Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
Current progress in the development of therapeutic vaccines for chronic hepatitis B virus infection
692
704
EN
Faezeh
Ghasemi
Department of New Sciences and Technology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
ghasemif891@mums.ac.ir
Sina
Rostami
The Influenza Centre, Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway
sina.rostami@alumni.um.ac.ir
Majid
Ghayour-Mobarhan
Biochemistry of Nutrition Research Center; School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
ghayour@mums.ac.ir
Zahra
Meshkat
0000-0002-4032-7599
Antimicrobial Resistance Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
meshkatz@mums.ac.ir
10.22038/ijbms.2016.7349
Chronic hepatitis B is still a major public health issue despite the successful prophylactic vaccination attempts. Chronicity of hepatitis B virus(HBV) is mainly due to its ability to debilitate host's immune system. Therefore, major measures have been taken to stop this process and help patients with chronic hepatitis B infection recover from their illness. While satisfactory results have been achieved using preventive HBV vaccines, a reliable and effective therapeutic treatment is still in need of extensive studies. Current treatments for chronic hepatitis B include direct antiviral agents and nucleoside/nucleotide analogs, which are not always effective and are also costly. In addition, due to the fact that chronic HBV is responsible for debilitation of the immune system, studies have focused on developing therapeutic vaccines to help host's immune system recover and limit the infection. Several approaches including but not restricted to recombinant peptide-based, DNA-based, viral vector-based, and cell-based approaches are currently in use to develop therapeutic vaccines against the chronic form of HBV infection. In the current review, the authors will first discuss the role of the immune system in chronic hepatitis B infection and will then focus on latest advancements in therapeutic vaccination of HBV especially the clinical trials that have been carried out so far.
Chronic hepatitis B virus-infection,HBV,Therapeutic vaccine
https://ijbms.mums.ac.ir/article_7349.html
https://ijbms.mums.ac.ir/article_7349_c8c973542e628541e3eaada4ca746a0b.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
Chloride channel protein 2 prevents glutamate-induced apoptosis in retinal ganglion cells
705
711
EN
Miao-Miao
Bi
Department of Ophthalmology, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, 130041, P.R. China
bimiaomiao1981@sohu.com
Sen
Hong
Department of Colon and Anal Surgery, the First hospital of Jilin University, Jilin University, Changchun, Jilin, 130021, P.R. China
86943587@qq.com
Ling-Jun
Ma
Department of Ophthalmology, The China-Japan Union Hospitial of Jilin University, Jilin University, Changchun, Jilin, 130033, Xiantai Street No. 126, Jilin Province, China
1299430898@qq.com
Hong-Yan
Zhou
Department of Ophthalmology, The China-Japan Union Hospitial of Jilin University, Jilin University, Changchun, Jilin, 130033, Xiantai Street No. 126, Jilin Province, China
zhouhongyan7301@sina.com
Jia
Lu
Department of Ophthalmology, The China-Japan Union Hospitial of Jilin University, Jilin University, Changchun, Jilin, 130033, Xiantai Street No. 126, Jilin Province, China
lujia@126.com
Jing
Zhao
Department of Ophthalmology, The China-Japan Union Hospitial of Jilin University, Jilin University, Changchun, Jilin, 130033, Xiantai Street No. 126, Jilin Province, China
jingzhg@yeah.net
Ya-Juan
Zheng
Department of Ophthalmology, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, 130041, P.R. China
zhengyajuan124@sina.com
10.22038/ijbms.2016.7351
<strong><em>Objective(s):</em></strong> The purpose of this study was to investigate the role of chloride channel protein 2 (ClC-2) in glutamate-induced apoptosis in the retinal ganglion cell line (RGC-5).
<strong><em>Materials and Methods: </em></strong>RGC-5 cells were treated with 1 mM glutamate for 24 hr. The expression of ClC-2, Bax, and Bcl-2 was detected by western blot analysis. Cell survival and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Caspase-3 and -9 activities were determined by a colorimetric assay. The roles of ClC-2 in glutamate-induced apoptosis were examined by using ClC-2 complementary deoxyribonucleic acid (cDNA) and small inference ribonucleic acid (RNA) transfection technology.
<strong><em>Results:</em></strong> Overexpression of ClC-2 in RGC-5 cells significantly decreased glutamate-induced apoptosis and increased cell viability, whereas silencing of ClC-2 with short hairpin (sh) RNA produced opposite effects. ClC-2 overexpression increased the expression of Bcl-2, decreased the expression of Bax, and decreased caspase-3 and -9 activation in RGC-5 cells treated with glutamate, but silencing of ClC-2 produced opposite effects.
<strong><em>Conclusion:</em></strong> Our data suggest that ClC-2 chloride channels might play a protective role in glutamate-induced apoptosis in retinal ganglion cells via the mitochondria-dependent apoptosis pathway.
Apoptosis,Chloride channels,Chloride channel protein 2 Neuroprotection,Retinal ganglion cells
https://ijbms.mums.ac.ir/article_7351.html
https://ijbms.mums.ac.ir/article_7351_dcb4fcc962af55efa7e1ce2bdce6db24.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
Toxicological evaluation of subchronic use of pioglitazone in mice
712
719
EN
Said
Said Elshama
Department of Forensic Medicine and Clinical Toxicology, College of Medicine, Taif University, Suez Canal University, Taif, KSA
Ayman El-Meghawry
El-Kenawy
Department of Pathology, College of Medicine, Taif University, Taif, KSA
elkenawyay@yahoo.com
Hosam-Eldin
Hussein Osman
Department of Anatomy, College of Medicine, Taif University, Al-Azhar University, Taif, KSA
10.22038/ijbms.2016.7353
<strong><em>Objective(s):</em></strong> Pioglitazone (Actos) is one of the most controversial recent oral antidiabetic drugs. It was originally authorized in the European Union in 2000, and approved as an oral monotherapy for overweight second type of diabetic patients in 2002. It belongs to the thiazolidinedione group which some of its members have been withdrawn from the market due to the hepatotoxicity or cardiotoxicity effects.This studyinvestigates sub-chronic use of pioglitazone induced toxicity in mice by the assessment of renal and liver function tests, cardiac enzymes, and some hematological indices with histological changes of liver, kidney, heart, and bladder. <br/><strong><em>Materials and Methods: </em></strong>120 albino mice were divided into four groups; 30 in each. The first group (control) received water, second (diabetic) group received alloxan only, while the third and the fourth groups received alloxan with 200 and 400 mg/kg/day of pioglitazone, respectively for 90 days. <br/><strong><em>Results:</em></strong> Prolonged use of pioglitazone induced significant abnormalities of hepatic, renal, and cardiac biomarkers and some hematological indices associated with histopathological changes in the liver, kidney, heart, and bladder that increased based on administered dose. <br/><strong><em>Conclusion:</em></strong> Subchronic use of pioglitazone leads to hepatic, renal, cardiac, hematological, and bladder affection depending on the applied dose.
Mice,Pioglitazone,Sub-chronic use,Toxicity
https://ijbms.mums.ac.ir/article_7353.html
https://ijbms.mums.ac.ir/article_7353_72ff114cff1e18c59ee0a5f039e3cee3.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
C-Kit expression in the gallbladder of guinea pig with chronic calculous cholecystitis and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal
720
725
EN
Hua
Feng
Department of General Surgery, First Affiliated Hospital, Dalian Medical University, Dalian 116000, China
hengguoa@yeah.net
Fang
Wang
Department of Physical Examination, First Affiliated Hospital, Dalian Medical University, Dalian 116000, China
rulinma@yeah.net
Changmiao
Wang
Department of General Surgery, First Affiliated Hospital, Dalian Medical University, Dalian 116000, China
changmiaowang@yeah.net
10.22038/ijbms.2016.7354
<strong><em>Objective(s):</em></strong> To study the c-Kit expression in the <em>gallbladder of </em>cholesterol lithogenic<em> guinea pig model and the effect of </em><em>Artemisia</em><em> </em><em>capillaris</em><em> </em>Thunb on interstitial cells of Cajal (ICCs). <br/><strong><em>Materials and Methods:</em></strong>A total of 45 guinea pigs were randomly assigned into three groups: the control group (guinea pigs fed a standard diet, normal group); the model group (guinea pigs fed a cholesterol gallstone-inducing diet); and the Chinese medicine group (guinea pigs fed the cholesterol gallstone-inducing diet and treated with <em>A.</em><em> </em><em>capillaris</em> through intragastric administration, therapy group). Each group had 15 guinea pigs. The g<em>allbladders of the guinea pigs were harvested after 8 weeks. C-Kit expression was detected using an immunohistochemistry </em><em>staining</em><em>, real-time PCR, and Western blot analyses</em><em>. The </em>effect of <em>A. capillaris</em> on ICCs was evaluated by muscle strip contraction experiments. <br/><strong><em>Results:</em></strong><em> C-Kit expression significantly decreased in the gallbladder of model group, but increased in the Chinese medicine group. </em>The Contractility of guinea pig gallbladder muscle strip significantly improved in the Chinese medicine group. <br/><strong><em>Conclusion:</em></strong><em> Our results indicated that </em><em>A.</em><em> </em><em>capillaris </em>improves gallbladder impairment by up-regulating c-Kit expression, and it also can improve the contractile response of <em>in vitro</em> guinea pig gallbladder muscle strips.
Artemisia capillaries Thunb,C-Kit,Gallstone,Interstitial cells of Cajal
https://ijbms.mums.ac.ir/article_7354.html
https://ijbms.mums.ac.ir/article_7354_7a8234e723b45780d6743cd1887c2730.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
Loss of heterozygosity and microsatellite instability as predictive markers among Iranian esophageal cancer patients
726
733
EN
Mohammad Mahdi
Forghanifard
0000-0002-7691-6897
Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
forghanifard@gmail.com
Elham
Emami Vahid
Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
Ezzat
Dadkhah
School of Systems Biology, George Mason University, Manassas, Virginia, U.S.A
dadkhah_k@yahoo.com
Mehran
Gholamin
Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
golaminm@mums.ac.ir
Samaneh
Broumand Noghabi
Department of hematopathology, Central Laboratory, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Martha
Ghahraman
Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
magh742002@yahoo.com
Mehdi
Farzadnia
Cancer Molecular Pathology Research Center, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
farzaniam@mums.ac.ir
Mohammad Reza
Abbaszadegan
Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
abbaszadegan@ams.ac.ir
10.22038/ijbms.2016.7356
<strong><em>Objective(s):</em></strong> Variation in microsatellite sequences that are dispersed in the genome has been linked to a deficiency in cellular mismatch repair system and defects in several genes of this system are involved in carcinogenesis. Our aim in this study was to illustrate microsatellite DNA alteration in esophageal cancer. <br/><strong><em>Materials and Methods:</em></strong> DNA was extracted from formalin fixed paraffin embedded (FFPE) tissues from surgical and matched margin-normal samples. Microsatellite instability (MSI) and loss of heterozygosity (LOH) were studied in 50 cases of esophageal squamous cell carcinoma (ESCC) by amplifying six microsatellite markers: D13S260 (13q12.3), D13S267 (13q12.3), D9S171 (9p21), D2S123 (2p), D5S2501 (5q21) and TP53 (17p13.1) analyzed on 6% denaturing polyacrylamide gel electrophoresis. <br/><strong><em>Results:</em></strong> Statistical analysis indicated a near significant reverse correlation between grade and LOH (<em>P</em>= 0.068, correlation coefficient= -0.272). Specifically, increased LOH in tumor DNA has a significant correlation with increased differentiation from poorly differentiated to well differentiated tumors (<em>P</em>= 0.002 and <em>P</em>= 0.016 respectively). In addition, higher number of chromosomal loci with LOH showed a reverse correlation with lymph node metastasis (<em>P</em>= 0.026, correlation coefficient= -0.485). Furthermore, there was a positive correlation between addiction and MSI (<em>P</em>= 0.026, correlation coefficient= 0.465). <br/><strong><em>Conclusion: </em></strong>Microsatellite DNA alterations may be a prognostic tool for detection and the evolution of prognosis in patients with SCC of esophagus. It can be concluded that regional lymph node metastasis would be less likely with increased heterozygote loci and addiction with any of opium, cigarette, water pipe or alcohol can be a susceptibility factor(s) for MSI.
Esophageal squamous cell -carcinoma,Loss of heterozygosity,Microsatellite instability
https://ijbms.mums.ac.ir/article_7356.html
https://ijbms.mums.ac.ir/article_7356_09e6f16f2c5afde2adc9d97dfc5c4f02.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
Repairing effects of interleukin 11 (IL-11) towards high dose methotrexate-induced rat small intestinal mucositis and its impacts on T-lymphoblastic leukemia cell line
734
740
EN
Yueqin
Han
Department of Pediatrics, Liaocheng People's Hospital, Liaocheng 252000, Shandong, China
yanpingzhua@126.com
Yanping
Zhu
Department of Pediatrics, Liaocheng People's Hospital, Liaocheng 252000, Shandong, China
xinyuadf@126.com
Jinshen
Wang
Department of Pediatrics, Liaocheng People's Hospital, Liaocheng 252000, Shandong, China
jinshenwang@yeah.net
Yanqin
Han
Departments of Pharmacy, the Fourth People's Hospital of Liaocheng, Liaocheng 252000, Shandong, China
ziminliu@yeah.net
Daogang
Qin
Department of Pediatrics, Liaocheng People's Hospital, Liaocheng 252000, Shandong, China
aiqinsong@yeah.net
Qiaozhi
Yang
Department of Pediatrics, Liaocheng People's Hospital, Liaocheng 252000, Shandong, China
ningliua@yeah.net
Xiaojing
Sun
Department of Pediatrics, Liaocheng People's Hospital, Liaocheng 252000, Shandong, China
haowangaa@yeah.net
Lijun
Chen
Department of Pediatrics, Shandong Province-owned Hospital, Jinan 250021, Shandong, China
hongyudf@126.com
10.22038/ijbms.2016.7357
Objective(s): To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. <br/>Materials and Methods: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E). After the intraperitoneal injection of MTX in the groups B-E, the rats were sacrificed at 1, 3, 5 and 7 days. The mortality, morphological and ultrastructural changes of small intestine of each group were observed. The cells were then cultured in vitro, and the MTT method was used to investigate the effects of different concentration of IL-11 on CEM proliferation and also on HDMTX-induced mucositis. <br/>Results: IL-11 could reduce the intestinal histopathological score, increase the height of small intestinal villi, promote the proliferation of intestinal lacunar cells and reduce the mortality rate of rats. The IL-11 pre-treatment group exhibited the best efficacies, demonstrating significant difference with the control group (P<0.01). In addition, the proliferation of CEM was not promoted, indicating that IL-11 could not inhibit HDMTX. <br/>Conclusion: IL-11 could reduce the severity of HDMTX-induced intestinal mucositis, and improve the survival rate of experimental rats, and could be safely used as the adjuvant treatment of HDMTX in childhood leukemia.
CEM cell line,Interleukin 11,Methotrexate,Mucositis
https://ijbms.mums.ac.ir/article_7357.html
https://ijbms.mums.ac.ir/article_7357_55c1e22930694a0c1351b4d53e0854a7.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
Mesenchymal stem cells that located in the electromagnetic fields improves rat model of Parkinson's disease
741
748
EN
Majid
Jadidi
0000-0001-6892-7695
Department of Medical Physics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
jadidim@semums.ac.ir
Saeed
Moghadas Biat
Research Center of Nervous System Stem Cells, Department of Anatomy, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
Hamid Reza
Sameni
Research Center of Nervous System Stem Cells, Department of Anatomy, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
Manouchehr
Safari
Research Center of Nervous System Stem Cells, Department of Anatomy, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
m.safari@semums.ac.ir
Abbas Ali
Vafaei
0000-0003-1178-3787
Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
aavaf43@yahoo.com
Laya
Ghahari
0000-0003-3946-8965
Department of Anatomy, School of Medicine, AJA Medical University, Tehran, Iran
drghahari.laya@gmail.com
10.22038/ijbms.2016.7358
<strong><em>Objective(s):</em></strong> The main characteristic of mesenchymal stem cells (MSCs) is their ability to produce other cell types. Electromagnetic field (EMF) stimulates differentiation of MSCs into other cells. In this study, we investigated whether EMF can effect on the differentiation of MSCs into dopaminergic (DA) neurons. <br/><strong><em>Materials and Methods:</em></strong> An EMF with a frequency of 50 Hz and two intensities of 40 and 400 µT 1hr/day was generated around the cells for a week. Afterwards, these cells were injected into the left ventricle of Parkinsonian rats. The rats survived for 2 weeks, and then sampling was performed. <br/><strong><em>Results:</em></strong> The injected cells differentiated into DA neurons and sporadically settled in the substantia nigra pars compacta (SNpc). Transplanted rats exhibited significant partial correction apomorphine-induced rotational behavior compared to Parkinsonian rats (5.0±0.1 vs 7.57±0.08). Results demonstrated that endogenous serum and brain derived neurotrophic factor (BDNF) were altered in all experimental groups. The greatest increase was in group of 400 µT EMF in comparison with Parkinsonian rats (398±15 vs. 312±11.79 pg ⁄ mg). Current study have shown that 6-Hydroxydopamine can cause severe loss of dopaminergic neurons (68±6.58), but injected MSCs that exposed to 40 and 400 µT EMF increased dopaminergic neurons in SNpc ( 108±2.33 & 126±3.89) (<em>P<</em>0.001). <br/><strong><em>Conclusion:</em></strong> Electromagnetic fields with particular frequencies stimulate MSCs. So, these cells had anti-Parkinsonian properties in our studies.
Dopaminergic neuron,Electromagnetic Field,Mesenchymal stem cells,Parkinson’s disease
https://ijbms.mums.ac.ir/article_7358.html
https://ijbms.mums.ac.ir/article_7358_2eae75e9bb96b343a7bf8de4579c873c.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
Antioxidant properties of repaglinide and its protections against cyclosporine A-induced renal tubular injury
749
754
EN
Dao
Li
Department of Pharmacology, City College, Wuhan University of Science and Technology, Wuhan, China
49804957@qq.com
Jin
Li
Department of Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, China
pearli1980@126.com
Hui
Li
Department of Pharmacology, City College, Wuhan University of Science and Technology, Wuhan, China
270888114@qq.com
Qiong
Wu
Department of Pharmacology, City College, Wuhan University of Science and Technology, Wuhan, China
43804792@qq.com
Qi-Xiong
Li
0000-0002-1484-8016
Department of Pharmacology, City College, Wuhan University of Science and Technology, Wuhan, China
1015563065@qq.com
10.22038/ijbms.2016.7360
<strong><em>Objective(s):</em></strong> Repaglinide (RG) is an antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus. It has a good safety and efficacy profile in diabetic patients with complications in renal impairment and is an appropriate treatment choice, even for individuals with more severe degrees of renal malfunctions. The aim of the present study was to examine the protective effect of RG on cyclosporine A (CsA)-induced rat renal impairment and to evaluate the antioxidant mechanisms by which RG exerts its protective actions. <br/><strong><em>Materials and Methods:</em></strong> Fifty male Sprague-Dawley rats weighing 250–300 g were randomly divided into five groups: administrations of olive oil (control, PO), RG (0.4 mg/kg, PO), CsA (30 mg/kg in olive oil, SC), RG (0.2 or 0.4 mg/kg, PO) plus CsA (30 mg/kg in olive oil SC) every day for 15 days. <br/><strong><em>Results:</em></strong> SC administration of CsA (30 mg/kg) to rats produced marked elevations in the levels of renal impairment parameters such as urinary protein, N-acetyl-beta-D-glucosaminidase (NAG), serum creatinine (SCr),and blood urea nitrogen (BUN). It also caused histologic injury to the kidneys. Oral administration of RG (0.2 and 0.4 mg/kg) markedly decreased all the aforementioned changes. In addition, CsA caused increases in the levels of malondialdehyde (MDA) and decreases in superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSR), glutathione-S-transferase (GST), and glutathione in kidney homogenate, which were reversed significantly by both doses of RG. <br/><strong><em>Conclusion:</em></strong> The findings of our study indicate that RG may play an important role in protecting the kidney from oxidative insult.
Cyclosporine A-induced renal tubular injury,Glutathione expression rat,Repaglinide antioxidant
https://ijbms.mums.ac.ir/article_7360.html
https://ijbms.mums.ac.ir/article_7360_e35910593191f509c449c149ec023cba.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
Methylation and mRNA expression levels of P15, death-associated protein kinase, and suppressor of cytokine signaling-1 genes in multiple myeloma
755
762
EN
Lin
Liu
Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China
30659757@qq.com
Lin
Tan
Department of Hematology, The First Affiliated Hospital of Kunming Medical University, Kunming 650041, China
tanlinz@126.com
Zhenxin
He
Department of Hematology, The First Affiliated Hospital of Kunming Medical University, Kunming 650041, China
hezxin@yeah.net
10.22038/ijbms.2016.7361
<strong><em>Objective(s):</em></strong> The aim of this study was to investigate the methylation status and mRNA expression levels of P<sub>15</sub>, death-associated protein kinase (DAPK), and suppressor of cytokine signaling-1 (SOCS<sub>1</sub>) genes in multiple myeloma (MM). <br/><strong><em>Materials and Methods:</em></strong> The bone marrow samples of 54 MM patients were collected and the methylation status of the P<sub>15</sub>, DAPK, and SOCS<sub>1</sub> gene promoter regions was determined by methylation-specific polymerase chain reaction. Automated sequencing technology was used to sequence the amplified products in order to analyze the base methylation sites. mRNA expression levels were determined using real-time fluorescent quantitative polymerase chain reaction . <br/><strong><em>Results:</em></strong> Among the 54 MM patients, the positive methylation rates of the P<sub>15</sub>, DAPK, and SOCS<sub>1</sub> genes were 27.78%, 18.52%, and 16.67%, respectively. The methylation results were confirmed by sequencing. The positive methylation rates of the P<sub>15</sub>, DAPK, and SOCS<sub>1</sub> genes showed no correlation with patient gender, age, typing, staging, and grouping (<em>P</em>>0.05). There was no significant difference in the mRNA expression levels of the P<sub>15</sub>, DAPK, and SOCS<sub>1</sub> genes between the MM patient group and the control group (<em>P</em>>0.05). <br/><strong><em>Conclusions:</em></strong> Aberrant methylation of the P<sub>15</sub>, DAPK, and SOCS<sub>1</sub> genes exists in MM, and these genes may play certain roles in pathogenesis of MM. There was no significant difference in mRNA expression levels between the methylated group and the non-methylated group, suggesting that these genes are regulated by other mechanisms during their transcription.
DAPK gene,DNA methylation,Multiple Myeloma,P15 gene,SOCS1 gene
https://ijbms.mums.ac.ir/article_7361.html
https://ijbms.mums.ac.ir/article_7361_9bf5b2ee1bef7e8fe5983f30d8b8e282.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
Acute stress does not affect the impairing effect of chronic stress on memory retrieval
763
771
EN
Jamile
Ozbaki
School of Biology, Damghan University, Damghan, Iran
j_ozbaki@yahoo.com
Iran
Goudarzi
0000-0002-6665-3202
School of Biology, Damghan University, Damghan, Iran
irangoudarzi@du.ac.ir
Mahmoud
Elahdadi Salmani
0000-0001-5237-3958
School of Biology, Damghan University, Damghan, Iran
elahdadi@du.ac.ir
Ali
Rashidy-Pour
Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
rashidy-pour@semums.ac.ir
10.22038/ijbms.2016.7362
<strong><em>Objective(s):</em></strong> Due to the prevalence and pervasiveness of stress in modern life and exposure to both chronic and acute stresses, it is not clear whether prior exposure to chronic stress can influence the impairing effects of acute stress on memory retrieval. This issue was tested in this study. <br/><strong><em>Materials and Methods: </em></strong>Adult male Wistar rats were randomly assigned to the following groups: control, acute, chronic, and chronic + acute stress groups. The rats were trained with six trials per day for 6 consecutive days in the water maze. Following training, the rats were either kept in control conditions or exposed to chronic stress in a restrainer 6 hr/day for 21 days. On day 22, a probe test was done to measure memory retention. Time spent in target and opposite areas, platform location latency, and proximity were used as indices of memory retention. To induce acute stress, 30 min before the probe test, animals received a mild footshock. <br/><strong><em>Results: </em></strong>Stressed animals spent significantly less time in the target quadrant and more time in the opposite quadrant than control animals. Moreover, the stressed animals showed significantly increased platform location latency and proximity as compared with control animals. No significant differences were found in these measures among stress exposure groups. Finally, both chronic and acute stress significantly increased corticosterone levels. <br/><strong><em>Conclusion: </em></strong>Our results indicate that both chronic and acute stress impair memory retrieval similarly. Additionally, the impairing effects of chronic stress on memory retrieval were not influenced by acute stress.
Acute stress,Chronic stress,Morris Water Maze,Rat,Spatial memory retrieval
https://ijbms.mums.ac.ir/article_7362.html
https://ijbms.mums.ac.ir/article_7362_17f8ed4b6be3f47444ff7e468487e1ec.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
Screening of DFNB3 in Iranian families with autosomal recessive non-syndromic hearing loss reveals a novel pathogenic mutation in the MyTh4 domain of the MYO15A gene in a linked family
772
778
EN
Somayeh
Reiisi
Department of Genetics, Faculty of Basic Sciences, University of Shahrekord, Shahrekord, Iran
reiisi@yahoo.com
Mohammad Amin
Tabatabaiefar
Medical Genetics Dept., Isfahan University of Medical Sciences, Medical Genetics Dept., National Institute of Genetic Engineering and Biotechnology (NIGEB), Isfahan, Iran
bioinfo2003@ajums.ac.ir
Mohammad Hosein
Sanati
Medical Genetics Dept., National Institute of Genetic Engineering and Biotechnology (NIGEB)
Morteza
Hashemzadeh Chaleshtori
Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
mchaleshtori@yahoo.com
10.22038/ijbms.2016.7363
Objective(s): Non-syndromic sensorineural hearing loss (NSHL) is a common disorder affecting approximately 1 in 500 newborns. This type of hearing loss is extremely heterogeneous and includes over 100 loci. Mutations in the GJB2 gene have been implicated in about half of autosomal recessive NSHL (ARNSHL) cases, making this the most common cause of ARNSHL. For the latter form of deafness, most frequent genes proposed include GJB2, SLC26A4, MYO15A, OTOF, and CDH23 worldwide. <br/>Materials and Methods: the aim of the present study was to determine the role of MYO15A gene mutations in Iranian families. Thirty Iranian families with over three deaf children and negative for GJB2 using genetic linkage analysis (GLA), followed by mutation screening by DNA sequencing were enrolled. <br/>Results: One family (3.33%) showed linkage to DFNB3 and a novel mutation was identified in the MYO15A gene (c.6442T>A) as the disease-causing mutation. Mutation co-segregated with hearing loss in the family but was not present in the 100 ethnicity-matched controls. <br/>Conclusion: Our results confirmed that the hearing loss of the linked Iranian family was caused by a novel missense mutation in the MYO15A gene. This mutation is the first to be reported in the world and affects the first MyTH4 domain of the protein.
Hearing Loss,Iran,Linkage analysis,MYO15A,Mutation
https://ijbms.mums.ac.ir/article_7363.html
https://ijbms.mums.ac.ir/article_7363_1cee96cbc2302edcc7811babbe37fdfe.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells
779
786
EN
Marie
Saghaeian Jazi
0000-0003-0647-9545
Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran
marie.saghaeian@yahoo.com
Saeed
Mohammadi
0000-0001-9895-8468
Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran
s.mohammadi@goums.ac.ir
Yaghoub
Yazdani
Infectious Diseases Research Center and Laboratory Science Research Center, Golestan University of Medical Sciences, Gorgan, Iran
yazdani@goums.ac.ir
Sima
Sedighi
Joint, Bone, and Connective tissue Research Center (JBCRC), Golestan University of Medical Sciences, Gorgan, Iran
Ali
Memarian
Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran
alimemarian@goums.ac.ir
Mehrdad
Aghaei
Joint, Bone, and Connective tissue Research Center (JBCRC), Golestan University of Medical Sciences, Gorgan, Iran
saeed.mohammadi6578@yahoo.com
10.22038/ijbms.2016.7364
<strong><em>Objective(s):</em></strong> T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor. Administration of chemical compounds influencing apoptosis and T cell development has been discussed as promising novel therapeutic strategies. Valproic acid (VPA) as a recently emerged anti-neoplastic histone deacetylase (HDAC) inhibitor and pioglitazone (PGZ) as a high-affinity peroxisome proliferator-activated receptor-gamma (PPARγ) agonist have been shown to induce apoptosis and cell cycle arrest in different studies. Here, we aimed to investigate the underlying molecular mechanisms involved in anti-proliferative effects of these compounds on human Jurkat cells. <br/><strong><em>Materials and Methods:</em></strong> Treated cells were evaluated for cell cycle progression and apoptosis using flowcytometry and MTT viability assay. Real-time RT-PCR was carried out to measure the alterations in key genes associated with cell death and cell cycle arrest. <br/><strong><em>Results</em></strong>: Our findings illustrated that both VPA and PGZ can inhibit Jurkat E6.1 cells <em>in vitro</em> after 24 hr; however, PGZ 400 μM presents the most anti-proliferative effect. Interestingly, treated cells have been arrested in G2/M with deregulated cell division cycle 25A (Cdc25A) phosphatase and cyclin-dependent kinase inhibitor 1B (CDKN1B or p27) expression. Expression of cyclin D1 gene was inhibited when DNA synthesis entry was declined. Cell cycle deregulation in PGZ and VPA-exposed cells generated an increase in the proportion of aneuploid cell population, which has not reported before. <br/><strong><em>Conclusion:</em></strong> These findings define that anti-proliferative effects of PGZ and VPA on Jurkat cell line are mediated by cell cycle deregulation. Thus, we suggest PGZ and VPA may relieve potential therapeutic application against apoptosis-resistant malignancies.
Pioglitazone,Proliferation,T-cell leukemia,Valproic acid
https://ijbms.mums.ac.ir/article_7364.html
https://ijbms.mums.ac.ir/article_7364_f26a238aaed8f3a1579682510a0d9c35.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
Inhibition of microRNA-21 decreases the invasiveness of fibroblast-like synoviocytes in rheumatoid arthritis via TGFβ/Smads signaling pathway
787
793
EN
Gaoxin
Xiong
Department of Orthopedics, The First People’s Hospital of Hefei, Hefei, Anhui 230001, P.R. China.
g_xiong_fphh@hotmail.com
Zhang
Huang
Department of Orthopedics, The First People’s Hospital of Hefei, Hefei, Anhui 230001, P.R. China.
zhang_huang_fphh@hotmail.com
Hua
Jiang
Department of Orthopedics, The First People’s Hospital of Hefei, Hefei, Anhui 230001, P.R. China.
hua_jiang_fphh@hotmail.com
Zhengjun
Pan
Department of Orthopedics, The First People’s Hospital of Hefei, Hefei, Anhui 230001, P.R. China.
zh_pan_fphh@hotmail.com
Jie
Xie
Department of Orthopedics, The First People’s Hospital of Hefei, Hefei, Anhui 230001, P.R. China.
jie_xie_fphh@hotmail.com
Shuangli
Wang
Department of Orthopedics, The First People’s Hospital of Hefei, Hefei, Anhui 230001, P.R. China.
sh_wang_fphh@hotmail.com
10.22038/ijbms.2016.7365
<strong><em>Objective(s):</em></strong> MicroRNA-21 (miR<sub>21</sub>) is aberrantly elevated in rheumatoid arthritis (RA) patients, the significance of this microRNA in RA pathogenesis and treatment, however, has not been investigated. In this study, by using RA-derived fibroblast-like synoviocyte (FLS) cells as a model, we investigated the effect and corresponding mechanism of miR<sub>21</sub> inhibition on FLSs invasion. <br/><strong><em>Materials and Methods</em></strong><strong><em>:</em></strong>miR<sub>21</sub> expression in synovial tissue and FLSs in RA patients and non-RA controls were determined by stem-loop RT-PCR. The effect of miR<sub>21</sub> on FLSs viability and invasiveness were evaluated using miR<sub>21</sub> inhibition. Cell viability was evaluated by MTT assay and the expression of genes at mRNA and protein levels was determined by RT-PCR and Western blot, respectively. <br/><strong><em>Results:</em></strong> Our results showed that miR<sub>21</sub> expression was highly increased in synovial tissue and FLSs in RA patients. Also, we reported that miR<sub>21</sub> inhibitor treatment could significantly suppress the invasiveness of FLSs without affecting cell viability. The decreased FLSs invasion by miR<sub>21</sub> inhibition was associated with down-regulated expression of matrix metalloproteinase (MMP)-1, MMP<sub>3</sub>, and MMP<sub>13</sub>. Further analysis revealed that miR<sub>21</sub> inhibition could suppress the expression of TGF<sub>β1</sub> and Smad<sub>4,</sub> but promote that of Smad<sub>7</sub>. Moreover, suppression of FLS invasion and MMPs expression by miR<sub>21</sub> treatment could be counteracted by additional TGF<sub>β1</sub> treatment. <br/><strong><em>Conclusion</em></strong><strong><em>:</em></strong>Our results indicated that miR<sub>21</sub> inhibition can down-regulate the expression of MMP<sub>1</sub>, MMP<sub>3</sub>, and MMP<sub>13</sub> and consequently suppress the invasiveness of FLS, which is achieved through TGF<sub>β1</sub>/Smad<sub>4/7 </sub>signaling pathway. The findings of this study could offer a novel approach for RA treatment.
Fibroblast-like synoviocyte,Invasion,MicroRNA-21,Rheumatoid arthritis,Smads,Transforming growth factor-beta
https://ijbms.mums.ac.ir/article_7365.html
https://ijbms.mums.ac.ir/article_7365_5624de3e9d54627200c0862e0fc53b44.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
Immune cell distribution and immunoglobulin levels change following sciatic nerve injury in a rat model
794
799
EN
Wei
Yuan
Department of Spine Surgery, Aviation General Hospital of China Medical University, Beijing Institute of Translational Medicine, Chinese Academy of Sciences, No. 3 Anwai beiyuan Road, Chaoyang District, Beijing, 100012, China
2000ywei@sina.com
Xinhong
Feng
Department of Neurology, Beijing Tsinghua Changgung Hospital Medical Center, Tsinghua University, No. 168 Li Tang Rd. Dongxiaokou Town, Tiantongyuan Area, Changping District, Beijing, 102218, China
docyw1977@yahoo.com
10.22038/ijbms.2016.7366
<strong><em>Objective(s):</em></strong> To investigate the systemic and local immune status of two surgical rat models of sciatic nerve injury, a crushed sciatic nerve, and a sciatic nerve transection <br/><strong><em>Materials and Methods:</em></strong>Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group), sciatic nerve crush, and sciatic nerve transaction. Sciatic nerve surgery was performed. The percentage of CD4<sup>+</sup> cells and the CD4<sup>+</sup>/CD8+ratio were determined by flow cytometry. Serum IgM and IgG levels were analyzed by ELISA. T-cells (CD3) and macrophages (CD68) in sciatic nerve tissue sections were identified through immunohistochemistry. <br/><strong><em>Results: </em></strong>Compared to sham-operated controls, in rats that underwent nerve injury, the percentage of CD4<sup>+</sup> cells and the CD4<sup>+</sup>/CD8<sup>+</sup> ratio in the peripheral blood were significantly decreased 7 days after surgery, serum IgM levels were increased 14 days after surgery, and serum IgG levels were increased 21 days after surgery. There were a large number of CD3<sup>+</sup> cells and a small number of CD68<sup>+</sup> cells in sciatic nerve tissue sections 21 days after surgery, indicating T-cell and macrophage activation and infiltration. Local IgG deposition was also detected at the nerve injury site 21 days after surgery. <br/><strong><em>Conclusion:</em></strong> Rat humoral and cellular immune status changed following sciatic nerve injury, particularly with regard to the cellular immune response at the nerve injury site.
Immune status,Nerve regeneration,Nerve repair,Sciatic nerve injury
https://ijbms.mums.ac.ir/article_7366.html
https://ijbms.mums.ac.ir/article_7366_48f6f6443efd50d157fbe0751a1954db.pdf
Mashhad University of Medical Sciences
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3874
19
7
2016
07
01
Effect of mobile phone radiation on pentylenetetrazole-induced seizure threshold in mice
800
803
EN
Ebrahim
Kouchaki
Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran
Morteza
Motaghedifard
Department of Neurology, Kashan University of Medical Sciences, Kashan, Iran
motaghedi.morteza@gmail.com
Hamid Reza
Banafshe
Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran
banafshe-h@kums.ac.ir
10.22038/ijbms.2016.7367
<strong><em>Objective(s):</em></strong> Scientific interest in potential mobile phone impact on human brain and performance has significantly increased in recent years. The present study was designed to evaluate the effects of mobile phone radiation on seizure threshold in mice. <br/><strong><em>Materials and methods:</em></strong>BALB/c male mice were randomly divided into three groups: control, acute, and chronic mobile phone radiation for 30, 60, and 90 min with frequency 900 to 950 MHz and pulse of 217 Hz. The chronic group received 30 days of radiation, while the acute group received only once. The intravenous infusion of pentylenetetrazole (5 mg/ml) was used to induce seizure signs. <br/><strong><em>Results:</em></strong> Although acute mobile radiation did not change seizure threshold, chronic radiation decreased the clonic and tonic seizure thresholds significantly. <br/><strong><em>Conclusion:</em></strong> Our data suggests that thecontinued and prolonged contact with the mobile phone radiation might increase the risk of seizure attacks and should be limited.
Mice,Mobile phone radiation,Pentylenetetrazole,Seizure
https://ijbms.mums.ac.ir/article_7367.html
https://ijbms.mums.ac.ir/article_7367_366f5c2809ee4fcb65dbe788baa8cf95.pdf