: In this study, the expression of recombinant BLF1-stxB protein was induced in the expression host, and the protein was purified by affinity chromatography. Then, nanoparticles were fabricated by ion gelation method and the size and shape of nanoparticles were assessed by electron microscopy and injected subcutaneously into mice four times. Antibody titration was evaluated by indirect ELISA. BLF1 toxin was used for immunogenicity. (Ethic code: 6272) Findings: The results of this study showed that protein-containing nanoparticles have higher size and PDI, and lower zeta potential than protein-free nanoparticles. The protein charge in nanoparticles was about 65%. The highest antibody titer belonged to the group receiving protein without nanoparticles. The results showed a 75% conservation challenge of the nanoparticle-free protein group. Discussion & Conclusion: This study showed that the nanoparticle form containing this recombinant protein leads to a weaker immune response, compared to the non-nanoparticle form by injection. The results of the challenge showed that this recombinant chimeric protein provides better protection when subcutaneously injected with an adjuvant. [ABSTRACT FROM AUTHOR]

Background Exercise and physical activity improve damage and destructive changes in the peripheral nervous system. Objective This study aims to investigate the effects of resistance aerobic training on the expression of SEMA3A and NCAM genes and proteins of soleus muscle in male rats of different age groups. Methods A total of 30 male Wistar rats in three groups of 2-week-old (infant) (n=10), 6-week-old (young) (n=10), and 96-week-old (elderly) (n=10) were divided into two groups of training and control. The training program included 6 days of resistance and aerobic training one day in between. The rats were euthanized and the soleus muscle was extracted 48 h after the last training session. A fluorescent microscope was used to measure SEMA3A and NCAM proteins in muscle fibers. Gene expressions were measured by real-time polymerase chain reaction. Results The results showed that SEMA3A gene expression was not significantly different between exercise and control groups in all three age groups; however, SEMA3A protein expression was significantly reduced in infant and young exercise groups (P≤0.001). Also, NCAM gene expression was not significantly different between training and control groups in all three age groups; while there was a significant decrease in NCAM protein expression in young and old training groups compared to the control group (P≤0.001). Conclusion The results showed that resistance aerobic training can inhibit the process of peripheral nerve damage in infant and young rats, as well as the growth and strength of the neuromuscular junction in young and elderly rats. [ABSTRACT FROM AUTHOR]

Background: Interleukin-8 (IL-8) is a member of the pro-inflammatory chemokine family that has been reported to be overexpressed in various human tumors. This chemokine contributes to cancer cell survival, proliferation, metastasis, and angiogenesis. The purpose of this study was to examine the expression level and clinicopathological significance of IL-8 in colorectal cancer (CRC) tissues compared with adjacent normal colorectal tissues in the Iranian population. Materials and Methods: The population of the study consisted of 45 pathologically confirmed patients with CRC, including CRC and adjacent control tissues. The expression levels of the IL-8 gene were evaluated by quantitative real-time polymerase chain reaction (RT-qPCR). The correlation between the expression levels and the clinicopathological features was determined. Results: IL-8 gene expression was overexpressed in CRC samples compared with controls (fold change=5.5; P= 0.02). The area under the ROC curve for IL-8 indicates the potential of IL-8 as the diagnostic marker in CRC (P=0.012). Conclusion: IL-8, which is up-regulated in CRC tissues, can be used to distinguish inflammation-induced CRC from control samples. The significantly up-regulated level of IL-8 needs future investigation for consideration as a biomarker to evaluate the prognosis of CRC. [ABSTRACT FROM AUTHOR]

Introduction1: Feed is the main cost part of poultry production. High feed efficiency poultry produce less feed and less excrement per unit weight gain. Therefore, a comprehensive understanding of the biological mechanisms that control feed efficiency is crucial for the development of optimal breeding and selection strategies. The serine biosynthesis pathway is one of the most important pathways in animals with high feed efficiency. The aim of this study was to investigate the expression of PHGDH, PSAT1 and PSPH genes by real-time PCR in Iranian native turkeys with high and low feed efficiencies. Materials and Methods: Iranian native male turkeys (n=500) were reared up to 20 weeks of age under standard production guidelines. Then 75 turkeys were randomly selected and placed in separate cages with free access to water and feed from 20 to 24 weeks. Turkeys were ranked based on feed conversion ratio (FCR) and three turkeys with the highest and three turkeys with lowest feed efficiency were selected as high feed efficiency (HFE) and low feed efficiency (LFE) birds, respectively. After slaughter of turkeys, RNA was extracted from breast tissue. Quantity and purity of the extracted RNAs were determined using a nanodrop device and its quality was evaluated using 1% agarose gel electrophoresis. Sequences of PSPH, PHGDH, PSAT1 and RPS7 genes were collected from the NCBI database. The primer was designed using Primer Premier version 5 software. All primers were synthesized by Sinaclon (Iran). In this study, RPS7 gene was used as a reference gene. Then, cDNA synthesis was performed. The best amplification temperature for simultaneous amplification of target and reference genes was determined. Samples were amplified for each gene with 3 replications using real-time PCR reaction. Significance level between treatments for each gene was determined separately using t-test in SAS software version 9.2 (P<0.05). Results and Discussion: Results of ultraviolet light absorption measurements at 260 and 280 nm by the nanodrop device showed that the quantity and quality of RNA extracted from the breast muscle samples were of high purity and not contaminated. The range of RNA concentration of the extracted samples was between 480 to 962 ng/μl and the ratio of absorption at 260 and 280 wavelength was about 2.1, which indicates the good quality of the extracted RNAs. The most suitable temperature was selected for specific binding of primers and simultaneous amplification of target genes and temperature control of 58 °C. To investigate and confirm the specificity of replication, melting curves were created to ensure the specificity of the amplified products, the absence of non-specific bands and secondary structures such as hairpin and primer-dimer structures. The results showed that there was only one narrow peak for each gene. The results of studying the expression of serine biosynthesis pathway genes (PSPH, PHGDH and PSAT1) showed that the expression level of these genes in HFE male turkeys was significantly higher than LFE male. Higher expression of PSPH, PHGDH and PSAT1 genes in HFE animals than in LFE animals indicates activation of the serine amino acid biosynthesis pathway, which itself can provide precursors for the Krebs cycle and purine biosynthesis. Glucose is the main source of metabolic energy in the body. When glucose enters the cell, glycolysis begins in the cytoplasm. The pathway of glycolysis and Glutamine catabolism produces an intermediate metabolite called 3-phosphoglycerate, which is gradually catalyzed to serine by PHGDH, PSAT1, and PSPH. Eventually serine is converted to glycine. Activation of this pathway indicates the higher ability of HFE animals to make better use of energy sources such as glucose, which increases protein production in breast muscle tissue and enhances volume and weight of muscle tissue in HFE turkeys. Conclusion: The results of this study showed that the expression of serine biosynthesis pathway genes (PSPH, PHGDH and PSAT1) was significantly higher in high feed efficiency turkeys than in low feed efficiency turkeys. In fact, these results at the level of molecular biology show that turkeys with higher feed efficiency cultivate better use of energy received from feed. Activation of this pathway increases the biosynthesis of various amino acids and thus increases protein and muscle mass in birds. The results of this study can be a promising window to introduce genes that affect feed efficiency in order to further investigate the population and larger flocks of birds. [ABSTRACT FROM AUTHOR]

Introduction: Oxidative stress-induced cell death is activated by free radicals. Exercise and nutrition appear to have the potential to modulate cell proliferation and death. This study aimed to evaluate the combined effect of aerobic exercise and crocin consumption on the prevention of myocardial tissue cell death in male Wistar rats. Material & Methods: In this experimental study, 36 male Wistar rats with a mean weight of 180-200g were randomly divided into six groups (oxygenated water, oxygenated water+crocin, oxygenated water+ exercise, oxygenated water+crocin+exercise, sham, and control). After two weeks of familiarity with the environment and learning the exercises, the training groups were given aerobic exercises for six weeks. All groups, except for the sham and control, were given 1 mM H2O2 and subcutaneously injected with 12.5 mg crocin. 48 hours after the last training session, the rats were anesthetized with CO2 after 10-12 hours of fasting, and their myocardial tissue was isolated. To measure the proapoptotic genes, Real-Time PCR was used; moreover, one-way analysis of variance and Scheffe post-Hoc test were employed for data analysis. A P-value of ≥0.05 was considered statistically significant. (Ethic code: IR.SSRI.REC.1397.254) Findings: The findings showed that six weeks of aerobic training in water, consumption of crocin supplementation, as well as the combination of aerobic exercise and crocin supplementation, reduced the expression of the genes of the internal apoptotic pathway at a significant level of ≥ 0.05. Discussion & Conclusion: According to the results of the present study, it seems that the interaction and combination of aerobic exercise in water and crocin antioxidant supplement should be used to reduce the apoptosis of the myocardial tissue, less cell damage, and ultimately the health of the myocardial tissue. [ABSTRACT FROM AUTHOR]

Introduction: The role of E-cadherin and CD44 has been proven in the development and progression of cancerous and precancerous lesions. It seems that these two markers have a high ability to evaluate the premalignancy of lichen planus lesions and oral leukoplakia. This study aimed to investigate and compare the expression of CD44 and E-cadherin markers in oral leukoplakia, lichen planus, and oral squamous cell carcinoma (SCC). Material & Methods: This analytical-descriptive study was conducted on 60 blocks of lichen planus, leukoplakia, and squamous cell carcinoma. The blocks were stained by CD44 and E-cadherin antibodies. The obtained data were analyzed in SPSS software (version 22), and a P-value of 0.05 was considered statistically significant. Findings: Only 30% of the SCC samples expressed the CD44 marker, while 40% and 50% of leukoplakia and lichen planus samples expressed the CD44 marker, respectively. The expression of the E-cadherin marker in SCC samples was 40% in the range of staining, while it was 50% and 60% in leukoplakia and lichen planus, respectively. There was not a significant difference between the staining intensity of CD44 and E-cadherin (P<0.16). However, in SCC, 70% of the cases showed mild to moderate expression intensity that was statistically significant, compared to lichen planus and leukoplakia (P<0.004). Discussion & Conclusion: It seems that the severity of CD44 and E-cadherin incidence can indicate the changes in dysplasia and premalignancy of oral lichen planus and leukoplakia, compared to oral carcinomas. [ABSTRACT FROM AUTHOR]

Objective: It has been shown that mutation in DNAH1 (Dynein Axonemal Heavy Chain 1) gene is associated with MMAF (multiple morphological anomalies of the flagella) and PCD (primary ciliary dyskinesia) phenotypes. MMAF has been widely studied in male reproductive traits and is often associated with abnormal sperm, which seriously affects male reproductive traits and even leads to infertility. Indeed, as a MMAF-dependent gene, many studies have identified the DNAH1 gene as a key and essential player in male and female gonadal development and have investigated the clinical applications of the DNAH1 gene. PCD is often associated with ciliary motility disorder, which is also an autosomal recessive genetic disease. Animals with severe PCD show infertility. This study aimed to study the expression pattern of the DNAH1 gene in the testicular tissue of Raini Cashmere goat using Real-Time PCR. Materials and Methods: Sampling was done from the testicular tissue of three heads (3 replicates from each head) of Raini Cashmere goats in the slaughterhouse. The isolated samples were placed in 1.5 mL microtubes. Total RNA was extracted from testicular tissue. Agarose gel electrophoresis and UV spectrophotometry were used to evaluate the quality and quantity of extracted RNA. Then cDNA was made and Real-Time PCR was performed. Also, the GAPDH housekeeping gene was used as a control. Melting curves were analyzed and data obtained from Real-Time PCR were performed. Results: The results of Real-Time PCR curves and observing the results of electrophoresis of PCR products on 2% agarose gel showed that the DNAH1 gene is expressed in testicular tissue. For the DNAH1 gene, a band of 140 bp was observed and for the GAPDH gene, a band of 143 bp was observed, and the accuracy of the amplification test was confirmed. Conclusions; According to the results of the present study and the results of other researchers, it can be concluded that the DNAH1 gene plays an important role in fertility. In the present study, it was found that the DNAH1 gene is expressed in testicular tissue. Therefore, the DNAH1 gene is most likely essential for male fertility, and the results of this research have provided a way for future studies to describe the role of the DNAH1 gene as a candidate gene for better fertility and normal physiology in domestic animals, especially goats. [ABSTRACT FROM AUTHOR]

Objective: One of the goals of the poultry industry is to select animals that increased growth rates and also muscle mass while maintaining meat quality. The present study was conducted to evaluate performance, some meat quality characteristics, and gene expression associated with growth (IGF-I, IGF-II, TGF-β1, Myostatin) in three strains of Arian, Ross, and Cobb. Materials and methods: To do this research 150 one-day-old (male and female) broiler chicks of Arian, Ross, and Cobb strains were categorized in a completely randomized design with three treatments, five replicates, and 10 observations per replicate. The function, some physical characteristics of meat, and the relative expression of their genes were investigated. Strain types had a significant effect on the feed conversion ratio (FCR). Results: In the whole the rearing period, the lowest FCR was for the Ross strain and the highest was for the Cobb strain. TPA test of the breast showed that hardness, cohesiveness, and chewiness in Arian, Ross, and Cobb strains were significantly different. Maximum hardness and chewiness were for the Arian and Cobb strains and maximum cohesiveness was for the Ross strain. There were no significant differences between strains for adhesiveness, springiness, or gumminess. TPA test of the thigh showed that hardness, chewiness, and gumminess were not significantly different, but cohesiveness, adhesiveness, and springiness were significantly different between strains. Maximum cohesiveness and springiness were observed in the Arian strain and maximum adhesiveness was for the Ross strain. Breast and thigh pressure tests of the three strains showed that hardness and deformation of hardness were not significantly different. IGF-I and IGF-II relative gene expression of breast meat had no significant difference between strains. TGF-β1 and myostatin relative gene expression were significantly different and the Cobb strain had the highest relative gene expression of TGF-β1. Also, IGF-I and IGF-II relative gene expression had no significant difference in the liver. Conclusions: Given the individual advantages of each strain in some traits, more research is needed with specialized diets for each strain to be able to comment conclusively on the superiority of their traits. [ABSTRACT FROM AUTHOR]

Background & Aims: Performing physical activity and having a healthy body is one of the most essential life needs of people with fatty liver. In recent years, studies have been performed on the relationship between fatty liver and arthrosclerosis. The results of these studies indicate the relationship between the Non-alcoholic fatty liver and arthrosclerosis of coronary artery disease. Non-alcoholic fatty liver disease is associated with a sedentary lifestyle and poor eating habits around the world Fatty liver is associated with an increased risk of cardiovascular disease and the formation of atherosclerotic plaques in the carotid arteries and coronary artery stenosis can affect extracellular matrix factors such as CTGF and RXFP1, which play a role in the formation or non-formation of fibrosis. Studies have shown that fatty liver disease can be effective in causing atherosclerotic changes in arteries and increasing the thickness of the carotid artery as an indicator of atherosclerosis, which can be seen even in mild degrees of fatty liver. Relaxin in all parts of the body can have different expressions of RXFP1 receptor in different arteries, so in rats this receptor is strongly expressed in aortic endothelial cells and RXFP1 activates cAMP, cGMP and cAMP signaling pathways in ERK1 / 2 endothelial cells On the other hand CTGF is mainly synthesized by liver cells in the liver and is strongly induced in liver fibrosis CTGF is induced by fibroblast TGF-β cells and mediates the growth and secretion of extracellular matrix. These results indicate that CTGF is the mediator of many TGF-β-probiotic activities Therefore, the aim is to investigate the effect of this disease on two extracellular matrix genes of the heart. Methods: In this experimental study, 24 male Wistar rats weighing 200-250 g were randomly divided into 3 groups: control, healthy and fatty liver steatosis. The control group was initially performed in the victim and tissue study And the two healthy and fatty liver groups spent two weeks in the same condition There was a healthy group from the beginning to the end of the study and they did not receive any intervention. Mice in the fatty liver group received oral tetracycline at a dose of 100 mg / kg at a dose of 1.5 ccs per mouse for two weeks. The average weight of the mice was 300 g, of which 100 mg / kg was used for 3 mice, of which 100 mg was dissolved in 4.5 cc and each rat was gavaged 1.5 cc. Fatty liver was modified by measuring liver enzymes (SGPT) and a number of biochemical variables. At the end of the second week, rats two groups were healthy and fatty liver48 hours after the last day (10 to 12 hours of fasting), the studied rats in each group were anesthetized by intraperitoneal injection of a mixture of 10% ketamine at a dose of 50 mg/kg and 2% xylosin at a dose of 10 mg/kg. became were sacrificed and heart tissue sample were taken to test for RXFP1 and CTGF gene expression. In each group, tissue analysis was performed by Real Time PCR technique. First, primer design was performed and then total RNA was extracted from tissues and converted to cDNA. Then cDNA was Replicated by PCR and examined for the expression of the mentioned genes. Results: After the second week and examining expression level of RXFP1 and CTGF genes between control, healthy and fatty liver groups, ANOVA test results showed that the expression level ofRXFP1 and CTGF genes (p = 0.0001 and p = 0.0001, respectively) In the fatty liver group, significantly increased compared to the healthy and control groups Considering the value of P<0.05, the null hypothesis that there is no significant difference between the level of RXFP1 in different research groups was rejected with 95% confidence. The results between the steatosis group and the other two groups were significant in increasing the level of RXFP1 gene expression. Therefore, it can be said that in the presence of fatty liver, the expression of RXFP1 gene increases in the heart tissue of male rats in order to inhibit fibrosis. Also, in terms of significance, the results between the steatosis group and the other two groups were significant in increasing the level of CTGF gene expression. Therefore, it can be said that in the presence of fatty liver in the steatosis model, the CTGF gene expression increases in line with the increase in cardiac fibrosis. Overall, our results showed that with the onset of fatty liver disease, both connective tissue growth factors and relaxin increased in the heart, and an increase in connective tissue growth factor indicates cardiac tissue damage, which can lead to heart tissue fibrosis. Therefore, these findings can help new therapies aimed at modulating the effects of CTGF and the use of RXFP1 as a new direction for further clinical studies. Our other findings showed that with induction of fatty liver, the level of RXFP1 in heart tissue increased from the beginning and did not change until the end of the two weeks. The expression level of RXFP1 gene in steatosis fatty liver groups (BS, CS) was significantly higher than the other 2 groups on the other hand the increase in connective tissue growth factor (CTGF) in this study was probably to produce extracellular matrix and compensate for their degradation, and the increase in RXFP1 was to prevent collagen deposition in ECM connective tissue growth factor (CTGF) in cardiac tissue increased sharply, such that its rate increased up to 7 times in the first two weeks compared to the control group, and this increase continued until the end of the two weeks, that increased 10 times However, this method should be considered with more caution because high expression of CTGF increases the level of fibronectin, collagen I and III proteins in the extracellular matrix, followed by myocardial infarction Conclusion: The fatty liver model of steatosis increases the expression of cardiac CTGF gene and fibrosis, and also increases the RXFP1 gene, which has anti-fibrosis activity. CTGF (CCN2) in response to tissue damage initiates signaling pathways of connective tissue regeneration Therefore, and cardiac tissue fibrosis. RXFP1, which is a component of the extracellular matrix and is most commonly expressed in aortic endothelial cells exerts most of its physiological effect on the cardiovascular system through NO (Nitric oxide). [ABSTRACT FROM AUTHOR]

Introduction: During exercise, angiogenesis occurs in active skeletal muscle; however, little is known about potential mechanisms for improving this adaptation. This study aimed to investigate a period of interval training on chemokine gene expression and its effect on vascular endothelial growth factors in male adult rats. Material & Methods: In this study, 24 rats were divided into three groups (n=8 in each): high-intensity training (HIT), low-intensity training (LIT), and control groups. HIT and LIT groups were trained for eight weeks (five days per week). The exercise program in the HIT group consisted of running on a treadmill for 8 min with 85-90% VO2max intensity and 2 min with 50-60% VO2max intensity. The LIT group exercise program consisted of running on a treadmill for 8 min with 55-60% VO2max intensity and 2 min with 45- 50% VO2max intensity. The control group had no training. The expression of chemokine and vascular endothelial growth factor genes was measured in soleus muscle. The data were analyzed using one-way ANOVA and Tukey post hoc test. Statistical differences were considered significant at P<0.05. (Ethic code: 141/370299) Findings: The results of this study, showed that the expression levels of chemokine and vascular endothelial growth factor gene in the HIT group were significantly higher than that in the control group (P=0.01, P=0.04), while the levels of chemokine and vascular endothelial growth factor in the LIT group were not significantly different from those in the control group (P=0.2, P=0.1). Discussion & Conclusion: According to the results of the present study, it seems that high-intensity exercises can be more effective than low-intensity exercises in increasing angiogenesis caused by the increase of chemokine that in turn depends on vascular endothelial growth factor levels. [ABSTRACT FROM AUTHOR]

Background and Objectives: Consumable fats in ruminant products are the main source of various conjugated linoleic acid isomers with a wide range of positive effects on human health. The biological role of various isomers of conjugated linoleic acid and some precursor compounds such as rumenic acid and vaccenic acid have been extensively studied. Various genetic factors such as race type are considered as effective factors on the effect of different environmental factors on plasma levels, growth, energy distribution between different tissues of the body, and the pattern of fatty acids and the chemical composition of the carcass. There are several studies on dairy cows on the role of various dietary factors including fatty acids in their effect on performance and energy metabolism. However, much research has been done in this field even in Iran and there is no comparison between the tailed and no-tailed sheep in the type of response to different sources of dietary energy. Therefore, this study was performed to evaluate the effect of high-energy diets rich in carbohydrates or protected fat sources on dry matter intake, weight gain, expression of the TNF-α gene, and some blood metabolites in male lambs of Taleshi and Zel. Materials and Methods: This study was performed in an experimental period of 116 days (14 days of habituation and 102 days of sampling). At the end of the habituation period before breakfast, the animals were weighed and kept individually (6 lambs of Taleshi breed and 6 lambs of Zel breed for each treatment). The control diet (fat-free diet), a diet containing 4% saturated fat supplement rich in stearic acid, and a diet containing 4% unsaturated fat supplement protected apparent digestibility of dry matter, organic matter, crude fat, crude protein, and insoluble fibers in neutral detergent and insoluble fibers in acid detergent was measured by the recommended method. The amount of dry matter consumed was measured by taking into account the amount of dry matter remaining in the manager (post-manager) and the amount of dry matter in the diet. To measure weight changes, lambs were weighed every two weeks before feeding until the end of the experiment using a digital calibrator. Blood samples were taken from the lambs intravenously every two weeks until the end of the experimental period, four hours after the morning meal. TNF-α gene expression was measured in the Rasta laboratory located in West Azerbaijan Science and Technology Park. Results: The highest level of feed intake at the end of the period belonged to Zel and Taleshi lambs that consumed the feed containing saturated stearic fatty acid. The digestibility of dry matter, organic matter, NDF, and ADF was affected by fat source, However, the effect of race and the interaction between race and type of fat did not affect their digestibility. The interaction effect of race and fat on the digestibility of crude protein and ether extract was significant (P<0.05). Crude protein digestibility was not affected by the fat type. The highest digestibility of crude protein was observed in the treatment of protected unsaturated fat of Taleshi breed and the lowest amount was observed in the treatment of protected unsaturated fat of Zel. The highest digestibility of ether extract was observed in the treatment of Taleshi protected unsaturated fat (P<0.05). The expression of the TNF-α gene was higher in the subcutaneous fat of the protected lambs of the unsaturated treatment (P<0.05). Also, the TNF-α gene expression was higher in tail fat and tail fat samples of talus lambs with protective unsaturated treatment and less stearic acid treatment in Zell lambs than in other treatments (<0.05). Blood triglycerides of Zel and Taleshi fattening lambs were subjected to the interaction of treatment factors over time, treatment in the race, and triple interaction of race over time treatment during the 16-week fattening period. Conclusion: In general, it can be concluded that the addition of fat supplements in the diet of Taleshi and Zel lambs improves blood parameters and thus improves performance (weight gain and feed intake). Since the best results were obtained in the treatment of protected unsaturated fat supplement, the use of this fat supplement at the level of 4% is recommended in Taleshi and Zel lambs' nutrition [ABSTRACT FROM AUTHOR]

Objective The growth and yield of plants in the arid and semiarid areas are limited by salinity stress. In these areas, salinity intensifies by high temperahires. Peppermint (Mentha piperita L.) is of great economic importance in the most of world areas due to their valuable essential oils. This study investigated the simultaneous effects of salinity and heat on rosmarinic acid production and expression of three effective genes (C4H, HPPR, and PAS) in rosmarinic biosynthesis in peppermint. Materials and methods The effect of two levels of salinity 60 and 120 mM of sodium chloride (irrigation water with salinity of 10 Mm as control) and heat stress at 35°c (25٥c as control) at three interval times (24, 48 and 72 hours) after treatments were measured in a completely randomized design with three replications. Results The results showed that salinity stress decreased the relative level of rosmarinic acid. The process intensified over time so that it reached its lowest level at salinity of 60 mM at 72 hours. RAS genes expression was significantly reduced under salinity of 120 mM and 60 mM under 25٥c and 35 ٥c. Changes in the expression level of C4H in peppermint seedlings at the salinity levels of 60 mM and 120 mM at 25٥c showed a significant increase (4.1 and 3.6 times respectively) at the first 24 hours compared to control. The expression of HPPR gene in peppermint seedlings at 35 ٥ c increased 2.68, 1.79 and 2.55 times at 24, 48 and 72 hours, respectively, compared to the control. Conclusions Simultaneous salinity and heat stress are a limitation factor for growing Mentha piperita L. These factors had a negative effect on the biosynthesis of rosmarinic acid in this plant. Salinity and heat stress decreased the expression of some genes and increased the expression of others in peppermint. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral ischemia-reperfusion causes complex pathological mechanisms that lead to tissue damage, such as neuronal apoptosis. Usnic acid is a secondary metabolite of lichen and has various biological properties including antioxidant and anti-inflammatory activities. This study aimed to investigate the neuroprotective effects of usnic acid on apoptotic cell death and apoptotic-related proteins (Bax and Bcl-2) in the CA1 area of the hippocampus following cerebral ischemia-reperfusion. Material & Methods: A total of 42 male Wistar rats were randomly divided into three groups (sham, ischemia-reperfusion, and ischemia-reperfusion+usnic acid). Ischemia was induced by occlusion of both common carotid arteries for 20 min. Usnic acid (25 mg/kg, intraperitoneally) was injected at the beginning of reperfusion time. The expression levels of Bax and Bcl-2 proteins were measured using the immunofluorescence method, and the rate of apoptotic cell death was determined using the TUNEL staining method. (Ethic code: IR.SHMU.REC.1397.186) Findings: In this study, cerebral ischemia increased apoptotic cell death in the CA1 area of the hippocampus. It was demonstrated that usnic acid significantly decreased apoptotic cell death by decreasing the expression of Bax pro-apoptotic protein and increasing the expression of Bcl-2 (anti-apoptotic protein). Discussion & Conclusion: It can be concluded that usnic acid has a neuroprotective effect against cerebral ischemia-reperfusion damages by reducing cell death. [ABSTRACT FROM AUTHOR]

Introduction: Abortion is a common complication that refers to the early termination of pregnancy with the death of the fetus before the 20th week of pregnancy. Previous studies show that many genes are involved in this disease, including the CX3CR1 gene, which is one of the inflammatory response genes in the immune system. The pathogenicity of these variants was determined in this study using bioinformatics analysis. Material & Methods: In this study, the effects of rs3732378 and rs3732379 mutation were predicted using bioinformatics tools including SIFT, PolyPhen2, PROVEAN, Predict SNP, and Exome Variant Server. Changes in the stability of mutant proteins were investigated using IMutant and DynaMut tools. Moreover, modeling of the protein structure, docking, and protein-ligand interaction were performed using SWISSMODEL, SwissDock, and FRODOCK tools as well as PyMOL, Hawkdock, and MolSoft software, respectively. Findings: Many polymorphisms related to the CX3CR1 gene have been known to date. Out of 244 missense mutations in the dbSNP database, two variants (rs3732378 and rs3732379) have been reported in association with recurrent pregnancy loss related to the CX3CR1 gene. The results of bioinformatics analyses showed that both variants were predicted as pathogenic mutations and changed the stability of the protein structure and played a key role in interaction with the ligand. Discussion & Conclusion: The findings of this study indicate that two missense mutations in the CX3CR1 gene are an important candidate for recurrent miscarriage and their identification in patients with recurrent miscarriage can be regarded as a risk factor. [ABSTRACT FROM AUTHOR]

Background and Objectives One of the molecules that associated with cancer progression are Long non coding RNA (LncRNAs). HOX transcript antisense RNA (HOTAIR) is a member of the lncRNA family. Homeobox C13 (HOXC13) gene is one of the several HOX genes that is located near the HOTAIR. This study was to evaluate the expression of HOTAIR and HOXC13 genes in tumor and normal tissues adjacent to tumor in patients with esophageal cancer. Methods This is an experimental study. 30 pairs of esophageal tumor tissue and tumor margin tissue were purchased. RNA of these tissues was extracted and Real-time PCR with Beta-actin gene was used for their relative expression. Statistical analysis of data, t-test and Analysis of variance (ANOVA) were performed in GraphPad Prism 8 software. Results Comparison of target gene expression in esophageal tumor samples relative to tumor margins showed that the relative expression of the HOTAIR genes was 1.95 time (P=0.0219) and the HOXC13 14.4 time (P=0.014) significantly increased expression. Also, the HOXC13 gene expression shows a significant relationship with metastasis to distant regions, type and degree of tumor. The correlation coefficient between the relative expression of the HOTAIR and the HOXC13 genes was 0.152. It was positive but not significant between the two genes (P=0.2). Conclusion According to the association of the HOTAIR and the HOXC13 genes with cancer, our study may partially express the role of these two genes in the tumorigenesis process in the development of esophageal cancer. [ABSTRACT FROM AUTHOR]

Nutrigenomics is the study of the effect of nutrition on gene expression which discusses how DNA is converted to mRNA and then converted mRNA to protein, and is the basis for understanding the biological activity of edible compounds. Nutritional manipulations and nutritional approaches are key tools to influence the performance and health of organisms. Today, it has been shown that better nutrition of animals selected for further production has a beneficial effect on their function. Despite the importance of this issue in production systems, there are no ways to clearly explain the molecular mechanisms of these changes. This review study aimed to investigate nutrigenomics as a molecular approach to the expression of genes involved in the health and growth of organisms. Searching was conducted in Scopus, PubMed, ScienceDirect, IranMedex, and Google Scholar databases on the studies conducted during 1990-2018 by using the keywords: “nutrigenomics”, “gene expression”, “nutrients”, “food formulation”. Initial stage yielded 120 articles. After excluding conferences papers, 58 remained for the final review. There are a limited number of nutrigenomics studies on the laboratory and farm animals, but it has been confirmed that there is an association between nutrition, genetics, fertility and growth. Therefore, the use of nutrients that can express gene expression in a way that improves the function and efficiency of organisms is essential in feed formulation as a new approach in nutrition.

Background Esophageal Squamous Cell Carcinoma (ESCC) is the seventh most common and lethal malignancy worldwide with a high incidence in Iran. Esophageal cancer has a poor prognosis and low 5-years survival rate. Despite several studies on esophageal cancer, its underlying mechanism remains unclear. Therefore, it is significant to analyze the molecular factors involved in disease for introducing effective diagnosis and therapeutic approaches. Accordingly, the aberrant expression of miRNA was demonstrated in the etiology of esophageal cancer, and applying them as detecting biomarkers was further considered by researchers. This study aimed to evaluate the expression level of miRNA-138 in the tumor tissues of ESCC and normal adjacent tissues. Objective In total, 35 samples of tumor and normal tissues of the esophagus were collected from ESCC patients. Methods Then, RNA extraction was conducted and the expression level of miRNA-138 was assessed in the collected tissue samples, applying real-time RT-PCR. Moreover, the relationship between the miRNA- 138 expression level and the patient’s clinical characteristics was assessed. Results According to the obtained results, the expression of miR-138 was significantly downregulated in the tumor tissues of ESCC, compared to normal adjacent tissues (P<0.05). Additionally, the level of miRNA-138 downregulation was significantly correlated with tumor differentiation degree and metastasis status (P<0.05). Conclusion The significant downregulation of miRNA-138 in the tumor samples of ESCC indicated the role of this epigenetic alteration in esophageal carcinogenesis. Therefore, applying the miRNA-138 could be considered as a potential molecular biomarker for ESCC diagnosis and screening. [ABSTRACT FROM AUTHOR]

The FAO Penman-Monteith is a baseline method to estimate reference evapotranspiration. In many cases, it is difficult to access all data, so replacing simpler models with lower input data and appropriate accuracy is necessary. The purpose of this study is to investigate the capability of the experimental models, gene expression programming, stepwise regression, and Bayesian network in estimating reference evapotranspiration. In this research, daily information of the Boroujerd synoptic station in the period of 1996 -2017 was used as model inputs. Based on the correlation between input and output parameters, six input patterns were determined for modeling. The results showed that the Kimberly-Penman model has the best performance among the experimental models. Gene expression programming with fourth pattern and Default Model Operators (R² = 0.98 and RMSE = 0.9), Bayesian Network with sixth pattern (R²=0.91 and RMSE = 1.01), and stepwise regression with sixth pattern have the most accurate patterns at R² = 0.91 and RMSE = 0.9 in the training stage. Comparison of the performance of the three models showed that the gene expression programming model was superior to the other two models with the Average Absolute Relative Error (AARE) of 0.12 and the Mean Ratio (MR) of 0.94. The results showed that gene expression programming had an acceptable ability to estimate reference evapotranspiration under the weather conditions of Boroujerd and could be introduced as a suitable model. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to determine the effect of Titanium carbide nanoparticles on stemness and senescence markers of mouse bone marrow derived mesenchymal stem cells. Methods: After isolation of mesenchymal stem cells from mouse’s bone marrow, their surface markers were studied using flowcytometry. MTT assay, cell cycle analysis; colony forming assay, and senescent beta galactosidase staining were performed for cells treated with titanium carbide nanoparticles. Then, the expression of OCT-4 and Nanog genes were studied by qRT-PCR in titanium carbide treated mouse’s bone marrow mesenchymal stem cells (mBMSCs). Results: All mBMSCs showed spindle shaped morphology. Their identity was confirmed by flow cytometry of stained cells for CD11b, CD90, CD45, and CD44 markers. The MTT assay results showed that titanium carbide effect is time-dependent and no cytotoxic effects were observed in short treatment times. But toxic effects were observed after 72 or 144 hours of post treatment with doses range from 0.1 to 1 mM (P<0.05). Besides, cell cycle study detected more cell populations in G0/G1 and less percentage in S phase. The colony forming assay in treated cells exhibited smaller size of colonies. The beta galactosidase staining of treated cells demonstrated more positive cells (more aged cells). Finally, qRT-PCR showed significant down regulation of OCT-4 and Nanog (p<0.05). Conclusion: Titanium carbide as an implant material could affect the viability, stemness and senescence of mBMSCs in negative manner. [ABSTRACT FROM AUTHOR]

Background and Aim Several microRNAs are involved in regulating muscle mass, which plays an essential role in hypertrophy and atrophy of skeletal muscle, The present study examined the expression of some genes as regulators of muscular atrophy following a period of inertia in rats. Methods & Materials For this purpose, 18 male Sprague-Dawley rats were divided into three groups (Control, Exercise+inactivity, and Inactivity). The exercise+inactivity group run on the treadmill for 18 weeks and five times per week. The hindlimb of the animal was immobilized for seven days with the casting method. Soleus muscle was extracted and the expression of the genes was measured by the RT-PCR method. Univariate ANOVA and Tukey post hoc test was used to determine the differences (α=0.05). Ethical Considerations The Ethics Committee of the Tehran University of Medical Sciences Research approved this study (Code: IR.SUMS.REC.1396.S 463). Results Results showed that immobilization in both Exercise+ inactivity and inactivity groups, compare to the control group, increased expression of miR-1 genes (P<0.10), FOXO3a (P<0.001) and decreased expression of miR-206 (P<0.007) and IGF-1 (P<0.001). This difference was statistically significant. Conclusion According to the results of this study, it can be said that changes in the expression of RNAs by chromatography cause changes in the expression of muscle regulating genes, and although endurance exercises have protective effects, they cannot prevent these changes. [ABSTRACT FROM AUTHOR]