فهرست مطالب

International Journal of Molecular and Cellular Medicine - Volume:7 Issue: 27, 2018
  • Volume:7 Issue: 27, 2018
  • تاریخ انتشار: 1397/10/01
  • تعداد عناوین: 6
|
  • Farid Ebnerasuly , Zahra Hajebrahimi*, Seyed Mehdi Tabaie , Mojtaba Darbouy Pages 146-157
    Adipose-derived stem cells (ADSCs) are widely used for tissue engineering and regenerative medicine. The beneficial effects of ADSCs on wound healing have already been reported. Remodeling of extracellular matrix (ECM) is the most important physiological event during the wound healing. ECM is sensitive to mechanical stresses and the expression of its components can be therefore influenced. The aim of this study was to investigate the effect of simulated microgravity on the gene expression of some ECM and adhesion molecules in human ADSCs. After isolation and characterization of ADSCs, cells were exposed to simulated microgravity for 1, 3 and 7 days.  Real-time PCR, fluorescence immunocytochemistry, and MTT assay were performed to evaluate the alterations of integrin subunit beta 1 (ITGB1), collagen type 3 (ColIII), matrix metalloproteinase-1 (MMP1), CD44, fibrillin (FBN1), vimentin (VIM) genes, and ColIII protein levels as well as cells viability. Microgravity simulation increased the expression of ITGB1, ColIII, MMP1, and CD44 and declined the expression of FBN1 and VIM genes. ColIII protein levels were also increased.  There were no significant changes in the viability of cells cultured in microgravity. Since the high expression of ECM components is known as one of the fibroblast markers, our data suggest that pretreatment of ADSCs by simulated microgravity may increase their differentiation capacity towards fibroblastic cells. Microgravity had not adversely affected the viability of ADSCs, and it is likely to be used alone or in combination with biochemical inducers for cell manipulation.
    Keywords: Adipose derived stem cells, simulated microgravity, extracellular matrix, adhesion
  • AVa Safaroghli, Azar , Atieh Pourbagheri, Sigaroodi , Davood Bashash*, Elaheh Nooshinfar , Ali Anjam, Najmedini , Soroush Sadeghi , Mostafa Rezaie, Tavirani , Mohammad Esmaeil Akbari Pages 158-168
    The advent of combination therapy unprecedentedly shifted the paradigm of cancer treatment by reconstructing the conventional protocols. By identifying the anti-tumoral activity for different natural products, recent interest has focused on inventing the combined-modality strategies in order to increase the cure rates of cancer, while reducing the toxic side effects of current intensive regimens. To evaluate whether melatonin, the indolic hormone produced mainly by the pineal gland, could enhance the pro-apoptotic effect of arsenic trioxide (As2O3) in breast cancer, MCF-7 cells were treated with As2O3-plus-melatonin and then the survival, proliferative rate, caspase-3 activity, and mRNA expression level of anti-apoptosis target genes of NF-κB were investigated. Our results delineated that exposure of MCF-7 cells to As2O3 not only reduced the survival of the cells but also induced a caspase-3-dependent apoptotic cell death. Noteworthy, an enhanced induction of apoptosis was found using As2O3 in combination with melatonin. Moreover, RQ-PCR analysis revealed that the enhanced cytotoxic effect of As2O3 in the presence of melatonin is mediated, at least partly, through suppressing the expression of NF-κB anti-apoptotic target genes such as MCL-1, BCL-2, survivin, XIAP, and c-IAP1 in breast cancer cells. The resulting data showed that As2O3, either alone or in combination with melatonin, exerted significant cytotoxic effect against MCF-7 cells. However, further investigations are needed to provide valuable clues for expediting this combination as a therapeutic strategy for breast cancer.
    Keywords: As2O3, Apoptosis, Combination therapy, Melatonin, NF-?B
  • Seyed Mohammad Salar Zaheryani , Mohammad Essmail Ebrahimi , Abdollah Kasaei , Amir Roointan , Mahmood Nejabat*, Mehdi Dianatpour , Meisam Ghanbari , Mohammad Reza Talebnejad , Fakhraddin Naghibalhossaini Pages 169-175
    Pterygium is one of the most common eye conditions without any clear etiology. Some studies have suggested an association between sun exposure and pterygium, but others have proposed the role of genetic variations in its pathogenesis. To date, no study has investigated the association of inflammatory transcription factor, NFκB genes with pterygium in the Middle East. We examined the changes in expression of 3 inflammatory related NFκB1, NFκB2, and RELA genes in patients with pterygium. Thirty patients with pterygium and 30 age and sex-matched controls were enrolled in this case-control study. None of the participants showed any clinical signs of inflammation in their conjunctiva. Demographic information was obtained and the expression levels of three genes including NFκB1, NFκB2, and RELA were measured in their conjunctiva by real-time RT-PCR using gene-specific primers. Mean expression level of NFκB1, NFκB2 and RELA genes in patients were 2.4±0.3, 1.9± 0.5, and 1.8±0.4 times higher than normal subjects, respectively. Higher levels of gene expression were observed in individuals with more outdoor activity and sun exposure. Moreover, a significant correlation was observed between the expression levels of NFκB2 and RELA genes, suggesting a possible NFκB2- RELA heterodimer formation in patients with pterygium. This study has indicated a significant association between expressions of inflammatory-related NFκB1, NFκB2 and RELA genes, and pterygium. Further studies to verify the role of inflammation in the pathogenesis of pterygium, may provide new targets for managing pterygia.
    Keywords: Pterygium, inflammation, gene expression, NF-kappa B, real-time RT-PCR
  • Soheila Asadi , Zohreh Rahimi , Massoud Sadijam , Nooshin Shabab , Mohammad Taghi Goodarzi * Pages 176-184
    Induced oxidative stress in diabetes mellitus (DM) plays a critical role in insulin resistance. Fork head-related transcription factor (FOXO) proteins are important transcriptional factors involved in oxidative stress and insulin resistance. Resveratrol (RSV) is a polyphenol with hypoglycemic and antioxidant properties. The aims of the present study were to examine the effects of RSV on FOXO gene expression, serum superoxide dismutase (SOD) activity, insulin level, and insulin resistance in type 2 diabetic (T2DM) rats. Thirty male Wistar rats were used in this study. DM was induced in rats (n=24) using streptozotocin (STZ) and nicotinamide; then, they were divided into 4 groups of 6 rats each. Six untreated normal rats were used as normal control group; diabetic rats in groups 2 to 5 were treated with 0, 1, 5 and 10 mg /kg body weight of RSV, respectively for 30 days. At the end of the experimental period, the rats were sacrificed, their sera were separated, and adipose tissues were obtained and stored at −80 °C. Serum glucose and SOD activity levels were determined biochemically, and serum insulin level was determined by ELISA method. Gere expression in FOXO1 and FOXO3a in adipose tissue was evaluated using real‐time PCR. Results indicated that RSV significantly reduced blood glucose level, increased insulin level and improved insulin sensitivity. RSV resulted in an increased serum SOD activity and caused decreased FOXO1 and FOXO3a expression in adipose tissue of rats with T2DM. Therefore, by attenuation of FOXO expression in adipose tissue of T2DM rats, RSV showed a hypoglycemic potential and antioxidant properties, and consequently ameliorated insulin resistance.
    Keywords: Oxidative stress, diabetes mellitus, FOXO, insulin resistance, resveratrol, superoxide dismutase
  • Athena Rajaie , Mostafa Allahyari , Mahdieh Nazari, Robati , Hossein Fallah * Pages 185-192
    Insulin resistance is a feature of most patients with type 2 diabetes mellitus. Epidemiological evidence suggests a correlation between inflammation and insulin resistant states such as obesity, but the underlying mechanisms are largely unknown. Interleukin-1 receptor-associated kinases (IRAK) play a central role in inflammatory responses by regulating the expression of various inflammatory genes in immune cells. This study was aimed to investigate the effect of IRAK inhibitor on gene transcription and serum concentration of adiponectin in insulin-resistant mice. Experimental mice were randomly divided into 6 groups: the healthy control group was fed a regular chow diet while other groups were fed with a high-fat diet for 12 weeks. After this period, animals were treated with IRAK inhibitor, pioglitazone, both IRAK and pioglitazone, and DMSO, for two weeks. Adiponectin gene expression level was analyzed by real-time PCR. Additionally, serum adiponectin levels were measured by ELISA. Homeostasis model assessment-adiponectin (HOMA-AD) as an insulin sensitivity index was calculated. IRAK inhibitor and pioglitazone increased significantly the expression of adiponectin gene. Also, adiponectin concentration in the control group (9.67±1.1 μg/ml) increased to 25.34±2.04 μg/ml in pioglitazone treatment group. IRAK inhibitor also increased adiponectin concentration (18.24±1.53 μg/ml) but did not show a synergistic effect with pioglitazone when administered simultaneously (26.66±2.5 μg/ml).  HOMA-AD was 0.33±0.04 in the pioglitazone-treated group, 0.6±0.13 in IRAK inhibitor group, and 0.31±0.03 in animals that received IRAKi and pioglitazone.  Our findings suggest that increased adiponectin secretion from adipose tissue mediated by IRAK inhibitor may increase the insulin sensitivity in an animal model of insulin resistance.
    Keywords: Insulin resistance, Inflammation, Adiponectin, IRAK inhibitor
  • Rasoul Yahyapour , Peyman Amini , Hana Saffar , Saeed Rezapoor , Elahe Motevaseli , Mohsen Cheki , Bagher Farhood , Farzad Nouruzi , Dheyauldeen Shabeeb , Ahmed Eleojo Musa , Masoud Najafi * Pages 193-202
    Radiation-induced heart toxicity is one of the serious side effects after  a radiation disaster or radiotherapy for patients with chest cancers, leading to a reduction in the quality of life of the patients. Evidence has shown that infiltration of inflammatory cells plays a key role in the development of functional damages to the heart via chronic up-regulation of some pro-fibrotic and pro-inflammatory cytokines. These changes are associated with continuous free radical production and increased stiffness of heart muscle. IL-4 and IL-13 are two important pro-fibrotic cytokines which contribute to the side effects of exposure to ionizing radiation. Recent studies have proposed that IL-4 through upregulation of DUOX2, and IL-13 via stimulation of DUOX1 gene expression, are involved in the development of late effects of radiation. In the present study, we aimed to detect changes in the expression of these pathways following irradiation of rat’s heart. Furthermore, we evaluated the possible protective effect of metformin on the development of these abnormal changes. 20 male rats were divided into 4 groups (control, radiation, metformin-treated, metformin + radiation). These rats were irradiated with 15 Gy 60Co gamma rays and sacrificed after 10 weeks for evaluation of the changes in the expression of IL4R1, IL-13R2a, DUOX1, and DUOX2. In addition, the levels of IL-4 and IL-13 cytokines, as well as infiltration of macrophages and lymphocytes were detected. Results showed an upregulation of both DUOX1 and DUOX2 pathways in the presence of metformin, while the level of IL-13 did not show any significant change. This was associated with infiltration of macrophages and lymphocytes. Also, treatment with metformin could significantly attenuate the accumulation of inflammatory cells, and upregulate these pathways. Therefore, suppression of dual oxidase genes by metformin may be a contributory factor to its protective effect.
    Keywords: Radiation, metformin, heart Injury, IL-4, IL-13, DUOX1, DUOX2