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This review elaborates on biochemical characteristics, in vivo metabolism, biological conversion through UV irradiation, as well as dietary fortification of vitamin D. Recent innovations in vitamin D utilization, including nanoencapsulation, direct or indirect addition, emulsion, ultrasound, microwave processing, CRISPR-Cas9 genome editing, as well as UV photoconversion, were summarized. Mushrooms, eggs, yeasts, as well as seafood, such as Barramundi and Atlantic salmon, were typical representatives of original natural food materials for vitamin D bioconversion in relevant research. The critical session thereof referred to the 295 nm UV-B irradiation triggering biological fortification of vitamin D2 and vitamin D3, which occurred in ergosterol from mushrooms, and cholesterol from egg yolk, respectively. The schematic biosynthesis of vitamin D precursors in yeasts regulated miscellaneous enzymes were clearly demonstrated. These summarized pathways played a role as a theoretical primer for vitamin D bioconversion when the UV irradiation technique is concerned. Besides, tomatoes had become the latest potential vitamin D sources after genetic modification. The safety consideration for vitamin D fortified functional food was discussed either. Further research is required to fill the gap of investigating optimized factors like types of eggs, meat, and grain, boarder range of wavelength, and dosage in UV irradiation. Vitamin D has a great potential market in the field of functional food development. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) remains a predominant form of malignant tumor globally, necessitating innovative non-surgical therapeutic approaches. This investigation aimed to delineate the expression landscape of macrophage-associated genes in GC and to evaluate their prognostic significance and influence on immunotherapeutic responsiveness. Utilizing the CellMarker2.0 database, we identified 69 immune cell markers with prognostic relevance in GC, including 12 macrophage-specific genes. A Weighted Gene Co-Expression Network Analysis (WGCNA) isolated 3,181 genes correlated with these macrophage markers. The Cancer Genome Atlas (TCGA-STAD) dataset was employed as the training set, while data from the GSE62254 served as the validation cohort. 13 genes were shortlisted through LASSO-Cox regression to formulate a prognostic model. Multivariable Cox regression substantiated that the calculated risk score serves as an imperative independent predictor of overall survival (OS). Distinct macrophage infiltration profiles, pathway associations, treatment susceptibilities, and drug sensitivities were observed between high- and low-risk groups. The preliminary validation of ANXA5 in predicting the survival rates of GC patients at 1 year, 3 years, and 5 years, as well as its expression levels were higher and role in promoting tumor angiogenesis in GC through immunohistochemistry and angiogenesis experiments. In summary, macrophage-related genes were potentially a novel crosstalk mechanism between macrophages and endothelial cells in the tumor microenvironment, and the interplay between inflammation and angiogenesis might have also offered new therapeutic targets, providing a new avenue for personalized treatment interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Studies have shown that SPP1 plays an important role in the progression of certain tumors, but the specific functional mechanism in gastric cancer (GC) is still unclear. Our goal was to reveal the prognostic value of SPP1 in GC and its role in the GC tumor microenvironment based on multi-transcriptomic analysis. We demonstrated that a high expression of SPP1 contributed to advanced gastric TNM stages and a poor prognosis for advanced GC patients, providing a solution to the controversy regarding the clinical relevance of SPP1 in GC. Furthermore, we found that SPP1+ macrophages were unique to GC cancerous tissues and cancer cell-containing regions, and that the SPP1/CD44-mediated crosstalk between SPP1+ macrophages and cancer cells formed a specific niche to accelerate the malignant progression of GC, which may serve as a therapeutic target with fewer side-effects in GC. GC is a fatal disease with high heterogeneity and invasiveness. Recently, SPP1 has been reported to be involved in the tumor progression of multiple human cancers; however, the role of SPP1 in GC heterogeneity and whether it is associated with the invasiveness and mortality of GC remain unclear. Here, we combined multiple RNA sequencing approaches to evaluate the impact of SPP1 on GC. Through bulk RNA sequencing (bulk RNA-seq) and immunohistochemistry (IHC), we found that SPP1 was highly expressed in GC, and high levels of SPP1 were associated with macrophage infiltration, an advanced tumor stage, and higher mortality for advanced GC patients. Furthermore, through simultaneous single-cell and spatial analysis, we demonstrated that SPP1+ macrophages are tumor-specific macrophages unique to cancer and enriched in the deep layer of GC tissue. Cell—cell communication analysis revealed that SPP1/CD44 interactions between SPP1+ macrophages and their localized tumor epithelial cells could activate downstream target genes in epithelial cells to promote dynamic changes in intratumor heterogeneity. Moreover, these activated genes were found to be closely associated with poor clinical GC outcomes and with cancer-related pathways that promote GC progression, as shown by survival analysis and enrichment analysis, respectively. Collectively, our study reveals that tumor-specific SPP1+ macrophages drive the architecture of intratumor heterogeneity to evolve with tumor progression and that SPP1 may serve as a prognostic marker for advanced GC patients, as well as a potential therapeutic target for GC. [ABSTRACT FROM AUTHOR]

Background and Aims: Endoscopic submucosal dissection (ESD) is a pivotal technique for excision of early-stage esophageal tumors. However, its primary complication, postoperative esophageal stricture, is a significant challenge owing to the absence of effective preventive measures. Adipose-derived stem cells (ADSCs) have emerged as a promising treatment modality to address this concern. In this study, we aimed to investigate, for the first time, the efficacy of allogenic ADSC injections in preventing esophageal stenosis after ESD., Methods: We administered allogeneic ADSC injections ((same-species but different individual)) to a porcine model of ESD as a way to observe the role of ADSC in preventing esophageal stricture. We also co-cultured rats ADSCs with rats esophageal fibroblasts and esophageal mucosal epithelial cells to investigate the mechanism., Results: ADSCs notably facilitated epithelial-mesenchymal transition (EMT) of epithelial cells. Furthermore, ADSC-conditioned medium exhibited a substantial inhibitory effect on fibroblast proliferation and migration, which was mediated by the transforming growth factor-beta pathway., Conclusions: Our findings underscore the potential of ADSC injections as a promising therapeutic intervention to enhance recovery and prevent post-ESD complications., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. Despite the widespread recognition of tumor immunotherapy in treating unresectable GC, challenges, including ineffective immunotherapy and drug resistance, persist. Therefore, understanding the regulatory mechanisms of PD-L1, particularly in the context of super-enhancers (SEs) and zinc finger protein 36 ring finger protein-like 1 (ZFP36L1) RNA-binding protein, is crucial. In this study, we performed H3K27ac Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing, investigated the heterogeneity of SEs between two GC subtypes with differential growth patterns, and revealed the immune escape signatures driven by ZFP36L1-SE in infiltrative GC through SEs inhibitors treatment. The regulation of ZFP36L1 to PD-L1 was evaluated by quantitative PCR, western blot, flow cytometry, and immunohistochemistry. Furthermore, we explored its regulatory mechanisms using a combination of molecular biology techniques, including luciferase reporter assay, GST/RNA pull-down, chromatin immunoprecipitation (ChIP)/RIP experiments, and in vivo functional assays. We demonstrated that ZFP36L1, driven by an SE, enhances IFN-γ-induced PD-L1 expression, with SPI1 identified as the specific transcription factor binding to ZFP36L1-SE. Mechanistically, ZFP36L1 binds to the adenylate uridylate-rich element in the 3' untranslated region (3'UTR) of HDAC3 mRNA, exacerbating its mRNA decay, and thereby facilitating PD-L1 abnormal transcriptional activation. Collectively, our findings provide mechanistic insights into the role of the SPI1-ZFP36L1-HDAC3-PD-L1 signaling axis in orchestrating immune escape mechanisms in GC, thereby offering valuable insights into the potential targets for immune checkpoint therapy in GC management., Competing Interests: XW, JL, JC, WC, WX, KW, LL, JH, JC, HZ No competing interests declared, (© 2024, Wei, Liu et al.)