Login Register Cart 0
Review Article

过氧化物酶体增殖物激活受体γ（PPARγ）在不同疾病状态中的作用：最近更新

卷 28, 期 16, 2021

发表于: 16 July, 2020

页: [3193 - 3215] 页: 23

弟呕挨: 10.2174/0929867327666200716113136

价格: $65

摘要

过氧化物酶体增殖物激活受体 (PPAR) 是一种配体依赖性转录因子，是核受体超家族的成员。 PPAR 以三种亚型存在，即 PPAR α (PPARα)、PPAR beta (PPARβ) 和 PPAR γ (PPARγ)。这些是多功能转录因子，有助于调节炎症、2 型糖尿病、体内脂质浓度、转移和肿瘤生长或血管生成。 PPARγ 的激活会抑制培养的人类乳腺癌、胃癌、肺癌、前列腺癌和其他癌细胞的生长。 PPARγ主要参与脂肪酸储存、糖代谢、体内平衡和脂肪生成调节。大量天然和合成配体与 PPARγ 结合并调节其活性。噻唑烷二酮、曲格列酮、罗格列酮、吡格列酮等配体有效结合 PPARγ；然而，其中大部分被发现显示出严重的副作用，如肝毒性、体重增加、心血管并发症和膀胱肿瘤。现在重点转向双作用或泛 PPAR 配体的开发。当前的评论文章描述了 PPARγ 在各种疾病状态中的功能和作用。此外，对最近报道的PPARγ配体和泛PPAR配体进行了详细讨论。预计本综述文章可能有助于开发没有副作用或副作用最小的有效 PPAR 配体。

关键词: 过氧化物酶体增殖物激活受体、PPAR γ、泛 PPAR 配体、糖尿病、癌症、膀胱肿瘤。

« Previous Next »
[1]
Ramos, K.; Nanez, A. Introduction and overview of receptor systems.In:Comprehensive Toxicology, 2nd ed; Elsevier Inc., 2010, pp. 71-80.
[http://dx.doi.org/10.1016/B978-0-08-046884-6.00205-0]
[2]
Kersten, S.; Desvergne, B.; Wahli, W. Roles of PPARs in health and disease. Nature, 2000, 405(6785), 421-424.
[http://dx.doi.org/10.1038/35013000] [PMID: 10839530]
[3]
Spiegelman, B.M. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes, 1998, 47(4), 507-514.
[http://dx.doi.org/10.2337/diabetes.47.4.507] [PMID: 9568680]
[4]
Mukherjee, R.; Davies, P.J.; Crombie, D.L.; Bischoff, E.D.; Cesario, R.M.; Jow, L.; Hamann, L.G.; Boehm, M.F.; Mondon, C.E.; Nadzan, A.M.; Paterniti, J.R. Jr.; Heyman, R.A. Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature, 1997, 386(6623), 407-410.
[http://dx.doi.org/10.1038/386407a0] [PMID: 9121558]
[5]
Ricote, M.; Glass, C.K. PPARs and molecular mechanisms of transrepression. Biochim. Biophys. Acta, 2007, 1771(8), 926-935.
[http://dx.doi.org/10.1016/j.bbalip.2007.02.013] [PMID: 17433773]
[6]
Viswakarma, N.; Jia, Y.; Bai, L.; Vluggens, A.; Borensztajn, J.; Xu, J.; Reddy, J.K. Coactivators in PPAR-regulated gene expression. PPAR Res., 2010, 2010,250126.
[http://dx.doi.org/10.1155/2010/250126] [PMID: 20814439]
[7]
Martin, H. Role of PPAR-gamma in inflammation. Prospects for therapeutic intervention by food components. Mutat. Res., 2010, 690(1-2), 57-63.
[http://dx.doi.org/10.1016/j.mrfmmm.2009.09.009] [PMID: 20973164]
[8]
AlSaleh, A.; Sanders, T.A.; O’Dell, S.D. Effect of interaction between PPARG, PPARA and ADIPOQ gene variants and dietary fatty acids on plasma lipid profile and adiponectin concentration in a large intervention study. Proc. Nutr. Soc., 2012, 71(1), 141-153.
[http://dx.doi.org/10.1017/S0029665111003181] [PMID: 22040870]
[9]
Olefsky, J.M. Treatment of insulin resistance with peroxisome proliferator-activated receptor γ agonists. J. Clin. Invest., 2000, 106(4), 467-472.
[http://dx.doi.org/10.1172/JCI10843] [PMID: 10953021]
[10]
Yu, X.; Shao, X.G.; Sun, H.; Li, Y.N.; Yang, J.; Deng, Y.C.; Huang, Y.G. Activation of cerebral peroxisome proliferator-activated receptors gamma exerts neuroprotection by inhibiting oxidative stress following pilocarpine-induced status epilepticus. Brain Res., 2008, 1200, 146-158.
[http://dx.doi.org/10.1016/j.brainres.2008.01.047] [PMID: 18289512]
[11]
Frankenberg, A.D.V.; Reis, A.F.; Gerchman, F. Relationships between adiponectin levels, the metabolic syndrome, and type 2 diabetes: a literature review. Arch. Endocrinol. Metab., 2017, 61(6), 614-622.
[http://dx.doi.org/10.1590/2359-3997000000316] [PMID: 29412387]
[12]
Grygiel-Górniak, B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications-a review. Nutr. J., 2014, 13, 17.
[http://dx.doi.org/10.1186/1475-2891-13-17] [PMID: 24524207]
[13]
Kliewer, S.A.; Xu, H.E.; Lambert, M.H.; Willson, T.M. Peroxisome proliferator-activated receptors: from genes to physiology. Recent Prog. Horm. Res., 2001, 56, 239-263.
[http://dx.doi.org/10.1210/rp.56.1.239] [PMID: 11237216]
[14]
Rakhshandehroo, M.; Knoch, B.; Müller, M.; Kersten, S. Peroxisome proliferator-activated receptor alpha target genes. PPAR Res., 2010, 2010,612089.
[http://dx.doi.org/10.1155/2010/612089] [PMID: 20936127]
[15]
Krey, G.; Keller, H.; Mahfoudi, A.; Medin, J.; Ozato, K.; Dreyer, C.; Wahli, W. Xenopus peroxisome proliferator activated receptors: genomic organization, response element recognition, heterodimer formation with retinoid X receptor and activation by fatty acids. J. Steroid Biochem. Mol. Biol., 1993, 47(1-6), 65-73.
[http://dx.doi.org/10.1016/0960-0760(93)90058-5] [PMID: 8274443]
[16]
Schmidt, A.; Endo, N.; Rutledge, S.J.; Vogel, R.; Shinar, D.; Rodan, G.A. Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol. Endocrinol., 1992, 6(10), 1634-1641.
[http://dx.doi.org/10.1210/mend.6.10.1333051] [PMID: 1333051]
[17]
Reilly, S.M.; Lee, C.H. PPAR δ as a therapeutic target in metabolic disease. FEBS Lett., 2008, 582(1), 26-31.
[http://dx.doi.org/10.1016/j.febslet.2007.11.040] [PMID: 18036566]
[18]
Hall, M.G.; Quignodon, L.; Desvergne, B. Peroxisome proliferator-activated receptor. PPAR Res., 2008, 2008,780452.
[http://dx.doi.org/10.1155/2008/780452] [PMID: 19009042]
[19]
Guan, Y.; Zhang, Y.; Schneider, A.; Davis, L.; Breyer, R.M.; Breyer, M.D. Peroxisome proliferator-activated receptor-γ activity is associated with renal microvasculature. Am. J. Physiol. Renal Physiol., 2001, 281(6), F1036-F1046.
[http://dx.doi.org/10.1152/ajprenal.0025.2001] [PMID: 11704554]
[20]
Seufert, S.; Coras, R.; Tränkle, C.; Zlotos, D.P.; Blümcke, I.; Tatenhorst, L.; Heneka, M.T.; Hahnen, E. PPAR gamma activators: off-target against glioma cell migration and brain invasion. PPAR Res., 2008, 2008,513943.
[http://dx.doi.org/10.1155/2008/513943] [PMID: 18815619]
[21]
Blanquicett, C.; Roman, J.; Hart, C.M. Thiazolidinediones as anti-cancer agents. Cancer Ther, 2008, 6(A), 25-34.
[PMID: 19079765]
[22]
Desvergne, B.; Wahli, W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr. Rev., 1999, 20(5), 649-688.
[http://dx.doi.org/10.1210/edrv.20.5.0380] [PMID: 10529898]
[23]
Chandra, V.; Huang, P.; Hamuro, Y.; Raghuram, S.; Wang, Y.; Burris, T.P.; Rastinejad, F. Structure of the intact PPAR-γ-RXR- nuclear receptor complex on DNA. Nature, 2008, 456(7220), 350-356.
[http://dx.doi.org/10.1038/nature07413] [PMID: 19043829]
[24]
Suzuki, S.; Sasaki, S.; Morita, H.; Oki, Y.; Turiya, D.; Ito, T.; Misawa, H.; Ishizuka, K.; Nakamura, H. The role of the amino-terminal domain in the interaction of unliganded peroxisome proliferator-activated receptor gamma-2 with nuclear receptor co-repressor. J. Mol. Endocrinol., 2010, 45(3), 133-145.
[http://dx.doi.org/10.1677/JME-10-0007] [PMID: 20587609]
[25]
Nolte, R.T.; Wisely, G.B.; Westin, S.; Cobb, J.E.; Lambert, M.H.; Kurokawa, R.; Rosenfeld, M.G.; Willson, T.M.; Glass, C.K.; Milburn, M.V. Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-γ. Nature, 1998, 395(6698), 137-143.
[http://dx.doi.org/10.1038/25931] [PMID: 9744270]
[26]
Ji, C.G.; Zhang, J.Z. Protein polarization is critical to stabilizing AF-2 and helix-2′ domains in ligand binding to PPAR-γ. J. Am. Chem. Soc., 2008, 130(50), 17129-17133.
[http://dx.doi.org/10.1021/ja807374x] [PMID: 19007119]
[27]
Zieleniak, A.; Wójcik, M.; Woźniak, L.A. Structure and physiological functions of the human peroxisome proliferator-activated receptor γ. Arch. Immunol. Ther. Exp. (Warsz.), 2008, 56(5), 331-345.
[http://dx.doi.org/10.1007/s00005-008-0037-y] [PMID: 18836859]
[28]
Gampe, R.T., Jr; Montana, V.G.; Lambert, M.H.; Miller, A.B.; Bledsoe, R.K.; Milburn, M.V.; Kliewer, S.A.; Willson, T.M.; Xu, H.E. Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors. Mol. Cell, 2000, 5(3), 545-555.
[http://dx.doi.org/10.1016/S1097-2765(00)80448-7] [PMID: 10882139]
[29]
Pochetti, G.; Godio, C.; Mitro, N.; Caruso, D.; Galmozzi, A.; Scurati, S.; Loiodice, F.; Fracchiolla, G.; Tortorella, P.; Laghezza, A.; Lavecchia, A.; Novellino, E.; Mazza, F.; Crestani, M. Insights into the mechanism of partial agonism: crystal structures of the peroxisome proliferator-activated receptor γ ligand-binding domain in the complex with two enantiomeric ligands. J. Biol. Chem., 2007, 282(23), 17314-17324.
[http://dx.doi.org/10.1074/jbc.M702316200] [PMID: 17403688]
[30]
Xu, H.E.; Stanley, T.B.; Montana, V.G.; Lambert, M.H.; Shearer, B.G.; Cobb, J.E.; McKee, D.D.; Galardi, C.M.; Plunket, K.D.; Nolte, R.T.; Parks, D.J.; Moore, J.T.; Kliewer, S.A.; Willson, T.M.; Stimmel, J.B. Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha. Nature, 2002, 415(6873), 813-817.
[http://dx.doi.org/10.1038/415813a] [PMID: 11845213]
[31]
Liu, D.; Zeng, B.X.; Zhang, S.H.; Yao, S.L. Rosiglitazone, an agonist of peroxisome proliferator-activated receptor γ, reduces pulmonary inflammatory response in a rat model of endotoxemia. Inflamm. Res., 2005, 54(11), 464-470.
[http://dx.doi.org/10.1007/s00011-005-1379-0] [PMID: 16307220]
[32]
Sharma, A.K.; Bharti, S.; Ojha, S.; Bhatia, J.; Kumar, N.; Ray, R.; Kumari, S.; Arya, D.S. Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes. Br. J. Nutr., 2011, 106(11), 1713-1723.
[http://dx.doi.org/10.1017/S000711451100225X] [PMID: 21736771]
[33]
Kim, E.H.; Tolhurst, A.T.; Szeto, H.H.; Cho, S.H. Targeting CD36-mediated inflammation reduces acute brain injury in transient, but not permanent, ischemic stroke. CNS Neurosci. Ther., 2015, 21(4), 385-391.
[http://dx.doi.org/10.1111/cns.12326] [PMID: 25216018]
[34]
Ikmal, S.I.Q.S.; Huri, H.Z.; Vethakkan, S.R.; Ahmad, W.A.W. Potential biomarkers of insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease. Int. J. Endocrinol., 2013, 2013,698567.
[http://dx.doi.org/10.1155/2013/698567] [PMID: 24282409]
[35]
Kim, S.H.; Hong, J.H.; Lee, Y.C. Ursolic acid, a potential PPARγ agonist, suppresses ovalbumin-induced airway inflammation and penh by down-regulating IL-5, IL-13, and IL-17 in a mouse model of allergic asthma. Eur. J. Pharmacol., 2013, 701(1-3), 131-143.
[http://dx.doi.org/10.1016/j.ejphar.2012.11.033] [PMID: 23201068]
[36]
Zhan, C.D.; Sindhu, R.K.; Pang, J.; Ehdaie, A.; Vaziri, N.D. Superoxide dismutase, catalase and glutathione peroxidase in the spontaneously hypertensive rat kidney: effect of antioxidant-rich diet. J. Hypertens., 2004, 22(10), 2025-2033.
[http://dx.doi.org/10.1097/00004872-200410000-00027] [PMID: 15361776]
[37]
Kallenberger, B.C.; Love, J.D.; Chatterjee, V.K.K.; Schwabe, J.W. A dynamic mechanism of nuclear receptor activation and its perturbation in a human disease. Nat. Struct. Biol., 2003, 10(2), 136-140.
[http://dx.doi.org/10.1038/nsb892] [PMID: 12536206]
[38]
Yuan, G.; Chen, X.; Li, D. Modulation of peroxisome proliferator-activated receptor gamma (PPAR γ) by conjugated fatty acid in obesity and inflammatory bowel disease. J. Agric. Food Chem., 2015, 63(7), 1883-1895.
[http://dx.doi.org/10.1021/jf505050c] [PMID: 25634802]
[39]
Villapol, S. Roles of peroxisome proliferator-activated receptor gamma on brain and peripheral inflammation. Cell. Mol. Neurobiol., 2018, 38(1), 121-132.
[http://dx.doi.org/10.1007/s10571-017-0554-5] [PMID: 28975471]
[40]
Ballesteros, I.; Cuartero, M.I.; Pradillo, J.M.; de la Parra, J.; Pérez-Ruiz, A.; Corbí, A.; Ricote, M.; Hamilton, J.A.; Sobrado, M.; Vivancos, J.; Nombela, F.; Lizasoain, I.; Moro, M.A. Rosiglitazone-induced CD36 up-regulation resolves inflammation by PPARγ and 5-LO-dependent pathways. J. Leukoc. Biol., 2014, 95(4), 587-598.
[http://dx.doi.org/10.1189/jlb.0613326] [PMID: 24338629]
[41]
Heneka, M.T.; Klockgether, T.; Feinstein, D.L. Peroxisome proliferator-activated receptor-γ ligands reduce neuronal inducible nitric oxide synthase expression and cell death in vivo. J. Neurosci., 2000, 20(18), 6862-6867.
[http://dx.doi.org/10.1523/JNEUROSCI.20-18-06862.2000] [PMID: 10995830]
[42]
Kapadia, R.; Yi, J.H.; Vemuganti, R. Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists. Front. Biosci., 2008, 13, 1813-1826.
[http://dx.doi.org/10.2741/2802] [PMID: 17981670]
[43]
Lenglet, S.; Montecucco, F.; Mach, F. Role of matrix metalloproteinases in animal models of ischemic stroke. Curr. Vasc. Pharmacol., 2015, 13(2), 161-166.
[http://dx.doi.org/10.2174/15701611113116660161] [PMID: 24188490]
[44]
Akiyama, T.E.; Meinke, P.T.; Berger, J.P. PPAR ligands: potential therapies for metabolic syndrome. Curr. Diab. Rep., 2005, 5(1), 45-52.
[http://dx.doi.org/10.1007/s11892-005-0067-3] [PMID: 15663917]
[45]
Chinetti, G.; Fruchart, J.C.; Staels, B. Peroxisome proliferator-activated receptors (PPARs): nuclear receptors with functions in the vascular wall. Z. Kardiol., 2001, 90(Suppl. 3), 125-132.
[http://dx.doi.org/10.1007/s003920170034] [PMID: 11374025]
[46]
Blaschke, F.; Takata, Y.; Caglayan, E.; Law, R.E.; Hsueh, W.A. Obesity, peroxisome proliferator-activated receptor, and atherosclerosis in type 2 diabetes. Arterioscler. Thromb. Vasc. Biol., 2006, 26(1), 28-40.
[http://dx.doi.org/10.1161/01.ATV.0000191663.12164.77] [PMID: 16239592]
[47]
Yao, Y.; Xu, X.H.; Jin, L. Macrophage polarization in physiological and pathological pregnancy. Front. Immunol., 2019, 10, 792.
[http://dx.doi.org/10.3389/fimmu.2019.00792] [PMID: 31037072]
[48]
Luo, W.; Xu, Q.; Wang, Q.; Wu, H.; Hua, J. Effect of modulation of PPAR-γ activity on Kupffer cells M1/M2 polarization in the development of non-alcoholic fatty liver disease. Sci. Rep., 2017, 7, 44612.
[http://dx.doi.org/10.1038/srep44612] [PMID: 28300213]
[49]
Cicchese, J.M.; Evans, S.; Hult, C.; Joslyn, L.R.; Wessler, T.; Millar, J.A.; Marino, S.; Cilfone, N.A.; Mattila, J.T.; Linderman, J.J.; Kirschner, D.E. Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology. Immunol. Rev., 2018, 285(1), 147-167.
[http://dx.doi.org/10.1111/imr.12671] [PMID: 30129209]
[50]
Phaniendra, A.; Jestadi, D.B.; Periyasamy, L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J. Clin. Biochem., 2015, 30(1), 11-26.
[http://dx.doi.org/10.1007/s12291-014-0446-0] [PMID: 25646037]
[51]
Kurutas, E.B. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr. J., 2016, 15(1), 71.
[http://dx.doi.org/10.1186/s12937-016-0186-5] [PMID: 27456681]
[52]
Lozano, D.; Gonzales-Portillo, G.S.; Acosta, S.; de la Pena, I.; Tajiri, N.; Kaneko, Y.; Borlongan, C.V. Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities. Neuropsychiatr. Dis. Treat., 2015, 11, 97-106.
[http://dx.doi.org/10.2147/ndt.s65815] [PMID: 25657582]
[53]
Dunning, S.; Ur Rehman, A.; Tiebosch, M.H.; Hannivoort, R.A.; Haijer, F.W.; Woudenberg, J.; van den Heuvel, F.A.; Buist-Homan, M.; Faber, K.N.; Moshage, H. Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death. Biochim. Biophys. Acta, 2013, 1832(12), 2027-2034.
[http://dx.doi.org/10.1016/j.bbadis.2013.07.008] [PMID: 23871839]
[54]
Zarzuelo, M.J.; López-Sepúlveda, R.; Sánchez, M.; Romero, M.; Gómez-Guzmán, M.; Ungvary, Z.; Pérez-Vizcaíno, F.; Jiménez, R.; Duarte, J. SIRT1 inhibits NADPH oxidase activation and protects endothelial function in the rat aorta: implications for vascular aging. Biochem. Pharmacol., 2013, 85(9), 1288-1296.
[http://dx.doi.org/10.1016/j.bcp.2013.02.015] [PMID: 23422569]
[55]
Heneka, M.T.; Landreth, G.E. PPARs in the brain. Biochim. Biophys. Acta, 2007, 1771(8), 1031-1045.
[http://dx.doi.org/10.1016/j.bbalip.2007.04.016]] [PMID: 17569578]
[56]
Park, E.Y.; Cho, I.J.; Kim, S.G. Transactivation of the PPAR-responsive enhancer module in chemopreventive glutathione S-transferase gene by the peroxisome proliferator-activated receptor-γ and retinoid X receptor heterodimer. Cancer Res., 2004, 64(10), 3701-3713.
[http://dx.doi.org/10.1158/0008-5472.CAN-03-3924] [PMID: 15150131]
[57]
Nishida, N.; Yano, H.; Nishida, T.; Kamura, T.; Kojiro, M. Angiogenesis in cancer. Vasc. Health Risk Manag., 2006, 2(3), 213-219.
[http://dx.doi.org/10.2147/vhrm.2006.2.3.213] [PMID: 17326328]
[58]
Arany, Z.; Foo, S.Y.; Ma, Y.; Ruas, J.L.; Bommi-Reddy, A.; Girnun, G.; Cooper, M.; Laznik, D.; Chinsomboon, J.; Rangwala, S.M.; Baek, K.H.; Rosenzweig, A.; Spiegelman, B.M. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1α. Nature, 2008, 451(7181), 1008-1012.
[http://dx.doi.org/10.1038/nature06613] [PMID: 18288196]
[59]
Reaven, G.M. Pathophysiology of insulin resistance in human disease. Physiol. Rev., 1995, 75(3), 473-486.
[http://dx.doi.org/10.1152/physrev.1995.75.3.473] [PMID: 7624391]
[60]
Wilcox, G. Insulin and insulin resistance. Clin. Biochem. Rev., 2005, 26(2), 19-39.
[PMID: 16278749]
[61]
Haber, L.M.; Hawkins, E.P.; Seilheimer, D.K.; Saleem, A. Fat overload syndrome. An autopsy study with evaluation of the coagulopathy. Am. J. Clin. Pathol., 1988, 90(2), 223-227.
[http://dx.doi.org/10.1093/ajcp/90.2.223] [PMID: 3394663]
[62]
Czech, M.P. Insulin action and resistance in obesity and type 2 diabetes. Nat. Med., 2017, 23(7), 804-814.
[http://dx.doi.org/10.1038/nm.4350] [PMID: 28697184]
[63]
Govers, R. Cellular regulation of glucose uptake by glucose transporter GLUT4. Adv. Clin. Chem., 2014, 66, 173-240.
[http://dx.doi.org/10.1016/B978-0-12-801401-1.00006-2] [PMID: 25344989]
[64]
Satoh, T. Molecular mechanisms for the regulation of insulin-stimulated glucose uptake by small guanosine triphosphatases in skeletal muscle and adipocytes. Int. J. Mol. Sci., 2014, 15(10), 18677-18692.
[http://dx.doi.org/10.3390/ijms151018677] [PMID: 25325535]
[65]
Russell, R.R., III; Bergeron, R.; Shulman, G.I.; Young, L.H. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. Am. J. Physiol., 1999, 277(2), H643-H649.
[http://dx.doi.org/10.1152/ajpheart.1999.277.2.h643] [PMID: 10444490]
[66]
Itoh, M.; Suganami, T.; Hachiya, R.; Ogawa, Y. Adipose tissue remodeling as homeostatic inflammation. Int. J. Inflamm., 2011, 2011,720926.
[http://dx.doi.org/10.4061/2011/720926] [PMID: 21755030]
[67]
Farmer, S.R. Regulation of PPARgamma activity during adipogenesis. Int. J. Obes., 2005, 29(Suppl. 1), S13-S16.
[http://dx.doi.org/10.1038/sj.ijo.0802907] [PMID: 15711576]
[68]
de Souza, C.J.; Eckhardt, M.; Gagen, K.; Dong, M.; Chen, W.; Laurent, D.; Burkey, B.F. Effects of pioglitazone on adipose tissue remodeling within the setting of obesity and insulin resistance. Diabetes, 2001, 50(8), 1863-1871.
[http://dx.doi.org/10.2337/diabetes.50.8.1863] [PMID: 11473050]
[69]
Glorian, M.; Duplus, E.; Beale, E.G.; Scott, D.K.; Granner, D.K.; Forest, C. A single element in the phosphoenolpyruvate carboxykinase gene mediates thiazolidinedione action specifically in adipocytes. Biochimie, 2001, 83(10), 933-943.
[http://dx.doi.org/10.1016/S0300-9084(01)01343-8] [PMID: 11728630]
[70]
Lin, J.; Handschin, C.; Spiegelman, B.M. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab., 2005, 1(6), 361-370.
[http://dx.doi.org/10.1016/j.cmet.2005.05.004] [PMID: 16054085]
[71]
Jamaluddin, M.S.; Weakley, S.M.; Yao, Q.; Chen, C. Resistin: functional roles and therapeutic considerations for cardiovascular disease. Br. J. Pharmacol., 2012, 165(3), 622-632.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01369.x] [PMID: 21545576]
[72]
Nieva-Vazquez, A.; Pérez-Fuentes, R.; Torres-Rasgado, E.; López-López, J.G.; Romero, J.R. Serum resistin levels are associated with adiposity and insulin sensitivity in obese Hispanic subjects. Metab. Syndr. Relat. Disord., 2014, 12(2), 143-148.
[http://dx.doi.org/10.1089/met.2013.0118] [PMID: 24266722]
[73]
Patel, L.; Buckels, A.C.; Kinghorn, I.J.; Murdock, P.R.; Holbrook, J.D.; Plumpton, C.; Macphee, C.H.; Smith, S.A. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem. Biophys. Res. Commun., 2003, 300(2), 472-476.
[http://dx.doi.org/10.1016/S0006-291X(02)02841-3] [PMID: 12504108]
[74]
Kadowaki, T.; Yamauchi, T.; Kubota, N.; Hara, K.; Ueki, K.; Tobe, K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J. Clin. Invest., 2006, 116(7), 1784-1792.
[http://dx.doi.org/10.1172/JCI29126] [PMID: 16823476]
[75]
Maeda, N.; Takahashi, M.; Funahashi, T.; Kihara, S.; Nishizawa, H.; Kishida, K.; Nagaretani, H.; Matsuda, M.; Komuro, R.; Ouchi, N.; Kuriyama, H.; Hotta, K.; Nakamura, T.; Shimomura, I.; Matsuzawa, Y. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes, 2001, 50(9), 2094-2099.
[http://dx.doi.org/10.2337/diabetes.50.9.2094] [PMID: 11522676]
[76]
Achari, A.E.; Jain, S.K. Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction. Int. J. Mol. Sci., 2017, 18(6), 1321.
[http://dx.doi.org/10.3390/ijms18061321] [PMID: 28635626]
[77]
Hirayama, D.; Iida, T.; Nakase, H. The phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis. Int. J. Mol. Sci., 2017, 19(1), 92.
[http://dx.doi.org/10.3390/ijms19010092] [PMID: 29286292]
[78]
Cancello, R.; Henegar, C.; Viguerie, N.; Taleb, S.; Poitou, C.; Rouault, C.; Coupaye, M.; Pelloux, V.; Hugol, D.; Bouillot, J.L.; Bouloumié, A.; Barbatelli, G.; Cinti, S.; Svensson, P.A.; Barsh, G.S.; Zucker, J.D.; Basdevant, A.; Langin, D.; Clément, K. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes, 2005, 54(8), 2277-2286.
[http://dx.doi.org/10.2337/diabetes.54.8.2277] [PMID: 16046292]
[79]
Apovian, C.M.; Bigornia, S.; Mott, M.; Meyers, M.R.; Ulloor, J.; Gagua, M.; McDonnell, M.; Hess, D.; Joseph, L.; Gokce, N. Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects. Arterioscler. Thromb. Vasc. Biol., 2008, 28(9), 1654-1659.
[http://dx.doi.org/10.1161/ATVBAHA.108.170316] [PMID: 18566296]
[80]
Kersten, S. Peroxisome proliferator activated receptors and lipoprotein metabolism. PPAR Res., 2008, 2008,132960.
[http://dx.doi.org/10.1155/2008/132960] [PMID: 18288277]
[81]
Elrod, H.A.; Sun, S.Y. PPARγ and apoptosis in cancer. PPAR Res., 2008, 2008,704165.
[http://dx.doi.org/10.1155/2008/704165] [PMID: 18615184]
[82]
Tontonoz, P.; Singer, S.; Forman, B.M.; Sarraf, P.; Fletcher, J.A.; Fletcher, C.D.; Brun, R.P.; Mueller, E.; Altiok, S.; Oppenheim, H.; Evans, R.M.; Spiegelman, B.M. Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor γ and the retinoid X receptor. Proc. Natl. Acad. Sci. USA, 1997, 94(1), 237-241.
[http://dx.doi.org/10.1073/pnas.94.1.237] [PMID: 8990192]
[83]
Yang, Z.; Bagheri-Yarmand, R.; Balasenthil, S.; Hortobagyi, G.; Sahin, A.A.; Barnes, C.J.; Kumar, R. HER2 regulation of peroxisome proliferator-activated receptor γ (PPARgamma) expression and sensitivity of breast cancer cells to PPARgamma ligand therapy. Clin. Cancer Res., 2003, 9(8), 3198-3203.
[PMID: 12912973]
[84]
Betz, M.J.; Shapiro, I.; Fassnacht, M.; Hahner, S.; Reincke, M.; Beuschlein, F. German and Austrian Adrenal Network. Peroxisome proliferator-activated receptor-γ agonists suppress adrenocortical tumor cell proliferation and induce differentiation. J. Clin. Endocrinol. Metab., 2005, 90(7), 3886-3896.
[http://dx.doi.org/10.1210/jc.2004-1267] [PMID: 15886257]
[85]
Shiau, C.W.; Yang, C.C.; Kulp, S.K.; Chen, K.F.; Chen, C.S.; Huang, J.W.; Chen, C.S. Thiazolidenediones mediate apoptosis in prostate cancer cells in part through inhibition of Bcl-xL/Bcl-2 functions independently of PPARgamma. Cancer Res., 2005, 65(4), 1561-1569.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-1677] [PMID: 15735046]
[86]
Tachibana, K.; Yamasaki, D.; Ishimoto, K.; Doi, T. The role of PPARs in cancer. PPAR Res., 2008, 2008,102737.
[http://dx.doi.org/10.1155/2008/102737] [PMID: 18584037]
[87]
Toyoda, M.; Takagi, H.; Horiguchi, N.; Kakizaki, S.; Sato, K.; Takayama, H.; Mori, M. A ligand for peroxisome proliferator activated receptor γ inhibits cell growth and induces apoptosis in human liver cancer cells. Gut, 2002, 50(4), 563-567.
[http://dx.doi.org/10.1136/gut.50.4.563] [PMID: 11889080]
[88]
Spencer, C.M.; Markham, A. Troglitazone. Drugs, 1997, 54(1), 89-101.
[http://dx.doi.org/10.2165/00003495-199754010-00010] [PMID: 9211083]
[89]
Buchanan, T.A.; Xiang, A.H.; Peters, R.K.; Kjos, S.L.; Marroquin, A.; Goico, J.; Ochoa, C.; Tan, S.; Berkowitz, K.; Hodis, H.N.; Azen, S.P. Preservation of pancreatic β-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk hispanic women. Diabetes, 2002, 51(9), 2796-2803.
[http://dx.doi.org/10.2337/diabetes.51.9.2796] [PMID: 12196473]
[90]
Faich, G.A.; Moseley, R.H. Troglitazone (rezulin) and hepatic injury. Pharmacoepidemiol. Drug Saf., 2001, 10(6), 537-547.
[http://dx.doi.org/10.1002/pds.652] [PMID: 11828837]
[91]
Bosch, J.; Yusuf, S.; Gerstein, H.C.; Pogue, J.; Sheridan, P.; Dagenais, G.; Diaz, R.; Avezum, A.; Lanas, F.; Probstfield, J.; Fodor, G.; Holman, R.R. DREAM Trial Investigators Effect of ramipril on the incidence of diabetes. N. Engl. J. Med., 2006, 355(15), 1551-1562.
[http://dx.doi.org/10.1056/NEJMoa065061] [PMID: 16980380]
[92]
Wagstaff, A.J.; Goa, K.L. Rosiglitazone: a review of its use in the management of type 2 diabetes mellitus. Drugs, 2002, 62(12), 1805-1837.
[http://dx.doi.org/10.2165/00003495-200262120-00007] [PMID: 12149047]
[93]
Gross, B.; Staels, B. PPAR agonists: multimodal drugs for the treatment of type-2 diabetes. Best Pract. Res. Clin. Endocrinol. Metab., 2007, 21(4), 687-710.
[http://dx.doi.org/10.1016/j.beem.2007.09.004] [PMID: 18054742]
[94]
Waugh, J.; Keating, G.M.; Plosker, G.L.; Easthope, S.; Robinson, D.M. Pioglitazone: a review of its use in type 2 diabetes mellitus. Drugs, 2006, 66(1), 85-109.
[http://dx.doi.org/10.2165/00003495-200666010-00005] [PMID: 16398569]
[95]
Lewis, J.D.; Ferrara, A.; Peng, T.; Hedderson, M.; Bilker, W.B.; Quesenberry, C.P., Jr; Vaughn, D.J.; Nessel, L.; Selby, J.; Strom, B.L. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care, 2011, 34(4), 916-922.
[http://dx.doi.org/10.2337/dc10-1068] [PMID: 21447663]
[96]
Lee, Y.H.; Kim, J.H.; Kim, S.R.; Jin, H.Y.; Rhee, E.J.; Cho, Y.M.; Lee, B.W. Lobeglitazone, a novel thiazolidinedione, improves non-alcoholic fatty liver disease in type 2 diabetes: its efficacy and predictive factors related to responsiveness. J. Korean Med. Sci., 2017, 32(1), 60-69.
[http://dx.doi.org/10.3346/jkms.2017.32.1.60] [PMID: 27914133]
[97]
Kaul, U.; Parmar, D.; Manjunath, K.; Shah, M.; Parmar, K.; Patil, K.P.; Jaiswal, A. New dual peroxisome proliferator activated receptor agonist-saroglitazar in diabetic dyslipidemia and non-alcoholic fatty liver disease: integrated analysis of the real world evidence. Cardiovasc. Diabetol., 2019, 18(1), 80.
[http://dx.doi.org/10.1186/s12933-019-0884-3] [PMID: 31208414]
[98]
Joshi, S.R. Saroglitazar for the treatment of dyslipidemia in diabetic patients. Expert Opin. Pharmacother., 2015, 16(4), 597-606.
[http://dx.doi.org/10.1517/14656566.2015.1009894] [PMID: 25674933]
[99]
Chen, Y.; Chen, H.; Birnbaum, Y.; Nanhwan, M.K.; Bajaj, M.; Ye, Y.; Qian, J. Aleglitazar, a dual peroxisome proliferator-activated receptor-α and -γ agonist, protects cardiomyocytes against the adverse effects of hyperglycaemia. Diab. Vasc. Dis. Res., 2017, 14(2), 152-162.
[http://dx.doi.org/10.1177/1479164116679081] [PMID: 28111985]
[100]
Shibata, T.; Takeuchi, S.; Yokota, S.; Kakimoto, K.; Yonemori, F.; Wakitani, K. Effects of peroxisome proliferator-activated receptor-α and -γ agonist, JTT-501, on diabetic complications in Zucker diabetic fatty rats. Br. J. Pharmacol., 2000, 130(3), 495-504.
[http://dx.doi.org/10.1038/sj.bjp.0703328] [PMID: 10821776]
[101]
Tenenbaum, A.; Motro, M.; Fisman, E.Z. Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons. Cardiovasc. Diabetol., 2005, 4(1), 14.
[http://dx.doi.org/10.1186/1475-2840-4-14] [PMID: 16168052]
[102]
Rudolph, J.; Chen, L.; Majumdar, D.; Bullock, W.H.; Burns, M.; Claus, T.; Dela Cruz, F.E.; Daly, M.; Ehrgott, F.J.; Johnson, J.S.; Livingston, J.N.; Schoenleber, R.W.; Shapiro, J.; Yang, L.; Tsutsumi, M.; Ma, X. Indanylacetic acid derivatives carrying 4-thiazolyl-phenoxy tail groups, a new class of potent PPAR α/γ/δ pan agonists: synthesis, structure-activity relationship, and in vivo efficacy. J. Med. Chem., 2007, 50(5), 984-1000.
[http://dx.doi.org/10.1021/jm061299k] [PMID: 17274610]
[103]
Wright, H.M.; Clish, C.B.; Mikami, T.; Hauser, S.; Yanagi, K.; Hiramatsu, R.; Serhan, C.N.; Spiegelman, B.M. A synthetic antagonist for the peroxisome proliferator-activated receptor γ inhibits adipocyte differentiation. J. Biol. Chem., 2000, 275(3), 1873-1877.
[http://dx.doi.org/10.1074/jbc.275.3.1873] [PMID: 10636887]
[104]
Seargent, J.M.; Yates, E.A.; Gill, J.H. GW9662, a potent antagonist of PPARgamma, inhibits growth of breast tumour cells and promotes the anticancer effects of the PPARgamma agonist rosiglitazone, independently of PPARgamma activation. Br. J. Pharmacol., 2004, 143(8), 933-937.
[http://dx.doi.org/10.1038/sj.bjp.0705973] [PMID: 15533890]
[105]
Park, H.S.; Kim, S.H.; Kim, Y.S.; Ryu, S.Y.; Hwang, J.T.; Yang, H.J.; Kim, G.H.; Kwon, D.Y.; Kim, M.S. Luteolin inhibits adipogenic differentiation by regulating PPARgamma activation. Biofactors, 2009, 35(4), 373-379.
[http://dx.doi.org/10.1002/biof.38] [PMID: 19353690]
[106]
Lee, G.; Elwood, F.; McNally, J.; Weiszmann, J.; Lindstrom, M.; Amaral, K.; Nakamura, M.; Miao, S.; Cao, P.; Learned, R.M.; Chen, J.L.; Li, Y. T0070907, a selective ligand for peroxisome proliferator-activated receptor γ, functions as an antagonist of biochemical and cellular activities. J. Biol. Chem., 2002, 277(22), 19649-19657.
[http://dx.doi.org/10.1074/jbc.M200743200] [PMID: 11877444]
[107]
Rieusset, J.; Touri, F.; Michalik, L.; Escher, P.; Desvergne, B.; Niesor, E.; Wahli, W. A new selective peroxisome proliferator-activated receptor γ antagonist with antiobesity and antidiabetic activity. Mol. Endocrinol., 2002, 16(11), 2628-2644.
[http://dx.doi.org/10.1210/me.2002-0036] [PMID: 12403851]
[108]
Huang, C.; Zhang, Y.; Gong, Z.; Sheng, X.; Li, Z.; Zhang, W.; Qin, Y. Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma pathway. Biochem. Biophys. Res. Commun., 2006, 348(2), 571-578.
[http://dx.doi.org/10.1016/j.bbrc.2006.07.095] [PMID: 16890192]
[109]
Niu, H.; Wang, W.; Li, J.; Lei, Y.; Zhao, Y.; Yang, W.; Zhao, C.; Lin, B.; Song, S.; Wang, S. A novel structural class of coumarin-chalcone fibrates as PPARα/γ agonists with potent antioxidant activities: Design, synthesis, biological evaluation and molecular docking studies. Eur. J. Med. Chem., 2017, 138, 212-220.
[http://dx.doi.org/10.1016/j.ejmech.2017.06.033] [PMID: 28667876]
[110]
Darwish, K.M.; Salama, I.; Mostafa, S.; Gomaa, M.S.; Helal, M.A. Design, synthesis, and biological evaluation of novel thiazolidinediones as PPARγ/FFAR1 dual agonists. Eur. J. Med. Chem., 2016, 109, 157-172.
[http://dx.doi.org/10.1016/j.ejmech.2015.12.049] [PMID: 26774923]
[111]
Hara, T.; Hirasawa, A.; Ichimura, A.; Kimura, I.; Tsujimoto, G. Free fatty acid receptors FFAR1 and GPR120 as novel therapeutic targets for metabolic disorders. J. Pharm. Sci., 2011, 100(9), 3594-3601.
[http://dx.doi.org/10.1002/jps.22639] [PMID: 21618241]
[112]
Yu, J.; Tang, L.; Yang, Y.; Ji, R. Synthesis and evaluation of a series of benzopyran derivatives as PPAR α/γ agonists. Eur. J. Med. Chem., 2008, 43(11), 2428-2435.
[http://dx.doi.org/10.1016/j.ejmech.2008.01.029] [PMID: 18329751]
[113]
Nazreen, S.; Alam, M.S.; Hamid, H.; Yar, M.S.; Shafi, S.; Dhulap, A.; Alam, P.; Pasha, M A Q.; Bano, S.; Alam, M.M.; Haider, S.; Ali, Y.; Kharbanda, C.; Pillai, K.K. Design, synthesis, in silico molecular docking and biological evaluation of novel oxadiazole based thiazolidine-2,4-diones bis-heterocycles as PPAR-γ agonists. Eur. J. Med. Chem., 2014, 87, 175-185.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.010] [PMID: 25255433]
[114]
Piemontese, L.; Fracchiolla, G.; Carrieri, A.; Parente, M.; Laghezza, A.; Carbonara, G.; Sblano, S.; Tauro, M.; Gilardi, F.; Tortorella, P.; Lavecchia, A.; Crestani, M.; Desvergne, B.; Loiodice, F. Design, synthesis and biological evaluation of a class of bioisosteric oximes of the novel dual peroxisome proliferator-activated receptor α/γ ligand LT175. Eur. J. Med. Chem., 2015, 90, 583-594.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.044] [PMID: 25497132]
[115]
Choi, J.; Ko, Y.; Lee, H.S.; Park, Y.S.; Yang, Y.; Yoon, S. Identification of (β-carboxyethyl)-rhodanine derivatives exhibiting peroxisome proliferator-activated receptor γ activity. Eur. J. Med. Chem., 2010, 45(1), 193-202.
[http://dx.doi.org/10.1016/j.ejmech.2009.09.042] [PMID: 19879669]
[116]
Piemontese, L.; Cerchia, C.; Laghezza, A.; Ziccardi, P.; Sblano, S.; Tortorella, P.; Iacobazzi, V.; Infantino, V.; Convertini, P.; Dal Piaz, F.; Lupo, A.; Colantuoni, V.; Lavecchia, A.; Loiodice, F. New diphenylmethane derivatives as peroxisome proliferator-activated receptor alpha/gamma dual agonists endowed with anti-proliferative effects and mitochondrial activity. Eur. J. Med. Chem., 2017, 127, 379-397.
[http://dx.doi.org/10.1016/j.ejmech.2016.12.047] [PMID: 28076827]
[117]
Furukawa, A.; Arita, T.; Fukuzaki, T.; Mori, M.; Honda, T.; Satoh, S.; Matsui, Y.; Wakabayashi, K.; Hayashi, S.; Nakamura, K.; Araki, K.; Kuroha, M.; Tanaka, J.; Wakimoto, S.; Suzuki, O.; Ohsumi, J. Synthesis and biological evaluation of novel (-)-cercosporamide derivatives as potent selective PPARγ modulators. Eur. J. Med. Chem., 2012, 54, 522-533.
[http://dx.doi.org/10.1016/j.ejmech.2012.05.040] [PMID: 22727448]
[118]
Shi, G.Q.; Dropinski, J.F.; McKeever, B.M.; Xu, S.; Becker, J.W.; Berger, J.P.; MacNaul, K.L.; Elbrecht, A.; Zhou, G.; Doebber, T.W.; Wang, P.; Chao, Y.S.; Forrest, M.; Heck, J.V.; Moller, D.E.; Jones, A.B. Design and synthesis of α-aryloxyphenylacetic acid derivatives: a novel class of PPARalpha/γ dual agonists with potent antihyperglycemic and lipid modulating activity. J. Med. Chem., 2005, 48(13), 4457-4468.
[http://dx.doi.org/10.1021/jm0502135] [PMID: 15974597]
[119]
Ohashi, M.; Nakagome, I.; Kasuga, J.; Nobusada, H.; Matsuno, K.; Makishima, M.; Hirono, S.; Hashimoto, Y.; Miyachi, H. Design, synthesis and in vitro evaluation of a series of α-substituted phenylpropanoic acid PPARγ agonists to further investigate the stereochemistry-activity relationship. Bioorg. Med. Chem., 2012, 20(21), 6375-6383.
[http://dx.doi.org/10.1016/j.bmc.2012.08.061] [PMID: 23022278]
[120]
Dixit, V.A.; Rathi, P.C.; Bhagat, S.; Gohlke, H.; Petersen, R.K.; Kristiansen, K.; Chakraborti, A.K.; Bharatam, P.V. Design and synthesis of novel Y-shaped barbituric acid derivatives as PPARγ activators. Eur. J. Med. Chem., 2016, 108, 423-435.
[http://dx.doi.org/10.1016/j.ejmech.2015.11.030] [PMID: 26708109]
[121]
Bajare, S.; Anthony, J.; Nair, A.; Marita, R.; Damre, A.; Patel, D.; Rao, C.; Sivaramakrishnan, H.; Deka, N. Synthesis of N-(5-chloro-6-(quinolin-3-yloxy)pyridin-3-yl)benz-enesulfonamide derivatives as non-TZD peroxisome proliferator-activated receptor γ (PPARγ) agonist. Eur. J. Med. Chem., 2012, 58, 355-360.
[http://dx.doi.org/10.1016/j.ejmech.2012.10.027] [PMID: 23142675]
[122]
Tyagi, S.; Gupta, P.; Saini, A.S.; Kaushal, C.; Sharma, S. The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases. J. Adv. Pharm. Technol. Res., 2011, 2(4), 236-240.
[http://dx.doi.org/10.4103/2231-4040.90879] [PMID: 22247890]
[123]
Celi, F.S.; Shuldiner, A.R. The role of peroxisome proliferator-activated receptor gamma in diabetes and obesity. Curr. Diab. Rep., 2002, 2(2), 179-185.
[http://dx.doi.org/10.1007/s11892-002-0078-2] [PMID: 12643137]
[124]
Green, S. PPAR: a mediator of peroxisome proliferator action. Mut. Res, 333(1-2), 101-109.
[http://dx.doi.org/10.1016/0027-5107(95)00136-0] [PMID: 8538617]

Rights & Permissions Print Cite
Article Metrics
79
2
© 2024 Bentham Science Publishers | Privacy Policy