فهرست مطالب

Basic Medical Sciences - Volume:21 Issue: 2, Feb 2018

Iranian Journal of Basic Medical Sciences
Volume:21 Issue: 2, Feb 2018

  • تاریخ انتشار: 1396/10/21
  • تعداد عناوین: 14
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  • Seyed Ali Reza Mortazavi, Seyed Mohammad Javad Mortazavi * Pages 112-115
    Breast cancer is the most common malignancy among women, both in the developed and developing countries. Women with mutations in the BRCA1 and BRCA2 genes have an increased risk of breast and ovarian cancers. Recent studies show that short-wavelength visible light disturb the secretion of melatonin and causes circadian rhythm disruption. We have previously studied the health effects of exposure to different levels of radiofrequency electromagnetic fields (RF-EMFs) such as mobile phones, mobile base stations, mobile phone jammers, laptop computers, and radars. Moreover, over the past several years, we investigated the health effects of exposure to the short wavelength visible light in the blue region emitted from digital screens. The reduction of melatonin secretion after exposure to blue light emitted from smartphone’s screen has been reported to be associated with the negative impact of smartphone use at night on sleep. We have shown that both the blue light and RF-EMFs generated by mobile phones are linked to the disruption of the circadian rhythm in people who use their phones at night. Therefore, if women with hereditary breast cancer predispositions use their smartphones, tablets and laptops at night, disrupted circadian rhythms (suppression of melatonin caused by exposure to blue light emitted from the digital screens), amplifies the risk of breast cancer. It can be concluded that women who carry mutated BRCA1 or BRCA2, or women with family history of breast cancer should avoid using their smartphones, tablets and laptops at night. Using sunglasses with amber lenses, or smartphone applications which decrease the users’ exposure to blue light before sleep, at least to some extent, can decrease the risk of circadian rhythm disruption and breast cancer.
    Keywords: Blue light, BRCA mutation, Circadian, Digital screens, Laptops, Melatonin, Rhythm, Smartphones
  • Farzad Khademi, Mohammad Derakhshan, Arshid Yousefi-Avarvand, Mohsen Tafaghodi * Pages 116-123
    Objective(s)
    Production of effective tuberculosis (TB) vaccine is necessity. However, the development of new subunit vaccines is faced with concerns about their weak immunogenicity. To overcome such problems, polymers-based vaccine delivery systems have been proposed to be used via various routes. The purpose of this study was to determine the potential of polymeric particles as future vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization against TB.
    Materials And Methods
    PubMed, Scopus, Science-Direct, and the ISI web of knowledge databases were searched for related keywords. A total of 420 articles, written up to June 25, 2016, were collected on the potential of polymeric particles as TB vaccine delivery systems after parenteral and non-parenteral immunization. Thirty-one relevant articles were selected by applying inclusion and exclusion criteria.
    Results
    It was shown that the immunogenicity of TB vaccines had been improved by using biodegradable and non-biodegradable synthetic polymers as well as natural polymers and they are better able to enhance the humoral and cellular immune responses, compared to TB vaccines alone. The present study revealed that various polymeric particles, after M. tuberculosis challenge in animal models, provide long-lasting protection against TB. PLGA (poly (lactide-co-glycolide)) and chitosan polymers were widely used as TB vaccine delivery systems/adjuvants.
    Conclusion
    It seems that PLGA and chitosan polymers are well-suited particles for the parenteral and non-parenteral administration of TB vaccines, respectively. Non-biodegradable synthetic polymers in comparison with biodegradable synthetic and natural polymers have been used less frequently. Therefore, further study on this category of polymers is required.
    Keywords: Mycobacterium tuberculosis, Non-parenteral immunization Parenteral immunization Polymeric particles Vaccine
  • Niloufar Hedayati Emami, Farzaneh Mahmoudi Lafout, Fahimeh Mohammadghasemi * Pages 124-129
    Objective(s)
    Melatonin, an important hormone secreted by the epiphysis, is a powerful anti-oxidant with a high potential to neutralize medical toxins. The goal of this study was to demonstrate the beneficial effect of melatonin on epididymal sperm and reproductive parameters in mice treated with acetylsalicylic acid (ASA).
    Materials And Methods
    Male adult mice were divided into four treatment groups: control, ASA, melatonin, and ASA駩媶觢. Mice were administered ASA (50 mg/kg, orally) and/or melatonin (10 mg/kg, intraperitoneally), or vehicle control, for 14 days. Sperm count, sperm motility, and sperm morphology were evaluated to assess fertility. A colorimetric assay was used to measure serum total antioxidant capacity (TAC). A sperm chromatin dispersion (SCD) test was used to assess sperm chromatin integrity. Sex hormone levels were measured by ELISA.
    Results
    Compared to the control group, ASA treatment resulted in a significant decrease in sperm parameters (P
    Conclusion
    Short-term administration of ASA (50 mg/kg) has adverse effects on male reproductive function in mice. Co-administration of melatonin protects against ASA-induced impairment of male reproductive function by preventing the reduction in serum TAC and testosterone levels seen with ASA treatment alone.
    Keywords: Acetylsalicylic acid, Antioxidants, Epididymis, Melatonin, Sperm, Testosterone
  • Kun Zhang, Shan Gao, Jiayi Guo, Guohua Ni, Zhe Chen, Feng Li, Xiaolei Zhu, Yongbing Wen, Yanxing Guo * Pages 130-137
    Objective(s)
    To elucidate the effects and potential mechanisms of hypericin-photodynamic therapy (HYP-PDT) for treating the human rheumatoid arthritis (RA) fibroblast-like synoviocyte (FLS) MH7A cell-line.
    Materials And Methods
    MH7A cells were subjected to HYP-PDT intervention and apoptosis was evaluated via MTT, nuclear staining, and flowcytometry analyses. Intracellular reactive oxygen species (ROS) were measured with the fluorescent probe 2’7’-dichlorofluorescein diacetate (DCFH-DA). To verify the effects of HYP on apoptotic and nuclear factor kappa-B (NF-κB) pathways, caspase-8, 9, poly-ADP-ribose polymerase (PARP), phosphorylated (p)-NF-κB p65, NF-κB p65 and p-IκBα protein expressions were quantified with western blot. Quantitative real-time PCR was used to assay NF-κB p65 mRNA.
    Results
    HYP-PDT inhibited MH7A cell viability and induced apoptosis in a dose-dependent manner. Meanwhile, intracellular ROS levels increased significantly after HYP-PDT treatment. Furthermore, the expression of cleaved caspase-9 and PARP was increased by HYP-PDT treatment, with a concurrent decline in NF-κB.
    Conclusion
    HYP-PDT induces apoptosis in MH7A cells, at least partially, via generation of ROS, regulation of the apoptotic pathway and suppression of the NF-κB pathway. These findings suggest that HYP-PDT may be a potential treatment for RA.
    Keywords: Apoptosis Fibroblast-like synoviocyte Hypericin-photodynamic, –therapy Nuclear factor kappa-B Rheumatoid arthritis Reactive oxygen species
  • Abolfazl Abbaszadeh, Saeideh Darabi, Amin Hasanvand*, Hossein Amini-Khoyi, Amir Abbasnezhad, Razieh Choghakhori, Asghar Aaliehpour Pages 138-144
    Objective(s)
    Several lines of evidence showed that minocycline possesses antioxidant and anti-inflammatory properties. This study aimed to demonstrate the effects of minocycline in rats subjected to chronic constriction injury (CCI).
    Materials And Methods
    In this study four groups (n = 6–8) of rats were used as follows: Sham, CCI, CCI minocycline (MIN) 10 mg/Kg (IP) and CCI MIN 30 mg/Kg (IP). On days 3, 7, 14, and 21 post-surgery hot-plate, acetone, and von Frey tests were carried out. Finally, Motor Nerve Conduction Velocity Evaluation (MNCV) assessment was performed and spinal cords were harvested in order to measure tissue concentrations of TNF_α, IL-1β, Glutathione peroxidase (GPx), Superoxide dismutase (SOD) and Malondialdehyde (MDA). Extent of perineural inflammation and damage around the sciatic nerve was histopathologically evaluated.
    Results
    Our results demonstrated that CCI significantly caused hyperalgesia and allodynia twenty-one days after CCI. MIN attenuated heat hyperalgesia, cold and mechanical allodynia and MNCV in animals. MIN also decreased the levels of TNF_α and IL-1β. Antioxidative enzymes (SOD, MDA, and GPx) were restored following MIN treatment. Our findings showed that MIN decreased perineural inflammation around the sciatic nerve. According to the results, the neuropathic pain reduced in the CCI hyperalgesia model using 30 mg/kg of minocycline.
    Conclusion
    It is suggested that antinociceptive effects of minocycline might be mediated through the inhibition of inflammatory response and attenuation of oxidative stress.
    Keywords: Chronic constriction-, Injury, Inflammatory response, Minocycline, Neuropathic pain, Oxidative stress, Rat
  • Pages 145-152
    Objective(s)
    Tanacetum species are traditionally used as insecticide, and externally wound healer as well as for anti-inflammatory and antihistaminic properties. The in vivo wound-healing and anti-inflammatory potential of four Tanacetum species, Tanacetum argenteum (Lam.) Willd. subsp. argenteum (TA), Tanacetum heterotomum (Bornm.) Grierson (TH), Tanacetum densum (Lab.) Schultz Bip. subsp. sivasicum (TD), and Tanacetum vulgare L. (TV) was investigated.
    Materials And Methods
    The chloroform (CHCl3) and methanol:water (80:20) extracts were prepared from the aerial parts of each plant. For assessment of the wound-healing activity, linear incision on rats and circular excision on mice wound models were used and histopathological analyses were conducted on the tissues treated with the test materials. For the evaluation of the anti-inflammatory activity, Whittle Method based on the inhibition of the acetic acid-induced increase in capillary permeability was used. In order to elucidate the phytochemical contents of the extracts, HPLC profiles of active fractions were screened and quantitative analysis was conducted within the scope of HPLC analysis.
    Results
    The CHCl3 extracts of TD, TAand TVwere found to have significant wound healing activity (37.1%, 30.8% and 26.1% tensile strength; 88.05%, 72.93% and 44.88% contraction values, respectively) and anti-inflammatory activities (31.5% and 26.6% inhibition values for TDand TA). Parthenolide content of the CHCl3 extracts of TA, THand TV were found 242.66±1.53, 190.16±5.62 and 177.51±3.73 µg/100 mg plant material, respectively.
    Conclusion
    According to the results, the other secondary metabolites present in the aerial parts of the Tanacetum species possibly exerted synergistic effects on the observed healing of the wounds.
    Keywords: Asteraceae, Anti-inflammatory, Excision, Incision, Tanacetum, Wound-healing
  • Mitra Alami-Milani, Parvin Zakeri-Milani, Hadi Valizadeh, Roya Salehi, Mitra Jelvehgari * Pages 153-164
    Objective(s)
    Micelles have been studied as nanoparticulate drug delivery systems for improving the topical ocular delivery of hydrophobic drugs. The objective of this study was to develop and characterize dexamethasone-loaded polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) micelles to improve patient compliance and enhance the ocular bioavailability of poorly water-soluble drugs.
    Materials And Methods
    The PCL-PEG-PCL copolymers were synthesized via the ring opening polymerization of ε-caprolactone in the presence of PEG. The resulting purified copolymers were characterized by GPC, NMR, FTIR, XRD and DSC. The critical micelle concentrations (CMCs) of the copolymers mentioned were determined. Dexamethasone was loaded into polymeric micelles by film hydration method, and dexamethasone-loaded micelles were characterized by TEM and DLS. Drug release kinetics and ex vivo corneal permeability were also determined.
    Results
    The CMC of the synthetized copolymers was approximately 0.03 mg/ml. Aqueous solutions of the resulting copolymers (400 mg/ml) rapidly formed a gel in situ at 34 °C. The TEM results exhibited the successful formation of spherical micelles. The size of the prepared micelles was approximately 40 nm. Formulated micelles sustained the release of the incorporated dexamethasone for 5 days.
    Conclusion
    Data from ex vivo permeability tests indicated that PCL-PEG-PCL micelles can be suitable candidates for the ocular delivery of dexamethasone and, likely, other hydrophobic drugs.
    Keywords: Block copolymer, Dexamethasone, Ocular drug delivery, Micelle, Critical micelle concentration
  • Mahnaz Ghowsi, Homayoun Khazali *, Sajjad Sisakhtnezhad Pages 165-174
    Objective(s)
    Some studies suggest that chronic low-grade inflammation is involved in insulin resistance in polycystic ovary syndrome (PCOS). This study assessed possible involvement of alteration in expression of two pro-inflammatory factors, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in adipose tissues of PCOS rats in the impairment of insulin actions. Also, effects of resveratrol as an anti-inflammatory agent were investigated.
    Materials And Methods
    Fifteen female Wistar rats (21 days old) were divided into three groups (n=5): Ι) Control, П) PCO-model-saline: served as PCOS rats and to induce PCOS, received subcutaneously testosterone enanthate 1 mg/100 g body weight subcutaneously for 35 days, Ш) PCO-model-resveratrol, after receiving testosterone, received resveratrol 10 mg/kg intraperitoneally for 28 days. The expression of Tnf-α and Il-6 mRNAs in adipose tissues was determined by the qRT-PCR method.
    Results
    The Il-6 mRNA expression in the visceral adipose tissue of PCOS rats was increased in comparison to controls (P
    Conclusion
    Increased expression of Il-6 mRNA in the visceral adipose tissue of polycystic ovarian rats may be one cause of insulin resistance observed in them and resveratrol as an anti-inflammatory and anti-hyperglycemic agent may decrease the risk of diabetes by reduction of expression of pro-inflammatory cytokines TNF-α and IL-6 in PCOS patients.
    Keywords: Adipose tissue, IL-6, Polycystic ovary –, syndrome, Rat, Resveratrol, TNF-?
  • Zulfiqar Mirani *, Muhammad Khan, Anila Siddiqui, Fouzia Khan, Mubashir Aziz, Shagufta Naz, Ayaz Ahmed, Seema Khan Pages 175-180
    Objective(s)
    Staphylococcus aureus is a Gram-positive pathogen, well known for its resistance andversatile lifestyle. Under unfavourable conditions, it adapts biofilm mode of growth. For staphylococcal biofilm formation, production of extracellular polymeric substances (EPS) is a pre-requisite, which is regulated by ica operon-encoded enzymes. This study was designed to know the impact of ascorbic acid on biofilm formation and colony spreading processes of S. aureus and MRSA.
    Materials And Methods
    The isolates of methicillin-resistant S. aureus (MRSA) used in present study, were recovered from different food samples. Various selective and differential media were used for identification and confirmation of S. aureus. Agar dilution method was used for determination of oxacillin and ascorbic acid resistance level. MRSA isolates were re-confirmed by E-test and by amplification of mecA gene. Tube methods and Congo-Red agar were used to study biofilm formation processes. Gene expression studies were carried on real-time reverse transcriptase-polymerase chain reaction (RT-PCR).
    Results
    The results revealed the presence of mecA gene belonging to SCCmecA type IV along with agr type II in the isolates. In vitro studies showed the sub-inhibitory concentration of oxacillin induced biofilm production. However, addition of sub-inhibitory dose of ascorbic acid was found to inhibit EPS production, biofilm formation and augment colony spreading on soft agar plates. The inhibition of biofilm formation and augmentation of colony spreading observed with ascorbic acid alone or in combination with oxacillin. Moreover, gene expression studies showed that ascorbic acid increases agr expression and decreases icaA gene expression.
    Conclusion
    The present study concluded thatascorbic acid inhibits biofilm formation, promotes colony spreading and increases agr gene expression in MRSA.
    Keywords: Ascorbic acid, Biofilms, Colony spreading, Methicillin-resistant S. aureus, Staphylococcus aureus
  • Leyla Norouzi-Barough, Mohammad Reza Sarookhani *, Rasoul Salehi, Mohammadreza Sharifi, Sahar Moghbelinejad Pages 181-187
    Objective(s)
    Multidrug resistance (MDR) is a major obstacle in the successful chemotherapy of ovarian cancer. Inhibition of P-glycoprotein (P-gp), a member of ATP-binding cassette (ABC) transporters, is a well-known strategy to overcome MDR in cancer. The aim of this study was to investigate the efficiency and ability of CRISPR/Cas9 genome editing technology to knockdown ABCB1 gene expression in adriamycin resistant (A2780/ADR) ovarian cancer cell line and evaluate the sensitivity changes to doxorubicin.
    Materials And Methods
    Three single-guide RNAs (sgRNAs) targeting the fourth and fifth exons of human ABCB1 gene were designed in this study. Expression level of ABCB1 was detected using quantitative real time PCR (qRT-PCR) after co-transfection of all three sgRNAs into A2780/ADR cell line and subsequent antibiotic selection. Drug sensitivity to doxorubicin was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
    Results
    The results showed that CRISPR/Cas9 system could significantly reduce the expression of P-gp. The dramatic decline in ABCB1 gene expression was associated with increased sensitivity of cells transfected with sgRNAs to doxorubicin.
    Conclusion
    Based on the results of this study, it is concluded that the CRISPR-based systems, used in the present study, effectively down-regulated the target gene and acted as an ideal and cost-effective tool for gene editing of A2780/ADR cell line resulting in restoration of nonmalignant phenotype.
    Keywords: CRISPR, Doxorubicin, Drug Resistance, Ovarian Cancer, P-glycoprotein
  • Fatemeh Jahandar, Jinous Asgarpanah, Parvaneh Najafizadeh, Zahra Mousavi * Pages 188-193
    Objective(s)
    Pycnocycla bashagardiana is an endemic species found only in Iran. Due to the presence of myristicin as the major component of the fruit’s oil we were prompted to assess the antinociceptive and anti-inflammatory properties of P. bashagardiana fruit’s essential oil (PBFEO).
    Materials And Methods
    The analgesic activities of PBFEO (100, 200, and 400 mg/kg, IP) were studied by hot-plate and formalin tests in mice. Control and standard groups received vehicle and morphine (5 mg/kg, IP), respectively. The acute anti-inflammatory effect of PBFEO (200 and 400 mg/kg, IP) were assessed by carrageenan-induced paw edema method in 30 min, 1, 2, 3, and 4 hr after carrageenan injection and the chronic anti-inflammatory effect of PBFEO (50 and 100 mg/kg, IP) were assessed by the cotton pellet-induced granuloma method in rats.
    Results
    In hot-plate and formalin tests, the studied doses of PBFEO were not effective. However, in carrageenan test, all studied doses ofPBFEO significantly reduced the paw edema in comparison to the control animals (P
    Conclusion
    The results suggest that PBFEOpossesses biologically active constituents that have significant peripheral anti-inflammatory effects.
    Keywords: Anti-inflammatory Antinociceptive, Essential oil, Mice, Pycnocycla bashagardiana Mozaff, Rat
  • Xue Xu, Zhiyong Chen, Xiaoxia Zhu, Dandan Wang, Jun Liang, Cheng Zhao, Xuebing Feng, Jiucun Wang, Hejian Zou, Lingyun Sun* Pages 194-201
    Objective(s)
    This study aims to investigate the pathogenicity and possible mechanisms of S100A9 function in mice models of scleroderma.
    Materials And Methods
    The content of S100A9 in the skin tissues of mice with scleroderma was determined. Different concentrations of bleomycin (BLM) and S100A9 were subcutaneously injected into the backs of mice simultaneously, and then pathological changes in the skin of these mice were monitored. Specifically, the levels of inflammatory cytokines and alpha smooth muscle actin (α-SMA), the activation of extracellular regulated kinase 1/2 (ERK1/2), mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways, and the expression of the receptor for advanced glycation end-product (RAGE) in the skin were determined.
    Results
    The content of S100A9 in the skin tissues of mice with scleroderma was determined. Different concentrations of BLM and S100A9 were subcutaneously injected into the backs of mice simultaneously, and then pathological changes in the skin of these mice were monitored. Specifically, the levels of inflammatory cytokines and alpha smooth muscle actin (α-SMA), the activation of extracellular regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways, and the expression of the receptor for advanced glycation end-product (RAGE) in the skin were determined.
    Conclusion
    S100A9 aggravates dermal fibrosis in BLM-induced scleroderma (BIS ) mice, and its mechanisms might be mediated by RAGE, ERK1/2, and NF-κB pathway.
    Keywords: S100A9, Scleroderma, Bleomycin, RAGE, ERK1-2 MAPK, NF-κB
  • Azar Tahghighi *, Safoura Karimi, Arezoo Rafie Parhizgar, Sedigheh Zakeri Pages 202-211
    Objective(s)
    Due to the rapid increased drug resistance to Plasmodium parasites, an urgent need to achieve new antiplasmodial drugs is felt. Therefore, in this study, the new synthetic phenanthroline derivatives were synthesized with antiplasmodial activity.
    Materials And Methods
    A series of 1,10-phenanthroline derivatives containing amino-alcohol and amino-ether substituents were synthesized via facile procedures, starting with 5,6-epoxy-1,10-phenanthroline. Their antiplasmodial activity was then evaluated using Peter's 4-day suppressive test against Plasmodium berghei-infected mice (ANKA strain). Furthermore, the mean survival time of the mice treated with synthetic compounds was compared with the negative control group.
    Results
    The results demonstrated that the compounds 6-(3-(dibutylamino)propylamino)-5,6-dihydro-1,10-phenanthroline-5-ol (7b) at the dose of 150 mg/kg/day and 4-(1,10-phenanthroline-5-yloxy)-N,N-dipropylbutan-1-amine (8b) at the dose of 15 mg/kg/day have 90.58% and 88.32% suppression, respectively. All synthetic compounds prolonged the mean survival time of treated mice in comparison with negative control groups, indicating the in vivo antiplasmodial activity of these new compounds.
    Conclusion
    The present study is the first attempt to achieve new, effective synthetic compounds based on phenanthroline scaffold with the antiplasmodial activity. However, more research is needed to optimize their antimalarial activity.
    Keywords: Antiplasmodial activity Malaria Plasmodium berghei Peter's test 1, 10-Phenanthroline Quinoline
  • Batul Hashemibeni, Ali Valiani, Mojtaba Esmaeili, Mohammad Kazemi, Maryam Aliakbari, Farhad Golshan Iranpour * Pages 212-218
    Objective(s)
    The aim of this study was to compare the chondrogenic induction potential of Piascledine and TGF-β1 on adipose-derived stem cells (ADSCs) in fibrin and fibrin-alginate scaffolds.
    Materials And Methods
    Human subcutaneous adipose tissues were harvested from three patients who were scheduled to undergo liposuction. Isolated ADSCs were proliferated in a culture medium. Then, the cells were seeded in fibrin or fibrin-alginate scaffolds and cultured for 14 days in a chondrogenic medium containing Piascledine, TGF-β1, or both. The rate of cell proliferation and survival was evaluated by using MTT [3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide] assay and the rate of the expression of type II collagen, aggrecan, and type X collagen genes was evaluated by real-time polymerase chain reaction (real-time PCR) method.
    Results
    The MTT results showed that Piascledine is able to enhance the proliferation and survival of ADSCs in fibrin scaffolds in comparison to other groups (P
    Conclusion
    Piascledine can enhance the proliferation and differentiation of ADSCs in fibrin scaffolds.
    Keywords: Chondrogenesis Piascledine, Stem cells, Tissue engineering, Transforming growth-, factor beta 1