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- Yusuf, D, et al.
(author)
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The transcription factor encyclopedia
- 2012
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906. ; 13:3, s. R24-
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Journal article (peer-reviewed)
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| 226. |
- Zhang, W, et al.
(author)
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INKILN is a novel long noncoding RNA promoting vascular smooth muscle inflammation via scaffolding MKL1 and USP10
- 2023
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In: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Journal article (other academic/artistic)abstract
- BackgroundActivation of vascular smooth muscle cells (VSMCs) inflammation is vital to initiate vascular disease. However, the role of human-specific long noncoding RNAs (lncRNAs) in VSMC inflammation is poorly understood.MethodsBulk RNA-seq in differentiated human VSMCs revealed a novel human-specific lncRNA calledINflammatory MKL1InteractingLongNoncoding RNA (INKILN).INKILNexpression was assessed in multiple in vitro and ex vivo models of VSMC phenotypic modulation and human atherosclerosis and abdominal aortic aneurysm (AAA) samples. The transcriptional regulation ofINKILNwas determined through luciferase reporter system and chromatin immunoprecipitation assay. Both loss- and gain-of-function approaches and multiple RNA-protein and protein-protein interaction assays were utilized to uncover the role ofINKILNin VSMC proinflammatory gene program and underlying mechanisms. Bacterial Artificial Chromosome (BAC) transgenic (Tg) mice were utilized to studyINKLINexpression and function in ligation injury-induced neointimal formation.ResultsINKILNexpression is downregulated in contractile VSMCs and induced by human atherosclerosis and abdominal aortic aneurysm.INKILNis transcriptionally activated by the p65 pathway, partially through a predicted NF-κB site within its proximal promoter.INKILNactivates the proinflammatory gene expression in cultured human VSMCs and ex vivo cultured vessels. Mechanistically,INKILNphysically interacts with and stabilizes MKL1, a key activator of VSMC inflammation through the p65/NF-κB pathway.INKILNdepletion blocks ILIβ-induced nuclear localization of both p65 and MKL1. Knockdown ofINKILNabolishes the physical interaction between p65 and MKL1, and the luciferase activity of an NF-κB reporter. Further,INKILNknockdown enhances MKL1 ubiquitination, likely through the reduced physical interaction with the deubiquitinating enzyme, USP10.INKILNis induced in injured carotid arteries and exacerbates ligation injury-induced neointimal formation in BAC Tg mice.ConclusionsThese findings elucidate an important pathway of VSMC inflammation involving anINKILN/MKL1/USP10 regulatory axis. Human BAC Tg mice offer a novel and physiologically relevant approach for investigating human-specific lncRNAs under vascular disease conditions.
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| 227. |
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| 228. |
- Zhang, ZZ, et al.
(author)
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Alcohol, Coffee, and Milk Intake in Relation to Epilepsy Risk
- 2022
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 14:6
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Journal article (peer-reviewed)abstract
- Alcohol, coffee and milk intakes have been explored in relation to epilepsy risk in observational studies; however, the results were not consistent. We performed a Mendelian randomisation (MR) study to evaluate the causality of these relationships. Genetic variants associated with alcohol, coffee and milk intake were adopted as instrumental variables. We obtained the summary data of epilepsy from the International League Against Epilepsy (ILAE) Consortium (15,212 cases and 29,677 controls) and FinnGen consortium (4588 cases and 144,780 controls). Genetically predicted alcohol intake was associated with a higher risk of epilepsy in the ILAE Consortium (odds ratio (OR): 1.22, 95% confidence intervals (CI): 1.02–1.45). The association in the FinnGen consortium remained consistent in direction. Combined analysis of ILAE and FinnGen databases further indicated that genetically predicted alcohol intake was associated with a higher risk of epilepsy (OR = 1.24; 95% CI, 1.06–1.47, p = 0.009). Genetically predicted coffee intake was not related to epilepsy risk, while higher genetically predicted milk intake was related to a lower risk of epilepsy (OR = 0.957; 95% CI, 0.917–0.999, p = 0.044). Our results suggest a detrimental effect of alcohol intake on the risk of epilepsy, while milk intake might be associated with a decreased risk of epilepsy.
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