دوره 28، شماره 127 - ( 12-1398 )                   جلد 28 شماره 127 صفحات 75-64 | برگشت به فهرست نسخه ها


XML English Abstract Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Ghadimi D, Hemmati M, Karimi N, Khadive T. Soy Isoflavone Genistein Is a Potential Agent for Metabolic Syndrome Treatment: A Narrative Review. J Adv Med Biomed Res 2020; 28 (127) :64-75
URL: http://journal.zums.ac.ir/article-1-5905-fa.html
Soy Isoflavone Genistein Is a Potential Agent for Metabolic Syndrome Treatment: A Narrative Review. Journal of Advances in Medical and Biomedical Research. 1398; 28 (127) :64-75

URL: http://journal.zums.ac.ir/article-1-5905-fa.html


چکیده:   (144944 مشاهده)

Metabolic syndrome has a high prevalence (about 22.4% in adult individuals) in developed countries. Inflammation due to obesity and fat accumulation is the most important factor in the progression of metabolic syndrome. In cells which have a receptor for insulin hormone, inflammatory mediators target the insulin signaling pathway and cause insulin resistance. Peroxisome proliferator-activated receptors are a group of ligand inducible transcription factors, whose activation can improve insulin resistance and their agonists such as Genistein, which seems to be useful in prevention of insulin resistance development. Genistein is one of the soy derived isoflavonoids that affects carbohydrate and lipid metabolism resulting in prevention of insulin resistance. The current narrative review has concentrated mainly on highlighting the usefulness of Genistein in the improvement of insulin resistance and therapeutic potential of it in both in-vitro and in-vivo models. Genistein can increase fatty acid β-oxidation, decrease lipogenesis and improve insulin resistance in hepatocytes. In adipocytes, Genistein prevents downregulation of adiponectin expression and facilitates the upregulation of adiponectin expression. In β-islet cells, Genistein initiates the special cascade which leads to proliferation of β cells, resulting in increased secretion of insulin. Based on findings of the studies, it can be concluded that Genistein can be a useful agent in prevention of de novo lipid synthesis as well as proliferation of β cells. In this way the development of metabolic syndrome can be prevented.

متن کامل [PDF 482 kb]   (155231 دریافت)    
نوع مطالعه: مقاله مروری | موضوع مقاله: Medical Biology
دریافت: 1398/10/4 | پذیرش: 1398/11/19 | انتشار: 1398/12/11

فهرست منابع
1. Samson SL, Garber AJ. Metabolic syndrome. Endocrinol Metab Clin North Am. 2014;43(1):1-23. [DOI:10.1016/j.ecl.2013.09.009]
2. Ansarimoghaddam A, Adineh HA, Zareban I, Iranpour S, HosseinZadeh A, Kh F. Prevalence of metabolic syndrome in Middle-East countries: Meta-analysis of cross-sectional studies. Diabetes Metab Syndr. 2018;12(2):195-201. [DOI:10.1016/j.dsx.2017.11.004]
3. Sherling DH, Perumareddi P, Hennekens CH. Metabolic Syndrome. J Cardiovasc Pharmacol Ther. 2017;22(4):365-7. [DOI:10.1177/1074248416686187]
4. Ghahremanloo A, Hajipour R, Hemmati M, Moossavi M, Mohaqiq Z. The beneficial effects of pumpkin extract on atherogenic lipid, insulin resistance and oxidative stress status in high-fat diet-induced obese rats. Journal of complementary & integrative medicine. 2017;15(2). [DOI:10.1515/jcim-2017-0051]
5. Hoshyar R, Hosseinian M, Rajabian Naghandar M, Hemmati M, Zarban A, Amini Z, et al. Anti-Dyslipidemic Properties of Saffron: Reduction in the Associated Risks of Atherosclerosis and Insulin Resistance. Iranian Red Crescent Medical Journal. 2016;18(12):22. [DOI:10.5812/ircmj.36226]
6. Kim MJ, Lim Y. Protective effect of short-term genistein supplementation on the early stage in diabetes-induced renal damage. Mediators Inflamm. 2013;2013:510212. [DOI:10.1155/2013/510212]
7. Motamedrad M, Shokouhifar A, Hemmati M, Moossavi M. The regulatory effect of saffron stigma on the gene expression of the glucose metabolism key enzymes and stress proteins in streptozotocin-induced diabetic rats. Research in pharmaceutical sciences. 2019;14(3):255-62. [DOI:10.4103/1735-5362.258494]
8. Mahboob Z, Hemmati M, Khorashadizadeh M, M G. Additive Effects of Resveratrol and Resveratrol/Quercetin in Prevention of Hyperglycemia-Mediated Cell Death through Downregulation of NADPH Oxidase and RAGE Expression. JOP J Pancreas. 2017;18(1):7.
9. Brown AE, Walker M. Genetics of Insulin Resistance and the Metabolic Syndrome. Curr Cardiol Rep. 2016;18(8):75. [DOI:10.1007/s11886-016-0755-4]
10. Sankar P, Zachariah B, Vickneshwaran V, Jacob SE, Sridhar MG. Amelioration of oxidative stress and insulin resistance by soy isoflavones (from Glycine max) in ovariectomized Wistar rats fed with high fat diet: the molecular mechanisms. Exp Gerontol. 2015;63:67-75. [DOI:10.1016/j.exger.2015.02.001]
11. Gilbert ER, Liu D. Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic beta-cell function. Food Funct. 2013;4(2):200-12. [DOI:10.1039/C2FO30199G]
12. Johar D, Maher A, Aboelmagd O, Hammad A, Morsi M, Warda HF, et al. Whole-food phytochemicals antioxidative potential in alloxan-diabetic rats. Toxicol Rep. 2018;5:240-50. [DOI:10.1016/j.toxrep.2018.01.002]
13. Abharzanjani F, Afshar M, Hemmati M, Moossavi M. Short-term High Dose of Quercetin and Resveratrol Alters Aging Markers in Human Kidney Cells. International journal of preventive medicine. 2017;8:64. [DOI:10.4103/ijpvm.IJPVM_139_17]
14. Thangavel N, Al Bratty M, Javed SA, Ahsan W, Alhazmi HA. Critical Insight into the Design of PPAR-gamma Agonists by Virtual Screening Techniques. Curr Drug Discov Technol. 2019;16(1):82-90. [DOI:10.2174/1570163815666180227164028]
15. Wang L, Waltenberger B, Pferschy-Wenzig EM, Blunder M, Liu X, Malainer C, et al. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARgamma): a review. Biochem Pharmacol. 2014;92(1):73-89. [DOI:10.1016/j.bcp.2014.07.018]
16. Guo L, Tabrizchi R. Peroxisome proliferator-activated receptor gamma as a drug target in the pathogenesis of insulin resistance. Pharmacol Ther. 2006;111(1):145-73. [DOI:10.1016/j.pharmthera.2005.10.009]
17. Shen P, Liu M, Ng T, Chan Y, Yong E. Differential effects of isoflavones, from Astragalus membranaceus and Pueraria thomsonii, on the activation of PPARα, PPARγ, and adipocyte differentiation in vitro. The Journal of nutrition. 2006;136(4):899-905. [DOI:10.1093/jn/136.4.899]
18. Choi JS, Song J. Effect of genistein on insulin resistance, renal lipid metabolism, and antioxidative activities in ovariectomized rats. Nutrition. 2009;25(6):676-85. [DOI:10.1016/j.nut.2008.11.027]
19. Behloul N, Wu G. Genistein: a promising therapeutic agent for obesity and diabetes treatment. Eur J Pharmacol. 2013;698(1-3):31-8. [DOI:10.1016/j.ejphar.2012.11.013]
20. Sureda A, Sanches Silva A, Sanchez-Machado DI, Lopez-Cervantes J, Daglia M, Nabavi SF, et al. Hypotensive effects of genistein: From chemistry to medicine. Chem Biol Interact. 2017;268:37-46. [DOI:10.1016/j.cbi.2017.02.012]
21. Huang G, Xu J, Lefever DE, Glenn TC, Nagy T, Guo TL. Genistein prevention of hyperglycemia and improvement of glucose tolerance in adult non-obese diabetic mice are associated with alterations of gut microbiome and immune homeostasis. Toxicol Appl Pharmacol. 2017;332:138-48. [DOI:10.1016/j.taap.2017.04.009]
22. Ghadimi D, Goodarzi M T , Ziamajidi N , Moradkhani S. The influence of biochanin a consumption on c-CBL-associated protein level in adipose tissue of streptozotocine-nicotinamide induced diabetic rats. International Journal of medical research and health sciences. 2016;5(7):195-201.
23. Khorami SAH, Movahedi A, Sokhini AMM. Review Article; PI3K/AKT pathway in modulating glucose homeostasis and its alteration in Diabetes. Annals of Medical and Biomedical Sciences. 2015;1(2).
24. Petersen MC, Shulman GI. Mechanisms of Insulin Action and Insulin Resistance. Physiol Rev. 2018;98(4):2133-223. [DOI:10.1152/physrev.00063.2017]
25. Leclercq IA, Da Silva Morais A, Schroyen B, Van Hul N, Geerts A. Insulin resistance in hepatocytes and sinusoidal liver cells: mechanisms and consequences. J Hepatol. 2007;47(1):142-56. [DOI:10.1016/j.jhep.2007.04.002]
26. Kim J, Yang G, Kim Y, Kim J, Ha J. AMPK activators: mechanisms of action and physiological activities. Exp Mol Med. 2016;48:e224. [DOI:10.1038/emm.2016.16]
27. Thomson DM, Herway ST, Fillmore N, Kim H, Brown JD, Barrow JR, et al. AMP-activated protein kinase phosphorylates transcription factors of the CREB family. J Appl Physiol (1985). 2008;104(2):429-38. [DOI:10.1152/japplphysiol.00900.2007]
28. Huang C, Qiao X, Dong B. Neonatal exposure to genistein ameliorates high-fat diet-induced non-alcoholic steatohepatitis in rats. Br J Nutr. 2011;106(1):105-13. [DOI:10.1017/S0007114510005799]
29. Choi JS, Koh IU, Song J. Genistein reduced insulin resistance index through modulating lipid metabolism in ovariectomized rats. Nutr Res. 2012;32(11):844-55. [DOI:10.1016/j.nutres.2012.10.002]
30. Ghadimi D, Goodarzi MT, Bahmani M, Khajehahmadi Z. The Effect of Biochanin A as PPAR γ agonist on LDL Particles Diameter and Type 2 Diabetic Dyslipidemia. International Journal of Medical Laboratory. 2019. [DOI:10.18502/ijml.v6i2.1028]
31. Liu H, Zhong H, Yin Y, Jiang Z. Genistein has beneficial effects on hepatic steatosis in high fat-high sucrose diet-treated rats. Biomed Pharmacother. 2017;91:964-9. [DOI:10.1016/j.biopha.2017.04.130]
32. Hwahng SH, Ki SH, Bae EJ, Kim HE, Kim SG. Role of adenosine monophosphate-activated protein kinase-p70 ribosomal S6 kinase-1 pathway in repression of liver X receptor-alpha-dependent lipogenic gene induction and hepatic steatosis by a novel class of dithiolethiones. Hepatology. 2009;49(6):1913-25. [DOI:10.1002/hep.22887]
33. Arunkumar E, Karthik D, Anuradha CV. Genistein sensitizes hepatic insulin signaling and modulates lipid regulatory genes through p70 ribosomal S6 kinase-1 inhibition in high-fat-high-fructose diet-fed mice. Pharm Biol. 2013;51(7):815-24. [DOI:10.3109/13880209.2013.766896]
34. Miinea CP, Sano H, Kane S, Sano E, Fukuda M, Peranen J, et al. AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain. Biochem J. 2005;391(Pt 1):87-93. [DOI:10.1042/BJ20050887]
35. Peck GR, Chavez JA, Roach WG, Budnik BA, Lane WS, Karlsson HK, et al. Insulin-stimulated phosphorylation of the Rab GTPase-activating protein TBC1D1 regulates GLUT4 translocation. The Journal of biological chemistry. 2009;284(44):30016-23. [DOI:10.1074/jbc.M109.035568]
36. Gutierrez-Rodelo C, Roura-Guiberna A, Olivares-Reyes JA. [Molecular Mechanisms of Insulin Resistance: An Update]. Gac Med Mex. 2017;153(2):214-28.
37. Whitmarsh AJ. Regulation of gene transcription by mitogen-activated protein kinase signaling pathways. Biochimica et biophysica acta. 2007;1773(8):1285-98. [DOI:10.1016/j.bbamcr.2006.11.011]
38. Chang E, Choi JM, Kim WJ, Rhee EJ, Oh KW, Lee WY, et al. Restoration of adiponectin expression via the ERK pathway in TNFalpha-treated 3T3-L1 adipocytes. Mol Med Rep. 2014;10(2):905-10. [DOI:10.3892/mmr.2014.2278]
39. Esmaeili S, Motamedrad M, Hemmati M, Mehrpour O, Khorashadizadeh M. Prevention of kidney cell damage in hyperglycaemia condition by adiponectin. Cell biochemistry and function. 2019;37(3):148-52. [DOI:10.1002/cbf.3380]
40. Esmaili S, Hemmati M, Karamian M. Physiological role of adiponectin in different tissues: a review. Archives of physiology and biochemistry. 2018:1-7. [DOI:10.1080/13813455.2018.1493606]
41. Hemmati M, Asghari S, E Z. Effects of Alcoholic and Aqueous Extract of Barberry, Jujube and Saffron Petals on Serum Level of Adiponectin and Lipid Profile in Diabetic Rats. Iranian Journal of Endocrinology and Metabolism. 2015;16(5):9.
42. Fang H, Judd RL. Adiponectin Regulation and Function. Compr Physiol. 2018;8(3):1031-63. [DOI:10.1002/cphy.c170046]
43. Ghadimi D, Goodarzi MT, Ziamajidi N, Moradkhani S. The effect of Biochanin A on the expression of Adiponectin in adipose tissue of Streptozotocin-Nicotinamide induced diabetic rats. International Journal of medical research and health sciences. 2016;5(7):223-30.
44. Yanagisawa M, Sugiya M, Iijima H, Nakagome I, Hirono S, Tsuda T. Genistein and daidzein, typical soy isoflavones, inhibit TNF-alpha-mediated downregulation of adiponectin expression via different mechanisms in 3T3-L1 adipocytes. Mol Nutr Food Res. 2012;56(12):1783-93. [DOI:10.1002/mnfr.201200284]
45. Muoio DM, Newgard CB. Obesity-related derangements in metabolic regulation. Annual review of biochemistry. 2006;75:367-401. [DOI:10.1146/annurev.biochem.75.103004.142512]
46. Unger RH, Orci L. Diseases of liporegulation: new perspective on obesity and related disorders. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2001;15(2):312-21. [DOI:10.1096/fj.00-0590]
47. Reaven GM. The insulin resistance syndrome: definition and dietary approaches to treatment. Annual review of nutrition. 2005;25:391-406. [DOI:10.1146/annurev.nutr.24.012003.132155]
48. Kim SJ, Tang T, Abbott M, Viscarra JA, Wang Y, Sul HS. AMPK Phosphorylates Desnutrin/ATGL and Hormone-Sensitive Lipase To Regulate Lipolysis and Fatty Acid Oxidation within Adipose Tissue. Molecular and cellular biology. 2016;36(14):1961-76. [DOI:10.1128/MCB.00244-16]
49. Carling D. AMPK signalling in health and disease. Current opinion in cell biology. 2017;45:31-7. [DOI:10.1016/j.ceb.2017.01.005]
50. Tabe Y, Yamamoto S, Saitoh K, Sekihara K, Monma N, Ikeo K, et al. Bone Marrow Adipocytes Facilitate Fatty Acid Oxidation Activating AMPK and a Transcriptional Network Supporting Survival of Acute Monocytic Leukemia Cells. Cancer research. 2017;77(6):1453-64. [DOI:10.1158/0008-5472.CAN-16-1645]
51. Boufroura FZ, Le Bachelier C, Tomkiewicz-Raulet C, Schlemmer D, Benoist JF, Grondin P, et al. A new AMPK activator, GSK773, corrects fatty acid oxidation and differentiation defect in CPT2-deficient myotubes. Human molecular genetics. 2018;27(19):3417-33. [DOI:10.1093/hmg/ddy254]
52. St-Pierre J, Tremblay ML. Modulation of leptin resistance by protein tyrosine phosphatases. Cell metabolism. 2012;15(3):292-7. [DOI:10.1016/j.cmet.2012.02.004]
53. Uotani S, Abe T, Yamaguchi Y. Leptin activates AMP-activated protein kinase in hepatic cells via a JAK2-dependent pathway. Biochemical and biophysical research communications. 2006;351(1):171-5. [DOI:10.1016/j.bbrc.2006.10.015]
54. Janovska A, Hatzinikolas G, Staikopoulos V, McInerney J, Mano M, Wittert GA. AMPK and ACC phosphorylation: effect of leptin, muscle fibre type and obesity. Molecular and cellular endocrinology. 2008;284(1-2):1-10. [DOI:10.1016/j.mce.2007.12.013]
55. Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C, Carling D, et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature. 2002;415(6869):339-43. [DOI:10.1038/415339a]
56. Lee WJ, Kim M, Park HS, Kim HS, Jeon MJ, Oh KS, et al. AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1. Biochemical and biophysical research communications. 2006;340(1):291-5. [DOI:10.1016/j.bbrc.2005.12.011]
57. Suzuki A, Okamoto S, Lee S, Saito K, Shiuchi T, Minokoshi Y. Leptin stimulates fatty acid oxidation and peroxisome proliferator-activated receptor alpha gene expression in mouse C2C12 myoblasts by changing the subcellular localization of the alpha2 form of AMP-activated protein kinase. Molecular and cellular biology. 2007;27(12):4317-27. [DOI:10.1128/MCB.02222-06]
58. Vega RB, Huss JM, Kelly DP. The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Molecular and cellular biology. 2000;20(5):1868-76. [DOI:10.1128/MCB.20.5.1868-1876.2000]
59. Mezei O, Banz WJ, Steger RW, Peluso MR, Winters TA, Shay N. Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells. The Journal of nutrition. 2003;133(5):1238-43. [DOI:10.1093/jn/133.5.1238]
60. Martin TL, Alquier T, Asakura K, Furukawa N, Preitner F, Kahn BB. Diet-induced obesity alters AMP kinase activity in hypothalamus and skeletal muscle. The Journal of biological chemistry. 2006;281(28):18933-41. [DOI:10.1074/jbc.M512831200]
61. Steinberg GR, Parolin ML, Heigenhauser GJ, Dyck DJ. Leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance. American journal of physiology Endocrinology and metabolism. 2002;283(1):E187-92. [DOI:10.1152/ajpendo.00542.2001]
62. Yu X, McCorkle S, Wang M, Lee Y, Li J, Saha AK, et al. Leptinomimetic effects of the AMP kinase activator AICAR in leptin-resistant rats: prevention of diabetes and ectopic lipid deposition. Diabetologia. 2004;47(11):2012-21. [DOI:10.1007/s00125-004-1570-9]
63. Irrcher I, Ljubicic V, Kirwan AF, Hood DA. AMP-activated protein kinase-regulated activation of the PGC-1alpha promoter in skeletal muscle cells. PloS one. 2008;3(10):e3614. [DOI:10.1371/journal.pone.0003614]
64. Palacios-Gonzalez B, Zarain-Herzberg A, Flores-Galicia I, Noriega LG, Aleman-Escondrillas G, Zarinan T, et al. Genistein stimulates fatty acid oxidation in a leptin receptor-independent manner through the JAK2-mediated phosphorylation and activation of AMPK in skeletal muscle. Biochimica et biophysica acta. 2014;1841(1):132-40. [DOI:10.1016/j.bbalip.2013.08.018]
65. van Bree BW, Lenaers E, Nabben M, Briede JJ, Jorgensen JA, Schaart G, et al. A genistein-enriched diet neither improves skeletal muscle oxidative capacity nor prevents the transition towards advanced insulin resistance in ZDF rats. Scientific reports. 2016;6:22854. [DOI:10.1038/srep22854]
66. Palacios-Gonzalez B, Vargas-Castillo A, Velazquez-Villegas LA, Vasquez-Reyes S, Lopez P, Noriega LG, et al. Genistein increases the thermogenic program of subcutaneous WAT and increases energy expenditure in mice. The Journal of nutritional biochemistry. 2019;68:59-68. [DOI:10.1016/j.jnutbio.2019.03.012]
67. Moore WT, Bowser SM, Fausnacht DW, Staley LL, Suh KS, Liu D. Beta Cell Function and the Nutritional State: Dietary Factors that Influence Insulin Secretion. Curr Diab Rep. 2015;15(10):76. [DOI:10.1007/s11892-015-0650-1]
68. Yousefi H, Karimi P, Alihemmati A, Alipour MR, Habibi P, Ahmadiasl N. Therapeutic potential of genistein in ovariectomy-induced pancreatic injury in diabetic rats: The regulation of MAPK pathway and apoptosis. Iran J Basic Med Sci. 2017;20(9):1009-15.
69. Yang W, Wang S, Li L, Liang Z, Wang L. Genistein reduces hyperglycemia and islet cell loss in a high-dosage manner in rats with alloxan-induced pancreatic damage. Pancreas. 2011;40(3):396-402. [DOI:10.1097/MPA.0b013e318204e74d]
70. Fu Z, Zhang W, Zhen W, Lum H, Nadler J, Bassaganya-Riera J, et al. Genistein induces pancreatic beta-cell proliferation through activation of multiple signaling pathways and prevents insulin-deficient diabetes in mice. Endocrinology. 2010;151(7):3026-37. [DOI:10.1210/en.2009-1294]
71. Fu Z, Gilbert ER, Pfeiffer L, Zhang Y, Fu Y, Liu D. Genistein ameliorates hyperglycemia in a mouse model of nongenetic type 2 diabetes. Appl Physiol Nutr Metab. 2012;37(3):480-8. [DOI:10.1139/h2012-005]
72. Liu D, Zhen W, Yang Z, Carter JD, Si H, Reynolds KA. Genistein acutely stimulates insulin secretion in pancreatic beta-cells through a cAMP-dependent protein kinase pathway. Diabetes. 2006;55(4):1043-50. [DOI:10.2337/diabetes.55.04.06.db05-1089]
73. Fu Z, Liu D. Long-term exposure to genistein improves insulin secretory function of pancreatic beta-cells. Eur J Pharmacol. 2009;616(1-3):321-7. [DOI:10.1016/j.ejphar.2009.06.005]
74. Incir S, Bolayirli IM, Inan O, Aydin MS, Bilgin IA, Sayan I, et al. The effects of genistein supplementation on fructose induced insulin resistance, oxidative stress and inflammation. Life Sci. 2016;158:57-62. [DOI:10.1016/j.lfs.2016.06.014]
75. Ji G, Yang Q, Hao J, Guo L, Chen X, Hu J, et al. Anti-inflammatory effect of genistein on non-alcoholic steatohepatitis rats induced by high fat diet and its potential mechanisms. Int Immunopharmacol. 2011;11(6):762-8. [DOI:10.1016/j.intimp.2011.01.036]
76. Wang M, Gao XJ, Zhao WW, Zhao WJ, Jiang CH, Huang F, et al. Opposite effects of genistein on the regulation of insulin-mediated glucose homeostasis in adipose tissue. Br J Pharmacol. 2013;170(2):328-40. [DOI:10.1111/bph.12276]
77. Zhong WW, Liu Y, Li CL. Mechanisms of genistein protection on pancreas cell damage in high glucose condition. Intern Med. 2011;50(19):2129-34. [DOI:10.2169/internalmedicine.50.5320]

بازنشر اطلاعات
Creative Commons License این مقاله تحت شرایط Creative Commons Attribution-NonCommercial 4.0 International License قابل بازنشر است.

کلیه حقوق این وب سایت متعلق به Journal of Advances in Medical and Biomedical Research می باشد.

طراحی و برنامه نویسی : یکتاوب افزار شرق

© 2024 CC BY-NC 4.0 | Journal of Advances in Medical and Biomedical Research

Designed & Developed by : Yektaweb