Does Adaptive T Cell Immunity Have Any Role in the Pathophysiology and Histopathology of Buerger's Disease? 2 2 Buerger's disease is a clot forming vasculitis which can lead to severe complications such as amputation of extremities. It is more prevalent in young male smokers and has a higher occurrence in eastern regions of the globe. The risk factors which raise the susceptibility to this condition include infection, tobacco consumption, and genetic factors. It is also hypothesized that the LPS of oral commensal bacteria can lead to various immune reactions that are seen in this disease. Several pathways have been proposed to be responsible for this disease, and the main pathways are through the innate and adaptive immune systems. One of the controversial aspects of the pathophysiology of this disease is its relation to the T cell immunity; histopathology findings have shown T cell infiltration in the arterial wall. In this literature review, our aim was to review the articles published in relation to Buerger’s disease, and the conclusion was that the T cell adaptive immunity might have a fundamental role in the disease pathophysiology, however, further investigation is needed. 1 9 2020/03/25 1399/1/6 2020/06/6 1399/3/17 Soheil Arekhi Soheil Arekhi Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Iran arekhis931@mums.ac.ir Alireza Ghodsi Alireza Ghodsi Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Iran ghodsia921@mums.ac.ir Alireza Omranzadeh Alireza Omranzadeh Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Iran omranzadeha@gmail.com Hamid Reza Rahimi Hamid Reza Rahimi Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Iran rahimihamidrezaa@gmail.com Buerger`s disease Thromboangiitis obliterans T cells Olin JW. Thromboangiitis obliterans. Curr Opin Rheumatol. 1994;6(1):44-50. doi: 10.1097/00002281-199401000-00008.##Rivera-Chavarría IJ, Brenes-Gutiérrez JD. Thromboangiitis obliterans (Buerger's disease). Ann Med Surg. 2016;7:79-82. doi: 10.1016/j.amsu.2016.03.028.##Arkkila PE. Thromboangiitis obliterans (Buerger's disease). Orphanet j rare dis. 2006;1(1):14. doi: 10.1186/1750-1172-1-14.##Olin JW. Thromboangiitis obliterans (Buerger's disease). N Engl J Med. 2000;343(12):864-9. doi: 10.1056/NEJM200009213431207.##Shionoya S. Buerger's disease: diagnosis and management. Vascular. 1993;1(3):207-15. (PMID: 8076031)##Puechal X, Fiessinger J-N. Thromboangiitis obliterans or Buerger's disease: challenges for the rheumatologist. Rheumatology. 2007;46(2):192-9. doi: 10.1093/rheumatology/kel388.##Buerger L. Thrombo-angiitis obliterans: a study of the vascular lesions leading to presenile spontaneous gangrene. Am J Med Sci. 1908;136(4):567-80.##Buerger L. The Circulatory Disturbances of the Extremities: Including Gangrene, Vasomotor, and Trophic Disorders: Saunders; 1924.##McLoughlin G, Helsby C, Evans C, Chapman D. Association of HLA-A9 and HLA-B5 with Buerger's disease. Br Med J. 1976;2(6045):1165-6. doi: 10.1136/bmj.2.6045.1165.##Moerloose P, Jeannet M, Mirimanoff P, Bouvier C. Evidence for an HLA‐Linked Resistance Gene in Buerger's Disease. Tissue Antigens. 1979;14(2):169-73. doi: 10.1111/j.1399-0039.1979.tb00835.x.##Bray SJ. Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol. 2006;7(9):678-89. doi: 10.1038/nrm2009.##Kopan R, Ilagan MXG. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009;137(2):216-33. doi: 10.1016/j.cell.2009.03.045.##Harrington LS, Sainson RC, Williams CK, Taylor JM, Shi W, Li J-L, et al. Regulation of multiple angiogenic pathways by Dll4 and Notch in human umbilical vein endothelial cells. Microvasc res. 2008;75(2):144-54. doi: 10.1016/j.mvr.2007.06.006.##Shionoya S. Venous involvement. Edited by Shionoya S. Buerger’s disease; Pathology, diagnosis, and treatment. Univ. of Nagoya Press; 1990.##Winiwarter F. Ueber eine eigenthümliche Form von Endarteriitis und Endophlebitis mit Gangrän des Fusses. v. Arch Klin Chir. 1879;23:202-26.##Mills JL, Porter JM. Buerger's disease (thromboangiitis obliterans). Ann Vasc Surg. 1991;5(6):570-2. doi: 10.1007/BF02015288.##Mills JL, editor Buerger’s disease in the 21st century: diagnosis, clinical features, and therapy. Seminars in vascular surgery; Elsevier. 2003Sep;16(3):179-89 doi: 10.1016/s0895-7967(03)00023-1.##Mills JL. Buerger's disease: current status. Vasc Med. 1994;5(2 vmr):139-50. doi: 10.1177/1358863X9400500206.##Lie J. The rise and fall and resurgence of thromboangiitis obliterans (Buerger's disease). Pathol Int. 1989;39(3):153-8. doi: 10.1111/j.1440-1827.1989.tb01494.x.##Grove W, Stansby G. Buerger's disease and cigarette smoking in Bangladesh. Ann R Coll Surg Engl. 1992;74(2):115-118. (PMID: 1567129)##Ohtawa T, Juji T, Kawano N, Mishima Y, TOHYAMA H, ISHIKAWA K. HL-A antigens in thromboangiitis obliterans. JAMA. 1974;230(8):1128. doi:10.1001/jama.1974.03240080018015##Gulati SM, Singh KS, Thusoo TK, Saha K. Immunological studies in thromboangiitis obliterans (Buerger's disease). J Surg Res. 1979;27(5):287-93. doi: 10.1016/0022-4804(79)90142-2.##Shionoya S. Diagnostic criteria of Buerger's disease. Int j cardiol. 1998;66:S243-S5. doi: 10.1016/s0167-5273(98)00175-2.##Olin JW. Thromboangiitis obliterans (Buerger's disease). The New England journal of medicine. 2000;343(12):864-9. doi: 10.1056/NEJM200009213431207.##Cope E. Thrombo-angitis obliterans of the spermatic cord. S Afr Med J. 1968;42(33):872-3. (PMID: 5682774)##Abercrombie GF. THROMBO-ANGIITIS OBLITERANS OF THE SPERMATIC CORD. Br J Surg. 1965;52:632-3. doi: 10.1002/bjs.1800520818.##Ohta T, Shionoya S. Fate of the ischaemic limb in Buerger's disease. Brit j surg. 1988;75(3):259-262. doi: 10.1002/bjs.1800750324.##Olin J, Young J, Graor R, Ruschhaupt W, Bartholomew J. The changing clinical spectrum of thromboangiitis obliterans (Buerger's disease). Circulation. 1990;82(5 Suppl):IV3-8. (PMID: 2225420)##ALLEN EV, BROWN GE. Thrombo-Angiitis Obliterans: A Clinical Study of 200 Cases: I. Etiology, Pathology, Symptoms, Diagnosis. Ann Intern Med. 1928;1(8):535-49. doi: 10.7326/0003-4819-1-8-535.##Williams G. Recent views on Buerger's disease. J clin pathol. 1969;22(5):573-8. doi: 10.1136/jcp.22.5.573.##Allen EV, Barker NW, Hines EA. Peripheral Vascular Diseases. Acad Med. 1946;21(5):319.##Schatz IJ, Fine G, Eyler WR. Thromboangiitis obliterans. Brit heart j. 1966;28(1):84-91. doi: 10.1136/hrt.28.1.84.##Iwai T, Inoue Y, Umeda M, Huang Y, Kurihara N, Koike M, et al. Oral bacteria in the occluded arteries of patients with Buerger disease. J vasc surg. 2005;42(1):107-15. doi: 10.1016/j.jvs.2005.03.016.##McKenzie BS, Kastelein RA, Cua DJ. Understanding the IL-23–IL-17 immune pathway. Trends immunol. 2006;27(1):17-23. doi: 10.1016/j.it.2005.10.003.##Mus A, Cornelissen F, Asmawidjaja PS, van Hamburg JP, Boon L, Hendriks RW, et al. Interleukin‐23 promotes Th17 differentiation by inhibiting T‐bet and FoxP3 and is required for elevation of interleukin‐22, but not interleukin‐21, in autoimmune experimental arthritis. Arthritis & Rheumatism. 2010;62(4):1043-50. doi: 10.1002/art.27336.##Morishima N, Mizoguchi I, Takeda K, Mizuguchi J, Yoshimoto T. TGF-β is necessary for induction of IL-23R and Th17 differentiation by IL-6 and IL-23. Bioch biophys res commun. 2009;386(1):105-10. doi: 10.1016/j.bbrc.2009.05.140.##Inomata M, Ishihara Y, Matsuyama T, Imamura T, Maruyama I, Noguchi T, et al. Degradation of vascular endothelial thrombomodulin by arginine-and lysine-specific cysteine proteases from Porphyromonas gingivalis. J periodontol. 2009;80(9):1511-7. doi: 10.1902/jop.2009.090114.##Takahashi Y, Davey M, Yumoto H, Gibson Iii FC, Genco CA. Fimbria‐dependent activation of pro‐inflammatory molecules in Porphyromonas gingivalis infected human aortic endothelial cells. Cell microbiol. 2006;8(5):738-57. doi: 10.1111/j.1462-5822.2005.00661.x.##Amar S, Wu S-c, Madan M. Is Porphyromonas gingivalis cell invasion required for atherogenesis? Pharmacotherapeutic implications. J Immunol. 2009;182(3):1584-92. doi: 10.4049/jimmunol.182.3.1584.##Gibson I, Frank C, Genco CA. Porphyromonas gingivalis mediated periodontal disease and atherosclerosis: disparate diseases with commonalities in pathogenesis through TLRs. Curr pharm des. 2007;13(36):3665-75. doi: 10.2174/138161207783018554.##Shapira L, Takashiba S, Amar S, Dyke T. Porphyromonas gingivalis lipopolysaccharide stimulation of human monocytes: dependence on serum and CD14 receptor. Oral Microbiol Immunol. 1994;9(2):112-7. doi: 10.1111/j.1399-302x.1994.tb00044.x.##Chow JC, Young DW, Golenbock DT, Christ WJ, Gusovsky F. Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J Biol. 1999;274(16):10689-92. doi: 10.1074/jbc.274.16.10689.##Devaney JM, Greene CM, Taggart CC, Carroll TP, O'Neill SJ, McElvaney NG. Neutrophil elastase up‐regulates interleukin‐8 via toll‐like receptor 4. FEBS lett. 2003;544(1-3):129-32. doi: 10.1016/S0014-5793(03)00482-4.##Banus S, Stenger RM, Gremmer ER, Dormans JA, Mooi FR, Kimman TG, et al. The role of Toll-like receptor-4 in pertussis vaccine-induced immunity. BMC immunol. 2008;9(1):1. doi: 10.1186/1471-2172-9-21.##Hajishengallis G, Sojar H, Genco RJ, DeNardin E. Intracellular Signaling and Cytokine Induction upon Interactions of Porphyromonas gingivalis Fimbriae with Pattern‐Recognition Receptors. Immunol invest. 2004;33(2):157-72. doi: 10.1081/imm-120030917.##Zhang X, Shan P, Qureshi S, Homer R, Medzhitov R, Noble PW, et al. Cutting edge: TLR4 deficiency confers susceptibility to lethal oxidant lung injury. J Immunol. 2005;175(8):4834-8. doi: 10.4049/jimmunol.175.8.4834.##Bachschmid M, Thurau S, Zou M-H, Ullrich V. Endothelial cell activation by endotoxin involves superoxide/NO-mediated nitration of prostacyclin synthase and thromboxane receptor stimulation. FASEB j. 2003;17(8):914-6. doi: 10.1096/fj.02-0530fje.##Jayachandran M, Brunn GJ, Karnicki K, Miller RS, Owen WG, Miller VM. In vivo effects of lipopolysaccharide and TLR4 on platelet production and activity: implications for thrombotic risk. J Appl Physiol. 2007;102(1):429-33. doi: 10.1152/japplphysiol.01576.2005.##Hirschfeld M, Ma Y, Weis JH, Vogel SN, Weis JJ. Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2. J Immunol. 2000;165(2):618-22. doi: 10.4049/jimmunol.165.2.618.##Funahashi Y, Shawber CJ, Vorontchikhina M, Sharma A, Outtz HH, Kitajewski J. Notch regulates the angiogenic response via induction of VEGFR-1. J angiogenesis res. 2010;2(1):1. doi: 10.1186/2040-2384-2-3.##Suchting S, Freitas C, le Noble F, Benedito R, Bréant C, Duarte A, et al. The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching. Proc Natl Acad Sci U S A. 2007;104(9):3225-30. doi: 10.1073/pnas.0611177104.##Matsuda T, Miyagawa S, Fukushima S, Kitagawa-Sakakida S, Akimaru H, Horii-Komatsu M, et al. Human cardiac stem cells with reduced notch signaling show enhanced therapeutic potential in a rat acute infarction model. Circ J. 2014;78(1):222-31. doi: 10.1253/circj.cj-13-0534.##Fukuda D, Aikawa M. The expanding role of delta-like 4 mediated Notch signaling in cardiovascular and metabolic diseases. Circ j. 2013;77(10):2462-8. doi: 10.1253/circj.cj-13-0873.##Gridley T. Notch signaling in vascular development and physiology. Development. 2007;134(15):2709-18. doi: 10.1242/dev.004184.##Phng L-K, Gerhardt H. Angiogenesis: a team effort coordinated by notch. Dev cell. 2009;16(2):196-208. doi: 10.1016/j.devcel.2009.01.015.##Tamai H, Kobayashi M, Takeshita K, Kodama A, Banno H, Narita H, et al. Possible involvement of notch signaling in the pathogenesis of Buerger’s disease. Surg today. 2014;44(2):307-13. doi: 10.1007/s00595-013-0566-9.##Kobayashi M, Ito M, Nakagawa A, Nishikimi N, Nimura Y. Immunohistochemical analysis of arterial wall cellular infiltration in Buerger's disease (endarteritis obliterans). J vasc surg. 1999;29(3):451-458. doi: 10.1016/S0741-5214(99)70273-9.##Arnson Y, Shoenfeld Y, Amital H. Effects of tobacco smoke on immunity, inflammation and autoimmunity. J autoimmun. 2010;34(3):J258-J65. doi: 10.1016/j.jaut.2009.12.003.##Zheng P, Fu P, Wang W, Xu W, Tang X, Ye M, et al. Immunological studies on thromboangiitis obliterans. Chin med j. 1989;102(2):129-36. (PMID: 2505978)##Roncon dAR, Delgado L, Correia P, Torrinha JF, Serrao D, Braga A. Circulating immune complexes in Buerger's disease. Endarteritis obliterans in young men. J card surg. 1989;30(5):821-5. (PMID: 2808505)##Li L. [Preliminary application of the immunogold-silver staining technique in diagnosing thromboangiitis obliterans]. Chin j surg. 1989;27(4):233-5, 54. (PMID: 2478349)##Papa M, Bass A, Adar R, Halperin Z, Schneiderman J, Becker C, et al. Autoimmune mechanisms in thromboangiitis obliterans (Buerger's disease): the role of tobacco antigen and the major histocompatibility complex. Surgery. 1992;111(5):527-31. (PMID: 1598672)##Dellalibera‐Joviliano R, Joviliano EE, Silva JSd, Evora PRB. Activation of cytokines corroborate with development of inflammation and autoimmunity in thromboangiitis obliterans patients. Clin Exp Immunol. 2012;170(1):28-35. doi: 10.1111/j.1365-2249.2012.04624.x.## ##

Study of the Antibacterial Effects of Kombucha on the Bacterial Isolates from Diabetic Foot Ulcer 2 2 Introduction: Diabetes is one of the most important metabolic diseases worldwide. Wound infections due to antibiotic resistant bacteria can cause lower limbs ulceration and amputation in diabetic patients.The present study was performed with the aim of the evaluation of antibacterial effects of cellulose disc from kombucha- on bacteria isolated from diabetic foot ulcers. Materials and Methods: In this descriptive-analytical study,bacterial were isolated from diabetic wounds and identified based on biochemical and molecular characterization. Then the antibacterial effect of Kombucha cellulose layer wasevaluated on the isolates using disc diffusion (qualitative) and agar dilution (quantitative) methods, and the data was statisticaly analyzed. Results: The most frequency of pathogenic bacteria that isolated in the present study from diabetic wounds were included 56% Escherichia coli (E.coli), 22% Enterobacter cloacae (E. cloacae), 6% Citrobacter diversus (C. diversus), 4% for each of Enterobacter aerogenes (E. aerogenes), Citrobacter freundii (C. freundii) and Klebsiella pneumonia (K. pneumonia), and 2% for each of methicillin-resistant Staphylococcus aureus (MRSA), and Staphylococcus aureus (S. aureus). TheResults of antimicrobial effect of kombucha cellulose disc showed that the disc weighing 0.5 mg was effective on all bacteria during agar disk diffusion method and the largest diameter of the growth inhibition zone was related to MRSA (27.5 mm).The minimum inhibitory concentrations (MICs) of Kombucha cellulose layer were 12.5 mg/ml on MRSA, 25 mg/ml on S. aureus, 75 mg/ml on E. aerogenes, C. diversus and K. pneumonia, 71.15 mg/ml on E.coli, 85 mg/ml on E.cloacae, and 100 mg/ml on C. freundii. Conclusion: The findings of this study showed that the cellulose layer of Kombucha has excellent antibacterial effects against infectious bacteria in diabetic wounds and can be used in various medical and therapeutic targets. 10 18 2020/03/252020/02/19 1398/11/30 2020/06/62020/05/9 1399/2/20 Soheila Rajaei Soheila Rajaei 1. Department of Microbiology, Falavarjan Branch, Islamic Azad University, Isfahan, Iran Iran soheilaa2892@yahoo.com Monir Doudi Monir Doudi isalamic azad university Iran monirdoudi@yahoo.com Mahbubeh Setorki Mahbubeh Setorki Department of Biology, Izeh Branch, Islamic Azad University, Izeh, Iran Iran doctor.setorgi@gmail.com Ali Mohammad Ahadi Ali Mohammad Ahadi Department of Genetics, Faculty of Science, Shahrekord University, Shahrekord, Iran Iran ahadi52@gmail.com Diabetic foot ulcer Kombucha scoby Antibiogram Disk diffusion method Ayuk SM, Abrahamse H, Nadene HN. The Role of matrixmetalloproteinases in diabetic wound healing in relation to Photobiomodulation. J Diabetes Res. 2016; 2016:1-9. doi:101155/2016/2897656.##Iyanar K, Premavath Y, Cecilia S, Jayalakshmi M , Priyadarsini S, Shantha S. Isolation and antibiotic susceptibility of bacteria from foot infections in the patients with diabetes mellitus type I and type II in the district of Kancheepuram, Tamil Nadu, India. Int J Res Med Sci. 2014; 2(2): 457-61.doi:10.545/2320-6012.ijrms20140515. ##Aloulou A, Hamden K, Elloumi D, Ali MB, Hargafi K, Jaouadi B, et al. Hypoglycemic and antilipidemic properties of kombucha tea in alloxan-induced diabetic rats. BMC Complement Altern Med. 2012;12: 63:1-9. doi:101186/1472-6882-12-63.##Taghipour A, Moski M, Mirzaei N. Determination of effective factor on self-carebehaviors in women with diabetes referring to mashhad healt center.Iran J Healt Educ Healt Promot. 2017;5(4):328-35.doi:10.30699/acadpub.ijhehp.5.4.328.##Kapp JM, Sumner W. Kombucha: a systematic review of the empirical evidence of human health benefit. Ann Epidemiol. 2019;30:66-70. doi: 10.1016/j.annepidem.2018.11.001. ##Guo S, DiPietro LA. Factors affecting wound healing. J Dent Res. 2010; 89(3):219-29. doi:10.1177/0022034509359125.##Kalish J, Hamdan A. Management of diabetic foot problems. J Vasc Surg. 2010;51(2):476-86. doi: 10.1016/j.jvs.2009.08.043. ##Joseph WS, Axler DA. Microbiology and antimicrobial therapy of diabetic foot infections. Clin Podiatr Med Surg. 1990;7(3):467-81. ##Lipsky BA, Pecoraro RE, Larson SA, Hanley ME, Ahroni JH. Outpatient management of uncomplicated lower-extremity infections in diabetic patients. Arch Intern Med. 1990;150(4):790-7. ##Gangania PS, Singh VA. Bacteriological profile of diabetic foot infection patients and their susceptial pattern. Int J Pure App Biosci. 2016;4(3):172-8. doi: 1018782/2320-7051.2305.##Abdulrazak A, Bitar ZI, Al-Shamali AA, Mobasher LA. Bacteriological study of diabetic foot infections. J Diabetes Complications. 2005;19(3):138-41. doi: 10.1016/j.jdiacomp.2004.06.001. ##Wang SH, Sun ZL, Jing Guo Y,Yang BQ, Yuan Y, Wei O, Ye KP. Meticillin –resistant Staphylococcus aureus isolated from foot ulcers in diabetic patients in Chinese care hospital : risk factors for infection and prevalence. J Med Mic. 2010;59:1219-24. doi:10.3201/eid1810.120468.##Shakil S, Khan AU. Infected foot ulcers in male and female diabetic patients: a clinico-bioinformative study. Ann Clin Microbiol Antimicrob. 2010;9:2. doi: 10.1186/1476-0711-9-2. ##Vaca FC, Macias AE, Alvarez JA, Cuevas A, Ramirez AJ, Ramirez WA, et al. Diabetic foot microbiology through biopsy culture. Rev Invest Clin. 2009;61(4):281-5.##Barati F, Javanbakht J, Adib-Hashemi F, Hosseini E, Safaeie R, Rajabian M, et al. Histopathological and clinical evaluation of Kombucha tea and Nitrofurazone on cutaneous full-thickness wounds healing in rats: an experimental study. Diagn Pathol. 2013;8:120. doi: 10.1186/1746-1596-8-120. Retraction in: Diagn Pathol. 2016 Nov 2;11(1):117. ##Jayabalan R, Malbaša RV, Lončar ES, Vitas JS, Sathishkumar M. A Review on Kombucha Tea—Microbiology, Composition, Fermentation, Beneficial Effects, Toxicity, and Tea Fungus. Compr Rev Food Sci Food Saf. 2014;13: 538-50. doi:10.1111/1541-4337.12073.##Martines Leal J ,Valenzuela Suarez L, RasuJayabalan R, Joselina Huerta Oros J, Escalante–Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CyTA-J Food. 2018;390-9. doi:10.1080/19476337.2017.1410499.##Dufrense C, Farnoworth E.Tea kombucha and health a review. Food Res Int. 2000;33(6):409-21. doi:10.1016/S0963-9969(00)00067-3.##Battikh H, Chaieb K, Bakhrouf A, Ammar E. Antimicrobial and antifungal activities of black and green kombucha teas. J Food Biochem. 2011;37(2): 231-6. doi:10.1111/j.1745-4514.2011.00629.x.##Cai Z, Kim J. Preparation and characterization of novel bacteria cellulose/gelatin scaffold for tissue regeneration using bacterial cellulose hydrogel. J Nanotech Engineer Med. 2010;1(2):021002. doi:10.1002/app.47067.##Ashrafi A, Jokar M, Mohammadi A. Preparation and characterization of biocomposite film-5 based on chitosan and kombucha tea as active food packaging. Int J Biolo Macro. 2018;108.444-54. doi:10.3390/molecules24122215.##Ismaiel A A , Rasha H, Zeinat k, Shaimaa M. Detooxification of patulin by kombucha tea culture La desintoxicacion de patulina mediante cultive de te de kombucha.CyTA-J Food. 2016;14(2):271-9. doi:10.1080/19476337.2015.1096828.##Gharib OA, Gharib MA. Kombucha tea ameliorates trichloroethylen induced hepatic damagesin rates via inhibition of oxadative stress and free radicals induction. J Rad Sci Applic. 2008;21(2).481-98.##Pezeshki Najafabadi M, Mohammadi-Sichani M, Kazemi M, Shirsalimian M, Tavakoli M. vestigation of the chemical composition nd Di erent E ects of a rumex dentatus ethanol Extract Against Drug Resistant seudomonas aeruginosa Isolates. Iran Red Crescent Med J. 2016;18(2):e27064. doi:10.5812/ircmj.27064.##Esam J, Kalifawi Al. Bacterial isolated from burn wound patients, study resistance to antimicrobials and effect of Kombucha (Khubdat Humza) tea on isolates bacteria. J Genet Environ Resour Conserv. 2014;2(2):159-68.##Shahnia M, Khahsar R. Antimicrobial effect and determation of minimum inhibitory concentration method of essential oils against pathogenic bacteria. Iran J Nut Sci Food Technol. 2013; 7(5):949-55.##Schito GC. The importance of the development of antibiotic resistance inStaphylococcus aureus. Clin Mic Infec. 2006; 12(2):3-8. doi:10.1111/j.1469-0691.2006.01343.x.##Caili F, Fen Y, Zeli C, Fanying X, Juan L. Antioxidant actives of kombucha prepared from three different substrates and changes in content of probiotics during storage. Food Sci Technol. 2013;34(1):123-6. doi:10.1590/s0101-20612014005000012.##Schneider N, Werkmeister K, Pischetsrieder M. Analysis of nisin A, nisin Z and their degradation products by LCMS/MS. Food Chem. 2011;127(2):847-54. doi: 10.1016/j.foodchem.2011.01.023. ##Kalifawi EJ. Study the antibacterial effect of kombucha tea on bacteria isolated from-diabetic foot ulcer. J Biotechnol Res Center. 2014;8(4):27-33.## ##

Prevalence and Predictors of Migraine Among Medical Students in Karachi 2 2 Introduction: Migraine is a chronic health issue having a global prevalence of more than one billion people. Migraine impairs daily activities of sufferers and hence the academic performance of medical students as well. This study aimed to investigate the migraine prevalence among a sample of university medical students and to examine the predictors, trigger factors and impact of migraine among these students. Materials and Methods: A cross-sectional study was conducted in three months, among the medical students of Karachi, Pakistan. Responses were collected using a self-administered questionnaire employing convenience sampling technique. The frequency, duration of attacks, severity, trigger factors, predictors and impact were measured for migraine cases. Independent t-test and chi-square test were used as the primary statistical tests. IBM Statistical Package for the Social Sciences (SPSS) Statistics (version 24) was used for all the analyses. Results: The overall migraine prevalence among students was 52.3% with the majority of migraines occurring in females. Year of study, age of onset, frequency and pain intensity were significantly associated with migraine in (P<0.05) whereas age and gender were not (P>0.05). Stress (96.4%) and lack of sleep (92.8%) were the most frequent trigger factors of migraine while family history was the most common predictor (32.1%). Conclusion: Almost half of the medical students suffered from migraine with the majority being females. Reducing stress and improving sleep quality might be helpful in decreasing the migraine attacks in this population. 19 27 2020/03/252020/02/192020/01/6 1398/10/16 2020/06/62020/05/92020/05/12 1399/2/23 Farah Anwar Farah Anwar Dow University of Health Sciences Pakistan farah.anwerkhan@gmail.com Anum Bilal Sheikh Anum Bilal Sheikh Dow University of Health Sciences Pakistan anumbilalsheikh@gmail.com Tasneem Taher Tasneem Taher Dow University of Health Sciences Pakistan tasneem.taher03@gmail.com Minaam Iqbal Khan Minaam Iqbal Khan Dow University of Health Sciences Pakistan minaamkhan97@gmail.com Aisha Masoom Aisha Masoom Dow University of Health Sciences Pakistan aishamasoom@hotmail.com Ashna Khursheed Ashna Khursheed Dow University of Health Sciences Pakistan ashnakhursheedd@gmail.com Sidra Saeed Sidra Saeed Dow University of Health Sciences Pakistan sidrasaeed351@gmail.com Mazia Nasim Mazia Nasim Dow University of Health Sciences Pakistan mazianasim@gmail.com Hassan Sohail Hassan Sohail Dow University of Health Sciences Pakistan hassansohail768@gmail.com Syeda Haya Fatima Syeda Haya Fatima Dow University of Health Sciences Pakistan shayafatima97@gmail.com Kehkashan Noor Kehkashan Noor Dow University of Health Sciences Pakistan kehkashan.noor.kn@gmail.com Mir Mahnoor Ellahi Mir Mahnoor Ellahi Dow University of Health Sciences Pakistan mahnoorellahi98@gmail.com Mahnoor Azam Mahnoor Azam Dow University of Health Sciences Pakistan mahnoor.jaliawala@hotmail.com Kaneez Fatima Kaneez Fatima Dow University of Health Sciences Pakistan Migraine Prevalence Predictors Triggers Impacts Medical students Pakistan Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M,et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2010; 380(9859):2163-96. doi: 10.1016/S0140-6736(12)61729-2.##Launer LJ, Terwindt GM, Ferrari MD. The prevalence and characteristics of migraine in a population- based cohort: the GEM study. Neurology. 1999; 53(3):537-42. doi: 10.1212/WNL.53.3.537.##Steiner TJ, Stovner LJ, Vos T. GBD 2015: migraine is the third cause of disability in under 50s. J Headache Pain. 2016; 17(1):104. doi: 10.1186/s10194-016-0699-5.##Ibrahim NK, Alotaibi AK, Alhazmi AM, Alshehri RZ, Saimaldaher RN, Murad MA. Prevalence, predictors and triggers of migraine headache among medical students and interns in King Abdul Aziz university, Jeddah, Saudi Arabia. Pak J Med Sci. 2017; 33(2):270-75. doi: 10.12669/pjms.332.12139.##Dyrbye LN, Thomas MR, Shanafelt TD. Systematic review of depression, anxiety, and other indicators of psychological distress among U.S. and Canadian medical students. Acad Med. 2006; 81:354-73. doi: 10.1097/00001888-200604000-00009.##Marmura MJ. Triggers, Protectors, and Predictors in Episodic Migraine. Curr Pain Headache Rep. 2018; 22(12):81. doi: 10.1007/s11916-018-0734-0.##Andress-Rothrock D1, King W, Rothrock J. An analysis of migraine triggers in a clinic-based population. Headache. 2010; 50(8):1366-70. doi: 10.1111/j.1526-4610.2010.01753.x.##Bigal ME, Bigal JM, Betti M, Bordini CA, Speciali JG. Evaluation of the impact of migraine and episodic tension-type headache on the quality of life and performance of a university student population. Headache. 2007; 15(7):710-9. doi: 10.1046/j.1526-4610.2001.041007710.x.##Smitherman TA, McDermott MJ, Buchanan EM. Negative impact of episodic migraine on a university population: Quality of life, functional impairment, and comorbid psychiatric symptoms. Headache. 2011; 51:581-9. doi: 10.1111/j.1526-4610.2011.01857.x.##MacGregor EA, Brandes J, Eikermann A. Migraine prevalence and treatment patterns: the global Migraine and Zolmitriptan Evaluation survey. Headache. 2003 Jan; 43(1):19-26. doi: 10.1046/j.1526-4610.2003.03004.x.##Hjermstad MJ, Fayers PM, Haugen DF, Caraceni A, Hanks GW, Loge JH, et al. Studies comparing Numerical Rating Scales, Verbal Rating Scales, and Visual Analogue Scales for assessment of pain intensity in adults: a systematic literature review. J Pain Symptom Manage. 2011; 41:1073-93. doi: 10.1016/j.jpainsymman.2010.08.016.##Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013; 33(9):629-808. doi: 10.1177/0333102413485658.##Stewart WF, Lipton RB, Kolodner K, Liberman J, Sawyer J. Reliability of the migraine disability assessment score in a population-based sample of headache sufferers. Cephalalgia. 1999; 19:107-14. doi: 10.1177/0333102413485658.##Menon B, Kinerra N. Prevalence and characteristics of migraine in medical students and its impact on their daily activities. Ann Indian Acad Neurol. 2013; 16(2):221-5. doi: 10.4103/0972-2327.112472.##Sanvito WL, Monzillo PH, Peres MF, Martinelli MO, Fera MP, Gouveia DA, et al. The epidemiology of migraine in medical students. Headache. 1996; 36:316-9. doi: 10.1046/j.1526-4610.1996.3605316.x.##Xiao Gu, Yaojie Xie. Migraine attacks among medical students in Soochow University, Southeast China: a cross-sectional study. J Pain Res. 2018; 11:771-81. doi: 10.2147/JPR.S156227.##Yazdanparast M, Abrishamizadeh AA, Mahboobi H, Omrani A, Ghasemi M, Ghorashi M, et al. Prevalence of and factors associated with migraine in medical students at Bandar Abbas Southern Iran, in 2012. Electron Physician. 2013; 5(3):679-84. doi: 10.14661/2013.679-684.##Merikangas KR. Contributions of epidemiology to our understanding of migraine. Headache. 2013; 53(2):230-46. doi: 10.1111/head.12038.##Stewart WF, Lipton RB, Liberman J. Variation in migraine prevalence by race. Neurology. 1996; 47:52-9. doi: 10.1212/wnl.47.1.52.##Delaruelle Z, Ivanova TA, Khan S, Negro A, Ornello R, Raffaelli B, et al. Male and female sex hormones in primary headaches. J Headache Pain. 2018; 19(1):117. doi: 10.1186/s10194-018-0922-7.##Brandes JL. The inﬂuence of estrogen on migraine: a systematic review. JAMA. 2006; 295:1824-30. doi: 10.1001/jama.295.15.1824.##Loewendorf AI, Matynia A, Saribekyan H, Gross N, Csete M, Harrington M, et al. Roads less traveled: sexual dimorphism and mast cell contributions to migraine pathology. Front Immunol. 2016; 7:140. doi: 10.3389/fimmu.2016.00140.##Al-Hashel JY, Ahmed SF, Alroughani R, Goadsby PJ. Migraine among medical students in Kuwait University. J Headache Pain. 2014; 15:26. doi: 10.1186/1129-2377-15-26.##Ojini FI, Okubadejo NU, Danesi MA. Prevalence and clinical characteristics of headache in medical students of the University of Lagos, Nigeria. Cephalalgia. 2009; 29:472-7. doi: 10.1111/j.1468-2982.2008.01766.x.##Lateef TM, Cui L, Nakamura E, Dozier J, Merikangas K. Accuracy of family history reports of migraine in a community-based family study of migraine. Headache. 2015; 55(3):407-12. doi: 10.1111/head.12501.##Huerta-Franco MR, Vargas-Luna M, Tienda P, Delgadillo-Holtfort I, Balleza-Ordaz M, Flores-Hernandez C. Effects of occupational stress on the gastrointestinal tract. World J Gastrointest Pathophysiol. 2013; 4(4):108-18. doi: 10.4291/wjgp.v4.i4.108.##Renjith V, Pai MS, Castelino F, Pai A, George A. Clinical profile and functional disability of patients with migraine. J Neurosci Rural Pract. 2016; 7(2):250-6. doi: 10.4103/0976-3147.176188.## ##

Methanolic Extract of Biarum Carduchrum Ameliorates Seizures, Oxidative Stress, and Cognitive Impairment in Experimental Models of Epilepsy in Rats 2 2 Abstract Introduction: Given the high prevalence of epilepsy and low availability of usual therapies, finding more effective drugs is essential for the treatment of epileptic patients. In the present study, the anti-epileptic property of the methanol extract of Biarum carduchrum (B. carduchrum) leaves was investigated on pentylenetetrazole (PTZ) kindled rats. Materials and methods: In this experimental study, fifty Wistar rats were randomly grouped into five groups including 1: Control, 2: PTZ, 3: PTZ + methanolic extract (100 and 200 mg/kg), and 4: PTZ + methanolic extract + flumazenil. The scores of epilepsy were investigated 30 min after PTZ injection. Behavioral tests including Shuttle box, Morris Water Maze, and tail suspension tests were done in the experimental groups. Finally, the rats under deep anesthesia; serum samples were given, and their brain tissue removed for biochemical tests, including malondialdehyde level, anti-oxidant capacity, and nitrite and nitrate levels. Results: B. carduchrum methanolic extract reduced the number of tunic seizures and jumps in treated animals. The extract also induced an improvement in the passive avoidance memory and spatial memory in the Morris Water Maze test and reduced the immobilization time in the tail suspension test. Treatment of PTZ kindled rats with B. carduchrum methanolic extract resulted in a decrease in the levels of nitric oxide and malondialdehyde as well as a significant increase in the antioxidant capacity of the brain tissue and serum. Conclusion: B. carduchrum methanolic extract can be used as an anti-epileptic agent for depression control, improvement of learning, and memory after complementary testing. 28 40 2020/03/252020/02/192020/01/62020/06/1 1399/3/12 2020/06/62020/05/92020/05/122020/09/1 1399/6/11 Youness Teymourivand Youness Teymourivand Department of Biology, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran Iran teymourivand0055@gmail.com Zahra Hooshmandi Zahra Hooshmandi Department of Biology, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran Iran zhoushmandi@yahoo.com Mahbubeh Setorki Mahbubeh Setorki Department of Biology, Izeh Branch, Islamic Azad University, Izeh, Iran Iran doctor.setorgi@gmail.com Sabrieh Amini Sabrieh Amini Department of Biology, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran Iran amini.biology@gmail.com Biarum carduchrum PTZ-kindled rats Behavioral tests Antioxidant activity Pahuja M, Mehla J, Reeta K, Joshi S, Gupta YK. Hydroalcoholic extract of Zizyphus jujuba ameliorates seizures, oxidative stress, and cognitive impairment in experimental models of epilepsy in rats. Epilepsy Behav. 2011;21(4):356-63. doi:10.1016/j.yebeh.2011.05.013.##Oliver C, Starke-Reed P, Stadtman E, Liu G, Carney J, Floyd R. Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain. Proc Natl Acad Sci. 1990;87(13):5144-7.##Feng Y, LeBlanc MH, Regunathan S. Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: a potential mechanism for the anticonvulsive effects. Neurosci Lett. 2005;390(3):129-33. doi:10.1016/j.neulet.2005.08.008.##Boyce PC. A taxonomic revision of biarum: Araceae. Curtis's Bot. 2008;25(1):2-17.##Williams CA, Harborne JB, Mayo SJ. Anthocyanin pigments and leaf flavonoids in the family Araceae. Phytochem. 1981;20(2):217-34. doi:10.1111/j.1467-8748.2007.00607.x.##Hegnauer R. Phytochemistry and chemotaxonomy of the Araceae. Aroideana. 1987; 10(2):17-19.##Hosseini E, Rousta E, Loghmany FT, Mahmoudpour M. In vitro antioxidant activity of hydromethanolic extract of Karde (Biarum carduchrum) and its effects on the serum lipids of rats. Iran J Nutr Sci Food Technol. 2014;9(3):1-8.##Rabiei Z, Rafieian-Kopaei M, Heidarian E, Saghaei E, Mokhtari S. Effects of Zizyphus jujube extract on memory and learning impairment induced by bilateral electric lesions of thenucleus Basalis of Meynert in rat. Neurochem Res. 2014;39(2):353-60. doi:10.1007/s11064-013-1232-8.##Rabiei Z, Naderi S, Rafieian-Kopaei M. Study of antidepressant effects of grape seed oil in male mice using tail suspension and forced swim tests. Bangl J Pharmacol. 2017;12(4):397-402 doi: 10.3329/bjp.v12i4.33520.##Rahnama S, Rabiei Z, Alibabaei Z, Mokhtari S, Rafieian-kopaei M, Deris F. Anti-amnesic activity of Citrus aurantium flowers extract against scopolamine-induced memory impairments in rats. Neurol Sci. 2015;36(4):553-560. doi:10.1007/s10072-014-1991-2.##Patsoukis N, Zervoudakis G, Georgiou CD, Angelatou F, Matsokis NA, Panagopoulos NT. Effect of pentylenetetrazol-induced epileptic seizure on thiol redox state in the mouse cerebral cortex. Epilepsy Res. 2004;62(1):65-74. doi:10.1016/j.eplepsyres.2004.08.005.##Bashkatova V , Narkevich V, Vitskova G, Vanin A. The influence of anticonvulsant and antioxidant drugs on nitric oxide level and lipid peroxidation in the rat brain during penthylenetetrazole-induced epileptiform model seizures. Prog Neuropsychopharmacol Biol Psych. 2003;27(3):487-92. doi:10.1016/S0278-5846(03)00037-X.##Nazıroğlu M, Kutluhan S, Yılmaz M. Selenium and topiramate modulates brain microsomal oxidative stress values, Ca2+-ATPase activity, and EEG records in pentylentetrazol-induced seizures in rats. J Membr Biol. 2008; 225(1-3):39-49. doi:10.1007/s00232-008-9132-6.##Kubera M, Budziszewska B, Jaworska-Feil L, Basta-Kaim A, Leskiewicz M, Tetich M, et al. Effect of topiramate on the kainate-induced status epilepticus, lipid peroxidation and immunoreactivity of rats. Pharmacol Rep. 2004;56(5):553-62.##Ergul OE, Arihan O, Kara M, Karatas E, Erten R, Demir H, et al. Effects of Leontice leontopetalum and Bongardia chrysogonum on oxidative stress and neuroprotection in PTZ kindling epilepsy in rats. Cell Mol Biol Lett. 2018;64(15):71-7.##Nassiri-Asl M, Moghbelinejad S, Abbasi E, Yonesi F, Haghighi M-R, Lotfizadeh M, et al. Effects of quercetin on oxidative stress and memory retrieval in kindled rats. Epilepsy Behav. 2013;28(2):151-5. doi:10.1016/j.yebeh.2013.04.019.##Hosseinzadeh H, Sadeghnia H. Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: involvement of GABAergic and opioids systems. Phytomed. 2007;14(4):256-62. doi:10.1016/j.phymed.2006.03.007.##Gao B, Wu Y, Yang Y-J, Li W-Z, Dong K, Zhou J, etal. Sinomenine exerts anticonvulsant profile and neuroprotective activity in pentylenetetrazole kindled rats: involvement of inhibition of NLRP1 inflammasome. J Neuroinflamm. 2018;15(1):152. doi:10.1186/s12974-018-1199-0.##Kaur H, Patro I, Tikoo K, Sandhir R. Curcuminattenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy. Neurochem Int. 2015;89:40-50.##Liu J, Yu H, Ning X. Effect of quercetin on chronic enhancement of spatial learning and memory of mice. Life Sci. 2006;49(6):583-90. doi:10.1016/j.neuint.2015.07.009.##Richetti S, Blank M, Capiotti K, Piato A, Bogo M, Vianna M, et al. Quercetin and rutin prevent scopolamine-induced memory impairment in zebrafish. Behav Brain Res. 2011;217(1):10-5. doi:10.1016/j.bbr.2010.09.027.##Bhutada P, Mundhada Y, Bansod K, Ubgade A, Quazi M, Umathe S, et al. Reversal by quercetin of corticotrophin releasing factor induced anxiety-and depression-like effect in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(6):955-60. doi:10.1016/j.pnpbp.2010.04.025.##Anjaneyulu M, Chopra K, Kaur I. Antidepressant activity of quercetin, a bioflavonoid, in streptozotocin-induced diabetic mice. J Med Food. 2003;6(4):391-5. doi:10.1089/109662003772519976.##Schmitz B. Depression and mania in patients with epilepsy. Epilepsia. 2005;46:45-9. doi:10.1111/j.1528-1167.2005.463009.x.##Bhutada P, Mundhada Y, Bansod K, Ubgade A, Quazi M, Umathe S, et al. Reversal by quercetin of corticotrophin releasing factor induced anxiety-and depression-like effect in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(6):955-60. doi:10.1016/j.pnpbp.2010.04.025.##Anjaneyulu M, Chopra K, Kaur I. Antidepressant activity of quercetin, a bioflavonoid, in streptozotocin-induced diabetic mice. J Med Food. 2003;6(4):391-5. doi:10.1089/109662003772519976.## ##

Evaluation of the Effect of PLGA-PAA Nano-Encapsulated Hydroxytyrosol on Inhibiting the Colorectal Cancer Cell Line HT-29 and Underlying Mechanism of Action 2 2 Introduction: Chemotherapy was known as a potential approach for colon cancer therapy. Polymer-based nanocarriers prolong the circulation time of chemotherapeutic drugs, therefore anti-tumor drugs can passively accumulate in the malignant tumor position through the improved permeability and retention effect. The aim of the present study was to investigate anticancer potency of biodegradable and pH-sensitive nano-encapsulated Hydroxytyrosol in HT-29 cancer cell line and the potential molecular mechanism of action of Hydroxytyrosol. Materials and Methods: The poly lactide-co-glycolide-co-polyacrylic acid (PLGA-co-PAA) nano-encapsulated Hydroxytyrosol was synthesized, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was performed to evaluate the anti-proliferative and anti-tumor effects of both free and nano-encapsulated Hydroxytyrosol. The relative expression of colorectal cancer associated-1 (COCA1) gene was investigated by quantitative Real-Time PCR (qRT-PCR). Results: We observed that free and nano-encapsulated Hydroxytyrosol significantly decreased the viability of HT-29 cancer cells. Moreover, the cytotoxic effect of nano-encapsulated Hydroxytyrosol on HT-29 cancer cells was significantly more than that of free Hydroxytyrosol. Also, the COLCA1 gene expression was up-regulated significantly in HT-29 cancer cells treated with either free or nano-encapsulated Hydroxytyrosol. Conclusion: Generally, we showed that the anticancer potency of Hydroxytyrosol was significantly increased by a biodegradable and pH-sensitive nanoparticle. However, further studies on animal models seem necessary. 41 48 2020/03/252020/02/192020/01/62020/06/12020/04/11 1399/1/23 2020/06/62020/05/92020/05/122020/09/12020/07/11 1399/4/21 Masoud Heidari Masoud Heidari Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Iran haidarymasoud2@gmail.com Mohammadali Hosseinpourfeizi Mohammadali Hosseinpourfeizi Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Iran m.hosseinpourfeizi Nasrin Seyyed Sani Nasrin Seyyed Sani Department of Genetic, Tabriz Branch, Islamic Azad University, Tabriz, Iran Iran seyyedsani.nasrin@yahoo.com Narges Dastmalchi Narges Dastmalchi Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Iran narges.bastmalchi@gmail.com Mohammad Saeid Moradzadeh Tehrani Mohammad Saeid Moradzadeh Tehrani Department of Molecular Biology, Islamic Azad University, University in Arsanjan, Iran Iran m.saeidmoradzadeh@gmail.com Morteza Soleyman-Nejad Morteza Soleyman-Nejad Ariagene Medical Genetics Laboratory, Mahmoudnejad Ave, Qom, Iran Iran soleymannejad@yahoo.com Reza Safaralizadeh Reza Safaralizadeh Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Iran safaralizadeh@tabrizu.ac.ir Colorectal cancer PLGA-PAA copolymer Hydroxytrylosol COLCA1 gene Taheri E, Ghorbani S, Safi M, Sani NS, Amoodizaj FF, Hajazimian S, et al. Inhibition of Colorectal Cancer Cell Line CaCo-2 by Essential Oil of Eucalyptus camaldulensis Through Induction of Apoptosis. Acta Med Iran. 2020;58(6):260-265.##Maroufi NF, Vahedian V, Akbarzadeh M, Mohammadian M, Zahedi M, Isazadeh A, et al. The apatinib inhibits breast cancer cell line MDA-MB-231 in vitro by inducing apoptosis, cell cycle arrest, and regulating nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Breast Cancer. 2020:1-8. doi: 10.1007/s12282-020-01055-6.##Soheilyfar S, Velashjerdi Z, Sayed Hajizadeh Y, Fathi Maroufi N, Amini Z, Khorrami A, et al. In vivo and in vitro impact of miR-31 and miR-143 on the suppression of metastasis and invasion in breast cancer. J Buon. 2018;23(5):1290-6.##Hajazimian S, Maleki M, Mehrabad SD, Isazadeh A. Human Wharton’s jelly stem cells inhibit endometriosis through apoptosis induction. Reproduction. 2020;159(5):549-58. doi: 10.1530/REP-19-0597.##Terzuoli E, Giachetti A, Ziche M, Donnini S. Hydroxytyrosol, a product from olive oil, reduces colon cancer growth by enhancing epidermal growth factor receptor degradation. Mol Nutr Food Res. 2016;60(3):519-29. doi: 10.1002/mnfr.201500498.##Pampaloni B, Mavilia C, Fabbri S, Romani A, Ieri F, Tanini A, et al. In vitro effects of extracts of extra virgin olive oil on human colon cancer cells. Nutr Cancer. 2014;66(7):1228-36. doi: 10.1080/01635581.2014.951727.##Fantini M, Benvenuto M, Masuelli L, Frajese GV, Tresoldi I, Modesti A, et al. In vitro and in vivo antitumoral effects of combinations of polyphenols, or polyphenols and anticancer drugs: perspectives on cancer treatment. Int J Mol Sci. 2015;16(5):9236-82. doi: 10.3390/ijms16059236.##Firouzi Amoodizaj F, Baghaeifar S, Taheri E, Farhoudi Sefidan Jadid M, Safi M, Seyyed Sani N, et al. Enhanced anticancer potency of doxorubicin in combination with curcumin in gastric adenocarcinoma. J Biochm Mol Toxicol. 2020:e22486. doi: 10.1002/jbt.22486.##Ahmadi E ZN, Jafarabadi MA, Alizadeh L, Khojastehfard M, Yamchi MR, Salehi R. Enhanced anticancer potency by combination chemotherapy of HT-29 cells with biodegradable, pH-sensitive nanoparticles for co-delivery of hydroxytyrosol and doxorubicin. J Drug Deliv Sci Tec. 2019;51:721-35. doi: 10.1016/j.jddst.2019.03.003.##Maroufi NF, Vahedian V, Hemati S, Rashidi M, Akbarzadeh M, Zahedi M, Pouremamali F, et al. Targeting cancer stem cells by melatonin: Effective therapy for cancer treatment. Pathol Res Pract. 2020:152919. doi: 10.1016/j.prp.2020.152919.##Peltekova VD, Lemire M, Qazi AM, Zaidi SH, Trinh QM, Bielecki R, et al. Identification of genes expressed by immune cells of the colon that are regulated by colorectal cancer-associated variants. Int J Cancer. 2014;134(10):2330-41. doi: 10.1002/ijc.28557.##Mahdavi S, Kheyrollahi M, Sheikhloei H, Isazadeh A. Antibacterial and Antioxidant Activities of Essential Oil on Food Borne Bacteria. Open Microbiol J. 2019;13(1):81-5.##Mahdavi S, Isazadeh A. Lactobacillus casei suppresses hfq gene expression in Escherichia coli O157: H7. Br J Biomed Sci. 2019;76(2):92-4. doi: 10.1080/09674845.2019.1567903.##Ahmadi M, Rasi H, Mostafazadeh M, Hajazimian S, Maroufi NF, Nahaei MR, et al. Analysis of cervical lesions for presence of HSV-2 and HPV-16 and HPV-18 in Iranian patients by PCR. Horm Mol Biol Clin Investig. 2017;31(3): 20170019. doi: 10.1515/hmbci-2017-0019.##Mahdavi S, Isazadeh AR. Investigation of contamination rate and determination of pattern of antibiotic resistance in coagulase positive staphylococcus aureus isolated from domestic cheeses in Maragheh, Iran. Pathobiol Res. 2019;22(2):85-9.##Yari Z, Mahdavi S, Khayati S, Ghorbani R, Isazadeh A. Evaluation of antibiotic resistance patterns in Staphylococcus aureus isolates collected from urinary tract infections in women referred to Shahid Beheshti educational and therapeutic center in Maragheh city, year 2016. Med J Tabriz Uni Med Sciences Health Services. 2019;41(6):106-12.##Mahdavi S, Azizi Dehbokri M, Isazadeh A. Contamination of chicken meat with salmonella spp distributed in mahabad city, iran. Int J Enteric Pathog. 2018;6(3):65-8. doi: 10.15171/ijep.2018.18.##Vahedian V, Asadi A, Esmaeili P, Zamani S, Zamani R, Hajazimian S, et al. Anti-inflammatory activity of emu oil-based nanofibrous scaffold through downregulation of IL-1, IL-6, and TNF-α pro-inflammatory cytokines. Horm Mol Biol Clin Investig. 2020;20190052. doi: 10.1515/hmbci-2019-0052.##Mahdavi S, Hajazimian S, Isazadeh A, Babashpour M, Shishehgar R. Study of the antioxidant and antimicrobial effects of the ethanolic extract of Eucalyptus camaldulensis Dehnh against infectious bacteria isolated from clinical and animal sources. J Comp Pathobiol 2017;13(4):2063-70.##Lopez de Las Hazas MC, Pinol C, Macia A, Motilva MJ. Hydroxytyrosol and the Colonic Metabolites Derived from Virgin Olive Oil Intake Induce Cell Cycle Arrest and Apoptosis in Colon Cancer Cells. J Agric Food Chem. 2017;65(31):6467-76. doi: 10.1021/acs.jafc.6b04933.##Closa A, Cordero D, Sanz-Pamplona R, Sole X, Crous-Bou M, Pare-Brunet L, et al. Identification of candidate susceptibility genes for colorectal cancer through eQTL analysis. Carcinogenesis. 2014;35(9):2039-46. doi: 10.1093/carcin/bgu092.## ##

The Effect of Assertiveness and Stress Management Training on Reducing High-Risk Behaviors in Adolescent Girls 2 2 Introduction: The present study was conducted to evaluate the effect of assertiveness and stress management skills training on the reduction of high-risk behaviors in adolescent girls. Materials and Methods: One hundred two female students from the high schools of Ilam participated in this quasi-experimental study in the year 2020. Samples were selected by cluster sampling and were randomly assigned to two intervention groups and one control group. The samples were trained with assertiveness and stress management skills. Data were collected using a standard High Risk Behavior Questionnaire at two stages of pre-test and post-test and were analyzed using SPSS V. 22 and the statistical tests, Kruskal-Wallis and U-Mann-Whitney. A P value <0.05 was considered significant. Results: High-risk behaviors in the assertiveness group were less than the control group (P = 0.03), but substance use in the assertiveness group was higher than the control group (P = 0.001), and the results of the intervention did not have the necessary consistency. Training intervention in the stress management group showed that high-risk behaviors in this group did not change after training (P = 0.7), but substance use in the stress management group was lower than the control group (P = 0.001). High-risk behaviors in the stress management and assertiveness groups showed a significant difference compared to the control group (P = 0.03) and the results of the training intervention in terms of assertiveness showed consistency, but in the stress management group, the results showed lack of consistency and significance. In addition, substance use in the stress management and assertiveness groups was less than the control group, which was statistically significant (P = 0.001). Conclusion: Simultaneous implementation of assertiveness and stress management skills training with emphasis on substance use and high-risk behaviors in female students can have satisfactory effects. 49 57 2020/03/252020/02/192020/01/62020/06/12020/04/112020/05/16 1399/2/27 2020/06/62020/05/92020/05/122020/09/12020/07/112020/10/25 1399/8/4 Fatemeh Shohani Fatemeh Shohani Department of Psychology, Ilam Branch, Islamic Azad University of Ilam, Ilam, Iran Iran msh282000@gmail.com Zeinab Mihandoust Zeinab Mihandoust Department of Psychology, Ilam Branch, Islamic Azad University of Ilam, Ilam, Iran Iran xozns2006@yahoo.com Shahram Mami Shahram Mami Department of Psychology, Ilam Branch, Islamic Azad University of Ilam, Ilam, Iran Iran Shahram.Mami@yahoo.com High-risk behavior Female students Stress management Assertiveness Adibnia F, Ahmadi A, Mousavi A. A review of the reasons for risky behaviors in adolescents. Soc Health Addict. 2016; 3(9):11-36. ##Panahi R, Rezaie Z, Teymoori P, Nouri B, Nouri E, Ahmadi O, et al. The factors associated to high-risk behaviors in Sanandaj city students based on health belief model. Iran J Health Educ Health Promot. 2018; 6 (4):393-402.##Eckstrand KL, Choukas-Bradley S, Mohanty A, Cross M, Allen NB, Silk JS, Forbes EE. Heightened activity in social reward networks is associated with adolescents’ risky sexual behaviors. Develop Cognit Neurosci. 2017; 27:1-9. doi.org/10.1016/j.dcn.2017.07.004.##Zadeh Mohammadi A, Ahmadabadi Z, Heidari M. Construction and assessment of psychometric features of Iranian adolescent’s risk-taking scale. Iranian J Psychiatr Clin Psychol. 2011; 17 (3):218-25.##Somerville LH, Jones RM, Casey BJ. A time of change: behavioral and neural correlates of adolescent sensitivity to appetitive and aversive environmental cues. Brain Cognit. 2010; 72(1):124-33. doi.org/10.1016/j.bandc.2009.07.003.##Casey BJ, Jones RM, Hare TA. The adolescent brain. Ann New York Acad Sci. 2008; 1124(1): 111-26. doi: 10.1196/annals.1440.010.##Zargham Hajebi M, Pourabdol S, Saravani S. A comparison of motivational self-regulation and high-risk behaviors in students suffering from attention deficit/hyperactivity disorder (ADHD) and normal students. J Shahrekord Univ Med Sci. 2016; 18 (3):87-97.##Baskin-Sommers A, Sommers I. The co-occurrence of substance uses and high-risk behaviors. J Adolesc Health. 2006; 38 (5): 609–11. doi: 10.1016/j.jadohealth.2005.07.010.##Votta E, Manion I. Suicide, high-risk behaviors, and coping style in homeless adolescent males' adjustment. J Adoles Health. 2004; 34(3): 237-43. doi.org/10.1016/j.jadohealth.2003.06.002. ##Sedighian M, Babazadeh T, Asghari Jafarabadi M, Allahverdipour H. Comparison of cognitive - emotional determinants of sexual high-risk behaviors amongst youth: An application of prototype willingness model. Koomesh. 2017; 19 (3):533-542.##Rashid K. Epidemiology of high-risk behaviors among Tehran adolescent girls and boys. REFAHJ. 2015; 15 (57):31-55.##Bahadori khosroshahi J, Habibikaleybar R, Farid A. The effect of education on health-promoting with academic stress, life skills and risky behaviors among students. Educ Strategy Med Sci. 2017; 10 (1) :64-73.##Samiee H, Beirami R. Investigation life skills training on decreasing high-risk behaviors among students. J Strateg Instruct Admin. 2018; 1(1): 1-9.##Abolfazl Karami A, Shahrestani M, Tavana'i Yousefian S, Asiabi M. Family communication patterns and stress-coping strategies as predictors of smoking: a case study of 13 -18 year-old male smokers and non-smokers of Mashhad. Clin Psychol Stud. 2012; 7(2): 127-47. ##Prshanth L, Nayak Sh. An optimized technique of increasing the performance of network adaptor on EML LAYER. Int J Comput Applic Info Technol. 2012; 1(2): 30-33.##Gholami jam F, Kheftan P, Eghlima M, Sepiddam M. Stress management techniques and its effects on health promotion. Social Work Mag. 2015; 4 (3) :18-27. ##Nejati Sooq S, Mohammadhossini Servak R, Mansoorian S, Bezorghyan L, Jamali Nasab Z, Jamali Nasab A. Determining the prevalence of high-risk behaviors among adolescents and Its relation to perceived social support in Yasuj, Iran, in 2016. Armaghane Danesh. 2019; 24(1) :110-121.##Helstela L, Sourander A. Self- reported competence and emotional and behavioral problems in finish adolescents. Nord J Psychiatr. 2001; 55(5):337-41. doi.org/10.1080/08039480152693264.##Ghanbari Zarandi Z, Mohammadkhani S, Hasheminasab M. Structural model of substance abuse in adolescents: direct and indirect roles of individual, psychological, family, and social factors. J Res Addict. 2016; 10(28): 87-102. ##Khodabakhshi koolaee A, Meherara M, Navidian A, Mossalanejad L. The effectiveness assertiveness skills training on students' mental health-related factors. Iran J Psychiatr Nurs. 2014; 1(4): 74-83. doi.org/10.1016/j.chiabu.2016.10.005.##Rezaie N. The effect of courage skill training on social damages among adolescents (study of risky factors in high-risk behaviors). Entezam-E-Ejtemaei. 2018; 10(2): 207-228.##Zamanlou Gargari S, Badri Gargari R. The effectiveness of courage training on improving the quality of life of adolescents Girl victim of violence. J Woman Stud Famil. 2016; 9(34): 7-26. ##Bahadori khosroshahi J. Comparison of risky behavior, process emotion regulation strategies, and prospective & retrospective memory in school students with and without drug use tendency. J Res Addict. 2017; 11(43): 71-88. ##Gholamijam F, Kheftan P, Eghlima M, Sepiddam M. Stress management techniques and its effects on health promotion. J Soc Work. 2015; 4 (3); 18-27.##Afrasiabi M, Akbarzadeh N. A survey and comparison of coping strategies between normal and delinquent adolescents in Tehran. Psychol Stud. 2007; 3(1): 7-20.## ##

The Effect of Acute Exercise on Vaspin and Chemerin Levels in Obese Men 2 2 Introduction: Vaspin and chemerin, secreted from adipose tissue, are associated with insulin resistance. vaspin and chemerin have been shown to increase insulin sensitivity, as well as decrease the risk of diabetes. The purpose of the research was to explain the effect of acute submaximal exercise on vaspin, chemerin and insulin resistance in obese men. Materials and Methods: Nine obese subjects were randomly selected with age (22.33 ± 1.87) and body mass index (31.16 ± 2.55). The acute exercise was the astrand bicycle ergometer test. The blood samples were taken from subjects before, immediately after exercise, and 30 minutes after exercise. Repeated measures ANOVA with SPSS 24 software were used to analysis of all data. Results: The results showed a significant decrease in vaspin level after acute exercise (P<0.05). There were no significant changes in insulin resistance and chemerin immediately after acute exercise and 30 minutes after exercise (P>0.05). There was a significant correlation, after exercise, between vaspin and chemerin (P<0.05). Conclusion: It seems that acute submaximal exercise was effective in decreasing vaspin. But, response of chemerin to submaximal exercise was not significant. However, the exact effects of acute exercise on other adipocytokines are not clear yet. 58 66 2020/03/252020/02/192020/01/62020/06/12020/04/112020/05/162020/04/19 1399/1/31 2020/06/62020/05/92020/05/122020/09/12020/07/112020/10/252020/07/21 1399/4/31 Shahin Riyahi Malayeri Shahin Riyahi Malayeri Department of Physical Education and Sport Sciences, East Tehran Branch, Islamic Azad University, Tehran, Iran Iran shahinriyahi@yahoo.com Masoumeh Hoseini Masoumeh Hoseini Department of Physical Education and Sport Sciences, East Tehran Branch, Islamic Azad University, Tehran, Iran Iran mhbisadi@yahoo.com Vaspin Chemerin Obese Acute exercis Das M, Gabriely I, Barzilai N. Caloric restriction, body fat and ageing in experimental models. Obes Rev. 2004;5(1):13-9. doi: 10.1111/j.1467-789x.2004.00115.x. ##Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw. 2006;17(1):4-12. ##Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40-50. doi: 10.1016/j.diabres.2017.03.024. ##Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271-81. doi: 10.1016/j.diabres.2018.02.023. ##Kakkar R. Rising burden of Diabetes-Public Health Challenges and way out. Nepal J Epidemiol. 2016 Jun 30;6(2):557-559. doi: 10.3126/nje.v6i2.15160. ##Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R. Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation. 2005;111(11):1448-54. doi: 10.1161/01.CIR.0000158483.13093.9D. ##Volek JS, Fernandez ML, Feinman RD, Phinney SD. Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome. Prog Lipid Res. 2008;47(5):307-18. doi: 10.1016/j.plipres.2008.02.003. ##Luft VC, Schmidt MI, Pankow JS, Couper D, Ballantyne CM, Young JH, et al. Chronic inflammation role in the obesity-diabetes association: a case-cohort study. Diabetol Metab Syndr. 2013;5(1):31. doi: 10.1186/1758-5996-5-31. ##Berggren JR, Hulver MW, Houmard JA. Fat as an endocrine organ: influence of exercise. Journal of Applied Physiology. 2005;99(2):757-64. doi: 10.1152/japplphysiol.00134.2005##de Ferranti S, Mozaffarian D. The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences. Clin Chem. 2008;54(6):945-55. doi: 10.1373/clinchem.2007.100156. ##Dimova R, Tankova T. The role of vaspin in the development of metabolic and glucose tolerance disorders and atherosclerosis. Biomed Res Int. 2015;2015:823481. dol: 10.1155/2015/823481.##Heiker JT, Kloting N, Kovacs P, Kuettner EB, Strater N, Schultz S, et al. Vaspin inhibits kallikrein 7 by serpin mechanism. Cell Mol Life Sci. 2013;70(14):2569-83. doi: 10.1007/s00018-013-1258-8. ##Youn BS, Klöting N, Kratzsch J, Lee N, Park JW, Song ES, Ruschke K, Oberbach A, Fasshauer M, Stumvoll M, Blüher M. Serum vaspin concentrations in human obesity and type 2 diabetes. Diabetes. 2008;57(2):372-7. doi: 10.2337/db07-1045. ##Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, et al. Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology. 2007;148(10):4687-94. doi: 10.1210/en.2007-0175. ##Rabe K, Lehrke M, Parhofer KG, Broedl UC. Adipokines and insulin resistance. Mol Med. 2008;14(11-12):741-51. doi: 10.2119/2008-00058.Rabe. Epub 2008 Sep 17. ##Hosseini M, Eftekhar B, Riyahi Malayeri S. Effect of Interval Training with Curcumin Consumption on Some Adipokines in Menopausal Obese Rats. Journal of Rafsanjan University of Medical Sciences. 2017;16(6):505-16. ##Asgari Hazaveh D, Riyahi Malayeri S, Babaei S. Effect of Eight Weeks High Intensity Interval Training and Medium Intensity Interval Training and Aloe vera Intake on Serum Vaspin and Insulin Resistance in Diabetic Male Rats. Journal of Arak University of Medical Sciences. 2018;20(11):67-75. ##Marwick TH, Hordern MD, Miller T, Chyun DA, Bertoni AG, Blumenthal RS, et al. Exercise training for type 2 diabetes mellitus: impact on cardiovascular risk: a scientific statement from the American Heart Association. Circulation. 2009;119(25):3244-62. doi: 10.1161/CIRCULATIONAHA.109.192521. ##Punyadeera C, Zorenc AH, Koopman R, McAinch AJ, Smit E, Manders R, et al. The effects of exercise and adipose tissue lipolysis on plasma adiponectin concentration and adiponectin receptor expression in human skeletal muscle. Eur J Endocrinol. 2005;152(3):427-36. doi: 10.1530/eje.1.01872. ##Hashemi M, Rezaei H, Eskandari-Nasab E, Kaykhaei MA, Zakeri Z, Taheri M. Association between chemerin rs17173608 and vaspin rs2236242 gene polymorphisms and the metabolic syndrome, a preliminary report. Gene. 2012;510(2):113-7. doi: 10.1016/j.gene.2012.08.048. ##Nomani H, Khanmohamadian H, Vaisi-Raygani A, Shakiba E, Tanhapour M, Rahimi Z. Chemerin rs17173608 and vaspin rs2236242 gene variants on the risk of end stage renal disease (ESRD) and correlation with plasma malondialdehyde (MDA) level. Ren Fail. 2018 Nov;40(1):350-356. doi: 10.1080/0886022X.2018.1459698. ##Cink RE, Thomas TR. Validity of the Astrand-Ryhming nomogram for predicting maximal oxygen intake. Br J Sports Med. 1981;15(3):182-5.##Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-9. doi: 10.1007/BF00280883. ##24. Ji Young K, Eun Sung K, Justin YJ, Yoonsuk J, lt, sup, et al. Improved Insulin Resistance, Adiponectin and Liver Enzymes without Change in Plasma Vaspin Level after 12 Weeks of Exercise Training among Obese Male Adolescents. Korean J Obes. 2011;20(3):138-46. doi: 10.1038/oby.2007.360. ##25. Oberbach A, Kirsch K, Lehmann S, Schlichting N, Fasshauer M, Zarse K, Stumvoll M, Ristow M, Blüher M, Kovacs P. Serum vaspin concentrations are decreased after exercise-induced oxidative stress. Obes Facts. 2010 Oct;3(5):328-31. doi: 10.1159/000321637. ##Bashir JI, Rahbaran A, Gholami F, Ahmadizad S, Nikoukheslat S, Moradi A. The Effect of Acute Exercise on Serum Vaspin Level and Its Relation to Insulin Sensitivity in Overweight Elderly Men. Zahedan J Res Med Sci. 2014;16(8). ##Dimova R, Tankova T. The role of vaspin in the development of metabolic and glucose tolerance disorders and atherosclerosis. Biomed Res Int. 2015;2015:823481. doi: 10.1155/2015/823481. ##Safarzade Ar, Gharakhanlou R, Hedayati M, Talebi-Garakani E. The Effect of 4 Weeks Resistance Training on Serum Vaspin, Il-6, CRP and TNF-Α Concentrations in Diabetic Rats. Iranian Journal of Endocrinology and Metabolism. 2012;14(1):68-74. ##Soori R, Ravasi A, Ranjbar K. T he comparison of between endurance and resistance training on vaspin and adiponectin in obese middle-age men. Sport Physiology. 2014;5(20):97-114.##Shaker OG, Sadik NA. Vaspin gene in rat adipose tissue: relation to obesity-induced insulin resistance. Mol Cell Biochem. 2013;373(1-2):229-39. doi: 10.1007/s11010-012-1494-5. ##Hida K, Wada J, Eguchi J, Zhang H, Baba M, Seida A, et al. Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. Proc Natl Acad Sci U S A. 2005;102(30):10610-5. doi: 10.1073/pnas.0504703102. ##32. Kloting N, Berndt J, Kralisch S, Kovacs P, Fasshauer M, Schon MR, et al. Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes. Biochem Biophys Res Commun. 2006;339(1):430-6. doi: 10.1016/j.bbrc.2005.11.039. ##33. Ye Y, Hou XH, Pan XP, Lu JX, Jia WP. Serum vaspin level in relation to postprandial plasma glucose concentration in subjects with diabetes. Chin Med J (Engl). 2009;122(21):2530-3. ##34. Chakaroun R, Raschpichler M, Klöting N, Oberbach A, Flehmig G, Kern M, et al. Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism - Clinical and Experimental. 2012;61(5):706-14. doi: 10.1016/j.metabol.2011.10.008. ##35. Stefanov T, Bluher M, Vekova A, Bonova I, Tzvetkov S, Kurktschiev D, et al. Circulating chemerin decreases in response to a combined strength and endurance training. Endocrine. 2014;45(3):382-91. doi: 10.1007/s12020-013-0003-2. ##36. Kim SH, Lee SH, Ahn KY, Lee DH, Suh YJ, Cho SG, et al. Effect of lifestyle modification on serum chemerin concentration and its association with insulin sensitivity in overweight and obese adults with type 2 diabetes. Clin Endocrinol (Oxf). 2014;80(6):825-33. doi: 10.1111/cen.12249. ##37. saremi a, fazel mosle habadi m, parastesh m. Effects of Twelve-week Strength Training on Serum Chemerin, TNF-α and CRP Level in Subjects with the Metabolic Syndrome. Iranian Journal of Endocrinology and Metabolism. 2011;12(5):536-43. ##38. Neuparth MJ, Proença JB, Santos-Silva A, Coimbra S. The Positive Effect of Moderate Walking Exercise on Chemerin Levels in Portuguese Patients With Type 2 Diabetes Mellitus. Journal of Investigative Medicine. 2014;62(2):350-3. doi: 10.2310/JIM.0000000000000025. ##39. Lloyd JW, Evans KA, Zerfass KM, Holmstrup ME, Kanaley JA, Keslacy S. Effect of an acute bout of aerobic exercise on chemerin levels in obese adults. Diabetes Metab Syndr. 2016 Jan-Mar;10(1):37-42. doi: 10.1016/j.dsx.2015.04.010.## ##

The Effect of High Intensity Interval Training and Moderate Intensity Continuous Training on the Levels of Cardiotrophin-1and Insulin Resistance in Women with Type 2 Diabetes 2 2 Introduction: Cardiotrophin-1 (CT-1) plays an important role in promoting the obesity related disorders including insulin resistance. The aim of present study was to investigate the effect of high intensity interval training (HIIT) and moderate intensity continuous training (MICT) on the levels of CT-1 and insulin resistance in women with type 2 diabetes. Materials and Methods: Thirty-six women (average age of 46.95±3.49 years old, average weight of 79.5±5.7 kg) with type 2 diabetes randomly assigned in three equal groups including HIIT, MICT and control groups. Both training program conducted for 12 weeks and three session per week. Blood samples collected before and after intervention and serum levels of CT-1 and insulin were measured by ELISA method. Results: Between group analysis indicated a significant decrease of CT-1 levels in HIIT (P=0.002) and MICT (P=0.016) groups compared to control group, but no significant difference observed between HIIT and MICT groups (P=1.000). Paired t test analysis indicated that serum levels of CT-1 significantly decreased in both HIIT and MICT groups (P<0.001). Moreover, insulin resistance significantly decreased in HIIT and MICT groups compared to control group (P<0.001). Intragroup analysis indicated a significant decrease of insulin resistance in HIIT and MICT groups (P<0.001). Conclusion: It seems that, positive effects of HIIT and MICT protocols including improvement the insulin resistance are exerted by decreased the serum levels of CT-1. In addition, HIIT was no superior compared to MICT for observed changes in CT-1 levels and insulin resistance. 67 75 2020/03/252020/02/192020/01/62020/06/12020/04/112020/05/162020/04/192020/03/4 1398/12/14 2020/06/62020/05/92020/05/122020/09/12020/07/112020/10/252020/07/212020/07/24 1399/5/3 Masoumeh Gholaman Masoumeh Gholaman Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran Iran masoumeh.gholaman@gmail.com Mandana Gholami Mandana Gholami Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran Iran m.gholami@srbiau.ac.ir Mohammad Ali Azarbayjani Mohammad Ali Azarbayjani Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran Iran m_azarbayjani@iauctb.ac.ir Hossein Abed Natanzi Hossein Abed Natanzi Department of Physical Education and Sport Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran Iran abednazari@gmail.com Exercise training Type 2 diabetes Cardiotrophin-1 Chen Y, Pan R, Pfeifer A. Fat tissues, the brite and the dark sides. Pflug Arch Eur J Phy Journal. 2016;468(11-12):1803-7. doi: 10.1007/s00424-016-1884-8.##Khan MA, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of type 2 diabetes–global burden of disease and forecasted trends. J Epidemiol Glob Health. 2020;10(1):107. doi: 10.2991/jegh.k.191028.001.##Nie Q, Chen J. HIIT and Moderate Intensity Training on the Latest Research Progress of Type 2 Diabetes. Int J Diabetes Endocrinol. 2019;3(4):63-67. doi: 10.11648/j.ijde.20180304.12.##Natal C, Fortuño MA, Restituto P, Bazán A, Colina I, Díez J, Varo N. Cardiotrophin-1 is expressed in adipose tissue and upregulated in the metabolic syndrome. Am J Physiol Endocrinol Metab. 2008; 294(1):52-60. doi: 10.1152/ajpendo.00506.2007.##Bustos M, Moreno-Aliaga MJ, Prieto J. Cardiotrophin-1: a new player in energy metabolism with potential therapeutic application. Aging. 2011;3(8):698. doi: 10.18632/aging.100359.##Moreno-Aliaga MJ, Pérez-Echarri N, Marcos-Gómez B, Larequi E, Gil-Bea FJ, Viollet B, et al. Cardiotrophin-1 is a key regulator of glucose and lipid metabolism. Cell metab. 2011;14(2):242-53. doi: 10.1016/j.cmet.2011.05.013.##Pemberton CJ, Raudsepp SD, Yandle TG, Cameron VA, Richards AM. Plasma cardiotrophin-1 is elevated in human hypertension and stimulated by ventricular stretch. Cardiovasc Res. 2005;68(1):109-17. doi: 10.1016/j.cardiores.2005.05.014.##Malavazos AE, Ermetici F, Morricone L, Delnevo A, Coman C, Ambrosi B, et al. Association of increased plasma cardiotrophin-1 with left ventricular mass indexes in normotensive morbid obesity. Hypertension. 2008;51(2):8-9. doi: 10.1161/hypertensionaha. 107.105346.##Hung HC, Lu FH, Ou HY, Wu HT, Wu JS, Yang YC, et al. Increased cardiotrophin-1 in subjects with impaired glucose tolerance and newly diagnosed diabetes. Int J Cardiol. 2013;169(3):33-4. doi: 10.1016/j.ijcard.2013.08.112.##Escoté X, Gómez-Zorita S, López-Yoldi M, Milton-Laskibar I, Fernández-Quintela A, Martínez JA, et al. Role of omentin, vaspin, cardiotrophin-1, TWEAK and NOV/CCN3 in obesity and diabetes development. Int J Mol Sci. 2017;18(8):1770. doi: 10.3390/ijms18081770.##Daryanoosh F, Amo-Ali N, Sherafati M.M, Dadvand S. The Effect of 12 Weeks of Resistance Exercise on Serum Cardiotrophin-1 Levels, Left Ventricular Hypertrophy and Blood Pressure in Hypertensive Elderly Women. J Appl Health Sport Physiol. 2016;3(2):11-16. doi: 10.22049/J ASSP.2016.13749.##Rendo-Urteaga T, García-Calzón S, Martínez-Ansó E, Chueca M, Oyarzabal M, Azcona-Sanjulián MC, et al. Decreased cardiotrophin-1 levels are associated with a lower risk of developing the metabolic syndrome in overweight/obese children after a weight loss program. Metabolism. 2013;62(10):1429-36. doi: 10.1016/j.metabol.2013.05.011.##Abd El-Kader SM. Aerobic versus resistance exercise training in modulation of insulin resistance, adipocytokines and inflammatory cytokine levels in obese type 2 diabetic patients. J Adv Res. 2011;2(2):179-83. doi: 10.1016/j.jare.2010.09.003.##Winding KM, Munch GW, Iepsen UW, Van Hall G, Pedersen BK, Mortensen SP. The effect on glycaemic control of low‐volume high‐intensity interval training versus endurance training in individuals with type 2 diabetes. Diabetes Obes Metab. 2018;20(5):1131-9. doi: 10.1111/dom.13198.##De Nardi AT, Tolves T, Lenzi TL, Signori LU, da Silva AM. High-intensity interval training versus continuous training on physiological and metabolic variables in prediabetes and type 2 diabetes: a meta-analysis. Diabetes Res Clin Pract. 2018;137:149-59. doi: 10.1016/j. diabres.2017.12.017.##Zafra MM, García-Cantó E, García PL, Pérez-Soto JJ, López PJ, Guillamón AR, et al. Influence of a physical exercise programme on VO2max in adults with cardiovascular risk factors. Clínica e Investigación en Arteriosclerosis (English Edition). 2018;30(3):95-101. doi: 10.1016/j.artere.2018.04.001.##Ahmad AM. Moderate-intensity continuous training: is it as good as high-intensity interval training for glycemic control in type 2 diabetes? J Exerc Rehabil. 2019;15(2):327. doi: 10.12965/jer.1836648.324.##Schjerve IE, Tyldum GA, Tjønna AE, Stølen T, Loennechen JP, Hansen HE, et al. Both aerobic endurance and strength training programmes improve cardiovascular health in obese adults. Clin Sci. 2008;115(9):283-93. doi: 10.1042/CS20070332.##Onishi Y, Hayashi T, Sato KK, Ogihara T, Kuzuya N, Anai M, et al. Fasting tests of insulin secretion and sensitivity predict future prediabetes in Japanese with normal glucose tolerance. J Diabetes Investig. 2010;1(5):191-5. doi: 10.1111/j.2040-1124.2010.00041. x.##Moreno-Aliaga MJ, Romero-Lozano MA, Castaño D, Prieto J, Bustos M. Role of cardiotrophin-1 in obesity and insulin resistance. Adipocyte. 2012;1(2):112-5. doi: 10.4161/adip. 19696.##Zvonic S. Hogan JC, Arbour-Reily P, Mynatt RL, Stephens JM. Effects of cardiotrophin on adipocytes. J Biol Chem. 2004; 279:47572-9. doi: 10.1074/jbc.M403998200.##Gamella-Pozuelo L, Fuentes-Calvo I, Gomez-Marcos MA, Recio-Rodriguez JI, Agudo-Conde C, et al. Plasma cardiotrophin-1 as a marker of hypertension and diabetes-induced target organ damage and cardiovascular risk. Medicine. 2015;94(30). e218. doi: 10.1097/MD. 0000000000001218.##López-Andrés N, Rousseau A, Akhtar R, Calvier L, Iñigo C, Labat C, et al. Cardiotrophin 1 is involved in cardiac, vascular, and renal fibrosis and dysfunction. Hypertension. 2012;60(2):563-73. doi: 10.1161/HYPERTENSIONAHA.112.194407.##Marti A, Morell‐Azanza L, Rendo‐Urteaga T, García‐Calzón S, Ojeda‐Rodríguez A, Martín‐Calvo N, et al. Serum and gene expression levels of CT‐1, IL‐6, and TNF‐α after a lifestyle intervention in obese children. Pediat Diabetes. 2018;19(2):217-22. doi: 10.1111/pedi.12561.##Wormgoor SG, Dalleck LC, Zinn C, Borotkanics R, Harris NK. High-intensity interval training is equivalent to moderate-intensity continuous training for short-and medium-term outcomes of glucose control, Cardiometabolic risk, and microvascular complication markers in men with type 2 diabetes. Front Endocrinol. 2018; 9:475. doi: 10.3389/fendo.2018.00475.##Liubaoerjijin Y, Terada T, Fletcher K, Boulé NG. Effect of aerobic exercise intensity on glycemic control in type 2 diabetes: a meta-analysis of head-to-head randomized trials. Acta Diabetol. 2016;53(5):769-81. doi: 10.1007/s00592-016-0870-0.##Francois ME, Little JP. Effectiveness and safety of high-intensity interval training in patients with type 2 diabetes. Diabetes Spectr. 2015;28(1):39-44. doi: 10.2337/d.## ##