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Assessment of the Therapeutic Potential of Persimmon Leaf Extract on Prediabetic Subjects

  • Khan, Mohd M. (Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland) ;
  • Tran, Bao Quoc (Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland) ;
  • Jang, Yoon-Jin (Department of Pharmacology, Chonbuk National University Medical School) ;
  • Park, Soo-Hyun (Clinical Trial Center for Functional Foods, Chonbuk National University Hospital) ;
  • Fondrie, William E. (University of Maryland School of Medicine) ;
  • Chowdhury, Khadiza (University of Maryland School of Medicine) ;
  • Yoon, Sung Hwan (Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland) ;
  • Goodlett, David R. (Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland) ;
  • Chae, Soo-Wan (Department of Pharmacology, Chonbuk National University Medical School) ;
  • Chae, Han-Jung (Department of Pharmacology, Chonbuk National University Medical School) ;
  • Seo, Seung-Young (Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital) ;
  • Goo, Young Ah (Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland)
  • Received : 2016.12.12
  • Accepted : 2017.05.15
  • Published : 2017.07.31

Abstract

Dietary supplements have exhibited myriads of positive health effects on human health conditions and with the advent of new technological advances, including in the fields of proteomics, genomics, and metabolomics, biological and pharmacological activities of dietary supplements are being evaluated for their ameliorative effects in human ailments. Recent interests in understanding and discovering the molecular targets of phytochemical-gene-protein-metabolite dynamics resulted in discovery of a few protein signature candidates that could potentially be used to assess the effects of dietary supplements on human health. Persimmon (Diospyros kaki) is a folk medicine, commonly used as dietary supplement in China, Japan, and South Korea, owing to its different beneficial health effects including anti-diabetic implications. However, neither mechanism of action nor molecular biomarkers have been discovered that could either validate or be used to evaluate effects of persimmon on human health. In present study, Mass Spectrometry (MS)-based proteomic studies were accomplished to discover proteomic molecular signatures that could be used to understand therapeutic potentials of persimmon leaf extract (PLE) in diabetes amelioration. Saliva, serum, and urine samples were analyzed and we propose that salivary proteins can be used for evaluating treatment effectiveness and in improving patient compliance. The present discovery proteomics study demonstrates that salivary proteomic profile changes were found as a result of PLE treatment in prediabetic subjects that could specifically be used as potential protein signature candidates.

Keywords

References

  1. Acosta-Martin, A.E., Panchaud, A., Chwastyniak, M., Dupont, A., Juthier, F., Gautier, C., Jude, B., Amouyel, P., Goodlett, D.R., and Pinet, F. (2011) Quantitative mass spectrometry analysis using PAcIFIC for the identification of plasma diagnostic biomarkers for abdominal aortic aneurysm. PLoS One 6, e28698. https://doi.org/10.1371/journal.pone.0028698
  2. Ahn, H.S., Jeon, T.I., Lee, J.Y., Hwang, S.G., Lim, Y., and Park, D.K. (2002) Antioxidative activity of persimmon and grape seed extract: in vitro and in vivo. Nutr. Res. 22, 1265-1273. https://doi.org/10.1016/S0271-5317(02)00429-3
  3. Amara, U., Rittirsch, D., Flierl, M., Bruckner, U., Klos, A., Gebhard, F., Lambris, J.D., and Huber-Lang, M. (2008) Interaction between the coagulation and complement system. Adv. Exp. Med. Biol. 632, 71-79.
  4. An, B.-J., Kwak, J.-H., Park, J.-M., Lee, J.-Y., Park, T.-S., Lee, J.-T., Son, J.-H., Jo, C., and Byun, M.-W. (2006). Inhibition of enzyme activities and the antiwrinkle effect of polyphenol isolated from the Persimmon Leaf (Diospyros kaki folium) on human skin. Dermatol. Surg. 31, 848-855. https://doi.org/10.1111/j.1524-4725.2005.31730
  5. Astle, J., Ferguson, J.T., German J.B., Harrigan, G.G., Kelleher, N.L., Kodadek, T., Parks, B.A., Roth, M.J., Singletary, K.W., Wenger, C.D., et al. (2007). Characterization of proteomic and metabolomic responses to dietary factors and supplements. J. Nutr. 137, 2787-2793. https://doi.org/10.1093/jn/137.12.2787
  6. Bae, U.J., Park, S.H., Jung, S.Y., Park, B.H., and Chae, S.W. (2015). Hypoglycemic effects of aqueous persimmon leaf extract in a murine model of diabetes. Mol. Med. Rep. 12, 2547-2554. https://doi.org/10.3892/mmr.2015.3766
  7. Barve, A., Chen, C., Hebbar, V., Desiderio, J., Saw, C.L.L., and Kong, A.N. (2009). Metabolism, oral bioavailability and pharmacokinetics of chemopreventive kaempferol in rats. Biopharm. Drug Dispos. 30, 356-365. https://doi.org/10.1002/bdd.677
  8. Bei, W., Peng, W., Ma, Y., and Xu, A. (2004). NaoXinQing, an antistroke herbal medicine, reduces hydrogen peroxide-induced injury in NG108-15 cells. Neurosci. Lett. 363, 262-265. https://doi.org/10.1016/j.neulet.2004.04.031
  9. Beretov, J., Wasinger V.C., Millar, E.K.A., Schwartz, P., Graham, P.H., and Li Y. (2015). Proteomic Analysis of Urine to Identify Breast Cancer Biomarker Candidates Using a Label-Free LC-MS/MS Approach. PLoS One 10, e0141876. https://doi.org/10.1371/journal.pone.0141876
  10. Centers for Disease Control and Prevention (2011). National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention.
  11. Chakraborty, J., Below, A.A., and Solaiman, D. (2004). Tamm-Horsfall protein in patients with kidney damage and diabetes. Urol. Res. 32, 79-83. https://doi.org/10.1007/s00240-003-0374-6
  12. Chee, C.S., Chang, K.M., Loke, M.F., Angela Loo, V.P., and Subrayan, V. (2016). Association of potential salivary biomarkers with diabetic retinopathy and its severity in type-2 diabetes mellitus: a proteomic analysis by mass spectrometry. PeerJ.12, 4:e2022.
  13. Chen, G., Lu, H., Wang, C., Yamashita, K., Manabe, M., Xu, S., and Kodama, H. (2002). Effect of five triterpenoid compounds isolated from leaves of Diospyros kaki on stimulus-induced superoxide generation and tyrosyl phosphorylation in human polymorphonuclear leukocytes. Clinica. Chimica. Acta 320, 11-16. https://doi.org/10.1016/S0009-8981(02)00021-9
  14. Cox, J., and Mann, M. (2008). MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367-1372. https://doi.org/10.1038/nbt.1511
  15. Cox, J., Neuhauser, N., Michalski, A., Scheltema, R.A., Olsen, J.V., and Mann, M. (2011). Andromeda: a peptide search engine integrated into the MaxQuant environment. J. Proteome Res. 10, 1794-1805. https://doi.org/10.1021/pr101065j
  16. Cox, J., Hein, M.Y., Luber, C.A., Paron, I., Nagaraj, N., and Mann, M. (2014). Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ . Mol. Cell. Proteom. 13, 2513-2526. https://doi.org/10.1074/mcp.M113.031591
  17. Das, S.K., and Elbein, S.C. (2006). The genetic basis of type 2 diabetes. Cell Sci. 2, 100-131.
  18. Derosa, G., and Maffioli, P. (2011). Thiazolidinediones plus metformin association on body weight in patients with type 2 diabetes. Diabetes Res. Clin. Pract. 91, 265-270. https://doi.org/10.1016/j.diabres.2010.08.001
  19. El-Achkar, T.M., and Wu, X.-R. (2012). Uromodulin in kidney injury: an instigator, bystander, or protector? Am. J. Kidney Dis. 59, 452-461. https://doi.org/10.1053/j.ajkd.2011.10.054
  20. Funayama, S., and Hikino, H. (1979). Hypotensive principles of Diospyros kaki leaves. Chem. Pharm. Bull. 27, 2865-2868. https://doi.org/10.1248/cpb.27.2865
  21. Gao, B.B., Chen, X., Timothy, N., Aiello, L.P., and Feener, E.P.(2008). Characterization of the vitreous proteome in diabetes without diabetic retinopathy and diabetes with proliferative diabetic retinopathy. J. Proteome Res. 7, 2516-2255. https://doi.org/10.1021/pr800112g
  22. Gao, Y., Wang, Y., Ma, Y., Yu, A., Cai, F., Shao, W., and Zhai, G. (2009), Formulation optimization and in situ absorption in rat intestinal tract of quercetin-loaded microemulsion. Colloids Surf. B 71, 306-314. https://doi.org/10.1016/j.colsurfb.2009.03.005
  23. Gerich, J.E. (1998). The Genetic Basis of Type 2 Diabetes Mellitus: Impaired Insulin Secretion versus Impaired Insulin Sensitivity. Endocr. Rev. 19, 491-503. https://doi.org/10.1210/edrv.19.4.0338
  24. Goo, Y.A., and Goodlett, D.R. (2010). Advances in proteomic prostate cancer biomarker discovery. J. Proteomics 73, 1839-1850. https://doi.org/10.1016/j.jprot.2010.04.002
  25. Goo, Y.A., Tsai, Y.S., Liu, A.Y., Goodlett, D.R., and Yang, C.C. (2010). Urinary proteomics evaluation in interstitial cystitis/painful bladder syndrome: a pilot study. Int. Braz J. Urol. 36, 464-479. https://doi.org/10.1590/S1677-55382010000400010
  26. Goo, Y.A., Cain, K., Jarrett, M., Smith, L., Voss, J., Tolentino, E., Tsuji, J., Tsai, Y.S., Panchaud, A., Goodlett, D.R., et al. (2012). Urinary proteome analysis of irritable bowel syndrome (IBS) symptom subgroups. J. Proteome Res., 5650-5662.
  27. Han, J., Kang, S., Choue, R., Kim, H., Leem, K., Chung, S., Kim, C., and Chung, J. (2002) Free radical scavenging effect of Diospyros kaki, Laminaria japonica and Undaria pinnatifida. Fitoterapia 73, 710-712. https://doi.org/10.1016/S0367-326X(02)00236-8
  28. Herrero, M., Simo, C., Garcia-Canas, V., Ibanez, E., and Cifuentes, A. (2012). Foodomics: MS-based strategies in modern food science and nutrition. Mass Spectrom. Rev. 31, 49-69. https://doi.org/10.1002/mas.20335
  29. Hu, S., Loo, J.A., and Wong, D.T. (2007). Human saliva proteome analysis and disease biomarker discovery. Exp. Rev. Proteom. 4, 531-538. https://doi.org/10.1586/14789450.4.4.531
  30. Huang, Q. (2011). Ezrin/Radixin/Moesin proteins in the development of diabetes and its cardiovascular complications. J. Diabetes Metab. Disord. 1, S4:005.
  31. Jung, U.J., Park, Y.B., Kim, S.R., and Choi, M.S. (2012). Supplementation of Persimmon leaf ameliorates hyperglycemia, dyslipidemia and hepatic fat accumulation in type 2 diabetic mice. PLoS One 7, e49030. https://doi.org/10.1371/journal.pone.0049030
  32. Merrell, K., Southwick, K., Graves, S.W., Esplin, M.S., Lewis, N.E., and Thulin, C.D. (2004). Analysis of low-abundance, low-molecularweight serum proteins using mass spectrometry. J. Biomol. Tech. 15, 238-248.
  33. Kameda, K., Takaku, T., Okuda, H., Kimura, Y., Okuda, T., Hatano, T., Agata, I., and Arichi, S. (1987). Inhibitory effects of various flavonoids isolated from leaves of persimmon on angiotensin-converting enzyme activity. J. Nat. Prod. 50, 680-683. https://doi.org/10.1021/np50052a017
  34. Kawakami, K., Aketa, S., Nakanami, M., Iizuka, S., and Hirayama, M. (2010). Major water-soluble polyphenols, proanthocyanidins, in leaves of persimmon (Diospyros kaki ) and their ${\alpha}$-amylase inhibitory activity. Biosci. Biotech. Bioch. 74, 1380-1385. https://doi.org/10.1271/bbb.100056
  35. Kawakami, K., Aketa, S., Sakai, H., Watanabe, Y., Nishida, H., and Hirayama, M. (2011). Antihypertensive and vasorelaxant effects of water-soluble Proanthocyanidins from persimmon leaf tea in spontaneously hypertensive rats. Biosci. Biotech. Bioch. 75, 1435-1439. https://doi.org/10.1271/bbb.100926
  36. Kim, J.H., Stevens, R.C., MacCoss, M.J., Goodlett, D.R., Scherl, A., Richter, R.J., Suzuki, S.M., and Furlong, C.E. (2010). Identification and characterization of biomarkers of organophosphorus exposures in humans. Adv. Exp. Med. Biol. 660, 61-71.
  37. Kim, J.K., Choi, S.J., Cho, H.Y., Hwang, H.J., Kim, Y.J., Lim, S.T., Kim, C.-J., Kim, H.K., Peterson, S., and Shin, D.-H. (2010). Protective effects of kaempferol (3,4′,5,7-tetrahydroxyflavone) against amyloid beta peptide (A${\beta}$)-induced neurotoxicity in ICR Mice. Biosci. Biotech. Bioch. 74, 397-401. https://doi.org/10.1271/bbb.90585
  38. Kotani, M., Matsumoto, M., Fujita, A., Higa, S., Wang, W., Suemura, M., Kishimoto, T., and Tanaka, T. (2000). Persimmon leaf extract and astragalin inhibit development of dermatitis and IgE elevation in NC/Nga mice. J. Allergy Clin. Immunol. 106, 159-166. https://doi.org/10.1067/mai.2000.107194
  39. Kottgen, A., Hwang, S.J., Larson, M.G., Van Eyk, J.E., Fu, Q., Benjamin, E.J., Dehghan, A., Glazer, N.L., Kao, W.H.L., Harris, T.B., et al. (2010). Uromodulin Levels Associate with a Common UMOD Variant and Risk for Incident CKD. J. Am. Soc. Nephrol. 21, 337-344. https://doi.org/10.1681/ASN.2009070725
  40. Kwon, S.H., Nam, J.I., Kim, S. H., Kim, J.H., Yoon, J.-H., and Kim, K.-S. (2009). Kaempferol and quercetin, essential ingredients in Ginkgo biloba extract, inhibit interleukin-$1{\beta}$-induced MUC5AC gene expression in human airway epithelial cells. Phytother. Res. 23, 1708-1712. https://doi.org/10.1002/ptr.2817
  41. Labbe, D., Provencal, M., Lamy, S., Boivin, D., Gingras, D., and Beliveau, R. (2009). The flavonols quercetin, kaempferol, and myricetin inhibit hepatocyte growth factor-induced medulloblastoma cell migration. J. Nutrition 139, 646-652. https://doi.org/10.3945/jn.108.102616
  42. Lapolla, A., Seraglia, R., Molin, L., Williams, K., Cosma, C., Reitano, R., Sechi, A., Ragazzi, E., and Traldi, P. (2009). Low molecular weight proteins in urines from healthy subjects as well as diabetic, nephropathic and diabetic-nephropathic patients: a MALDI study. J. Mass Spectr. 44, 419-425. https://doi.org/10.1002/jms.1520
  43. Lee, J.S., Lee, M.K., Ha, T.Y., Bok, S.H., Park, H.M., Jeong, K.S., Woo, M.N., Do, G.M., Yeo, J.Y., and Choi, M.S. (2006). Supplementation of whole persimmon leaf improves lipid profiles and suppresses body weight gain in rats fed high-fat diet. Food Chem. Toxicol. 44, 1875-1883. https://doi.org/10.1016/j.fct.2006.06.014
  44. Li, W., Yi, S., Wang, Z., Chen, S., Xin, S., Xie, J., and Zhao, C. (2011). Self-nanoemulsifying drug delivery system of persimmon leaf extract: Optimization and bioavailability studies. Int. J. Pharm. 420, 161-171. https://doi.org/10.1016/j.ijpharm.2011.08.024
  45. Lin, X., Cook, T.J., Zabetian, C.P., Leverenz, J.B., Peskind, E.R., Hu, S.-C., Cain, K.C., Pan, C., Edgar, J.S., Goodlett, D.R., et al. (2012). DJ-1 isoforms in whole blood as potential biomarkers of Parkinson disease. Sci. Rep. 2, 954, 1-10.
  46. Lo, D.J., Kaplan, B., and Kirk, A.D. (2014). Biomarkers for kidney transplant rejection. Nat. Rev. Nephrol. 10, 215-225. https://doi.org/10.1038/nrneph.2013.281
  47. Lynn, K.L., and Marshall, R. (1984). Excretion of Tamm-Horsfall glycoprotein in renal disease. Clin. Nephrol. 22, 253-257.
  48. Ma, C.-Y., Musoke, S.F., Tan, G.T., Sydara, K., Bouamanivong, S., Southavong, B., Soejarto, D.D., Fong, H.H.S., and Zhang, H.-J. (2008). Study of antimalarial activity of chemical constituents from diospyros quaesita. Chem. Biodivers. 5, 2442-2448. https://doi.org/10.1002/cbdv.200890209
  49. Mallavadhani, U.V., Panda, A.K., and Rao, Y.R. (1998). Review article number 134 pharmacology and chemotaxonomy of diospyros. Phytochemistry 49, 901-951. https://doi.org/10.1016/S0031-9422(97)01020-0
  50. Matheson, A., Willcox, M.D.P., Flanagan, J., and Walsh, B.J. (2010). Urinary biomarkers involved in type 2 diabetes: a review. Diabetes Metab. Res. Rev. 26, 150-171. https://doi.org/10.1002/dmrr.1068
  51. Matsumoto, M., Kotani, M., Fujita, A., Higa, S., Kishimoto, T., Suemura, M., and Milner, J.A. (2002). Functional foods and health: a US perspective. Br. J. Nutr. 88, S152. https://doi.org/10.1079/BJN2002680
  52. Mitri, J., and Hamdy, O. (2009). Diabetes medications and body weight. Exp. Opin. Drug Saf. 8, 573-584. https://doi.org/10.1517/14740330903081725
  53. Pan, S., Chen, R., Brand, R.E., Hawley, S., Tamura, Y., Gafken, P.R., Milless, B.P., Goodlett, D.R., Rush, J., and Brentnall, T.A. (2012). Multiplex targeted proteomic assay for biomarker detection in plasma: a pancreatic cancer biomarker case study. J. Proteome Res. 11, 1937-1948. https://doi.org/10.1021/pr201117w
  54. Pfleiderer, S., Zimmerhackl, L.B., Kinne, R., Manz, F., Schuler, G., and Brandis, M. (1993). Renal proximal and distal tubular function is attenuated in diabetes mellitus type 1 as determined by the renal excretion of ?1-microglobulin and Tamm-Horsfall protein. Clin. Invest. 71, 972-977.
  55. Rogerio, A.P., Dora, C.L., Andrade, E.L., Chaves, J.S., Silva, L.F.C., Lemos-Senna, E., and Calixto, J.B. (2010). Anti-inflammatory effect of quercetin-loaded microemulsion in the airways allergic inflammatory model in mice. Pharmacol. Res. 61, 288-297. https://doi.org/10.1016/j.phrs.2009.10.005
  56. Roscioni, S.S., de Zeeuw, D., Hellemons, M.E., Mischak, H., Zürbig, P., Bakker, S.J.L., Gansevoort, R.T., Reinhard, H., Persson, F., Lajer, M., et al. (2013). A urinary peptide biomarker set predicts worsening of albuminuria in type 2 diabetes mellitus. Diabetologia 56, 259-267. https://doi.org/10.1007/s00125-012-2755-2
  57. Sanna, M., Firinu, D., Manconi, P.E., Pisanu, M., Murgia, G., Piras, V., Castagnola, M., Messana, I., del Giacco, S.R., and Cabras, T. (2015). The salivary proteome profile in patients affected by SAPHO syndrome characterized by a top-down RP-HPLC-ESI-MS platform. Mol. BioSyst. 11, 1552-1562. https://doi.org/10.1039/C4MB00719K
  58. Shaw, J.E., Sicree, R.A., and Zimmet, P.Z. (2010). Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res. Clin. Pract. 87, 4-14. https://doi.org/10.1016/j.diabres.2009.10.007
  59. Shi, T., Song, E., Nie, S., Rodland, K.D., Liu, T., Qian, W.J., and Smith, R.D. (2016) Advances in targeted proteomics and applications to biomedical research. Proteomics 16, 2160-2182. https://doi.org/10.1002/pmic.201500449
  60. Sun, L., Zhang, J., Lu, X., Zhang, L., and Zhang, Y. (2011). Evaluation to the antioxidant activity of total flavonoids extract from persimmon (Diospyros kaki L.) leaves. Food Chem. Toxicol. 49, 2689-2696. https://doi.org/10.1016/j.fct.2011.07.042
  61. Takeda, T., McQuistan, T., Orlando, R.A., and Farquhar, M.G. (2001). Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton. J Clin. Invest. 108, 289-301. https://doi.org/10.1172/JCI12539
  62. Tanaka, T. (2002) Oral administration of persimmon leaf extract ameliorates skin symptoms and transepidermal water loss in atopic dermatitis model mice, NC/Nga. Br. J. Dermatol. 146, 221-227. https://doi.org/10.1046/j.1365-2133.2002.04557.x
  63. Thuong, P.T., Lee, C.H., Dao, T.T., Nguyen, P.H., Kim, W.G., Lee, S.J., and Oh, W.K. (2008). Triterpenoids from the Leaves of Diospyros kaki (Persimmon) and Their Inhibitory Effects on Protein Tyrosine Phosphatase 1B. J. Nat. Prod. 71, 1775-1778. https://doi.org/10.1021/np800298w
  64. Torffvit, O., and Agardh, C.-D. (1994). Urinary excretion rate of NC1 and Tamm-Horsfall protein in the microalbuminuric type I diabetic patient. J. Diabetes Complications 8, 77-83. https://doi.org/10.1016/1056-8727(94)90055-8
  65. Tyanova, S., Temu, T., Sinitcyn, P., Carlson, A., Hein, M.Y., Geiger, T., Mann, M., and Cox, J. (2016). The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat. Methods 13, 731-740. https://doi.org/10.1038/nmeth.3901
  66. Vitorino, R., Barros, A.S., Caseiro, A., Ferreira, R., and Amado, F. (2012). Evaluation of different extraction procedures for salivary peptide analysis. Talanta 94, 209-215. https://doi.org/10.1016/j.talanta.2012.03.023
  67. Wang, L., Xu, M.L., Rasmussen, S.K., and Wang, M.-H. (2011). Vomifoliol 9-O-${\alpha}$-arabinofuranosyl $(1{\rightarrow}6)-{\beta}$-d-glucopyranoside from the leaves of Diospyros Kaki stimulates the glucose uptake in HepG2 and 3T3-L1 cells. Carbohydr. Res. 346, 1212-1216. https://doi.org/10.1016/j.carres.2011.04.021
  68. Wasik, A.A., Koskelainen, S., Hyvönen, M.E., Musante, L., Lehtonen, E., Koskenniemi, K., Tienari, J., Vaheri, A., Kerjaschki, D., Szalay, C., et al. (2014). Ezrin is down-regulated in diabetic kidney glomeruli and regulates actin reorganization and glucose uptake via GLUT1 in cultured podocytes. Am. J. Pathol. 184, 1727-1739. https://doi.org/10.1016/j.ajpath.2014.03.002
  69. Wisniewski, J.R., Zougman, A., Nagaraj, N., and Mann, M. (2009). Universal sample preparation method for proteome analysis. Nat. Methods 6, 359-362. https://doi.org/10.1038/nmeth.1322
  70. Yamagishi, S.I., and Imaizumi, T. (2005). Diabetic vascular complications: pathophysiology, biochemical basis and potential therapeutic strategy. Curr. Pharm. Des. 11, 2279-2299. https://doi.org/10.2174/1381612054367300
  71. Zhang, J., Goodlett, D.R., Peskind, E.R., Quinn, J.F., Zhou, Y., Wang, Q., Pan, C., Yi, E., Eng, J., Aebersold, R.H., et al. (2005). Quantitative proteomic analysis of age-related changes in human cerebrospinal fluid. Neurobiol. Aging 26, 207-227. https://doi.org/10.1016/j.neurobiolaging.2004.03.012

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