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      International Journal of Nanomedicine (submit here)

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      Quercetin nanoparticle complex attenuated diabetic nephropathy via regulating the expression level of ICAM-1 on endothelium

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          Abstract

          The purpose of the study was to reveal the therapeutic effect of quercetin (QUE) nanoparticle complex on diabetic nephropathy (DN) by regulating the expression of intercellular adhesion molecular-1 (ICAM-1) on endothelium as compared to free QUE. QUE 10 mg/kg as a single abdominal subcutaneous injection daily for 8 weeks continuously in diabetic rats and 10 mg/kg QUE nanoparticle complex as a single abdominal subcutaneous injection every 5 days, continuously administered for 8 weeks to diabetic rats. Blood and left kidneys were collected; pathological change of kidney, renal function, oxidative stress level, blood glucose level, serum lipid, urine protein, and albumin/creatinine ratio were measured; and neutrophil adhesion, ICAM-1 expression, and CD11b + cells infiltration were observed. Both QUE and QUE nanoparticle complex preconditioning ameliorated the pathological damage of kidney and improved renal function, alleviated renal oxidative stress injury, restricted inflammatory cells infiltration, and downregulated the ICAM-1 expression as compared to DN group, while QUE nanoparticle complex significantly alleviated this effect.

          Most cited references49

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          Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus.

          The Na-glucose cotransporter SGLT2 mediates high-capacity glucose uptake in the early proximal tubule and SGLT2 inhibitors are developed as new antidiabetic drugs. We used gene-targeted Sglt2 knockout (Sglt2(-/-)) mice to elucidate the contribution of SGLT2 to blood glucose control, glomerular hyperfiltration, kidney growth, and markers of renal growth and injury at 5 wk and 4.5 mo after induction of low-dose streptozotocin (STZ) diabetes. The absence of SGLT2 did not affect renal mRNA expression of glucose transporters SGLT1, NaGLT1, GLUT1, or GLUT2 in response to STZ. Application of STZ increased blood glucose levels to a lesser extent in Sglt2(-/-) vs. wild-type (WT) mice (∼300 vs. 470 mg/dl) but increased glucosuria and food and fluid intake to similar levels in both genotypes. Lack of SGLT2 prevented STZ-induced glomerular hyperfiltration but not the increase in kidney weight. Knockout of SGLT2 attenuated the STZ-induced renal accumulation of p62/sequestosome, an indicator of impaired autophagy, but did not attenuate the rise in renal expression of markers of kidney growth (p27 and proliferating cell nuclear antigen), oxidative stress (NADPH oxidases 2 and 4 and heme oxygenase-1), inflammation (interleukin-6 and monocyte chemoattractant protein-1), fibrosis (fibronectin and Sirius red-sensitive tubulointerstitial collagen accumulation), or injury (renal/urinary neutrophil gelatinase-associated lipocalin). SGLT2 deficiency did not induce ascending urinary tract infection in nondiabetic or diabetic mice. The results indicate that SGLT2 is a determinant of hyperglycemia and glomerular hyperfiltration in STZ-induced diabetes mellitus but is not critical for the induction of renal growth and markers of renal injury, inflammation, and fibrosis.
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            Endothelial mitochondria: contributing to vascular function and disease.

            Disturbances in vascular function contribute to the development of several diseases of increasing prevalence and thereby contribute significantly to human mortality and morbidity. Atherosclerosis, diabetes, heart failure, and ischemia with attendant reperfusion injury share many of the same risk factors, among the most important being oxidative stress and alterations in the blood concentrations of compounds that influence oxidative stress, such as oxidized low-density lipoprotein. In this review, we focus on endothelial cells: cells in the frontline against these disturbances. Because ATP supplies in endothelial cells are relatively independent of mitochondrial oxidative pathways, the mitochondria of endothelial cells have been somewhat neglected. However, they are emerging as agents with diverse roles in modulating the dynamics of intracellular calcium and the generation of reactive oxygen species and nitric oxide. The mitochondria may also constitute critical "targets" of oxidative stress, because survival of endothelial cells can be compromised by opening of the mitochondrial permeability transition pore or by mitochondrial pathways of apoptosis. In addition, evidence suggests that endothelial mitochondria may play a "reconnaissance" role. For example, although the exact mechanism remains obscure, endothelial mitochondria may sense levels of oxygen in the blood and relay this information to cardiac myocytes as well as modulating the vasodilatory response mediated by endothelial nitric oxide.
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              Diabetes is an inflammatory disease: evidence from traditional Chinese medicines.

              W. Xie, L DU (2011)
              Diabetes is usually associated with inflammation. Inflammation contributes to the development of diabetes. Traditional Chinese medicines (TCM) play an important role in lowering blood glucose and controlling inflammation. Many studies show that TCM with hypoglycaemic effects, for example Radix Astragali, Radix Rehmanniae, Radix Trichosanthis, Panax Ginseng, Fructus Schisandrae, Radix Ophiopogonis, Rhizoma Anemarrhenae, Radix Puerariae, Fructus Lycii, Poria, Rhizoma Coptidis, Rhizoma Dioscoreae, Rhizoma Polygonati, Radix Salviae Miltiorrhizae, Radix Glycyrrhizae, Semen Trigonellae, Momordica charantia, Allium sativum, Opuntia stricta, Aloe vera, Cortex Cinnamomi, Rhizoma Curcumae Longae, and so on, have nearly independent anti-inflammatory action. Antihyperglycaemic compounds, for example berberine, puerarin, quercetin, ferulic acid, astragaloside IV, curcumin, epigallocatechin gallate, resveratrol, tetrandrine, glycyrrhizin, emodin and baicalin, used in TCM also have anti-inflammatory effects. These studies suggest that TCM might exert hypoglycaemic effects that are partly mediated by the anti-inflammatory mechanisms. However, small amounts of TCM with potent anti-inflammatory action does not have any hypoglycaemic effect. This indirectly indicates that diabetes may be a low-grade inflammatory disease and potent regulation of inflammatory mediators may not be required. Studies of TCM add new evidences, which indicate that diabetes may be an inflammatory disease and slight or moderate inhibition of inflammation might be useful to prevent the development of diabetes. Through this review, we aim to develop more perspectives to indicate that diabetes may be an inflammatory disease and diverse TCM may share a common antidiabetic property: anti-inflammatory action. Further studies should focus on and validate inflammation-regulating targets of TCM that may be involved in inhibiting the development of diabetes. © 2011 Blackwell Publishing Ltd.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2017
                24 October 2017
                : 12
                : 7799-7813
                Affiliations
                [1 ]Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen
                [2 ]Department of Pathology and Pathophysiology, Provincial Key Discipline of Pharmacology, Jiaxing University Medical College, Jiaxing, Zhejiang
                [3 ]Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China
                Author notes
                Correspondence: Shuyu Yang, Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Siming District of Xiamen Town Road No 55, Xiamen 361003, Republic of China, Tel +86 139 5006 2003, Email xmyangshuyu@ 123456126.com
                Article
                ijn-12-7799
                10.2147/IJN.S146978
                5661459
                29123394
                000746eb-2df6-4ece-89bf-9cb09c81beda
                © 2017 Tong et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Molecular medicine
                nanoparticle complex,quercetin,dn,icam-1,cd11b+,endothelium
                Molecular medicine
                nanoparticle complex, quercetin, dn, icam-1, cd11b+, endothelium

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