The Experts below are selected from a list of 4482 Experts worldwide ranked by ideXlab platform
Jun Chen - One of the best experts on this subject based on the ideXlab platform.
-
microrna 15a 16 1 Antagomir ameliorates ischemic brain injury in experimental stroke
Stroke, 2017Co-Authors: Xinxin Yang, Xuelian Tang, Sulaiman H Hassan, Anne R Stetler, Jun ChenAbstract:Background and Purpose—Dysregulation of the miR-15a/16-1 cluster in plasma has been reported in patients with stroke as a potential biomarker for diagnostic and prognostic use. However, the essenti...
-
MicroRNA-15a/16-1 Antagomir Ameliorates Ischemic Brain Injury in Experimental Stroke.
Stroke, 2017Co-Authors: Xinxin Yang, Xuelian Tang, Sulaiman H Hassan, R. Anne Stetler, Jun ChenAbstract:Background and Purpose—Dysregulation of the miR-15a/16-1 cluster in plasma has been reported in patients with stroke as a potential biomarker for diagnostic and prognostic use. However, the essenti...
-
abstract tp264 microrna 15a 16 1 Antagomir ameliorates ischemic brain injury in experimental stroke
Stroke, 2017Co-Authors: Xinxin Yang, Jun ChenAbstract:MicroRNAs (miRs) are small endogenous RNA molecules that repress gene translation by hybridizing to 3’-UTRs of mRNAs. Accumulating evidence has shown that miRs play a critical regulatory role in the pathogenesis of ischemic stroke. MiR-15a and miR-16-1 are two highly conserved miRs, which act similarly by binding to their common mRNA targets, thus forming both a structural and functional cluster. Dysregulated plasma levels of miR-15a/16-1 have been reported in stroke patients. Inhibition of miR-15a has been shown to protect against myocardial infarction and selected by pharmaceutical companies as one of the most attractive miR-based therapeutics. Up to now, the essential role and therapeutic potential of the miR-15a/16-1 cluster in ischemic stroke are poorly understood. In this study, adult male miR-15a/16-1 knockout and wildtype mice were subjected to 45 min of middle cerebral artery occlusion (MCAO) and 72h of reperfusion. In a separate experiment, miR-15a/16-1 specific inhibitor (Antagomir, 30 pmol/g) was injected into tail vein of stroke mice and the animals were allowed to survive for 72h. The neurological scores, brain infarct volume, and edema content were then evaluated and analyzed. To explore the underlying mechanism, inflammatory factors were measured by qPCR or ELISA and anti-apoptotic proteins were examined by western blotting. We found that genetic deletion of miR-15a/16-1 or intravenous delivery of miR-15a/16-1 Antagomir significantly reduced cerebral infarct size, decreased brain edema and improved neurological outcomes in stroke mice. Mechanistically, treatment of miR-15a/16-1 Antagomir significantly ameliorated the expression of several key inflammatory factors and increased the Bcl-2 and Bcl-w levels in the ischemic brain regions. These results demonstrated that pharmacological inhibition of miR-15a/16-1 reduces ischemic brain injury via both anti-apoptotic and anti-inflammatory mechanisms and the miR-15a/16-1 cluster is a novel therapeutic target for ischemic stroke.
-
Abstract TP264: MicroRNA-15a/16-1 Antagomir Ameliorates Ischemic Brain Injury in Experimental Stroke
Stroke, 2017Co-Authors: Xinxin Yang, Jun ChenAbstract:MicroRNAs (miRs) are small endogenous RNA molecules that repress gene translation by hybridizing to 3’-UTRs of mRNAs. Accumulating evidence has shown that miRs play a critical regulatory role in the pathogenesis of ischemic stroke. MiR-15a and miR-16-1 are two highly conserved miRs, which act similarly by binding to their common mRNA targets, thus forming both a structural and functional cluster. Dysregulated plasma levels of miR-15a/16-1 have been reported in stroke patients. Inhibition of miR-15a has been shown to protect against myocardial infarction and selected by pharmaceutical companies as one of the most attractive miR-based therapeutics. Up to now, the essential role and therapeutic potential of the miR-15a/16-1 cluster in ischemic stroke are poorly understood. In this study, adult male miR-15a/16-1 knockout and wildtype mice were subjected to 45 min of middle cerebral artery occlusion (MCAO) and 72h of reperfusion. In a separate experiment, miR-15a/16-1 specific inhibitor (Antagomir, 30 pmol/g) was injected into tail vein of stroke mice and the animals were allowed to survive for 72h. The neurological scores, brain infarct volume, and edema content were then evaluated and analyzed. To explore the underlying mechanism, inflammatory factors were measured by qPCR or ELISA and anti-apoptotic proteins were examined by western blotting. We found that genetic deletion of miR-15a/16-1 or intravenous delivery of miR-15a/16-1 Antagomir significantly reduced cerebral infarct size, decreased brain edema and improved neurological outcomes in stroke mice. Mechanistically, treatment of miR-15a/16-1 Antagomir significantly ameliorated the expression of several key inflammatory factors and increased the Bcl-2 and Bcl-w levels in the ischemic brain regions. These results demonstrated that pharmacological inhibition of miR-15a/16-1 reduces ischemic brain injury via both anti-apoptotic and anti-inflammatory mechanisms and the miR-15a/16-1 cluster is a novel therapeutic target for ischemic stroke.
Xinxin Yang - One of the best experts on this subject based on the ideXlab platform.
-
microrna 15a 16 1 Antagomir ameliorates ischemic brain injury in experimental stroke
Stroke, 2017Co-Authors: Xinxin Yang, Xuelian Tang, Sulaiman H Hassan, Anne R Stetler, Jun ChenAbstract:Background and Purpose—Dysregulation of the miR-15a/16-1 cluster in plasma has been reported in patients with stroke as a potential biomarker for diagnostic and prognostic use. However, the essenti...
-
MicroRNA-15a/16-1 Antagomir Ameliorates Ischemic Brain Injury in Experimental Stroke.
Stroke, 2017Co-Authors: Xinxin Yang, Xuelian Tang, Sulaiman H Hassan, R. Anne Stetler, Jun ChenAbstract:Background and Purpose—Dysregulation of the miR-15a/16-1 cluster in plasma has been reported in patients with stroke as a potential biomarker for diagnostic and prognostic use. However, the essenti...
-
abstract tp264 microrna 15a 16 1 Antagomir ameliorates ischemic brain injury in experimental stroke
Stroke, 2017Co-Authors: Xinxin Yang, Jun ChenAbstract:MicroRNAs (miRs) are small endogenous RNA molecules that repress gene translation by hybridizing to 3’-UTRs of mRNAs. Accumulating evidence has shown that miRs play a critical regulatory role in the pathogenesis of ischemic stroke. MiR-15a and miR-16-1 are two highly conserved miRs, which act similarly by binding to their common mRNA targets, thus forming both a structural and functional cluster. Dysregulated plasma levels of miR-15a/16-1 have been reported in stroke patients. Inhibition of miR-15a has been shown to protect against myocardial infarction and selected by pharmaceutical companies as one of the most attractive miR-based therapeutics. Up to now, the essential role and therapeutic potential of the miR-15a/16-1 cluster in ischemic stroke are poorly understood. In this study, adult male miR-15a/16-1 knockout and wildtype mice were subjected to 45 min of middle cerebral artery occlusion (MCAO) and 72h of reperfusion. In a separate experiment, miR-15a/16-1 specific inhibitor (Antagomir, 30 pmol/g) was injected into tail vein of stroke mice and the animals were allowed to survive for 72h. The neurological scores, brain infarct volume, and edema content were then evaluated and analyzed. To explore the underlying mechanism, inflammatory factors were measured by qPCR or ELISA and anti-apoptotic proteins were examined by western blotting. We found that genetic deletion of miR-15a/16-1 or intravenous delivery of miR-15a/16-1 Antagomir significantly reduced cerebral infarct size, decreased brain edema and improved neurological outcomes in stroke mice. Mechanistically, treatment of miR-15a/16-1 Antagomir significantly ameliorated the expression of several key inflammatory factors and increased the Bcl-2 and Bcl-w levels in the ischemic brain regions. These results demonstrated that pharmacological inhibition of miR-15a/16-1 reduces ischemic brain injury via both anti-apoptotic and anti-inflammatory mechanisms and the miR-15a/16-1 cluster is a novel therapeutic target for ischemic stroke.
-
Abstract TP264: MicroRNA-15a/16-1 Antagomir Ameliorates Ischemic Brain Injury in Experimental Stroke
Stroke, 2017Co-Authors: Xinxin Yang, Jun ChenAbstract:MicroRNAs (miRs) are small endogenous RNA molecules that repress gene translation by hybridizing to 3’-UTRs of mRNAs. Accumulating evidence has shown that miRs play a critical regulatory role in the pathogenesis of ischemic stroke. MiR-15a and miR-16-1 are two highly conserved miRs, which act similarly by binding to their common mRNA targets, thus forming both a structural and functional cluster. Dysregulated plasma levels of miR-15a/16-1 have been reported in stroke patients. Inhibition of miR-15a has been shown to protect against myocardial infarction and selected by pharmaceutical companies as one of the most attractive miR-based therapeutics. Up to now, the essential role and therapeutic potential of the miR-15a/16-1 cluster in ischemic stroke are poorly understood. In this study, adult male miR-15a/16-1 knockout and wildtype mice were subjected to 45 min of middle cerebral artery occlusion (MCAO) and 72h of reperfusion. In a separate experiment, miR-15a/16-1 specific inhibitor (Antagomir, 30 pmol/g) was injected into tail vein of stroke mice and the animals were allowed to survive for 72h. The neurological scores, brain infarct volume, and edema content were then evaluated and analyzed. To explore the underlying mechanism, inflammatory factors were measured by qPCR or ELISA and anti-apoptotic proteins were examined by western blotting. We found that genetic deletion of miR-15a/16-1 or intravenous delivery of miR-15a/16-1 Antagomir significantly reduced cerebral infarct size, decreased brain edema and improved neurological outcomes in stroke mice. Mechanistically, treatment of miR-15a/16-1 Antagomir significantly ameliorated the expression of several key inflammatory factors and increased the Bcl-2 and Bcl-w levels in the ischemic brain regions. These results demonstrated that pharmacological inhibition of miR-15a/16-1 reduces ischemic brain injury via both anti-apoptotic and anti-inflammatory mechanisms and the miR-15a/16-1 cluster is a novel therapeutic target for ischemic stroke.
Hongxia He - One of the best experts on this subject based on the ideXlab platform.
-
mir 155 Antagomir protect against dss induced colitis in mice through regulating th17 treg cell balance by jarid2 wnt β catenin
Biomedicine & Pharmacotherapy, 2020Co-Authors: Huarong Li, Hui Wu, Yalan Dong, Ting Yu, Hongxia HeAbstract:Abstract Background Th subsets particularly T helper 17 and regulatory T cells play a critical role in immune balance in colonic mucosa of Inflammatory Bowel Disease. Recent studies have indicated miR-155 is overexpressed in the colonic mucosa in IBD patients. Thus, whether and how miR-155 influences Th17/Treg cell balance in IBD patients is worthy of researching. Methods We divided mice into four groups: the mice oral administration of 3.0 % DSS in fresh drinking water for 7 days except normal group. In this period, starting from the fifth day, the miR-155 and NC Antagomir group were carried out by intraperitoneal injection of miR-155 Antagomirs and corresponding negative controls. In vitro, we isolated naive CD4+T cells and divided into two groups: the cells were transfected with mmu-miR-155-5p inhibitor or corresponding negative controls and then induced differentiation. Results We found miR-155 Antagomir can reach colon tissues in DSS-induced colitis and indeed ameliorated DSS-induced experimental colitis. Subsequently, we proved the levels of Th17 cells in spleens and Mesenteric lymph nodes and its associated IL-6, IL-17A and RORγt in colonic tissues were dramatically decreased and TGF-β1 raised in DSS + miR-155 Antagomir group. However, miR-155 Antagomir significantly increased the expression of Tregs. In vitro, we found miR-155 inhibitor could improve the Tregs but decrease Th17 cells. Finally, we dig out that Jarid2 was apparently improved by miR-155 Antagomir, Wnt/β-catenin and its associated T cell factor-4 (TCF-4) and Cyclin D1 expression were positively correlated with Jarid2. Conclusion Silencing of miR-155 attenuates DSS-induced colitis by regulating Th17/Treg cell balance and Jarid2/Wnt/β-catenin participated in the process.
Xiaowei Yu - One of the best experts on this subject based on the ideXlab platform.
-
the promotion of bone regeneration through cs gp cth Antagomir 133a b sustained release system
Nanomedicine: Nanotechnology Biology and Medicine, 2020Co-Authors: Fusong Jiang, Lihui Zhou, Nan Wang, Haojie Shan, Zubin Zhou, Xiaowei YuAbstract:Abstract Few studies reported the application of miRNA in bone regeneration. In this study, the expression of miR133a and miR133b in murine BMSCs was inhibited via Antagomir-133a/b and the osteogenic differentiation in murine BMSCs was evaluated. The RT-PCR, flow cytometry, cell counting kit-8, and annexin V-FITC/PI double staining assays were performed. Double knockdown miR133a and miR133b can promote BMSC osteogenic differentiation. At optimum N/P ration (15:1), the loading efficiency can reach over 90%. CTH-Antagomir-133a/b showed no cytotoxicity to BMSCs and diminished miR133a and miR133b expression in BMSCs. Furthermore, chitosan-based sustained delivery system can facilitate continuous dosing of Antagomir-133a/b, which enhanced calcium deposition and osteogenic specific gene expression in vitro. The new bone formation was enhanced after the sustained delivery system containing CTH-Antagomir-133a/b nanoparticles was used in mouse calvarial bone defect model. Our results demonstrate that CTH nanoparticles could facilitate continuous dosing of Antagomir133a/b, which can promote osteogenic differentiation.
-
The promotion of bone regeneration through CS/GP-CTH/Antagomir-133a/b sustained release system.
Nanomedicine: Nanotechnology Biology and Medicine, 2019Co-Authors: Fusong Jiang, Lihui Zhou, Nan Wang, Haojie Shan, Zubin Zhou, Xiaowei YuAbstract:Abstract Few studies reported the application of miRNA in bone regeneration. In this study, the expression of miR133a and miR133b in murine BMSCs was inhibited via Antagomir-133a/b and the osteogenic differentiation in murine BMSCs was evaluated. The RT-PCR, flow cytometry, cell counting kit-8, and annexin V-FITC/PI double staining assays were performed. Double knockdown miR133a and miR133b can promote BMSC osteogenic differentiation. At optimum N/P ration (15:1), the loading efficiency can reach over 90%. CTH-Antagomir-133a/b showed no cytotoxicity to BMSCs and diminished miR133a and miR133b expression in BMSCs. Furthermore, chitosan-based sustained delivery system can facilitate continuous dosing of Antagomir-133a/b, which enhanced calcium deposition and osteogenic specific gene expression in vitro. The new bone formation was enhanced after the sustained delivery system containing CTH-Antagomir-133a/b nanoparticles was used in mouse calvarial bone defect model. Our results demonstrate that CTH nanoparticles could facilitate continuous dosing of Antagomir133a/b, which can promote osteogenic differentiation.
Yangmin Zheng - One of the best experts on this subject based on the ideXlab platform.
-
intravenous Antagomir 494 lessens brain infiltrating neutrophils by increasing hdac2 mediated repression of multiple mmps in experimental stroke
The FASEB Journal, 2020Co-Authors: Fangfang Li, Haiping Zhao, Guangwen Li, Sijia Zhang, Rongliang Wang, Yangmin ZhengAbstract:Neutrophil infiltration and phenotypic transformation are believed to contribute to neuronal damage in ischemic stroke. Emerging evidence suggests that histone deacetylase 2 (HDAC2) is an epigenetic regulator of inflammatory cells. Here, we aimed to investigate whether microRNA-494 (miR-494) affects HDAC2-mediated neutrophil infiltration and phenotypic shift. MiR-494 levels in neutrophils from acute ischemic stroke (AIS) patients were detected by real-time PCR. Chromatin Immunoprecipitation (ChIP)-Seq was performed to clarify which genes are the binding targets of HDAC2. Endothelial cells and cortical neurons were subjected to oxygen-glucose deprivation (OGD), transwell assay was conducted to examine neutrophil migration through endothelial cells, and neuronal injury was examined after stimulating with supernatant from Antagomir-494-treated neutrophils. C57BL/6J mice were subjected to transient middle cerebral artery occlusion (MCAO) and Antagomir-494 was injected through tail vein immediately after reperfusion, and neutrophil infiltration and phenotypic shift was examined. We found that the expression of miR-494 in neutrophils was significantly increased in AIS patients. HDAC2 targeted multiple matrix metalloproteinases (MMPs) and Fc-gamma receptor III (CD16) genes in neutrophils of AIS patients. Furthermore, Antagomir-494 repressed expression of multiple MMPs genes, including MMP7, MMP10, MMP13, and MMP16, which reduced the number of brain-infiltrating neutrophils by regulating HDAC2. Antagomir-494 could also exert its neuroprotective role through inhibiting the shift of neutrophils toward pro-inflammatory N1 phenotype in vivo and in vitro. Taken together, miR-494 may serve as an alternative predictive biomarker of the outcome of AIS patients, and Antagomir-494 treatment decreases the expression of multiple MMPs and the infiltration of neutrophils and inhibits the shift of neutrophils into N1 phenotype partly by targeting HDAC2.
-
Intravenous Antagomir-494 lessens brain-infiltrating neutrophils by increasing HDAC2-mediated repression of multiple MMPs in experimental stroke
2019Co-Authors: Fangfang Li, Haiping Zhao, Guangwen Li, Sijia Zhang, Rongliang Wang, Yangmin ZhengAbstract:Abstract Background: Neutrophil infiltration and phenotypic transformation are believed to contribute to neuronal damage and clinical outcome in ischemic stroke. Emerging evidence suggests that HDAC2 is an epigenetic regulator of inflammatory cells. Here, we investigated whether miR-494 affects HDAC2-mediated neutrophil infiltration and phenotypic shift. Methods: The miR-494 levels in neutrophils from AIS patients were detected by real-time PCR. C57BL/6J mice were subjected to transient middle cerebral artery occlusion, and the N1/N2 neutrophil shift was examined. Cortical neurons were subjected to oxygen-glucose deprivation and stimulated with supernatant from differently treated neutrophils or were cocultured with neutrophils; neuronal injury was detected, and ChIP-Seq was performed to clarify which genes are the binding targets of HDAC2. Finally, a transwell assay was conducted to examine neutrophil migration. Results: Compared to the control subjects, AIS patients had increased neutrophil expression of miR-494, and in AIS patients, elevated miR-494 expression in neutrophils was a predictor of worse neurological outcomes. MiR-494 correlates with the upregulation of adhesion molecules in neutrophils of AIS patients. Systemically administered Antagomir-494 partly shifts neutrophils into the N2 phenotype in MCAO mice. Antagomir-494-treated neutrophils exert a neuroprotective role in vitro. ChIP-seq revealed that HDAC2 targets multiple MMP genes in neutrophils of AIS patients. Further in vitro and in vivo experiments showed that Antagomir-494 repressed expression of MMP genes, including MMP7, MMP10, MMP13, and MMP16, to reduce the number of brain-infiltrating neutrophils by regulating HDAC2. Conclusion: MiR-494 may serve as an alternative predictive biomarker of the outcome of AIS patients, and Antagomir-494 treatment decreased the expression of multiple MMPs and the infiltration of neutrophils partly by targeting HDAC2.
