Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801Emerging insights into the biology of metastasis: A review article8338471324210.22038/ijbms.2019.32786.7839ENSoussan IraniDental Research Centre, Oral Pathology Department, Dental Faculty, Hamadan University of Medical Sciences, Hamadan,Iran, Lecturer at Griffith University,Gold Coast,Australia0000-0003-3679-0449Journal Article20180617Metastasis means the dissemination of the cancer cells from one organ to another which is not directly connected to the primary site. Metastasis has a crucial role in the prognosis of cancer patients. A few theories, different types of cell and several molecular pathways have been proposed to explain the mechanism of metastasis. In this work, the related articles in the limited period of time, 2000–mid -2018 were reviewed, through search in PubMed, Google Scholar and Scopus database. The articles published in the last two decades related to the biology of cancer metastasis were selected and the most important factors were discussed. Metastasis is critical factor to predict survival in patients with advanced cancer and prognosis determines the treatment plan. Many different cell types and various signaling pathways control the metastatic process. Metastasis is a multistep process. Many signaling pathways and molecules are involved in metastasis. Increasing knowledge about the mechanism of metastasis can help in finding the promising targets of cancer therapy.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801An overview of therapeutic applications of ultrasound based on synergetic effects with gold nanoparticles and laser excitation8488551331910.22038/ijbms.2019.29584.7142ENAhmad ShaneiMedical Physics Department, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran0000-0001-5999-0932Ameneh SazgarniaMedical Physics research Center, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-9542-6423Journal Article20180202Acoustic cavitation which occurs at high intensities of ultrasound waves can be fatal for tumor cells. The existence of dissolved gases and also the presence of nanoparticles (NPs) in a liquid, irradiated by ultrasound, decrease the acoustic cavitation onset threshold and the resulting bubbles collapse. On the other hand, due to unique capabilities and optical properties of gold nanoparticles (GNPs), they have been emphasized as effective NPs in the field of tumor therapy. Absorption of the laser light by GNPs causes the water molecules around the NPs to evaporate and produces vapor cavities. In this paper, we have reviewed published studies in the fields of ultrasound therapy, sonodynamic therapy (SDT) and synergism of low-level ultrasound and also laser radiation in the presence of GNPs.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801Pharmacological evidence for lithium-induced neuroprotection against methamphetamine-induced neurodegeneration via Akt-1/GSK3 and CREB-BDNF signaling pathways8568651323510.22038/ijbms.2019.30855.7442ENShafagh MehrafzaDepartment of pharmaceutical chemistry, faculty of pharmaceutical chemistry, pharmaceutical sciences branch, Islamic Azad University (IUAPS), Tehran, Iran0000-0002-2107-9067Sareh KermanshaiDepartment of pharmaceutical chemistry, faculty of pharmaceutical chemistry, pharmaceutical sciences branch, Islamic Azad University (IUAPS), Tehran, IranShahnaz MostafidiDepartment of pharmaceutical chemistry, faculty of pharmaceutical chemistry, pharmaceutical sciences branch, Islamic Azad University (IUAPS), Tehran, IranMajid MotaghinejadResearch Center for Addiction and Risky Behaviors (ReCARB), Iran Psychiatric Center, Iran University of Medical Sciences, Tehran, Iran0000-0003-3449-4224Manijeh MotevalianDepartment of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, IranSulail FatimaDepartment of Physiology, Tehran University of Medical Sciences-International Campus (TUMS-IC), Tehran, IranJournal Article20180401<em><strong>Objective(s):</strong></em> Neurodegeneration is an outcome of Methamphetamine (METH) abuse. Studies have emphasized on the neuroprotective properties of lithium. The current study is designed towards evaluating the role of Akt-1/GSK3 and CREB-BDNF signaling pathways in mediating lithium neuroprotection against METH-induced neurodegeneration in rats. <br /><em><strong>Materials and Methods:</strong></em> Sixty adult male rats were randomly divided into five groups: control group (received 0.7 ml normal saline per rat for 28 days), METH group (given 10 mg/kg of METH intraperitoneally for 28 days), groups 3, 4, and 5 (given METH (10 mg/kg) and lithium (75, 150, and 300 mg/kg intraperitoneally, individually for 28 days). Morris water maze (MWM) was used to assess mental functions. In addition to hippocampal neurodegeneration, Brain-derived neurotrophic factor (BDNF), cAMP response element binding (CREB), Glycogen synthase kinase 3 (GSK3), and Protein kinase B (Akt-1) were assessed in isolated hippocampus. <br /><em><strong>Results:</strong></em> METH abuse caused marked disorders in learning and memory that were dramatically improved with various doses of lithium. Furthermore, METH increased lipid peroxidation and the levels of oxidized form of interleukin 1 beta (IL-1β), glutathione (GSSG), Bax, tumor necrosis factor alpha (TNF-α), and GSK3, while attenuating the extent of glutathione (reduced form (GSH)), P-CREB, Bcl-2, BDNF, and Akt-1 in the hippocampus. Moreover, METH declined superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx) activity in the hippocampus. Conversely, lithium attenuated METH-stimulated apoptosis, oxidative stress, and inflammation; while improving the extent of BDNF and P-CREB.<br /><em><strong>Conclusion:</strong></em> Probably lithium possesses neuroprotection against METH-stimulated neurodegeneration in the hippocampus via Akt-1/GSK3β and CREB/BDNF signaling pathways.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801The efficacy and molecular mechanism of the effect of schisandrin b on the treatment of erectile dysfunction8668711332010.22038/ijbms.2019.27455.6701ENWEI LIUDepartment of Urology and Andrology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200001, People’s Republic of China0000-0002-3522-9935CHEN ZHAODepartment of Urology and Andrology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200001, People’s Republic of ChinaYanping HuangDepartment of Urology and Andrology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200001, People’s Republic of ChinaYidong LiuDepartment of Urology and Andrology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200001, People’s Republic of ChinaMujun LuDepartment of Urology and Andrology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200001, People’s Republic of ChinaJournal Article20171107<em><strong>Objective(s):</strong></em> The purpose of this study is to determine the efficacy and molecular mechanism of the effect of schisandrin b (SCHB) on treating erectile dysfunction (ED) in a rat model with bilateral cavernous crushing nerve injury. <br /><em><strong>Materials and Methods:</strong></em> The ED rat model was established with bilateral cavernous nerve crushing, and then confirmed by apomorphine. Fifty healthy eight-week-old ED rats were randomly assigned into five group, including control group (sham surgery), bilateral cavernous nerve crushing injury group (BCNC), BCNC with low SCHB (100 mg/d), BCNC with medium SCHB (200 mg/d) and BCNC with high SCHB (400 mg/d). For the last three groups, SCHB was given for 2 months. Then, we examined intracavernosal pressure (ICP), cyclic nucleotides (cAMP, cGMP), endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) in all groups. <br /><em><strong>Results:</strong></em> In the study of ICP, SCHB was able to improve ED in a dose-dependent manner. In addition, as compared to the BCNC group, the relative expression of eNOS and nNOS in medium and high concentration of SCHB-treated groups are higher than BCNC group. Moreover, all groups treated with SCHB showed a significant higher expression level of cAMP and cGMP.<br /><em><strong>Conclusion:</strong></em> These results suggested that SCHB were able to significantly improve the ED on rat model through the NO-cGMP and cAMP- protein kinase A (PKA) pathway.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801Prevalence of antibiotic resistance and integrons, sul and Smqnr genes in clinical isolates of Stenotrophomonas maltophilia from a tertiary care hospital in Southwest Iran8728771324110.22038/ijbms.2019.31291.7540ENHadi Sedigh Ebrahim-SaraieRazi Clinical Research Development Center, Guilan University of Medical Sciences, Rasht, Iran0000-0001-8339-5199Hamid HeidariDepartment of Microbiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran0000-0002-6869-2301Behnaz SoltaniDepartment of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranJalal MardanehDepartment of Microbiology, School of Medicine, Gonabad University of Medical Sciences, Gonabad, IranMohammad MotamedifarDepartment of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranShiraz HIV/AIDS Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran0000-0003-4993-4034Journal Article20180420<em><strong>Objective(s):</strong></em> Stenotrophomonas maltophilia has emerged as an important opportunistic nosocomial pathogen due to its intrinsic and acquired resistance to a wide range of antimicrobial agents. The present study aimed to investigate the occurrence of antibiotic resistance and resistance mechanisms among clinical isolates of S. maltophilia from Iranian patients.<br /><em><strong>Materials and Methods:</strong></em> This cross-sectional study was performed on 44 S. maltophilia isolates that were recovered from different clinical specimens in 2015 and 2016. Conventional microbiologic methods were used for primary identification of isolates and confirmed by specific polymerase chain reaction (PCR) primers. Minimum inhibitory concentrations (MICs) were determined by the E-test. PCR was applied to determine antibiotic resistance genes.<br /><em><strong>Results:</strong></em> All of S. maltophilia isolates were susceptible to trimethoprim/sulfamethoxazole (TMP/SMX) and colistin. Moreover, the susceptibility rates of isolates toward ceftazidime and ciprofloxacin were 93.2%, and 84.1%, respectively. Class 1 integrons was detected in 24 (54.5%) isolates by the presence of int1 gene. Moreover, the prevalence of antibiotic resistance genes sul1, sul2, and Smqnr were found in 16 (36.4%), 15 (34.1%), and 29 (65.9%) isolates, respectively.<br /><em><strong>Conclusion:</strong></em> In summary, the prevalence of sul and Smqnr genes in integrons-contained isolates point out the significant risk of sulfonamides and fluoroquinolones resistance among clinical isolates of S. maltophilia in our region.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801Effect of let-7a overexpression on the differentiation of conjunctiva mesenchymal stem cells into photoreceptor-like cells8788831323710.22038/ijbms.2019.32736.7859ENFatemeh RanjbarnejadDepartment of Genetics and Molecular Medicine, Zanjan University of Medical Sciences, End of Mahdavi Blvd, Shahrak-e Karmandan, 4513956111, Zanjan, Iran0000-0003-3410-7730Samad NadriDepartment of Medical Nanotechnology, Zanjan University of Medical Sciences, End of Mahdavi Blvd, Shahrak-e Karmandan, 4513956111, Zanjan, IranCancer Gene Therapy Research Center, Zanjan University of Medical Sciences, End of Mahdavi Blvd, Shahrak-e Karmandan, 4513956111, Zanjan, Iran0000-0002-2710-3128Alireza BiglariDepartment of Genetics and Molecular Medicine, Zanjan University of Medical Sciences, End of Mahdavi Blvd, Shahrak-e Karmandan, 4513956111, Zanjan, IranCancer Gene Therapy Research Center, Zanjan University of Medical Sciences, End of Mahdavi Blvd, Shahrak-e Karmandan, 4513956111, Zanjan, IranSamira Mohammadi YeganehDepartment of Biotechnology, Shahid Beheshti University of Medical Sciences, Velenjak, 7th Floor, Bldg No 2 SBUMS, Arabi Ave, 19839-63113, Tehran, Iran0000-0003-0430-6325Mahdi ParyanDepartment of Research and Development, Production and Research Complex, Pasteur Institute, No 69, Pasteur Ave, 1316943551, Tehran, Iran0000-0002-2592-3528Journal Article20180622<em><strong>Objective(s):</strong></em> MicroRNAs (miRNAs) could regulate many cellular processes such as proliferation and differentiation. let-7a miRNA is one of the key regulators in the developmental transition of retinal progenitor cells into differentiated cells. Current evidence suggests that mesenchymal stem cells (MSCs) can isolate from various tissues such as bone marrow and conjunctiva. In this study, we investigated the effect of let-7a overexpression on induced differentiation of conjunctiva mesenchymal stem cells (CJMSCs) into photoreceptor-like cells.<br /><em><strong>Materials and Methods:</strong></em> After isolation and characterization, CJMSCs were transduced with lentiviruses containing let-7a or empty vector. The effect of let-7a overexpression on expression of photoreceptor-specific markers was evaluated by quantitative real-time PCR (RT-qPCR) after 28 and 42 days of transduction.<br /><em><strong>Results:</strong></em> The relative expression of rhodopsin and recoverin genes was evaluated by RT-qPCR in let-7a overexpressing cells, control vector transduced cells and untransduced CJMSCs (control cells). Our results indicated that following overexpression of let-7a, after 28 and 42 days of transduction, significant up-regulation in the expression of recoverin (574.7 and 43.9 folds) and rhodopsin (3334.7 and 53.1 folds) were observed, respectively.<br /><em><strong>Conclusion:</strong></em> Our findings indicate that overexpression of let-7a microRNA can increase the expression of photoreceptor-specific genes in CJMSCs. Moreover, it is prospective that let-7a overexpression can use as an alternative protocol for the differentiation of mesenchymal stem cells into photoreceptors. It seems that the effect of let-7a on the differentiation of CJMSCs into photoreceptors is also time-dependent.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801Pioglitazone abrogates testicular damage induced by testicular torsion/detorsion in rats8848921330410.22038/ijbms.2019.33199.7929ENNevertyty Mohamed MahmoudDepartment of Pharmacology, Faculty of Medicine, Zagazig University, Egypt0000-0002-7952-9112Soad Lotfy KabilDepartment of Pharmacology, Faculty of Medicine, Zagazig University, EgyptJournal Article20180705<em><strong>Objective(s):</strong></em> Testicular torsion/detorsion (T/D) is a well-known cause for infertility. Pioglitazone is an agonist of peroxisome proliferator activated receptor-gamma (PPAR-γ). Previous studies have shown that pioglitazone has anti-inflammatory, antioxidant and antiapoptotic properties. The present study hypothesized that pioglitazone may be protective against the testicular T/D tissue insults, and the possible pathophysiological mechanisms involved in this effect were also investigated. <br /><em><strong>Materials and Methods:</strong></em> Rats were randomly divided into four groups: sham group, T/D group where testicular torsion was performed for 4 hr followed by 4 hr of detorsion and two pioglitazone-treated groups (1 mg/kg and 3 mg/kg, by single intraperitoneal injection 30 min prior to detorsion). At the end of reperfusion period, blood, ipsilateral and contralateral testicular tissue samples were obtained for biochemical and histopathological examination. <br /><em><strong>Results:</strong></em> Pioglitazone reduced oxidative tissue damages, inflammatory mediators, and apoptotic markers and enhanced the total antioxidant status, and AMP-activated protein kinase level. Moreover, pioglitazone improved spermatogenesis evidenced by increased Johnsen’s score and reversed the histopathological damages induced by testicular T/D. The effects of pioglitazone were higher with the dose of 3 mg/kg.<br /><em><strong>Conclusion:</strong></em> Pioglitazone exhibited a protective effect against the deleterious actions of testicular T/D. This beneficial potential of pioglitazone may be attributed to its antioxidant, anti-inflammatory and antiapoptotic properties, which was more obvious with the dose of 3 mg/kg. Pioglitazone may be a promising therapy for testicular T/D.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801Enhancing immunogenicity of novel multistage subunit vaccine of Mycobacterium tuberculosis using PLGA:DDA hybrid nanoparticles and MPLA : subcutaneous administration8939001332110.22038/ijbms.2019.33962.8079ENFarzad KhademiDepartment of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran0000-0001-6181-4903Arshid YousefiDepartment of Medical Bacteriology and Virology, Qaem University Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IranMohammad DerakhshanDepartment of Medical Bacteriology and Virology, Qaem University Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-8416-3792Adel NajafiDepartment of Medical Bacteriology and Virology, Qaem University Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-1308-6339Mohsen TafaghodiNanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-8286-0973Journal Article20180806<em><strong>Objective(s):</strong></em> A new strategy in recent studies is using effective tuberculosis (TB) subunit vaccines combined with appropriate carriers and adjuvants which have shown promising results in preclinical and clinical studies. The aim of the present study was to evaluate the PLGA:DDA hybrid nanoparticles (NPs) for subcutaneous delivery of a novel multistage subunit vaccine along with MPLA adjuvant against Mycobacterium tuberculosis (M. tuberculosis). <br /><em><strong>Materials and Methods:</strong></em> PLGA and PLGA:DDA NPs containing HspX/EsxS fusion protein and MPLA were prepared by double emulsion method (w/o/w). After characterization, these NPs were subcutaneously administered to BALB/c mice aged 6-8 weeks old. Immunogenicity of formulations were assessed by measuring the level of IFN-γ, IL-4, IL-17 and TGF-β cytokines as well as IgG1, IgG2a and IgA antibodies using ELISA. <br /><em><strong>Results:</strong></em> Both particles had spherical shape and smooth surface with 316.7 ± 12.7 nm in size, surface charge of -33 ± 1.7 mV, and encapsulation efficiency of 92.2 ± 2% for PLGA NPs and 249.7 ± 16.7 nm in size, surface charge of 39 ± 1.8 mV, and encapsulation efficiency of 35.7 ± 1.4% for PLGA:DDA NPs. The highest IFN-γ response and also IgG2a and IgG1 antibodies titers were observed in groups immunized with PLGA:DDA/HspX/EsxS/MPLA and PLGA:DDA/HspX/EsxS/MPLA as booster as well as PLGA:DDA/HspX/EsxS and PLGA:DDA/HspX/EsxS as booster. <br /><em><strong>Conclusion:</strong></em> With regard to effective induction of IFN-γ and IgG2a immune responses, PLGA:DDA hybrid NP along with MPLA adjuvant have good potentials for improving the immunogenicity of HspX/EsxS multistage subunit vaccine as well as promoting BCG efficacy as a BCG prime-boost.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801Assessment of DNA vaccine encoding Toxoplasma gondii microneme complete gene and IL-12 as adjuvant in BALB/c mice9019071330610.22038/ijbms.2019.34872.8276ENFatemeh GhafarifarDepartment of Parasitology and Entomology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran0000-0003-0891-8214Mohammad JafarimodrekDepartment of Medical Parasitology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, IranHossein VaziniNursing Department, Basic Sciences faculty, Hamedan Branch, Islamic Azad University, Hamedan, IranZohreh SharifiBlood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran0000.0001-6297-7656Abdolhossein DalimiDepartment of Parasitology and Entomology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran0000-0001-5591-5513Mohammad Saaid DayerDepartment of Parasitology and Entomology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranJournal Article20180914<em><strong>Objective(s):</strong></em> Toxoplasma gondii is an obligate intracellular protozoan parasite that causes toxoplasmosis in humans and animals. Micronemes (MICs) are effective candidates for DNA vaccine.<br /> <em><strong>Materials and Methods:</strong></em> In this study, we evaluated the immune response of BALB/c mice against MIC3 gene of Toxoplasma gondii and interleukin 12 (IL-12) as DNA vaccine. The MIC3 gene was cloned into the PTZ57R/T vector before sub-cloning in pcDNA3. Recombinant pc-MIC3 was transformed into Escherichia coli (TOP10 strain). The pc-MIC3 plasmid was then transfected into Chinese Hamster Ovary (CHO) cells, and the expression of the MIC3 gene was evaluated by SDS-PAGE and Western blotting. Sixty female BALB/c mice were divided into 6 groups. Each group received 3 intramuscular immunizations on days 0, 21st and 42nd using one of the following stimulants: phosphate-buffered saline, pcDNA3, pCAGGS-IL12, pc-MIC3 (100 µg), pc-MIC3 (50 µg), or combined pCAGGS-IL12 (50 µg) and pc-MIC3 (50 µg). The enzyme-linked immunosorbent assays was applied to evaluate interferon gamma (IFN-γ) and IL-4 cytokines excretion of lymphocytes stimulated with tachyzoites lysate antigen, as well as the total levels of immunoglobulin G (IgG), IgG2a and IgG1 in immunized mice sera.<br /><em><strong>Results:</strong></em> Our results showed that mice challenged with pc-MIC3 (100 µg) had the highest longevity and quantity of immunoglobulin. Moreover, the highest expression level of IFN-γ was found in mice injected with combined pcMIC3 and pCAGGS-IL12 (P<0.05). <br /><em><strong>Conclusion:</strong></em> The MIC3 gene can be an efficient DNA vaccine candidate against toxoplasmosis. While, the single-gene vaccine can confer partial protection to mice against toxoplasmosis, the multigene vaccine can significantly enhance immune responses.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801MiR-96 induced non-small-cell lung cancer progression through competing endogenous RNA network and affecting EGFR signaling pathway9089141323810.22038/ijbms.2019.33654.8023ENHao DingDivision of Respiratory Disease, Affiliated People’s Hospital of Jiangsu University, Dianli Road No.8, Zhenjiang, 212002, China0000-0003-1176-7998Mingqiang ChuDivision of Respiratory Disease, Affiliated People’s Hospital of Jiangsu University, Dianli Road No.8, Zhenjiang, 212002, ChinaJingjing YueDivision of Respiratory Disease, Affiliated People’s Hospital of Jiangsu University, Dianli Road No.8, Zhenjiang, 212002, ChinaHuaying HuangDivision of Respiratory Disease, Affiliated People’s Hospital of Jiangsu University, Dianli Road No.8, Zhenjiang, 212002, ChinaJian WangDivision of Respiratory Disease, Affiliated People’s Hospital of Jiangsu University, Dianli Road No.8, Zhenjiang, 212002, ChinaLi ZhuDivision of Nephrology, Affiliated People’s Hospital of Jiangsu University, Dianli Road No.8, Zhenjiang, 212002, ChinaJournal Article20180724<em><strong>Objective(s):</strong></em> Non-small cell lung cancer (NSCLC) has become a serious global health problem in the 21st century, and tumor proliferation and metastasis are the leading causes of death in patients with lung cancer. The present study aimed to verify the function of miR-96 and miR-96 in relation to competing with endogenous RNA regulatory network in NSCLC progression including proliferation and metastasis.<br /><em><strong>Materials and Methods:</strong></em> Clinical data of miR-96 expression was collected from StarBase 2.0 developed by Sun Yat-sen University. We used wound-healing, transwell and MTT assays to measure migration, invasion and proliferation of NSCLC cell lines after different treatment. Quantitative real time PCR and western blot were used to test differential genes expression. In order to identify target between genes (FOXO1 and DUSP1) and miR-96, luciferase assay was used. Luciferase activities in FOXO1 and DUSP1 wild type plasmid groups were compared to mutant groups.<br /><em><strong>Results:</strong></em> qRT-PCR and online database results indicated that miR-96 is highly associated with NSCLC when compared to normal patients. In addition, miR-96 indeed induced migration, invasion and proliferation of NSCLC cell line. In addition, FOXO1 and DUSP1 are targets of miR-96 and these three molecules form competing endogenous RNA network. miR-96 related competing endogenous RNA network affects cell metastasis via epidermal growth factor receptor (EGFR) signaling.<br /><em><strong>Conclusion:</strong></em> miR-96 can be considered as one of tumor-inducer and form competing endogenous RNA network with FOXO1 and DUSP1, which affects downstream EGFR signaling.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801The effect of intra-cerebroventricular injection of insulin on the levels of monoamines on the raphe magnus nucleus of non-diabetic and short-term diabetic rats in the formalin test9159211316810.22038/ijbms.2019.35580.8485ENShima Balali DehkordiDepartment of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran0000-0003-3884-4973Javad SajedianfardDepartment of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran0000000168432983Ali Akbar OwjiDepartment of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranJournal Article20181015<em><strong>Objective(s):</strong></em> Systemic and intracerebroventricular (ICV) injection of insulin possess analgesic effects. The raphe magnus nucleus (RMN) is part of the endogenous analgesia system. The objective of the present study was to evaluate the effects of ICV injection of insulin on the levels of monoamines and their related metabolites in the RMN during the formalin test in non-diabetic and short-term diabetic rats.<br /><em><strong>Materials and Methods:</strong></em> Sixty four adult male rats were used. Diabetes was induced by Streptozotocin (STZ) (60 mg/kg, IP); insulin (5 mU/animal, 5 μl) was injected into the left ventricle. Microdialysis was performed in each rat. Samples were collected at 15 min intervals. After taking the base sample of microdialysis, 50 μl of 2.5% formalin was injected into the plantar surface of the hind paw, and the level of nociception was recorded every 15 sec for 1 hr. Monoamines and their metabolites concentrations were measured using the HPLC-ECD method.<br /><em><strong>Results:</strong></em> Findings showed that ICV injection of insulin in non-diabetic rats increased the concentration of monoamines and their related metabolites in the RMN. In diabetic rats, injection of insulin decreased the concentrations of monoamines and their related metabolites in the RMN (P<0.5). Our results determined that, at least in part, insulin is associated with antinociceptive effect in non-diabetic rats.<br /><em><strong>Conclusion:</strong></em> Based on the results, it seems that ICV injection of insulin in non-diabetic rats increased the activity of the central pain control pathways leading to antinociceptive response, but this condition was not seen in diabetic rats.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801Immunogenicity and protection effects of cationic liposome containing imiquimod adjuvant on leishmaniasis in BALB/c mice9229311330310.22038/ijbms.2019.35739.8515ENAhmad MehravaranInfectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, IranDepartment of Parasitology and Mycology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran0000-0002-2079-7972Maryam Rezaei NasabDepartment of Parasitology and Mycology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, IranHadi MirahmadiInfectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, IranDepartment of Parasitology and Mycology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, IranIraj SharifiLeishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, IranEbrahim AlijaniClinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran0000-0001-9921-8947Amin Reza NikpoorImmunogenetic and Cell Culture Department, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-5619-8771Javad AkhtariImmunogenetics Research Center, Department of Medical Nanotechnology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran0000-0001-9040-0267Mansure HojatizadeDepartment of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, IranJournal Article20181021<em><strong>Objective(s):</strong></em> Protection against leishmaniasis, in the murine model, is dependent on developing a potent CD4+ mediated Th1 type response. Liposomes can be applied as immunoadjuvants to stimulate immune responses to different antigens. In the present study, it was investigated whether DOTAP liposomes having SLA and imiquimod adjuvant, can induce a Th1 response and protect against Leishmania major challenge in BALB/c mice. <br /><em><strong>Materials and Methods:</strong></em> Liposomes were provided applying the lipid film procedure. BALB/C mice were subcutaneously immunized, three times with 2-week intervals, with various formulations. Assessment of lesion development and parasite burden in the foot and spleen after challenge with L. major, assessment of Th1 cytokine (IFN-γ), and titration of IgG isotypes assessed the type of generated immune reaction and the protection extent. <br /><em><strong>Results:</strong></em> The mice immunized with Liposome DOTAP+imiquimod+SLA showed smaller footpad swelling which was meaningfully different (P<0.05) compared with other groups. The highest level of IgG2a was observed with Lip DOTAP+imiquimod+SLA more than the control (P<0.001). Mice immunized with Lip DOTAP+SLA+imiquimod demonstrated the least number of live parasites in the footpad and spleen. Cytokine assay showed that the greatest IFN- γ secretion was seen in the splenocytes of mice immunized with all formulations as compared to the control group (P<0.0001). In contrast, the lowest IL-4 production was detectable in Lip+imiquimod+SLA spleen, which was not significantly different compared with other groups.<br /><em><strong>Conclusion:</strong></em> The results of this study show that liposome DOTAP+SLA+imiquimod formulation generates a cellular immune response that is protective against challenge against L. major.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801Pterocarpus santalinus ameliorates streptozotocin-induced diabetes mellitus via anti-inflammatory pathways and enhancement of insulin function9329391301210.22038/ijbms.2019.34998.8325ENRamy E El-BadawyMedical lab specialist, Cleopatra hospital, Cairo0000-0003-2877-8837Khairy A IbrahimMammalian Toxicology Department, Central Agriculture Pesticides Lab, Agriculture Research Center, Dokki, Giza, 12618, EgyptNahla S HassanUniversity of Ain Shams, Faculty of Science, Department of BiochemistryWael M El-SayedUniversity of Ain Shams, Faculty of Science, Department of Zoology, Abbassia 11566, Cairo, Egypt0000-0002-3622-1417Journal Article20180921<em><strong>Objective(s):</strong></em> Morbidity and mortality due to diabetes mellitus (DM) result in exorbitant psycho-economical costs, so there is a strong need to create new strategies and drugs for controlling DM. The aim of the current study was to investigate the anti-diabetic effect of the aqueous extract of Pterocarpus santalinus on streptozotocin (STZ)-induced DM as compared to glustin. <br /><em><strong>Materials and Methods:</strong></em> Thirty male rats were divided into five groups of six rats each as follows: control; the second group, received the aqueous plant extract (250 mg/kg) orally and daily for three weeks; the third group, was intraperitoneally injected with a single dose of 65 mg/kg of STZ and sacrificed after four weeks; the fourth and fifth groups, were injected with STZ, then after one week these were treated orally with either plant extract or with 3 mg/kg of glustin for three weeks, then sacrificed. <br /><em><strong>Results:</strong></em> HPLC analysis of the plant aqueous extract showed that it contains many polyphenols and flavonoids. Treatment with STZ resulted in significant reductions in body weight, insulin level, and the expression of Fetuin-A and IRS-1. It also caused significant elevations in glucose, HOMA-IR, glycated hemoglobin, urea, and the expression of JNK and SIRT-1. STZ also caused an extensive β-cell degranulation and decreased cellular density. The aqueous extract of red sandalwood was able to abrogate the deleterious effects caused by STZ and improved the histological architecture of pancreas<br /><em><strong>Conclusion:</strong></em> The aqueous extract of P. santalinus ameliorates diabetes mellitus via anti-inflammatory pathways and enhancement of insulin function.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801The effects of PPAR-γ agonist pioglitazone on hippocampal cytokines, brain-derived neurotrophic factor, memory impairment, and oxidative stress status in lipopolysaccharide-treated rats9409481323910.22038/ijbms.2019.36165.8616ENFarimah BeheshtiDivision of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Basic Science and Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran0000-0003-1524-2339Mahmoud HosseiniDivision of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-6425-5123Milad HashemzehiIranshahr University of Medical Sciences, Iranshahr, IranMohammad SoukhtanlooDepartment of Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0003-2145-125XMajid KhazaeiNeurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran0000-0002-3150-5883Mohammad Naser ShafeiDepartment of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-5148-9895Journal Article20181111<em><strong>Objective(s):</strong></em> The aim of current study was to evaluate improving effects of pioglitazone as an agonist of peroxisome proliferator-activated receptor gamma (PPARγ), on brain-derived neurotrophic factor (BDNF) and cytokines as well as tissue oxidative damage criteria in the hippocampus in a rat model of lipopolysaccharide (LPS) induced memory impairment.<br /><em><strong>Materials and Methods:</strong></em> The rats were classified and treated as follows (10 rats per group): (1) vehicle, (2) vehicle before LPS (1 mg/kg, 120 min before memory tests), (3-5) pioglitazone 10, 20 or 30 mg/kg 30 min before LPS. Finally, the hippocampal tissues were collected for biomedical analyses.<br /><em><strong>Results:</strong></em> In the Morris water maze test, the LPS group, had a longer latency to find the platform while they spent a shorter time in the target quadrant in the probe trial. In the passive avoidance test, the animals of the LPS group had shorter delay times to enter the dark compartment than those of the control group. Treatment with 20 and 30 mg of pioglitazone corrected these parameters. In the hippocampus of LPS group interleukin-6, tumor necrosis factor-α, nitric oxide metabolites, and malondialdehyde were higher while thiol, BDNF, and IL-10 concentrations and the activities of catalase (CAT) and superoxide dismutase (SOD) were lower than the control group. Treatment by both doses of 20 and 30 mg of pioglitazone corrected the biochemical parameters in the hippocampus.<br /> <em><strong>Conclusion:</strong></em> The current findings revealed that pioglitazone protected the rats from learning and memory impairment induced by LPS. The effects were associated with improvement of cytokines, oxidative stress criteria, and BDNF.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801p-Coumaric acid protects cardiac function against lipopolysaccharide-induced acute lung injury by attenuation of oxidative stress9499551324310.22038/ijbms.2019.36316.8650ENMaryam KheiryDepartment of Physiology, Physiology Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran0000-0003-2238-3295Mahin DianatDepartment of Physiology, Physiology Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran0000-0002-0305-5715Mohammad BadaviDepartment of Physiology, Physiology Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran0000-0003-2290-8565Seyyed Ali MardDepartment of Physiology, Physiology Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran0000-0002-4323-1672Vahid BayatiCellular and Molecular Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranJournal Article20181129<em><strong>Objective(s):</strong></em> Acute lung injury (ALI) has a high mortality rate and is characterized by damage to pulmonary system giving rise to symptoms such as histological alteration, lung tissue edema and production of proinflammatory cytokine. p-Coumaric acid (p-CA), as a phenolic compound, that is found in many types of fruits and vegetables has been reported to exhibit a therapeutic effect in several inflammatory disorders. The aim of our study was evaluation of pretreatment with p-CA against heart dysfunction, oxidative stress and nuclear factor-erythroid 2 -related factor 2 (Nrf2) modifications following lipopolysaccharide (LPS)-induced acute lung inflammation. <br /><em><strong>Materials and Methods:</strong></em> The rats were divided into four groups (n=8): Control, LPS (5 mg/kg, it), p-CA (100 mg/kg, IP), and LPS+pCA. Inflammatory response and oxidative stress were evaluated by measurement of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) levels in heart tissue. For evaluation of the effect of LPS on cardiac response, electrocardiography (ECG) and hemodynamic parameters were recorded.<br /><em><strong>Results:</strong></em> A significant increase in lipid peroxidation (P<0.001, cytokine parameters (TNF-α and IL-6 (P<0.01), gene expression of Nrf2 (P<0.05), and antioxidant activity of superoxide dismutase and glutathione (P< 0.05) in addition to glutathione peroxidase (P<0.01) was demonstrated in heart tissue of ALI rats. LPS can impair cardiac function (in in vitro measurement of hemodynamic parameters by using Langendorff setup, and in in vivo measurement of ECG parameters), and pretreatment with p-CA recovered these parameters to control levels in heart. Pretreatment with p-CA causes modulation of cytokines and MDA level that protected cardiac injury caused by LPS in ALI model. <br /><em><strong>Conclusion:</strong></em> Our results showed anti-inflammatory and antioxidative effect of p-CA on LPS-induced ALI.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801The impact of Lactobacillus acidophilus on hepatic and colonic fibrosis induced by ethephon in a rat model9569621334610.22038/ijbms.2019.32936.7866ENHoda I BahrBiochemistry Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt0000-0002-7012-8427Rania HamadPathology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, EgyptShimaa A A IsmailClinical Pathology Department, Faculty of Veterinary Medicine, Zagazig University, EgyptJournal Article20180624<em><strong>Objective(s):</strong></em> The study is aimed to elucidate the impact of antioxidant, anti-inflammatory and antifibrosis properties of Lactobacillus acidophilus (L. acidophilus) on liver and colon in ethephon treated rats through measuring Pro- inflammatory cytokines, oxidative stress index, lysosomal cathepsin-D enzyme activity and fibrosis markers.<br /><em><strong>Materials and Methods:</strong></em> Rats divided into three groups; Group 1: distilled water control, Group 2: rats at day 16 from experiment beginning were orally received ethephon 50 mg/ kg BW in distilled water once daily for 60 days. Group 3: rats were orally received L. acidophilus enriched diet 1% (w/w) for 15 days as prophylactic, then received both L. acidophilus enriched diet 1% (w/w) and ethephon 50 mg/kg BW for 60 days. <br /><em><strong>Results:</strong></em> Ethephon exerts hepatic and colonic oxidative stress, inflammatory response and fibrosis through NF-κB activation. On contrary, L. acidophilus supplementation evokes hepatoprotective properties as revealed by decreased serum AST, ALT, γ -GT and increased IGF-1. L. acidophilus exerts antioxidant and anti-inflammatory properties as indicated by decreased TOS, OSI, TNF-α, IL-1β, cathepsins D activity, NF-κB expression and increased TAC, lysosomal membrane stability. L. acidophilus shows antifibrotic activity as demonstrated by down-regulation of TGF-β1, α-SMA, collagen expression. <br /><em><strong>Conclusion:</strong></em> L. acidophilus possess antioxidant, anti -inflammatory and antifibrotic activity through inhibition of NF-kB.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-386622820190801Stronger antioxidant enzyme immunoreactivity of Populus tomentiglandulosa extract than ascorbic acid in rat liver and kidney9639671330510.22038/ijbms.2019.34926.8296ENChoong-Hyun LeeDepartment of Pharmacy, College of Pharmacy, Dankook University, Cheonan, Chungnam 31116, Republic of Korea0000-0001-5508-9004Joon Ha ParkDepartment of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Republic of KoreaJi Hyeon AhnDepartment of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Republic of KoreaJong Dai KimDivision of Food Biotechnology, School of Biotechnology, Kangwon National University, Chuncheon, Gangwon 24341, Republic of KoreaJun Hwi ChoDepartment of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of KoreaTae-Kyeong LeeDepartment of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of KoreaMoo-Ho WonDepartment of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea0000-0002-7178-6501Journal Article20180917<em><strong>Objective(s):</strong></em> Populus species have various pharmacological properties, including antioxidant activity. In this study, the effects of Populus tomentiglandulosa extract (PTE) on histopathology and antioxidant enzymes in the rat liver and kidney were examined. <br /><em><strong>Materials and Methods:</strong></em> Sprague-Dawley rats were assigned to three groups; (1) normal diet fed group, (2) ascorbic acid-containing diet-fed group as a positive control, (3) PTE-containing diet-fed group. The histopathology in the rat liver and kidney was examined by hematoxylin and eosin staining. The effect of PTE was examined in the rat liver and kidney by immunohistochemistry for antioxidant enzymes, such as superoxide dismutases (SOD1 and SOD2), catalase (CAT), and glutathione peroxidase (GPx). <br /><em><strong>Results:</strong></em> No marked histopathological alterations were observed in the liver and kidney of the PTE-containing diet-fed group. In the liver, the mean numbers of SOD1, SOD2, CAT, and GPx immunoreactive cells were significantly increased in the PTE-containing diet-fed rats, compared with those in the normal- and ascorbic acid-containing diet-fed rats. In the kidney, all SOD1, SOD2, CAT, and GPx immunoreactive structures were significantly increased in the PTE-containing diet-fed group, compared with those in the normal- and ascorbic acid-containing diet-fed groups. <br /><em><strong>Conclusion:</strong></em> Results showed that PTE treatment significantly increased antioxidant enzymes in the rat liver and kidney, and we suggest that PTE might have hepato- and nephro-protective potentials against oxidative stress.