Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie
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Biomed. Pharmacother. · Mar 2018
Baicalin alleviates IL-1β-induced inflammatory injury via down-regulating miR-126 in chondrocytes.
Baicalin is a flavonoid extracted from Scutellaria baicalensis Georgi, with anti-inflammatory and anti-apoptotic activities. The objective of this study was to explore the effect and mechanism of baicalin on chondrocyte inflammatory response in OA. Different concentrations of IL-1β (0, 0.1, 2, 5 and 10 ng/mL) were used to simulate inflammatory injury in CHON-001 cells. ⋯ Further, NF-κB signaling pathway was activated by IL-1β, and deactivated by addition of baicalin. The deactivation of NF-κB signaling pathway induced by baicalin upon IL-1β exposure was recovered by miR-126 overexpression. In conclusion, this study demonstrated that baicalin protected CHON-001 cells against IL-1β-induced inflammatory injury possibly via down-regulation of miR-126 and thereby deactivation of NF-κB signaling pathway.
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Biomed. Pharmacother. · Mar 2018
Co-targeting poly(ADP-ribose) polymerase (PARP) and histone deacetylase (HDAC) in triple-negative breast cancer: Higher synergism in BRCA mutated cells.
Despite similarities with BRCA-mutated breast cancers, triple-negative breast cancers (TNBC) remain resistant to poly(ADP-ribose) polymerase (PARP) inhibitors as single agents. Histone deacetylase inhibitors (HDACi) can decrease expression of proteins involved in DNA repair. We thus hypothesized that a HDACi (suberoylanilide hydroxamic acid (SAHA) or belinostat) could sensitize TNBC to the PARP inhibitor olaparib. ⋯ In summary, these results provide a preclinical rationale to combine a HDACi with a PARP inhibitor to reduce HR efficiency in TNBC and sensitize these aggressive tumors to PARP inhibition.
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Biomed. Pharmacother. · Mar 2018
MiR-21 promotes ECM degradation through inhibiting autophagy via the PTEN/akt/mTOR signaling pathway in human degenerated NP cells.
Intervertebral disc degeneration (IDD) is the most common cause leading to low back pain, a highly prevalent, costly and crippling condition worldwide. Overexpression of miR-21 has been shown to promote proliferation of nucleus pulposus (NP) cells. However, it remains unclear whether miR-21 can promote the degradation of type II collagen (Col II) and aggrecan, two main extracellular matrix components within the disc. ⋯ Through gain-of-function and loss-of-function studies in human NP cells, miR-21 was shown to inhibit autophagy and then upregulate the expression of matrix metalloproteinase (MMP)-3 and MMP-9, leading to increased degradation of Col II and aggrecan. Mechanistically, phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-21, and activated PTEN/ Akt/mammalian target of rapamycin (mTOR) signaling pathway was involved in miR-21-induced autophagy inhibition and Col II and aggrecan breakdown. Taken together, these results suggest that miR-21 contributes to Col II and aggrecan catabolism by inhibiting autophagy via the PTEN/Akt/mTOR signaling pathway in human NP cells.