ORIGINAL_ARTICLE
Iranian Journal of Basic Medical Sciences comes of age on the 20th anniversary of publication
https://ijbms.mums.ac.ir/article_9916_a99a9b2a8ca92e29614ff6e4c836dd9b.pdf
2018-01-01
1
2
10.22038/ijbms.2017.28276.6862
Bibi Sedigheh
Fazly bazzaz
fazlis@mums.ac.ir
1
Biotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
ORIGINAL_ARTICLE
Changes in expression of klotho affect physiological processes, diseases, and cancer
Klotho (KL) encodes a single-pass transmembrane protein and is predominantly expressed in the kidney, parathyroid glands, and choroid plexus. Genetic studies on the KL gene have revealed that DNA hypermethylation is one of the major risk factors for aging, diseases, and cancer. Besides, KL exerts anti-inflammatory and anti-tumor effects by regulating signaling pathways and the expression of target genes. KL participates in modulation of the insulin/insulin-like growth factor-1 (IGF-1) signaling, which induces the growth hormone (GH) secretion. Accordingly, KL mutant mice display multiple aging-like phenotypes, which are ameliorated by overexpression of KL. Therefore, KL is an important contributor to lifespan. KL is further identified as a regulator of calcium (Ca2+) channel-dependent cell physiological processes. KL has been also shown to induce cancer cell apoptosis, thus, it is considered as a potential tumor suppressor. Our recent studies have indicated that KL modulates an influx of Ca2+ from the extracellular space, leading to a change in CCL21-dependent migration in dendritic cells (DCs). Interestingly, the regulation of the expression of KL was mediated through a phosphoinositide 3-kinase (PI3K) pathway in DCs. Moreover, downregulating of KL expression by using siRNA knockdown technique, we observed that the expression of Ca2+ channels including Orai3, but not Orai1, Orai2, TRPV5 and TRPV6 was significantly reduced in KL-silenced as compared to control BMDCs. Clearly, additional research is required to define the role of KL in the regulation of organismic and cellular functions through the PI3K signaling and the expression of the Ca2+ channels.
https://ijbms.mums.ac.ir/article_9892_28125904f08cd9146deb296fba32759e.pdf
2018-01-01
3
8
10.22038/ijbms.2017.21892.5616
Aging
Ca2+ channel
Cancer
Dendritic cells
Klotho
Nguyen
Xuan
ntxuan@igr.ac.vn
1
Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam
LEAD_AUTHOR
Nong
Van Hai
nvhai.igr@yahoo.com
2
Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam
AUTHOR
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64
ORIGINAL_ARTICLE
Design, synthesis, and biological evaluation of 6-methoxy-2-arylquinolines as potential P-glycoprotein inhibitors
Objective(s): In the present study,a new series of 6-methoxy-2-arylquinoline analogues was designed and synthesized as P-glycoprotein (P-gp) inhibitors using quinine and flavones as the lead compounds. Materials and Methods: The cytotoxic activity of the synthesized compounds was evaluated against two human cancer cell lines including EPG85-257RDB, multidrug-resistant gastric carcinoma cells (P-gp-positive gastric carcinoma cell line), and EPG85-257P, drug-sensitive gastric carcinoma cells. Compounds showing low to moderate toxicity in the MTT test were selected to investigate their P-gp inhibition activity. Moreover, trying to explain the results of biological experiments, docking studies of the selected compounds into the homology-modeled human P-gp, were carried out. The physicochemical and ADME properties of the compounds as drug candidate were also predicted. Results: Most of our compounds exhibited negligible or much lower cytotoxic effect in both cancer cells. Among the series, 5a and 5b, alcoholic quinoline derivatives were found to inhibit the efflux of rhodamine 123 at the concentration of 10 μM significantly. Conclusion: Among the tested quinolines, 5a and 5b showed the most potent P-gp inhibitory activity in the series and were 1.3-fold and 2.1-fold stronger than verapamil, respectively. SAR data revealed that hydroxyl methyl in position 4 of quinolines has a key role in P-gp efflux inhibition of our compounds. ADME studies suggested that all of the compounds included in this study may have a good human intestinal absorption.
https://ijbms.mums.ac.ir/article_9917_8ed4de841fcb62e0e8ed927ed1bc91b4.pdf
2018-01-01
9
18
10.22038/ijbms.2017.24476.6092
Molecular docking
P-glycoprotein
P-gp inhibition
Quinoline
Synthesis
Sayyed Mohammad
Abutorabzadeh
aboutorabzade26@gmail.com
1
Biotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Fatemeh
Mosafa
mosaffaf@mums.ac.ir
2
Biotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Farzin
Hadizadeh
hadizadehf@mums.ac.ir
3
Biotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Razieh
Ghodsi
ghodsir@mums.ac.ir
4
Biotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65: 5-29.
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2. Cozzi P. The discovery of a new potential anticancer drug: a case history. Farmaco 2003; 58: 213-220.
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4. Capparelli E, Zinzi L, Cantore M, Contino M, Perrone MG, Luurtsema G, et al. SAR studies on tetrahydroisoquinoline derivatives: the role of flexibility and bioisosterism to raise potency and selectivity toward P-glycoprotein. J Med Chem 2014; 57: 9983-9994.
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5. Wang Z, Wong IL, Li FX, Yang C, Liu Z, Jiang T, et al. Optimization of permethyl ningalin B analogs as P-glycoprotein inhibitors. Bioorg Med Chem 2015; 23: 5566-5573.
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6. Chen CY, Liu NY, Lin HC, Lee CY, Hung CC, Chang CS. Synthesis and bioevaluation of novel benzodipyranone derivatives as P-glycoprotein inhibitors for multidrug resistance reversal agents. Eur J Med Chem 2016; 118: 219-229.
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8. Lopes-Rodrigues V, Oliveira A, Correia-da-Silva M, Pinto M, Lima RT, Sousa E, et al. A novel curcumin derivative which inhibits P-glycoprotein, arrests cell cycle and induces apoptosis in multidrug resistance cells. Bioorg Med Chem 2017; 25: 581-596.
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19. Wu Y, Pan M, Dai Y, Liu B, Cui J, Shi W, et al. Design, synthesis and biological evaluation of LBM-A5 derivatives as potent P-glycoprotein-mediated multidrug resistance inhibitors. Bioorg Med Chem 2016; 24: 2287-2297.
19
20. Malayeri SO, Abnous K, Arab A, Akaberi M, Mehri S, Zarghi A, et al. Design, synthesis and biological evaluation of 7-(aryl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinoline derivatives as potential Hsp90 inhibitors and anticancer agents. Bioorg Med Chem 2017; 25: 1294-1302.
20
21. Shobeiri N, Rashedi M, Mosaffa F, Zarghi A, Ghandadi M, Ghasemi A, et al. Synthesis and biological evaluation of quinoline analogues of flavones as potential anticancer agents and tubulin polymerization inhibitors. Eur J Med Chem. 2016; 114: 14-23.
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22. Wu Y, Chen Z, Liu Y, Yu L, Zhou L, Yang S, et al. Quinoline-4-methyl esters as human nonpancreatic secretory phospholipase A(2) inhibitors. Bioorg Med Chem 2011; 19: 3361-3366.
22
23. Ghodsi R, Azizi E, Grazia Ferlin M, Pezzi V, Zarghi A. Design, synthesis and biological evaluation of 4-(imidazolylmethyl)-2-aryl-quinoline derivatives as aromatase inhibitors and anti-breast cancer agents. Lett Drug Des Discov 2016; 13: 89-97.
23
24. Baumert C, Günthel M, Krawczyk S, Hemmer M, Wersig T, Langner A, et al. Development of small-molecule P-gp inhibitors of the N-benzyl 1,4-dihydropyridine type: Novel aspects in SAR and bioanalytical evaluation of multidrug resistance (MDR) reversal properties. Bioorg Med Chem 2013; 21: 166-177.
24
25. Li XQ, Wang L, Lei Y, Hu T, Zhang FL, Cho CH, et al. Reversal of P-gp and BCRP-mediated MDR by tariquidar derivatives. Eur J Med Chem 2015; 101: 560-572.
25
26. Hosseinzadeh H, Mazaheri F, Ghodsi R. Pharmacological effects of a synthetic quinoline, a hybrid of tomoxiprole and naproxen, against acute pain and inflammation in mice: a behavioral and docking study. Iran J Basic Med Sci 2017; 20: 446-450.
26
27. Abdizadeh T, Kalani MR, Abnous K, Tayarani-Najaran Z, Khashyarmanesh BZ, Abdizadeh R, et al. Design, synthesis and biological evaluation of novel coumarin-based benzamides as potent histone deacetylase inhibitors and anticancer agents. Eur J Med Chem 2017; 132: 42-62.
27
ORIGINAL_ARTICLE
Protective effect of metformin on D-galactose-induced aging model in mice
Objective(s): Metformin (Met), an antidiabetic biguanide, reduces hyperglycemia via improving glucose utilization and reducing the gluconeogenesis. Met has been shown to exert neuroprotective, antioxidant and anti-inflammatory properties. The present study investigated the possible effect of Met on the D-galactose (D-gal)-induced aging in mice. Materials and Methods: Met (1 and 10 mg/kg/p.o.), was administrated daily in D-gal-received (500 mg/kg/p.o.) mice model of aging for six weeks. Anxiety-like behavior, cognitive function, and physical power were evaluated by the elevated plus-maze, novel object recognition task (NORT), and forced swimming capacity test, respectively. The brains were analyzed for the level of superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF). Results: Met decreased the anxiety-like behavior in D-gal-treated mice. Also, Met treated mice showed significantly improved learning and memory ability in NORT compared to the D-gal-treated mice. Furthermore, Met increased the physical power as well as the activity of SOD and BDNF level in D-gal-treated mice. Conclusion: Our results suggest that the use of Met can be an effective strategy for prevention and treatment of D-gal-induced aging in animal models. This effect seems to be mediated by attenuation of oxidative stress and enhancement of the neurotrophic factors.
https://ijbms.mums.ac.ir/article_9918_8485c501384b5a8c6369749b6ca9f3f6.pdf
2018-01-01
19
25
10.22038/ijbms.2017.24331.6071
Aging
D-galactose
Metformin
Mouse
Oxidative stress
Iman
Fatemi
imanfatemi@gmail.com
1
Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
AUTHOR
Amin
khaluoi
akhaloyee@gmail.com
2
Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
AUTHOR
Ayat
Kaeidi
a.kayedi@gmail.com
3
Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
AUTHOR
Ali
Shamsizadeh
alishamsy@gmail.com
4
Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
AUTHOR
Sara
Heydari
saraheydari990@yahoo.com
5
Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
AUTHOR
Mohammad
Allahtavakoli
m_alahtavakoli@rums.ac.ir
6
Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
LEAD_AUTHOR
1. Shin KR, Kim MY, Kim YH. Study on the lived experience of aging. Nurs Health Sci 2003; 5:245-252.
1
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22. Pourmemar E, Majdi A, Haramshahi M, Talebi M, Karimi P, Sadigh-Eteghad S. Intranasal cerebrolysin attenuates learning and memory impairments in D-galactose-induced senescence in mice. Exp Gerontol 2017; 87:16-22.
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25. Ashabi G, Sarkaki A, Khodagholi F, Zareh Shahamati S, Goudarzvand M, Farbood Y, et al. Subchronic metformin pretreatment enhances novel object recognition memory task in forebrain ischemia: behavioural, molecular, and electrophysiological studies. Can J Physiol Pharmacol 2016; 95:388-395.
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42
ORIGINAL_ARTICLE
Immunogenicity of chimeric MUC1-HER2 vaccine against breast cancer in mice
Objective(s): Breast cancer is one of the most common cancers in the world and is on the increase. MUC1 and HER2 as tumor-associated antigens (TAAs) are abnormally expressed to some extent in 75–80% of breast cancers. In our present research, a novel chimeric MUC1-HER2 (HM) protein was designed and used to study whether an immune response can be generated against these TAAs. In vitro analysis of the HER2-MUC1 construct confirmed the co-expression of MUC1 and HER2. Materials and Methods: BALB/c mice were immunized with this novel chimeric protein. The humoral immune response was assessed by enzyme-linked immunosorbent assay (ELISA). Then, BALB/c mice were injected subcutaneously 2×105 4T1-MUC1-HER2 tumor cells. Subsequently, tumor size and tumor necrosis measurements, MTT, cytokines assay and survival test were performed. Results: The results implied a critical role of HER2 and MUC1 antibodies in vaccination against breast cancer. This engineered protein can be a good vaccine to stop breast cancer. Conclusion: The results implied a critical role of HER2 and MUC1 antibodies in vaccination against breast cancer. This engineered protein can be a good vaccine to stop breast cancer.
https://ijbms.mums.ac.ir/article_9919_84248188e236e6b6f85909cbd6bb44df.pdf
2018-01-01
26
32
10.22038/ijbms.2017.25686.6335
Breast Cancer
HER2
MUC1
Recombinant antigen
Vaccine
Elaheh
Gheybi
elaheh.gheybi@gmail.com
1
Applied Biotechnology Research Center, System Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
AUTHOR
Ali Hatef
Salmanian
salman@nigeb.ac.ir
2
Plant Bioproducts Department, Institute of Agricultural Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
AUTHOR
Abbas Ali
Imani Fooladi
imanifouladi.a@bmsu.ac.ir
3
Applied Microbiology Research Center, System Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
AUTHOR
Jafar
Salimian
jafar.salimian@gmail.com
4
Chemical Injuries Research Center, System Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
AUTHOR
Hamideh
Mahmoodzadeh Hosseini
hosseini361@yahoo.com
5
Applied Microbiology Research Center, System Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
AUTHOR
Raheleh
Halabian
r.halabian@yahoo.com
6
Applied Microbiology Research Center, System Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
AUTHOR
Jafar
Amani
jafar.amani@gmail.com
7
Applied Microbiology Research Center, System Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
LEAD_AUTHOR
1. Shayan R, Achen MG, Stacker SA. Lymphatic vessels in cancer metastasis: bridging the gaps. Carcinogenesis 2006; 27:1729-1738.
1
2. Emens L, Reilly R, Jaffee E. Breast cancer vaccines: maximizing cancer treatment by tapping into host immunity. Endocrine-Related Cancer 2005; 12:1-17.
2
3. Schlom J, Gulley JL, Arlen PM. Paradigm shifts in cancer vaccine therapy. Exp Biol Med 2008; 233:522-534.
3
4. Milani A, Sangiolo D, Montemurro F, Aglietta M, Valabrega G. Active immunotherapy in HER2 overexpressing breast cancer: current status and future perspectives. Ann Oncol 2013; 24:1740-1748.
4
5. Pietersz GA, Li W, Osinski C, Apostolopoulos V, McKenzie IF. Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1. Vaccine2000; 18:2059-2071.
5
6. Mittendorf EA, Holmes JP, Ponniah S, Peoples GE. The E75 HER2/neu peptide vaccine. Cancer immunol immunother 2008; 57:1511-1521.
6
7. Gilewski T, Adluri S, Ragupathi G, Zhang S, Yao TJ, Panageas K, et al. Vaccination of high-risk breast cancer patients with mucin-1 (MUC1) keyhole limpet hemocyanin conjugate plus QS-21. Clin Cancer Res 2000; 6:1693-1701.
7
8. Wilkie S, Picco G, Foster J, Davies DM, Julien S, Cooper L, et al. Retargeting of human T cells to tumor-associated MUC1: the evolution of a chimeric antigen receptor. J Immunol 2008; 180:4901-4909.
8
9. Tang Y, Wang L, Zhang P, Wei H, Gao R, Liu X, et al. Detection of circulating anti-mucin 1 (MUC1) antibodies in breast tumor patients by indirect enzyme-linked immunosorbent assay using a recombinant MUC1 protein containing six tandem repeats and expressed in Escherichia coli Clin Vaccine Immunol 2010; 17:1903-1908.
9
10. Zhang S, Graeber LA, Helling F, Ragupathi G, Adluri S, Lloyd KO, et al. Augmenting the immunogenicity of synthetic MUC1 peptide vaccines in mice Cancer Res 1996; 56:3315-3319.
10
11. Hikita ST, Kosik KS, Clegg DO, Bamdad C. MUC1* mediates the growth of human pluripotent stem cells. PLoS One 2008; 3:e3312.
11
12. Hanna M Jr. Human vaccines & immunotherapeutics: news. Hum Vaccin Immunother 2014; 10:1773-1777.
12
13. Wilkie S, van Schalkwyk MC, Hobbs S, Davies DM, van der Stegen SJ, Pereira AC, et al. Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling. J Clin Immunol 2012; 32:1059-1070.
13
14. Geourjon C, Deleage G. SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments. Comput Appl Biosci 1995; 11:681-684.
14
15. Zhang Y. I-TASSER server for protein 3D structure prediction. BMC Bioinformatics 2008; 9:40.
15
16. Gheybi E, Amani J, Salmanian AH, Mashayekhi F, Khodi S. Designing a recombinant chimeric construct contain MUC1 and HER2 extracellular domain for prediagnostic breast cancer. Tumour Biol 2014; 35:11489-11497.
16
17. Gavin AL, Hoebe K, Duong B, Ota T, Martin C, Beutler B, et al. Adjuvant-enhanced antibody responses in the absence of toll-like receptor signaling. Science 2006; 314:1936-1938.
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18. Castiglione F, Mantile F, De Berardinis P, Prisco A. How the interval between prime and boost injection affects the immune response in a computational model of the immune system. Comput Math Methods Med 2012; 842329.
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19. Coffman RL, Sher A, Seder RA. Vaccine adjuvants: putting innate immunity to work. Immunity 2010; 33:492-503.
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20. Panthel K, Meinel KM, Sevil Domenech VE, Geginat G, Linkemann K, Busch DH, et al. Prophylactic anti-tumor immunity against a murine fibrosarcoma triggered by the Salmonella type III secretion system. Microbes Infect 2006; 8:2539-2546.
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21. Ma W, Yu H, Wang Q, Jin H, Solheim J, Labhasetwar V. A novel approach for cancer immunotherapy: tumor cells with anchored superantigen SEA generate effective antitumor immunity. J Clin Immunol 2004; 24:294-301.
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23. Fooladi AA, Sattari M, Nourani MR. Study of T-cell stimulation and cytokine release induced by Staphylococcal enterotoxin type B and monophosphoryl lipid A. Arch Med Sci 2009; 5:335-341.
23
24. Singha H, Mallick AI, Jana C, Fatima N, Owais M, Chaudhuri P. Co-immunization with interlukin-18 enhances the protective efficacy of liposomes encapsulated recombinant Cu-Zn superoxide dismutase protein against Brucella abortus. Vaccine 2011; 29:4720-4727.
24
25. Brossart P, Heinrich KS, Stuhler G, Behnke L, Reichardt VL, Stevanovic S, et al. Identification of HLA-A2-restricted T-cell epitopes derived from the MUC1 tumor antigen for broadly applicable vaccine therapies. Blood 1999; 93:4309-4317.
25
26. Fooladi AA, Sattari M, Hassan ZM, Mahdavi M, Azizi T, Horii A. In vivo induction of necrosis in mice fibrosarcoma via intravenous injection of type B staphylococcal enterotoxin. Biotechnol Lett 2008; 30:2053-2059.
26
27. Kindy MS, Yu J, Zhu H, Smith MT, Gattoni-Celli S. A therapeutic cancer vaccine against GL261 murine glioma. J Transl Med2016;14:1.
27
28. Mohanty K, Saha A, Pal S, Mallick P, Chatterjee SK, Foon KA, et al. Anti-tumor immunity induced by an anti-idiotype antibody mimicking human Her-2/neu. Breast Cancer Res Treat 2007;104:1-11.
28
29. Naz RK, Dabir P. Peptide vaccines against cancer, infectious diseases, and conception. Front Biosci 2007; 12:1833-1844.
29
30. Soliman H. Developing an effective breast cancer vaccine. Cancer Control 2010; 17:183-190.
30
31. Pejawar-Gaddy S, Rajawat Y, Hilioti Z, Xue J, Gaddy DF, Finn OJ, et al. Generation of a tumor vaccine candidate based on conjugation of a MUC1 peptide to polyionic papillomavirus virus-like particles. Cancer Immunol Immunother 2010; 59:1685-1696.
31
32. Freudenberg JA, Wang Q, Katsumata M, Drebin J, Nagatomo I, Greene MI. The role of HER2 in early breast cancer metastasis and the origins of resistance to HER2-targeted therapies. Exp Mol Pathol 2009; 87:1-11.
32
33. Lakshminarayanan V, Thompson P, Wolfert MA, Buskas T, Bradley JM, Pathangey LB, et al. Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine. Proc Natl Acad Sci U S A 2012; 109:261-266.
33
34. Luo D, Ni B, Li P, Shi W, Zhang S, Han Y, et al. Protective immunity elicited by a divalent DNA vaccine encoding both the L7/L12 and Omp16 genes of Brucella abortus in BALB/c mice. Infect Immun 2006; 74:2734-2741.
34
35. Piechocki MP, Ho YS, Pilon S, Wei WZ. Human ErbB-2 (Her-2) transgenic mice: a model system for testing Her-2 based vaccines. J Immunol 2003; 171:5787-5794.
35
ORIGINAL_ARTICLE
Protosappanin A protects against atherosclerosis via anti- hyperlipidemia, anti-inflammation and NF-κB signaling pathway in hyperlipidemic rabbits
Objective(s): Protosappanin A (PrA) is an effective and major ingredient of Caesalpinia sappan L. The current study was aimed to explore the effect of PrA on atherosclerosis (AS). Materials and Methods: Firstly, the experimental model of AS was established in rabbits by two-month feeding of high fat diet. Then, the rabbits were randomly divided into five groups and treated with continuous high lipid diet (model control), high lipid diet containing rosuvastatin (positive control), 5 mg/kg PrA (low dose) or 25 mg/kg PrA (high dose). Results: Our results showed that PrA markedly alleviated AS as indicated by hematoxylin/eosin (HE) staining. PrA also reduced hyperlipidemia (as demonstrated by the serum levels of total blood cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL)) in a time and dose-dependent manner, and decreased inflammation (as indicated by the serum levels of matrix metalloproteinase-9 [MMP-9], interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]). Moreover, PrA significantly inactivated nuclear factor kappa B (NF-κB) signaling as indicated by nuclear NF-κB p65 protein expression, as well as the mRNA expression and serum levels of downstream genes, interferon-γ (IFN-γ) and interferon-gamma-inducible protein 10 (IP10). Conclusion: This study proved that PrA might protect against atherosclerosis via anti-hyperlipidemia, anti-inflammation and NF-κB signaling pathways in hyperlipidemic rabbits.
https://ijbms.mums.ac.ir/article_9922_4e7bf23e25981183725bb50ddd98559c.pdf
2018-01-01
33
38
10.22038/ijbms.2017.18840.5029
Anti-hyperlipidemic
Anti-inflammatory
Atherosclerosis
NF-κB
Protosappanin A
Ying
Huang
huangying1520@163.com
1
Department of Cardiology, Shang Hai PuDong New Area People’s hospital, Shanghai, China
AUTHOR
Yuan
Qi
qiyaun1520@sina.com
2
Department of Cardiology, Shanghai East Hospital, New Area of Pu Dong, Shanghai, China
AUTHOR
JianQing
Du
djq1122334@sina.com
3
Department of Cardiology, Shang Hai PuDong New Area People’s hospital, Shanghai, China
AUTHOR
DaiFu
Zhang
dfzhangpd@163.com
4
Department of Cardiology, Shang Hai PuDong New Area People’s hospital, Shanghai, China
LEAD_AUTHOR
1. Badami S, Moorkoth S, Rai SR, Kannan E, Bhojraj S. Antioxidant activity of Caesalpinia sappan heartwood. Biol Pharm Bull. 2003; 26:1534-1537.
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2. Hikino H, Taguchi T, Fujimura H, Hiramatsu Y. Antiinflammatory principles of Caesalpinia sappan wood and of Haematoxylon campechianum wood. Planta Med 1977.
2
3. Kim E-C, Hwang Y-S, Lee H-J, Lee S-K, Park M-H, Jeon B-H, et al. Caesalpinia sappan induces cell death by increasing the expression of p53 and p21WAF1/CIP1 in head and neck cancer cells. Am J Chin Med. 2005; 33:405-414.
3
4. Sireeratawong S, Piyabhan P, Singhalak T, Wongkrajang Y, Temsiririrkkul R, Punsrirat J, et al. Toxicity evaluation of sappan wood extract in rats. J Med Assoc Thai 2011; 93:50.
4
5. Wu J, Hou J, Zhang M, Zou Y, Yu B, editors. Protosappanin a, an immunosuppressive constituent from a Chinese herb, prolongs graft survival and attenuates acute rejection in rat heart allografts. Transplantation proceedings; 2008: Elsevier.
5
6. Wu J, Zhang M, Jia H, Huang X, Zhang Q, Hou J, et al. Protosappanin A induces immunosuppression of rats heart transplantation targeting T cells in grafts via NF-κB pathway. Naunyn Schmiedebergs Arch Pharmacol 2010; 381:83-92.
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34. Chen X, Xun K, Chen L, Wang Y. TNF‐α, a potent lipid metabolism regulator. Cell Biochem Funct 2009; 27:407-416.
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35. Feingold KR, Grunfeld C. Role of cytokines in inducing hyperlipidemia. Diabetes 1992;41(Supplement 2):97-101.
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36
37. Van Gaal LF, Mertens IL, Christophe E. Mechanisms linking obesity with cardiovascular disease. Nature 2006;444:875-880.
37
ORIGINAL_ARTICLE
The toxicity study of synthesized inverse carnosine peptide analogues on HepG2 and HT-29 cells
Objective: Cancer has risen as the main cause of diseases with the highest rate of mortality in the world. Drugs used in cancer, usually demonstrate side effects on normal tissues. On the other hand, anticancer small peptides, effective on target tissues, should be safe on healthy organs, as being naturally originated compounds. In addition, they may have good pharmacokinetic properties. carnosine, a natural dipeptide, has shown many biological functions, including anti-oxidant, anti-senescence, anti-inflammatory and anticancer activities. This study, with the aim of introducing new anticancer agents with better properties, is focused on the synthesis and cytotoxic evaluation of some peptide analogues of carnosine. Materials and Methods: The cytotoxic activity of the synthesized peptides, prepared by the solid-phase peptide synthesis method, was evaluated against two cell lines of HepG2 and HT-29 using MTT assay, lactate dehydrogenase (LDH) assay and flow cytometry analysis. Results: Linear and cyclic analogues of carnosine peptide showed cytotoxicity, demonstrated by several experiments, against HepG2 and HT-29 cell lines with mean IC50 values ranging from 9.81 to 16.23 µg/ml. Among the peptides, compounds 1c, 3c and 6b (linear analogue of 3c) showed a considerable toxic activity on the cancerous cell lines. Conclusion: The cyclic peptide analogues of carnosine withHis-β-Ala-Pro-β-Ala-His (1c) and β-Ala-His- Pro-His-β-Ala (3c) sequences showed cytotoxic activity on cancerous cells of HepG2 and HT-29, better than carnosine, and thus can be good candidates to develop new anticancer agents. The mechanism of cytotoxicity may be through cell apoptosis.
https://ijbms.mums.ac.ir/article_9860_33565322529d15e805cf6028ee619af0.pdf
2018-01-01
39
46
10.22038/ijbms.2017.23153.5852
Anticancer agents
Carnosine analogues
Cytotoxicity
Flow cytometry
Peptide synthesis
MTT Assay
Mohammad Hassan
Houshdar Tehrani
m_houshdar@sbmu.ac.ir
1
Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
LEAD_AUTHOR
Abdolhamid
Bamoniri
bamoniri@kashanu.ac.ir
2
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran
AUTHOR
Mohammadreza
Gholibeikian
mgholibeikian@gmail.com
3
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran
AUTHOR
1. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3: 2011-2030.
1
2. Kang TH, Mao CP, He L, Tsai YC, Liu K, La V, et al. Tumor targeted delivery of IL-2 by NKG2D leads to accumulation of antigen-specific CD8+ T cells in the tumor loci and enhanced anti-tumor effects. PLoS ONE 2012; 7: 1-9.
2
3. Dongdong W, Yanfeng G, Yuanming Q, Lixiang C, Yuanfang M, Yanzhang L. Peptide-based cancer therapy: Opportunity and challenge. Cancer Lett 2014; 351: 13–22.
3
4. Boldyrev AA. Carnosine and oxidative stress in cells and tissues. Nova Publishers 2007: 1-286.
4
5. Gaunitz F, Hipkiss AR. Carnosine and cancer: a perspective. Amino Acids 2012; 43: 135-142.
5
6. Alpsoy L, Akcayoglu G, Sahin H. Anti-oxidative and anti-genotoxic effects of carnosine on human lymphocyte culture. Hum Exp Toxicol 2011; 30: 1979-1985.
6
7. Sale C, Saunders B, Harris RC. Effect of beta-alanine supplementation on muscle carnosine concentrations and exercise performance. Amino acids 2010; 39: 321-333.
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8. Boldyrev AA, Aldini G, Derave W. Physiology and pathophysiology of carnosine. Physiol Rev 2013; 93: 1803-1845.
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9. Guiotto A, Calderan A, Ruzza P, Borin G. Carnosine and carnosine-related antioxidants: a review. Curr Med Chem 2005; 12: 2293-2315.
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10. Chan KM, Decker EA, Feustman C. Endogenous skeletal muscle antioxidants. Crit Rev Food Sci Nutr 1994; 34: 403-426.
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11. Nagai K, Suda T. Antineoplastic effects of carnosine and betaalanine–physiological considerations of its antineoplastic effects. Nihon Seirigaku Zasshi 1986; 48:741–747.
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12. Holliday R, McFarland GA. Inhibition of the growth of transformed and neoplastic cells by the dipeptide carnosine. Br J Cancer 1996; 73:966–971.
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13. Renner C, Seyffarth A, de Arriba S, Meixensberger J, Gebhardt R, Gaunitz F. Carnosine inhibits growth of cells isolated from human glioblastoma multiforme. Int J Pept Res Ther 2008; 14:127–135.
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14. Horii Y, Shen J, Fujisaki Y, Yoshida K, Nagai K. Effects of Lcarnosine on splenic sympathetic nerve activity and tumor proliferation. Neurosci Lett 2012; 510:1–5.
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15. Iovine B, Oliviero G, Garofalo M, Orefice M, Nocella F, Borbone N, et al. The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells. PloS One 2014; 9: 1–10.
15
16. Hipkiss AR, Gaunitz F. Inhibition of tumour cell growth by carnosine: some possible mechanisms Amino Acids 2014; 46: 327–337.
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17. Gaunitz F, Hipkiss AR. Carnosine and cancer—a perspective. Amino Acids 2012; 43:135–142.
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18. Yun B, Saidan D, Jiaoyan C, Yuan L, Bingyu W, Huijuan X, et al. Carnosine inhibits the proliferation of human cervical gland carcinoma cells throughinhibiting both mitochondrial bioenergetics and glycolysis pathways and retarding cell cycle progression. Integr Cancer Ther 2016; 1–12.
18
19. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55-63.
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20. Amador E, Dorfman LE, Wacker WE. Serum lactic dehydrogenase activity: an analytical assessment of current assays. Clin Chem 1963; 9: 391-399.
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21. Han X, Gelein R, Corson N, Wade-Mercer P, Jiang J, Biswas P, et al. Validation of an LDH assay for assessing nanoparticle toxicity. Toxicology 2011; 287:99-104.
21
22. Jang M, Neuzil P, Volk T, Manz A, Kleber A. On-chip three-dimensional cell culture in phaseguides improves hepatocyte functions in vitro. Biomicrofluidics. 2015; 9: 034113, 1-12
22
23. Riccardi C, Nicoletti I. Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat Protoc 2006; 1: 1458-1461.
23
24. Farha AK, Geetha BS, Mangalam SN, Dhanya SR, Latha PG, Remani P. Apoptosis mediated cytotoxicity induced by isodeoxyelephantopin on nasopharyngeal carcinoma cells. Asian J Pharm Clin Res. 2013; 6: 51-56.
24
25. Park JG, Langenwalter KJ, Weinbaum CA, Casey PJ, Pang Y-P. Improved loading and cleavage methods for solid-phase synthesis using chlorotrityl resins: synthesis and testing of a library of 144 discrete chemicals as potential farnesyl transferase inhibitors. J Comb Chem. 2004; 6: 407-413.
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26. Olsen CA, Witt M, Jaroszewski JW, Franzyk H. Solid-Phase Synthesis of Rigid Acylpolyamines Using Temporary N-4,4‘-Dimethoxytrityl Protection in the Presence of Trityl Linkers. J Org Chem 2004; 69: 6149-6152.
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27 Lundquist IV JT, Satterfield AD, Pelletier JC. Mild and adaptable silver triflate-assisted method for trityl protection of alcohols in solution with solid-phase loading applications. Org Lett 2006; 8: 3915-3918.
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28. Crestey F, Ottesen LK, Jaroszewski JW, Franzyk H. Efficient loading of primary alcohols onto a solid phase using a trityl bromide linker. Tetrahedron Lett 2008; 49: 5890-5893.
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29. Rothman DM, Vazquez ME, Vogel EM, Imperiali B. Caged phospho-amino acid building blocks for solid-phase peptide synthesis. J Org Chem 2003; 68: 6795-6798.
29
ORIGINAL_ARTICLE
Histomorphometric evaluation of mice testicular tissue following short- and long-term effects of lipopolysaccharide-induced endotoxemia
Objective(s):Lipopolysaccharide (LPS)-induced endotoxemia is known to cause male infertility. This study was designed to explore the effects of bacterial LPS on histomorphometric changes of mice testicular tissues. Materials and Methods: In experiment 1, a pilot dose responsive study was performed with mice that were divided into five groups, receiving 36000, 18000, 9000, and 6750 µg/kg body weight (B.W) of LPS or only saline (control). White blood cells (WBC) were observed for 3 days after LPS inoculation. In experiment 2, two groups of mice were treated with 6750 µg/kg B.W of LPS or only saline (control). Five cases from each experimental group were sacrificed at 3, 30, and 60 days after LPS inoculation. Left testes were fixed in Bouin’s solution, and stained for morphometrical assays. Results: Time-course changes of WBC obtained from different doses of LPS-treated mice showed that inoculation of 6750 µg/kg B.W produced a reversible endotoxemia that lasts for 72 hr and so it was used in the second experiment. In experiment 2, during the first 3 days, no significant changes were observed in the evaluated parameters instead of seminiferous tubules diameter. Spermatogenesis, Johnsen’s score, meiotic index, and epithelial height were significantly affected at 30th day. However, complete recovery was only observed for the spermatogenesis at day 60. Interestingly, deleterious effects of LPS on spermatogonia were only seen at 60th day (P<0.05). Conclusion: Endotoxemia induced by LPS has long-term detrimental effects on spermatogonia and later stage germ cells, which are reversible at the next spermatogenic cycle.
https://ijbms.mums.ac.ir/article_9895_2c34d26905a27a7e64361ba06aa55a04.pdf
2018-01-01
47
52
10.22038/ijbms.2017.24415.6083
Endotoxemia Lipopolysaccharide
Meiotic index
Spermatogenesis Spermatogonia
Oveis
Jafari
oveis.vet@gmail.com
1
Graduate Student of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
AUTHOR
Homayoon
Babaei
babaei_h@uk.ac.ir
2
Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
LEAD_AUTHOR
Reza
Kheirandish
kheirandish@uk.ac.ir
3
Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
AUTHOR
Amir-Saied
Samimi
amirsamimi90@yahoo.com
4
Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
AUTHOR
Ali
Zahmatkesh
alizahmatkesh8970@gmail.com
5
Graduate Student of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
AUTHOR
1. Sarkar O, Bahrainwala J, Chandrasekaran S, Kothari S, Mathur PP, Agarwal A. Impact of inflammation on male fertility. Front Biosci (Elite Ed) 2011; 3:89-95.
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2. Lynn WA, Cohen J. Adjunctive therapy for septic shock: a review of experimental approaches. Clin Infect Dis 1995; 20:143-158.
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5. Zhou J, Schmidt M, Johnston B, Wilfart F, Whynot S, Hung O, et al. Experimental endotoxemia induces leukocyte adherence and plasma extravasation within the rat pial microcirculation. Physiol Res 2011; 60:853-859.
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6. Turnbull AV, Rivier C. Regulation of the HPA axis by cytokines. Brain Behav Immun 1995; 9:253-275.
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7. Knotek M, Rogachev B, Wang W, Ecder T, Melnikov V, Gengaro PE, et al. Endotoxemic renal failure in mice: Role of tumor necrosis factor independent of inducible nitric oxide synthase. Kidney Int 2001; 59:2243-2249.
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11. Reddy MM, Mahipal SV, Subhashini J, Reddy MC, Roy KR, Reddy GV, et al. Bacterial lipopolysaccharide-induced oxidative stress in the impairment of steroidogenesis and spermatogenesis in rats. Reprod Toxicol 2006; 22:493-500.
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12. Kajihara T, Okagaki R, Ishihara O. LPS-induced transient testicular dysfunction accompanied by apoptosis of testicular germ cells in mice. Med Mol Morphol 2006; 39:203-208.
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13. Bosmann HB, Hales KH, Li X, Liu Z, Stocco DM, Hales DB. Acute in vivo inhibition of testosterone by endotoxin parallels loss of steroidogenic acute regulatory (StAR) protein in Leydig cells. Endocrinology 1996; 137:4522-4525.
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14. Brecchia G, Cardinali R, Mourvaki E, Collodel G, Moretti E, Dal Bosco A, et al. Short- and long-term effects of lipopolysaccharide-induced inflammation on rabbit sperm quality. Anim Reprod Sci 2010; 118:310-316.
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15. Collodel G, Castellini C, del Vecchio MT, Cardinali R, Geminiani M, Rossi B, et al. Effect of a bacterial lipopolysaccharide treatment on rabbit testis and ejaculated sperm. Reprod Domest Anim 2012; 47:372-378.
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16. Johnsen SG. Testicular biopsy score count--a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones 1970; 1:2-25.
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17. Azizollahi S, Babaei H, Derakhshanfar A, Oloumi MM. Effects of co-administration of dopamine and vitamin C on ischaemia-reperfusion injury after experimental testicular torsion-detorsion in rats. Andrologia 2011; 43:100-105.
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18. Kheirandish R, Askari N, Babaei H. Zinc therapy improves deleterious effects of chronic copper administration on mice testes: histopathological evaluation. Andrologia 2014; 46:80-85.
18
19. Inoue T, Aoyama-Ishikawa M, Kamoshida S, Nishino S, Sasano M, Oka N, et al. Endogenous interleukin 18 regulates testicular germ cell apoptosis during endotoxemia. Reproduction 2015; 150:105-114.
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20. Watanabe-Fukunaga R, Brannan CI, Itoh N, Yonehara S, Copeland NG, Jenkins NA, et al. The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen. J Immunol 1992; 148:1274-1279.
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21. Suda T, Takahashi T, Golstein P, Nagata S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell 1993; 75:1169-1178.
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22. Palladino MA, Savarese MA, Chapman JL, Dughi MK, Plaska D. Localization of Toll-like receptors on epididymal epithelial cells and spermatozoa. Am J Reprod Immunol 2008; 60:541-555.
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23. Sahnoun S, Sellami A, Chakroun N, Mseddi M, Attia H, Rebai T, et al. Human sperm Toll-like receptor 4 (TLR4) mediates acrosome reaction, oxidative stress markers, and sperm parameters in response to bacterial lipopolysaccharide in infertile men. J Assist Reprod Genet 2017; 34:1067-1077.
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24. Bhushan S, Schuppe HC, Fijak M, Meinhardt A. Testicular infection: microorganisms, clinical implications and host-pathogen interaction. J Reprod Immunol 2009; 83:164-167.
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25. Jegou B, Cudicini C, Gomez E, Stephan JP. Interleukin-1, interleukin-6 and the germ cell-Sertoli cell cross-talk. Reprod Fertil Dev 1995; 7:723-730.
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26. Lin T, Wang D, Stocco DM. Interleukin-1 inhibits Leydig cell steroidogenesis without affecting steroidogenic acute regulatory protein messenger ribonucleic acid or protein levels. J Endocrinol 1998; 156:461-467.
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27. Troiano L, Fustini MF, Lovato E, Frasoldati A, Malorni W, Capri M, et al. Apoptosis and spermatogenesis: evidence from an in vivo model of testosterone withdrawal in the adult rat. Biochem Biophys Res Commun 1994; 202:1315-1321.
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28. Wang RS, Yeh S, Tzeng CR, Chang C. Androgen receptor roles in spermatogenesis and fertility: lessons from testicular cell-specific androgen receptor knockout mice. Endocr Rev 2009; 30:119-132.
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29. Sadasivam M, Ramatchandirin B, Ayyanar A, Prahalathan C. Bacterial lipopolysaccharide differently modulates steroidogenic enzymes gene expressions in the brain and testis in rats. Neurosci Res 2014; 83:81-88.
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30. Tsai MY, Yeh SD, Wang RS, Yeh S, Zhang C, Lin HY, et al. Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells. Proc Natl Acad Sci U S A 2006; 103:18975-18980.
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31. Jegou B, Risbridger GP, de Kretser DM. Effects of experimental cryptorchidism on testicular function in adult rats. J Androl 1983; 4:88-94.
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32. Haywood M, Spaliviero J, Jimemez M, King NJ, Handelsman DJ, Allan CM. Sertoli and germ cell development in hypogonadal (hpg) mice expressing transgenic follicle-stimulating hormone alone or in combination with testosterone. Endocrinology 2003; 144:509-517.
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33. Turner TT, Lysiak JJ. Oxidative stress: a common factor in testicular dysfunction. J Androl 2008; 29:488-498.
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39. Paul C, Murray AA, Spears N, Saunders PT. A single, mild, transient scrotal heat stress causes DNA damage, subfertility and impairs formation of blastocysts in mice. Reproduction 2008; 136:73-84.
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41
ORIGINAL_ARTICLE
Neuroprotective effect of berberine chloride on cognitive impairment and hippocampal damage in experimental model of vascular dementia
Objective(s):The major objective of the present study was to investigate the potential neuroprotective effect of berberine chloride on vascular dementia. Berberine, as an ancient medicine in China and India, is the main active component derived from the Berberis sp. Several studies have revealed the beneficial effects of berberine in various neurodegenerative disorders. Materials and Methods: To induce vascular dementia, chronic bilateral common carotid artery occlusion was performed on male Wistar rats. After surgery, the rats were treated daily by oral administration of berberine chloride (50 mg/kg) for two months. The cognition function of treated rats, were evaluated by Morris Water Maze (MWM) test. In addition, Nissl and TUNEL staining were chosen to assess neuronal damage within the hippocampal CA1 area. Results: It was obvious that chronic cerebral hypoperfusion (CCH), caused cognitive impairment and neuronal damages within CA1 hippocampal subregion. Berberine chloride was able to prevent cognitive deficits, (P<0.05) and reversed CCH-induced hippocampal neuronal loss and apoptosis, (P<0.05). Conclusion: Berberine chloride may be considered as a potential treatment for cognitive deficits and neuronal injury caused by CCH in the hippocampal CA1 area.
https://ijbms.mums.ac.ir/article_9923_33a664e45f4f420afbab0a8a3a80f5d6.pdf
2018-01-01
53
58
10.22038/ijbms.2017.23195.5865
Apoptosis
Berberine
Hippocampus
Memory
Vascular dementia
Mahila
Lotfi Aski
mahilalotfiaski@gmail.com
1
International Campuse, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
AUTHOR
Mohammad Ebrahim
Rezvani
erezvani@yahoo.com
2
Neurobiomedical Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
AUTHOR
Mehdi
Khaksari
khaksari417@yahoo.com
3
Addiction Research Center, Shahroud University of Medical Sciences, Shahroud, Iran
AUTHOR
Zeynab
Hafizi
hafizi.z1991@gmail.com
4
Neurobiomedical Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
AUTHOR
Zeynab
Pirmoradi
z.pirmoradi.94@gmail.com
5
Neurobiomedical Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
AUTHOR
Somayeh
Niknazar
niknazar@gmail.com
6
Hearing Disorders Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
AUTHOR
Fatemeh
Zare Mehrjerdi
zaremehrjerdi_f@yahoo.com
7
Neurobiomedical Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
LEAD_AUTHOR
1. Lee JS, Im DS, An Y-S, Hong JM, Gwag BJ, Joo IS. Chronic cerebral hypoperfusion in a mouse model of Alzheimer's disease: an additional contributing factor of cognitive impairment. Neurosci Lett 2011;489:84-88.
1
2. Farkas E, Luiten PG, Bari F. Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Res Rev 2007;54:162-180.
2
3. Liu H, Zhang J. Cerebral hypoperfusion and cognitive impairment: the pathogenic role of vascular oxidative stress. Int J Neurosci 2012;122:494-499.
3
4. Pereira FM, Ferreira EDF, de Oliveira RMW, Milani H. Time-course of neurodegeneration and memory impairment following the 4-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion in middle-aged rats. Behav Brain Res 2012;229:340-348.
4
5. Jian H, Yi-Fang W, Qi L, Xiao-Song H, Gui-Yun Z. Cerebral blood flow and metabolic changes in hippocampal regions of a modified rat model with chronic cerebral hypoperfusion. ActaNeurol Belg 2013; 113:313-317.
5
6. Shamsaei N, Khaksari M, Erfani S, Rajabi H, Aboutaleb N. Exercise preconditioning exhibits neuroprotective effects on hippocampal CA1 neuronal damage after cerebral ischemia.Neural Regen Res 2015; 10:1245-50.
6
7. Ye M, Fu S, Pi R, He F. Neuropharmacological and pharmacokinetic properties of berberine: a review of recent research. J Pharm Pharmacol 2009;61:831-837.
7
8. Moghaddam HK, Baluchnejadmojarad T, Roghani M, Khaksari M, Norouzi P, Ahooie M, et al. Berberine ameliorate oxidative stress and astrogliosis in the hippocampus of STZ-induced diabetic rats. MolNeurobiol 2014;49:820-826.
8
9. Ji H-F, Shen L. Berberine: a potential multipotent natural product to combat Alzheimer’s disease. Molecules 2011;16:6732-6740.
9
10. Kim SO, Kim HJ. Berberine ameliorates cold and mechanical allodynia in a rat model of diabetic neuropathy. J Med Food 2013;16:511-517.
10
11. Kim M, Cho K-H, Shin M-S, Lee J-M, Cho H-S, Kim C-J, et al. Berberine prevents nigrostriatal dopaminergic neuronal loss and suppresses hippocampal apoptosis in mice with Parkinson's disease. Int J Mol Med 2014;33:870-878.
11
12. Pires ENS, Frozza RL, Hoppe JB, de Melo Menezes B, Salbego CG. Berberine was neuroprotective against an in vitro model of brain ischemia: survival and apoptosis pathways involved. Brain Res 2014;1557:26-33.
12
13. Cechetti F, Worm PV, Pereira L, Siqueira IR, A Netto C. The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method, but with a better survival rate. Braz J Med Biol Res 2010;43:1178-1183.
13
14. Mehrjerdi FZ, Aboutaleb N, Pazoki-Toroudi H, Soleimani M, Ajami M, Khaksari M, et al. The protective effect of remote renal preconditioning against hippocampal ischemia reperfusion injury: role of kATP channels. J MolNeurosci 2015;57:554-560.
14
15. Khaksari M, Mehrjerdi FZ, Rezvani ME, Safari F, Mirgalili A, Niknazar S. The role of erythropoietin in remote renal preconditioning on hippocampus ischemia/reperfusion injury. J Physiol Sci 2016:1-9.
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16. Ni J-W, Matsumoto K, Li H-B, Murakami Y, Watanabe H. Neuronal damage and decrease of central acetylcholine level following permanent occlusion of bilateral common carotid arteries in rat. Brain Res 1995;673:290-296.
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17. Román GC. Cholinergic dysfunction in vascular dementia. Curr Psychiatry Rep 2005;7:18-26.
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18. Giacobini E. Cholinergic receptors in human brain: effects of aging and Alzheimer disease. J Neurosci Res 1990;27:548-560.
18
19. Bhutada P, Mundhada Y, Bansod K, Tawari S, Patil S, Dixit P, et al. Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes. Behav Brain Res 2011; 220:30-41.
19
20. Huang L, Su T, Shan W, Luo Z, Sun Y, He F, et al. Inhibition of cholinesterase activity and amyloid aggregation by berberine-phenyl-benzoheterocyclic and tacrine-phenyl-benzoheterocyclic hybrids. Bioorganic Med Chem 2012;20:3038-3048.
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22. Matsuo Y, Kihara T, Ikeda M, Ninomiya M, Onodera H, Kogure K. Role of neutrophils in radical production during ischemia and reperfusion of the rat brain: effect of neutrophil depletion on extracellular ascorbyl radical formation. J Cereb Blood Flow Metab 1995;15:941-947.
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23. Erfani S, Aboutaleb N, Oryan S, Shamsaei N, Khaksari M, Kalalian-Moghaddam H, et al. Visfatin inhibits apoptosis and necrosis of hippocampus CA3 cells following transient global ischemia/reperfusion in rats. Int J Pept Res Ther 2015;21:223-228.
23
24. Hur JM, Hyun MS, Lim SY, Lee WY, Kim D. The combination of berberine and irradiation enhances anti‐cancer effects via activation of p38 MAPK pathway and ROS generation in human hepatoma cells. J Cell Biochem 2009;107:955-964.
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25. Ahmed T, Abdollahi M, Daglia M, Nabavi SF, Nabavi SM. Berberine and neurodegeneration: A review of literature. Pharmacol Rep 2015;67:970-979.
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26. Saxena AK, Majeed A, Saad S, Oothuman P, Mahmoud M, Al-Deen MI. Lipid peroxidation in chronic cerebral hypoperfusion-induced neurodegeneration in rats. Inter Med J Malaysia 2011;10:3-6.
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27. Zhang J, Yang J-Q, He B-C, Zhou Q-X, Yu H-R, Tang Y, et al. Berberine and total base from rhizoma coptis chinensis attenuate brain injury in an aluminum-induced rat model of neurodegenerative disease. Saudi Med J 2009;30:760-766.
27
28. Tomimoto H, Ihara M, Wakita H, Ohtani R, Lin J-X, Akiguchi I, et al. Chronic cerebral hypoperfusion induces white matter lesions and loss of oligodendroglia with DNA fragmentation in the rat.Acta Neuropathol 2003;106:527-534.
28
29. Kim S, Choi JH, Kim JB, Nam SJ, Yang J-H, Kim J-H, et al. Berberine suppresses TNF-α-induced MMP-9 and cell invasion through inhibition of AP-1 activity in MDA-MB-231 human breast cancer cells. Molecules 2008;13:2975-2985.
29
30. Domitrović R, Cvijanović O, Pernjak-Pugel E, Škoda M, Mikelić L, Crnčević-Orlić Ž. Berberine exerts nephroprotective effect against cisplatin-induced kidney damage through inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis. Food Chem Toxicol 2013;62:397-406.
30
ORIGINAL_ARTICLE
Metabolomics diagnostic approach to mustard airway diseases: a preliminary study
Objective(s): This study aims to evaluate combined proton nuclear magnetic resonance (1H NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS) metabolic profiling approaches, for discriminating between mustard airway diseases (MADs) and healthy controls and for providing biochemical information on this disease. Materials and Methods: In the present study, analysis of serum samples collected from 17 MAD subjects and 12 healthy controls was performed using NMR. Of these subjects, 14 (8 patients and 6 controls) were analyzed by GC-MS. Then, their spectral profiles were subjected to principal component analysis (PCA) and orthogonal partial least squares regression discriminant analysis (OPLS-DA). Results: A panel of twenty eight metabolite biomarkers was generated for MADs, sixteen NMR-derived metabolites (3-methyl-2-oxovaleric acid, 3-hydroxyisobutyrate, lactic acid, lysine, glutamic acid, proline, hydroxyproline, dimethylamine, creatine, citrulline, choline, acetic acid, acetoacetate, cholesterol, alanine, and lipid (mainly VLDL)) and twelve GC-MS-derived metabolites (threonine, phenylalanine, citric acid, myristic acid, pentadecanoic acid, tyrosine, arachidonic acid, lactic acid, propionic acid, 3-hydroxybutyric acid, linoleic acid, and oleic acid). This composite biomarker panel could effectively discriminate MAD subjects from healthy controls, achieving an area under receiver operating characteristic curve (AUC) values of 1 and 0.79 for NMR and GC-MS, respectively. Conclusion: In the present study, a robust panel of twenty-eight biomarkers for detecting MADs was established. This panel is involved in three metabolic pathways including aminoacyl-tRNA biosynthesis, arginine, and proline metabolism, and synthesis and degradation of ketone bodies, and could differentiate MAD subjects from healthy controls with a higher accuracy.
https://ijbms.mums.ac.ir/article_9924_68e116fbf106b759dd44ce3e151908a6.pdf
2018-01-01
59
69
10.22038/ijbms.2017.23792.5982
GC-MS
Metabolomics
Multivariate analysis
NMR spectroscopy
Sulfur mustard
BiBi Fatemeh
Nobakht Mothlagh Ghoochani
fatemeh.nobakht@yahoo.com
1
Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran
AUTHOR
Rasoul
Aliannejad
raliannejad@gmail.com
2
Pulmonary Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
LEAD_AUTHOR
Afsaneh
Arefi Oskuei
a.arefi@sbmu.ac.ir
3
Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
AUTHOR
Mostafa
Rezaei-Tavirani
tavirany@yahoo.com
4
Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
AUTHOR
Shiva
Kalantari
shivakalantari_81@yahoo.com
5
Chronic Kidney Disease Research Center, Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
AUTHOR
Mohammad Taghi
Naseri
m_t_naseri@yahoo.com
6
Department of Chemistry, Faculty of Sciences, Tarbiat Modares University, Tehran, Iran
AUTHOR
Alireza
Bagheban
akbarzad@gmail.com
7
Physiotherapy Research Center, School of Rehabilitation, Shahid Beheshti University of Medical Sciences, Tehran, Iran
AUTHOR
Hadi
Parastar
h.parastar@gmail.com
8
Department of Chemistry, Sharif University of Technology, Tehran, Iran
AUTHOR
Ghazale
Aliakbarzadeh
gh.aliakbarzadeh@gmail.com
9
Department of Chemistry, Faculty of Science, University of Tehran, Tehran, Iran
AUTHOR
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14. Nobakht M. Gh BF, Arefi Oskouie A, Rezaei-Tavirani M, Aliannejad R, Taheri S, Fathi F, et al. NMR spectrometry-based metabolomic study of serum in sulfur mustard exposed patients with lung disease. Biomarkers 2016; 22:413-419.
14
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22. Xu WF, Upur H, Wu YH, Mamtimin B, Yang J, Ga YJ, et al. Metabolomic changes in patients with chronic obstructive pulmonary disease with abnormal Savda syndrome. Exp Ther Med 2015; 9:425-431.
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30. Nobakht M. Gh BF, Oskouie AA, Aliannejad R, Rezaei-Tavirani M, Tavallaie S, Baghban AA, et al. Pro-oxidant–antioxidant balance in Iranian veterans with sulfur mustard toxicity and different levels of pulmonary disorders. Drug Chem Toxicol 2015:39: 362-366.
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48. Gao X, Ray R, Xiao Y, Ishida K, Ray P. Macrolide antibiotics improve chemotactic and phagocytic capacity as well as reduce inflammation in sulfur mustard-exposed monocytes. Pulm Pharmacol Ther 2010; 23:97-106.
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49
ORIGINAL_ARTICLE
Monitoring wound healing of burn in rat model using human Wharton’s jelly mesenchymal stem cells containing cGFP integrated by lentiviral vectors
Objective(s): Human Wharton’s Jelly mesenchymal stem cells (hWMSCs) are undifferentiated cells commonly used in regenerative medicine. The aim of this study was to develop a reliable tool for tracking hWMSCs when utilized as therapeutics in burnt disorders and also to optimize the cell-based treatment procedure. Materials and Methods: The hWMSCs were first isolated from fresh umbilical cord Wharton’s jelly and cultured. The 293LTV cell line was transfected by cGFP containing lentiviral vector and the helper plasmids for production of the viral particle. The viral particles were collected to transduce the hWMSCs. The transduced cells were finally selected based on resistance to puromycin. The burned rats (n=24) were treated with cGFP expressing hWMSCs using the cell spray method, with the cells being tracked 7, 14 and 21 days later. The rats were sacrificed 7, 14 and 21 days following treatment and paraffin embedded sections prepared from the burned area for downstream pathological analyses. Results: The lentiviral particles carrying the cGFP gene were generated and the hWMSCs were transduced. The cGFP-expressing hWMSCs were detected in the burned tissue and the burned injuries were improved dramatically as compared to control. Conclusion: Because of the establishment of stably transduced cGFP expressing cells and the ability to detect cGFP for a relatively long-time interval, the method was found to be quite efficient for the purpose of cell tracking. The combination of hWMSC-based cell therapy and sterile Gauze Vaseline (GV) as covering was proven much more efficient than the traditional methods based on GV alone.
https://ijbms.mums.ac.ir/article_9861_433e929277c30a0be50fe469a10a0f57.pdf
2018-01-01
70
76
10.22038/ijbms.2017.19783.5212
Cell and tissue-based therapy
Cell Tracking
Lentivirus
Mesenchymal stem cells
Wound healing
Mohammad Reza
Pourfath
mpourfath@gmail.com
1
Burn and Wound Healing Research Center, Shiraz University of Medical Science, Shiraz, Iran
AUTHOR
Abbas Behzad
Behbahani
behzadba@gmail.com
2
Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
AUTHOR
Seyedeh Sara
Hashemi
sara_hashemi@sums.ac.ir
3
Burn and Wound Healing Research Center, Shiraz University of Medical Science, Shiraz, Iran
LEAD_AUTHOR
Amin
Derakhsahnfar
derakhshanfar@sums.ac.ir
4
Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
AUTHOR
Mohammad Naser
Taheri
mohamadnasertaheri@gmail.com
5
Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
AUTHOR
Saeede
Salehi
saeede.salehi@yahoo.com
6
Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
AUTHOR
1. Leclerc T, Thepenier C, Jault P, Bey E, Peltzer J, Trouillas M, et al. Cell therapy of burns. Cell Prolif 2011; 44: 48–54.
1
2. Kagan RJ, Peck MD, Ahrenholz DH, Hickerson WL, Holmes J 4th, Korentager R, et al. Surgical management of the burn wound and use of skin substitutes: an expert panel white paper. J Burn Care Res 2013; 34: e60–79.
2
3. Puri V, Khare NA, Chandramouli MV, Shende N, Bharadwaj S. Comparative analysis of early excision and grafting vs delayed grafting in burn patients in a developing country. J Burn Care Res 2016; 37:278-282.
3
4. Hermans, M. H. Porcine xenografts vs. (cryopreserved) allografts in the management of partial thickness burns: is there a clinical difference? Burns 2014; 40: 408-415.
4
5. Troyer DL, Weiss ML. Concise review: Wharton’s jelly-derived cells are a primitive stromal cell population. Stem Cells 2008; 26: 591-599.
5
6. Fong CY, Richards M, Manasi N, Biswas A, Bongso A. Comparative growth behaviour and characterization of stem cells from human Wharton’s jelly. Reprod Biomed Online 2007; 15: 708–718.
6
7. Baksh D, Yao R, Tuan RS. Comparison of Proliferative and Multilineage Differentiation Potential of Human Mesenchymal Stem Cells Derived from Umbilical Cord and Bone Marrow. STEM CELLS 2007; 25: 1384 –1392.
7
8. Xue L, Xu YB, Xie JL, Tang JM, Shu B, Chen L, et al. Effects of human bone marrow mesenchymal stem cells on burn injury healing in a mouse model. Int J Clin Exp Pathol 2013; 6: 1327-1336.
8
9. Liu L, Yu Y, Hou Y, Chai J, Duan H, Chu W, et al. Human Umbilical Cord Mesenchymal Stem Cells Transplantation Promotes Cutaneous Wound Healing of Severe Burned Rats. PLoS ONE 2014; 9: 1-7.
9
10. Burd A, Ahmed K, Lam S, Ayyappan T, Huang L, Stem cell strategies in burns care. Burns 2007; 33: 282-291.
10
11. Liu P, Deng Z, Han S, Liu T, Wen N, Lu W, et al. Tissue-engineered skin containing mesenchymal stem cells improves burn wounds. Artif Organs 2008; 32: 925-931.
11
12. Wu Y, Wang J, Scott PG, Tredget EE. Bone marrow-derived stem cells in wound healing: a review. Wound Repair Regen 2007; 15: 18-26.
12
13. Salehinejad P, Alitheen NB, Ali AM, Omar AR, Mohit M, Janzamin E, et al. Comparison of different methods for the isolation of mesenchymal stem cells from human umbilical cord Wharton's jelly. In Vitro Cell Dev Biol 2012;48:75-83
13
14. Klages N, Zufferey R, Trono D. A stable system for the high-titer production of multiply attenuated lentiviral vectors. Mol Ther 2000; 2:170-176.
14
15. Wong D, Makowska IJ, Weary DM. Rat aversion to isoflurane versus carbon dioxide. Biology letters. 2012; 9: 1-4.
15
16. MEYER, Tufi Neder; SILVA, Alcino Lázaro da. A standard burn model using rats. Acta Cir. Bras 1999;14.
16
17. Navarro FA, Stoner ML, Park CS, Huertas JC, Lee HB, Wood FM, et al. Sprayed keratinocyte suspensions accelerate epidermal coverage in a porcine micro-wound model. J Burn Care Rehabil 2000; 21: 513-518.
17
18. Fischer A H, Jacobson K A, Rose J, & Zeller R. Hematoxylin and eosin staining of tissue and cell sections. Cold Spring Harbor Protocols 2008; 3.
18
19. Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF. Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacologica Sinica 2013; 34: 747–754.
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20. Korbling M, Estrove Z. Adult stem cells for tissue repair-a new therapeutic concept? N Engl J Med 2003;349: 570-582.
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21. De Girolamo L, Lucarelli E, Alessandri G, et al. Mesenchymal Stem/Stromal Cells: A New "Cells as Drugs" Paradigm. Efficacy and Critical Aspects in Cell Therapy. Current Pharmaceutical Design 2013;19: 2459-2473.
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22. Marguerie E, Michael P. Scherrer, Frank D. Ferrari, Mikhail V. Matz. Very Bright Green Fluorescent Proteins from the Ponellid Copepod Pontella mimocerami. PLoS ONE 2010; 5: e11517.
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23. Yannas, Ioannis V. Tissue and organ regeneration in adults. Springer Publishing Co; 2015.
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24. Ankrum J, Jeffrey M K. Mesenchymal stem cell therapy: Two steps forward, one step back. Trends in Molecular Medicine 2010; 5: 203-209.
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25. Hocking AM, Gibran NS. Mesenchymal stem cells: paracrine signaling and differentiation during cutaneous wound repair. Exp Cell Res 2010; 2213–2219.
25
26. Ko IK, Lee SJ, Atala A, Yoo JJ. In situ tissue regeneration through host stem cell recruitment. Experimental & Molecular Medicine 2013; 45: e57.
26
ORIGINAL_ARTICLE
99mTc-Glucarate for assessment of paclitaxel therapy in human ovarian cancer in mice
Objectives: The monitoring of cancer treatment response to chemotherapy is considered an essential strategy for follow-up of patients. The aim of this study was to evaluate the use of 99mTc-glucarate as a radiotracer for in vivo quantification and visualization of necrotic area and therapeutic effect of paclitaxel in ovarian cancer xenografted nude mice. Materials and Methods: After implantation of human ovarian cancer (SKOV-3) in nude mice, tumor xenografted mice were enrolled in two groups as control and treatment (paclitaxel) groups. 99mTc-glucarate uptakes were quantified in tumors of control and treatment groups and also tumor imaging was performed with a gamma camera. The necrotic and viable areas of tumor and tumoral masses were evaluated through histopathological and macroscopic observations, respectively. Results: 99mTc-glucarate uptake in tumor of treatment group was higher than control group.99mTc-glucarate uptake in ovarian tumor was clearly visualized with gamma imaging in both groups, but paclitaxel treated group showed higher radioactive uptake than control mice. The necrotic area in tumoral mass of mice treated with paclitaxel was confirmed by histopathological observations. Conclusion: 99mTc-glucarate is an effective radiotracer for evaluation and monitoring of tumor necrosis caused by chemotherapy, and it may be helpful for therapy monitoring in patients with cancer.
https://ijbms.mums.ac.ir/article_9894_716dc0ce6baa87893a3bb957a15af8a1.pdf
2018-01-01
77
82
10.22038/ijbms.2017.24707.6138
99mTc-glucarate
Imaging
Necrosis
Ovarian cancer
Paclitaxel
Hossein
Sadeghi
hosseinsadeghi1991@yahoo.com
1
Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
AUTHOR
Najmeh
Rahmanian
najme.rahmanian@yahoo.com
2
Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
AUTHOR
Fereshteh
Talebpour Amiri
ftaleb2001@yahoo.co.uk
3
Department of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran
AUTHOR
Hossein
Amirfakhrian
hosseinamirfakhrian@yahoo.com
4
Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
AUTHOR
Seyed Mohammad
Abedi
mabedi167@yahoo.com
5
Department of Radiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
AUTHOR
Seyed Jalal
Hosseinimehr
sjhosseinim@yahoo.com
6
Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
LEAD_AUTHOR
1. Tortolero-Luna G, Mitchell MF. The epidemiology of ovarian cancer. J Cell Biochem Suppl 1995; 23:200-207.
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2. Baldwin LA, Huang B, Miller RW, Tucker T, Goodrich ST, Podzielinski I, et al. Ten-year relative survival for epithelial ovarian cancer. Obstet Gynecol 2012; 120:612-618.
2
3. Muggia FM, Braly PS, Brady MF, Sutton G, Niemann TH, Lentz SL, et al. Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: a gynecologic oncology group study. J Clin Oncol 2000; 18:106-115.
3
4. Zhang D, Yang R, Wang S, Dong Z. Paclitaxel: new uses for an old drug. Drug Des Devel Ther 2014; 8:279-284.
4
5. Kampan NC, Madondo MT, McNally OM, Quinn M, Plebanski M. Paclitaxel and its evolving role in the management of ovarian cancer. Biomed Res Int 2015; 2015:413076.
5
6. Yeung TK, Germond C, Chen X, Wang Z. The mode of action of taxol: apoptosis at low concentration and necrosis at high concentration. Biochem Biophys Res Commun 1999; 263:398-404.
6
7. Mailloux A, Grenet K, Bruneel A, Beneteau-Burnat B, Vaubourdolle M, Baudin B. Anticancer drugs induce necrosis of human endothelial cells involving both oncosis and apoptosis. Eur J Cell Biol 2001; 80:442-449.
7
8. Wu Y, Chu Q, Tan S, Zhuang X, Bao Y, Wu T, et al. D-alpha-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery. Int J Nanomedicine 2015; 10:5219-5235.
8
9. Neesham D. Ovarian cancer screening. Aust Fam Physician 2007; 36:126-128.
9
10. Kumar S, Mahdi H, Bryant C, Shah JP, Garg G, Munkarah A. Clinical trials and progress with paclitaxel in ovarian cancer. Int J Womens Health 2010; 2:411-427.
10
11. Iyer VR, Lee SI. MRI, CT, and PET/CT for ovarian cancer detection and adnexal lesion characterization. AJR Am J Roentgenol 2010; 194:311-321.
11
12. Berger M, Gould MK, Barnett PG. The cost of positron emission tomography in six United States Veterans Affairs hospitals and two academic medical centers. AJR Am J Roentgenol 2003; 181:359-365.
12
13. Arteaga de Murphy C, Ferro-Flores G, Villanueva-Sanchez O, Murphy-Stack E, Pedraza-Lopez M, Melendez-Alafort L, et al. 99mTc-glucarate for detection of isoproterenol-induced myocardial infarction in rats. Int J Pharm 2002; 233:29-34.
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14. Khaw B-A, Nakazawa A, O'donnell SM, Pak K-Y, Narula J. Avidity of technetium 99m glucarate for the necrotic myocardium: in vivo and in vitro assessment. J Nucl Cardiol 1997; 4:283-290.
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32
ORIGINAL_ARTICLE
Tanshinone IIA inhibits AGEs-induced proliferation and migration of cultured vascular smooth muscle cells by suppressing ERK1/2 MAPK signaling
Objective(s): Vascular smooth muscle cells (VSMCs) play a key role in the pathogenesis of diabetic vascular disease. Our current study sought to explore the effects of tanshinone IIA on the proliferation and migration of VSMCs induced by advanced glycation end products (AGEs). Materials and Methods: In this study, we examined the effects of tanshinone IIA by cell proliferation assay and cell migration assay. And we explored the underlying mechanism by Western blotting. Results: AGEs significantly induced the proliferation and migration of VSMCs, but treatment with tanshinone IIA attenuated these effects. AGEs could increase the activity of the ERK1/2 and p38 pathways but not the JNK pathway. Treatment with tanshinone IIA inhibited the AGEs-induced activation of the ERK1/2 pathway but not the p38 pathway. Conclusion: Tanshinone IIA inhibits AGEs-induced proliferation and migration of VSMCs by suppressing the ERK1/2 MAPK signaling pathway.
https://ijbms.mums.ac.ir/article_9925_28e01b97026f81ad151815134a0a228d.pdf
2018-01-01
83
88
10.22038/ijbms.2017.20100.5276
Advanced
ERK1/2
Glycation end products
JNK
p38
Tanshinone IIA
Vascular Smooth Muscle
Ming
Lu
18857173520@163.com
1
Department of Cardiology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China, 310005
AUTHOR
Ying
Luo
819359084@qq.com
2
Department of Cardiology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China, 310005
AUTHOR
Pengfei
Hu
hupengfei5566@163.com
3
Department of Cardiology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China, 310005
AUTHOR
Liping
Dou
13185717751@163.com
4
Department of Cardiology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China, 310005
AUTHOR
Shuwei
Huang
hsw1104@126.com
5
Department of Cardiology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China, 310005
LEAD_AUTHOR
1. Allalou A, Nalla A, Prentice KJ, Liu Y, Zhang M, Dai FF, et al. A Predictive metabolic signature for the transition from gestational diabetes to type 2 diabetes. Diabetes 2016; 65:2529-2539.
1
2. Jain A, Tantia P, Saini K, Sulemani AA, Sirohi P, Rizwani P, et al. Ratio of waist-to-calf circumference and carotid atherosclerosis in patients of type 2 diabetes mellitus. J Assoc Physicians India 2016; 64:32-35.
2
3. Berezin AE, Kremzer AA, Berezina TA, Martovitskaya YV. The pattern of circulating microparticles in patients with diabetes mellitus with asymptomatic atherosclerosis. Acta Clin Belgica 2016:38-45.
3
4. Doran AC, Meller N, Mcnamara CA. Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arterioscler Thromb Vasc Biol 2008; 28:812-819.
4
5. Chen WJ, Lin KH, Lai YJ, Yang SH, Pang JH. Protective effect of propylthiouracil independent of its hypothyroid effect on atherogenesis in cholesterol-fed rabbits: PTEN induction and inhibition of vascular smooth muscle cell proliferation and migration. Circulation 2004; 110:1313-1319.
5
6. Onalan O, Adar A, Keles H, Ertugrul G, Ozkan N, Aktas H, et al. Onychomycosis is associated with subclinical atherosclerosis in patients with diabetes. Vasa 2015; 44:59-64.
6
7. He M, Xue ZM, Li J, Zhou BQ. Breviscapine inhibits high glucose-induced proliferation and migration of cultured vascular smooth muscle cells of rats via suppressing the ERK1/2 MAPK signaling pathway. Acta Pharmacol Sin 2012; 33:606-614.
7
8. Ganguly R, Sahu S, Chavez RJ, Raman P. Trivalent chromium inhibits TSP-1 expression, proliferation, and O-GlcNAc signaling in vascular smooth muscle cells in response to high glucose in vitro. Am J Physiol Cell 2015; 308:C111-22.
8
9. Liu Y, Wang WM, Zhang XL, He HQ, Sun XL, Zeng H, et al. AGE/RAGE promotes thecalcification of human aortic smooth muscle cells via the Wnt/β-catenin axis. Am J Transl Res 2016; 8:4644-4656.
9
10. Zeng H, Huang Z, Zhang Y, Sun H. Role of p38MAPK/eNOS signaling pathway in the inhibition of AGEs-induced apoptosis of human umbilical vein endothelial cells by glucagon-like peptide-1. Nan Fang Yi Ke Da Xue Xue Bao 2016; 36:116-119.
10
11. Forbes JM, Yee LT, Thallas V, Lassila M, Candido R, Jandeleit-Dahm KA, et al. Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis. Diabetes 2004; 53:1813-1823.
11
12. Basta G, Lazzerini G, Turco SD, Ratto GM, Schmidt AM, De Caterina R. At least 2 distinct pathways generating reactive oxygen species mediate vascular cell adhesion molecule-1 induction by advanced glycation end products. Arterioscler Thromb Vasc Biol 2005; 25:1401-1407.
12
13. Xu B, Chibber R, Ruggiero D, Kohner E, Ritter J, Ferro A, et al. Impairment of vascular endothelial nitric oxide synthase activity by advanced glycation end products. FASEB J 2003; 17:1289-1291.
13
14. Li H, Cheng Y, Simoncini T, Xu S. 17β-Estradiol inhibits TNF-α-induced proliferation and migration of vascular smooth muscle cells via suppression of TRAIL. Gynecol Endocrinol 2016; 32:581-586.
14
15. Quan KT, Park HS, Oh J, Park HB, Ferreira D, Myung CS, et al. Arborinane triterpenoids from rubia philippinensis inhibit proliferation and migration of vascular smooth muscle cells induced by the platelet-derived growth factor. J Nat Prod 2016; 79:2559-2569.
15
16. Gong Z, Huang C, Sheng X, Zhang Y, Li Q, Wang MW, et al. The role of tanshinone IIA in the treatment of obesity through peroxisome proliferator-activated receptor gamma antagonism. Endocrinology 2009; 150:104-113.
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17. Li X, Du JR, Yu Y, Bai B, Zheng XY. Tanshinone IIA inhibits smooth muscle proliferation and intimal hyperplasia in the rat carotid balloon-injured model through inhibition of MAPK signaling pathway. J Ethnopharmacol 2010; 129:273-279.
17
18. Pan C, Lou L, Huo Y, Singh G, Chen M, Zhang D, et al. Salvianolic acid B and tanshinone IIA attenuate myocardial ischemia injury in mice by NO production through multiple pathways. Ther Adv Cardiovasc Dis 2011; 5:99-111.
18
19. Wu WY, Yan H, Wang XB, Gui YZ, Gao F, Tang X, et al. Sodium Tanshinone IIA silate inhibits high glucose-induced vascular smooth muscle cell proliferation and migration through activation of amp-activated protein kinase. PloS One 2014; 9:e94957.
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20. Hou FF, Chertow GM, Kay J, Boyce J, Lazarus JM, Braatz JA, et al. Interaction between beta 2-microglobulin and advanced glycation end products in the development of dialysis related-amyloidosis. Kidney Int 1997; 51:1514-1519.
20
21. Lv L, Zhang J, Wang P, Meng Q, Liang W, Zhang L. Zinc finger protein 191 deficiency attenuates vascular smooth muscle cell proliferation, migration, and intimal hyperplasia after endovascular arterial injury. J Vascular Surg 2013; 59(2):500-509.
21
22. Hu P, Lai D, Lu P, Gao J, He H. ERK and Akt signaling pathways are involved in advanced glycation end product-induced autophagy in rat vascular smooth muscle cells. Int J Mol Med 2012; 29:613-618.
22
23. Rubinat E, Marsal JR, Vidal T, Cebrian C, Falguera M, Vilanova MB, et al. Subclinical carotid atherosclerosis in asymptomatic subjects with type 2 diabetes mellitus. J Cardiovasc Nurs 2015; 31:E1-E7.
23
24. Xiao J, Jin K, Wang J, Jing M, Jin Z, Nan J, et al. Conditional knockout of TFPI-1 in VSMCs of mice accelerates atherosclerosis by enhancing AMOT/YAP pathway. Int J Cardiol 2016; 228:605-614.
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25. Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 2006; 114:597-605.
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26. Jang JY, Kim J, Cai J, Kim Y, Shin K, Kim TS, et al. An ethanolic extract of Angelica gigas improves atherosclerosis by inhibiting vascular smooth muscle cell proliferation. Lab Anim Res 2014; 30:84-89.
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27. Yoon YW, Kang TS, Lee BK, Chang W, Hwang KC, Rhee JH, et al. Pathobiological role of advanced glycation endproducts via mitogen-activated protein kinase dependent pathway in the diabetic vasculopathy. Exp Mol Med 2008; 40:398-406.
27
28. Liang Y, Hou C, Kong J, Wen H, Zheng X, Wu L, et al. HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1/2. Mol Cell Biochem 2015; 405:63-71.
28
29. Rzepka R, Dołęgowska B, Sałata D, Rajewska A, Budkowska M, Domański L, et al. Soluble receptors for advanced glycation end products and receptor activator of NF-κB ligand serum levels as markers of premature labor. BMC Pregnancy Childbirth 2015; 15:134.
29
30. Temaru R, Urakaze M, Satou A, Yamazaki K, Nakamura N, Kobayashi M. High glucose enhances the gene expression of interleukin-8 in human endothelial cells, but not in smooth muscle cells: possible role of interleukin-8 in diabetic macroangiopathy. Diabetologia 1997; 40:610-613.
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31
32. Kim SK, Jung KH, Lee BC. Protective effect of tanshinone IIA on the early stage of experimental diabetic nephropathy. Biol Pharm Bull 2009; 32:220-224.
32
33. Hwang SL, Yang JH, Jeong YT, Kim YD, Li X, Lu Y, et al. Tanshinone IIA improves endoplasmic reticulum stress-induced insulin resistance through AMP-activated protein kinase. Biochem Biophys Res Commun 2013; 430:1246-1252.
33
ORIGINAL_ARTICLE
Intrauterine xenotransplantation of human Wharton jelly-derived mesenchymal stem cells into the liver of rabbit fetuses: A preliminary study for in vivo expression of the human liver genes
Objective(s): End-stage hepatic failure is a potentially life-threatening condition for which orthotopic liver transplantation is the only effective treatment. However, a shortage of available donor organs for transplantation each year results in the death of many patients waiting for liver transplantation. Xenotransplantation, or the transplantation of cells, tissues, or organs between different species, was proposed as a possible solution to the worldwide shortage of human organs and tissues for transplantation. The purpose of this preliminary study was to reconstruct human liver tissue by xenotransplantation of human Wharton jelly mesenchymal stem cells (hWJ-MSCs) into fetal rabbit. Materials and Methods: Isolation and confirmation of hWJ-MSCs from human umbilical cord was performed. Eight rabbits at gestational day 14 were anesthetized. All rabbits carried pregnancies to term yielding 40 rabbit fetuses. Intrauterine injection of hWJ-MSCs was performed in 24 fetuses. Twenty-seven fetuses were born alive. Ten liver samples from injected fetuses were sampled, eight rabbits 3 days after birth and two rabbits 21 days after birth. The non-injected fetuses served as positive control. Fetuses of non-injected rabbits were negative controls. Using real-time polymerase chain reaction (RT-PCR), mRNA expression of albumin (ALB), α-fetoprotein (AFP), hepatic nuclear factor 4 (HNF4), and CYP2B6 (CYP) were detected in liver samples. Results: The human ALB, AFP, HNF4, and CYP mRNAs were expressed in the injected sampled fetuses by hWJ-MSCs into fetuses of rabbits in utero. Conclusion: Developing xenotransplantation of hWJ-MSCs into rabbit uterus can introduce an applied approach for producing human liver tissue in rabbits.
https://ijbms.mums.ac.ir/article_9926_0d97b957deb40fba1120f9a5bf380ceb.pdf
2018-01-01
89
96
10.22038/ijbms.2017.24501.6098
Human
Liver
Mesenchymal stem cells
Rabbit
Wharton jelly
Xenotransplantation
Leila
Rezaeian
lrezaean92@gmail.com
1
Department of Biology, College of Science, Fars Science and Research Branch, Islamic Azad University, Fars, Iran
AUTHOR
Seyed Ebrahim
Hosseini
ebhoseini@srbiau.ac.ir
2
Department of Biology, College of Science, Shiraz Branch, Islamic Azad University, Shiraz, Iran
AUTHOR
Mehdi
Dianatpur
mdianatpur@gmail.com
3
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
LEAD_AUTHOR
Mohammad Amin
Edalatmanesh
amin.edalatmanesh@gmail.com
4
Department of Biology, College of Science, Shiraz Branch, Islamic Azad University, Shiraz, Iran
AUTHOR
Nader
Tanideh
tanidehn@gmail.com
5
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
AUTHOR
Asghar
Mogheiseh
mogheiseh@yahoo.com
6
6 Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
AUTHOR
Amin
Tamadon
amintamaddon@yahoo.com
7
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
AUTHOR
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51. Shaterzadeh-Yazdi H, Mehrabani D, Khodakaram-Tafti A, Dianatpour M, Zare SH, Tamadon A, et al. Osteogenic potential of subcutaneous adipose-derived stem cells in a rabbit model. Online J Vet Res 2015; 19:436-445.
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52. Mehrabani D, Hassanshahi MA, Tamadon A, Zare S, Keshavarz S, Rahmanifar F, et al. Adipose tissue-derived mesenchymal stem cells repair germinal cells of seminiferous tubules of busulfan-induced azoospermic rats. J Hum Reprod Sci 2015; 8:103-110.
52
53. Tamadon A, Mehrabani D, Zarezadeh Y, Rahmanifar F, Dianatpour M, Zare S. Caprine endometrial mesenchymal stromal stem cell: multi-lineage potential, characterization and growth kinetics in breeding and anestrous stages. Vet Med Int 2017; 2017:5052801.
53
54. Mehrabani D, Rahmanifar F, Mellinejad M, Tamadon A, Dianatpour M, Zare S, et al. Isolation, culture, characterization, and adipogenic differentiation of heifer endometrial mesenchymal stem cells. Comp Clin Pathol 2015; 24:1159-1164.
54
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55
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56
ORIGINAL_ARTICLE
Mast cells and pro-inflammatory cytokines roles in assessment of grape seeds extract anti-inflammatory activity in rat model of carrageenan-induced paw edema
Objective(s): Reactive oxygen species (ROS)-produced oxidative disorders were involved at the pathophysiology of many inflammatory processes via the generation of pro-inflammatory cytokines and antioxidant defense system suppression. Although herbal antioxidants as mono-therapy relief many inflammatory diseases including, autoimmunity rheumatoid arthritis, but as combination therapy with other proven anti-inflammatory drugs in order to decreasing their toxic impacts has not yet been studied clearly, especially against chemical substances that’s induced local inflammation with characteristic edema. Materials and Methods: Grape seeds extract (GSE) at a concentration of 40 mg/kg B. wt alone or in combination with indomethacin (Indo.) at a dose of 5 mg/Kg B. wt orally given for 10 days prior (gps VI, VII, VIII) or as a single dose after edema induction (gps IX, X, XI) in rat's left hind paw by sub-planter single injection of 0.1 carrageenan: saline solution (1%) (gp. V) to assess the prophylactic and therapeutic anti-inflammatory activities of both through the estimation of selective inflammatory mediators and oxidative damage-related biomarkers as well as tissue mast cell scoring. Furthermore, both substances were given alone (gps II, III, IV) for their blood, liver and kidney safety evaluation comparing with negative control rats (gp. I) which kept without medication. Results: A marked reduction on the inflammatory mediators, edema volume and oxidative byproducts in edema bearing rats' prophylactic and treated with grape seeds extract and indomethacin was observed. Indomethacin found to induce some toxicological impacts which minimized when administered together with GSE. Conclusion: GSE is a safe antioxidant agent with anti-inflammatory property.
https://ijbms.mums.ac.ir/article_9859_96d8bfc4d4525460445445f78f81944d.pdf
2018-01-01
97
107
10.22038/ijbms.2017.25067.6219
Gastritis
TNF-α
IgE
Indomethacin
Proanthocyanidins
Toluidine-blue
Amany Ahmed
Mohamed Abd-Allah
1
Department of Clinical Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
AUTHOR
Nasr Abdelwahab
Mohamed Nasr El-Deen
2
Department of Clinical Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
AUTHOR
wafaa
mohamed
waffa.clinical@yahoo.com
3
lecturer of clinical pathology,faculty of veterinary medicine,zagazig university
LEAD_AUTHOR
Fatma
Mohamed Naguib
4
MVSc of Clinical Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
AUTHOR
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81
ORIGINAL_ARTICLE
Novel frameshift mutation in the KCNQ1 gene responsible for Jervell and Lange-Nielsen syndrome
Objective(s): Jervell and Lange–Nielsen syndrome is an autosomal recessive disorder caused by mutations in KCNQ1 or KCNE1 genes. The disease is characterized by sensorineural hearing loss and long QT syndrome. Methods: Here we present a 3.5-year-old female patient, an offspring of consanguineous marriage, who had a history of recurrent syncope and congenital sensorineural deafness. The patient and the family members were screened for mutations in KCNQ1 gene by linkage analysis and DNA sequencing. Results: DNA sequencing showed a c.1532_1534delG (p. A512Pfs*81) mutation in the KCNQ1 gene in homozygous form. The results of short tandem repeat (STR) markers showed that the disease in the family is linked to the KCNQ1 gene. The mutation was confirmed in the parents in heterozygous form. Conclusion: This is the first report of this variant in KCNQ1 gene in an Iranian family. The data of this study could be used for early diagnosis of the condition in the family and genetic counseling.
https://ijbms.mums.ac.ir/article_9900_af4ea92404f64e2b7beb535b3c832e8b.pdf
2018-01-01
108
111
10.22038/ijbms.2017.23207.5908
Arrhythmia
Iran
Jervell and Lange-Nielsen syndrome
KCNQ1
Long-QT syndrome
Romano-Ward syndrome
Azam
Amirian
azxamirian2000@yahoo.com
1
Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
AUTHOR
Seyed Mohammad
Dalili
drdalili@yahoo.com
2
Cardiac Electrophysiology Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
AUTHOR
Zahra
Zafari
z.zafari@modares.ac.ir
3
Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
AUTHOR
Siamak
Saber
s_saber2002@yahoo.com
4
Cardiac Electrophysiology Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
AUTHOR
Morteza
Karimipour
mortezakarimi@yahoo.com
5
Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
AUTHOR
Vahid
Akbari
vahid.akbari1369@yahoo.com
6
Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
AUTHOR
Amirfarjam
Fazelifar
fazelifar@gmail.com
7
Cardiac Electrophysiology Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
AUTHOR
Sirous
Zeinali
zeinalipasteur@yahoo.com
8
Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
LEAD_AUTHOR
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3
4. Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, et al. Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION® long QT syndrome genetic test. Heart Rhythm 2009;6:1297-1303.
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5. Bhuiyan ZA, Wilde AA. IKs in heart and hearing, the ear can do with less than the heart. Circ Cardiovasc Genet 2013;6:141-143.
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6. Giudicessi JR, Ackerman MJ. Prevalence and potential genetic determinants of sensorineural deafness in KCNQ1 homozygosity and compound heterozygosity. Circ Cardiovasc Genet 2013;6:193-200.
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8. Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K, et al. The Jervell and Lange-Nielsen syndrome natural history, molecular basis, and clinical outcome. Circulation 2006;113:783-90.
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9. Chacon-Cortes D, Griffiths LR. Methods for extracting genomic DNA from whole blood samples: current perspectives. J biorepos sci appl med 2014; 2014:1-9.
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10. Amirian A, Karimipoor M, Jafarinejad M, Taghavi M, Kordafshari A, Azar SF, et al. First report on the co-inheritance of beta-globin IVS-I-5 (G--> C) thalassemia with delta globin CD12 {Asn--> Lys (AAT--> AAA)} HbA₂-NYU in Iran. Arch Iran Med 2011;14:8-11.
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11. Kılıç E, Ertuğrul İ, Özer S, Alikaşifoğlu M, Aktaş D, Boduroğlu K, et al. Jervell and Lange-Nielsen syndrome with homozygous missense mutation of the KCNQ1 gene. Turk J Pediatr 2014;56:542-545.
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12. Siem G, Früh A, Leren TP, Heimdal K, Teig E, Harris S. Jervell and Lange-Nielsen syndrome in Norwegian children: aspects around cochlear implantation, hearing, and balance. Ear Hear 2008;29:261-269.
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13. Neyroud N, Richard P, Vignier N, Donger C, Denjoy I, Demay L, et al. Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome. Circ Res1999;84:290-297.
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14. Chen S, Zhang L, Bryant R, Vincent G, Flippin M, Lee J, et al. KCNQ1 mutations in patients with a family history of lethal cardiac arrhythmias and sudden death. Clin Genet 2003;63:273-282.
14
15. Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, et al. Spectrum of mutations in long-QT syndrome genes KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 2000;102:1178-1185.
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17. Qureshi SF, Ali A, Ananthapur V, Jayakrishnan M, Calambur N, Thangaraj K, et al. Novel mutations of KCNQ1 in Long QT syndrome. Indian Heart J 2013;65:552-560.
17
18. Larsen LA, Fosdal I, Andersen PS, Kanters JK, Vuust J, Wettrell G, et al. Recessive Romano-Ward syndrome associated with compound heterozygosity for two mutations in the KVLQT1 gene. European Journal of Hum Genet 1999;7:724-728.
18
19. Winbo A, Stattin EL, Diamant UB, Persson J, Jensen SM, Rydberg A. Prevalence, mutation spectrum, and cardiac phenotype of the Jervell and Lange-Nielsen syndrome in Sweden. Europace 2012;14:1799-1806.
19