scholarly journals Patients with APECED possess altered NFkB pathway gene expression.

2020 ◽  
Author(s):  
Shahan Mamoor

APECED, or autoimmune polyendocrinopathy candidiasis ectodermal dystrophy, is an autoimmune disorder caused by mutations in the autoimmune regulator gene AIRE (1, 2). Though it is known that 42 separate mutations in the AIRE gene can cause APECED (3), it not understood how these mutations lead to the pathology seen in APECED patients, and there are limited systems-level studies of the underlying transcriptional behavior of the immune cells of patients with APECED (4). In this study, we used a dataset (5) to compare the transcriptomes of monocyte-derived dendritic cells (moDCs) from patients with APECED and from control, non-affected patients in order to understand and describe the basic transcriptional nature of cells from patients with APECED. We found that four separate components of the NF-kB signaling pathway were among the genes most differentially expressed by moDCs from APECED patients. These included the NF-kB subunit REL, the NF-kB inhibitor alpha NFKBIA, the NF-kB inhibitor beta NFKBIZ, and the NF-kB inhibitor interacting Ras like 2 gene NKIRAS2. This is the first systems-level analysis of moDCs from patients with APECED to document perturbed gene expression in the NF-kB signaling pathway.

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Silu Meng ◽  
Xinran Fan ◽  
Jianwei Zhang ◽  
Ran An ◽  
Shuang Li

Gap Junction Protein Alpha 1 (GJA1) belongs to the gap junction family and has been widely studied in cancers. We evaluated the role of GJA1 in cervical cancer (CC) using public data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. The difference of GJA1 expression level between CC and normal tissues was analyzed by the Gene Expression Profiling Interactive Analysis (GEPIA), six GEO datasets, and the Human Protein Atlas (HPA). The relationship between clinicopathological features and GJA1 expression was analyzed by the chi-squared test and the logistic regression. Kaplan–Meier survival analysis and Cox proportional hazard regression analysis were used to assessing the effect of GJA1 expression on survival. Gene set enrichment analysis (GSEA) was used to screen the signaling pathways regulated by GJA1. Immune Cell Abundance Identifier (ImmuCellAI) was chosen to analyze the immune cells affected by GJA1. The expression of GJA1 in CC was significantly lower than that in normal tissues based on the GEPIA, GEO datasets, and HPA. Both the chi-squared test and the logistic regression showed that high-GJA1 expression was significantly correlated with keratinization, hormone use, tumor size, and FIGO stage. The Kaplan–Meier curves suggested that high-GJA1 expression could indicate poor prognosis ( p = 0.0058 ). Multivariate analysis showed that high-GJA1 expression was an independent predictor of poor overall survival (HR, 4.084; 95% CI, 1.354-12.320; p = 0.013 ). GSEA showed many cancer-related pathways, such as the p53 signaling pathway and the Wnt signaling pathway, were enriched in the high-GJA1-expression group. Immune cell abundance analysis revealed that the abundance of CD8 naive, DC, and neutrophil was significantly increased in the high-GJA1-expression group. In conclusion, GJA1 can be regarded as a potential prognostic marker of poor survival and therapeutic target in CC. Moreover, many cancer-related pathways may be the critical pathways regulated by GJA1. Furthermore, GJA1 can affect the abundance of immune cells.


Bone ◽  
2011 ◽  
Vol 48 ◽  
pp. S159
Author(s):  
T. Koromila ◽  
Z. Dailiana ◽  
S. Samara ◽  
C. Chassanidis ◽  
V. Aleporou - Marinou ◽  
...  

2018 ◽  
Vol 470 ◽  
pp. 151-159 ◽  
Author(s):  
Eun Kyung Ko ◽  
Lynn P. Chorich ◽  
Megan E. Sullivan ◽  
Richard S. Cameron ◽  
Lawrence C. Layman

PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
pp. e11749 ◽  
Author(s):  
Patric J. D. Delhanty ◽  
Yuxiang Sun ◽  
Jenny A. Visser ◽  
Anke van Kerkwijk ◽  
Martin Huisman ◽  
...  

2019 ◽  
Vol 17 (4) ◽  
pp. 106-110
Author(s):  
F. M. Kipkeeva ◽  
Т. А. Muzaffarova ◽  
M. P. Nikulin ◽  
P. V. Apanovich ◽  
S. N. Nered ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yanfei Lin ◽  
Yujuan Sun ◽  
Yufang Weng ◽  
Akira Matsuura ◽  
Lan Xiang ◽  
...  

Parishin is a phenolic glucoside isolated fromGastrodia elata, which is an important traditional Chinese medicine; this glucoside significantly extended the replicative lifespan of K6001 yeast at 3, 10, and 30 μM. To clarify its mechanism of action, assessment of oxidative stress resistance, superoxide dismutase (SOD) activity, malondialdehyde (MDA), and reactive oxygen species (ROS) assays, replicative lifespans ofsod1,sod2,uth1, andskn7yeast mutants, and real-time quantitative PCR (RT-PCR) analysis were conducted. The significant increase of cell survival rate in oxidative stress condition was observed in parishin-treated groups. Silent information regulator 2 (Sir2) gene expression and SOD activity were significantly increased after treating parishin in normal condition. Meanwhile, the levels of ROS and MDA in yeast were significantly decreased. The replicative lifespans ofsod1,sod2,uth1,andskn7mutants of K6001 yeast were not affected by parishin. We also found that parishin could decrease the gene expression ofTORC1, ribosomal protein S26A (RPS26A), and ribosomal protein L9A (RPL9A) in the target of rapamycin (TOR) signaling pathway. Gene expression levels ofRPS26AandRPL9Ainuth1, as well as inuth1,sir2double mutants, were significantly lower than those of the control group. Besides,TORC1gene expression inuth1mutant of K6001 yeast was inhibited significantly. These results suggested that parishin exhibited antiaging effects via regulation of Sir2/Uth1/TOR signaling pathway.


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