Login Register Cart 0
Generic placeholder image

Current Nanomedicine

Editor-in-Chief

ISSN (Print): 2468-1873
ISSN (Online): 2468-1881

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Antidiabetic Potential of Silver/Chitosan/Ascorbic Acid Nanocomposites

Author(s): Esraa Ahmed Abu El Qassem Mahmoud, Ayman S Mohamed *, Sohair R. Fahmy, Amel Mahmoud Soliman and Khadiga Gaafar

Volume 11, Issue 4, 2021

Page: [237 - 248] Pages: 12

DOI: 10.2174/2468187312666211220115859

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Diabetes mellitus is the most common health problem in the world. Silver nanoparticles (AgNPs) exposed great intrinsic anti-inflammatory, antibacterial, antiviral, and antifungal activities. Chitosan is an oligosaccharide biopolymer with a great ability to lower hyperglycemia, and ascorbic acid is a water-soluble vitamin with strong antioxidant activity.

Objective: The present study aimed to estimate AgNPs/chitosan/ascorbic acid nanocomposite (Ag- NCs) anti-diabetic properties in streptozotocin-induced diabetic rats.

Methods: Eighteen male Wistar albino rats were divided into three main groups (6 rats/group); control, diabetic, and Ag-NCs groups. Control group: after a single dose of citrate buffer at PH 4.5 (0.1 mol/L, i.p), the rats orally received 1 ml distilled water daily for four weeks. The diabetic model was induced by a single dose of streptozotocin (60 mg/kg, i.p) for type 1 diabetes and the rats orally received 1 ml distilled water daily for four weeks. The diabetic group was treated orally with Ag-NCs (0.25 mg/Kg body weight) daily for four weeks.

Results: AgNPs/chitosan/ascorbic acid nanocomposite group showed a reduction in the concentrations of glucose, NO, MDA, LDL, and the activities of AST, ALT, ALP, and GGT. At the same time, it caused a general increase in insulin, albumin, TB, TC, TG, HDL, CAT, SOD, and GSH levels. The histopathological investigation illustrated regeneration of damaged pancreatic beta cells and a clear improvement in the hepatic architecture.

Conclusion: The suggested mechanism of action for Ag-NCs in decreasing diabetic complications in the liver involved two pathways; the hypoglycemic activity and the antioxidant role of AgNPs, chitosan, and ascorbic acid.

Keywords: Type 1 Diabetes, AgNPs/chitosan/ascorbic acid nanocomposites, oxidative stress, liver function, lipid profile, blood.

« Previous Next »
Graphical Abstract

[1]
IDF. International diabetes federation, 2019. Available from: https://www.diabetesatlas.org/en/
[2]
Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract 2019; 157: 107843.
[http://dx.doi.org/10.1016/j.diabres.2019.107843] [PMID: 31518657]
[3]
Polat K, Güneş S. An expert system approach based on principal component analysis and adaptive neuro-fuzzy inference system to diagnosis of diabetes disease. Dig Signal Proc 2007; 17(4): 702-10.
[http://dx.doi.org/10.1016/j.dsp.2006.09.005]
[4]
Devendra D, Liu E, Eisenbarth GS. Type 1 diabetes: recent developments. BMJ 2004; 328(7442): 750-4.
[http://dx.doi.org/10.1136/bmj.328.7442.750] [PMID: 15044291]
[5]
Vana DR, Adapa D, Choudhury A, et al. Diabetes mellitus types: Key genetic determinants and risk assessment. Genet Mol Res 2019; 18(2): 27.
[6]
Galtier F. Definition, epidemiology, risk factors. Diabetes Metab 2010; 36(6 Pt 2): 628-51.
[http://dx.doi.org/10.1016/j.diabet.2010.11.014] [PMID: 21163426]
[7]
Harding JL, Pavkov ME, Magliano DJ, Shaw JE, Gregg EW. Global trends in diabetes complications: a review of current evidence. Diabetologia 2019; 62(1): 3-16.
[http://dx.doi.org/10.1007/s00125-018-4711-2] [PMID: 30171279]
[8]
Katsarou A, Gudbjörnsdottir S, Araz Rawshani A, et al. Type 1 diabetes mellitus. Nat Rev Dis Primers 2017; 3(1): 1-17.
[http://dx.doi.org/10.1038/nrdp.2017.16]
[9]
Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes. Diabetes Care 2019; 42(1)(Suppl. 1): S90-S102.
[PMID: 30559235]
[10]
Silver B, Ramaiya K, Andrew SB, et al. EADSG guidelines: insulin therapy in diabetes. Diabetes Ther 2018; 9(2): 449-92.
[http://dx.doi.org/10.1007/s13300-018-0384-6] [PMID: 29508275]
[11]
Wong M, Balakrishnan T. Anasarca in newly diagnosed type 1 diabetes: Review of pathophysiology of insulin edema. Cureus 2020; 12(3): e7234.
[http://dx.doi.org/10.7759/cureus.7234] [PMID: 32280575]
[12]
Dos Santos CA, Seckler MM, Ingle AP, et al. Silver nanoparticles: Therapeutical uses, toxicity, and safety issues. J Pharm Sci 2014; 103(7): 1931-44.
[http://dx.doi.org/10.1002/jps.24001] [PMID: 24824033]
[13]
Kargozar S, Mozafari M. Nanotechnology and Nanomedicine: Start small, think big. Mater Today Proc 2018; 5(7): 15492-500.
[http://dx.doi.org/10.1016/j.matpr.2018.04.155]
[14]
Siwach R, Pandey P, Chawla V, Dureja H. Role of nanotechnology in diabetic management. Recent Pat Nanotechnol 2019; 13(1): 28-37.
[http://dx.doi.org/10.2174/1872210513666190104122032] [PMID: 30608045]
[15]
Shanker K, et al. A sub-acute oral toxicity analysis and comparative in vivo anti-diabetic activity of zinc oxide, cerium oxide, silver nanoparticles, and Momordica charantia in streptozotocin-induced diabetic Wistar. RSC Advances 2017; 7(59): 37158-67.
[http://dx.doi.org/10.1039/C7RA05693A]
[16]
Regiel-Futyra A, Kus-Liśkiewicz M, Sebastian V, et al. Development of noncytotoxic silver-chitosan nanocomposites for efficient control of biofilm forming microbes. RSC Advances 2017; 7(83): 52398-413.
[http://dx.doi.org/10.1039/C7RA08359A] [PMID: 29308194]
[17]
Burdușel A-C, Gherasim O, Grumezescu AM, et al. Biomedical applications of silver nanoparticles: An up-to-date oerveiw. Nanomaterials (Basel) 2018; 8(9): 681.
[http://dx.doi.org/10.3390/nano8090681]
[18]
Prabhu S, Vinodhini S, Elanchezhiyan C, Rajeswari D. Evaluation of antidiabetic activity of biologically synthesized silver nanoparticles using Pouteria sapota in streptozotocin-induced diabetic rats. J Diabetes 2018; 10(1): 28-42.
[http://dx.doi.org/10.1111/1753-0407.12554] [PMID: 28323393]
[19]
Mahmoudi F, Mahmoudi F, Gollo KH, et al. Biosynthesis of Novel Silver Nanoparticles Using Eryngium thyrsoideum Boiss Extract and Comparison of their Antidiabetic Activity with Chemical Synthesized Silver Nanoparticles in Diabetic rats. Biol Trace Elem Res 2021; 199(5): 1967-78.
[http://dx.doi.org/10.1007/s12011-020-02315-4] [PMID: 32749577]
[20]
Sarkar S, Das D, Dutta P, Kalita J, Wann SB, Manna P. Chitosan: A promising therapeutic agent and effective drug delivery system in managing diabetes mellitus. Carbohydr Polym 2020; 247: 116594.
[http://dx.doi.org/10.1016/j.carbpol.2020.116594] [PMID: 32829787]
[21]
Santosh HN, David CM. Role of ascorbic acid in diabetes mellitus: a comprehensive review. J Med, Radiol Pathol Surg 2017; 4(1): 1-3.
[22]
Sobczak-Kupiec A, Malina D, Wzorek Z, Zimowska M. Influence of silver nitrate concentration on the properties of silver nanoparticles. Micro & Nano Lett 2011; 7(8): 656-60.
[http://dx.doi.org/10.1049/mnl.2011.0152]
[23]
Sibiya PN, Moloto MJ. Effect of precursor concentration and pH on the shape and size of starch capped silver selenide (Ag2Se) nanoparticles. Chalcogenide Lett 2014; 11(11): 577-88.
[24]
Kaushik M, Fraschini C, Grégory Chauve, G, Putaux J-L, Moores A. Transmission electron microscopy for the characterization of cellulose nanocrystals. 2015.
[25]
Chen X, Fu XS, Li CP, Zhao HX. ER stress and ER stress-induced apoptosis are activated in gastric SMCs in diabetic rats. World J Gastroenterol 2014; 20(25): 8260-7.
[http://dx.doi.org/10.3748/wjg.v20.i25.8260] [PMID: 25009401]
[26]
Elbehiry A, et al. Antibacterial effects and resistance induction of silver and gold nanoparticles against Staphylococcus aureus-induced and the potential toxicity in rats. MicrobiologyOpen 2018; 2018: e698.
[PMID: 30079629]
[27]
Bancroft JD, Gamble M. Theory and practice of histological techniques. 1990; 616, 07583 T4.
[28]
Freund A, Johnson SB, Rosenbloom A, Alexander B, Hansen CA. Subjective symptoms, blood glucose estimation, and blood glucose concentrations in adolescents with diabetes. Diabetes Care 1986; 9(3): 236-43.
[http://dx.doi.org/10.2337/diacare.9.3.236] [PMID: 3731991]
[29]
Herbert V, Lau KS, Gottlieb CW, Bleicher SJ. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab 1965; 25(10): 1375-84.
[http://dx.doi.org/10.1210/jcem-25-10-1375] [PMID: 5320561]
[30]
Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957; 28(1): 56-63.
[http://dx.doi.org/10.1093/ajcp/28.1.56] [PMID: 13458125]
[31]
Belfield A, Goldberg DM. Normal ranges and diagnostic value of serum 5'nucleotidase and alkaline phosphatase activities in infancy. Arch Dis Child 1971; 46(250): 842-6.
[http://dx.doi.org/10.1136/adc.46.250.842] [PMID: 5129186]
[32]
Rosalki SB. Determination of serum gamma glutamyltransferase activity. Adv Clin Chem 1975; 17: 53-5.
[http://dx.doi.org/10.1016/S0065-2423(08)60248-6] [PMID: 236637]
[33]
Walters MI, Gerarde HW. Ultramicromethod for the determination of conjugated and total bilirubin in serum or plasma. Microchem J 1970; 15: 231-43.
[http://dx.doi.org/10.1016/0026-265X(70)90045-7]
[34]
Zlatkis A, Zak B, Boyle AJ. A new method for the direct determination of serum cholesterol. J Lab Clin Med 1953; 41(3): 486-92.
[PMID: 13035283]
[35]
Van Handel E, Zilversmit DB. Micromethod for the direct determination of serum triglycerides. J Lab Clin Med 1957; 50(1): 152-7.
[PMID: 13439279]
[36]
Burstein M, Scholnick HR, Morfin R. Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res 1970; 11(6): 583-95.
[http://dx.doi.org/10.1016/S0022-2275(20)42943-8] [PMID: 4100998]
[37]
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95(2): 351-8.
[http://dx.doi.org/10.1016/0003-2697(79)90738-3] [PMID: 36810]
[38]
Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963; 61: 882-8.
[PMID: 13967893]
[39]
Montgomery HA, Dymock JF. Determination of nitrite in water. Analyst (Lond) 1961; 86(102): 414.
[40]
Nishikimi M, Roa NA, Yogi K. Measurement of superoxide dismutase. Biochem Biophys Res Commun 1972; 46: 849-54.
[http://dx.doi.org/10.1016/S0006-291X(72)80218-3] [PMID: 4400444]
[41]
Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121-6.
[http://dx.doi.org/10.1016/S0076-6879(84)05016-3] [PMID: 6727660]
[42]
Wei S, et al. A size-controlled green synthesis of silver nanoparticles by using the berry extract of Sea Buckthorn and their biological activities. New J Chem 2020; 44(22): 9304-12.
[http://dx.doi.org/10.1039/D0NJ01335H]
[43]
Dara PK, et al. Synthesis and biochemical characterization of silver nanoparticles grafted chitosan (Chi-Ag-NPs): in vitro studies on antioxidant and antibacterial applications. SN Applied Sciences 2020; 2(4): 1-12.
[http://dx.doi.org/10.1007/s42452-020-2261-y]
[44]
Shi GJ, Shi GR, Zhou JY, et al. Involvement of growth factors in diabetes mellitus and its complications: A general review. Biomed Pharmacother 2018; 101: 510-27.
[http://dx.doi.org/10.1016/j.biopha.2018.02.105] [PMID: 29505922]
[45]
Arora S, Ojha SK, Vohora D. Characterisation of streptozotocin induced diabetes mellitus in swiss albino mice. Glob J Pharmacol 2009; 3(2): 81-4.
[46]
Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004; 24(5): 816-23.
[http://dx.doi.org/10.1161/01.ATV.0000122852.22604.78] [PMID: 14976002]
[47]
Kakkar R, Mantha SV, Radhi J, Prasad K, Kalra J. Increased oxidative stress in rat liver and pancreas during progression of streptozotocin-induced diabetes. Clin Sci (Lond) 1998; 94(6): 623-32.
[http://dx.doi.org/10.1042/cs0940623] [PMID: 9854460]
[48]
Vakilian M, Tahamtani Y, Ghaedi K. A review on insulin trafficking and exocytosis. Gene 2019; 706: 52-61.
[http://dx.doi.org/10.1016/j.gene.2019.04.063] [PMID: 31039435]
[49]
Wilcox G. Insulin and insulin resistance. Clin Biochem Rev 2005; 26(2): 19-39.
[PMID: 16278749]
[50]
Akbarzadeh A, Norouzian D, Mehrabi MR, et al. Induction of diabetes by Streptozotocin in rats. Indian J Clin Biochem 2007; 22(2): 60-4.
[http://dx.doi.org/10.1007/BF02913315] [PMID: 23105684]
[51]
Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 2008; 51(2): 216-26.
[http://dx.doi.org/10.1007/s00125-007-0886-7] [PMID: 18087688]
[52]
Hussein J, El-Naggar ME, Latif YA, et al. Solvent-free and one-pot synthesis of silver and zinc oxide nanoparticles: Activity toward cell membrane component and insulin signaling pathway in experimental diabetes. Colloids Surf B Biointerfaces 2018; 170: 76-84.
[http://dx.doi.org/10.1016/j.colsurfb.2018.05.058] [PMID: 29883845]
[53]
Meng Q Y, Wang H, Cui Z-B, Yu W-G, Lu X-Z. Chitosan oligosaccharides attenuate amyloid formation of hIAPP and protect pancreatic β-Cells from cytotoxicity. Molecules 2020; 25(6): 1314.
[http://dx.doi.org/10.3390/molecules25061314] [PMID: 32183067]
[54]
Ju C, Yue W, Yang Z, et al. Antidiabetic effect and mechanism of chitooligosaccharides. Biol Pharm Bull 2010; 33(9): 1511-6.
[http://dx.doi.org/10.1248/bpb.33.1511] [PMID: 20823566]
[55]
Watt MJ, Miotto PM, De Nardo W, Montgomery MK. the liver as an endocrine organ—linking NAFLD and insulin resistance. Endocr Rev 2019; 40(5): 1367-93.
[http://dx.doi.org/10.1210/er.2019-00034] [PMID: 31098621]
[56]
Zafar M, Naeem-ul-Hassan Naqvi S, Masood Ahmed M, Ali Kaimkhani ZA. Altered Liver Morphology and Enzymes in Streptozotocin Induced Diabetic Rats. Int J Morphol 2009; 27(3): 719-25.
[http://dx.doi.org/10.4067/S0717-95022009000300015]
[57]
Yakhchalian N. Hematological and serum biochemical analysis of streptozotocin-induced insulin dependent diabetes mellitus in male adult Wistar rats BioRxiv 2018.
[http://dx.doi.org/10.1101/359844]
[58]
Kasetti RB, Rajasekhar MD, Kondeti VK, et al. Antihyperglycemic and antihyperlipidemic activities of methanol:water (4:1) fraction isolated from aqueous extract of Syzygium alternifolium seeds in streptozotocin induced diabetic rats. Food Chem Toxicol 2010; 48(4): 1078-84.
[http://dx.doi.org/10.1016/j.fct.2010.01.029] [PMID: 20122979]
[59]
Mohamed AS. Silver/chitosan/ascorbic acid nanocomposites attenuates bacterial sepsis. Int J Pharmacol 2021.
[60]
Islam S, Rahman Bhuiyan MA. Chitin and chitosan: structure,properties and applications in biomedical engineering. J Polym Environ 2017; 25(3): 854-66.
[http://dx.doi.org/10.1007/s10924-016-0865-5]
[61]
Vítek L. The role of bilirubin in diabetes, metabolic syndrome, and cardiovascular diseases. Front Pharmacol 2012; 3: 55.
[http://dx.doi.org/10.3389/fphar.2012.00055] [PMID: 22493581]
[62]
Gazzin S, Vitek L, Watchko J, Shapiro SM, Tiribelli C. A novel perspective on the biology of bilirubin in health and disease. Trends Mol Med 2016; 22(9): 758-68.
[http://dx.doi.org/10.1016/j.molmed.2016.07.004] [PMID: 27515064]
[63]
Soji-Omoniwa O, Muhammad NO, Usman LA, Omoniwa BP. Effect of leaf essential oil of Citrus sinensis at different harvest time on some liver and kidney function indices of diabetic rats. Int J Bioeng Life Sci 2014; 8(5): 487-91.
[64]
Karam GA, Reisi M, Kaseb AA, Khaksari M, Mohammadi A, Mahmoodi M. Effects of opium addiction on some serum factors in addicts with non-insulin-dependent diabetes mellitus. Addict Biol 2004; 9(1): 53-8.
[http://dx.doi.org/10.1080/13556210410001674095] [PMID: 15203439]
[65]
Pangestuti R, Kim SK. Neuroprotective properties of chitosan and its derivatives. Mar Drugs 2010; 8(7): 2117-28.
[http://dx.doi.org/10.3390/md8072117] [PMID: 20714426]
[66]
Taslidere E, Gul M, Elbe H, et al. The effects of caffeic acid phenethyl ester on streptozotocin-induced diabetic liver injury. Bratisl Lek Listy 2016; 117(5): 276-82.
[http://dx.doi.org/10.4149/BLL_2016_054] [PMID: 27215964]
[67]
Sztalryd C, Kraemer FB. Regulation of hormone-sensitive lipase in streptozotocin-induced diabetic rats. Metabolism 1995; 44(11): 1391-6.
[http://dx.doi.org/10.1016/0026-0495(95)90135-3] [PMID: 7476323]
[68]
Jain AP, Gupta DP. Study of blood lipid in Diabetics without any manifest vascular complications. J Dia Asso Ind 1980; 20: 29-34.
[69]
Young NL, Lopez D, Mcnamara D. Contributions of absorbed dietary cholesterol and cholesterol synthesized in small intestine to hypercholesterolemia in diabetic rats. Diabetes 1988; 37(8): 1151-6.
[http://dx.doi.org/10.2337/diab.37.8.1151] [PMID: 3391347]
[70]
Mona HM, Sahar SA, Hend SM, Nanees Al-W. A. Dyslipidemia in type 1 diabetes mellitus: relation to diabetes duration, glycemic control, body habitus, dietaryintake and other epidemiological risk factors. Egyptian Pediatric Association Gazette 2015; 63(2): 63-8.
[http://dx.doi.org/10.1016/j.epag.2015.03.001]
[71]
Suryawanshi NP, Bhutey AK, Nagdeote AN, Jadhav AA, Manoorkar GS. Study of lipid peroxide and lipid profile in diabetes mellitus. Indian J Clin Biochem 2006; 21(1): 126-30.
[http://dx.doi.org/10.1007/BF02913080] [PMID: 23105583]
[72]
Barski L, Brandstaetter E, Sagy I, Jotkowitz A. Basal insulin for the management of diabetic ketoacidosis. Eur J Intern Med 2018; 47: 14-6.
[http://dx.doi.org/10.1016/j.ejim.2017.08.025] [PMID: 28864157]
[73]
Owu DU, Antai AB, Udofia KH, Obembe AO, Obasi KO, Eteng MU. Vitamin C improves basal metabolic rate and lipid profile in alloxan-induced diabetes mellitus in rats. J Biosci 2006; 31(5): 575-9.
[http://dx.doi.org/10.1007/BF02708409] [PMID: 17301495]
[74]
Finaud J, Lac G, Filaire E. Oxidative stress. Sports Med 2006; 36(4): 327-58.
[http://dx.doi.org/10.2165/00007256-200636040-00004] [PMID: 16573358]
[75]
Freeman BA, Crapo JD. Biology of disease: free radicals and tissue injury. Lab Invest 1982; 47(5): 412-26.
[PMID: 6290784]
[76]
Takasu N, Komiya I, Asawa T, Nagasawa Y, Yamada T. Streptozocin- and alloxan-induced H2O2 generation and DNA fragmentation in pancreatic islets. H2O2 as mediator for DNA fragmentation. Diabetes 1991; 40(9): 1141-5.
[http://dx.doi.org/10.2337/diab.40.9.1141] [PMID: 1834504]
[77]
Fu MX, Wells-Knecht KJ, Blackledge JA, Lyons TJ, Thorpe SR, Baynes JW. Glycation, glycoxidation, and cross-linking of collagen by glucose. Kinetics, mechanisms, and inhibition of late stages of the Maillard reaction. Diabetes 1994; 43(5): 676-83.
[http://dx.doi.org/10.2337/diab.43.5.676] [PMID: 8168645]
[78]
Janero DR. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 1990; 9(6): 515-40.
[http://dx.doi.org/10.1016/0891-5849(90)90131-2] [PMID: 2079232]
[79]
Bruckdorfer R. The basics about nitric oxide. Mol Aspects Med 2005; 26(1-2): 3-31.
[http://dx.doi.org/10.1016/j.mam.2004.09.002] [PMID: 15722113]
[80]
Lowenstein CJ, Dinerman JL, Snyder SH. Nitric oxide: a physiologic messenger. Ann Intern Med 1994; 120(3): 227-37.
[http://dx.doi.org/10.7326/0003-4819-120-3-199402010-00009] [PMID: 8273987]
[81]
Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991; 43(2): 109-42.
[PMID: 1852778]
[82]
Corbett JA, Sweetland MA, Wang JL, Lancaster JR Jr, McDaniel ML. Nitric oxide mediates cytokine-induced inhibition of insulin secretion by human islets of Langerhans. Proc Natl Acad Sci USA 1993; 90(5): 1731-5.
[http://dx.doi.org/10.1073/pnas.90.5.1731] [PMID: 8383325]
[83]
Wang ZF, Wang MY, Yu DH, et al. Therapeutic effect of chitosan on CCl4‑induced hepatic fibrosis in rats. Mol Med Rep 2018; 18(3): 3211-8.
[http://dx.doi.org/10.3892/mmr.2018.9343] [PMID: 30085342]

Rights & Permissions Print Cite
Article Metrics
22
2
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy