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      Regulation of Dendrobium Polysaccharides on Proliferation and Oxidative Stress of Human Umbilical Vein Endothelial Cells in the High Glucose Environment

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          Abstract

          Backgrounds

          Polysaccharides of Dendrobium candidum (PDC) showed a strong antioxidant effect on islet cells while the effects of PDC on human umbilical vein endothelial cells (HUVECs) under the high glucose condition remain unclear. Material and Method. HUVECs were incubated with high glucose (33.3 mmol/L) for 48 hours to induce injury, and cells were treated with PDC (100, 200, and 400  μg/mL) for 48 hours. The tetrazolium blue colorimetric (MTT) assay was used to detect cell proliferation, superoxide dismutase (SOD), and nitric oxide (NO) content in cell supernatants. Flow cytometry was used to detect reactive oxygen species (ROS) and calcium levels.

          Results

          (1) Compared with the control group, the proliferation of HUVECs cells in the high glucose (33.3 mmol/L) group decreased ( P < 0.05). The intracellular calcium ion concentration and the intracellular ROS level increased ( P < 0.01 and P < 0.05). SOD activity and the level of NO in the culture medium were reduced ( P <0.05). (2) Compared with the control group, PDC (50, 100, 200, 400, and 800  μg/mL) did not significantly affect the cell proliferation of HUVECs ( P > 0.05). (3) Compared with the high glucose group, the HUVEC cell viability of the high glucose + PDC (100, 200, and 400  μg/mL) group increased while the intracellular calcium ion concentration decreased in a concentration-dependent manner ( P < 0.05). Intracellular ROS levels were reduced, while SOD activity and the level of NO in culture fluids increased ( P < 0.05).

          Conclusion

          PDC can promote the proliferation of HUVECs in the high glucose environment by reducing oxidative stress injury of HUVECs induced by high glucose.

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          Most cited references30

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          Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases.

          Reactive oxygen species (ROS) are reactive intermediates of molecular oxygen that act as important second messengers within the cells; however, an imbalance between generation of reactive ROS and antioxidant defense systems represents the primary cause of endothelial dysfunction, leading to vascular damage in both metabolic and atherosclerotic diseases. Endothelial activation is the first alteration observed, and is characterized by an abnormal pro-inflammatory and pro-thrombotic phenotype of the endothelial cells lining the lumen of blood vessels. This ultimately leads to reduced nitric oxide (NO) bioavailability, impairment of the vascular tone and other endothelial phenotypic changes collectively termed endothelial dysfunction(s). This review will focus on the main mechanisms involved in the onset of endothelial dysfunction, with particular focus on inflammation and aberrant ROS production and on their relationship with classical and non-classical cardiovascular risk factors, such as hypertension, metabolic disorders, and aging. Furthermore, new mediators of vascular damage, such as microRNAs, will be discussed. Understanding mechanisms underlying the development of endothelial dysfunction is an important base of knowledge to prevent vascular damage in metabolic and cardiovascular diseases.
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            Cellular death, reactive oxygen species (ROS) and diabetic complications

            Chronic or intermittent hyperglycemia is associated with the development of diabetic complications. Several signaling pathways can be altered by having hyperglycemia in different tissues, producing oxidative stress, the formation of advanced glycation end products (AGEs), as well as the secretion of the pro-inflammatory cytokines and cellular death (pathological autophagy and/or apoptosis). However, the signaling pathways that are directly triggered by hyperglycemia appear to have a pivotal role in diabetic complications due to the production of reactive oxygen species (ROS), oxidative stress, and cellular death. The present review will discuss the role of cellular death in diabetic complications, and it will suggest the cause and the consequences between the hyperglycemia-induced signaling pathways and cell death. The signaling pathways discussed in this review are to be described step-by-step, together with their respective inhibitors. They involve diacylglycerol, the activation of protein kinase C (PKC) and NADPH-oxidase system, and the consequent production of ROS. This was initially entitled the “dangerous metabolic route in diabetes”. The historical usages and the recent advancement of new drugs in controlling possible therapeutical targets have been highlighted, in order to evaluate the evolution of knowledge in this sensitive area. It has recently been shown that the metabolic responses to stimuli (i.e., hyperglycemia) involve an integrated network of signaling pathways, in order to define the exact responses. Certain new drugs have been experimentally tested—or suggested and proposed—for their ability to modulate the possible biochemical therapeutical targets for the downregulation of retinopathy, nephropathy, neuropathy, heart disease, angiogenesis, oxidative stress, and cellular death. The aim of this study was to critically and didactically evaluate the exact steps of these signaling pathways and hence mark the indicated sites for the actions of such drugs and their possible consequences. This review will emphasize, besides others, the therapeutical targets for controlling the signaling pathways, when aimed at the downregulation of ROS generation, oxidative stress, and, consequently, cellular death—with all of these conditions being a problem in diabetes.
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              Analysis of Cell Viability by the MTT Assay

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                Author and article information

                Contributors
                Journal
                J Diabetes Res
                J Diabetes Res
                JDR
                Journal of Diabetes Research
                Hindawi
                2314-6745
                2314-6753
                2021
                13 June 2021
                : 2021
                : 6685055
                Affiliations
                1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
                2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
                3Ningxia Geriatric Disease Clinical Research Center, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region, China
                4Department of Spine Surgery, The Xiangya Hospital, Central South University, Changsha, Hunan, China
                5Loudi Central Hospital, the Loudi Affiliated Hospital of Nanhua University, Hunan province, Loudi, 417000, China
                6Hunan People's Hospital, Department of Hunan Institute of Geriatrics, Changsha, China
                Author notes

                Academic Editor: Almudena G mez Hern ndez

                Author information
                https://orcid.org/0000-0003-4710-087X
                https://orcid.org/0000-0002-2465-5701
                https://orcid.org/0000-0002-7089-9934
                https://orcid.org/0000-0003-4816-4613
                Article
                10.1155/2021/6685055
                8216809
                34235226
                2944f1bc-67d2-4612-8be2-ac1c4a628820
                Copyright © 2021 Yajia Li et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 October 2020
                : 2 May 2021
                : 31 May 2021
                Funding
                Funded by: Discipline Leader Project of “225” Project for High-level Health Talents Training in Hunan Province
                Funded by: COVID-19 Special Project of Changsha Science and Technology Bureau
                Award ID: KQ2001019
                Funded by: Natural Science Foundation of Hunan Province
                Award ID: 2020JJ8012
                Funded by: Scientific Research Foundation of Hunan Provincial Health Commission
                Award ID: C2019055
                Funded by: Education Department of Hunan Province
                Award ID: 160546
                Funded by: Philosophy and Social Science Foundation of Hunan Province
                Award ID: 18YBA325
                Funded by: 2017 Project of Hunan Provincial Finance Department
                Award ID: [2017] 61
                Funded by: Key Research and Development Program of Ningxia Hui Autonomous Region in 2020
                Award ID: 2020beg03051
                Funded by: Philosophy and Social Science Planning Annual Project of Ningxia Hui Autonomous Region
                Award ID: 19NXAGL01
                Funded by: Central Government to Guide Local Science and Technology Development
                Award ID: 2020YDDF0043
                Categories
                Research Article

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