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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]

Background and Aims Group 3 innate lymphoid cells [ILC3s] sense environmental signals and are critical in gut homeostasis and immune defence. G-protein-coupled receptors [GPCRs] mediate cellular responses to diverse environmental signals. However, the GPCRs' regulation mechanisms of ILC3s is largely unknown. Methods We used wild-type [WT] and GPRC6A -/- mice to investigate the role of GPRC6A in the population and the function of ILC3s. We then purified ILC3s from WT and GPRC6A -/- mice. Colitis was induced in WT mice and GPRC6A -/- mice through dextran sodium sulphate [DSS] administration or C. rodentium infection. Furthermore L-arginine, a selective GPRC6A agonist, was administered to mice with colitis. Results We found that colonic ILC3s expressed GPRC6A. The deficiency of GPRC6A decreased ILC3-derived interleukin-22 [IL-22] production and the number of proliferating ILC3s, which led to increased susceptibility to colon injury and pathogen infection and impaired inflamed mucosal healing. Further studies showed that L-arginine, a GPRC6A agonist, promoted colonic ILC3 expansion and function via the mammalian target of rapamycin complex 1 [mTORC1] signalling in vitro. In addition, L-arginine attenuated DSS-induced colitis in vivo. This was associated with a significant increase in IL-22 secretion by ILC3s. Conclusions Our findings unveil a role for the nutrient-sensing receptor GPRC6A in colonic ILC3 function and identify a novel ILC3 receptor signalling pathway modulating inflamed mucosal healing. [ABSTRACT FROM AUTHOR]

Objectives. Previous experiments have shown that growth factor receptors play important role in tumor proliferation, metastasis, and therapeutic effect of chemotherapeutic drugs. At the same time, forkhead box D1 (FOXD1) plays an important role in a variety of signal transmission, but its expression profile was known little about head and neck cancer. The purpose of this experiment was to explore the regulation of FOXD1 on the tumor progression of head and neck cancer and to explore the correlation of FOXD1 on the expression of growth factor receptors (EGFR). Methods. The bioinformatics online database analyzed the expression of FOXD1 and EGFR in tumor tissues and nontumor tissues. Real-time quantitative PCR was used to detect the FOXD1 and EGFR expression in 45 tumor tissues and 15 nontumor tissues. The plasmid was used to construct FOXD1 overexpressing head and neck squamous cell cancer lines and observe the clonal formation and invasion of tumor cells under the intervention of EGFR-specific antibody—cetuximab. Results. The expression of FOXD1 and EGFR in tumor tissues was higher than that in nontumor tissues. The higher expression of FOXD1 and EGFR was not conducive to the prognosis of patients. The expression of FOXD1 and EGFR was positively correlated, and immunohistochemical analysis showed the high expression of FOXD1 and EGFR has close relation to the advanced stage of the tumor. In vitro cell experiments proved that overexpression of FOXD1 can partially offset the cloning ability of cetuximab on head and neck tumor cells. Conclusion. FOXD1 has an important regulatory role in the progression of head and neck cancer, and its abnormally high expression was not conducive to the prognosis of cancer patients. FOXD1 can regulate the expression of growth factor receptors in head and neck cancer, which provides a new idea for the better use of tumor growth factor receptor-specific antibodies for collaborative therapy. [ABSTRACT FROM AUTHOR]

The mammalian intestine is the largest immune organ that contains the intestinal stem cells (ISC), differentiated epithelial cells (enterocytes, Paneth cells, goblet cells, tuft cells, etc.), and gut resident-immune cells (T cells, B cells, dendritic cells, innate lymphoid cell, etc.). Inflammatory bowel disease (IBD), a chronic inflammatory disease characterized by mucosa damage and inflammation, threatens the integrity of the intestine. The continuous renewal and repair of intestinal mucosal epithelium after injury depend on ISCs. Inflamed mucosa healing could be a new target for the improvement of clinical symptoms, disease recurrence, and resection-free survival in IBD treated patients. The knowledge about the connections between ISC and immune cells is expanding with the development of in vitro intestinal organoid culture and single-cell RNA sequencing technology. Recent findings implicate that immune cells such as T cells, ILCs, dendritic cells, and macrophages and cytokines secreted by these cells are critical in the regeneration of ISCs and intestinal epithelium. Transplantation of ISC to the inflamed mucosa may be a new therapeutic approach to reconstruct the epithelial barrier in IBD. Considering the links between ISC and immune cells, we predict that the integration of biological agents and ISC transplantation will revolutionize the future therapy of IBD patients. [ABSTRACT FROM AUTHOR]

Age-related gastrointestinal decline contributes to whole-organism frailty and mortality. Genistein is known to have beneficial effects on age-related diseases, but its precise role in homeostasis of the aging gut remains to be elucidated. Here, wild-type aging mice and Zmpste24 -/- progeroid mice were used to investigate the role of genistein in lifespan and homeostasis of the aging gut in mammals. A series of longitudinal, clinically relevant measurements were performed to evaluate the effect of genistein on healthspan. It was found that dietary genistein promoted a healthier and longer life and was associated with a decrease in the levels of systemic inflammatory cytokines in aging mice. Furthermore, dietary genistein ameliorated gut dysfunctions, such as intestinal inflammation, leaky gut, and impaired epithelial regeneration. A distinct genistein-mediated alteration in gut microbiota was observed by increasing Lachnospira abundance and short-chain fatty acid (SCFA) production. Further fecal microbiota transplantation and dirty cage sharing experiments indicated that the gut microbiota from genistein-fed mice rejuvenated the aging gut and extended the lifespan of progeroid mice. It was demonstrated that genistein-associated SCFAs alleviated tumor necrosis factor alpha-induced intestinal organoid damage. Moreover, genistein-associated propionate promoted regulatory T cell-derived interleukin 10 production, which alleviated macrophage-derived inflammation. This study provided the first data, to the authors' knowledge, indicating that dietary genistein modulates homeostasis in the aging gut and extends the healthspan and lifespan of aging mammals. Moreover, the existence of a link between genistein and the gut microbiota provides a rationale for dietary interventions against age-associated frailty. [Display omitted] [ABSTRACT FROM AUTHOR]

The importance of lighting regimen is increasing with the industrialization of poultry production, as lighting has been intimately associated with not only the establishment of rhythm and synchronous physiology of broiler chickens, but also the secretion of hormones associated with broiler maturation and growth. In recent years, increasing attention has been paid to the effects of lighting management on growth performance, immune status, and welfare of broilers. An appropriate lighting regimen, including proper source of lighting, intensity, duration, and wavelength (color) of light, is crucial to improve the growth performance and welfare of broilers. In this review, we updated the impacts of different light regimens on health and growth performance of broilers. [Display omitted] [ABSTRACT FROM AUTHOR]

BackgroundSocial media is currently becoming a new channel for information acquisition and exchange. In China, with the growing popularity of WeChat and WeChat official accounts (WOAs), health promotion agencies have an opportunity to use them for successful information distribution and diffusion online. ObjectiveWe aimed to identify features of articles pushed by WOAs of Chinese provincial Centers for Disease Control and Prevention (CDC) that are associated with user engagement. MethodsWe searched and subscribed to 28 WOAs of provincial CDCs. Data for this study consisted of WeChat articles on these WOAs between January 1, 2017 and December 31, 2017. We developed a features frame containing title type, article content, article type, communication skills, number of marketing elements, and article length for each article and coded the data quantitatively using a coding scheme that assigned numeric values to article features. We examined the descriptive characteristics of articles for every WOA and generated descriptive statistics for six article features. The amount of reading and liking was converted into the level of reading and liking by the 75% position. Two-category univariate logistic regression and multivariable logistic regression were conducted to explore associations between the features of the articles and user engagement, operationalized as reading level and liking level. ResultsAll provincial CDC WOAs provided a total of 5976 articles in 2017. Shanghai CDC articles attracted the most user engagement, and Ningxia CDC articles attracted the least. For all articles, the median reading was 551.5 and the median liking was 10. Multivariable logistic regression analysis revealed that article content, article type, communication skills, number of marketing elements, and article length were associated with reading level and liking level. However, title type was only associated with liking level. ConclusionsHow social media can be used to best achieve health information dissemination and public health outcomes is a topic of much discussion and study in the public health community. Given the lack of related studies based on WeChat or official accounts, we conducted this study and found that article content, article type, communication skills, number of marketing elements, article length, and title type were associated with user engagement. Our study may provide public health and community leaders with insight into the diffusion of important health topics of concern.