GBDN Collaborators. International, regional, and nationwide burden of neurological problems, 1990–2016: a scientific evaluation for the International Burden of Illness Research 2016. Lancet Neurol. 2019;18:459–80.
Ahuja CS, Wilson JR, Nori S, Kotter MRN, Druschel C, Curt A, Fehlings MG. Traumatic spinal wire harm. Nat Rev Dis Primers. 2017;3:17018.
Badhiwala JH, Wilson JR, Fehlings MG. International burden of traumatic mind and spinal wire harm. Lancet Neurol. 2019;18:24–5.
Hu X, Li P, Guo Y, Wang H, Leak RK, Chen S, Gao Y, Chen J. Microglia/macrophage polarization dynamics reveal novel mechanism of harm growth after focal cerebral ischemia. Stroke. 2012;43:3063–70.
Zhang M, Wu X, Xu Y, He M, Yang J, Li J, Li Y, Ao G, Cheng J, Jia J. The cystathionine beta-synthase/hydrogen sulfide pathway contributes to microglia-mediated neuroinflammation following cerebral ischemia. Mind Behav Immun. 2017;66:332–46.
David S, Kroner A. Repertoire of microglial and macrophage responses after spinal wire harm. Nat Rev Neurosci. 2011;12:388–99.
Mosser DM, Edwards JP. Exploring the total spectrum of macrophage activation. Nat Rev Immunol. 2008;8:958–69.
Willenborg S, Lucas T, van Bathroom G, Knipper JA, Krieg T, Haase I, Brachvogel B, Hammerschmidt M, Nagy A, Ferrara N, et al. CCR2 recruits an inflammatory macrophage subpopulation important for angiogenesis in tissue restore. Blood. 2012;120:613–25.
Zajac E, Schweighofer B, Kupriyanova TA, Juncker-Jensen A, Minder P, Quigley JP, Deryugina EI. Angiogenic capability of M1- and M2-polarized macrophages is set by the degrees of TIMP-1 complexed with their secreted proMMP-9. Blood. 2013;122:4054–67.
Welser JV, Li L, Milner R. Microglial activation state exerts a biphasic affect on mind endothelial cell proliferation by regulating the steadiness of TNF and TGF-beta1. J Neuroinflamm. 2010;7:89.
Sorensen KK, McCourt P, Berg T, Crossley C, Le Couteur D, Wake Ok, Smedsrod B. The scavenger endothelial cell: a brand new participant in homeostasis and immunity. Am J Physiol Regul Integr Comp Physiol. 2012;303:R1217-1230.
Pober JS, Tellides G. Participation of blood vessel cells in human adaptive immune responses. Tendencies Immunol. 2012;33:49–57.
Chang YJ, Li YS, Wu CC, Wang KC, Huang TC, Chen Z, Chien S. Extracellular microRNA-92a mediates endothelial cell-macrophage communication. Arterioscler Thromb Vasc Biol. 2019;39:2492–504.
Milich LM, Ryan CB, Lee JK. The origin, destiny, and contribution of macrophages to spinal wire harm pathology. Acta Neuropathol. 2019;137:785–97.
He H, Xu J, Warren CM, Duan D, Li X, Wu L, Iruela-Arispe ML. Endothelial cells present an instructive area of interest for the differentiation and purposeful polarization of M2-like macrophages. Blood. 2012;120:3152–62.
Valadi H, Ekstrom Ok, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated switch of mRNAs and microRNAs is a novel mechanism of genetic alternate between cells. Nat Cell Biol. 2007;9:654–9.
Alexander M, Hu R, Runtsch MC, Kagele DA, Mosbruger TL, Tolmachova T, Seabra MC, Spherical JL, Ward DM, O’Connell RM. Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nat Commun. 2015;6:7321.
Thoms M, Thomson E, Bassler J, Gnadig M, Griesel S, Harm E. The exosome is recruited to RNA substrates by particular adaptor proteins. Cell. 2015;162:1029–38.
Njock MS, Cheng HS, Dang LT, Nazari-Jahantigh M, Lau AC, Boudreau E, Roufaiel M, Cybulsky MI, Schober A, Fish JE. Endothelial cells suppress monocyte activation by secretion of extracellular vesicles containing antiinflammatory microRNAs. Blood. 2015;125:3202–12.
Feng Z, Zhou J, Liu Y, Xia R, Li Q, Yan L, Chen Q, Chen X, Jiang Y, Chao G, et al. Epithelium- and endothelium-derived exosomes regulate the alveolar macrophages by focusing on RGS1 mediated calcium signaling-dependent immune response. Cell Demise Differ. 2021;28:2238–56.
Hellebrekers DM, Castermans Ok, Vire E, Dings RP, Hoebers NT, Mayo KH, Oude Egbrink MG, Molema G, Fuks F, van Engeland M, Griffioen AW. Epigenetic regulation of tumor endothelial cell anergy: silencing of intercellular adhesion molecule-1 by histone modifications. Most cancers Res. 2006;66:10770–7.
Manz XD, Szulcek R, Pan X, Symersky P, Dickhoff C, Majolee J, Kremer V, Michielon E, Jordanova ES, Radonic T, et al. Epigenetic modification of the VWF promotor drives platelet aggregation on the pulmonary endothelium in power thromboembolic pulmonary hypertension. Am J Respir Crit Care Med. 2022;205:806.
Inoue Ok, Ogonuki N, Kamimura S, Inoue H, Matoba S, Hirose M, Honda A, Miura Ok, Hada M, Hasegawa A, et al. Lack of H3K27me3 imprinting within the Sfmbt2 miRNA cluster causes enlargement of cloned mouse placentas. Nat Commun. 2020;11:2150.
Guo Z, Li C, Cao Y, Qin T, Jiang L, Xu Y, Li M, Luo Z, Hu J, Lu H. UTX/KDM6A deletion promotes the restoration of spinal wire harm by epigenetically triggering intrinsic neural regeneration. Mol Ther Strategies Clin Dev. 2021;20:337–49.
Ni S, Luo Z, Jiang L, Guo Z, Li P, Xu X, Cao Y, Duan C, Wu T, Li C, et al. UTX/KDM6A deletion promotes restoration of spinal wire harm by epigenetically regulating vascular regeneration. Mol Ther. 2019;27:2134–46.
Luo Z, Peng W, Xu Y, Xie Y, Liu Y, Lu H, Cao Y, Hu J. Exosomal OTULIN from M2 macrophages promotes the restoration of spinal wire accidents through stimulating Wnt/beta-catenin pathway-mediated vascular regeneration. Acta Biomater. 2021;136:519–32.
Théry C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell tradition supernatants and organic fluids. Curr Protoc Cell Biol. 2006. https://doi.org/10.1002/0471143030.cb0322s30.
Basso DM, Fisher LC, Anderson AJ, Jakeman LB, McTigue DM, Popovich PG. Basso Mouse Scale for locomotion detects variations in restoration after spinal wire harm in 5 widespread mouse strains. J Neurotrauma. 2006;23:635–59.
Schlag MG, Hopf R, Redl H. Serial recording of sensory, corticomotor, and brainstem-derived motor evoked potentials within the rat. Somatosens Mot Res. 2001;18:106–16.
Meng Q, Zhuang Y, Ying Z, Agrawal R, Yang X, Gomez-Pinilla F. Traumatic mind harm induces genome-wide transcriptomic, methylomic, and community perturbations in mind and blood predicting neurological problems. EBioMedicine. 2017;16:184–94.
Tay EXY, Chia Ok, Ong DST. Epigenetic plasticity and redox regulation of neural stem cell state and destiny. Free Radic Biol Med. 2021;170:116–30.
Murphy MD, Heller EA. Convergent actions of stress and stimulants through epigenetic regulation of neural circuitry. Tendencies Neurosci. 2022;45:955–67.
Hu J, Zeng L, Huang J, Wang G, Lu H. miR-126 promotes angiogenesis and attenuates irritation after contusion spinal wire harm in rats. Mind Res. 2015;1608:191–202.
Cao Y, Wu T-D, Wu H, Lang Y, Li D-Z, Ni S-F, Lu H-B, Hu J-Z. Synchrotron radiation micro-CT as a novel instrument to judge the impact of agomir-210 in a rat spinal wire harm mannequin. Mind Res. 2017;1655:55–65.
Wang Q, He Z, Huang M, Liu T, Wang Y, Xu H, Duan H, Ma P, Zhang L, Zamvil SS, et al. Vascular area of interest IL-6 induces various macrophage activation in glioblastoma by HIF-2α. Nat Commun. 2018;9:559.
Cohen M, Ben-Yehuda H, Porat Z, Raposo C, Gordon S, Schwartz M. Newly shaped endothelial cells regulate myeloid cell exercise following spinal wire harm through expression of CD200 ligand. J Neurosci. 2017;37:972–85.
Daidone M, Cataldi M, Pinto A, Tuttolomondo A. Non-coding RNAs and different determinants of neuroinflammation and endothelial dysfunction: regulation of gene expression within the acute part of ischemic stroke and potential therapeutic purposes. Neural Regen Res. 2021;16:2154–8.
Chen J, Xu X, Li Y, Li F, Zhang J, Xu Q, Chen W, Wei Y, Wang X. Kdm6a suppresses the choice activation of macrophages and impairs vitality expenditure in weight problems. Cell Demise Differ. 2021;28:1688–704.
Cribbs A, Hookway ES, Wells G, Lindow M, Obad S, Oerum H, Prinjha RK, Athanasou N, Sowman A, Philpott M, et al. Inhibition of histone H3K27 demethylases selectively modulates inflammatory phenotypes of pure killer cells. J Biol Chem. 2018;293:2422–37.
Kobatake Ok, Ikeda Ok-I, Nakata Y, Yamasaki N, Ueda T, Kanai A, Sentani Ok, Sera Y, Hayashi T, Koizumi M, et al. Kdm6a deficiency prompts inflammatory pathways, promotes M2 macrophage polarization, and causes bladder most cancers in cooperation with p53 dysfunction. Clin Most cancers Res. 2020;26:2065–79.
Li X, Zhang Q, Shi Q, Liu Y, Zhao Ok, Shen Q, Shi Y, Liu X, Wang C, Li N, et al. Demethylase Kdm6a epigenetically promotes IL-6 and IFN-β manufacturing in macrophages. J Autoimmun. 2017;80:85–94.
Wen Y, Chen X, Feng H, Wang X, Kang X, Zhao P, Zhao C, Wei Y. Kdm6a deficiency in microglia/macrophages epigenetically silences Lcn2 expression and reduces photoreceptor dysfunction in diabetic retinopathy. Metabolism. 2022;136: 155293.
Li M, Rong Z-J, Cao Y, Jiang L-Y, Zhong D, Li C-J, Sheng X-L, Hu J-Z, Lu H-B. Utx regulates the NF-κB signaling pathway of pure stem cells to modulate macrophage migration throughout spinal wire harm. J Neurotrauma. 2021;38:353–64.
Simeoli R, Montague Ok, Jones HR, Castaldi L, Chambers D, Kelleher JH, Vacca V, Pitcher T, Grist J, Al-Ahdal H, et al. Exosomal cargo together with microRNA regulates sensory neuron to macrophage communication after nerve trauma. Nat Commun. 2017;8:1778.
Kalani A, Tyagi A, Tyagi N. Exosomes: mediators of neurodegeneration, neuroprotection and therapeutics. Mol Neurobiol. 2014;49:590–600.
Barile L, Vassalli G. Exosomes: remedy supply instruments and biomarkers of illnesses. Pharmacol Ther. 2017;174:63–78.
Chen X, Liang H, Zhang J, Zen Ok, Zhang CY. Horizontal switch of microRNAs: molecular mechanisms and medical purposes. Protein Cell. 2012;3:28–37.
Fruhbeis C, Frohlich D, Kuo WP, Amphornrat J, Thilemann S, Saab AS, Kirchhoff F, Mobius W, Goebbels S, Nave KA, et al. Neurotransmitter-triggered switch of exosomes mediates oligodendrocyte-neuron communication. PLoS Biol. 2013;11: e1001604.
Choi DS, Kim DK, Kim YK, Gho YS. Proteomics, transcriptomics and lipidomics of exosomes and ectosomes. Proteomics. 2013;13:1554–71.
Tetta C, Ghigo E, Silengo L, Deregibus MC, Camussi G. Extracellular vesicles as an rising mechanism of cell-to-cell communication. Endocrine. 2013;44:11–9.
He S, Wu C, Xiao J, Li D, Solar Z, Li M. Endothelial extracellular vesicles modulate the macrophage phenotype: potential implications in atherosclerosis. Scand J Immunol. 2018;87: e12648.
Hu X, Leak RK, Shi Y, Suenaga J, Gao Y, Zheng P, Chen J. Microglial and macrophage polarization-new prospects for mind restore. Nat Rev Neurol. 2015;11:56–64.
Ding Y, Zhang D, Wang S, Zhang X, Yang J. Hematogenous macrophages: a brand new therapeutic goal for spinal wire harm. Entrance Cell Dev Biol. 2021;9: 767888.
Pan Y, Hui X, Hoo RLC, Ye D, Chan CYC, Feng T, Wang Y, Lam KSL, Xu A. Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to advertise obesity-induced adipose irritation. J Clin Investig. 2019;129:834–49.
Yin Z, Han Z, Hu T, Zhang S, Ge X, Huang S, Wang L, Yu J, Li W, Wang Y, et al. Neuron-derived exosomes with excessive miR-21-5p expression promoted polarization of M1 microglia in tradition. Mind, Behav, Immun. 2020;83:270–82.
Yin J, Zhao X, Chen X, Shen G. Emodin suppresses hepatocellular carcinoma progress by regulating macrophage polarization through microRNA-26a/remodeling progress issue beta 1/protein kinase B. Bioengineered. 2022;13:9548–63.
Abba ML, Patil N, Leupold JH, Moniuszko M, Utikal J, Niklinski J, Allgayer H. MicroRNAs as novel targets and instruments in most cancers remedy. Most cancers Lett. 2017;387:84–94.
Pouya FD, Rasmi Y, Gazouli M, Zografos E, Nemati M. MicroRNAs as therapeutic targets in breast most cancers metastasis. Drug Deliv Transl Res. 2022;12:1029–46.
Lei X, Jiao J. UTX impacts neural stem cell proliferation and differentiation by PTEN signaling. Stem Cell Experiences. 2018;10:1193–207.
Jiang Q, Huang X, Hu X, Shan Z, Wu Y, Wu G, Lei L. Histone demethylase KDM6A promotes somatic cell reprogramming by epigenetically regulating the PTEN and IL-6 sign pathways. Stem Cells. 2020;38:960–72.
Sahin E, Haubenwallner S, Kuttke M, Kollmann I, Halfmann A, Dohnal AM, Chen L, Cheng P, Hoesel B, Einwallner E, et al. Macrophage PTEN regulates expression and secretion of arginase I modulating innate and adaptive immune responses. J Immunol. 2014;193:1717–27.
Kral JB, Kuttke M, Schrottmaier WC, Birnecker B, Warszawska J, Wernig C, Paar H, Salzmann M, Sahin E, Brunner JS, et al. Sustained PI3K activation exacerbates BLM-induced lung fibrosis through activation of pro-inflammatory and pro-fibrotic pathways. Sci Rep. 2016;6:23034.
Pfeifer M, Grau M, Lenze D, Wenzel S-S, Wolf A, Wollert-Wulf B, Dietze Ok, Nogai H, Storek B, Madle H, et al. PTEN loss defines a PI3K/AKT pathway-dependent germinal heart subtype of diffuse giant B-cell lymphoma. Proc Natl Acad Sci USA. 2013;110:12420–5.
Kaneda MM, Messer KS, Ralainirina N, Li H, Leem CJ, Gorjestani S, Woo G, Nguyen AV, Figueiredo CC, Foubert P, et al. PI3Kγ is a molecular change that controls immune suppression. Nature. 2016;539:437–42.
Li Z, Jiang H, Xie W, Zhang Z, Smrcka AV, Wu D. Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant-mediated sign transduction. Science. 2000;287:1046–9.
Schmid MC, Avraamides CJ, Dippold HC, Franco I, Foubert P, Ellies LG, Acevedo LM, Manglicmot JRE, Music X, Wrasidlo W, et al. Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kγ, a single convergent level selling tumor irritation and development. Most cancers Cell. 2011;19:715–27.
Kaneda MM, Cappello P, Nguyen AV, Ralainirina N, Hardamon CR, Foubert P, Schmid MC, Solar P, Mose E, Bouvet M, et al. Macrophage PI3Kγ drives pancreatic ductal adenocarcinoma development. Most cancers Discov. 2016;6:870–85.
Rocher C, Singla DK. SMAD-PI3K-Akt-mTOR pathway mediates BMP-7 polarization of monocytes into M2 macrophages. PLoS ONE. 2013;8: e84009.
Covarrubias AJ, Aksoylar HI, Horng T. Management of macrophage metabolism and activation by mTOR and Akt signaling. Semin Immunol. 2015;27:286–96.
Weichhart T, Hengstschläger M, Linke M. Regulation of innate immune cell perform by mTOR. Nat Rev Immunol. 2015;15:599–614.