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      Anti-Oxidative and Immuno-Protective Effect of Camel Milk on Radiation-Induced Intestinal Injury in C57BL/6 J Mice

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          Abstract

          Purpose:

          The main objective is to investigate the protective effect of camel milk (CM) on radiation-induced intestinal injury.

          Methods:

          The C57BL/6 J mice in 2 experiments were assigned into control group (Con), irradiation group (IR), and CM+irradiation group (CM+IR). After receiving the CM via gavage for 14 days, the mice in the first experiment were exposed to 6 Gy X-ray whole body irradiation, and survival rate was compared among the groups. Mice in the second experiment were exposed to 4 Gy irradiation and sacrificed at day 7. The small intestines were collected to examine the histopathological changes and to determine the anti-oxidative index and HMGB1/TLR4 inflammatory pathway. Fasting blood was used to measure serum pro-inflammatory factors.

          Results:

          Compared with the IR group, the survival time was prolonged, and survival rate was increased in the CM+IR group. CM increased levels of SOD and GSH and decreased MDA in the jejunum. Furthermore, intestinal protein expression of HMGB1/TLR4 pathway (TLR4, NF-κB, and HMGB1) was up-regulated by CM intervention. CM decreased the serum levels of TNF-α and IL-1β and increased IL-10 level.

          Conclusions:

          CM extended the survival time and had a protective effect against radiation-induced jejunum injury by regulation of antioxidant capacity and HMGB1/TLR4/NF-κB/MyD88 inflammatory signaling pathway.

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          Most cited references34

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          MD-2 is required for disulfide HMGB1–dependent TLR4 signaling

          Yang et al. show that a disulfide isoform of HMGB1, with a role in TLR4 signaling, physically interacts with and binds MD-2. MD-2 deficiency in macrophage cell lines or in primary mouse macrophages stimulated with HMGB1 implicates MD-2 in TLR4 signaling. They also identify an HGMB1 peptide inhibitor, P5779, which when administered in vivo can protect mice from acetaminophen-induced hepatoxicity, ischemia/reperfusion injury, and sepsis.
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            HMGB1, IL-1α, IL-33 and S100 proteins: dual-function alarmins

            Our immune system is based on the close collaboration of the innate and adaptive immune systems for the rapid detection of any threats to the host. Recognition of pathogen-derived molecules is entrusted to specific germline-encoded signaling receptors. The same receptors have now also emerged as efficient detectors of misplaced or altered self-molecules that signal tissue damage and cell death following, for example, disruption of the blood supply and subsequent hypoxia. Many types of endogenous molecules have been shown to provoke such sterile inflammatory states when released from dying cells. However, a group of proteins referred to as alarmins have both intracellular and extracellular functions which have been the subject of intense research. Indeed, alarmins can either exert beneficial cell housekeeping functions, leading to tissue repair, or provoke deleterious uncontrolled inflammation. This group of proteins includes the high-mobility group box 1 protein (HMGB1), interleukin (IL)-1α, IL-33 and the Ca2+-binding S100 proteins. These dual-function proteins share conserved regulatory mechanisms, such as secretory routes, post-translational modifications and enzymatic processing, that govern their extracellular functions in time and space. Release of alarmins from mesenchymal cells is a highly relevant mechanism by which immune cells can be alerted of tissue damage, and alarmins play a key role in the development of acute or chronic inflammatory diseases and in cancer development.
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              Inhibition of Bcl-2/xl With ABT-263 Selectively Kills Senescent Type II Pneumocytes and Reverses Persistent Pulmonary Fibrosis Induced by Ionizing Radiation in Mice

              Purpose: Ionizing radiation (IR)einduced pulmonary fibrosis (PF) is an irreversible and severe late effect of thoracic radiation therapy. The goal of this study was to determine whether clearance of senescent cells with ABT-263, a senolytic drug that can selectively kill senescent cells, can reverse PF. Methods and Materials: C57BL/6J mice were exposed to a single dose of 17 Gy on the right side of the thorax. Sixteen weeks after IR, they were treated with 2 cycles of vehicle or ABT-263 (50 mg/kg per day for 5 days per cycle) by gavage. The effects of ABT-263 on IR-induced increases in senescent cells; elevation in the expression of selective inflammatory cytokines, matrix metalloproteinases, and tissue inhibitors of matrix metalloproteinases; and the severity of the tissue injury and fibrosis in the irradiated lungs were evaluated 3 weeks after the last treatment, in comparison with the changes observed in the irradiated lungs before treatment or after vehicle treatment. Results: At 16 weeks after exposure of C57BL/6 mice to a single dose of 17 Gy, thoracic irradiation resulted in persistent PF associated with a significant increase in senescent cells. Treatment of the irradiated mice with ABT-263 after persistent PF had developed reduced senescent cells and reversed the disease. Conclusions: To our knowledge, this is the first study to demonstrate that PF can be reversed by a –senolytic drug such as ABT-263 after it becomes a progressive disease. Therefore, ABT-263 has the potential to be developed as a new treatment for PF.
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                Author and article information

                Journal
                Dose Response
                Dose Response
                DOS
                spdos
                Dose-Response
                SAGE Publications (Sage CA: Los Angeles, CA )
                1559-3258
                30 March 2021
                Jan-Mar 2021
                : 19
                : 1
                : 15593258211003798
                Affiliations
                [1 ]State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Ringgold 12582, universitySoochow University; , Suzhou, China
                [2 ]Ringgold 545455, universitySuzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine; , Suzhou, China
                [3 ]Department of Nutrition and Food Hygiene School of Public Health, Ringgold 12582, universitySoochow University; , Suzhou, China
                Author notes
                [*]Lin Zhao and Jia-Ying Xu, State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China. Email: zhaolin@ 123456suda.edu.cn ; xujiaying@ 123456suda.edu.cn
                Author information
                https://orcid.org/0000-0002-6920-9967
                https://orcid.org/0000-0002-5365-9779
                Article
                10.1177_15593258211003798
                10.1177/15593258211003798
                8020251
                ea2a209f-6af1-4be1-a2fe-96d458373693
                © The Author(s) 2021

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 24 February 2021
                : 24 February 2021
                : 24 February 2021
                Funding
                Funded by: the Natural Science Foundation of the Jiangsu Higher Education institutions of China, FundRef https://doi.org/10.13039/501100001809;
                Award ID: 18KJA310006
                Categories
                Original Article
                Custom metadata
                January-March 2021
                ts3

                camel milk,radiation,jejunum injury,inflammatory factors,antioxidant

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