Anti-inflammatory cerium-containing nano-scaled mesoporous bioactive glass for promoting regenerative capability of dental pulp cells.

AIMS: This study aimed to investigate the anti-inflammatory and odontoblastic effects of cerium-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) on dental pulp cells as novel pulp-capping agents. METHODOLOGY: Ce-MBGNs were synthesized using a post-impregnation strategy based on the antioxidant properties of Ce ions and proposed the first use of Ce-MBGNs for pulp-capping application. The biocompatibility of Ce-MBGNs was analysed using the CCK-8 assay and apoptosis detection. Additionally, the reactive oxygen species (ROS) scavenging ability of Ce-MBGNs was measured using the 2,7-Dichlorofuorescin Diacetate (DCFH-DA) probe. The anti-inflammatory effect of Ce-MBGNs on THP-1 cells was further investigated using flow cytometry and quantitative real-time polymerase chain reaction (RT-qPCR). Moreover, the effect of Ce-MBGNs on the odontoblastic differentiation of the dental pulp cells (DPCs) was assessed by combined scratch assays, RT-qPCR, western blotting, immunocytochemistry, Alizarin Red S staining and tissue-nonspecific alkaline phosphatase staining. Analytically, the secretions of tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS: Ce-MBGNs were confirmed to effectively scavenge ROS in THP-1-derived macrophages and DPCs. Flow cytometry and RT-qPCR assays revealed that Ce-MBGNs significantly inhibited the M1 polarization of macrophages (Mφ). Furthermore, the protein levels of TNF-α and IL-1ß were downregulated in THP-1-derived macrophages after stimulation with Ce-MBGNs. With a step-forward virtue of promoting the odontoblastic differentiation of DPCs, we further confirmed that Ce-MBGNs could regulate the formation of a conductive immune microenvironment with respect to tissue repair in DPCs, which was mediated by macrophages. CONCLUSIONS: Ce-MBGNs protected cells from self-produced oxidative damage and exhibited excellent immunomodulatory and odontoblastic differentiation effects on DPCs. As a pulp-capping agent, this novel biomaterial can exert anti-inflammatory effects and promote restorative dentine regeneration in clinical treatment. We believe that this study will stimulate further correlative research on the development of advanced pulp-capping agents.

Regulation of Immune Inflammation and Promotion of Periodontal Bone Regeneration by Irisin-Loaded Bioactive Glass Nanoparticles.

Clinical solutions of bone defects caused by periodontitis involve surgical treatment and subsequent anti-infection treatment using antibiotics. Such a strategy faces a key challenge in that the excessive host immune response results in the damage of periodontal tissues. Consequently, it is of great importance to develop novel periodontitis treatment that allows the regulation of the host immune response and promotes the generation of periodontal tissues. Irisin has a good bone regeneration ability and could reduce the inflammatory reaction by regulating the differentiation of macrophages. In this study, we loaded irisin onto bioactive glass nanoparticles (BGNs) to prepare a composite, irisin-BGNs (IR-BGNs) with anti-inflammatory, bacteriostatic, and tissue regeneration functions, providing a novel idea for the design of ideal materials for repairing oral tissue defects caused by periodontitis. We also verified that the IR-BGNs had better anti-inflammatory properties on RAW264.7 cells compared to irisin and BGNs alone. Strikingly, when hPDLCs were stimulated with IR-BGNs, they exhibited increased expression of markers linked to osteogenesis, ALP activity, and mineralization ability in comparison to the negative control. Furthermore, on the basis of RNA sequencing results, we validated that the p38 pathway can contribute to the osteogenic differentiation of the IR-BGNs. This work may offer new thoughts on the design of ideal materials for repairing oral tissue defects.

Prenatal bisphenol S exposure induces hepatic lipid deposition in male mice offspring through downregulation of adipose-derived exosomal miR-29a-3p.

The increased usage of bisphenol S (BPS) results in wide distribution in pregnant women. In this study, pregnant mice were given multiple-dose BPS during gestation. Results showed that prenatal BPS exposure (50 µg/kg/day) induced increased weight gain, dyslipidemia, higher liver triglyceride (TG), adipocyte hypertrophy, and hepatic lipid deposition in male offspring. Exosomes play important roles in regulating lipid metabolism. Here, serum exosomes and adipose miRNA sequencing of male offspring indicated a remarkable decrease in miR-29a-3p expression. To clarify whether adipocyte-derived exosomes mediate hepatic lipid deposition, exosomes were extracted from BPS-treated adipocytes and co-cultured with hepatocytes. These exosomes could be taken up by hepatocytes and promoted lipid deposition, and notably, exosomal miR-29a-3p was downregulated. Furthermore, miR-29a-3p knockdown in adipocyte-derived exosomes promoted hepatocyte lipid deposition, whereas overexpression led to the opposite effect. Also, the role of miR-29a-3p was demonstrated in hepatocytes by overexpressing or knocking it down. Subsequent studies have shown that miR-29a-3p can promote lipid deposition by directly targeting Col4a1. Taken together, prenatal BPS exposure could lead to lower miR-29a-3p yield in adipocyte-derived exosomes and decrease miR-29a-3p content transported to hepatocytes, which further negatively regulate Col4a1 and promote hepatic lipid deposition. Our findings provided clues to maternal environmental exposure-induced liver metabolic diseases.

Palladium-catalyzed enantioselective alkenylation of alkenylbenzene derivatives.

A regioselective and enantioselective palladium-catalyzed relay Heck alkenylation of alkenylbenzene derivatives to construct remote stereocenters is disclosed. Various ß-substituted styrenes were readily obtained in moderate yields with good to excellent levels of enantioselectivity. This strategy provides rapid access to enantioenriched δ, ε, ζ, and η-alkenyl aryl compounds from simple starting materials. Mechanistic studies suggest that termination of the relay reaction is controlled by affinity of the arene for the Pd complex during migration.

Predictive and mechanistic multivariate linear regression models for reaction development.

Multivariate Linear Regression (MLR) models utilizing computationally-derived and empirically-derived physical organic molecular descriptors are described in this review. Several reports demonstrating the effectiveness of this methodological approach towards reaction optimization and mechanistic interrogation are discussed. A detailed protocol to access quantitative and predictive MLR models is provided as a guide for model development and parameter analysis.

Asymmetric Synthesis of Axially Chiral Isoquinolones: Nickel-Catalyzed Denitrogenative Transannulation.

The first Ni(0)/bis(oxazoline)-catalyzed asymmetric denitrogenative transannulation of 1,2,3-benzotriazin-4(3H)-ones with bulky internal alkynes to form novel axially chiral isoquinolones in an atroposelective manner has been developed. This method provides direct asymmetric access to axially chiral isoquinolones with excellent functional-group tolerance in excellent yields and stereoselectivities from readily available starting materials under mild reaction conditions. These axially chiral isoquinolones exhibit high cytotoxicity against a number of human cancer cell lines. DFT calculations reveal the nature of the transition state in the key annulation step.

Amide groups switch selectivity: C-H trifluoromethylation of α,ß-unsaturated amides and subsequent asymmetric transformation.

The first direct C-H ß-trifluoromethylation of unsubstituted or α-alkyl-substituted α,ß-unsaturated carbonyl compounds under metal-free conditions was realized with excellent regio- and stereoselectivity as well as a very broad substrate scope. Both olefinic and allylic trifluoromethylation products are accessible with high selectivities by altering the substrate substitutions. The resultant olefinic products, namely (E)-ß-trifluoromethyl (CF3) α,ß-unsaturated hydroxamic acid derivatives, served as acceptors in organocatalytic asymmetric Michael addition reactions to give hydroxamic acid derivatives bearing a chiral CF3-substituted stereocenter with high enantioselectivities.