Goat Anti-Human RELA Polyclonal Antibody

Purpose The ceramide pathway is strongly associated with the regulation of tumor proliferation, differentiation, senescence, and apoptosis. This study aimed to explore the gene signatures, prognostic value, and immune-related effects of ceramide-regulated genes in lung adenocarcinoma (LUAD). Methods Public datasets of LUAD from The Cancer Genome Atlas and Gene Expression Omnibus were selected. Consensus clustering was adopted to classify LUAD patients, and a least absolute shrinkage and selection operator (LASSO) regression model was employed to develop a prognostic risk signature. CIBERSORT algorithm was used to estimate the association between the risk signature and the tumor immune microenvironment. Results Most of the 22 ceramide-regulated genes were differentially expressed between LUAD and normal samples. LUAD patients were classified into two subgroups (cluster 1 and 2) and cluster 2 was associated with a poor prognosis. Furthermore, a prognostic risk signature was developed based on the three ceramide-regulated genes, Cytochrome C (CYCS), V-rel reticuloendotheliosis viral oncogene homolog A (RELA) and Fas-associated via death domain (FADD). LUAD patients with low- and high-risk scores differed concerning the subtypes of tumor-infiltrating immune cells. A moderate to weak correlation was observed between the risk score and tumor-infiltrating immune cells. Conclusions Ceramide-regulated genes could predict clinical prognostic risk and affect the tumor immune microenvironment in LUAD.

Objectives. Xerostomia in SS patients has been associated with low quality and quantity of salivary mucins, which are fundamental for the hydration and protection of the oral mucosa. The aim of this study was to evaluate if cytokines induce aberrant mucin expression and whether tauroursodeoxycholic acid (TUDCA) is able to counteract such an anomaly. Methods. Labial salivary glands from 16 SS patients and 15 control subjects, as well as 3D acini or human submandibular gland cells stimulated with TNF-alpha or IFN-gamma and co-incubated with TUDCA, were analysed. mRNA and protein levels of Mucin 1 (MUC1) and MUC7 were determined by RT-qPCR and western blot, respectively. Co-immunoprecipitation and immunofluorescence assays for mucins and GRP78 [an endoplasmic reticulum (ER)-resident protein] were also performed. mRNA levels of RelA/p65 (nuclear factor-kappa B subunit), TNF-alpha, IL-1 beta, IL-6, SEL1L and EDEM1 were determined by RT-qPCR, and RelA/p65 localization was evaluated by immunofluorescence. Results. MUC1 is overexpressed and accumulated in the ER of labial salivary gland from SS patients, while MUC7 accumulates throughout the cytoplasm of acinar cells; however, MUC1, but not MUC7, co-precipitated with GRP78. TUDCA diminished the overexpression and aberrant accumulation of MUC1 induced by TNF-alpha and IFN-gamma, as well as the nuclear translocation of RelA/p65, together with the expression of inflammatory and ER stress markers in 3D acini. Conclusion. Chronic inflammation alters the secretory process of MUC1, inducing ER stress and affecting the quality of saliva in SS patients. TUDCA showed anti-inflammatory properties decreasing aberrant MUC1 accumulation. Further studies are necessary to evaluate the potential therapeutic effect of TUDCA in restoring glandular homeostasis in SS patients.