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      From balance to imbalance: disruption of plasma glutathione concentration in micropapillary thyroid carcinoma

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          Abstract

          Background

          Despite the presence of evidence that establishes a strong correlation between oxidative stress and thyroid cancer, there exists a scarcity of research that investigates the specific role of glutathione as an important antioxidant in this particular context. The objective of this study was to assess the altered balance of oxidative stress in cases of thyroid cancer, which includes both papillary thyroid carcinoma (PTC) and micro PTC (mPTC), by examining and comparing the total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), reduced glutathione (GSH), oxidized glutathione (GSSG), and GSSG/GSH ratio with those of individuals diagnosed with multinodular goiter (MNG) as well as Healthy subjects.

          Materials and methods

          Plasma samples were collected from 92 patients (23 mPTC, 23 PTC, 23 MNG, 23 Healthy). The levels of TAC, TOS, GSH, and GSSG were measured using a commercial assay kits, and the OSI and GSSG/GSH ratio were calculated for each sample. Statistical analyses were performed to compare the oxidative stress between the groups.

          Results

          The plasma levels of TOS were significantly higher in the mPTC, PTC, and MNG groups compared to the Healthy individuals ( p < 0.05). The OSI in the mPTC and PTC groups showed a significant increase compared to the Healthy group ( p < 0.05). The levels of GSH in mPTC and PTC were markedly lower compared to the Healthy subjects ( p < 0.01). Interestingly, the concentration of GSH in mPTC was found to be considerably lower than in PTC and MNG patients ( p < 0.01).

          Conclusion

          These findings indicate that GSH may be a useful biomarker for evaluating oxidative stress and antioxidant system status in patients with PTC, especially mPTC. Low levels of GSH may indicate increased levels of oxidative stress, which may contribute to the development and progression of mPTC to PTC.

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          Most cited references20

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          The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging.

          The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment. The rapid evolution of knowledge in cancer biology and the discovery and validation of biologic factors that predict cancer outcome and response to treatment with better accuracy have led some cancer experts to question the utility of a TNM-based approach in clinical care at an individualized patient level. In the Eighth Edition of the AJCC Cancer Staging Manual, the goal of including relevant, nonanatomic (including molecular) factors has been foremost, although changes are made only when there is strong evidence for inclusion. The editorial board viewed this iteration as a proactive effort to continue to build the important bridge from a "population-based" to a more "personalized" approach to patient classification, one that forms the conceptual framework and foundation of cancer staging in the era of precision molecular oncology. The AJCC promulgates best staging practices through each new edition in an effort to provide cancer care providers with a powerful, knowledge-based resource for the battle against cancer. In this commentary, the authors highlight the overall organizational and structural changes as well as "what's new" in the Eighth Edition. It is hoped that this information will provide the reader with a better understanding of the rationale behind the aggregate proposed changes and the exciting developments in the upcoming edition. CA Cancer J Clin 2017;67:93-99. © 2017 American Cancer Society.
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            Oxidative Stress and Antioxidant Defense

            Abstract Reactive oxygen species (ROS) are produced by living organisms as a result of normal cellular metabolism and environmental factors, such as air pollutants or cigarette smoke. ROS are highly reactive molecules and can damage cell structures such as carbohydrates, nucleic acids, lipids, and proteins and alter their functions. The shift in the balance between oxidants and antioxidants in favor of oxidants is termed “oxidative stress.” Regulation of reducing and oxidizing (redox) state is critical for cell viability, activation, proliferation, and organ function. Aerobic organisms have integrated antioxidant systems, which include enzymatic and nonenzymatic antioxidants that are usually effective in blocking harmful effects of ROS. However, in pathological conditions, the antioxidant systems can be overwhelmed. Oxidative stress contributes to many pathological conditions and diseases, including cancer, neurological disorders, atherosclerosis, hypertension, ischemia/perfusion, diabetes, acute respiratory distress syndrome, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and asthma. In this review, we summarize the cellular oxidant and antioxidant systems and discuss the cellular effects and mechanisms of the oxidative stress.
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              The role of antioxidants in the chemistry of oxidative stress: A review.

              This Review Article is focused on the action of the reactive oxygenated species in inducing oxidative injury of the lipid membrane components, as well as on the ability of antioxidants (of different structures and sources, and following different mechanisms of action) in fighting against oxidative stress. Oxidative stress is defined as an excessive production of reactive oxygenated species that cannot be counteracted by the action of antioxidants, but also as a perturbation of cell redox balance. Reactive oxygenated/nitrogenated species are represented by superoxide anion radical, hydroxyl, alkoxyl and lipid peroxyl radicals, nitric oxide and peroxynitrite. Oxidative stress determines structure modifications and function modulation in nucleic acids, lipids and proteins. Oxidative degradation of lipids yields malondialdehyde and 4-hydroxynonenal, but also isoprostanes, from unsaturated fatty acids. Protein damage may occur with thiol oxidation, carbonylation, side-chain oxidation, fragmentation, unfolding and misfolding, resulting activity loss. 8-hydroxydeoxyguanosine is an index of DNA damage. The involvement of the reactive oxygenated/nitrogenated species in disease occurrence is described. The unbalance between the oxidant species and the antioxidant defense system may trigger specific factors responsible for oxidative damage in the cell: over-expression of oncogene genes, generation of mutagen compounds, promotion of atherogenic activity, senile plaque occurrence or inflammation. This leads to cancer, neurodegeneration, cardiovascular diseases, diabetes, kidney diseases. The concept of antioxidant is defined, along with a discussion of the existent classification criteria: enzymatic and non-enzymatic, preventative or repair-systems, endogenous and exogenous, primary and secondary, hydrosoluble and liposoluble, natural or synthetic. Primary antioxidants are mainly chain breakers, able to scavenge radical species by hydrogen donation. Secondary antioxidants are singlet oxygen quenchers, peroxide decomposers, metal chelators, oxidative enzyme inhibitors or UV radiation absorbers. The specific mechanism of action of the most important representatives of each antioxidant class (endogenous and exogenous) in preventing or inhibiting particular factors leading to oxidative injury in the cell, is then reviewed. Mutual influences, including synergistic effects are presented and discussed. Prooxidative influences likely to occur, as for instance in the presence of transition metal ions, are also reminded.
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                Author and article information

                Contributors
                s.adeleh.razavi@gmail.com , s.a.razavi@endocrine.ac.ir
                Journal
                Thyroid Res
                Thyroid Res
                Thyroid Research
                BioMed Central (London )
                1756-6614
                1 July 2024
                1 July 2024
                2024
                : 17
                : 16
                Affiliations
                [1 ]Department of Stem Cell and Regenerative Medicine, National Institute of Genetic Engineering and Biotechnology, ( https://ror.org/03ckh6215) Tehran, Iran
                [2 ]GRID grid.411600.2, Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, , Shahid Beheshti University of Medical Sciences, ; No 23, Shahid Arabi St. Yemen St. Velenjak, PO Box: 1985717413, Tehran, Iran
                [3 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Department of Pathology, Shariati Hospital, , School of Medicine, Tehran University of Medical Sciences, ; Tehran, Iran
                [4 ]Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, ( https://ror.org/01c4pz451) Tehran, Iran
                [5 ]Department of Cellular and Molecular Biology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences Branch, Islamic Azad University, ( https://ror.org/01kzn7k21) Tehran, Iran
                [6 ]Department of Anesthesia, Faculty of Paramedical, Qom University of Medical Sciences, ( https://ror.org/03ddeer04) Qom, Iran
                Author information
                http://orcid.org/0000-0002-9093-3255
                Article
                204
                10.1186/s13044-024-00204-9
                11215827
                38946003
                3af7233a-56c5-4925-b9e4-6ad02078a7a6
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 26 February 2024
                : 25 May 2024
                Categories
                Research
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Endocrinology & Diabetes
                papillary thyroid cancer,oxidative stress,antioxidant system,glutathione,reduced/oxidized glutathione ratio

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