Tanshinone IIA promotes the proliferation and differentiation ability of primary muscle stem cells via MAPK and Akt signaling.

Salvia miltiorrhiza Bunge is a widely-used traditional Chinese medicine to treat a variety of diseases including muscle disorders. The underlying pharmacological mechanisms of which active component and how it functions are still unknown. Tanshinone IIA (Tan IIA) is the main active lipophilic compound in Salvia miltiorrhiza Bunge. Muscle stem cells (MuSCs) play a crucial role in maintaining healthy physiological function of skeletal muscle. For the purpose of this study, we investigated the effects of Tan IIA on primary MuSCs as well as mechanism. The EdU staining, cell counts assay and RT-qPCR results of proliferative genes revealed increased proliferation ability of MuSCs after Tan IIA treatment. Immunofluorescent staining of MyHC and RT-qPCR results of myogenic genes found Tan IIA contributed to promoting differentiation of MuSCs. In addition, enrichment analysis of RNA-seq data and Western blot assay results demonstrated activated MAPK and Akt signaling after treatment of Tan IIA during proliferation and differentiation. The above proliferative and differentiative phonotypes could be suppressed by the combination of MAPK inhibitor U0126 and Akt inhibitor Akti 1/2, respectively. Furthermore, HE staining found significantly improved myofiber regeneration of injured muscle after Tan IIA treatment, which also contributed to muscle force and running performance recovery. Thus, Tan IIA could promote proliferation and differentiation ability of MuSCs through activating MAPK and Akt signaling, respectively. These beneficial effects also significantly contributed to muscle regeneration and muscle function recovery after muscle injury.

Circ_0002984 promotes proliferation, migration and inflammatory cytokine secretion and inhibits apoptosis of rheumatoid arthritis fibroblast-like synoviocytes by inducing PCSK6 through miR-543.

BACKGROUND: Rheumatoid arthritis (RA) is inflammatory arthritic disease, and circular RNA is involved in RA development. The aim of the present work is to analyze the role of circ_0002984 in the process of RA fibroblast-like synoviocytes (RAFLSs) and the underlying mechanism. METHODS: Circ_0002984, miR-543, and proprotein convertase subtilisin/kexin type 6 (PCSK6) expression levels were analyzed by quantitative real-time polymerase chain reaction or western blotting. Cell proliferation, migration, inflammatory response, and apoptosis were investigated through 5-Ethynyl-2'-deoxyuridine assay, wound-healing assay, enzyme-linked immunosorbent assay, and flow cytometry analysis. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed to assess the binding relationship. RESULTS: Circ_0002984 and PCSK6 expression were increased, while miR-543 expression was decreased in the synovial tissues of RA patients and RAFLSs. Circ_0002984 introduction facilitated RAFLS cell proliferation, migration and inflammatory response and repressed apoptosis, but circ_0002984 knockdown had an opposite role. Circ_0002984 targeted miR-543, and PCSK6 was targeted by miR-543. MiR-543 downregulation or PCSK6 overexpression restored the effects of circ_0002984 interference on RAFLS phenotypes. CONCLUSION: Circ_0002984 promoted RAFLS proliferation, migration and inflammatory cytokine secretion and inhibited apoptosis by binding to miR-543 to induce PCSK6 production, providing a potential target for RA therapy.

Noble metal nanoparticle-functionalized Zr-metal organic frameworks with excellent photocatalytic performance.

Noble metal nanoparticles (NPs) functionalized MOFs are attractive materials for photocatalytic reactions, and outstanding catalytic performances can be expected, especially when they have intrinsically matched crystal faces between metals and MOFs. This study discovered that the photocatalytic oxidation of aromatic alcohols to aldehydes was enhanced over Au/UiO-66-NH2 or Au/UiO-66 but suppressed over Pt loaded counterparts, whereas the reduction of Cr(VI) was boosted over both two catalysts. In reactions, the conversion of benzyl alcohol was 17.1% over UiO-66-NH2 and 7.6% over UiO-66, and an enhanced conversion was obtained over Au/UiO-66-NH2 (30.5%) and Au/UiO-66 (24.1%). However, the conversion was decreased over Pt/UiO-66-NH2 (9.3%) and Pt/UiO-66 (<1%). Experimental results revealed strong correlations between Zr-MOFs and loaded metal NPs, as Zr centers promoted the formation of Pt(200) planes that suppressed the production of ·O2- intermediates to oxidize aromatic alcohols, whereas Pt(200) exhibited no effect on the Cr(VI) reduction triggered by photo-induced electrons. The findings in this study on constructing noble metal NPs functionalized Zr-MOFs catalysts with specially-matched crystal structures and on distinguishing photocatalytic mechanisms on oxidation of alcohols and reduction of Cr(VI) would provide valuable information for designer (photo)catalysts based on MOFs and their applications in such as catalysis and environmental remediation.

Preparation and in vitro evaluation of strontium-doped calcium silicate/gypsum bioactive bone cement.

The combination of two or more bioactive components with different biodegradability could cooperatively improve the physicochemical and biological performances of the biomaterials. Here we explore the use of α-calcium sulfate hemihydrate (α-CSH) and calcium silicate with and without strontium doping (Sr-CSi, CSi) to fabricate new bioactive cements with appropriate biodegradability as bone implants. The cements were fabricated by adding different amounts (0-35 wt%) of Sr-CSi (or CSi) into the α-CSH-based pastes at a liquid-to-solid ratio of 0.4. The addition of Sr-CSi into α-CSH cements not only led to a pH rise in the immersion medium, but also changed the surface reactivity of cements, making them more bioactive and therefore promoting apatite mineralization in simulated body fluid (SBF). The impact of additives on long-term in vitro degradation was evaluated by soaking the cements in Tris buffer, SBF, and α-minimal essential medium (α-MEM) for a period of five weeks. An addition of 20% Sr-CSi to α-CSH cement retarded the weight loss of the samples to 36% (in Tris buffer), 43% (in SBF) and 54% (in α-MEM) as compared with the pure α-CSH cement. However, the addition of CSi resulted in a slightly faster degradation in comparison with Sr-CSi in these media. Finally, the in vitro cell-ion dissolution products interaction study using human fetal osteoblast cells demonstrated that the addition of Sr-CSi improved cell viability and proliferation. These results indicate that tailorable bioactivity and biodegradation behavior can be achieved in gypsum cement by adding Sr-CSi, and such biocements will be of benefit for enhancing bone defect repair.