CircFKBP5 Suppresses Apoptosis and Inflammation and Promotes Osteogenic Differentiation.

OBJECTIVES: Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cell possessing self-renewal and multilineage differentiation capabilities. The dysfunction of DPSCs is related to the pathologic process of pulpitis. The participation of circular RNAs (circRNAs) in DPSC differentiation has been identified. This work focussed on exploring the functions and mechanism of circFKBP5 in DPSC dysfunction evoked by lipopolysaccharide (LPS). MATERIALS AND METHODS: The viability and apoptosis of human DPSCs (hDPSCs) were determined using Cell Counting Kit-8 assay and flow cytometry. Inflammation was analysed by measuring the release of inflammatory cytokines. The osteogenic differentiation of hDPSCs was investigated by performing alkaline phosphatase (ALP) staining and alizarin red S staining and detecting the changes of ALP and runt-related transcription factor 2 (RUNX2) proteins. The dual-luciferase reporter, RNA immunoprecipitation (RIP), and pull-down assays were used to confirm the binding between miR-708-5p and circFKBP5 or G-protein-coupled receptor (GPCR)-kinase interacting protein 2 (GIT2). RESULTS: CircFKBP5 expression was decreased in hDPSCs and, functionally, reexpression of circFKBP5 attenuated LPS-induced apoptosis, inflammation, and inhibition of proliferation ability and osteogenic differentiation in hDPSCs. Mechanistically, circFKBP5 acted as a sponge for miR-708-5p, which was verified to target GIT2. LPS induced miR-708-5p expression in hDPSCs, and knockdown of miR-708-5p protected against LPS-evoked hDPSC dysfunction. Besides, GIT2 expression was decreased in hDPSCs after LPS treatment. Rescue experiments showed that GIT2 could mediate the protective functions of circFKBP5 on hDPSCs under LPS treatment. CONCLUSIONS: CircFKBP5 could protect against LPS-induced apoptosis, inflammation, and osteogenic differentiation inhibition in hDPSCs via the miR-708-5p/GIT2 axis.

An iron-base oxygen-evolution electrode for high-temperature electrolyzers.

High-temperature molten-salt electrolyzers play a central role in metals, materials and chemicals production for their merit of favorable kinetics. However, a low-cost, long-lasting, and efficient high-temperature oxygen evolution reaction (HT-OER) electrode remains a big challenge. Here we report an iron-base electrode with an in situ formed lithium ferrite scale that provides enhanced stability and catalytic activity in both high-temperature molten carbonate and chloride salts. The finding is stemmed from a discovery of the ionic potential-stability relationship and a basicity modulation principle of oxide films in molten salt. Using the iron-base electrode, we build a kiloampere-scale molten carbonate electrolyzer to efficiently convert CO2 to carbon and oxygen. More broadly, the design principles lay the foundations for exploring cheap, Earth-abundant, and long-lasting HT-OER electrodes for electrochemical devices with molten carbonate and chloride electrolytes.

A sulfated glucuronorhamnan from the green seaweed Monostroma nitidum: Characteristics of its structure and antiviral activity.

A water-soluble polysaccharide from Monostroma nitidum, designated MWS, was isolated using water extraction, anion-exchange and size-exclusion chromatography. MWS was a sulfated glucuronorhamnan consisting of →3)-α-l-Rhap-(1→, →4)-ß-d-GlcpA-(1→ and →2)-α-l-Rhap-(1→ units. Sulfate ester groups located at C-4/C-2 of →3)-α-l-Rhap-(1→ and C-4/C-3 of →2)-α-l-Rhap-(1→ units. In in vitro tests, it was proved that MWS possessed broad spectrum against different viruses, especially for enterovirus 71 (EV71) with nearly no toxicity in relation to cell lines used. MWS may largely inhibit EV71 infection before or during viral adsorption through binding to virus particles and block some early steps of virus life cycle by down-regulating host phosphoinositide 3-kinase /protein kinase B signaling pathway. Intramuscular injection of MWS markedly reduced viral titers in EV71-infected mice. The data demonstrated that MWS could have great promising to become an antiviral drug for prevention and therapy of EV71 infection.

Inhibition of herpes simplex virus by myricetin through targeting viral gD protein and cellular EGFR/PI3K/Akt pathway.

Myricetin, a common dietary flavonoid, was reported to possess many different biological activities such as anti-oxidant, anti-inflammatory, and antiviral effects. In this study, we explored the anti-HSV effects and mechanisms of myricetin both in vitro and in vivo. The results showed that myricetin possessed anti-HSV-1 and HSV-2 activities with very low toxicity, superior to the effects of acyclovir. Myricetin may block HSV infection through direct interaction with virus gD protein to interfere with virus adsorption and membrane fusion, which was different from the nucleoside analogues such as acyclovir. Myricetin also down-regulate the cellular EGFR/PI3K/Akt signaling pathway to further inhibit HSV infection and its subsequent replication. Most importantly, intraperitoneal therapy of myricetin markedly improved mice survival and reduced virus titers in both lungs and spinal cord. Therefore, the natural dietary flavonoid myricetin has potential to be developed into a novel anti-HSV agent targeting both virus gD protein and cellular EGFR/PI3K/Akt pathway.

Guanidine modifications enhance the anti-herpes simplex virus activity of (E,E)-4,6-bis(styryl)-pyrimidine derivatives in vitro and in vivo.

BACKGROUND AND PURPOSE: The worldwide prevalence of herpes simplex virus (HSV) and shortage of efficient therapeutic strategies to counteract it are global concerns. In terms of treatment, the widely utilized anti-HSV drugs such as acyclovir have serious limitations, for example, drug resistance and side effects. Here, we have identified the guanidine-modified (E,E)-4,6-bis(styryl)-pyrimidine (BS-pyrimidine) derivative compound 5d as an inhibitor of HSV and further elucidated the anti-HSV mechanisms of compound 5d both in vitro and in vivo. EXPERIMENTAL APPROACH: Cytopathic effect inhibition assay, plaque assay, and immunofluorescence assay were used to evaluate the anti-HSV effects of compound 5d in vitro. Membrane fusion assays, immunofluorescence assays, Western blotting assays, and pull-down assays were used to explore the anti-HSV mechanisms of compound 5d. HSV-1-infected mice, combined with haematoxylin-eosin staining and quantitative RT-PCR, were used to study the anti-HSV effects of compound 5d in vivo. KEY RESULTS: The guanidine-modified compound 5d rather than the un-modified compound 3a effectively inhibited both HSV-1 and HSV-2 multiplication in different cell lines, more effectively than acyclovir. Compound 5d may block virus binding and post-binding processes such as membrane fusion, by targeting virus gB protein. In addition, compound 5d may also down-regulate the cellular PI3K/Akt signalling pathway to interfere with HSV replication. Treatment with compound 5d also markedly improved survival and decreased viral titres in HSV-infected mice. CONCLUSIONS AND IMPLICATIONS: Thus, the guanidine-modified BS-pyrimidine derivatives have the potential to be developed into novel anti-HSV agents targeting both virus gB protein and cellular PI3K/Akt signalling pathways.