Search

Ulcerative colitis (UC) is associated with the shedding of the gut mucus. Decellularized porcine small intestinal submucosa (SIS‐ECM) contains numerous active forms of extracellular matrix as well as growth factors. Herein, a mucus‐mimetic hydrogel (MAG) is designed as a barrier therapy by integrating SIS‐ECM with hyaluronic acid and epigallocatechin‐3‐gallate. MAG not only presented the viscoelastic behaviors with G' of 4000 Pa but also good thixotropy. Moreover, MAG as a physical shielding is effective to hinder E. coli invasion. Besides, the good repairing effect on the injured Caco‐2 cells is presented by MAG. When MAG as a biomimetic mucus is rectally administrated to colitis mouse, it alleviated effectively the colitis symptoms and improved the colonic shorting. Moreover, expression of IL‐1β, IL‐6, and TNF‐α at the laminae propria is substantially inhibited by MAG. Besides, the colonic epitheliums are well rearranged, and the tight junction proteins (ZO‐1, Occludin‐1, Claudin‐5) between them are greatly upregulated after MAG treatment. Meanwhile, the mucus secretion of goblets cells is effectively repaired by MAG treatment. The repairing mechanism of intestinal mucosa barriers is associated with promoting the proliferation and differentiation of intestinal stem cells. Collectively, MAG might be a promising strategy of barrier therapy for UC. [ABSTRACT FROM AUTHOR]

Background: Acute pancreatitis (AP) is a potentially lethal acute disease highly involved in coagulation disorders. Pyroptosis has been reported to exacerbate coagulation disorders, yet this implication has not been illustrated completely in AP. Methods: RNA sequencing data of peripheral blood of AP patients were downloaded from the Gene Expression Omnibus database. Gene set variation analysis and single sample gene set enrichment analysis were used to calculate the enrichment score of coagulation‐related signatures and pyroptosis. Spearman and Pearson correlation analysis was used for correlation analysis. Peripheral blood samples and related clinical parameters were collected from patients with AP and healthy individuals. A severe AP (SAP) model of mice was established using caerulein and lipopolysaccharide. Enzyme‐linked immunosorbent assay, chemiluminescence immunoassay and immunohistochemical analysis were employed to detect the level of coagulation indicators and pyroptosis markers in serum and pancreas tissues. Additionally, we evaluated the effect of pyroptosis inhibition and NLRC4 silence on the function of human umbilical vein endothelial cells (HUVECs). Results: Coagulation disorders were significantly positively correlated to the severity of AP, and they could be a predictor for AP severity. Further analyses indicated that six genes—DOCK9, GATA3, FCER1G, NLRC4, C1QB and C1QC—may be involved in coagulation disorders of AP. Among them, NLRC4 was positively related to pyroptosis that had a positive association with most coagulation‐related signatures. Data from patients showed that NLRC4 and other pyroptosis markers, including IL‐1β, IL‐18, caspase1 and GSDMD, were significant correlation to AP severity. In addition, NLRC4 was positively associated with coagulation indicators in AP patients. Data from mice showed that NLRC4 was increased in the pancreas tissues of SAP mice. Treatment with a pyroptosis inhibitor effectively alleviated SAP and coagulation disorders in mice. Finally, inhibiting pyroptosis or silencing NLRC4 could relieve endothelial dysfunction in HUVECs. Conclusions: NLRC4‐mediated pyroptosis damages the function of endothelial cells and thereby exacerbates coagulation disorders of AP. Inhibiting pyroptosis could improve coagulation function and alleviate AP. [ABSTRACT FROM AUTHOR]

Although the emerging of immunotherapy conferred a new landscape of gastric cancer (GC) treatment, its response rate was of significant individual differences. Insight into GC immune microenviroment may contribute to breaking the dilemma. To this end, the enrichment score of NF- κ B signaling pathway was calculated in each GC sample from The Cancer Genome Atlas (TCGA) via ssGSEA algorithm, and its association with immune infiltration was estimated. Based on NF- κ B-related genes, a risk score was established and its involvement in immune infiltration, tumor mutational burden (TMB), and N6-methyladenosine (M6A) modification was analyzed in GC. The results showed that NF- κ B signaling pathway promoted the infiltration of immune cells in GC. In addition, GC samples were divided into low- and high-risk groups according to a seven-gene ( CARD11 , CCL21 , GADD45B , LBP , RELB , TRAF1 , and VCAM1 ) risk score. Although the high-risk group displayed high immune infiltration and high expression of M6A regulatory genes, it remains in an immunosuppressive microenviroment and whereby suffers a poorer outcome. Of note, most of hub genes were related to immune infiltration and could serve as an independent prognostic biomarker. Conclusively, our study emphasized the crucial role of NF- κ B signaling pathway in GC immune microenviroment and provided several candidate genes that may participate in immune infiltration., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Qiuxiang Chen et al.)

Background: Sufficient evidence indicated the crucial role of NF- κ B family played in gastric cancer (GC). The novel discovery that NF- κ B could regulate cancer metabolism and immune evasion greatly increased its attraction in cancer research. However, the correlation among NF- κ B, metabolism, and cancer immunity in GC still requires further improvement., Methods: TCGA, hTFtarget, and MSigDB databases were employed to identify NF- κ B-related metabolic genes (NFMGs). Based on NFMGs, we used consensus clustering to divide GC patients into two subtypes. GSVA was employed to analyze the enriched pathway. ESTIMATE, CIBERSORT, ssGSEA, and MCPcounter algorithms were applied to evaluate immune infiltration in GC. The tumor immune dysfunction and exclusion (TIDE) algorithm was used to predict patients' response to immunotherapy. We also established a NFMG-related risk score by using the LASSO regression model and assessed its efficacy in TCGA and GSE62254 datasets., Results: We used 27 NFMGs to conduct an unsupervised clustering on GC samples and classified them into two clusters. Cluster 1 was characterized by high active metabolism, tumor mutant burden, and microsatellite instability, while cluster 2 was featured with high immune infiltration. Compared to cluster 2, cluster 1 had a better prognosis and higher response to immunotherapy. In addition, we constructed a 12-NFMG ( ADCY3 , AHCY , CHDH , GUCY1A2 , ITPA , MTHFD2 , NRP1 , POLA1 , POLR1A , POLR3A , POLR3K , and SRM ) risk score. Followed analysis indicated that this risk score acted as an effectively prognostic factor in GC., Conclusion: Our data suggested that GC subtypes classified by NFMGs may effectively guide prognosis and immunotherapy. Further study of these NFMGs will deepen our understanding of NF- κ B-mediated cancer metabolism and immunity., Competing Interests: All authors have no conflict of interest to declare., (Copyright © 2022 Qiuxiang Chen et al.)