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Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

Regenerative Medicine and Nanotechnology approaches against Cardiovascular Diseases: Recent Advances and Future Prospective

In Press, (this is not the final "Version of Record"). Available online 09 February, 2024
Author(s): Muhammad Waseem Sajjad, Fatima Muzamil, Maida Sabir and Usman Ali Ashfaq*
Published on: 09 February, 2024

DOI: 10.2174/011574888X263530230921074827

Price: $95

Abstract

Regenerative medicine refers to medical research focusing on repairing, replacing, or regenerating damaged or diseased tissues or organs. Cardiovascular disease (CVDs) is a significant health issue globally and is the leading cause of death in many countries. According to the Centers for Disease Control and Prevention (CDC), one person dies every 34 seconds in the United States from cardiovascular diseases, and according to a World Health Organization (WHO) report, cardiovascular diseases are the leading cause of death globally, taking an estimated 17.9 million lives each year. Many conventional treatments are available using different drugs for cardiovascular diseases, but these treatments are inadequate. Stem cells and nanotechnology are promising research areas for regenerative medicine treating CVDs. Regenerative medicines are a revolutionary strategy for advancing and successfully treating various diseases, intending to control cardiovascular disorders. This review is a comprehensive study of different treatment methods for cardiovascular diseases using different types of biomaterials as regenerative medicines, the importance of different stem cells in therapeutics, the expanded role of nanotechnology in treatment, the administration of several types of stem cells, their tracking, imaging, and the final observation of clinical trials on many different levels as well as it aims to keep readers up to pace on emerging therapeutic applications of some specific organs and disorders that may improve from regenerative medicine shortly.

[1]
Edgardo Olvera Lopez BDB. Cardiovascular Disease. StarPearls. 2022.
[2]
Benjamin EJ, Virani SS, Callaway CW, et al. Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association. Circulation 2018; 137(12): e67-e492.
[http://dx.doi.org/10.1161/CIR.0000000000000558] [PMID: 29386200]
[3]
Farley A, McLafferty E, Hendry C. The cardiovascular system. Nurs Stand 2012; 27(9): 35-9.
[http://dx.doi.org/10.7748/ns.27.9.35.s52] [PMID: 23240514]
[4]
Munger MA, Van Tassell BW, LaFleur J. Medication nonadherence: An unrecognized cardiovascular risk factor. Medscape general medicine 2007; 9(3): 58.
[5]
Curry SJ, Krist AH, Owens DK, et al. Risk assessment for cardiovascular disease with nontraditional risk factors. JAMA 2018; 320(3): 272-80.
[http://dx.doi.org/10.1001/jama.2018.8359] [PMID: 29998297]
[6]
Fox CS, Coady S, Sorlie PD, et al. Trends in cardiovascular complications of diabetes. JAMA 2004; 292(20): 2495-9.
[http://dx.doi.org/10.1001/jama.292.20.2495] [PMID: 15562129]
[7]
McGill HC Jr, McMahan CA, Gidding SS. Preventing heart disease in the 21st century: implications of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Circulation 2008; 117(9): 1216-27.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.717033] [PMID: 18316498]
[8]
Stewart J, Manmathan G, Wilkinson P. Primary prevention of cardiovascular disease: A review of contemporary guidance and literature. JRSM Cardiovasc Dis 2020; 9: 2048004020949323.
[http://dx.doi.org/10.1177/2048004016687211] [PMID: 28286646]
[9]
Organization, W.H. Cardiovascular diseases World Health Organization.Cardiovascular diseases. Fact Sheet 2007; 317.
[10]
Yu H, Lu K, Zhu J, Wang J. Stem cell therapy for ischemic heart diseases. Br Med Bull 2017; 121(1): 135-54.
[http://dx.doi.org/10.1093/bmb/ldw059] [PMID: 28164211]
[11]
Suarez S, Almutairi A, Christman K. Micro-and nanoparticles for treating cardiovascular disease. J Biomat Sci 2015; 3(4): 564-80.
[12]
Rosalyn Abbott PA, Ambrosio F, Almarza AJ. What Is Regenerative Medicine? McGowan Institute for Regenerative Medicine. A program of the University of Pittsburgh and the University of Pittsburgh Medical Center 2022.
[13]
Rubino CM, Bradley JS. Optimizing therapy with antibacterial agents: Use of pharmacokinetic-pharmacodynamic principles in pediatrics. Paediatr Drugs 2007; 9(6): 361-9.
[http://dx.doi.org/10.2165/00148581-200709060-00003] [PMID: 18052406]
[14]
Liu KKYWX. Nanotechnology meets regenerative medicine: A new frontier? Nanotechnol Rev 2013; 2(1).
[15]
Miller-Kasprzak E, Jagodziński PP. Endothelial progenitor cells as a new agent contributing to vascular repair. Arch Immunol Ther Exp 2007; 55(4): 247-59.
[http://dx.doi.org/10.1007/s00005-007-0027-5] [PMID: 17659378]
[16]
Weaver CV, Garry DJ. Regenerative biology: A historical perspective and modern applications. Regen Med 2008; 3(1): 63-82.
[http://dx.doi.org/10.2217/17460751.3.1.63] [PMID: 18154463]
[17]
Sunderland ME. Regeneration: Thomas Hunt Morgan’s window into development. J Hist Biol 2010; 43(2): 325-61.
[http://dx.doi.org/10.1007/s10739-009-9203-2] [PMID: 20665231]
[18]
Martin G. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells Developmental Biology. Proceed Nation Acad Sci United States of America 1981; 78(12): 7634-8.
[19]
Gianluca Sampognaa SYGb, Forgionea A. Regenerative medicine: Historical roots and potential strategies in modern medicine. J Microsc Ultrastruct 2015; 3(3): 101-7.
[20]
Illingworth CM. Trapped fingers and amputated finger tips in children. J Pediatr Surg 1974; 9(6): 853-8.
[http://dx.doi.org/10.1016/S0022-3468(74)80220-4] [PMID: 4473530]
[21]
Horseman B. “Regeneration of a Finger”, History of Regenerative Medicine. J Microsc Ultrastruct 2015; 3(3): 101-7.
[PMID: 30023189]
[22]
Anat J. Form and function in regenerative medicine. Introduction 2015.
[23]
Spine GOa. Five Benefits of Regenerative Medicine Genesis Orthopaedic and Spine
[24]
Mendez GF, Cowie MR. The epidemiological features of heart failure in developing countries: A review of the literature. Int J Cardiol 2001; 80(2-3): 213-9.
[http://dx.doi.org/10.1016/S0167-5273(01)00497-1] [PMID: 11578717]
[25]
Sanderson JE, Tse TF. Heart failure: A global disease requiring a global response. Br Heart J 2003; 89(6): 585-6.
[http://dx.doi.org/10.1136/heart.89.6.585] [PMID: 12748201]
[26]
Lloyd-Jones DM, Larson MG, Beiser A, Levy D. Lifetime risk of developing coronary heart disease. Lancet 1999; 353(9147): 89-92.
[http://dx.doi.org/10.1016/S0140-6736(98)10279-9] [PMID: 10023892]
[27]
Roth GA, Mensah GA, Johnson CO, et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study. J Am Coll Cardiol 2020; 76(25): 2982-3021.
[http://dx.doi.org/10.1016/j.jacc.2020.11.010] [PMID: 33309175]
[28]
Fernández-Avilés F, Sanz-Ruiz R, Climent AM, et al. Global position paper on cardiovascular regenerative medicine. Eur Heart J 2017; 38(33): 2532-46.
[http://dx.doi.org/10.1093/eurheartj/ehx248] [PMID: 28575280]
[29]
Jane R. Applications of biomaterials in regenerative medicine. J Stem Cell Res Medicin 2019; 4
[30]
Nii T, Katayama Y. Biomaterial-assisted regenerative medicine. Int J Mol Sci 2021; 22(16): 8657.
[http://dx.doi.org/10.3390/ijms22168657] [PMID: 34445363]
[31]
Reddy MSB, Ponnamma D, Choudhary R, Sadasivuni KK. A comparative review of natural and synthetic biopolymer composite scaffolds. Polymers 2021; 13(7): 1105.
[http://dx.doi.org/10.3390/polym13071105] [PMID: 33808492]
[32]
Sumrita Bhat AK. Biomaterials in regenerative medicine. J Postgrad Med Educat Res 2012; 46(2)
[33]
Schmidt CE, Baier JM. Acellular vascular tissues: Natural biomaterials for tissue repair and tissue engineering. Biomaterials 2000; 21(22): 2215-31.
[http://dx.doi.org/10.1016/S0142-9612(00)00148-4] [PMID: 11026628]
[34]
Place ES, Stevens MM. Complexity in biomaterials for tissue engineering. Nat Mater 2009; 8(6): 457-70.
[35]
Lee KY, Mooney DJ. Alginate: Properties and biomedical applications. Prog Polym Sci 2012; 37(1): 106-26.
[http://dx.doi.org/10.1016/j.progpolymsci.2011.06.003] [PMID: 22125349]
[36]
Hand I. Natural Biomaterials. OpenWetWare contributors 2017.
[37]
Xu T, Molnar P, Gregory C, Das M, Boland T, Hickman JJ. Electrophysiological characterization of embryonic hippocampal neurons cultured in a 3D collagen hydrogel. Biomaterials 2009; 30(26): 4377-83.
[http://dx.doi.org/10.1016/j.biomaterials.2009.04.047] [PMID: 19501396]
[38]
O’Leary C, Cavanagh B, Unger RE, et al. The development of a tissue-engineered tracheobronchial epithelial model using a bilayered collagen-hyaluronate scaffold. Biomaterials 2016; 85(111): 111-27.
[http://dx.doi.org/10.1016/j.biomaterials.2016.01.065] [PMID: 26871888]
[39]
Nour Almouemen HMK. Computational and Structural Biotechnology Unit 2019; 17(17): 591-8.
[http://dx.doi.org/10.1016/j.csbj.2019.04.008]
[40]
Mertsching H, Walles T, Hofmann M, Schanz J, Knapp WH. Engineering of a vascularized scaffold for artificial tissue and organ generation. Biomaterials 2005; 26(33): 6610-7.
[http://dx.doi.org/10.1016/j.biomaterials.2005.04.048] [PMID: 15979139]
[41]
Homminga GN, Buma P, Koot HWJ, van der Kraan PM, van den Berg WB. Chondrocyte behavior in fibrin glue in vitro. Acta Orthop Scand 1993; 64(4): 441-5.
[http://dx.doi.org/10.3109/17453679308993663] [PMID: 8213124]
[42]
Reis LA, Chiu LLY, Feric N, Fu L, Radisic M. Biomaterials in myocardial tissue engineering. J Tissue Eng Regen Med 2016; 10(1): 11-28.
[http://dx.doi.org/10.1002/term.1944] [PMID: 25066525]
[43]
Hughes CS, Postovit LM, Lajoie GA. Matrigel: A complex protein mixture required for optimal growth of cell culture. Proteomics 2010; 10(9): 1886-90.
[http://dx.doi.org/10.1002/pmic.200900758] [PMID: 20162561]
[44]
Perea-Gil I, Prat-Vidal C, Bayes-Genis A. In vivo experience with natural scaffolds for myocardial infarction: The times they are a-changin’. Stem Cell Res Ther 2015; 6(1): 248.
[http://dx.doi.org/10.1186/s13287-015-0237-4] [PMID: 26670389]
[45]
Tiziana Nardo IC. Francesca Ruini, Silvia Caddeo, Stefano Calzone, Valeria Chiono and Gianluca Ciardelli, CHAPTER 65, Synthetic Biomaterial for Regenerative Medicine Applications, kidney Transplantation, Bioengineering, and Regeneration. Academic Press 2017; pp. 901-21.
[46]
Gosau M, et al. Gesichtsschädelaugmentationen mit porösen Polyethylenimplantaten (Medpor®). Oral Maxillofac Surg 2006; 10(3): 178-84.
[47]
Menderes A, Baytekin C, Topcu A, Yilmaz M, Barutcu A. Craniofacial reconstruction with high-density porous polyethylene implants. J Craniofac Surg 2004; 15(5): 719-24.
[http://dx.doi.org/10.1097/00001665-200409000-00004] [PMID: 15346006]
[48]
Gaétan Laroche YM, Guidoin R, Martin WK, Martin L, How T, Douville Y. Polyvinylidene fluoride (PVDF) as a biomaterial: From polymeric raw material to monofilament vascular suture. J Biomed Mater Res 1995; 29(12): 1525-36.
[49]
Mary C, Marois Y, King MW, et al. Comparison of the in vivo behavior of polyvinylidene fluoride and polypropylene sutures used in vascular surgery. ASAIO J 1998; 44(3): 199-206.
[http://dx.doi.org/10.1097/00002480-199805000-00015] [PMID: 9617952]
[50]
Baleani M, Cristofolini L, Minari C, Toni A. Fatigue strength of PMMA bone cement mixed with gentamicin and barium sulphate vs pure PMMA. Proc Inst Mech Eng H 2003; 217(1): 9-12.
[http://dx.doi.org/10.1243/095441103762597683] [PMID: 12578214]
[51]
Bruens ML, Pieterman H, de Wijn JR, Vaandrager JM. Porous polymethylmethacrylate as bone substitute in the craniofacial area. J Craniofac Surg 2003; 14(1): 63-8.
[http://dx.doi.org/10.1097/00001665-200301000-00011] [PMID: 12544223]
[52]
Ikada Y, Tsuji H. Biodegradable polyesters for medical and ecological applications. Macromol Rapid Commun 2000; 21(3): 117-32.
[http://dx.doi.org/10.1002/(SICI)1521-3927(20000201)21:3<117::AID-MARC117>3.0.CO;2-X]
[53]
Ma Z, KM, Yong T, He W, Ramakrishna S. Surface engineering of electrospun polyethyleneterephthalate (PET) nanofibers towards development of a new material for blood vessel engineering. Biomaterial 2005; 26(15)
[54]
van Wachem PV, Feijen JSJ, Beugeling T, et al. Adhesion and spreading of cultured endothelial cells on modified and unmodified poly (ethylene terephthalate): A morphological study. Biomaterial 1989; pp. 532-9.
[55]
Sáenz A, Brostow W, Castaño V. Ceramic biomaterials: An introductory overview. J Mater Educ 1999; 21(5-6): 297-306.
[56]
Satyavrata Samavedia LKP. Synthetic biomaterials for regenerative medicine applications. 81-99.
[57]
Stanisławska A. Biomaterials and implants in cardiac and vascular surgery. Adv Mater Sci 2014; 14
[58]
Sakr MA, Sakthivel K, Hossain T, et al. Recent trends in gelatin methacryloyl nanocomposite hydrogels for tissue engineering. J Biomed Mater Res A 2022; 110(3): 708-24.
[http://dx.doi.org/10.1002/jbm.a.37310] [PMID: 34558808]
[59]
Xing M, Jiang Y, Bi W, et al. Strontium ions protect hearts against myocardial ischemia/reperfusion injury. Sci Adv 2021; 7(3): eabe0726.
[http://dx.doi.org/10.1126/sciadv.abe0726] [PMID: 33523909]
[60]
Muster D. Biomaterials: Hard tissue repair and replacement. SpringerLink 1992; pp. 347-80.
[61]
JE L. Perspectives on biomaterials, materials. Sci Monog 1986; 25(27)
[62]
Morsink M, Severino P, Luna-Ceron E, Hussain MA, Sobahi N, Shin SR. Effects of electrically conductive nano-biomaterials on regulating cardiomyocyte behavior for cardiac repair and regeneration. Acta Biomater 2022; 139: 141-56.
[http://dx.doi.org/10.1016/j.actbio.2021.11.022] [PMID: 34818579]
[63]
Beltran-Vargas NE, Peña-Mercado E, Sánchez-Gómez C, et al. Sodium alginate/chitosan scaffolds for cardiac tissue engineering: The influence of its three-dimensional material preparation and the use of gold nanoparticles. Polymers 2022; 14(16): 3233.
[http://dx.doi.org/10.3390/polym14163233] [PMID: 36015490]
[64]
Pera MF, Reubinoff B, Trounson A. Human embryonic stem cells. J Cell Sci 2000; 113(1): 5-10.
[http://dx.doi.org/10.1242/jcs.113.1.5] [PMID: 10591620]
[65]
Mahla RS. Stem cells applications in regenerative medicine and disease therapeutics. Int J Cell Biol 2016; 2016(11): 6940283.
[http://dx.doi.org/10.1155/2016/6940283]
[66]
Zakrzewski W, Dobrzyński M, Szymonowicz M, Rybak Z. Stem cells: Past, present, and future. Stem Cell Res Ther 2019; 10(1): 68.
[http://dx.doi.org/10.1186/s13287-019-1165-5] [PMID: 30808416]
[67]
Jency George MWA, Jegan SR, Mahija SP, Josphin JS. A review of stem cells in regenerative medicine. International Journal of Scientific Research and Technology 2017; 3(8): 806-15.
[68]
Staff BMC. Stem cells: What they are and what they do?. Myoclinic 2022.
[69]
Nasser MI, Qi X, Zhu S, et al. Current situation and future of stem cells in cardiovascular medicine. Biomed Pharmacother 2020; 132: 110813.
[http://dx.doi.org/10.1016/j.biopha.2020.110813] [PMID: 33068940]
[70]
Dahlqvist C, Blokzijl A, Chapman G, et al. Functional Notch signaling is required for BMP4-induced inhibition of myogenic differentiation. Development 2003; 130(24): 6089-99.
[http://dx.doi.org/10.1242/dev.00834] [PMID: 14597575]
[71]
Fang X, Miao S, Yu Y, et al. MIR148A family regulates cardiomyocyte differentiation of human embryonic stem cells by inhibiting the DLL1-mediated NOTCH signaling pathway. J Mol Cell Cardiol 2019; 134: 1-12.
[http://dx.doi.org/10.1016/j.yjmcc.2019.06.014] [PMID: 31233755]
[72]
Stepniewski J, Pacholczak T, Skrzypczyk A, et al. Heme oxygenase-1 affects generation and spontaneous cardiac differentiation of induced pluripotent stem cells. IUBMB Life 2018; 70(2): 129-42.
[http://dx.doi.org/10.1002/iub.1711] [PMID: 29316264]
[73]
Girlovanu M, Susman S, Soritau O, et al. Stem cells-biological update and cell therapy progress. Clujul Med 2015; 88(3): 265-71.
[PMID: 26609255]
[74]
Terashvili M, Bosnjak ZJ. Stem cell therapies in cardiovascular disease. J Cardiothorac Vasc Anesth 2019; 33(1): 209-22.
[http://dx.doi.org/10.1053/j.jvca.2018.04.048] [PMID: 30029992]
[75]
Partovian C, Simons M. Stem cell therapies in cardiovascular disease. Drug Discov Today Ther Strateg 2008; 5(1): 73-8.
[http://dx.doi.org/10.1016/j.ddstr.2008.05.001] [PMID: 19343101]
[76]
Sharma R. Stem cells in clinical practice and tissue engineering. Curr Drug Targets 2018; 352.
[77]
Singh A, Singh A, Sen D. Mesenchymal stem cells in cardiac regeneration: A detailed progress report of the last 6 years (2010–2015). Stem Cell Res Ther 2016; 7(1): 82.
[http://dx.doi.org/10.1186/s13287-016-0341-0] [PMID: 27259550]
[78]
Guo Y, Yu Y, Hu S, Chen Y, Shen Z. The therapeutic potential of mesenchymal stem cells for cardiovascular diseases. Cell Death Dis 2020; 11(5): 349.
[http://dx.doi.org/10.1038/s41419-020-2542-9] [PMID: 32393744]
[79]
Mosca RS. Potential uses of cord blood in cardiac surgery. J Blood Transfusion 2012; 2012: 568132.
[http://dx.doi.org/10.1155/2012/568132]
[80]
Mehta A, Sequiera GL, Ramachandra CJA, et al. Re-trafficking of hERG reverses long QT syndrome 2 phenotype in human iPS-derived cardiomyocytes. Cardiovasc Res 2014; 102(3): 497-506.
[http://dx.doi.org/10.1093/cvr/cvu060] [PMID: 24623279]
[81]
Musunuru K, Sheikh F, Gupta RM, et al. Induced pluripotent stem cells for cardiovascular disease modeling and precision medicine: A scientific statement from the American Heart Association. Circ Genom Precis Med 2018; 11(1): e000043.
[http://dx.doi.org/10.1161/HCG.0000000000000043] [PMID: 29874173]
[82]
Srivastava D, Ivey KN. Potential of stem-cell-based therapies for heart disease. Nature 2006; 441(7097): 1097-9.
[http://dx.doi.org/10.1038/nature04961] [PMID: 16810246]
[83]
Cambria E, Steiger J, Günter J, et al. Cardiac regenerative medicine: The potential of a new generation of stem cells. Transfus Med Hemother 2016; 43(4): 275-81.
[http://dx.doi.org/10.1159/000448179] [PMID: 27721703]
[84]
Steinhoff G, Nesteruk J, Wolfien M, et al. Stem cells and heart disease-brake or accelerator? Adv Drug Deliv Rev 2017; 120: 2-24.
[http://dx.doi.org/10.1016/j.addr.2017.10.007] [PMID: 29054357]
[85]
Lui PPY. A practical guide for the isolation and maintenance of stem cells from tendon. Stem Cell Renewal and Cell-Cell Communication. Springer 2014; pp. 127-40.
[http://dx.doi.org/10.1007/7651_2014_92]
[86]
Moog R. Mobilization and harvesting of peripheral blood stem cells. Curr Stem Cell Res Ther 2006; 1(2): 189-201.
[http://dx.doi.org/10.2174/157488806776956869] [PMID: 18220866]
[87]
Mushahary D, Spittler A, Kasper C, Weber V, Charwat V. Isolation, cultivation, and characterization of human mesenchymal stem cells. Cytometry A 2018; 93(1): 19-31.
[http://dx.doi.org/10.1002/cyto.a.23242] [PMID: 29072818]
[88]
McKee C, Chaudhry GR. Advances and challenges in stem cell culture. Colloids Surf B Biointerfaces 2017; 159: 62-77.
[http://dx.doi.org/10.1016/j.colsurfb.2017.07.051] [PMID: 28780462]
[89]
Perin EC, López J. Methods of stem cell delivery in cardiac diseases. Nat Clin Pract Cardiovasc Med 2006; 3(S1) (Suppl. 1): S110-3.
[http://dx.doi.org/10.1038/ncpcardio0447] [PMID: 16501616]
[90]
Sheng CC, Zhou L, Hao J. Current stem cell delivery methods for myocardial repair. BioMed Res Int 2013; 2013
[http://dx.doi.org/10.1155/2013/547902]
[91]
Wollert KC, Drexler H. Clinical applications of stem cells for the heart. Circ Res 2005; 96(2): 151-63.
[http://dx.doi.org/10.1161/01.RES.0000155333.69009.63] [PMID: 15692093]
[92]
Bel A. Composite cell sheets: A further step toward safe and effective myocardial regeneration by cardiac progenitors derived from embryonic stem cells. Circulation 2010; 122(11): S118-23.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.927293]
[93]
Ramireddy A, Brodt CR, Mendizabal AM, et al. Effects of transendocardial stem cell injection on ventricular proarrhythmia in patients with ischemic cardiomyopathy: Results from the POSEIDON and TAC-HFT trials. Stem Cells Transl Med 2017; 6(5): 1366-72.
[http://dx.doi.org/10.1002/sctm.16-0328] [PMID: 28252842]
[94]
Heldman AW, DiFede DL, Fishman JE, et al. Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: The TAC-HFT randomized trial. JAMA 2014; 311(1): 62-73.
[http://dx.doi.org/10.1001/jama.2013.282909] [PMID: 24247587]
[95]
Thompson CA, Nasseri BA, Makower J, et al. Percutaneous transvenous cellular cardiomyoplasty. J Am Coll Cardiol 2003; 41(11): 1964-71.
[http://dx.doi.org/10.1016/S0735-1097(03)00397-8] [PMID: 12798567]
[96]
Nishimura K, Ishiwata H, Sakuragi Y, Hayashi Y, Fukuda A, Hisatake K. Live-cell imaging of subcellular structures for quantitative evaluation of pluripotent stem cells. Sci Rep 2019; 9(1): 1777.
[http://dx.doi.org/10.1038/s41598-018-37779-x] [PMID: 30741960]
[97]
Arora P, Sindhu A, Dilbaghi N, Chaudhury A, Rajakumar G, Rahuman AA. Nano-regenerative medicine towards clinical outcome of stem cell and tissue engineering in humans. J Cell Mol Med 2012; 16(9): 1991-2000.
[http://dx.doi.org/10.1111/j.1582-4934.2012.01534.x] [PMID: 22260258]
[98]
Accomasso L. Stem cell tracking with nanoparticles for regenerative medicine purposes: An overview. Stem cells international 2016; 2016: 7920358.
[http://dx.doi.org/10.1155/2016/7920358]
[99]
Wang J, Jokerst JV. Stem cell imaging: Tools to improve cell delivery and viability. Stem Cells International 2016; 2016: 9240652.
[http://dx.doi.org/10.1155/2016/9240652]
[100]
Tsien RY. Constructing and exploiting the fluorescent protein paintbox (Nobel Lecture). Angew Chem Int Ed 2009; 48(31): 5612-26.
[http://dx.doi.org/10.1002/anie.200901916] [PMID: 19565590]
[101]
Semenov OV. Multipotent mesenchymal stem cells from human placenta: critical parameters for isolation and maintenance of stemness after isolation. American J Obstet Gynecol 2010; 202(2): 193-e1-193. e13.
[102]
Kubinová ES. Nanotechnologies in regenerative medicine. Official J Study Minimally Invas Ther 2010; 19(3)
[103]
Khang D, Carpenter J, Chun YW, Pareta R, Webster TJ. Nanotechnology for regenerative medicine. Biomed Microdevices 2010; 12(4): 575-87.
[http://dx.doi.org/10.1007/s10544-008-9264-6] [PMID: 19096767]
[104]
Wang DK, Rahimi M, Filgueira CS. Nanotechnology applications for cardiovascular disease treatment: Current and future perspectives. Nanomedicine 2021; 34: 102387.
[http://dx.doi.org/10.1016/j.nano.2021.102387] [PMID: 33753283]
[105]
Deng Y, Zhang X, Shen H, et al. Application of the nano-drug delivery system in treatment of cardiovascular diseases. Front Bioeng Biotechnol 2020; 7: 489.
[http://dx.doi.org/10.3389/fbioe.2019.00489] [PMID: 32083068]
[106]
Chen J, Song Y, Huang Z, et al. Modification with CREKA improves cell retention in a rat model of myocardial ischemia reperfusion. Stem Cells 2019; 37(5): 663-76.
[http://dx.doi.org/10.1002/stem.2983] [PMID: 30779865]
[107]
Dvir T, Bauer M, Schroeder A, et al. Nanoparticles targeting the infarcted heart. Nano Lett 2011; 11(10): 4411-4.
[http://dx.doi.org/10.1021/nl2025882] [PMID: 21899318]
[108]
Lehner S. Temporal changes in phosphatidylserine expression and glucose metabolism after myocardial infarction: An in vivo imaging study in mice. Molecular imaging 2012; 11(6): 7290.
[http://dx.doi.org/10.2310/7290.2012.00010]
[109]
Torchilin VP, Narula J, Halpern E, Khaw BA. Poly(ethylene glycol)-coated anti-cardiac myosin immunoliposomes: factors influencing targeted accumulation in the infarcted myocardium. Biochim Biophys Acta Biomembr 1996; 1279(1): 75-83.
[http://dx.doi.org/10.1016/0005-2736(95)00248-0] [PMID: 8624365]
[110]
Chandarana M, Curtis A, Hoskins C. The use of nanotechnology in cardiovascular disease. Appl Nanosci 2018; 8(7): 1607-19.
[http://dx.doi.org/10.1007/s13204-018-0856-z]
[111]
Monteiro N, Martins A, Reis RL, Neves NM. Liposomes in tissue engineering and regenerative medicine. J R Soc Interface 2014; 11(101): 20140459.
[http://dx.doi.org/10.1098/rsif.2014.0459] [PMID: 25401172]
[112]
Namdari M, Cheraghi M, Negahdari B, Eatemadi A, Daraee H. Recent advances in magnetoliposome for heart drug delivery. Artif Cells Nanomed Biotechnol 2017; 45(6): 1051-7.
[http://dx.doi.org/10.1080/21691401.2017.1299159] [PMID: 28272903]
[113]
Ghezzi M, Pescina S, Padula C, et al. Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions. J Control Release 2021; 332: 312-36.
[http://dx.doi.org/10.1016/j.jconrel.2021.02.031] [PMID: 33652113]
[114]
Kajal A, Kishore L, Kaur N, Gollen R, Singh R. Therapeutic agents for the management of atherosclerosis from herbal sources. Beni Suef Univ J Basic Appl Sci 2016; 5(2): 156-69.
[http://dx.doi.org/10.1016/j.bjbas.2016.02.004]
[115]
Pala R, Anju VT, Dyavaiah M, Busi S, Nauli SM. Nanoparticle- mediated drug delivery for the treatment of cardiovascular diseases. Int J Nanomedicine 2020; 15: 3741-69.
[http://dx.doi.org/10.2147/IJN.S250872] [PMID: 32547026]
[116]
Geldenhuys WJ, Khayat MT, Yun J, Nayeem MA. Drug delivery and Nanoformulations for the cardiovascular system. Research reviews. Drug Deliv 2017; 1(1): 32-40.
[PMID: 28713881]
[117]
Banerjee SS. Poly (ethylene glycol)-prodrug conjugates: Concept, design, and applications. J Drug Delivery 2012; 2012
[118]
Pan Q, Xu J, Wen CJ, Xiong YY, Gong ZT, Yang YJ. Nanoparticles: Promising tools for the treatment and prevention of myocardial infarction. Int J Nanomedicine 2021; 16: 6719-47.
[http://dx.doi.org/10.2147/IJN.S328723] [PMID: 34621124]
[119]
Bennett MR. In-stent stenosis: Pathology and implications for the development of drug eluting stents. Br Heart J 2003; 89(2): 218-24.
[http://dx.doi.org/10.1136/heart.89.2.218] [PMID: 12527687]
[120]
Acharya G, Lee CH, Lee Y. Optimization of cardiovascular stent against restenosis: Factorial design-based statistical analysis of polymer coating conditions. PLoS One 2012; 7(8): e43100.
[http://dx.doi.org/10.1371/journal.pone.0043100] [PMID: 22937015]
[121]
Cutlip DE, Garratt KN, Novack V, et al. 9-month clinical and angiographic outcomes of the COBRA polyzene-F nanocoated coronary stent system. JACC Cardiovasc Interv 2017; 10(2): 160-7.
[http://dx.doi.org/10.1016/j.jcin.2016.10.037] [PMID: 28104210]
[122]
Ferreira L. Nanoparticles as tools to study and control stem cells. J Cell Biochem 2009; 108(4): 746-52.
[http://dx.doi.org/10.1002/jcb.22303] [PMID: 19708027]
[123]
Sridharan I, Kim T, Wang R. Adapting collagen/CNT matrix in directing hESC differentiation. Biochem Biophys Res Commun 2009; 381(4): 508-12.
[http://dx.doi.org/10.1016/j.bbrc.2009.02.072] [PMID: 19233124]
[124]
Lund AW, Yener B, Stegemann JP, Plopper GE. The natural and engineered 3D microenvironment as a regulatory cue during stem cell fate determination. Tissue Eng Part B Rev 2009; 15(3): 371-80.
[http://dx.doi.org/10.1089/ten.teb.2009.0270] [PMID: 19505193]
[125]
Ghaedi M, Soleimani M, Shabani I, Duan Y, Lotfi A. Hepatic differentiation from human mesenchymal stem cells on a novel nanofiber scaffold. Cell Mol Biol Lett 2012; 17(1): 89-106.
[http://dx.doi.org/10.2478/s11658-011-0040-x] [PMID: 22207333]
[126]
Kam NWS, Jan E, Kotov NA. Electrical stimulation of neural stem cells mediated by humanized carbon nanotube composite made with extracellular matrix protein. Nano Lett 2009; 9(1): 273-8.
[http://dx.doi.org/10.1021/nl802859a] [PMID: 19105649]
[127]
Cho BHS, Park JR, Nakamura MT, Odintsov BM, Wallig MA, Chung BH. Synthetic dimyristoylphosphatidylcholine liposomes assimilating into high-density lipoprotein promote regression of atherosclerotic lesions in cholesterol-fed rabbits. Exp Biol Med 2010; 235(10): 1194-203.
[http://dx.doi.org/10.1258/ebm.2010.009320] [PMID: 20876082]
[128]
Winter PM, Caruthers SD, Zhang H, Williams TA, Wickline SA, Lanza GM. Antiangiogenic synergism of integrin-targeted fumagillin nanoparticles and atorvastatin in atherosclerosis. JACC Cardiovasc Imaging 2008; 1(5): 624-34.
[http://dx.doi.org/10.1016/j.jcmg.2008.06.003] [PMID: 19356492]
[129]
Fredman G, Kamaly N, Spolitu S, et al. Targeted nanoparticles containing the proresolving peptide Ac2-26 protect against advanced atherosclerosis in hypercholesterolemic mice. Sci Transl Med 2015; 7(275): 275ra20.
[http://dx.doi.org/10.1126/scitranslmed.aaa1065] [PMID: 25695999]
[130]
Lobatto ME, Fayad ZA, Silvera S, et al. Multimodal clinical imaging to longitudinally assess a nanomedical anti-inflammatory treatment in experimental atherosclerosis. Mol Pharm 2010; 7(6): 2020-9.
[http://dx.doi.org/10.1021/mp100309y] [PMID: 21028895]
[131]
Reddy MK, Vasir JK, Sahoo SK, Jain TK, Yallapu MM, Labhasetwar V. Inhibition of apoptosis through localized delivery of rapamycin-loaded nanoparticles prevented neointimal hyperplasia and reendothelialized injured artery. Circ Cardiovasc Interv 2008; 1(3): 209-16.
[http://dx.doi.org/10.1161/CIRCINTERVENTIONS.108.830018] [PMID: 20031680]
[132]
Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011; 473(7347): 317-25.
[http://dx.doi.org/10.1038/nature10146] [PMID: 21593864]
[133]
Peters D, Kastantin M, Kotamraju VR, et al. Targeting atherosclerosis by using modular, multifunctional micelles. Proc Natl Acad Sci USA 2009; 106(24): 9815-9.
[http://dx.doi.org/10.1073/pnas.0903369106] [PMID: 19487682]
[134]
Myerson J, He L, Lanza G, Tollefsen D, Wickline S. Thrombin‐inhibiting perfluorocarbon nanoparticles provide a novel strategy for the treatment and magnetic resonance imaging of acute thrombosis. J Thromb Haemost 2011; 9(7): 1292-300.
[http://dx.doi.org/10.1111/j.1538-7836.2011.04339.x] [PMID: 21605330]
[135]
Ashtari K, Nazari H, Ko H, et al. Electrically conductive nanomaterials for cardiac tissue engineering. Adv Drug Deliv Rev 2019; 144: 162-79.
[http://dx.doi.org/10.1016/j.addr.2019.06.001] [PMID: 31176755]
[136]
Feiner R, Engel L, Fleischer S, et al. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function. Nat Mater 2016; 15(6): 679-85.
[http://dx.doi.org/10.1038/nmat4590] [PMID: 26974408]
[137]
Malki M, Fleischer S, Shapira A, Dvir T. Gold nanorod-based engineered cardiac patch for suture-free engraftment by near IR. Nano Lett 2018; 18(7): 4069-73.
[http://dx.doi.org/10.1021/acs.nanolett.7b04924] [PMID: 29406721]
[138]
Bashshur RL, Shannon GW, Smith BR, et al. The empirical foundations of telemedicine interventions for chronic disease management. Telemed J E Health 2014; 20(9): 769-800.
[http://dx.doi.org/10.1089/tmj.2014.9981] [PMID: 24968105]
[139]
Tang J, Su T, Huang K, et al. Targeted repair of heart injury by stem cells fused with platelet nanovesicles. Nat Biomed Eng 2018; 2(1): 17-26.
[http://dx.doi.org/10.1038/s41551-017-0182-x] [PMID: 29862136]
[140]
Tang J, Wang J, Guo L, et al. Mesenchymal stem cells modified with stromal cell-derived factor 1α improve cardiac remodeling via paracrine activation of hepatocyte growth factor in a rat model of myocardial infarction. Mol Cells 2010; 29(1): 9-19.
[http://dx.doi.org/10.1007/s10059-010-0001-7] [PMID: 20016947]
[141]
Mirotsou M, Jayawardena TM, Schmeckpeper J, Gnecchi M, Dzau VJ. Paracrine mechanisms of stem cell reparative and regenerative actions in the heart. J Mol Cell Cardiol 2011; 50(2): 280-9.
[http://dx.doi.org/10.1016/j.yjmcc.2010.08.005] [PMID: 20727900]
[142]
Tang YL, Zhao Q, Qin X, et al. Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. Ann Thorac Surg 2005; 80(1): 229-37.
[http://dx.doi.org/10.1016/j.athoracsur.2005.02.072] [PMID: 15975372]
[143]
Barnes CP, Sell SA, Boland ED, Simpson DG, Bowlin GL. Nanofiber technology: Designing the next generation of tissue engineering scaffolds. Adv Drug Deliv Rev 2007; 59(14): 1413-33.
[http://dx.doi.org/10.1016/j.addr.2007.04.022] [PMID: 17916396]
[144]
Engel E, Michiardi A, Navarro M, Lacroix D, Planell JA. Nanotechnology in regenerative medicine: The materials side. Trends Biotechnol 2008; 26(1): 39-47.
[http://dx.doi.org/10.1016/j.tibtech.2007.10.005] [PMID: 18036685]
[145]
Cui Z, Yang B, Li RK. Application of biomaterials in cardiac repair and regeneration. Engineering 2016; 2(1): 141-8.
[http://dx.doi.org/10.1016/J.ENG.2016.01.028]
[146]
Khan K, Gasbarrino K, Mahmoud I, et al. Bioactive scaffolds in stem-cell-based therapies for cardiac repair: Protocol for a meta-analysis of randomized controlled preclinical trials in animal myocardial infarction models. Syst Rev 2018; 7(1): 225.
[http://dx.doi.org/10.1186/s13643-018-0845-z] [PMID: 30518435]
[147]
Do AV, Khorsand B, Geary SM, Salem AK. 3D printing of scaffolds for tissue regeneration applications. Adv Healthc Mater 2015; 4(12): 1742-62.
[http://dx.doi.org/10.1002/adhm.201500168] [PMID: 26097108]
[148]
Cruz-Samperio R, Jordan M, Perriman A. Cell augmentation strategies for cardiac stem cell therapies. Stem Cells Transl Med 2021; 10(6): 855-66.
[http://dx.doi.org/10.1002/sctm.20-0489] [PMID: 33660953]
[149]
Taghavi S, George JC. Homing of stem cells to ischemic myocardium. Am J Transl Res 2013; 5(4): 404-11.
[PMID: 23724164]
[150]
Karpov AA, Udalova DV, Pliss MG, Galagudza MM. Can the outcomes of mesenchymal stem cell-based therapy for myocardial infarction be improved? Providing weapons and armour to cells. Cell Prolif 2017; 50(2): e12316.
[http://dx.doi.org/10.1111/cpr.12316] [PMID: 27878916]
[151]
Won YW, Patel AN, Bull DA. Cell surface engineering to enhance mesenchymal stem cell migration toward an SDF-1 gradient. Biomaterials 2014; 35(21): 5627-35.
[http://dx.doi.org/10.1016/j.biomaterials.2014.03.070] [PMID: 24731711]
[152]
Segers VF, Lee RT. Biomaterials to enhance stem cell function in the heart. Circulat Res 2011; 109(8): 910-22.
[153]
Xiao W, Green TIP, Liang X, et al. Designer artificial membrane binding proteins to direct stem cells to the myocardium. Chem Sci 2019; 10(32): 7610-8.
[http://dx.doi.org/10.1039/C9SC02650A] [PMID: 31588312]
[154]
Armstrong JP. Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue. Nat Communicat 2015; 6(1): 1-6.
[155]
Rasouli M, Rahimi A, Soleimani M, keshel SH. The interplay between extracellular matrix and progenitor/stem cells during wound healing: Opportunities and future directions. Acta Histochem 2021; 123(7): 151785.
[http://dx.doi.org/10.1016/j.acthis.2021.151785] [PMID: 34500185]
[156 ]
Brizzi MF, Tarone G, Defilippi P. Extracellular matrix, integrins, and growth factors as tailors of the stem cell niche. Curr Opin Cell Biol 2012; 24(5): 645-51.
[http://dx.doi.org/10.1016/j.ceb.2012.07.001] [PMID: 22898530]
[157]
Gattazzo F, Urciuolo A, Bonaldo P. Extracellular matrix: A dynamic microenvironment for stem cell niche. Biochim Biophys Acta, Gen Subj 2014; 1840(8): 2506-19.
[http://dx.doi.org/10.1016/j.bbagen.2014.01.010] [PMID: 24418517]
[158]
Avigdor A, Goichberg P, Shivtiel S, et al. CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow. Blood 2004; 103(8): 2981-9.
[http://dx.doi.org/10.1182/blood-2003-10-3611] [PMID: 15070674]
[159]
Smith-Berdan S, Nguyen A, Hassanein D, et al. Robo4 cooperates with CXCR4 to specify hematopoietic stem cell localization to bone marrow niches. Cell Stem Cell 2011; 8(1): 72-83.
[http://dx.doi.org/10.1016/j.stem.2010.11.030] [PMID: 21211783]
[160]
Hung HS, Chang CH, Chang CJ, et al. In vitro study of a novel nanogold-collagen composite to enhance the mesenchymal stem cell behavior for vascular regeneration. PLoS One 2014; 9(8): e104019.
[http://dx.doi.org/10.1371/journal.pone.0104019] [PMID: 25093502]
[161]
Sun Y, Lu Y, Yin L, Liu Z. The roles of nanoparticles in stem cell-based therapy for cardiovascular disease. Front Bioeng Biotechnol 2020; 8: 947.
[http://dx.doi.org/10.3389/fbioe.2020.00947] [PMID: 32923434]
[162]
La Francesca S. Nanotechnology and stem cell therapy for cardiovascular diseases: Potential applications. Methodist DeBakey Cardiovasc J 2012; 8(1): 28-35.
[http://dx.doi.org/10.14797/mdcj-8-1-28] [PMID: 22891108]
[163]
Lai RC, Chen TS, Lim SK. Mesenchymal stem cell exosome: A novel stem cell-based therapy for cardiovascular disease. Regen Med 2011; 6(4): 481-92.
[http://dx.doi.org/10.2217/rme.11.35] [PMID: 21749206]
[164]
Quiat D, Olson EN. MicroRNAs in cardiovascular disease: From pathogenesis to prevention and treatment. J Clin Invest 2013; 123(1): 11-8.
[http://dx.doi.org/10.1172/JCI62876] [PMID: 23281405]
[165]
Schäffler A, Büchler C. Concise review: Adipose tissue-derived stromal cells-basic and clinical implications for novel cell-based therapies. Stem Cells 2007; 25(4): 818-27.
[http://dx.doi.org/10.1634/stemcells.2006-0589] [PMID: 17420225]
[166]
Mimeault M, Batra SK. Concise review: Recent advances on the significance of stem cells in tissue regeneration and cancer therapies. Stem Cells 2006; 24(11): 2319-45.
[http://dx.doi.org/10.1634/stemcells.2006-0066] [PMID: 16794264]
[167]
Mimeault M, Hauke R, Batra SK. Stem cells: A revolution in therapeutics-recent advances in stem cell biology and their therapeutic applications in regenerative medicine and cancer therapies. Clin Pharmacol Ther 2007; 82(3): 252-64.
[http://dx.doi.org/10.1038/sj.clpt.6100301] [PMID: 17671448]
[168]
Madonna R, Van Laake LW, Botker HE, et al. ESC working group on cellular biology of the heart: position paper for cardiovascular research: Tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure. Cardiovasc Res 2019; 115(3): 488-500.
[http://dx.doi.org/10.1093/cvr/cvz010] [PMID: 30657875]
[169]
Camci-Unal G, Cuttica D, Annabi N, Demarchi D, Khademhosseini A. Synthesis and characterization of hybrid hyaluronic acid-gelatin hydrogels. Biomacromolecules 2013; 14(4): 1085-92.
[http://dx.doi.org/10.1021/bm3019856] [PMID: 23419055]
[170]
Wang C, Varshney R, Wang DJA. herapeutic cell delivery and fate control in hydrogels and hydrogel hybrids. Adv Drug Deliv Rev 2010; 62(7-8): 699-710.
[http://dx.doi.org/10.1016/j.addr.2010.02.001]
[171]
Tiburcy M, Didié M, Boy O, et al. Terminal differentiation, advanced organotypic maturation, and modeling of hypertrophic growth in engineered heart tissue. Circ Res 2011; 109(10): 1105-14.
[http://dx.doi.org/10.1161/CIRCRESAHA.111.251843] [PMID: 21921264]
[172]
Yang J, Yamato M, Nishida K, et al. Cell delivery in regenerative medicine: The cell sheet engineering approach. J Control Release 2006; 116(2): 193-203.
[http://dx.doi.org/10.1016/j.jconrel.2006.06.022] [PMID: 16890320]
[173]
Narita T, Shintani Y, Ikebe C, et al. The use of scaffold-free cell sheet technique to refine mesenchymal stromal cell-based therapy for heart failure. Mol Ther 2013; 21(4): 860-7.
[http://dx.doi.org/10.1038/mt.2013.9] [PMID: 23358187]
[174]
Sanchez-Rexach E, Meaurio E, Sarasua JR. Recent developments in drug eluting devices with tailored interfacial properties. Adv Colloid Interface Sci 2017; 249: 181-91.
[http://dx.doi.org/10.1016/j.cis.2017.05.005] [PMID: 28532663]
[175]
Ahmad Dr. Regenerative medicine vs. conventional pain treatment. Advanced Sports Spine 2022.
[176]
Zita M. Transforming healthcare through regenerative medicine. BMC Med 2016; 14: 115.
[http://dx.doi.org/10.1186/s12916-016-0669-4] [PMID: 27510095]
[177]
Berthiaume F, Maguire TJ, Yarmush ML. Tissue engineering and regenerative medicine: History, progress, and challenges. Annu Rev Chem Biomol Eng 2011; 2(1): 403-30.
[http://dx.doi.org/10.1146/annurev-chembioeng-061010-114257] [PMID: 22432625]
[178]
Grounds MD. Obstacles and challenges for tissue engineering and regenerative medicine: Australian nuances. Clin Exp Pharmacol Physiol 2018; 45(4): 390-400.
[http://dx.doi.org/10.1111/1440-1681.12899] [PMID: 29193254]
[179]
Verjans R, van Bilsen M, Schroen B. Reviewing the limitations of adult mammalian cardiac regeneration: Noncoding RNAs as regulators of cardiomyogenesis. Biomolecules 2020; 10(2): 262.
[http://dx.doi.org/10.3390/biom10020262] [PMID: 32050588]
[180]
Wu P, Deng G, Sai X, Guo H, Huang H, Zhu P. Maturation strategies and limitations of induced pluripotent stem cell-derived cardiomyocytes. Biosci Rep 2021; 41(6): BSR20200833.
[http://dx.doi.org/10.1042/BSR20200833] [PMID: 33057659]
[181]
Volarevic V, Markovic BS, Gazdic M, et al. Ethical and safety issues of stem cell-based therapy. Int J Med Sci 2018; 15(1): 36-45.
[http://dx.doi.org/10.7150/ijms.21666] [PMID: 29333086]
[182]
Dresselhaus M. Fifty years in studying carbon-based materials. Phys Scr 2012; 2012(146: 014002)
[183]
Seabra AB, Paula AJ, de Lima R, Alves OL, Durán N. Nanotoxicity of graphene and graphene oxide. Chem Res Toxicol 2014; 27(2): 159-68.
[http://dx.doi.org/10.1021/tx400385x] [PMID: 24422439]
[184]
Harik VM. Geometry of carbon nanotubes and mechanisms of phagocytosis and toxic effects. Toxicol Lett 2017; 273: 69-85.
[http://dx.doi.org/10.1016/j.toxlet.2017.03.016] [PMID: 28341208]
[185]
Wang YJ, Larsson M, Huang W-T, et al. The use of polymer-based nanoparticles and nanostructured materials in treatment and diagnosis of cardiovascular diseases: Recent advances and emerging designs. Prog Polym Sci 2016; 57: 153-78.
[http://dx.doi.org/10.1016/j.progpolymsci.2016.01.002]
[186]
Labusca L, Herea DD, Mashayekhi K. Stem cells as delivery vehicles for regenerative medicine-challenges and perspectives. World J Stem Cells 2018; 10(5): 43-56.
[http://dx.doi.org/10.4252/wjsc.v10.i5.43] [PMID: 29849930]
[187]
Ikuta Y, Kamei N, Ishikawa M, Adachi N, Ochi M. In vivo kinetics of mesenchymal stem cells transplanted into the knee joint in a rat model using a novel magnetic method of localization. Clin Transl Sci 2015; 8(5): 467-74.
[http://dx.doi.org/10.1111/cts.12284] [PMID: 25963065]
[188]
Golchin A, Chatziparasidou A, Ranjbarvan P, Niknam Z, Ardeshirylajimi A. Embryonic stem cells in clinical trials: Current overview of developments and challenges. Adv Exp Med Biol 2020; 1312: 19-37.
[http://dx.doi.org/10.1007/5584_2020_592] [PMID: 33159303]
[189]
Gupta R, Losordo DW. Challenges in the translation of cardiovascular cell therapy. J Nucl Med 2010; 51(Suppl 1): 122S-7S.
[http://dx.doi.org/10.2967/jnumed.109.068304] [PMID: 20395342]
[190]
Vanneaux V. Induced pluripotent stem cells for clinical use.Update on mesenchymal and induced pluripotent stem cells. IntechOpen 2019.
[191]
Lukomska B. Challenges and controversies in human mesenchymal stem cell therapy. Stem Cells Inter 2019; 2019
[http://dx.doi.org/10.1155/2019/9628536]
[192]
Squillaro T, Peluso G, Galderisi U. Clinical trials with mesenchymal stem cells: An update. Cell Transplant 2016; 25(5): 829-48.
[http://dx.doi.org/10.3727/096368915X689622] [PMID: 26423725]
[193]
T Harris D. Cord blood stem cells: Current uses and future challenges. AIMS Cell Tissue Eng 2017; 1(2): 158-64.
[http://dx.doi.org/10.3934/celltissue.2017.2.158]
[194]
Harris DT, Badowski M, Ahmad N, Gaballa MA. The potential of cord blood stem cells for use in regenerative medicine. Expert Opin Biol Ther 2007; 7(9): 1311-22.
[http://dx.doi.org/10.1517/14712598.7.9.1311] [PMID: 17727322]
[195]
Garbern JC, Lee RT. Cardiac stem cell therapy and the promise of heart regeneration. Cell Stem Cell 2013; 12(6): 689-98.
[http://dx.doi.org/10.1016/j.stem.2013.05.008] [PMID: 23746978]
[196]
Sun R, Li X, Liu M, Zeng Y, Chen S, Zhang P. Advances in stem cell therapy for cardiovascular disease (Review). Int J Mol Med 2016; 38(1): 23-9.
[http://dx.doi.org/10.3892/ijmm.2016.2607] [PMID: 27220939]
[197]
Ma T, Sun J, Zhao Z, et al. A brief review: Adipose-derived stem cells and their therapeutic potential in cardiovascular diseases. Stem Cell Res Ther 2017; 8(1): 124.
[http://dx.doi.org/10.1186/s13287-017-0585-3] [PMID: 28583198]
[198]
Mathur A, Fernández-Avilés F, Dimmeler S, et al. The consensus of the Task Force of the European Society of Cardiology concerning the clinical investigation of the use of autologous adult stem cells for the treatment of acute myocardial infarction and heart failure: Update 2016. Eur Heart J 2017; 38(39): 2930-5.
[http://dx.doi.org/10.1093/eurheartj/ehw640] [PMID: 28204458]
[199]
Turksen K. Adult stem cells and cardiac regeneration. Stem Cell Rev 2013; 9(5): 537-40.
[http://dx.doi.org/10.1007/s12015-013-9448-1] [PMID: 23775698]
[200]
Kessler PD, Byrne BJ. Myoblast cell grafting into heart muscle: Cellular biology and potential applications. Annu Rev Physiol 1999; 61(1): 219-42.
[http://dx.doi.org/10.1146/annurev.physiol.61.1.219] [PMID: 10099688]
[201]
Mack D. Using biomaterials for fetal stem cell isolation, expansion and directed-differentiation. Biomaterials and Regenerative Medicine. Cambridge University Press 2015; pp. 64-79.
[202]
Petsche Connell J, Camci-Unal G, Khademhosseini A, Jacot JG. Amniotic fluid-derived stem cells for cardiovascular tissue engineering applications. Tissue Eng Part B Rev 2013; 19(4): 368-79.
[http://dx.doi.org/10.1089/ten.teb.2012.0561] [PMID: 23350771]
[203]
Huang P, Li Y, Nasser MI, et al. Urine-derived induced pluripotent stem cells in cardiovascular disease. Cardiol Res Pract 2020; 2020: 1-8.
[http://dx.doi.org/10.1155/2020/3563519] [PMID: 32377426]
[204]
Zhu FL, Zhang N, Ma XJ, et al. Circulating hematopoietic stem/progenitor cells are associated with coronary stenoses in patients with coronary heart disease. Sci Rep 2019; 9(1): 1680.
[http://dx.doi.org/10.1038/s41598-018-38298-5] [PMID: 30737465]
[205]
Yamoah MA, Thai PN, Zhang XD. Transgene delivery to human induced pluripotent stem cells using nanoparticles. Pharmaceuticals 2021; 14(4): 334.
[http://dx.doi.org/10.3390/ph14040334] [PMID: 33917388]
[206]
Yokoyama R, Ii M, Tabata Y, et al. Cardiac regeneration by statin-polymer nanoparticle-loaded adipose-derived stem cell therapy in myocardial infarction. Stem Cells Transl Med 2019; 8(10): 1055-67.
[http://dx.doi.org/10.1002/sctm.18-0244] [PMID: 31157513]
[207]
Sarathkumar E, Victor M, Menon JA, Jibin K, Padmini S, Jayasree RS. Nanotechnology in cardiac stem cell therapy: Cell modulation, imaging and gene delivery. RSC Advances 2021; 11(55): 34572-88.
[http://dx.doi.org/10.1039/D1RA06404E] [PMID: 35494731]
[208]
Kim DH, Kshitiz , Smith RR, et al. Nanopatterned cardiac cell patches promote stem cell niche formation and myocardial regeneration. Integr Biol 2012; 4(9): 1019-33.
[http://dx.doi.org/10.1039/c2ib20067h] [PMID: 22890784]
[209]
Santoso MR, Yang PC. Magnetic nanoparticles for targeting and imaging of stem cells in myocardial infarction. Stem cells international 2016; 2016: 4198790.
[http://dx.doi.org/10.1155/2016/4198790]
[210]
Zhao C, Tan A, Pastorin G, Ho HK. Nanomaterial scaffolds for stem cell proliferation and differentiation in tissue engineering. Biotechnol Adv 2013; 31(5): 654-68.
[http://dx.doi.org/10.1016/j.biotechadv.2012.08.001] [PMID: 22902273]
[211]
Liu WH, Chang YL, Lo WL, et al. Human induced pluripotent stem cell and nanotechnology-based therapeutics. Cell Transplant 2015; 24(11): 2185-95.
[http://dx.doi.org/10.3727/096368914X685113] [PMID: 25299513]
[212]
Luo W, Gong Y, Qiu F, et al. NGF nanoparticles enhance the potency of transplanted human umbilical cord mesenchymal stem cells for myocardial repair. Am J Physiol Heart Circ Physiol 2021; 320(5): H1959-74.
[http://dx.doi.org/10.1152/ajpheart.00855.2020] [PMID: 33769916]
[213]
Sintov AC, Velasco-Aguirre C, Gallardo-Toledo E, Araya E, Kogan MJ. Metal nanoparticles as targeted carriers circumventing the blood–brain barrier. Int Rev Neurobiol 2016; 130: 199-227.
[http://dx.doi.org/10.1016/bs.irn.2016.06.007] [PMID: 27678178]
[214]
Tokunaga M. Implantation of cardiac progenitor cells using self-assembling peptide improves cardiac function after myocardial infarction. J Mol 2010; 49(6): 972-83.
[215]
Simpson D, Liu H, Fan THM, Nerem R, Dudley SC Jr. A tissue engineering approach to progenitor cell delivery results in significant cell engraftment and improved myocardial remodeling. Stem Cells 2007; 25(9): 2350-7.
[http://dx.doi.org/10.1634/stemcells.2007-0132] [PMID: 17525236]
[216]
Jin J, et al. Transplantation of mesenchymal stem cells within a poly (lactide-co-ɛ-caprolactone) scaffold improves cardiac function in a rat myocardial infarction model. Circulation 2009; 11(2): 147-53.
[PMID: 20031708]
[217]
Lin YD, Yeh ML, Yang YJ, et al. Intramyocardial peptide nanofiber injection improves postinfarction ventricular remodeling and efficacy of bone marrow cell therapy in pigs. Circulation 2010; 122(11_suppl_1): S132-41.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.939512] [PMID: 20837904]
[218]
Augustine R, Dan P, Sosnik A, et al. Electrospun poly(vinylidene fluoride-trifluoroethylene)/zinc oxide nanocomposite tissue engineering scaffolds with enhanced cell adhesion and blood vessel formation. Nano Res 2017; 10(10): 3358-76.
[http://dx.doi.org/10.1007/s12274-017-1549-8]

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Request history8.2.27PHP Version289msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
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    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
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      1.09msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('309779056','/article/138387',1,1740514324,1740514324)
      220μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 309779056 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 309779056) limit 1
      20.03msalphaeurekaselec_live_10_06_2022UserAccess.php#784
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      • 1: 309779056
      • 2: 309779056
      • 3: 309779056
      • 4: 309779056
      • 5: 309779056
      • 6: 309779056
      • 7: 309779056
      • 8: 309779056
      • 9: 309779056
      • 10: 309779056
      • 11: 309779056
      • 12: 309779056
      • 13: 309779056
      • 14: 309779056
      • 15: 309779056
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=138387
      710μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 60 limit 1
      840μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 60
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=60) and sj.journal_id!=60 group by `j`.`nid`) as `aggregate_table`
      900μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=60) and sj.journal_id!=60 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      730μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=60) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      4.6msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=60) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      3.87msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '138387'
      250μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 138387
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '138387'
      4.78msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 138387
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '138387' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.5msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 138387
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      280μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      660μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 60 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      37.62msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 60 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      12.57msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 60 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      9.19msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 138387 limit 1
      180μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 138387
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 138387 and content_type = 'article' order by status desc limit 1
      210μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 226784 limit 1
      180μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 226784
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      220μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CSCRT' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      260μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CSCRT
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '138387' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      350μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '3453' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      270μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309779056 and j.to_ip >=309779056 )) and ((j.from_date <= 1740514324 and j.to_date >= 1740514324 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3453) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309779056 and j.to_ip >=309779056 )) and ((j.from_date <= 1740514324 and j.to_date >= 1740514324 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3453) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309779056 and j.to_ip >=309779056 )) and ((j.from_date <= 1740514324 and j.to_date >= 1740514324 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3453)
      20.35msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      200μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      180μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 138387 limit 1
      2.34msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 138387
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 60 and `b`.`banner_from_date` <= 1740514324 and `b`.`banner_to_date` >= 1740514324 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.26msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 60
      • 3: 1740514324
      • 4: 1740514324
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 60 and `b`.`banner_from_date` <= 1740514324 and `b`.`banner_to_date` >= 1740514324 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.16msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 60
      • 3: 1740514324
      • 4: 1740514324
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='88de8da7fac969cbba55500ad7a578e2'
      210μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        bqqj1Kb90T6ad8XveL39uf96gOuteDA5svKV48jE
        uc_cart_id
        88de8da7fac969cbba55500ad7a578e2
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/article/138387" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/138387
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6Iit5Vm9tbzU3WlVnRWVtalpKMWZ4eVE9PSIsInZhbHVlIjoiOWZ4UDg5Q3hlTVljd20xeFFnVHIxOGErQm91L1NXZnFXTVBtK0xBTUJzdz0iLCJtYWMiOiI3ZGRjNmQ3MjMwMTY5N2JkNzA5NGQyZWM5NjI4ZTBlNzYxYmQ0OTlmMWNlMmVlZjJlMDE0MzQxYWVmMWViNDdjIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6Iit5Vm9tbzU3WlVnRWVtalpKMWZ4eVE9PSIsInZhbHVlIjoiOWZ4UDg5Q3hlTVljd20xeFFnVHIxOGErQm91L1NXZnFXTVBtK0xBTUJzdz0iLCJtYWMiOiI3ZGRjNmQ3MjMwMTY5" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 20:12:04 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjlybkJQSEphVHBDdkU0dnZTRnQyWHc9PSIsInZhbHVlIjoibjByZUNLNXN5YUVQWHBuemNKU3dFY3A5bHJyWmY5NHFCb1RxeHdGWDgrdFdmMXJoQWE4YitQVTY1MEtuclYvbm9EM0p3bUg0TEliVnIxSDJRY1VOMWlLK3FyOWFZUTFWWll2V0ExblhxVXYwQ1JtUWhDblkrU2lJVU5MTlJsQVciLCJtYWMiOiJhZGY1YmZlZDY1NmFhYWQxZjQ4MzBjN2E4Njg0NDc4YTZkYTY0NTdkN2MzZTU1YjRjODAyM2MyYThiNjM1MDYyIiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 08:12:04 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IjlybkJQSEphVHBDdkU0dnZTRnQyWHc9PSIsInZhbHVlIjoibjByZUNLNXN5YUVQWHBuemNKU3dFY3A5bHJyWmY5NHFCb1RxeHdGWDgrdFdmMXJoQWE4YitQVTY1MEtuclYvbm9EM0p3b" 1 => "alphaeurekaselectnet_session=eyJpdiI6IngrN0NBNnhlWXk2RDZZWnZWajZ2dXc9PSIsInZhbHVlIjoiZERUVDI4U0tMekZZOVdpMEFubS9BUWxmZEdhTTRnV0s2TG5uVk53eGU0S2xFR0xLV091a0JaTEIxT1hqN2NheDJEcG80YnVMbis5aGF1UE1BeVlMSFdIanpQOXVLaHdYWHExUnNSaXpZb2NjVjNDaTA1ME55MVJldStEZFMvNmciLCJtYWMiOiJiMjljZDA4YTZkY2M4MWJjZGM0MTEwZTc1NGI0YWVjZjQxZWMwZjlhYWM5MTFhNzYzOTBjZjZhOTAwNGZhYmM1IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IngrN0NBNnhlWXk2RDZZWnZWajZ2dXc9PSIsInZhbHVlIjoiZERUVDI4U0tMekZZOVdpMEFubS9BUWxmZEdhTTRnV0s2TG5uVk53eGU0S2xFR0xLV091a0JaTEI" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjlybkJQSEphVHBDdkU0dnZTRnQyWHc9PSIsInZhbHVlIjoibjByZUNLNXN5YUVQWHBuemNKU3dFY3A5bHJyWmY5NHFCb1RxeHdGWDgrdFdmMXJoQWE4YitQVTY1MEtuclYvbm9EM0p3bUg0TEliVnIxSDJRY1VOMWlLK3FyOWFZUTFWWll2V0ExblhxVXYwQ1JtUWhDblkrU2lJVU5MTlJsQVciLCJtYWMiOiJhZGY1YmZlZDY1NmFhYWQxZjQ4MzBjN2E4Njg0NDc4YTZkYTY0NTdkN2MzZTU1YjRjODAyM2MyYThiNjM1MDYyIiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 08:12:04 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IjlybkJQSEphVHBDdkU0dnZTRnQyWHc9PSIsInZhbHVlIjoibjByZUNLNXN5YUVQWHBuemNKU3dFY3A5bHJyWmY5NHFCb1RxeHdGWDgrdFdmMXJoQWE4YitQVTY1MEtuclYvbm9EM0p3b" 1 => "alphaeurekaselectnet_session=eyJpdiI6IngrN0NBNnhlWXk2RDZZWnZWajZ2dXc9PSIsInZhbHVlIjoiZERUVDI4U0tMekZZOVdpMEFubS9BUWxmZEdhTTRnV0s2TG5uVk53eGU0S2xFR0xLV091a0JaTEIxT1hqN2NheDJEcG80YnVMbis5aGF1UE1BeVlMSFdIanpQOXVLaHdYWHExUnNSaXpZb2NjVjNDaTA1ME55MVJldStEZFMvNmciLCJtYWMiOiJiMjljZDA4YTZkY2M4MWJjZGM0MTEwZTc1NGI0YWVjZjQxZWMwZjlhYWM5MTFhNzYzOTBjZjZhOTAwNGZhYmM1IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IngrN0NBNnhlWXk2RDZZWnZWajZ2dXc9PSIsInZhbHVlIjoiZERUVDI4U0tMekZZOVdpMEFubS9BUWxmZEdhTTRnV0s2TG5uVk53eGU0S2xFR0xLV091a0JaTEI" ] ]
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