{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough the provided abstracts offer extensive insights into the regulation and adaptation of the ubiquitin–proteasome system (UPS) under various cellular stresses—including endotoxin‐induced inflammatory signaling in macrophages—they do not report any specific role for MIR4455. For example, stimulation of mouse macrophages with LPS was shown to differentially trigger proteasome activities that govern the secretion of mediators such as nitric oxide and tumor necrosis factor–α, yet no evidence is presented linking MIR4455 to these events."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSimilarly, studies investigating the cardiac responses to pressure overload and the associated remodeling of UPS activity have delineated how proteasome inhibition or enhanced proteasome maturation influences hypertrophy and myocardial function. These findings, together with investigations into the maturation of proteasome complexes in inflammatory conditions, underscore the critical role of proteasomal regulation in cellular adaptation. However, in these contexts no mention is made of MIR4455 or any putative involvement of this microRNA in modulating proteasomal function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional work has highlighted neuroprotective strategies whereby activation of the P2Y2 receptor enhances specific proteasome activities in the brain, contributing to cellular resilience during UPS impairment. Even though these studies detail mechanisms by which extracellular nucleotides modulate proteasome subunit expression and activity to confer neuroprotection, none of the surveyed results identify any functional contribution of MIR4455. Thus, based on the evidence contained in these abstracts, MIR4455 does not appear to be involved in the described regulatory processes of the UPS."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Julia Reis, Xiu Qin Guan, Alexei F Kisselev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LPS-induced formation of immunoproteasomes: TNF-α and nitric oxide production are regulated by altered composition of proteasome-active sites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biochem Biophys (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12013-011-9182-8"}], "href": "https://doi.org/10.1007/s12013-011-9182-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21455682"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21455682"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mark J Ranek, Hanqiao Zheng, Wei Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetically induced moderate inhibition of 20S proteasomes in cardiomyocytes facilitates heart failure in mice during systolic overload."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Cardiol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yjmcc.2015.06.014"}], "href": "https://doi.org/10.1016/j.yjmcc.2015.06.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26116868"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26116868"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Thorsten Joeris, Nicole Schmidt, David Ermert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The proteasome system in infection: impact of β5 and LMP7 on composition, maturation and quantity of active proteasome complexes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0039827"}], "href": "https://doi.org/10.1371/journal.pone.0039827"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22768135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22768135"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Laura de Diego-García, Mercedes Ramírez-Escudero, Álvaro Sebastián-Serrano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of proteasome activity by P2Y"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "2"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": " receptor underlies the neuroprotective effects of extracellular nucleotides."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Basis Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2016.10.012"}], "href": "https://doi.org/10.1016/j.bbadis.2016.10.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27768902"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27768902"}]}]}]}