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The aryl hydrocarbon receptor (AhR) is a transcription factor that regulates the immune system through complicated transcriptional programs. Genistein, an AhR ligand, exhibits anti-inflammatory properties. However, its role in modulating immune responses via the AhR signaling pathway remains unclear. In this study, 360 male Arbor Acre broilers (1-day-old) were fed a basal diet supplemented with 40 or 80 mg/kg genistein and infected with or without Clostridium perfringens (Cp). Our results demonstrated that genistein ameliorated Cp-induced intestinal damage, as reflected by the reduced intestinal lesion scores and improved intestinal morphology and feed-to-gain ratio. Moreover, genistein increased intestinal sIgA, TGF-β, and IL-10, along with elevated serum IgG, IgA, and lysozyme levels. Genistein improved intestinal AhR and cytochrome P450 family 1 subfamily A member 1 (CYP1A1) protein levels and AhR+ cell numbers in Cp-challenged broilers. The increased number of AhR+CD163+ cells in the jejunum suggested a potential association between genistein-induced AhR activation and anti-inflammatory effects mediated through M2 macrophage polarization. In IL-4-treated RAW264.7 cells, genistein increased the levels of AhR, CYP1A1, CD163, and arginase (Arg)-1 proteins, as well as IL-10 mRNA levels. This increase was attenuated by the AhR antagonist CH223191. In summary, genistein activated the AhR signaling pathway in M2 macrophages, which enhanced the secretion of anti-inflammatory cytokines and attenuated intestinal damage in Cp-infected broilers Cp. [ABSTRACT FROM AUTHOR]

The integration of hydroxyapatite (HA) with broad-spectrum bactericidal nano-silver within biopolymer-based bone scaffolds not only promotes new bone growth, but also effectively prevents bacterial infections. However, there are problems such as a poor interface compatibility and easy agglomeration. In this project, zeolitic imidazolate frameworks (ZIF-8) were grown in situ on nano-HA to construct a core–shell structure, and silver was loaded into the ZIF-8 shell through ion exchange. Finally, the core–shell structure (HA@Ag) was composited with polylactic acid (PLLA) to prepare bone scaffolds. In this case, the metal zinc ions of ZIF-8 could form ionic bonds with the phosphate groups of HA by replacing calcium ions, and the imidazole ligands of ZIF-8 could form hydrogen bonds with the carboxyl groups of the PLLA, thus enhancing the interface compatibility between the biopolymers and ceramics. Additionally, the frame structure of MOFs enabled controlling the release of silver ions to achieve a long-term antibacterial performance. The test results showed that the HA@Ag nanoparticles endowed the scaffold with good antibacterial and osteogenic activity. Significantly, the HA@Ag naoaprticle exhibited a good interfacial compatibility with the PLLA matrix and could be relatively evenly dispersed within the matrix. Moreover, the HA@ZIF-8 also effectively enhanced the mechanical strength and degradation rate of the PLLA scaffold. [ABSTRACT FROM AUTHOR]

Background: Lysosomal cathepsin D (CTSD) can degrade internalized advanced glycation end products (AGEs) in dermal fibroblasts. CTSD expression is decreased in photoaged fibroblasts, which contributes to intracellular AGEs deposition and further plays a role in AGEs accumulation of photoaged skin. The mechanism under downregulated CTSD expression is unclear. Objective: To explore possible mechanism of regulating CTSD expression in photoaged fibroblasts. Methods: Dermal fibroblasts were induced into photoaging with repetitive ultraviolet A (UVA) irradiation. The competing endogenous RNA (ceRNA) networks were constructed to predict candidate circRNAs or miRNAs related with CTSD expression. AGEs‐BSA degradation by fibroblasts was studied with flow cytometry, ELISA, and confocal microscopy. Effects of overexpressing circRNA‐406918 via lentiviral transduction on CTSD expression, autophagy, AGE‐BSA degradation were analyzed in photoaged fibroblasts. The correlation between circRNA‐406918 and CTSD expression or AGEs accumulation in sun‐exposed and sun‐protected skin was studied. Results: CTSD expression, autophagy, and AGEs‐BSA degradation were significantly decreased in photoaged fibroblasts. CircRNA‐406918 was identified to regulate CTSD expression, autophagy, and senescence in photoaged fibroblasts. Overexpressing circRNA‐406918 potently decreased senescence and increased CTSD expression, autophagic flux, and AGEs‐BSA degradation in photoaged fibroblasts. Moreover, circRNA‐406918 level was positively correlated with CTSD mRNA expression and negatively associated with AGEs accumulation in photodamaged skin. Further, circRNA‐406918 was predicted to mediate CTSD expression through sponging eight miRNAs. Conclusion: These findings suggest that circRNA‐406918 regulates CTSD expression and AGEs degradation in UVA‐induced photoaged fibroblasts and might exert a role in AGEs accumulation in photoaged skin. [ABSTRACT FROM AUTHOR]

Appropriate biomimetic scaffolds created via 3D bioprinting are promising methods for treating damaged menisci. However, given the unique anatomical structure and complex stress environment of the meniscus, many studies have adopted various techniques to take full advantage of different materials, such as the printing combined with infusion, or electrospining, to chase the biomimetic meniscus, which makes the process complicated to some extent. Some researchers have tried to tackle the challenges only by 3D biopringting, while its alternative materials and models have been constrained. In this study, based on a multilayer biomimetic strategy, we optimized the preparation of meniscus-derived bioink, gelatin methacrylate (GelMA)/meniscal extracellular matrix (MECM), to take printability and cytocompatibility into account together. Subsequently, a customized 3D bioprinting system featuring a dual nozzle + multitemperature printing was used to integrate the advantages of polycaprolactone (PCL) and meniscal fibrocartilage chondrocytes (MFCs)-laden GelMA/MECM bioink to complete the biomimetic meniscal scaffold, which had the best biomimetic features in terms of morphology and components. Furthermore, cell viability, mechanics, biodegradation and tissue formation in vivo were performed to ensure that the scaffold had sufficient feasibility and functionality, thereby providing a reliable basis for its application in tissue engineering.