@article { author = {Khanizadeh, Sayyad and Hasanvand, Banafshe and Esmaeil Lashgarian, Hamed and Almasian, Mohammad and Goudarzi, Gholamreza}, title = {Interaction of viral oncogenic proteins with the Wnt signaling pathway}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {651-659}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.28903.6982}, abstract = {It is estimated that up to 20% of all types of human cancers worldwide are attributed to viruses. The genome of oncogenic viruses carries genes that have protein products that act as oncoproteins in cell proliferation and transformation. The modulation of cell cycle control mechanisms, cellular regulatory and signaling pathways by oncogenic viruses, plays an important role in viral carcinogenesis. Different signaling pathways play a part in the carcinogenesis that occurs in a cell. Among these pathways, the Wnt signaling pathway plays a predominant role in carcinogenesis and is known as a central cellular pathway in the development of tumors. There are three Wnt signaling pathways that are well identified, including the canonical or Wnt/β-catenin dependent pathway, the noncanonical or β-catenin-independent planar cell polarity (PCP) pathway, and the noncanonical Wnt/Ca2+ pathway. Most of the oncogenic viruses modulate the canonical Wnt signaling pathway. This review discusses the interaction between proteins of several human oncogenic viruses with the Wnt signaling pathway.}, keywords = {β-catenin,Canonical pathway,Carcinogenesis,Oncogenic viruses,Wnt signaling}, url = {https://ijbms.mums.ac.ir/article_10839.html}, eprint = {https://ijbms.mums.ac.ir/article_10839_ceae564ce0b0eea16e0a0acdc853a3a0.pdf} } @article { author = {Karimaghai, Negar and Tamadon, Amin and Rahmanifar, Farhad and Mehrabani, Davood and Raayat Jahromi, Alireza and Zare, Shahrokh and Khodabandeh, Zahra and Razeghian Jahromi, Iman and Koohi-Hosseinabadi, Omid and Dianatpour, Mehdi}, title = {Spermatogenesis after transplantation of adipose tissue-derived mesenchymal stem cells in busulfan-induced azoospermic hamster}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {660-667}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.29040.7010}, abstract = {Objective(s): Adipose tissue-derived mesenchymal stem cells (AT-MSCs) with more potent immunomodulatory effects, greater proliferative potential and secretion of growth factors and cytokines in comparison with bone marrow derived MSCs are more appropriate for cell therapy. The aims of the present study were to evaluate the histomorphometric effect of AT-MSCs allotransplantation on regeneration of germinal layer cells of seminiferous tubules in busulfan-induced azoospermic hamsters.Materials and Methods: In the present experimental case-control study, AT-MSCs were isolated from adipose tissue of two female and six male donor albino hamsters, and testes of the males were simultaneously used as negative control group. Six mature male recipient hamsters received two doses of busulfan with three weeks interval to stop endogenous spermatogenesis. Right testis of hamsters was intratubular injected with AT-MSCs via efferent duct 35 days after induction of azoospermia and was used as cell therapy group. The left testis without cell therapy was served as azoospermia group.Results: After 35 days, testes and epididymis in all groups were removed for histological evaluation. Histomorphometric analyses of AT-MSCs-treated testes and epididymis showed that the epithelial tissue of seminiferous tubules was normally repaired in most cell-treated seminiferous tubules, and spermatozoa were present in epididymis tubes in comparison with intact testes. The untreated seminiferous tubules and epididymis tubes of azoospermia group were empty.Conclusion: Allotransplanted AT-MSCs could successfully induce spermatogenesis in azoospermic seminiferous tubules of hamster. Therefore, AT-MSCs can be suggested as an attractive candidate in cell transplantation of azoospermia.}, keywords = {Adipose tissue,Azoospermia,Cell therapy,Hamster,Mesenchymal stem cells}, url = {https://ijbms.mums.ac.ir/article_10789.html}, eprint = {https://ijbms.mums.ac.ir/article_10789_e3805e9cee8f091d942292d821986470.pdf} } @article { author = {Anbara, Hojat and Shahrooz, Rasoul and Razi, Mazdak and Malekinejad, Hassan and Najafi, GholamReza}, title = {The effect of vitamin C on mice hemolytic anemia induced by phenylhydrazine: an animal model study using histological changes in testis, pre-implantation embryo development and biochemical changes}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {668-677}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.25819.6356}, abstract = {Objective(s): The aim of the present study was to assess the effects of vitamin C (Vit C) on hemolytic anemia induced by phenylhydrazine (PHZ). Materials and Methods: Twenty-four healthy male mice were divided into four groups, randomly: Control group (0.1 ml/day, normal slaine, IP), PHZ group that received only PHZ 8 mg/100 g/48 hr, IP, PHZ+Vit C group that received PHZ 8 mg/100 g/48 hr, IP and Vit C 100 mg/kg BW-1/day by gavage and Vit C group that received 100 mg/kg BW-1/day Vit C by gavage. After 35 days, germinal cells, RNA damage, sperm parameters, testis malondialdehyde (MDA) content, serum total antioxidant capacity (TAC), pre-implantation embryo development and mRNA levels of cyclin D1 and c-myc in two-cell, and morula and blastocyst stages were assessed.  Results: Vit C reduced the RNA damage, enhanced sperm quality, promoted pre-implantation embryo development and improved testicular antioxidant and endocrine status (P<0.05). Vit C reduced cyclin D1 expression and up-regulated c-myc mRNA level in two-cell, morula, and blastocyst embryonic cells. Conclusion: Vit C enhanced the fertilizing potential by ameliorating the endocrine status, antioxidant capacity, and sperm quality. Finally, the cyclin D1 and c-myc gene expressions were regulated in PHZ+Vit C treated group that promoted the embryo development.}, keywords = {Hemolytic anemia,Histology,Mice,Testis,Vitamin C}, url = {https://ijbms.mums.ac.ir/article_10754.html}, eprint = {https://ijbms.mums.ac.ir/article_10754_d853132478d01adc50115c21fff53b34.pdf} } @article { author = {Barati, Tahereh and Haddadi, Mahnaz and Sadeghi, Fatemeh and Muhammadnejad, Samad and Muhammadnejad, Ahad and Heidarian, Ronak and Arjomandnejad, Motahareh and Amanpour, Saeid}, title = {AGS cell line xenograft tumor as a suitable gastric adenocarcinoma model: growth kinetic characterization and immunohistochemistry analysis}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {678-681}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.22938.5835}, abstract = {Objective(s): Gastric cancer is the third leading cause of cancer-related death worldwide. The overall survival rate of patients is poor because gastric cancers are usually diagnosed at the late stages. Therefore, further research is needed and appropriate research tools are required to develop novel therapeutic approaches.Materials and Methods: Eight female athymic nude mice with a C57BL/6 background were used in this study. AGS cells were inoculated into the flank. The tumor volumes were calculated and growth curves were drawn. When the volume of the tumors reached 1000 mm3, the animals were humanely euthanized with CO2 gas. After harvesting, tumors were analyzed with Hematoxylin and Eosin (H&E) and immunohistochemistry (IHC). A pathologist confirmed tumor entity through H&E staining. Tumors were evaluated for expression of HER-2, P53, Ki-67, CD34, cytokeratin 8 (CK8), vimentin, estrogen receptor (ER), and progesterone receptor (PR) utilizing immunohistochemistry.Results: The tumor take rate was 62.5%, mean doubling time was 40.984 d, and the latency period was 30.62 days. The H&E staining results showed highly malignant hyperchromatin epithelial cells. IHC assessment showed the mutation status of P53 gene. The expression score of the CK8 protein in the tumor cells was +3. Vimentin protein was not expressed and changes in mesenchymal phenotype were not observed. Ki-67 IHC indicated that the proliferation rate was >43% and angiogenesis was defined as high MVD.Conclusion: The respective AGS xenograft model provides an opportunity to understand the pattern of tumor growth as well as to evaluate new gastric cancer therapies in in vivo studies.}, keywords = {AGS,Athymic nude mice,immunohistochemistry,Stomach neoplasm,Xenograft model}, url = {https://ijbms.mums.ac.ir/article_10753.html}, eprint = {https://ijbms.mums.ac.ir/article_10753_096deec63b7ee03c862392137d5f78fd.pdf} } @article { author = {Diba, Rogaye and Mohaddes, Gisou and Mirzaie Bavil, Fariba and Farajdokht, Fereshteh and Bayandor, Parvin and Hosseindoost, Maryam and Mehri, Keivan and Zavvari Oskuye, Zohreh and Babri, Shirin}, title = {Protective effects of troxerutin on maternal high-fat diet-induced impairments of spatial memory and apelin in the male offspring}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {682-687}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.28170.6901}, abstract = {Objective(s): Maternal high-fat diet (HFD) is linked with metabolic and cognitive deficits in offspring. Neuroprotective effects of troxerutin, a natural bioflavonoid, have been reported recently. This study aimed to investigate the effects of troxerutin on spatial memory and serum and hippocampal apelin levels in the male offspring of HFD fed mothers.Materials and Methods: Three-week-old female Wistar rats (n= 40) received HFD or control diet (CD) for 8 weeks. After mating, pregnant animals were divided into two subgroups according to the troxerutin (TRO) supplementation: CD, CD+TRO, HFD, and HFD+TRO. HFD continued to the end of lactation in HFD and HFD+TRO groups. TRO was gavaged (150 mg/kg/day) during pregnancy. After weaning, the male offspring were fed a normal diet until 12 weeks of age. Spatial memory was evaluated in the Morris water maze (MWM) on postnatal day (PND) 90. Total apelin concentration was measured in the serum of maternal rats before mating and after lactation and also in the serum and hippocampus of their male offspring.Results: Both traveled distance (P<0.05) and time spent (P<0.05) in the target quadrant were significantly decreased in the offspring of HFD-fed dams, which were reversed by TRO treatment. Moreover, TRO significantly (P<0.05) decreased serum apelin levels in dams. Furthermore, TRO treatment in dams significantly (P<0.05) increased serum and hippocampal levels of apelin in their offspring.Conclusion: These results indicated that TRO treatment during pregnancy improved maternal HFD-induced spatial memory impairments of the offspring possibly through modulation of serum and hippocampal apelin levels.}, keywords = {Apelin,Maternal high fat diet,Memory,Morris Water Maze,Troxerutin}, url = {https://ijbms.mums.ac.ir/article_10762.html}, eprint = {https://ijbms.mums.ac.ir/article_10762_025f85b86ae8701e06de55c8ed6ec563.pdf} } @article { author = {Abedi, Mohsen and Mesbah-Namin, Seyed Alireza and Noori-Zadeh, Ali and Tiraihi, Taki and Taheri, Taher}, title = {Human wild-type superoxide dismutase 1 gene delivery to rat bone marrow stromal cells: its importance and potential future trends}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {688-694}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.27721.6879}, abstract = {Objective(s): Human superoxide dismutase 1 (SOD1) is the cytosolic form of this enzyme it detoxifies superoxide anions and attenuates their toxicities and concomitant detrimental effects on the cells. It is believed that the amount of these enzymes present in the oxidative stress-induced diseases is crucial for preventing disease progression. Transfection of rat bone marrow stromal cells (BMSCs) by a constructed vector carrying the human wild-type SOD1 gene, a non-viral gene transfer method, was the main aim of this study. Materials and Methods: For this purpose, the rat BMSCs were transfected with the vector using Turbofect reagent and then stabilized. Western-blot and real-time PCR were also used for evaluation of SOD1 expression. Results: Data analysis from RT-PCR and Western-blot techniques revealed that the stable transfected cells could secrete human wild-type SOD1 in the supernatant. Also, the total activity of SOD1 was about 0.5±0.09 U/ml and 0.005±0.002 U/ml in the supernatants of the transfected and not-transfected of rat BMSCs, respectively. Conclusion: This study showed that expansion of the stable transfected rat BMSCs by a constructed vector carrying the human wild-type SOD1 gene is capable of secreting the active SOD1 enzyme under ex-vivo conditions.  The recommendation of this study is that the same experiment would be applicable for expression of the other form of this enzyme, SOD3, as well. More valuable information could probably be provided about the variety of the diseases caused by superoxide anions toxicities by intervention and application of the non-viral method for expressions of SOD1 and SOD3 enzymes.}, keywords = {Vector,Expression,Ex-vivo,Gene delivery,Human SOD1,Rat BMSCs}, url = {https://ijbms.mums.ac.ir/article_10802.html}, eprint = {https://ijbms.mums.ac.ir/article_10802_0ff073a776e07b21cffea3e5d65ce8b3.pdf} } @article { author = {AYDOĞAN, Ayşe and BİNGÖL, Seyit Ali}, title = {Examination of the immunohistochemical localization and gene expression by RT-PCR of the oxytocin receptor in diabetic and non-diabetic mouse testis}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {695-700}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.28069.6820}, abstract = {Objective(s): The aim of this study was to determine Oxytocin receptor (OTR) gene expression and localization in diabetic and non-diabetic mouse testes by RT-PCR and immunohistochemistry, respectively. Materials and Methods: In this study, 18 male BALB/c mice (8–12 weeks old) were used and divided into three groups: diabetic, sham, and control. Streptozotocin (STZ) was applied to the diabetic group and sodium citrate was administered to the sham group in the same way, however, the control group was left untouched. The testicular tissues were removed on the thirtieth day of testing; the right testis tissues were passed through a routine histologic process and sections were stained with H&E and PAS staining techniques. The avidin-biotin-peroxidase method was applied to determine OTR immunoreactivity, while the left testis tissues were used for RT-PCR. Results: It was found that the body weight had decreased in the diabetic group and the diameter of the seminiferous tubules in the said group was shorter than those of the other groups. There were no obvious differences with regard to the histologic appearance between the groups. The immunohistochemical examination showed that the OTR immunoreactivity was strong in the control and sham groups but weak in the diabetic group, and the immunoreactivity was only seen in the Leydig cells. In addition, the OTR gene expression was lower in the diabetic group than in the other groups.Conclusion: We concluded that diabetes reduces the OTR expression in the testis. It is suggested that OTR protection should be researched in diabetes for healthy reproduction and sexuality.}, keywords = {Diabetes,immunohistochemistry,Oxytocin receptor,RT-PCR,Testis}, url = {https://ijbms.mums.ac.ir/article_10761.html}, eprint = {https://ijbms.mums.ac.ir/article_10761_5ec7d94a6104668435164472e7a53457.pdf} } @article { author = {Nejati, Majid and Atlasi, Mohammad Ali and Karimian, Mohammad and Nikzad, Hossein and Azami, Abolfazl}, title = {Lipoprotein lipase gene polymorphisms as risk factors for stroke: a computational and meta-analysis}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {701-708}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.29009.7001}, abstract = {Objective(s): Stroke is the most common neurological disorder and genetic susceptibility has an important role in its etiology. Polymorphism in several genes such as lipoprotein lipase (LPL) is propounded as a risk for stroke. This meta-analysis investigated the association of rs285 and rs320 LPL polymorphism with stroke risk. Materials and Methods: We searched PubMed, Clarivate Analytics Web of Science, Google Scholar, and Science Direct databases for appropriate studies. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of this association. Also, the effects of four common polymorphisms (rs268, rs285, rs320, and rs328) on the molecular aspects of LPL were evaluated by in silico tools. Five studies were included in meta-analysis after screening. Results: Our data indicated that rs320 significantly decreased the risk of stroke (G vs. T: OR= 0.64, 95%CI=0.54-0.76; GG vs. TT: OR=0.47, 95%CI=0.29-0.75; TG vs. TT: OR=0.65, 95%CI=0.53-0.80; TG+GG vs. TT: OR=0.62, 95%CI=0.51-0.75; GG vs. TT+TG: OR=0.51, 95%CI=0.32-0.82). Moreover, a significant association between rs285 and diminution of stroke risk was seen (P- vs. P+: OR=0.72, 95%CI=0.58-0.91; P-P- vs. P+P+: OR=0.50, 95%CI=0.31-0.82; P+P-+P-P- vs. P+P+: OR=0.72, 95%CI=0.53-0.96; P-P- vs. P+P++P+P-: OR=0.581, 95%CI=0.369-0.916). Also, the same results were observed after stratifying, without any publication bias (PEgger>0.05). Furthermore, computational analysis revealed that rs268 and rs328 may affect the protein structure (prediction: non-neutral; score=19; expected accuracy=59%) while rs320 could affect the RNA structure (distance=0.2264, P-value=0.0534; PConclusion: This meta-analysis indicated that risk of stroke was decreased in rs320 and rs285 polymorphisms in the LPL gene.}, keywords = {Computational biology,Genetic polymorphism,Lipoprotein lipase,Meta-analysis,Stroke}, url = {https://ijbms.mums.ac.ir/article_10759.html}, eprint = {https://ijbms.mums.ac.ir/article_10759_82ef2600e524ccb6a8eebeab97b0eab8.pdf} } @article { author = {Mohammadali, Fatemeh and Abroun, saeid and Atashi, Amir}, title = {Mild hypoxia and human bone marrow mesenchymal stem cells synergistically enhance expansion and homing capacity of human cord blood CD34+ stem cells}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {709-716}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.26820.6561}, abstract = {Objective(s): Cord blood (CB) is known as a valuable source of hematopoietic stem cells (HSC). Identifying strategies that enhance expansion and maintain engraftment and homing capacity of HSCs can improve transplant efficiency. In this study, we examined different culture conditions on ex vivo expansion and homing capacity of CB-HSCs. Materials and Methods: In this study, 4-5 different units of human CB in each of 3 independent experiments were collected.CD34+ HSC was isolated, cultured in the serum-free medium(Stem line II) and supplemented with cytokines: FMS-like tyrosine kinase 3 ligand (FLt3L), Thrombopoietin (TPO), stem cell factor (SCF) with/without bone marrow mesenchymal stem cell (BM-MSC) feeder layer in normoxia (20% O2) and mild hypoxia (5% O2) for 7 days. Before and after this period, total nucleated cell count (TNC), CD34+ cells count, Colony-forming cell (CFC) assay, migration assay and CXCR4 expression were evaluated by real time PCR. Data analysis was performed with t- test and ANOVA. P-value less than 0.05 was considered as statistically significant differences.Results: At the end of 7 days of culture, the highest count of TNC, CD34+ cells, CFUs, migration percentage and CXCR4 mRNA level were observed in feeder+cytokine group at 5% O2 tension. Our findings demonstrated statistically significant (1.7-3.2 fold) increase of CXCR4 gene expression in hypoxia versus normoxia.Conclusion: Combination of BM-MSC and mild hypoxia (5% O2) not only improves HSC expansion but also enhances homing capacity of HSC and better mimickes the niche microenvironment conditions.}, keywords = {CD34+ cells,Cord blood,CXCR4,Hematopoietic stem cell,Hypoxia,Mesenchymal stem cell}, url = {https://ijbms.mums.ac.ir/article_10790.html}, eprint = {https://ijbms.mums.ac.ir/article_10790_acff17dbc5498cbbe36402326986adde.pdf} } @article { author = {Jianjun, Ma and Huang, Kangmao and Ma, Yan and Chen, Shuai and Liu, Chao and Shan, Zhi and Fang, Xiangqian}, title = {Gambogic acid inhibits LPS-induced macrophage pro-inflammatory cytokine production mainly through suppression of the p38 pathway}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {717-723}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.23897.5995}, abstract = {Objective(s): In traditional Chinese medicine, gamboge can detoxify bodies, kill parasites, and act as a hemostatic agent. Recent studies have demonstrated that gambogic acid (GBA) suppressed inflammation in arthritis, and also presented antitumor effect. Thus, this study investigated the new biological properties of GBA on macrophages.Materials and Methods: RAW 264.7 cells were pretreated with GBA at different concentrations (10, 20, 40, 80, 160, 320 nM) for 24 hrs, and then cell viability was measured using Cell Counting Kit (CCK)-8 assays. Pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β were determined using ELISA kits and qPCR. Then nitrite concentration was calculated according to a standard curve. At last, the effect of GBA on MAPK and NF-κB signaling pathways was assessed by western blot and luciferase reporter gene assay.Results: GBA (IC50: 260 nM) suppressed the TNF-α, IL-6 and IL-1β expression induced by lipopolysaccharide (LPS) in RAW 264.7 cells. The expression of TNF-α, IL-6 and IL-1β decreased to 30-50% and 70-75% in the high-dose (160 nM) and low-dose (40 and 80 nM) GBA groups, respectively. Furthermore, the nitric oxide (NO) production and the activation of NF-κB, ERK, and JNK pathways were significantly reduced in high-dose (160 nM) GBA only, while p38 pathway was inhibited at both low (40 and 80 nM) and high (160 nM) concentration of GBA. Conclusion: These data suggested that GBA inhibited LPS-induced production of pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β mainly through the suppression of the p38 pathway.}, keywords = {Anti-inflammatory agents,Gambogic acid,MAPK,NF-κB,p38,RAW 264.7 cells}, url = {https://ijbms.mums.ac.ir/article_10758.html}, eprint = {https://ijbms.mums.ac.ir/article_10758_6ec1b1cfe4edbd6abf8f8f687093e92e.pdf} } @article { author = {Mozafari, Nazanin and Shamsizadeh, Ali and Fatemi, Iman and Allahtavakoli, Mohammad and Moghadam-Ahmadi, Amir and Kaviani, Elham and Kaeidi, Ayat}, title = {CX691 as an AMPA receptor positive modulator, improves the learning and memory in a rat model of Alzheimer’s disease}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {724-730}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.28544.6934}, abstract = {Objective(s): Growing evidence suggests that dysfunction of the glutamatergic system and α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptors are involved in pathology of Alzheimer’s disease (AD). Because AMPA receptors play a key role in plasticity synaptic regulation, positive modulation of these receptors may rescue the cognitive deficits in the AD. The aim of this study was to explore the effect of CX691, a specific positive allosteric modulator of the AMPA-type glutamate receptors (Ampakine), on spatial learning and memory in a rat model of AD. Materials and Methods: For induction of AD, amyloid-beta 1-42 (Aβ1-42) was microinjected into the hippocampus of male Wistar rats (250-300 g). The Morris water maze (MWM) test was used to evaluate the effect of CX691 (0.03 and 0.3 mg/kg, twice a day for 10 days, orally) on spatial learning and memory of rats. In order to evaluate the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampus tissue, ELISA test was used. Results: The obtained data showed that treatment with CX691 (0.3 mg/kg) improves the impairment of spatial learning and memory in AD rats. Also, treatment with CX691 (0.3 mg/kg), increased the BDNF protein level in hippocampus tissue of AD rats compared to non-treated animals.Conclusion: The CX691 can improve the BDNF protein expression as well as spatial performance of learning and memory in AD rats.}, keywords = {Alzheimer’s disease,AMPA receptors,BDNF,CX691,Memory,Rat}, url = {https://ijbms.mums.ac.ir/article_10760.html}, eprint = {https://ijbms.mums.ac.ir/article_10760_8bdeb1455cbdce80a0dc8c5f31b64d8e.pdf} } @article { author = {Kong, Hong-liang and Hou, Ai-jie and Liu, Ning-ning and Chen, Bo-han and Huang, Hua-ting and Dai, Sheng-nan}, title = {The effects of ginsenoside Rb1 on fatty acid β-oxidation, mediated by AMPK, in the failing heart}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {731-737}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.24002.6016}, abstract = {Objective(s): This study intended to investigate the effects of Ginsenoside-Rbl (Gs-Rbl) on fatty acid β-oxidation (FAO) in rat failing heart and to identify potential mechanisms of Gs-Rbl improving heart failure (HF) by FAO pathway dependent on AMP-activated protein kinase (AMPK). Materials and Methods: Rats with chronic HF, induced by adriamycin (Adr), were randomly grouped into 7 groups. Gs-Rb1, adenine 9-β-D-arabinofuranoside (Ara A, specific AMPK inhibitor), and 5'-aminoimidazole-4-carboxamide riboside (Aicar, specific AMPK activator) were administered to rats with HF, singly and/or combinedly. Myocardial high-energy phosphate (such as phosphocreatine, ADP, and ATP), free L-Carnitine, malonyl-CoA, and the activity of FAO-related enzymes in left ventricle from different groups were measured by using the corresponding molecular biological techniques. Results: Gs-Rb1 improved HF significantly, accompanied by a significant increase in phosphocreatine (PCr), ADP, ATP, PCr/ATP ratio, free carnitine, malonyl-CoA, mRNA, activity of carnitine palmitoyltransferase (Cpt), medium-chain Acyl-CoA Dehydrogenase (MCAD) and long-chain acyl-CoA Synthetase (ACSL) and a significant decrease of the ADP/ATP ratio in the left ventricular myocardium. However, all those effects were almost abolished by Ara A and were not further improved by Aicar. Conclusion: Taken together, it suggests that Gs-Rb1 may modulate cardiac metabolic remodeling by improving myocardial fatty acid β-oxidation in failing heart. In addition, the effects of Gs-Rb1 may be mediated via activating AMPK.}, keywords = {AMP-activated protein kinase,Carnitine palmitoyl-transferase 1,Ginsenosides-Rbl,heart failure,L-carnitine,Long-chain acyl-CoA synthetase,Malonyl-CoA,Medium-chain acyl-CoA dehydrogenase}, url = {https://ijbms.mums.ac.ir/article_10799.html}, eprint = {https://ijbms.mums.ac.ir/article_10799_738310e75df0cd60895cd71bc8cb5bd1.pdf} } @article { author = {Sadeghian, Hamid and Seyedi, Seyed Mohammad and Jafari, Zeinab}, title = {Design and synthesis of new esters of terpenoid alcohols as 15-lipoxygenase inhibitors}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {738-744}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.27910.6794}, abstract = {Objective(s): 15-Lipoxygenases are one of the iron-containing proteins capable of performing peroxidation of unsaturated fatty acids in animals and plants. The critical role of enzymes in the formation of inflammations, sensitivities, and some cancers has been demonstrated in mammals. The importance of enzymes has led to the development of mechanistic studies, product analysis, and synthesis of inhibitors. Materials and Methods: The inhibitory activity of all synthetic compounds against SLO (soybean 15-lipoxygenase: L1; EC 1,13,11,12) was determined using the peroxide formation method. In this method, the basis of evaluation of lipoxygenase activity is measuring the concentration of fatty acid peroxide. All measurements were compared with  4-​methyl-​2-​(4-​methylpiperazinyl)pyrimido[4,​5-​b]benzothiazine (4-MMPB) as one of the known lipoxygenase inhibitors. The radical scavenging ability of all synthetic compounds using stable free radicals (DPPH: 2,2-diphenyl-1-picrylhydrazyl) was measured for further investigation.Results: In this study, a series of esters from phenolic acids with terpenoid alcohols was synthesized and their inhibitory potency against soybean 15-lipoxygenase and their free radical scavenging properties were determined. Among the synthetic compounds, adamantyl protocatetuate 2j and bornyl protocatetuate 2o showed the most potent inhibitory activity with IC50 values of 0.95 and 0.78 μm, respectively.Conclusion: By changing the alcohol and acyl portions of stylosin, it was found that electronic properties play main role in lipoxygenase inhibition potency in contrast with steric features. Insertion of more reductive phenolic moiety such as catechuate and gallate lead to more lipoxygenase inhibition potency of the esters as observed in their radical scavenging activity.}, keywords = {Inhibitors,Phenolic acid,Radical scavenging,Terpenoids,15-lipoxygenase}, url = {https://ijbms.mums.ac.ir/article_10763.html}, eprint = {https://ijbms.mums.ac.ir/article_10763_b671f07c65669017ad8668ab9b1956a5.pdf} } @article { author = {Widowati, Wahyu and Afifah, Ervi and Mozef, Tjandrawati and Sandra, Ferry and Rizal, Rizal and Amalia, Annisa and Arinta, Yukko and Bachtiar, Indra and Murti, Harry}, title = {Effects of insulin-like growth factor-induced Wharton jelly mesenchymal stem cells toward chondrogenesis in an osteoarthritis model}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {745-752}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.28205.6840}, abstract = {Objective(s): This study aimed to determine the collagen type II (COL2) and SOX9 expression in interleukin growth factor (IGF-1)-induced Wharton’s Jelly mesenchymal stem cells (WJMSCs) and the level of chondrogenic markers in co-culture IGF1-WJMSCs and IL1β-CHON002 as osteoarthritis (OA) cells model. Materials and Methods: WJMSCs were induced with IGF1 (75, 150, and 300 ng/ml) to enhance their chondrogenesis capability. The gene expression of SOX9 and COL2 was evaluated with quantitative RT-PCR. Furthermore, IGF1-WJMSCs were co-cultured with IL1β-CHON002 cells in varied ratios (1:2, 1:1, 2:1). Chondrogenic markers ADAMTS1, ADAMTS5, MMP3, MMP1, and RANKL were measured with ELISA. Results: The IGF1-WJMSCs had an increased expression of COL2 and SOX9. ADAMTS1, ADAMTS5, MMP1, MMP3, and RANKL levels were decreased in the co-culture IGF1-WJMSCs and IL1β-CHON002. Conclusion: The IGF1-induced WJMSCs were capable to enhance chondrogenesis, indicated by increased expression of SOX9 and COL2 and decreased expression of ADAMTS1, ADAMTS5, MMP3, MMP1, and RANKL. These findings can be further used in the osteoarthritis treatment.}, keywords = {Chondrogenesis,IGF-1,Mesenchymal stem cell MMPs,Osteoarthritis}, url = {https://ijbms.mums.ac.ir/article_10800.html}, eprint = {https://ijbms.mums.ac.ir/article_10800_c2a5e0e49d2515c338f92027a45c9e8a.pdf} } @article { author = {Torkashvand, Ali and Bahrami, Fariborz and Adib, Minoo and Ajdary, Soheila}, title = {Subcutaneous administration of a fusion protein composed of pertussis toxin and filamentous hemagglutinin from Bordetella pertussis induces mucosal and systemic immune responses}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {753-759}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.29112.7026}, abstract = {Objective(s): After decades of containment, pertussis disease, caused by Bordetella pertussis seems to be re-emerging and still remains a major cause of reported vaccine-preventable deaths worldwide. The current licensed whole-cell vaccines display reactogenicity while acellular vaccines are expensive and do not induce Th1-type immune responses that are required for optimum protection against the disease. Thus, there is an urgent need to develop new vaccines and the recombinant technology seems to be the method of choice for this purpose. The present study was an attempt to develop a new, simplified, cost-effective and well-defined vaccine against Bordetella pertussis, with capacity to induce a Th1 response. Materials and Methods: A fusion DNA fragment encoding the N-terminal region of pertussis toxin S1 subunit and filamentous hemagglutinin type 1 immunodominant domain was constructed and the corresponding fusion protein (F1S1) was produced in Escherichia coli. F1S1 in conjunction with imiquimod was administered by subcutaneous (SC) and intranasal (IN) routes to BALB/c mice. Results: This vaccine formulation could elicit high levels of IFN-γ, serum IgG (with higher IgG2a/IgG1 ratio) and lung IgA after the SC and, to a lesser extent, following the IN administration.  Conclusion: Our results indicate that the above-mentioned important proteins of B. pertussis could be successfully produced in E. coli as a single fusion protein. Furthermore, this protein could induce proper systemic and mucosal immune responses after administration via SC or IN routes.}, keywords = {Bordetella,Filamentous hemagglutinin,Imiquimod,Pertussis,Pertussis toxin,Recombinant}, url = {https://ijbms.mums.ac.ir/article_10801.html}, eprint = {https://ijbms.mums.ac.ir/article_10801_df19dc6847d67a6f7b8704cabb0c9b8d.pdf} } @article { author = {Ali Mirani, Zulfiqar and Fatima, Aiman and Urooj, Shaista and Aziz, Mubashir and Khan, Muhammad and Abbas, Tanveer}, title = {Relationship of cell surface hydrophobicity with biofilm formation and growth rate: A study on Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {21}, number = {7}, pages = {760-769}, year = {2018}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2018.28525.6917}, abstract = {Objective(s): This study was designed to determine the relationship of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli isolates in multispecies biofilms and their individual phenotypic characters in biofilm consortia. Materials and Methods:  The subject isolates were recovered from different food samples and identified on the basis of growth on differential and selective media.  Tube methods, Congo-red agar method, and scanning electron microscopy (SEM) were used to study biofilms phenotypes. The hydrophobicity of the strains was evaluated by the adhesion to apolar solvent. Results: The results showed that E. coli dominated the pre-biofilm stage. It has been observed that E. coli adopted biofilm life much before S. aureus and P. aeruginosa. However, after adopting biofilm lifestyle, slowly and gradually, P. aeruginosa dominated the consortia and dispersed other stakeholders. The subject isolates of P. aeruginosa produce cis-2-decanoic acid to disperse or inhibit S. aureus and E. coli biofilms. Gas-chromatography and mass spectrometry results showed that cis-2-decanoic was higher in the co-culture condition and increased at late log-phase or at stationary phase. Although majority of S. aureus were unable to compete with P. aeruginosa, however, a minor population competed, survived, and persisted in biofilm consortia as small colony variants. The survivors showed higher expression of sigB and sarA genes. P. aeruginosa showed comparatively higher hydrophobic surface properties. Conclusion: Comparative analysis showed that cell surface hydrophobicity, growth rate, and small colony variants (SCVs) are correlated in biofilm consortia of the P. aeruginosa, S. aureus, and E. coli.}, keywords = {Biofilms,Escherichia coli,Hydrophobicity,Pseudomonas aeruginosa,Small colony variants,Staphylococcus aureus}, url = {https://ijbms.mums.ac.ir/article_10840.html}, eprint = {https://ijbms.mums.ac.ir/article_10840_3aefa19a5b4783051f0a95bc4e46403e.pdf} }