{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:26:22Z","timestamp":1790961982206,"version":"4.1.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T00:00:00Z","timestamp":1660348800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T00:00:00Z","timestamp":1660348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Autologous stem cell therapy is a promising strategy for cardiovascular diseases including diabetic cardiomyopathy (DCM), but conclusions from clinical trials were compromised. We assumed that diabetes might induce the dysfunction of stem cells and thus limit its therapeutic effect. This study aimed to compare the effect of diabetes and nondiabetes-derived bone marrow mesenchymal stem cells (BMSCs) transplantation on DCM and explored the potential mechanism.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Rats with diabetes were induced using high-fat diets and streptozotocin (STZ) injection. BMSCs harvested from diabetic and nondiabetic rats were infused into DCM rats, and the effects on the heart were identified by echocardiography and histopathology. The inhibition or overexpression of SAHH in nondiabetic and diabetic BMSCs was used to confirm its key role in stem cell activity and cardiac therapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Compared with normal BMSCs, the therapeutic effects of diabetic rat-derived stem cells on improving cardiac function and adverse remodeling were significantly attenuated. In vitro, diabetic BMSCs had lower cell viability and paracrine function than nondiabetic BMSCs. It was further found that diabetic BMSCs had obvious mitochondrial oxidative stress damage and S-adenosylhomocysteine (SAH) accumulation due to S-adenosylhomocysteine hydrolase (SAHH) deficiency. SAHH inhibition by adenosine dialdehyde (ADA) or shSAHH plasmid in normal BMSCs significantly reduced the favorable effects on endothelial cell proliferation and tube-forming capacity. In contrast, SAHH overexpression in diabetic BMSCs significantly improved cellular activity and paracrine function. Transplantation of BMSCs with SAHH overexpression improved cardiac adverse remodeling and angiogenesis. Activation of the Nrf2 signaling pathway may be one of the key mechanisms of SAHH-mediated improvement of stem cell viability and cardiac repair.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Diabetes leads to compromised bioactivity and repair capacity of BMSCs. Our study suggests that SAHH activation may improve the cardioprotective effect of autologous transplantation of diabetes-derived BMSCs on patients with DCM.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                <jats:p>Diabetes induced the inhibition of S-adenosylhomocysteine (SAH) expression and aging phenotype in BMSCs and thus decreased the cell viability and paracrine function. Compared with normal BMSCs, the therapeutic effects of diabetic rat-derived BMSCs on improving cardiac function and adverse remodeling were significantly attenuated. SAHH overexpression in diabetic BMSCs significantly rescued cellular function partly via activating Nrf2\/HO-1 signal. Transplantation of diabetic BMSCs with SAHH overexpression improved angiogenesis and cardiac adverse remodeling in rats.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13287-022-03099-1","type":"journal-article","created":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T06:02:45Z","timestamp":1660370565000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Insufficient S-adenosylhomocysteine hydrolase compromises the beneficial effect of diabetic BMSCs on diabetic cardiomyopathy"],"prefix":"10.1186","volume":"13","author":[{"given":"Ying","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kegong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,13]]},"reference":[{"key":"3099_CR1","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/nrendo.2017.151","volume":"14","author":"Y Zheng","year":"2018","unstructured":"Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14:88\u201398.","journal-title":"Nat Rev Endocrinol."},{"key":"3099_CR2","doi-asserted-by":"publisher","first-page":"235","DOI":"10.2337\/dc19-0550","volume":"43","author":"A Brouwer","year":"2020","unstructured":"Brouwer A, van Raalte DH, Rutters F, Elders P, Snoek FJ, Beekman A, et al. Sleep and HbA1c in patients with type 2 diabetes: which sleep characteristics matter most? Diabetes Care. 2020;43:235\u201343.","journal-title":"Diabetes Care."},{"key":"3099_CR3","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1161\/CIRCRESAHA.118.314665","volume":"124","author":"WH Dillmann","year":"2019","unstructured":"Dillmann WH. Diabetic cardiomyopathy. Circ Res. 2019;124:1160\u20132.","journal-title":"Circ Res."},{"key":"3099_CR4","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/s41569-020-0339-2","volume":"17","author":"Y Tan","year":"2020","unstructured":"Tan Y, Zhang Z, Zheng C, Wintergerst KA, Keller BB, Cai L. Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence. Nat Rev Cardiol. 2020;17:585\u2013607.","journal-title":"Nat Rev Cardiol."},{"key":"3099_CR5","first-page":"784","volume":"8","author":"X Fu","year":"2019","unstructured":"Fu X, Liu G, Halim A, Ju Y, Luo Q, Song AG. Mesenchymal stem cell migration and tissue repair. Cells (Basel). 2019;8:784.","journal-title":"Cells (Basel)."},{"key":"3099_CR6","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1161\/CIRCRESAHA.117.310712","volume":"121","author":"J Bartolucci","year":"2017","unstructured":"Bartolucci J, Verdugo FJ, Gonzalez PL, Larrea RE, Abarzua E, Goset C, et al. Safety and efficacy of the intravenous infusion of umbilical cord mesenchymal stem cells in patients with heart failure: a phase 1\/2 randomized controlled trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]). Circ Res. 2017;121:1192\u2013204.","journal-title":"Circ Res."},{"key":"3099_CR7","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1093\/bmb\/ldw059","volume":"121","author":"H Yu","year":"2017","unstructured":"Yu H, Lu K, Zhu J, Wang J. Stem cell therapy for ischemic heart diseases. Br Med Bull. 2017;121:135\u201354.","journal-title":"Br Med Bull."},{"key":"3099_CR8","doi-asserted-by":"publisher","first-page":"608","DOI":"10.2174\/1574888X15666200309144906","volume":"16","author":"P Liang","year":"2021","unstructured":"Liang P, Ye F, Hou CC, Pi L, Chen F. Mesenchymal stem cell therapy for patients with ischemic heart failure- past, present, and future. Curr Stem Cell Res Ther. 2021;16:608\u201321.","journal-title":"Curr Stem Cell Res Ther."},{"key":"3099_CR9","doi-asserted-by":"publisher","first-page":"S14","DOI":"10.12968\/jowc.2021.30.Sup4.S14","volume":"30","author":"JH Gong","year":"2021","unstructured":"Gong JH, Dong JY, Xie T, Zhao Q, Lu SL. Different therapeutic effects between diabetic and non-diabetic adipose stem cells in diabetic wound healing. J Wound Care. 2021;30:S14-23.","journal-title":"J Wound Care."},{"key":"3099_CR10","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/j.stem.2018.05.016","volume":"22","author":"JB Sneddon","year":"2018","unstructured":"Sneddon JB, Tang Q, Stock P, Bluestone JA, Roy S, Desai T, et al. Stem cell therapies for treating diabetes: progress and remaining challenges. Cell Stem Cell. 2018;22:810\u201323.","journal-title":"Cell Stem Cell."},{"key":"3099_CR11","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1186\/s13287-019-1474-8","volume":"10","author":"S Yu","year":"2019","unstructured":"Yu S, Cheng Y, Zhang L, Yin Y, Xue J, Li B, et al. Treatment with adipose tissue-derived mesenchymal stem cells exerts anti-diabetic effects, improves long-term complications, and attenuates inflammation in type 2 diabetic rats. Stem Cell Res Ther. 2019;10:333.","journal-title":"Stem Cell Res Ther."},{"key":"3099_CR12","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1016\/j.athoracsur.2019.05.094","volume":"108","author":"KS Ayyat","year":"2019","unstructured":"Ayyat KS, Argawi A, Mende M, Steinhoff G, Borger MA, Deebis AM, et al. Combined coronary artery bypass surgery with bone marrow stem cell transplantation: Are we there yet? Ann Thorac Surg. 2019;108:1913\u201321.","journal-title":"Ann Thorac Surg."},{"key":"3099_CR13","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1093\/eurheartj\/ehp536","volume":"31","author":"S Grajek","year":"2010","unstructured":"Grajek S, Popiel M, Gil L, Breborowicz P, Lesiak M, Czepczynski R, et al. Influence of bone marrow stem cells on left ventricle perfusion and ejection fraction in patients with acute myocardial infarction of anterior wall: randomized clinical trial: Impact of bone marrow stem cell intracoronary infusion on improvement of microcirculation. Eur Heart J. 2010;31:691\u2013702.","journal-title":"Eur Heart J."},{"key":"3099_CR14","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1093\/cvr\/cvaa027","volume":"116","author":"M Prasad","year":"2020","unstructured":"Prasad M, Corban MT, Henry TD, Dietz AB, Lerman LO, Lerman A. Promise of autologous CD34+ stem\/progenitor cell therapy for treatment of cardiovascular disease. Cardiovasc Res. 2020;116:1424\u201333.","journal-title":"Cardiovasc Res."},{"key":"3099_CR15","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/s41419-020-2367-6","volume":"11","author":"SK Yadav","year":"2020","unstructured":"Yadav SK, Kambis TN, Kar S, Park SY, Mishra PK. MMP9 mediates acute hyperglycemia-induced human cardiac stem cell death by upregulating apoptosis and pyroptosis in vitro. Cell Death Dis. 2020;11:186.","journal-title":"Cell Death Dis."},{"key":"3099_CR16","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.3390\/ijms18102147","volume":"18","author":"S Fujimaki","year":"2017","unstructured":"Fujimaki S, Kuwabara T. Diabetes-induced dysfunction of mitochondria and stem cells in skeletal muscle and the nervous system. Int J Mol Sci. 2017;18:2147.","journal-title":"Int J Mol Sci."},{"key":"3099_CR17","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s13287-020-01633-7","volume":"11","author":"L Jin","year":"2020","unstructured":"Jin L, Zhang J, Deng Z, Liu J, Han W, Chen G, et al. Mesenchymal stem cells ameliorate myocardial fibrosis in diabetic cardiomyopathy via the secretion of prostaglandin E2. Stem Cell Res Ther. 2020;11:122.","journal-title":"Stem Cell Res Ther."},{"key":"3099_CR18","doi-asserted-by":"publisher","first-page":"689","DOI":"10.2337\/db19-1009","volume":"69","author":"RA Kowluru","year":"2020","unstructured":"Kowluru RA. Retinopathy in a diet-induced type 2 diabetic rat model and role of epigenetic modifications. Diabetes. 2020;69:689\u201398.","journal-title":"Diabetes."},{"key":"3099_CR19","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1186\/s12967-019-1999-8","volume":"17","author":"L Jin","year":"2019","unstructured":"Jin L, Deng Z, Zhang J, Yang C, Liu J, Han W, et al. Mesenchymal stem cells promote type 2 macrophage polarization to ameliorate the myocardial injury caused by diabetic cardiomyopathy. J Transl Med. 2019;17:251.","journal-title":"J Transl Med."},{"key":"3099_CR20","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.837780","volume":"9","author":"K Chen","year":"2022","unstructured":"Chen K, Bai L, Lu J, Chen W, Liu C, Guo E, et al. Human decidual mesenchymal stem cells obtained from early pregnancy improve cardiac revascularization postinfarction by activating ornithine metabolism. Front Cardiovasc Med. 2022;9: 837780.","journal-title":"Front Cardiovasc Med."},{"key":"3099_CR21","doi-asserted-by":"publisher","first-page":"3346","DOI":"10.1111\/jcmm.15008","volume":"24","author":"X Liu","year":"2020","unstructured":"Liu X, Xie J, Yang L, Li Y, He Y, Liu Z, et al. Bone marrow mesenchymal stem cells enhance autophagy and help protect cells under hypoxic and retinal detachment conditions. J Cell Mol Med. 2020;24:3346\u201358.","journal-title":"J Cell Mol Med."},{"key":"3099_CR22","doi-asserted-by":"publisher","first-page":"2260","DOI":"10.1161\/CIRCULATIONAHA.118.036336","volume":"139","author":"Y Xiao","year":"2019","unstructured":"Xiao Y, Xia J, Cheng J, Huang H, Zhou Y, Yang X, et al. Inhibition of S-adenosylhomocysteine hydrolase induces endothelial dysfunction via epigenetic regulation of p66shc-mediated oxidative stress pathway. Circulation. 2019;139:2260\u201377.","journal-title":"Circulation."},{"key":"3099_CR23","doi-asserted-by":"publisher","first-page":"3880","DOI":"10.18632\/aging.102857","volume":"12","author":"X Xing","year":"2020","unstructured":"Xing X, Li Z, Yang X, Li M, Liu C, Pang Y, et al. Adipose-derived mesenchymal stem cells-derived exosome-mediated microRNA-342-5p protects endothelial cells against atherosclerosis. Aging (Albany NY). 2020;12:3880\u201398.","journal-title":"Aging (Albany NY)."},{"key":"3099_CR24","first-page":"5950195","volume":"2020","author":"N Liu","year":"2020","unstructured":"Liu N, Li Y, Nan W, Zhou W, Huang J, Li R, et al. Interaction of TPPP3 with VDAC1 promotes endothelial injury through activation of reactive oxygen species. Oxid Med Cell Longev. 2020;2020:5950195.","journal-title":"Oxid Med Cell Longev."},{"key":"3099_CR25","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1161\/CIRCRESAHA.120.316509","volume":"127","author":"X Fang","year":"2020","unstructured":"Fang X, Cai Z, Wang H, Han D, Cheng Q, Zhang P, et al. Loss of cardiac ferritin h facilitates cardiomyopathy via slc7a11-mediated ferroptosis. Circ Res. 2020;127:486\u2013501.","journal-title":"Circ Res."},{"key":"3099_CR26","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/s41418-019-0372-z","volume":"27","author":"X Zhang","year":"2020","unstructured":"Zhang X, Hu C, Kong CY, Song P, Wu HM, Xu SC, et al. FNDC5 alleviates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via activating AKT. Cell Death Differ. 2020;27:540\u201355.","journal-title":"Cell Death Differ."},{"key":"3099_CR27","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1016\/j.bbadis.2018.04.009","volume":"1865","author":"S Wang","year":"2019","unstructured":"Wang S, Zhao Z, Fan Y, Zhang M, Feng X, Lin J, et al. Mst1 inhibits Sirt3 expression and contributes to diabetic cardiomyopathy through inhibiting Parkin-dependent mitophagy. Biochim Biophys Acta Mol Basis Dis. 2019;1865:1905\u201314.","journal-title":"Biochim Biophys Acta Mol Basis Dis."},{"key":"3099_CR28","first-page":"9983725","volume":"2021","author":"R Luo","year":"2021","unstructured":"Luo R, Zhao L, Li S, Chen P, Wang YuH, et al. Curcumin alleviates palmitic acid-induced LOX-1 upregulation by suppressing endoplasmic reticulum stress in HUVECs. Biomed Res Int. 2021;2021:9983725.","journal-title":"Biomed Res Int."},{"key":"3099_CR29","doi-asserted-by":"publisher","first-page":"5132","DOI":"10.1111\/jcmm.13802","volume":"22","author":"S Wang","year":"2018","unstructured":"Wang S, Zhao Z, Feng X, Cheng Z, Xiong Z, Wang T, et al. Melatonin activates Parkin translocation and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 inhibition. J Cell Mol Med. 2018;22:5132\u201344.","journal-title":"J Cell Mol Med."},{"key":"3099_CR30","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1100\/tsw.2011.137","volume":"11","author":"MH Nguyen","year":"2011","unstructured":"Nguyen MH, Cheng M, Koh TJ. Impaired muscle regeneration in ob\/ob and db\/db mice. Sci World J. 2011;11:1525\u201335.","journal-title":"Sci World J"},{"key":"3099_CR31","first-page":"6","volume":"8","author":"S Fujimaki","year":"2016","unstructured":"Fujimaki S, Wakabayashi T, Asashima M, Takemasa T, Kuwabara T. Treadmill running induces satellite cell activation in diabetic mice. Biochem Biophys Rep. 2016;8:6\u201313.","journal-title":"Biochem Biophys Rep."},{"key":"3099_CR32","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1161\/CIRCRESAHA.119.314951","volume":"125","author":"KM Borow","year":"2019","unstructured":"Borow KM, Yaroshinsky A, Greenberg B, Perin EC. Phase 3 DREAM-HF trial of mesenchymal precursor cells in chronic heart failure. Circ Res. 2019;125:265\u201381.","journal-title":"Circ Res."},{"key":"3099_CR33","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.trsl.2015.09.004","volume":"166","author":"J Tashiro","year":"2015","unstructured":"Tashiro J, Elliot SJ, Gerth DJ, Xia X, Pereira-Simon S, Choi R, et al. Therapeutic benefits of young, but not old, adipose-derived mesenchymal stem cells in a chronic mouse model of bleomycin-induced pulmonary fibrosis. Transl Res. 2015;166:554\u201367.","journal-title":"Transl Res."},{"key":"3099_CR34","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.neurobiolaging.2021.11.001","volume":"110","author":"O Binyamin","year":"2022","unstructured":"Binyamin O, Frid K, Keller G, Saada A, Gabizon R. Comparing anti-aging hallmark activities of Metformin and Nano-PSO in a mouse model of genetic Creutzfeldt-Jakob Disease. Neurobiol Aging. 2022;110:77\u201387.","journal-title":"Neurobiol Aging."},{"key":"3099_CR35","doi-asserted-by":"publisher","first-page":"102033","DOI":"10.1016\/j.redox.2021.102033","volume":"45","author":"X Dai","year":"2021","unstructured":"Dai X, Liao R, Liu C, Liu S, Huang H, Liu J, et al. Epigenetic regulation of TXNIP-mediated oxidative stress and NLRP3 inflammasome activation contributes to SAHH inhibition-aggravated diabetic nephropathy. Redox Biol. 2021;45:102033.","journal-title":"Redox Biol."},{"key":"3099_CR36","doi-asserted-by":"publisher","first-page":"11837","DOI":"10.1111\/jcmm.15800","volume":"24","author":"L Bai","year":"2020","unstructured":"Bai L, Sun L, Chen W, Liu KY, Zhang CF, Wang F, et al. Evidence for the existence of CD34(+) angiogenic stem cells in human first-trimester decidua and their therapeutic for ischaemic heart disease. J Cell Mol Med. 2020;24:11837\u201348.","journal-title":"J Cell Mol Med."}],"container-title":["Stem Cell Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-022-03099-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-022-03099-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-022-03099-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T18:03:48Z","timestamp":1660413828000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-03099-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,13]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["3099"],"URL":"https:\/\/doi.org\/10.1186\/s13287-022-03099-1","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,13]]},"assertion":[{"value":"5 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Procedures involving animals and their care were conducted in conformity with the revised guidelines (Animals Act 1986) and were approved by the Committee on Animal Care of Harbin Medical University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors give their full consent to publish the present article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"418"}}