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      Serum irisin associates with breast cancer to spinal metastasis

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          Abstract

          The aim of this study was to determine whether the serum level of irisin can be a candidate to predict the spinal metastasis in patients with breast cancer.

          In a cross-sectional study, 148 patients were recruited. Of those, 53 (35.8%) had spinal metastasis. The baseline characteristics were compared by status of spinal metastasis. Multiple logistic regression analysis was used to determine whether the serum irisin can be a candidate for predicting breast cancer to spinal metastasis. The correlation coefficient analysis was used to confirm the correlation between the serum irisin and lipid metabolic parameters and body mass index (BMI), respectively.

          The serum irisin was higher in patients without spinal metastasis (7.60 ± 3.80). Multivariable analysis showed that the serum irisin was protective to the presence of spinal metastasis in patients with breast cancer after adjustments of age and BMI (odds ratio, 0.873; 95% confidence interval, 0.764–0.999). Furthermore, there was a positive correlation between the serum irisin and BMI ( r = 0.263). The patients with metabolisc syndrome (MetS) had a higher level in serum irisin. In addition, the higher numbers of MetS components were associated with higher serum irisin.

          Higher serum irisin can be a protective factor of spinal metastasis in patients with breast cancer. The BMI is positively associated with the serum level of irisin. Furthermore, patients with MetS tended to have a higher level of serum irisin.

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          Most cited references34

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          Exercise-induced myokines and their role in chronic diseases.

          Physical inactivity has recently been identified as a major and independent risk factor for the development of dementia and cognitive decline. In addition to the effect of exercise with regard to protection against neurodegenerative diseases, it is well-established that physical inactivity increases the risk of type 2 diabetes, cardiovascular diseases (CVD), colon cancer and postmenopausal breast cancer. These diseases constitute a network of related diseases, also called "the diseasome of physical inactivity". In this review, physical inactivity is given the central role as an independent and strong risk factor for accumulation of visceral fat and consequently the activation of a network of systemic inflammatory pathways, which promote development of neurodegeneration as well as insulin resistance, atherosclerosis, and tumour growth. The recent finding that muscles produce and release myokines provides a conceptual basis for understanding some of the molecular mechanisms underlying organ cross talk, including muscle-fat cross talk. Accumulating data suggest that contracting skeletal muscles release myokines, which may work in a hormone-like fashion, exerting specific endocrine effects on visceral fat or mediating direct anti-inflammatory effects. Other myokines work locally within the muscle via paracrine mechanisms, exerting their effects on signalling pathways involved in fat oxidation. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Effects of the exercise-inducible myokine irisin on malignant and non-malignant breast epithelial cell behavior in vitro.

            Exercise has been shown to reduce risk and improve prognosis of several types of cancers. Irisin is a myokine linked to exercise and lean body mass, which is thought to favorably alter metabolism systemically, potentially providing benefit for metabolic disease (including cancer). We evaluated the effects of various concentrations of irisin (with and without post-translational modifications) on malignant and non-malignant breast epithelial cell number, migration and viability. Irisin significantly decreased cell number, migration and viability in malignant MDA-MB-231 cells, without affecting non-malignant MCF-10a cells. Moreover, irisin enhanced the cytotoxic effect of doxorubicin (Dox) when added to a wide spectrum of irisin concentrations in the malignant cell type (with simultaneous reduction in Dox uptake), which was not observed in non-malignant MCF-10a cells. Additionally, we found that irisin decreases malignant cell viability in part through stimulation of caspase activity leading to apoptotic death. Interestingly, we found that irisin suppresses NFκB activation, an opposite effect of other myokines such as tumor necrosis factor alpha (TNF-α). Our observations suggest that irisin may offer therapeutic benefits for breast cancer prevention and treatment possibly through an anti-inflammatory response, induction of apoptotic cell death, or through enhanced tumor sensitivity to common antineoplastic agents such as Dox.
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              Irisin Enhances Osteoblast Differentiation In Vitro

              It has been recently demonstrated that exercise activity increases the expression of the myokine Irisin in skeletal muscle, which is able to drive the transition of white to brown adipocytes, likely following a phenomenon of transdifferentiation. This new evidence supports the idea that muscle can be considered an endocrine organ, given its ability to target adipose tissue by promoting energy expenditure. In accordance with these new findings, we hypothesized that Irisin is directly involved in bone metabolism, demonstrating its ability to increase the differentiation of bone marrow stromal cells into mature osteoblasts. Firstly, we confirmed that myoblasts from mice subjected to 3 weeks of free wheel running increased Irisin expression compared to nonexercised state. The conditioned media (CM) collected from myoblasts of exercised mice induced osteoblast differentiation in vitro to a greater extent than those of mice housed in resting conditions. Furthermore, the differentiated osteoblasts increased alkaline phosphatase and collagen I expression by an Irisin-dependent mechanism. Our results show, for the first time, that Irisin directly targets osteoblasts, enhancing their differentiation. This finding advances notable perspectives in future studies which could satisfy the ongoing research of exercise-mimetic therapies with anabolic action on the skeleton.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                April 2018
                27 April 2018
                : 97
                : 17
                : e0524
                Affiliations
                Department of Orthopedics, Hong Hui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an, China.
                Author notes
                []Correspondence: Ding-jun Hao, Department of Orthopedics, Hong Hui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an 710054, China (e-mail: hdjpaper@ 1234562980.com ).
                Article
                MD-D-17-06428 00524
                10.1097/MD.0000000000010524
                5944558
                29703023
                0ddc190f-4e5c-4be8-8856-98453105e8aa
                Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                : 17 October 2017
                : 3 January 2018
                : 29 March 2018
                Categories
                5750
                Research Article
                Observational Study
                Custom metadata
                TRUE

                breast cancer,cross-sectional study,metabolic syndrome,serum irisin,spinal metastasis

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