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Background and objective: The application of curcumin is limited by its instability. Mono‐carbonyl analogues of curcumin (MCACs) are structurally stable, yet the intermediate bridging ketones in their skeletons account for increased toxicity. This study aimed to synthesize and screen MCACs that exhibit low cytotoxicity and high antioxidant ability, and the effects of MCACs on experimental periodontitis were also investigated. Materials and methods: The cytotoxicity of MCACs on MC3 T3‐E1 was determined by MTT assay. The antioxidant capacity was investigated by the cell viability against H2O2‐induced damage and the level of reactive oxygen species (ROS) and malondialdehyde (MDA). The localization and protein expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) was detected by immunofluorescence and western blot, respectively. In addition, MCAC was intragastrically administrated in rats with ligature‐induced experimental periodontitis. The effects were assessed by bone resorption, as well as the immunohistology staining of inflammatory and oxidative stress markers. Results: MCACs with cyclopentanone and containing pyrone showed lower toxicity than natural curcumin were synthesized (1A‐10A, 1H‐10H), among which, 1A exhibited the most potent cytoprotective effect against H2O2‐induced damage. Such effects could be explained by the reduced MDA and ROS level, possibly through the nucleus translocation of Nrf2 and the induction of HO‐1. Micro‐CT results further indicated that 1A significantly reduced bone loss, along with an increased level of Nrf2 and HO‐1, and decreased TNF‐α and IL‐1β. Conclusion: The present study has synthesized a novel antioxidant MCAC 1A with good biosafety and stability. MCAC 1A could serve as a host response modulator with preventive and protective effects on periodontitis. [ABSTRACT FROM AUTHOR]

Osseointegration commences with foreign body inflammation upon implant placement, where macrophages play a crucial role in the immune response. Subsequently, during the intermediate and late stages of osseointegration, mesenchymal stem cells (MSCs) migrate and initiate their osteogenic functions, while macrophages support MSCs in osteogenesis. The utilization of ferroelectric P(VDF-TrFE) covered ITO planar microelectrodes facilitated the simulation of various surface charge to investigate their effects on MSCs' osteogenic differentiation and macrophage polarization and the results indicated a parabolic increase in the promotional effect of both with the rise in piezoelectric coefficient. Furthermore, the surface charge with a piezoelectric coefficient of -18 exhibited the strongest influence on the promotion of M1 polarization of macrophages and the promotion of MSCs' osteogenic differentiation. The impact of macrophage polarization and MSC osteogenesis following the interaction of macrophages affected by surface charge and MSC was ultimately investigated. It was observed that macrophages affected by the surface charge of -18 piezoelectric coefficient still exerted the most profound induced osteogenic effect, validating the essential role of M1-type macrophages in the osteogenic differentiation of MSCs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Xu, Huang, Chen, Cheng, Wang and Chen.)

This experiment investigates how the miR-99b/let-7e/miR-125a cluster regulates the mechanism of NR6A1 involved in the invasive and metastatic effects of pancreatic cancer (PCa). Bioinformatics prediction and dual luciferase reporter gene assay were applied to verify the targeted relationship between miR-99b/let-7e/miR-125a and NR6A1. ASPC1 cells underwent transfection with lentiviruses to overexpress miR-99b/let-7e/miR-125a (individual or together) to explore functions of miR-99b/let-7e/miR-125a cluster governing NR6A1 in PCa. The detection of tumorigenesis was verified by tumor formation assay in nude mice in vivo, and mouse models of liver metastasis of PCa observed cell metastasis of PCa. MiR-99b/let-7e/miR-125a cluster was screened for differential expression in PCa. NR6A1 was confirmed as a target gene of the miR-99b/let-7e/miR-125a cluster. Findings demonstrated that overexpression of the miR-99b/let-7e/miR-125a cluster inhibited cell invasion, metastasis, proliferation, and tumorigenesis in PCa. Conversely, overexpressed NR6A1, a crucial gene in the miR-99b/let-7e/miR-125a cluster, promoted cell invasion, migration, and proliferation in PCa. Moreover, the overexpression of the miR-99b/let-7e/miR-125a cluster inhibited liver metastases and tumor formation. Thus, the study concludes that the miR-99b/let-7e/miR-125a cluster impedes the invasion and metastasis of PCa cells via targeting the NR6A1 gene., Competing Interests: None., (AJCR Copyright © 2024.)

Structural parameters of the implants such as shape, size, and porosity of the pores have been extensively investigated to promote bone tissue repair, however, it is unknown how the pore interconnectivity affects the bone growth behaviors in the scaffolds. Herein we systematically evaluated the effect of biodegradable bioceramics as a secondary phase filler in the macroporous networks on the mechanical and osteogenic behaviors in sparingly dissolvable bioceramic scaffolds. The pure hardystonite (HT) scaffolds with ∼550 & 800 μm in pore sizes were prepared by digital light processing, and then the Sr-doped calcium silicate (SrCSi) bioceramic slurry without and with 30 % organic porogens were intruded into the HT scaffolds with 800 μm pore size and sintered at 1150 °C. It indicated that the organic porogens could endow spherical micropores in the SrCSi filler, and the invasion of the SrCSi component could not only significantly enhance the compressive strength and modulus of the HT-based scaffolds, but also induce osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The pure HT scaffolds showed extremely slow bio-dissolution in Tris buffer after immersion for 8 weeks (∼1 % mass decay); in contrast, the SrCSi filler would readily dissolve into the aqueous medium and produced a steady mass decay (>6 % mass loss). In vivo experiments in rabbit femoral bone defect models showed that the pure HT scaffolds showed bone tissue ingrowth but the bone growth was impeded in the SrCSi-intruded scaffolds within 4 weeks; however, the group with higher porosity of SrCSi filler showed appreciable osteogenesis after 8 weeks of implantation and the whole scaffold was uniformly covered by new bone tissues after 16 weeks. These findings provide some new insights that the pore interconnectivity is not inevitable to impede bone ingrowth with the prolongation of implantation time, and such a highly biodegradable and bioactive filler intrusion strategy may be beneficial for optimizing the performances of scaffolds in bone regenerative medicine applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)