LncRNA GAS5 Overexpression Reverses LPS-Induced Inflammatory Injury and Apoptosis Through Up-Regulating KLF2 Expression in ATDC5 Chondrocytes

Background/Aims: Osteoarthritis (OA) is the most frequently occurring joint disease and characterized by degeneration of cartilage. As the unique cell type in cartilage, chondrocytes play a crucial role during OA. Our study explored the influence of long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) on lipopolysaccharides (LPS)-induced injury in ATDC5 cells. Methods: Cell viability, apoptosis and expression of inflammatory cytokines were all assessed to evaluate LPS-induce inflammatory injury. Expression of GAS5 in LPS-induced cells was evaluated by qRT-PCR. After cell transfection, effect of abnormally expressed GAS5 on LPS-induced inflammatory injury was determined. Then, the possible target of GAS5 was screened by bioinformatics and verified by qRT-PCR and luciferase activity assay. Together, whether aberrant expression of target gene affected the modulation of GAS5 in LPS-induced inflammatory injury was also assessed. Finally, the influences of aberrant expressed Kruppel-like factor 2 (KLF2) on nuclear factor κB (NF-κB) and Notch pathways were detected by Western blot analysis. Results: LPS reduced cell viability and promoted cell apoptosis and secretion of inflammatory cytokines, along with down-regulation of GAS5. LPS-induced injury was alleviated by GAS5 overexpression while was exacerbated by GAS5 silence. KLF2 was predicted and verified as a target of GAS5, and GAS5 functioned through regulating expression of KLF2. Besides, aberrant expression of KLF2 regulated expressions of key kinases involved in the NF-κB and Notch pathways. Conclusion: GAS5 might ameliorate LPS-induced inflammatory injury in ATDC5 chondrocytes by inhibiting the NF-κB and Notch signaling pathways

HMGB1 Is Involved in the Protective Effect of the PPARα Agonist Fenofibrate against Cardiac Hypertrophy

High mobility group box 1 (HMGB1) is a ubiquitous nuclear DNA-binding protein whose function is dependent on its cellular location. Extracellular HMGB1 is regarded as a delayed mediator of proinflammatory cytokines for initiating and amplifying inflammatory responses, whereas nuclear HMGB1 has been found to prevent cardiac hypertrophy and heart failure. Because fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, has shown both protective effects against cardiac hypertrophy and inhibitory effects against inflammation, the potential modulation of HMGB1 expression and secretion by fenofibrate is of great interest. We herein provide evidence that fenofibrate modulates basal and LPS-stimulated HMGB1 expression and localization in addition to secretion of HMGB1 in cardiomyocytes. In addition, administration of fenofibrate to mice prevented the development of cardiac hypertrophy induced by thoracic transverse aortic constriction (TAC) while increasing levels of nuclear HMGB1. Altogether, these data suggest that fenofibrate may inhibit the development of cardiac hypertrophy by regulating HMGB1 expression, which provides a new potential strategy to treat cardiac hypertrophy

Biodegradable, Biomimetic Elastomeric, Photoluminescent, and Broad-Spectrum Antibacterial Polycitrate-Polypeptide-based Membrane toward Multifunctional Biomedical Implants

Current biomedical membranes in guided tissue regeneration applications are almost nonbiodegradable or deficient in functionality. The development of biodegradable biomaterials with multifunctional properties including biomimetic elastomeric behavior, self-anti-infection, noninvasive monitoring, and good biocompatibility has attracted much attention. Here, we report a biodegradable and biocompatible polycitrate-(ε-polypeptide)-based (PCE) biomedical elastomer membrane with intrinsic broad-spectrum antibacterial activity and photoluminescent capacity for multifunctional guided tissue regenerative applications. PCE showed highly elastomeric mechanical behavior (∼300% elongation and ∼100% recovery) and biomimetic mechanical properties against several native tissues. PCE film also possessed highly efficient broad-spectrum antibacterial activity <i>in vitro</i> and <i>in vivo</i>. The inherent photoluminescent properties of PCE film endowed their real-time noninvasive monitoring capacity <i>in vivo</i>. Owing to the biocompatible structure (polycitrate and natural polypeptide), PCE film demonstrated significantly high cytocompatibility and hemocompatibility <i>in vitro</i> and low inflammatory response <i>in vivo</i>. Our study may provide a new strategy to design next generation multifunctional biodegradable biomedical implant membranes for smart guided tissue regenerative medicine applications

JUNO sensitivity to the annihilation of MeV dark matter in the galactic halo

International audienceWe discuss JUNO sensitivity to the annihilation of MeV dark matter in the galactic halo via detecting inverse beta decay reactions of electron anti-neutrinos resulting from the annihilation. We study possible backgrounds to the signature, including the reactor neutrinos, diffuse supernova neutrino background, charged- and neutral-current interactions of atmospheric neutrinos, backgrounds from muon-induced fast neutrons and cosmogenic isotopes. A fiducial volume cut, as well as the pulse shape discrimination and the muon veto are applied to suppress the above backgrounds. It is shown that JUNO sensitivity to the thermally averaged dark matter annihilation rate in 10 years of exposure would be significantly better than the present-day best limit set by Super-Kamiokande and would be comparable to that expected by Hyper-Kamiokande