An overview of glucagon-like peptide-1 receptor agonists for the treatment of metabolic syndrome: A drug repositioning
Maryam
Rameshrad
Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
author
Bibi Marjan
Razavi
Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
author
Jean-Daniel
Lalau
Université de Picardie Jules Verne, Department of Endocrinology, Amiens, France
author
Marc E.
De Broe
Universiteit Antwerpen, Department of Biomedical Sciences, Antwerpen, Belgium
author
Hossein
Hosseinzadeh
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
author
text
article
2020
eng
Metabolic syndrome (MetS) is a clustering of several cardiovascular risk factors that include: obesity, dyslipidemia, hypertension and high blood glucose, and often requires multidrug pharmacological interventions. The management of MetS therefore requires high healthcare cost, and can result in poor drug treatment compliance. Hence drug therapies that have pleiotropic beneficial effects may be of value. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are the newest anti-diabetic drugs that mimic incretin effects in the body. They appear to be safe and well tolerable. Herein, the pharmacology of GLP-1RAs, their side effects, drug interactions and their effects in MetS is assessed. We conducted a Google Scholar, PubMed, Scopus, and Web of Science search since 2010 to identify publications related to the use of GLP-1RAs in treating component features of the MetS. Keywords used for the search were: GLP-1 receptor agonist, exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, MetS, obesity, triglyceride, cholesterol, lipid, hypercholesterolemia hyperlipidemia, atherosclerosis, hypertension, blood pressure, hyperglycemia, hypoglycemia and blood glucose. According to the gathered data, GLP-1RAs appear safe and well tolerated. Pre-clinical and clinical studies have evaluated the lipid-lowering, anti-atherosclerotic, anti-hypertensive and anti-diabetic effects of this class of drugs. Some these effects are related to a reduction in food-seeking behavior, an increase in atrial natriuretic peptide level and hence vascular relaxation and natriuresis, and an increase of pancreas β-cell mass and protection against glucotoxicity. Collectively, this review indicates that there may be some value in GLP-1RAs repositioning to manage MetS risk factors beyond their anti-diabetic effects.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
556
568
https://ijbms.mums.ac.ir/article_15196_3dbabbd9eac6de56878a7b63c37d2bc2.pdf
dx.doi.org/10.22038/ijbms.2020.41638.9832
Evaluation of the anti-oxidant effect of ascorbic acid on apoptosis and proliferation of germinal epithelium cells of rat testis following malathion-induced toxicity
Faezeh
Ghorbani-Taherdehi
Department of Anatomy and Cell Biology, Mashhad University of Medical Sciences, Mashhad, Iran
author
Mohammad Reza
Nikravesh
Department of Anatomy and Cell Biology, Mashhad University of Medical Sciences, Mashhad, Iran
author
Mahdi
Jalali
Department of Anatomy and Cell Biology, Mashhad University of Medical Sciences, Mashhad, Iran
author
Alireza
Fazel
Microanatomy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
author
Mahmoud
Gorji Valokola
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
author
text
article
2020
eng
Objective(s): The aim of this study was to determine the protective role of ascorbic acid on apoptosis and proliferation of spermatogonia and primary spermatocyte cells after malathion administration as an organophosphate pesticide in rat testis.Materials and Methods: Thirty male Wistar rats were randomly divided into five groups of 6 rats each, including control (no intervention), sham (normal saline 0.09%), malathion (50 mg/kg), malathion plus ascorbic acid (50 mg/kg and 200 mg/kg, respectively), and ascorbic acid (200 mg/kg) groups. Malathion and ascorbic acid were administrated via intraperitoneal injection once per day and seven times per week. After 6 weeks, animals were sacrificed, and testis tissue was used for evaluation of apoptosis and proliferation of germinal epithelium cells using the TUNEL and PCNA staining techniques. Results: The results of TUNEL staining showed that the numbers of apoptotic cells in spermatogonia and primary spermatocyte cells were significantly increased in the malathion 50 mg/kg group vs control group (P<0.001). Co-administration of malathion 50 mg/kg and ascorbic acid 200 mg/kg significantly decreased the apoptotic cells in both cell types in comparison with malathion 50 mg/kg group (P<0.001). The results of PCNA staining revealed that the proliferation of these cells was significantly decreased in malathion 50 mg/kg group vs control group (P<0.001), and malathion 50 mg/kg plus ascorbic acid 200 mg/kg administration increased the proliferation of cells compared with malathion 50 mg/kg group (P<0.001).Conclusion: The results provide evidence that ascorbic acid showed preventive effects on malathion-induced toxicity in male rat testis.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
569
575
https://ijbms.mums.ac.ir/article_15197_a5800745ded60349e8efaa480e17158c.pdf
dx.doi.org/10.22038/ijbms.2020.35952.8608
Bisphenol-A analogue (bisphenol-S) exposure alters female reproductive tract and apoptosis/oxidative gene expression in blastocyst-derived cells
Alireza
Nourian
Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
author
Ali
Soleimanzadeh
Department of Theriogenology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
author
Ali
Shalizar Jalali
Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
author
GholamReza
Najafi
Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
author
text
article
2020
eng
Objective(s): One of the major endocrine-disrupting chemicals, Bisphenol-S (BPS) has replaced bisphenol-A due to public health anxiety. The present study evaluated low dosage BPS effect on female reproductive potential, hormonal disruption, and gene expression pathways of blastocyst-derived cells.Materials and Methods: NMRI female mice (5-6 weeks) in the estrous stage were chosen following vaginal smear examination for estrus cycle detection and BPS (0, 1, 5, 10, 50 and 100 µg/kg) was administrated subcutaneously for twenty-one consecutive days. After the last administration, blood, ovary tissue and oocytes were collected for further examination. Results: BPS induced oxidative stress in ovarian tissue and reduced hormonal status, LH and FSH, even at low concentration. Furthermore, apoptosis was induced in blastocyst derived cells in BPS administrated mice groups even at low BPS concertation, however, P53 and E2f1 expression were downregulated in doses more than 50 µg/kg, which might indicate apoptosis pathway exchange from P53 dependent to p53 independent pathways. IVF outcome was negatively associated with blastocyst apoptosis gene expression, estrogen receptor beta (ERβ) as well as oxidative status in ovaries. Finally, Stepwise regression indicated that E2f1, Nrf2, catalase (CAT), and Malondialdehyde (MDA) could be chosen as predictor values for hatch percentage in IVF outcome.Conclusion: In summary, this study revealed BPS might have detrimental potential in the female reproductive system by oxidation induction and hormonal alteration as well as next generation blastocyst derived cells apoptosis induction. Further studies are recommended for public health assurance of BPS safety especially for female consumed products.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
576
585
https://ijbms.mums.ac.ir/article_15209_f5d3e726ad3aca12dd35c16692bf0f69.pdf
dx.doi.org/10.22038/ijbms.2020.40893.9664
Prevalence of plasmid-encoded carbapenemases in multi-drug resistant Escherichia coli from patients with urinary tract infection in northern Iran
Mahshid
Deldar Abad Paskeh
University of Guilan, University Campus 2, Rasht, Iran
author
Mohammad Javad
Mehdipour Moghaddam
Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran
author
Zivar
Salehi
Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran
author
text
article
2020
eng
Objective(s): Resistance to carbapenems as the last line for controlling resistant bacteria is increasing due to production of carbapenemase. The aim of this study was to detect the plasmid-encoded carbapenemases using phenotypic methods and multiplex PCR among the multi-drug resistant (MDR) isolates from patients with urinary tract infection (UTI) in northern Iran.Materials and Methods: Antimicrobial susceptibility testing and extended spectrum β-lactamase (ESBL) production test were performed for 91 MDR Escherichia coli strains by disc diffusion and double disk synergy tests (DDST), respectively. Carbapenemases production was confirmed using Hodge test, EDTA double disk synergy test (EDST) and combined disk test (CDT). The isolates were subjected to PCR targeting blaIMP, blaVIM, blaKPC and blaOXA-48 β-Lactamase genes. Results: Resistance of isolates to 1st, 2nd, 3rd, and 4th generations of cephalosporins, carbapenems, and penicillins were 73%, 84.5%, 62%, 37.5%, 17.5%, and 76%, respectively. Based on CDT and Hodge test, 1 (3%) and based on EDST, 2 (6%) of 33 ESBL producers synthesize a type of carbapenemase. The frequency of blaIMP, blaVIM, blaKPC, and blaOXA-48 genes was 8.7%, 9.8%, 2.1%, and 15.3%, respectively. Existence of blaIMP conferred more resistance to cephalotin, fosfomycin, and piperacillin (P≤0.01) and carrying blaVIM caused more resistance to cephalotin, cefepime, and ceftazidime (P≤0.01). The presence of blaKPC conferred more resistance to cephalotin and presence of blaOXA-48 caused more resistance to chloramphenicol and piperacillin (P≤0.05).Conclusion: Identification and controlling of this nearly low frequent ESBL and carbapenemase producing strains are important due to the presence of plasmid genes encoding carbapenemase.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
586
593
https://ijbms.mums.ac.ir/article_14823_aa62e003e5035647aa1391317d12c769.pdf
dx.doi.org/10.22038/ijbms.2020.34563.8199
Effect of myricetin on the gene expressions of NOX3, TGF-β1, prestin, and HSP-70 and anti-oxidant activity in the cochlea of noise-exposed rats
Maryam
Bahaloo
Industrial Diseases Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
author
Mohammad Ebrahim
Rezvani
Department of Physiology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
author
Ehsan
Farashahi Yazd
Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
author
Fatemeh
Zare Mehrjerdi
Department of Physiology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
author
Mohammad Hossein
Davari
Department of Occupational Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
author
Ali
Roohbakhsh
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
author
Abolfazl
Mollasadeghi
Industrial Diseases Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
author
Haniyeh
Nikkhah
Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
author
Maryam
Vafaei
Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
author
Amir Houshang
Mehrparvar
Industrial Diseases Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
author
text
article
2020
eng
Objective(s): Noise-induced hearing loss is one of the most common occupational diseases in industrialized countries and can be affected by various environmental and genetic factors. This study was designed to examine the effect of myricetin in preventing this disorder.Materials and Methods: Twenty-one Wistar rats were randomly divided into five groups: Non-exposed, noise exposure only, noise exposure with vehicle, noise exposure with myricetin 5 mg/Kg, and noise exposure with myricetin 10 mg/kg. All animals were sacrificed after last noise exposure. The left cochlea was dissected from each rat. It was used for mRNA expression analysis (NOX3, TGF-β1, prestin, and HSP-70). Blood samples were collected to assess superoxide dismutase (SOD) activity, 1, 1 diphenyl picrylhydrazyl (DPPH), and malondialdehyde (MDA) measurements.Results: Real time-PCR assay revealed that noise decreased NOX3 and increased TGF-β1, prestin, and HSP-70 gene expressions. Administration of myricetin at the dose of 5 mg/kg, but not at 10 mg/kg, significantly reversed these changes. Noise also increased MDA levels and decreased SOD and DPPH scavenging activities. Myricetin at the doses of 5 and 10 mg/kg also reversed these changes. Conclusion: The findings of this study showed that myricetin at the dose of 5 mg/Kg was able to reverse noise-induced abnormalities in gene expression and oxidant/anti-oxidant balance. It is a possibility that myricetin via enhancement of anti-oxidant activity induced these effects.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
594
599
https://ijbms.mums.ac.ir/article_14789_5dee104a41771ca9a7a5b0c6173ec646.pdf
dx.doi.org/10.22038/ijbms.2020.41007.9693
Nos2 deficiency enhances carbon tetrachloride-induced liver injury in aged mice
Deming
Li
State Key Laboratory Cell Differentiation and Regulation
author
Yaping
Song
State Key Laboratory Cell Differentiation and Regulation
author
Yahao
Wang
State Key Laboratory Cell Differentiation and Regulation
author
Yuedong
Guo
State Key Laboratory Cell Differentiation and Regulation
author
Zhaoke
Zhang
State Key Laboratory Cell Differentiation and Regulation
author
Ganggang
Yang
State Key Laboratory Cell Differentiation and Regulation
author
Gaiping
Wang
State Key Laboratory Cell Differentiation and Regulation
author
Cunshuan
Xu
State Key Laboratory Cell Differentiation and Regulation
author
text
article
2020
eng
Objective(s): As a multifunctional molecule, NO has different effects on liver injury. The present work aimed to investigate the effects of Nos2 knockout (KO) on acute liver injury in aged mice treated with carbon tetrachloride (CCl4). Materials and Methods: The acute liver injury model was produced by CCl4 at 10 ml/kg body weight in 24-month-old Nos2 KO mice and wild type (WT) mice groups. The histological changes, transaminase and glutathione (GSH) contents, and the expressions of liver function genes superoxide dismutase (SOD2) and butyrylcholinesterase (BCHE), as well as apoptosis- and inflammation-associated genes were detected at 0, 6, 16, 20, 28, and 48 hr, respectively. Results: Compared with WT aged mice, there are more fat droplets in liver tissues of Nos2 KO aged mice, and the serum levels of ALT and AST were elevated in the KO group; in addition, there was a decrease in the expression of SOD2 and BCHE and GSH content at multiple time-points. Furthermore, the expression of apoptosis protein CASPASE-3 was elevated from 20 to 48 hr, the same as CASPASE-9 at 28 and 48 hr and pro-apoptotic protein BAX at 6 and 28 hr, while the expression of apoptosis inhibitory protein BCL2 declined at 6 and 28 hr; at the same time the mRNA expressions of genes related to inflammation were increased at different extents in liver extracts of Nos2 KO aged mice. Conclusion: Nos2 KO exacerbated liver injury probably by elevated oxidative stress, apoptosis and inflammation response in CCl4-induced aged mice liver intoxication model.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
600
605
https://ijbms.mums.ac.ir/article_15213_71c3f2c2aa3adf8f46f392f72dc77756.pdf
dx.doi.org/10.22038/ijbms.2020.39528.9380
Selegiline acts as neuroprotective agent against methamphetamine-prompted mood and cognitive related behavior and neurotoxicity in rats: Involvement of CREB/BDNF and Akt/GSK3 signal pathways
Saba
Feizipour
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University (IUAPS), Tehran, Iran
author
Sarvenaz
Sobhani
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
author
Shafagh
Mehrafza
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University (IUAPS), Tehran, Iran
author
Mina
Gholami
Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
author
Majid
Motaghinejad
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
author
Manijeh
Motevalian
Department of medicine, Qom branch, Islamic Azad University, Iran
author
Sepideh
Safari
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
author
Reza
Davoudizadeh
Department of medicine, Qom branch, Islamic Azad University, Iran
author
text
article
2020
eng
Objective(s): Present study investigated the neuroprotective effects of selegiline and the molecular mechanisms involved in methamphetamine-induced neurotoxicity.Materials and Methods: Male wistar rats were randomly divided into six groups (10 rats in each group). Group 1 and group 2 received normal saline and methamphetamine (10 mg/kg), respectively. Groups 3, 4, 5 and 6 were treated simultaneously with methamphetamine and selegiline. From day 22 to day 28, forced swim test, elevated plus maze, and open field test were conducted to assess mood (anxiety and depression) levels, and from day 17 to day 21, Morris Water Maze was conducted for cognition assessment. On day 29, hippocampus of the animals were isolated and evaluated by ELISA method for oxidative, antioxidant, and inflammatory factors and expression levels of active (total) and inactive (phosphorylated) forms of cyclic AMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), Akt (Protein Kinase B) and glycogen synthase kinase 3 (GSK3) proteins. Results: Selegiline reduced behavioral impacts caused by methamphetamine in all doses. Methamphetamine administration may improve malondialdehyde, tumor necrosis factor-alpha, interleukin-1 beta and GSK3 (both forms). Moreover, methamphetamine reduced the activity of superoxide dismutase, glutathione peroxidase, glutathione reductase, amount of BDNF, CREB and Akt (both forms).Conclusion: Current research showed that selegiline can protect the brain from methamphetamine-prompted neurodegeneration, and this could be intervened by CREB -BDNF or Akt-GSK3 signaling pathways.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
606
615
https://ijbms.mums.ac.ir/article_14687_4390c00de09e9097e969d34364b73d0a.pdf
dx.doi.org/10.22038/ijbms.2020.38827.9221
Synergy between parthenolide and arsenic trioxide in adult T-cell leukemia/lymphoma cells in vitro
Hamideh
Kouhpaykar
Cancer Molecular Pathology Research Center, Department of Hematology and Blood Bank, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
author
Mohammad Hadi
Sadeghian
Cancer Molecular Pathology Research Center, Department of Hematology and Blood Bank, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
author
Houshang
Rafatpanah
Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
author
Mohadeseh
Kazemi
Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
author
Mehrdad
Iranshahi
Department of Pharmacognosy and Biotechnology, Biotechnology Research Center, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
author
Zahra
Delbari
Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
author
Faezeh
Khodadadi
Cancer Molecular Pathology Research Center, Department of Hematology and Blood Bank, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
author
Hossein
Ayatolahi
Cancer Molecular Pathology Research Center, Department of Hematology and Blood Bank, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
author
Fatemeh B.
Rassouli
Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
author
text
article
2020
eng
Objective(s): Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoid malignancy with low survival rate and distinct geographical distribution. In search for novel chemotherapeutics against ATLL, we investigated the combinatorial effects of parthenolide, a sesquiterpene lactone with valuable pharmaceutical activities, and arsenic trioxide (ATO) in vitro. Materials and Methods: MT2 cells, an ATLL cell line, were treated with increasing concentrations of parthenolide (1.25, 2.5, and 5 μg/ml) and ATO (2, 4, 8, and 16 µM) to determine their IC50. Then, cells were treated with a combination of sub-IC50 concentrations of parthenolide (1 μg/ml) and ATO (2 µM) for 72 hr. Cell viability and cell cycle changes were assessed by Alamar blue and PI staining, respectively. To understand the mechanisms responsible for observed effects, expression of CD44, NF-κB (REL-A), BMI-1, and C-MYC were investigated by real-time PCR.Results: Assessment of cell viability indicated that parthenolide significantly increased the toxicity of ATO, as confirmed by accumulation of MT2 cells in the sub G1 phase of the cell cycle. Moreover, molecular analysis revealed significant down-regulation of CD44, NF-κB (REL-A), BMI-1, and C-MYC upon combinatorial administration of parthenolide and ATO in comparison with relevant controls.Conclusion: Taken together, present results showed that parthenolide significantly enhanced the toxicity of ATO in MT2 cells. Therefore, the future possible clinical impact of our study could be combinatorial use of parthenolide and ATO as a novel and more effective approach for ATLL.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
616
622
https://ijbms.mums.ac.ir/article_14630_e21494ea546f5116aef975b291183715.pdf
dx.doi.org/10.22038/ijbms.2020.40650.9610
Protective effect of interleukin-36 receptor antagonist on liver injury induced by concanavalin A in mice
Xiao
Peng
Department of Immunology, Medical School of Ningbo University, Ningbo 315211, China
author
Xiuhe
Pan
Department of Immunology, Medical School of Ningbo University, Ningbo 315211, China
author
Jun
Tan
Department of Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China
author
Yan
Li
Department of Immunology, Medical School of Ningbo University, Ningbo 315211, China
author
Mingcai
Li
Department of Immunology, Medical School of Ningbo University, Ningbo 315211, China
author
text
article
2020
eng
Objective(s): Interleukin-36 receptor antagonist (IL-36Ra) is a new member of the IL-1 family that exhibits anti-inflammatory activity in a variety of inflammatory and immune diseases. Our purpose was to determine the effect of IL-36Ra on liver injury in a mouse hepatitis model induced by concanavalin A (ConA). Materials and Methods: Mice were treated with IL-36Ra DNA or pcDNA3.1 control plasmid using a hydrodynamic gene delivery approach. Results: Our data reveal that treatment with IL-36Ra decreased liver inflammation and serum level of aminotransferases. Furthermore, IL-36Ra reduced ConA-induced pro-inflammatory cytokines (interferon-γ, tumor necrosis factor-α, and IL-17A) production when compared to control plasmid. Conclusion: Our results demonstrated that IL-36Ra is a critical protector against ConA-induced liver injury.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
623
628
https://ijbms.mums.ac.ir/article_15195_6e5884ce12d78572be6c50c1c2397037.pdf
dx.doi.org/10.22038/ijbms.2020.35614.8492
Evaluation of changes in cytochrome P450 2C19 activity in type 2 diabetic rats before and after treatment, by using isolated perfused liver model
Navid
Neyshaburinezhad
Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
author
Mohammad Reza
Rouini
Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
author
Hanieh
Entezari
Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
author
Hoda
Lavasani
Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
author
Yalda
Hosseinzadeh Ardakani
Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
author
text
article
2020
eng
Objective(s): Alteration in drug metabolism is very likely in diabetes mellitus. This study assessed changes in CYP2C19 enzymatic activity in the liver using omeprazole as a probe in the animal model of type II diabetes (T2DM) before and after treatment with metformin and cinnamon.Materials and Methods: Twenty-eight male Wistar rats were randomly divided into seven groups. Fourteen days after induction of type 2 diabetic mellitus (T2DM), rats in the test group received metformin, cinnamon, and metformin plus cinnamon daily for 14 days. On day 28, rats were subjected to liver perfusion by Krebs-Henseleit buffer containing omeprazole as a CYP2C19 probe. Perfusate samples were analyzed by HPLC-UV to evaluate the activity of CYP2C19.Results: Mean metabolic ratio of omeprazole was changed from 0.091±0.005 in the control group to 0.054±0.005 in the untreated-diabetic rats. This average was increased inordinately to 0.218±0.036 in the treated rats with metformin. Interestingly, the administration of cinnamon in combination with metformin in diabetic rats caused the enzyme activity to return to (0.085±0.002) approximately the observed levels in the control group (0.091±0.005).Conclusion: Results showed that despite the suppression of the CYP2C19 enzyme activity in T2DM rats, metformin treatment could increase the enzyme activity. Simultaneous application of cinnamon and metformin can modulate the function of CYP2C19 to the observed level in the control group and make it more predictable to treat diabetes mellitus and fate of drugs that are metabolized by this enzyme.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
629
635
https://ijbms.mums.ac.ir/article_15035_f9201983e0681e4b312aabb6fd43183c.pdf
dx.doi.org/10.22038/ijbms.2020.40836.9642
Incorporation of T-cell epitopes from tetanus and diphtheria toxoids into in-silico-designed hypoallergenic vaccine may enhance the protective immune response against allergens
Ali
Ghasemi
Department of Biochemistry and Hematology, Faculty of Medicine Semnan University of Medical Sciences, Semnan, Iran
author
Reza
Falak
Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
author
Mohsen
Mohamadi
The Persian Gulf Marine Biotechnology Research Center, the Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
author
Soheila
June Maleki
US Department of Agriculture, Agricultural Research Service, Southern Regional Research Center, New Orleans, Louisiana, USA
author
Mohammad-Ali
Assarezadegan
Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
author
Mojtaba
Jafary
The Persian Gulf Marine Biotechnology Research Center, the Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
author
text
article
2020
eng
Objective(s): New generation of allergy vaccines is capable of promoting the development of protective IgG and blocking the functionality of allergen-specific IgE. We incorporated universal and powerful T-cell epitopes from tetanus and diphtheria toxoids (TD epitope) into recombinant Che a 2, the well-known allergic profilin of Chenopodium album, to determine its immunological properties.Materials and Methods: The sequence and accordingly the structure of the recombinant Che a 2 was altered to generate a hypoallergenic variant (rChe a 2.rs). Moreover, TD epitope was incorporated to produce a novel vaccine that was nominated as rChe a 2.rsT.D. The effect of treatment with these variants was evaluated on the generation of allergen-specific IgG class, as well as lymphocyte proliferation in mice. Moreover, IgE-binding characteristics of the allergic patients’ sera were determined by ELISA and proliferation and cytokine production was measured in T-cells. Results: ELISA and dot blot revealed strong reduction of the IgE-reactivity of human sera to the variants of Che a 2 as compared to the wild-type molecule. Furthermore, Che a 2.rs and Che a 2.rsT.D induced much lower levels of IL5 and IL13 secretion from allergic patients’ PBMCs in comparison to wild-type Che a 2 protein. In mice, rChe a 2.rsT.D induced high titers of Che a 2-specific IgG antibody capable of blocking IgE-binding to rChe a 2 and induced lymphocyte proliferation more potently than rChe a 2.rs. Conclusion: Collectively, incorporation of T-cell epitopes of tetanus and diphtheria into hypoallergenic vaccines can dramatically enhance anti-allergic immune mechanisms, particularly in poor responders.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
636
644
https://ijbms.mums.ac.ir/article_15227_c8ec9b94d1baad7e4772b2e82334613a.pdf
dx.doi.org/10.22038/ijbms.2020.39749.9422
Ellagic acid attenuates post-cerebral ischemia and reperfusion behavioral deficits by decreasing brain tissue inflammation in rats
Khadijeh
Hassonizadeh Falahieh
Department of Physiology, College of Sciences, Science and Research Branch, Islamic Azad University, Fars, Iran
author
Alireza
Sarkaki
Persian Gulf Physiology Research Center and Department of Physiology, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran
author
Mohammadamin
Edalatmanesh
Department of Physiology, College of Sciences, Shiraz Branch, Islamic Azad University, Shiraz, Iran
author
Mohammad Kazem
Gharib Naseri
Persian Gulf Physiology Research Center and Department of Physiology, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran
author
Yaghoob
Farbood
Persian Gulf Physiology Research Center and Department of Physiology, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran
author
text
article
2020
eng
Objective(s): Cerebral ischemia/reperfusion (I/R) causes brain inflammation that ultimately causes long time brain function disturbances. We aimed to evaluate the effect of ellagic acid (EA) on anxiety, depression, locomotion behaviors, blood-brain barrier (BBB) permeability, brain edema, and inflammation in male rats with cerebral I/R. Materials and Methods: Sixty male Wistar rats (250-300 g) divided into 6 groups randomly with 10 in each: 1) Sham+Veh; rats submitted to the surgery without any I/R and received vehicle (10% DMSO in normal saline 5 ml/kg, gavages). 2) I/R+Veh; 3-5) I/R+EA; I/R rats received 50, 75 and 100 EA mg/kg, by gavages 3 times daily for one week. The cerebral I/R injury was induced by clamping the bilateral common carotid arteries for 20 minutes followed by reperfusion. Behaviors were tested one week after treatment, and brain tissue cytokines were measured by special ELISA kits. Results: Cerebral I/R disrupted BBB function (P<0.001), increased brain water content (P<0.01), anxiety-like (P<0.001), depression-like (P<0.001) behaviors and cytokines in the brain tissue (P<0.001), while decreased locomotion and exploratory behaviors significantly (PConclusion: The results suggest that EA could be a potential therapeutic agent against cerebral I/R, possibly through its intertwined anti-inflammatory effects. Further research is required to investigate the involved mechanisms in details.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
645
653
https://ijbms.mums.ac.ir/article_15215_c3e6f39256dcb4f2fb911c49fc52f2f6.pdf
dx.doi.org/10.22038/ijbms.2020.41821.9882
Relationship between calcium circulation-related factors and muscle strength in rat sciatic nerve injury model
Xiaoming
Sun
Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, P. R. China
author
Wei
Wang
Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, P. R. China
author
Yangyi
Dong
Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, P. R. China
author
Yue
Wang
Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, P. R. China
author
Meixiang
Zhang
Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, P. R. China
author
Zhao
Wang
Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, P. R. China
author
Xiaowei
Yu
Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, P. R. China
author
Jiao
Huang
Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, P. R. China
author
Hongxing
Cai
Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, P. R. China
author
text
article
2020
eng
Objective(s): The purpose of this study is to investigate the indication function of the calcium circulation-related factors on the damage to muscle strength and contraction function after nerve injury. The target factors include ryanodine receptor (RyR), inositol-1,4,5-triphosphate receptor (IP3R), phospholamban (PLN), cryptocalcitonin (CASQ), ATPase and troponin C (TNNC).Materials and Methods: Sprague-Dawley (SD) rats were randomly divided into sham-operated group (SO), sciatic nerve injury group (SNI) and sciatic nerve disconnection group (SNT). Sciatic nerve function index and stretching test were used to examine the changes to muscle strength; bilateral gastrocnemius muscles were extracted after execution for gastrocnemius wet weight ratio test. HE staining slides and average cross-sectional area of muscle fibers were acquired to analyze the muscle atrophy. The transcription level of the factors was also measured.Results: Sciatic nerve damage in SNI group was significantly higher than that in SO group in the 6 weeks, but there was no significant difference between SNT and SO groups fallowing sciatic nerve damage. Sciatic nerve function in SNT group was worse than that in SNI group. The average cross-sectional area of gastrocnemius muscle fibers in SNI and SNT groups was significantly reduced compared to that in SO group. The transcriptional levels of RyR, PLN, CASQ, ATPase and TNNC in SNI and SNT groups were significantly different from those in SO group.Conclusion: Calcium circulation-related factors could be used as potential indicators for assessment of damages to muscle strength.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
654
662
https://ijbms.mums.ac.ir/article_15230_242709ebde649539c0aa9e438c2a9b6a.pdf
dx.doi.org/10.22038/ijbms.2020.40915.9695
Comparative proteomics study of proteins involved in induction of higher rates of cell death in mitoxantrone-resistant breast cancer cells MCF-7/MX exposed to TNF-α
saeed
Norouzi
Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
author
Rezvan
Yazdian
Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
author
Morteza
Ghanaian
Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran
author
Khalil
Abnous
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
author
Javad
Behravan
School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada
author
Fatemeh
Mosaffa
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
author
text
article
2020
eng
Objective(s): Resistance to medications is one of the main complications in chemotherapy of cancer. It has been shown that some multidrug resistant cancer cells indicate more sensitivity against cytotoxic effects of TNF-α compared to their parental cells. Our previous findings indicated vulnerability of the mitoxantrone-resistant breast cancer cells MCF-7/MX to cell death induced by TNF-α compared to the parent cells MCF-7. In this study, we performed a comparative proteomics analysis for identification of proteins involved in induction of higher susceptibility of MCF-7/MX cells to cytotoxic effect of TNF-α.Materials and Methods: Intensity of protein spots in 2D gel electrophoresis profiles of MCF-7 and MCF-7/MX cells were compared with Image Master Platinum 6.0 software. Selected differential protein-spots were identified with MALDI-TOF/TOF mass spectrometry and database searching. Pathway analyses of identified proteins were performed using PANTHER, KEGG PATHWAY, Gene MANIA and STRING databases. Western blot was performed for confirmation of the proteomics results.Results: Our results indicated that 48 hr exposure to TNF-α induced 87% death in MCF-7/MX cells compared to 19% death in MCF-7 cells. Forty landmarks per 2D gel electrophoresis were matched by Image Master Software. Six proteins were identified with mass spectrometry. Western blot showed that 14-3-3γ and p53 proteins were expressed higher in MCF-7/MX cells treated with TNF-α compared to MCF-7 cells treated with TNF-α.Conclusion: Our results showed that 14-3-3 γ, prohibitin, peroxiredoxin 2 and P53 proteins which were expressed differentially in MCF-7/MX cells treated with TNF-α may involve in the induction of higher rates of cell death in these cells compared to TNF-α-treated MCF-7 cells.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
663
672
https://ijbms.mums.ac.ir/article_15226_7b835a4d2115ed9a0c35e4f98e12f550.pdf
dx.doi.org/10.22038/ijbms.2020.40029.9486
The role of labeled cell therapy with and without scaffold in early excision burn wounds in a rat animal model
Seyedeh Sara
Hashemi
urn and Wound Healing Research Center, Shiraz University of Medical Science, Shiraz, Iran
author
Mohammad Reza
Pourfath
urn and Wound Healing Research Center, Shiraz University of Medical Science, Shiraz, Iran
author
Amin
Derakhshanfar
Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
author
Abbas
Behzad-Behbahani
Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
author
Javad
Moayedi
Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
author
text
article
2020
eng
Objective(s): One of the essential problems in burn therapy is performing the permanent replacement of skin in full and deep thickness injuries. Human Wharton’s Jelly mesenchymal stem cells (HWJMSCs) have a unique combination of prenatal and postnatal properties. Decellularized human amniotic membrane (DHAM) can be used as a scaffold for HWJMSCs-therapy. We aimed to evaluate the quantity and quality of healing in the early excision burn wound dressing with 3-dimensional and 2- dimensional cell cultures.Materials and Methods: Amniotic and umbilical cords were isolated from the mothers who were candidates for cesarean section. HAM was decellularized using the mechanical and enzymatic method. HWJMSCs were isolated and cultured; cell surface markers were examined for authentication of MSCs and labeled using a viral vector containing the cGFP gene. Burns were created using brass bar in 32 adult male Albino rats and randomly divided into four groups (DHAM+HWJMSCs, injection of HWJMSCs, HWJMSCs was spread on the wound, and DHAM alone). Rats were sacrificed on the 7th and 14th days for pathological examination of the wound. Comparisons between the study groups were made by one-way analysis of variance.Results: Wound healing process in DHAM+HWJMSCs was much more progressed during the first week in comparison to other groups, and exhibited significant differences in re-epithelialization, formation of granulation tissue, and hemorrhage (P<0.05).Conclusion: The utility of the amniotic scaffold seeded by the human mesenchymal stem cells is recommended for accelerating the healing process.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
673
679
https://ijbms.mums.ac.ir/article_15194_2cf70831207f0f2c988a25989255ee37.pdf
dx.doi.org/10.22038/ijbms.2020.34324.8156
Complete ablation of tumor necrosis factor decreases the production of IgA, IgG, and IgM in experimental central nervous system tuberculosis
Ngiambudulu
Francisco
Program of Infection and Immunity, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China
author
Nasiema
Allie
SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Stellenbosch, South Africa
author
Boipelo
Sebesho
Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
author
Bernhard
Ryffel
Institut de Transgenose, CNRS, GEM2358, Orleans, France, University of Orleans and CNRS UMR7355, Experimental and Molecular Immunology and Neurogenetics, Orleans, France
author
Muazzam
Jacobs
Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
author
text
article
2020
eng
Objective(s): This study aimed to explore the contribution of tumor necrosis factor (TNF) in the recruitment of B-cell and secretion of immunoglobulins (Igs) during cerebral tuberculosis (TB).Materials and Methods: In this work, the contributing role of TNF in regulating Ig secretions was investigated by comparing wild type TNF (TNFf/f), B-cell-derived TNF (BTNF-/-), and complete TNF ablation (TNF-/-) in a mouse cerebral Mycobacterium tuberculosis infection. Using flow cytometry and ELISA, we were able to examine the recruitment of B-cell subsets, and the production of Igs; also assessed the expression of surface markers on B cell subsets. Results: Here, we found that TNF-/- mice showed defective expression of IgA, IgG, and IgM antibodies compared with TNFf/f and BTNF-/- mice, which was significantly decreased in the expression of surface markers and co-stimulatory molecules. Moreover, mice that produced low antibody levels were not able to control infection, therefore progressed to disease; providing direct evidence for the TNF gene-regulating humoral immunity during central nervous system (CNS) M. tuberculosis infection. In contrast, BTNF-/- mice controlled the infection and had levels of IgA, IgG, and IgM comparable to TNFf/f mice.Conclusion: Together, our results demonstrate that TNF may serve as an essential regulator of antibody-mediated immune responses in CNS TB. However, the protective level exhibited by TNF-producing B cells could be defined as baseline protection that could be used in the development of new therapeutic targets or designing new vaccines.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
680
690
https://ijbms.mums.ac.ir/article_15228_8c80a7efd44173f1738137108131952d.pdf
dx.doi.org/10.22038/ijbms.2020.37947.9021
Characterization of biofilm formation and virulence factors of Staphylococcus aureus isolates from paediatric patients in Tehran, Iran
Hiva
Kadkhoda
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
author
Zohreh
Ghalavand
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
author
Bahram
Nikmanesh
Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
author
Mansoor
Kodori
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
author
Hamidreza
Houri
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
author
Donya
Taghizadeh Maleki
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
author
Ali
Karimi Bavandpour
Department of Bacteriology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran
author
Gita
Eslami
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
author
text
article
2020
eng
Objective(s): Staphylococcus aureus can cause several infections. Its capability to form biofilm has been reported to be a vital property involved in the bacteria’s pathogenesis. Various genes contributing to biofilm formation have not yet been completely clarified. This study was designed to evaluate the factors influencing adherence and biofilm formation in S. aureus isolated from paediatric patients.Materials and Methods: One hundred and ninety-seven S. aureus isolates were obtained from pediatric patients and confirmed with phenotypic and molecular examinations. Antimicrobial susceptibility testing and biofilm formation were evaluated using standard methods. The genes encoding adhesion and virulence factors were investigated by the PCR method. Results: The most efficient antibiotics against S. aureus isolates were vancomycin and linezolid. Approximately, 54.2% of MSSA and 85.6% of MRSA isolates were biofilm producers according to the microtiter test. Our analysis indicated that MRSA isolates are better able to form biofilm compared with MSSA isolates. All isolates harbored clfA, fnbpA, icaA, icaB, icaC, and icaD, while clfB, fnbB, hlg, and pvl were detected in 99.5%, 42.1%, 97.5%, and 5.6% of isolates, respectively. In addition, a significant difference was found in fnhB gene and biofilm formation.Conclusion: Our findings showed a significant correlation between mecA and pvl genes and MRSA and biofilm formation in S. aureus isolates. Additionally, this study indicated the significant role of the fnhB gene as a major marker for S. aureus biofilm formation. Therefore, further experiments are warranted to exactly elucidate the function of the fnhB gene in the formation of biofilm.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
23
v.
5
no.
2020
691
698
https://ijbms.mums.ac.ir/article_15036_98b9a28ceb211a5a41129d74ade2d1a9.pdf
dx.doi.org/10.22038/ijbms.2020.36299.8644