39 research outputs found

    Table1_The new ceRNA crosstalk between mRNAs and miRNAs in intervertebral disc degeneration.XLS

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    Degeneration of the intervertebral disc has been linked to lower back pain. To date, pathophysiological mechanisms of intervertebral disc degeneration (IDD) remain unclear; it is meaningful to find effective diagnostic biomarkers and new therapeutic strategies for IDD. This study aimed to reveal the molecular mechanism of IDD pathogenesis from the multidimensional transcriptomics perspective. Here, we acquired IDD bulk omics datasets (GSE67567 and GSE167199) including mRNA, microRNA expression profiles, and single-cell RNA sequencing (GSE199866) from the public Gene Expression Omnibus (GEO) database. Through principal component analysis and Venn analysis, we found different expression patterns in the IDD transcription level and identified 156 common DEGs in both bulk datasets. GO and KEGG functional analyses showed these dysregulators were mostly enriched in the collagen-containing extracellular matrix, cartilage development, chondrocyte differentiation, and immune response pathways. We also constructed a potentially dysregulated competing endogenous RNA (ceRNA) network between mRNAs and miRNAs related to IDD based on microRNA target information and co-expression analysis of RNA profiles and identified 36 ceRNA axes including ZFP36/miR-155-5p/FOS, BTG2/hsa-miR-185-5p/SOCS3, and COL9A2/hsa-miR-664a-5p/IBA57. Finally, in integrating bulk and single-cell transcriptome data analyses, a total of three marker genes, COL2A1, PAX1, and ZFP36L2, were identified. In conclusion, the key genes and the new ceRNA crosstalk we identified in intervertebral disc degeneration may provide new targets for the treatment of IDD.</p

    Image1_The new ceRNA crosstalk between mRNAs and miRNAs in intervertebral disc degeneration.TIFF

    No full text
    Degeneration of the intervertebral disc has been linked to lower back pain. To date, pathophysiological mechanisms of intervertebral disc degeneration (IDD) remain unclear; it is meaningful to find effective diagnostic biomarkers and new therapeutic strategies for IDD. This study aimed to reveal the molecular mechanism of IDD pathogenesis from the multidimensional transcriptomics perspective. Here, we acquired IDD bulk omics datasets (GSE67567 and GSE167199) including mRNA, microRNA expression profiles, and single-cell RNA sequencing (GSE199866) from the public Gene Expression Omnibus (GEO) database. Through principal component analysis and Venn analysis, we found different expression patterns in the IDD transcription level and identified 156 common DEGs in both bulk datasets. GO and KEGG functional analyses showed these dysregulators were mostly enriched in the collagen-containing extracellular matrix, cartilage development, chondrocyte differentiation, and immune response pathways. We also constructed a potentially dysregulated competing endogenous RNA (ceRNA) network between mRNAs and miRNAs related to IDD based on microRNA target information and co-expression analysis of RNA profiles and identified 36 ceRNA axes including ZFP36/miR-155-5p/FOS, BTG2/hsa-miR-185-5p/SOCS3, and COL9A2/hsa-miR-664a-5p/IBA57. Finally, in integrating bulk and single-cell transcriptome data analyses, a total of three marker genes, COL2A1, PAX1, and ZFP36L2, were identified. In conclusion, the key genes and the new ceRNA crosstalk we identified in intervertebral disc degeneration may provide new targets for the treatment of IDD.</p

    Image2_The new ceRNA crosstalk between mRNAs and miRNAs in intervertebral disc degeneration.TIFF

    No full text
    Degeneration of the intervertebral disc has been linked to lower back pain. To date, pathophysiological mechanisms of intervertebral disc degeneration (IDD) remain unclear; it is meaningful to find effective diagnostic biomarkers and new therapeutic strategies for IDD. This study aimed to reveal the molecular mechanism of IDD pathogenesis from the multidimensional transcriptomics perspective. Here, we acquired IDD bulk omics datasets (GSE67567 and GSE167199) including mRNA, microRNA expression profiles, and single-cell RNA sequencing (GSE199866) from the public Gene Expression Omnibus (GEO) database. Through principal component analysis and Venn analysis, we found different expression patterns in the IDD transcription level and identified 156 common DEGs in both bulk datasets. GO and KEGG functional analyses showed these dysregulators were mostly enriched in the collagen-containing extracellular matrix, cartilage development, chondrocyte differentiation, and immune response pathways. We also constructed a potentially dysregulated competing endogenous RNA (ceRNA) network between mRNAs and miRNAs related to IDD based on microRNA target information and co-expression analysis of RNA profiles and identified 36 ceRNA axes including ZFP36/miR-155-5p/FOS, BTG2/hsa-miR-185-5p/SOCS3, and COL9A2/hsa-miR-664a-5p/IBA57. Finally, in integrating bulk and single-cell transcriptome data analyses, a total of three marker genes, COL2A1, PAX1, and ZFP36L2, were identified. In conclusion, the key genes and the new ceRNA crosstalk we identified in intervertebral disc degeneration may provide new targets for the treatment of IDD.</p

    Boron Nitride Ultrathin Fibrous Nanonets: One-Step Synthesis and Applications for Ultrafast Adsorption for Water Treatment and Selective Filtration of Nanoparticles

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    Novel boron nitride (BN) ultrathin fibrous networks are firstly synthesized via an one-step solvothermal process. The average diameter of BN nanofibers is only ∼8 nm. This nanonets exhibit excellent performance for water treatment. The maximum adsorption capacity for methyl blue is 327.8 mg g<sup>–1</sup>. Especially, they present the property of ultrafast adsorption for dye removal. Only ∼1 min is enough to almost achieve the adsorption equilibrium. In addition, the BN fibrous nanonets could be applied for the size-selective separation of nanoparticles via a filtration process

    Effects of Berberine on the phosphorylation of AMPK-Thr 172 and ACC-Ser79, AMP/ATP ratios, and superoxide production in BAEC.

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    <p><i>A & B</i>, Dose-dependent increase of of AMPK-Thr172 and Ser79 phosphorylation by berberine in BAEC. Confluent BAEC were incubated with different doses of Berberine (1 µM to 200 µM) for 2 h. The blot is representative of three individual experiments. n = 3 *<i>p</i><0.05, control versus Berberine-treated. <i>C & D</i>, Time-dependent increase of AMP-Thr172 and Ser79 by Berberine (10 µM) in BAEC. The blot is representative of three blots obtained from three separate experiments. n = 3 * <i>p</i><0.05, control versus Berberine-treated.</p

    Increased LKB1 Serine 307 phosphorylation by Berberine in BAEC.

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    <p><b><i>A. </i></b><b>Inhibition of AMPK activity by ONOO<sup>−</sup>.</b> Recombinant AMPKα1β1γ1 was treated with chemically synthetized ONOO- at concentrations indicated for 5 minutes and AMPK activity was assayed as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015420#s2" target="_blank">Methods and Materials</a>. N = 5 *P<0.05; control verse ONOO<sup>−</sup>-treated; <i>B</i>. Effects of okadaic acid (OA) on Berberine-enhanced phosphorylation of AMPK-Thr172 and ACC-Ser79 in BAEC. The blot is representative of three blots. from three individual experiments. <i>C</i>. Effects of transfection of PP2A siRNA on Berberine-enhanced phosphorylation of AMPK-Thr172 and ACC-Ser79 in BAEC. The blot is representative of three blots from three individual experiments. <i>D</i>. Effects of STO-609 on Berberine-enhanced phosphorylation of AMPK-Thr172 and ACC-Ser79 in BAEC. The blot is representative of three blots. <i>E.</i> Effects of berberine on the phosphorylation of LKB1 serine 307 in BAEC. The blot is representative of three blots from three individual experiments. <i>F</i>. Genetic inhibition of LKB1 abolishes Berberine-induced phosphorylation of AMPK-Thr172 in BAEC. The blot is representative of three blots from three individual experiments. <i>G</i> Effects of Berberine on AMPK phosphorylation at Thr172 in LKB1-deficient A549 cells.</p

    ONOO<sup>−</sup> nitrates PA700/S10B and increases 26S proteasome activity both <i>in vitro</i> and in intact cell.

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    <p><i>In vitro</i> (A–C): ONOO<sup>−</sup> (1 µM) was incubated with the purified 26S proteasome for 5 min; in intact cell (D–E): HUVEC was incubated with ONOO<sup>−</sup> for 0.5 h, in the presence or absence of uric acid (50 µM pre-incubation for 1 h). Cell free system (<i>in vitro</i>) was subjected to (A) Western blot to detect levels of PA700/S10B and the tyrosine nitration of 26S proteasome/PA700/S10B, (B) 26S proteasome activity (chymotrypsin-like activity), (C) an alternative 26S proteasome activity assay: a substrate-in-gel assay with a fluorogenic substrate followed by fluorescence capturing under the UV light. HUVEC cell lysate was subjected to (D) Western blotting of PA700/S10B tyrosine nitration and (E) assay of 26S proteasome activity (chymotrypsin-like activity). All blots shown are representative of three independent experiments. All results (n = 3) were analyzed with a one-way ANOVA.</p

    Activation of AMPK by Berberine is mediated by reactive oxygen species (ROS).

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    <p><i>A</i>, Time-course of Berberine (10 µM) on AMP/ATP ratios in BAEC. After exposure to Berberine (10 µM) for the time indicated, BAEC were subjected to HPLC assays to measure the AMP/ATP ratio. n = 5, *<i>p</i><0.05, control versus Berberine-treated. <i>B</i>, Time-dependent increase of superoxide anions caused by Berberine (10 µM) in BAEC. After incubation with Berberine (10 µM) for the time indicated, intracellular ROS were detected by the DHE fluorescence/HPLC assay as described in “<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015420#s2" target="_blank">Materials and Methods</a>.” n = 5, *<i>p</i><0.05, control versus Berberine-treated. <i>C</i>, BAEC were pre-treated with anti-oxidants tempol (10 µM), NAc (2 mM), or DTT (1 mM) for 30 min, and then treated with Berberine for 2 h. <i>D</i>, Summary data for the effects of anti-oxidants n = 5 *<i>p</i><0.05, control versus Berberine-treated, # <i>p</i><0.05, Berberine alone versus Berberine with one or the other of the two anti-oxidants.</p

    Reactive oxygen species (ROS) involved in Berberine induced AMPK activation are derived from mitochondria.

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    <p><i>A</i>, Effects of xanthine oxidase inhibitors, allopurinol and oxypurinol, on Berberine-enhanced phosphorylation of AMPK-Thr172 and ACC-Ser79 in BAEC. BAEC were pre-treated with mitochondrial tempol (50 µM) for 30 min, and then treated with Berberine (10 µM) for 2 h. The blots are representative of three independent experiments. <i>B</i>, Effects of adenoviral overexpression of p47phox dominant negative mutants on Berberine-enhanced phosphorylation of AMPK-Thr172 and ACC-Ser79 in BAEC. The blots are representative of three independent experiments. <i>C & D</i>, Effects of mitochondrial tempol (*<i>p</i><0.05, control versus Berberine-treated, #<i>p</i><0.05, Berberine-alone versus Berberine plus mitochondrial tempol). <i>E & F</i>, Effects of UCP-2 siRNA transfection on Berberine-enhanced phosphorylation of AMPK-Thr172 and ACC-Ser79 in BAEC. BAEC were transfected with UCP2 siRNA for 24 hr, and then treated with Berberine (10 µM) for 2 hr. n = 3, *<i>p</i><0.05, control versus Berberine-treated, # <i>p</i><0.05, Berberine-alone versus Berberine plus UCP2 siRNA.<i>G.</i> Effects of adenoviral overexpression of UCP-2 on Berberine-enhanced phosphorylation of AMPK-Thr172 and ACC-Ser79 in BAEC. n = 3 *<i>p</i><0.05, control versus UCP-2; #<i>p</i><0.05, control verus Berberine-alone; +<i>p</i><0.05 Berberine-treated versus Berberine plus UCP2.</p

    The 26S proteasome is activated and results in degradation of the target proteins, which can be prevented either by ONOO<sup>−</sup> inhibition or by MG132 administration, in aortic homogenates from mouse models of diabetes, hypertension, and dyslipidemia.

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    <p>Mouse models of (A) diabetes (STZ: 50 mg/kg/d, sham: sodium citrate, i.p., 5d; MG132, 5 mg/kg/d, i.p., 2d; n = 5/group); (B) hypertension (angiotensin II: 0.8 mg/kg/d, sham: saline; osmotic pump infusion, 14d.; PA700/S10B/control siRNA, i.v. 7d; n = 5/group) and (C) high fat-diets-induced atherosclerosis (LDLr<sup>−/−</sup> mice, normal chow or HFD, 8 wks; MG132: 0.8 mg/kg/d; sham: saline; osmotic pump infusion, 2 wks after HFD, 6 wks; n = 5/group). AT the end of the animal experiment, aortas were removed and their homogenates were either subjected to 26S proteasome activity assay (chymotrypsin-like activity) (A–C), or Western blotting with the corresponding antibodies as indicated. All results (n = 5) were analyzed with a one-way ANOVA. * indicates significant <i>vs.</i> control; NS: not significant <i>vs</i>. control.</p
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