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      Drug Design, Development and Therapy (submit here)

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      Sustained curcumin release from PLGA microspheres improves bone formation under diabetic conditions by inhibiting the reactive oxygen species production

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          Abstract

          Background

          Excessive reactive oxygen species production caused by type 2 diabetes conditions can disrupt normal bone metabolism and greatly impair bone regeneration.

          Materials and methods

          In the present study, curcumin (Cur)-loaded microspheres were incorporated into a fish collagen nano-hydroxyapatite scaffold to promote bone repair under diabetic conditions by inhibiting the reactive oxygen species production.

          Results

          The drug release kinetic study showed that the Cur release from the composite scaffolds lasted up to 30 days. The sustained curcumin release from the scaffold significantly inhibited the overproduction of reactive oxygen species in mesenchymal stem cells caused by diabetic serum. Moreover, the Cur-loaded scaffold also remarkedly alleviated the negative effects of diabetic serum on the proliferation, migration, and osteogenic differentiation of mesenchymal stem cells. When implanted into bone defects in type 2 diabetic rats, the Cur-loaded scaffold also showed a greater bone formation capability compared to the pure scaffold.

          Conclusion

          The results of this study suggested that the novel controlled Cur release system may provide a promising route to improve bone regeneration in type 2 diabetic patients.

          Most cited references31

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          Oxidative toxicity in diabetes and Alzheimer’s disease: mechanisms behind ROS/ RNS generation

          Reactive oxidative species (ROS) toxicity remains an undisputed cause and link between Alzheimer’s disease (AD) and Type-2 Diabetes Mellitus (T2DM). Patients with both AD and T2DM have damaged, oxidized DNA, RNA, protein and lipid products that can be used as possible disease progression markers. Although the oxidative stress has been anticipated as a main cause in promoting both AD and T2DM, multiple pathways could be involved in ROS production. The focus of this review is to summarize the mechanisms involved in ROS production and their possible association with AD and T2DM pathogenesis and progression. We have also highlighted the role of current treatments that can be linked with reduced oxidative stress and damage in AD and T2DM.
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            Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury

            Diabetes induces the onset and progression of renal injury through causing hemodynamic dysregulation along with abnormal morphological and functional nephron changes. The most important event that precedes renal injury is an increase in permeability of plasma proteins such as albumin through a damaged glomerular filtration barrier resulting in excessive urinary albumin excretion (UAE). Moreover, once enhanced UAE begins, it may advance renal injury from progression of abnormal renal hemodynamics, increased glomerular basement membrane (GBM) thickness, mesangial expansion, extracellular matrix accumulation, and glomerulosclerosis to eventual end-stage renal damage. Interestingly, all these pathological changes are predominantly driven by diabetes-induced reactive oxygen species (ROS) and abnormal downstream signaling molecules. In diabetic kidney, NADPH oxidase (enzymatic) and mitochondrial electron transport chain (nonenzymatic) are the prominent sources of ROS, which are believed to cause the onset of albuminuria followed by progression to renal damage through podocyte depletion. Chronic hyperglycemia and consequent ROS production can trigger abnormal signaling pathways involving diverse signaling mediators such as transcription factors, inflammatory cytokines, chemokines, and vasoactive substances. Persistently, increased expression and activation of these signaling molecules contribute to the irreversible functional and structural changes in the kidney resulting in critically decreased glomerular filtration rate leading to eventual renal failure.
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              Curcumin: An age-old anti-inflammatory and anti-neoplastic agent

              Curcumin is a natural anti-inflammatory agent that has been used for treating medical conditions for many years. Several experimental and pharmacologic trials have demonstrated its efficacy in the role as an anti-inflammatory agent. Curcumin has been shown to be effective in treating chronic conditions like rheumatoid arthritis, inflammatory bowel disease, Alzheimer's and common malignancies like colon, stomach, lung, breast, and skin cancers. As treatments in medicine become more and more complex, the answer may be something simpler. This is a review article written with the objective to systematically analyze the wealth of information regarding the medical use of curcumin, the “curry spice”, and to understand the existent gaps which have prevented its widespread application in the medical community.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2018
                24 May 2018
                : 12
                : 1453-1466
                Affiliations
                [1 ]Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China
                [2 ]Department of Aesthetic Surgery, Hangzhou Raily Aesthetic Plastic Hospital, Hangzhou 310003, People’s Republic of China
                Author notes
                Correspondence: Zhan-Zhao Zhang, Department of Aesthetic Surgery, Hangzhou Raily Aesthetic Plastic Hospital, 290 North Zhongshan Road, Hangzhou 310003, People’s Republic of China, Tel +86 15900671092, Email zhang031130@ 123456sjtu.edu.cn
                Article
                dddt-12-1453
                10.2147/DDDT.S154334
                5973436
                9787a7f5-39c3-499f-8af7-6c30a82f6f5f
                © 2018 Li and Zhang. 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

                Pharmacology & Pharmaceutical medicine
                curcumin,plga,drug delivery system,type 2 diabetes mellitus,bone repair

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