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      Notoginseng Triterpenes Inhibited Autophagy in Random Flaps via the Beclin-1/VPS34/LC3 Signaling Pathway to Improve Tissue Survival

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          Abstract

          Random flaps are widely used in tissue reconstruction, attributed to the lack of vascular axial limitation. Nevertheless, the distal end of the flap is prone to necrosis due to the lack of blood supply. Notoginseng triterpenes (NTs) are the active components extracted from Panax notoginseng, reducing oxygen consumption and improving the body’s tolerance to hypoxia. However, their role in random flap survival has not been elucidated. In this study, we used a mouse random skin flap model to verify that NT can promote cell proliferation and migration and that increasing blood perfusion can effectively improve the survival area of a skin flap. Our study also showed that the autophagy of random flaps after NT treatment was activated through the Beclin-1/VPS34/LC3 signaling pathway, and the therapeutic effect of NT significantly decreased after VPS34 IN inhibited autophagy. In conclusion, we have demonstrated that NT can significantly improve the survival rate of random flaps through the Beclin-1/VPS34/LC3 signaling pathway, suggesting that it might be a promising clinical treatment option.

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          Most cited references51

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          Autophagy pathway: Cellular and molecular mechanisms

          Macroautophagy/autophagy is an essential, conserved self-eating process that cells perform to allow degradation of intracellular components, including soluble proteins, aggregated proteins, organelles, macromolecular complexes, and foreign bodies. The process requires formation of a double-membrane structure containing the sequestered cytoplasmic material, the autophagosome, that ultimately fuses with the lysosome. This review will define this process and the cellular pathways required, from the formation of the double membrane to the fusion with lysosomes in molecular terms, and in particular highlight the recent progress in our understanding of this complex process.
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            Life, death and autophagy

            Autophagy influences cell survival through maintenance of cell bioenergetics and clearance of protein aggregates and damaged organelles. Several lines of evidence indicate that autophagy is a multifaceted regulator of cell death, but controversy exists over whether autophagy alone can drive cell death under physiologically relevant circumstances. Here, we review the role of autophagy in cell death and examine how autophagy interfaces with other forms of cell death including apoptosis and necrosis.
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              Mechanisms of Autophagy Initiation.

              Autophagy is the process of cellular self-eating by a double-membrane organelle, the autophagosome. A range of signaling processes converge on two protein complexes to initiate autophagy: the ULK1 (unc51-like autophagy activating kinase 1) protein kinase complex and the PI3KC3-C1 (class III phosphatidylinositol 3-kinase complex I) lipid kinase complex. Some 90% of the mass of these large protein complexes consists of noncatalytic domains and subunits, and the ULK1 complex has essential noncatalytic activities. Structural studies of these complexes have shed increasing light on the regulation of their catalytic and noncatalytic activities in autophagy initiation. The autophagosome is thought to nucleate from vesicles containing the integral membrane protein Atg9 (autophagy-related 9), COPII (coat protein complex II) vesicles, and possibly other sources. In the wake of reconstitution and super-resolution imaging studies, we are beginning to understand how the ULK1 and PI3KC3-C1 complexes might coordinate the nucleation and fusion of Atg9 and COPII vesicles at the start of autophagosome biogenesis.
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                Author and article information

                Contributors
                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                19 November 2021
                2021
                : 9
                : 771066
                Affiliations
                [ 1 ]Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
                [ 2 ]Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
                Author notes

                Edited by: Xudong Deng, Northwestern Polytechnical University, China

                Reviewed by: Chong Yin, Affiliated Hospital of North Sichuan Medical College, China

                Fei Xu, McMaster University, Canada

                Xueliang Zhang, Shanghai Jiaotong University, China

                *Correspondence: Xiaoyang Li, lixiaoyang1166@ 123456foxmail.com ; Sipin Zhu, sipinzhu@ 123456163.com ; Shengwu Yang, yangswcn@ 123456foxmail.com
                [ † ]

                These authors have contributed equally to this work

                This article was submitted to Biomaterials, a section of the journal Frontiers in Bioengineering and Biotechnology

                Article
                771066
                10.3389/fbioe.2021.771066
                8640242
                34869285
                ff22f6a2-5034-4160-87c9-47e76c885bd2
                Copyright © 2021 Huang, Luo, Zhang, Ying, Cai, Lu, Zhao, Wang, Lin, Tu, Xiang, Wu, Yang, Zhu and Li.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 05 September 2021
                : 15 October 2021
                Categories
                Bioengineering and Biotechnology
                Original Research

                random flap,notoginseng triterpenes,oxidative stress,autophagy,angiogenesis

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