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      Frontiers of ferroptosis research: An analysis from the top 100 most influential articles in the field

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          Abstract

          In recent years, ferroptosis has become a research hotspot in programmed cell death. Since the concept of ferroptosis was proposed, a growing number of articles have been published on this topic. Nevertheless, to our knowledge, these ferroptosis-related publications that have received a great deal of attention have not been quantitatively evaluated. In this study, we analyzed the top 100 most influential articles over the past decade through a bibliometric method to characterize the research status and trends in this field. Web of Science Core Collection was searched to identify relevant studies. After being manually screened, the top 100 most cited studies with original data were identified and analyzed. Bibliometric software including VOSviewer and R-Bibliometrix were used to perform visualization analysis. The citation frequency for the top 100 selected articles ranged from 135 to 3603 (326.6 citations on average). These articles originated from 25 countries/regions, with more than half originating from the United States and China. The most frequently nominated author was Stockwell BR from the Columbia University, and of the top 100 articles, 19 listed his name. Three core journals were Nature, Cell and Proceedings of the National Academy of Sciences of the United States of America. In addition to term of ferroptosis, these terms or phrases including cell death, cancer cell, GPX4, pathway, inhibitor, mechanism, iron, lipid peroxidation, resistance, erastin, sorafenib, P53, reactive oxygen species, necroptosis, apoptosis, glutathione peroxidase, ACSL4, autophagy, and SLC7A11 appeared more frequently in the top 100 articles. Overall, although much progress has been made, the research on ferroptosis is still at an early stage. The current attention in this field mainly focuses on potential regulatory mechanism and pathways including key ferroptosis-related genes/molecules, oxidant and antioxidant system, ferroptosis-inducing agents or nanomedicine for cancer therapy, as well as the role of ferroptosis in non-neoplastic disorders. Meanwhile, combination therapeutic strategies targeting ferroptosis in radiotherapy or immunotherapy also deserve further attention.

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          Most cited references93

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          Ferroptosis: an iron-dependent form of nonapoptotic cell death.

          Nonapoptotic forms of cell death may facilitate the selective elimination of some tumor cells or be activated in specific pathological states. The oncogenic RAS-selective lethal small molecule erastin triggers a unique iron-dependent form of nonapoptotic cell death that we term ferroptosis. Ferroptosis is dependent upon intracellular iron, but not other metals, and is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. We identify the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes. Indeed, erastin, like glutamate, inhibits cystine uptake by the cystine/glutamate antiporter (system x(c)(-)), creating a void in the antioxidant defenses of the cell and ultimately leading to iron-dependent, oxidative death. Thus, activation of ferroptosis results in the nonapoptotic destruction of certain cancer cells, whereas inhibition of this process may protect organisms from neurodegeneration. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Software survey: VOSviewer, a computer program for bibliometric mapping

            We present VOSviewer, a freely available computer program that we have developed for constructing and viewing bibliometric maps. Unlike most computer programs that are used for bibliometric mapping, VOSviewer pays special attention to the graphical representation of bibliometric maps. The functionality of VOSviewer is especially useful for displaying large bibliometric maps in an easy-to-interpret way. The paper consists of three parts. In the first part, an overview of VOSviewer’s functionality for displaying bibliometric maps is provided. In the second part, the technical implementation of specific parts of the program is discussed. Finally, in the third part, VOSviewer’s ability to handle large maps is demonstrated by using the program to construct and display a co-citation map of 5,000 major scientific journals.
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              Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease

              Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                11 August 2022
                2022
                : 12
                : 948389
                Affiliations
                [1] 1 Department of Intensive Care Unit, The Second Affiliated Hospital of Zhengzhou University , Zhengzhou, China
                [2] 2 Department of Orthopaedic Surgery, Baodi Clinical College of Tianjin Medical University , Tianjin, China
                [3] 3 Sun Yat-Sen Memorial Hospital, Graduate School of Sun Yat-sen University , Guangzhou, China
                [4] 4 Graduate School of Tianjin Medical University , Tianjin, China
                [5] 5 Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University , Tianjin, China
                [6] 6 Department of Orthopaedic Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science , Xiangyang, China
                [7] 7 Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital , Tianjin, China
                Author notes

                Edited by: Zhijie Xu, Xiangya Hospital, Central South University, China

                Reviewed by: Susu Guo, Shanghai Jiao Tong University, China; Jiao Wu, Fourth Military Medical University, China; Demeng Xia, Shanghai University, China; Fei-Long Wei, Fourth Military Medical University (Air Force Medical University), China

                *Correspondence: Kunming Cheng, chengkm2013@ 123456163.com ; Xiuhua Yao, yao_xiuhua87@ 123456163.com ; Haiyang Wu, wuhaiyang2021@ 123456tmu.edu.cn

                †These authors have contributed equally to this work

                This article was submitted to Pharmacology of Anti-Cancer Drugs, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2022.948389
                9403769
                36033530
                094dadb4-a69a-4f2c-a89c-71004d644ba9
                Copyright © 2022 Cheng, Guo, Shen, Yang, Zhou, Sun, Yao and Wu

                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
                : 25 May 2022
                : 25 July 2022
                Page count
                Figures: 9, Tables: 4, Equations: 0, References: 93, Pages: 18, Words: 7207
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                ferroptosis,citation,hotspot,bibliometric analysis,cancer
                Oncology & Radiotherapy
                ferroptosis, citation, hotspot, bibliometric analysis, cancer

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