HECT domain E3 ubiquitin ligase 1 ( HECTD1) has been shown to be involved in mediating epithelial-mesenchymal transition (EMT) and in regulating the development of cervical cancer. 18 We found that circUCK2 and FUS have binding sites through starBase ( ) online predictions, but the regulatory mechanism of circUCK2 and FUS in IS is not yet clear. 17 FUS expressions are downregulated in the mouse heart after myocardial infarction (MI), and circFndc3b combines with FUS to regulate endothelial cell apoptosis and angiogenesis. FUS can participate in the control of reverse splicing events that lead to formation of circRNA. 16 Fused in sarcoma (FUS) is an RBP that is related to splicing regulation. 15 For example, circ_cIARS interacts with ALKBH5 to regulate autophagy and ferroptosis in liver cancer cells. Some specific circRNAs have been shown to regulate the expressions of downstream host genes by interacting with RBPs. RBPs are a class of proteins that bind to double-stranded or single-stranded RNA and play a vital role in RNA-related regulation. 14 Therefore, it is necessary to demonstrate the temporal relationship between circUCK2 and EndoMT and how this process can be beneficial in IS. Upregulation of circUCK2 can reduce neuronal damage, thereby contributing to neuroprotection. CircUCK2, a newly discovered circRNA, is expressed at low levels in IS patients. 13 CircRNAs are found in high levels in the brain and central nervous system. CircRNAs have the characteristics of tissue-specific expression and participate in regulating physiological and pathophysiological processes mainly through sponge adsorption of miRNA or interaction with RNA binding protein (RBP). 12 These studies suggest that inhibition of EndoMT may play an important role in protecting the BBB after IS.Ĭircular RNA (circRNA) is a type of noncoding RNA with a stable circular structure. confirmed that EndoMT may cause BBB damage in multiple sclerosis of the brain. 9 EndoMT is a dynamic cellular process that may occur in adult tissues and is associated with a variety of diseases. 8 Endothelial-mesenchymal transition (EndoMT) is closely related to BBB dysfunction. 7 The inflammatory response after stroke is mainly caused by destruction of the blood–brain barrier (BBB), which causes an increase in inflammatory factors and immune infiltration, ultimately leading to neuronal damage. One of the main pathological events occurring after IS is inflammation, which can lead to brain tissue damage. 5, 6 Therefore, new treatments for IS still need to be explored continuously. 4 However, existing methods to treat IS still have many limitations, including inflammation, oxidative stress reperfusion injury and the short-term limitations of the treatment window. 3 Intravenous thrombolysis and mechanical thrombectomy within 4–6 h of stroke are the standard treatments for IS. 2 IS is mainly an infarction of the brain, spinal cord or retina caused by arterial occlusion. 1 Among them, the risk of ischemic stroke (IS) exceeds that of hemorrhagic stroke, and the worldwide incidence of IS is increasing year by year. Stroke causes high adult mortality and long-term disability and places massive economic burdens on the patient families and social medicine.
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