ELDA is a software application for limiting dilution analysis (LDA), with particular attention to the needs of stem cell assays. It is the first limiting dilution analysis software to provide ...meaningful confidence intervals for all LDA data sets, including those with 0% or 100% responses. Other features include a test of the adequacy of the single-hit hypothesis, tests for frequency differences between multiple data sets, and the ability to take advantage of cases where the number of cells in the sample is counted exactly. A webtool at
http://bioinf.wehi.edu.au/software/elda/ provides an easy user interface.
Endometrial cancer (EC) is associated with significant risk factors such as polycystic ovarian syndrome (PCOS) and sedentary behavior. In our study, we aim to employ machine learning algorithms to ...investigate the potential molecular processes that underlie their interaction and explore their respective roles in the diagnosis and immunotherapy of EC. The GEO database provides access to microarray data, which was utilized in this study to identify gene expression modules associated with PCOS and sedentary behavior, using weighted gene expression network analysis (WGCNA). Cluego software was then employed to investigate the energy enrichment of shared pathways in both PCOS and sedentary individuals, and differential gene analysis was used to confirm another two databases. The miRNAs–mRNAs controlled network was constructed to verify the pathway. The immune-related factors of the shared pathway in EC were then analyzed. Finally, to validate our findings, we conducted cell experiments using EC cell lines (AN3CA, KLE, Ishikawa, RL95-2, and HEC-1A). We found that increased intracellular aromatic compound anabolism is a common feature of both PCOS and sedentary individuals. We then developed a disease pathway model that was based on the common genetic characteristics of PCOS and sedentary behavior. We utilized pathway typing in EC samples and found a significant survival difference between the two subgroups, with the upregulated expression type exhibiting an immune-hot phenotype. Finally, the experimental results confirmed the expression of the hub gene (NAA15) in EC. The findings of our study suggest that genes related to the intracellular aromatic compound metabolic pathway can be used for immunotherapy of EC.
The relationship between pancreatic cancer (PC) and type 2 diabetes mellitus (T2DM) has long been widely recognized, but the interaction mechanisms are still unknown. This study was aimed to ...investigate the shared gene signatures and molecular processes between PC and T2DM.
The Gene Expression Omnibus (GEO) database was used to retrieve the RNA sequence and patient information of PC and T2DM. Weighted gene co-expression network analysis (WGCNA) was performed to discover a co-expression network associated with PC and T2DM. Enrichment analysis of shared genes present in PC and T2DM was performed by ClueGO software. These results were validated in the other four cohorts based on differential gene analysis. The predictive significance of S100A6 in PC was evaluated using univariate and multivariate Cox analyses, as well as Kaplan-Meier plots. The biological process of S100A6 enrichment in PC was detected using Gene Set Enrichment Analysis (GSEA). The involvement of S100A6 in the tumor immune microenvironment (TIME) was assessed by CIBERSORT.
assays were used to further confirm the function of S100A6 in PC.
WGCNA recognized three major modules for T2DM and two major modules for PC. There were 44 shared genes identified for PC and T2DM, and Gene Ontology (GO) analysis showed that regulation of endodermal cell fate specification was primarily enriched. In addition, a key shared gene
was derived in the validation tests. S100A6 was shown to be highly expressed in PC compared to non-tumor tissues. PC patients with high S100A6 expression had worse overall survival (OS) than those with low expression. GSEA revealed that S100A6 is involved in cancer-related pathways and glycometabolism-related pathways. There is a strong relationship between S100A6 and TIME.
functional assays showed that S100A6 helped to induce the PC cells' proliferation and migration. We also proposed a diagram of common mechanisms of PC and T2DM.
This study firstly revealed that the regulation of endodermal cell fate specification may be common pathogenesis of PC and T2DM and identified S100A6 as a possible biomarker and therapeutic target for PC and T2DM patients.
Glioma is a highly malignant brain tumor with a poor survival rate. The involvement of fatty acid metabolism in glioma was examined to find viable treatment options. The information was gathered from ...the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases. A prognostic signature containing fatty acid metabolism-dependent genes (FAMDs) was developed to predict glioma outcome by multivariate and most minor absolute shrinkage and selection operator (LASSO) regression analyses. In the TCGA cohort, individuals with a good score had a worse prognosis than those with a poor score, validated in the CGGA cohort. According to further research by “pRRophetic” R package, higher-risk individuals were more susceptible to crizotinib. According to a complete study of the connection between the predictive risk rating model and tumor microenvironment (TME) features, high-risk individuals were eligible for activating the immune cell-associated receptor pathway. We also discovered that anti-PD-1/PD-L1 and anti-CTLA4 immunotherapy are more effective in high-risk individuals. Furthermore, we demonstrated that CCNA2 promotes glioma proliferation, migration, and invasion and regulates macrophage polarization. Therefore, examining the fatty acid metabolism pathway aids our understanding of TME invasion properties, allowing us to develop more effective immunotherapies for glioma.
Pyroptosis is widely involved in many diseases, including periodontitis. Nonetheless, the functions of pyroptosis-related genes (PRGs) in periodontitis are still not fully elucidated. Therefore, we ...aimed to investigate the role of PRGs in periodontitis. Three datasets (GSE10334, GSE16134, and GSE173078) from the Gene Expression Omnibus (GEO) were selected to analyze the differences in expression values of the PRGs between nonperiodontitis and periodontitis tissue samples using difference analysis. Following this, five hub PRGs (charged multivesicular body protein 2B, granzyme B, Z-DNA-binding protein 1, interleukin-1β, and interferon regulatory factor 1) predicting periodontitis susceptibility were screened by establishing a random forest model, and a predictive nomogram model was constructed on the basis of these genes. Decision curve analysis suggested that the PRG-based predictive nomogram model could provide clinical benefits to patients. Three distinct PRG patterns (cluster A, cluster B, and cluster C) in the periodontitis samples were revealed according to the 48 significant PRGs, and the difference in the immune cell infiltration among the three patterns was explored. We observed that all infiltrating immune cells, except type 2 T helper cells, differ significantly among the three patterns. To quantify the PRG patterns, the PRG score was calculated by principal component analysis. According to the results, cluster B had the highest PRG score, followed by cluster A and cluster C. In conclusion, PRGs significantly contribute to the development of periodontitis. Our study of PRG patterns might open up a new avenue to guide individualized treatment plans for patients with periodontitis.
Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until bone is ...remodeled. The interconnected osteocyte network within the bone matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. This is not caused by low bone mass, but by defective bone material. While osteoid mineralization is initiated at normal rate, mineral accrual is accelerated, indicating that EphrinB2 in osteocytes limits mineral accumulation. No known regulators of mineralization are modified in the brittle cortical bone but a cluster of autophagy-associated genes are dysregulated. EphrinB2-deficient osteocytes displayed more autophagosomes in vivo and in vitro, and EphrinB2-Fc treatment suppresses autophagy in a RhoA-ROCK dependent manner. We conclude that secondary mineralization involves EphrinB2-RhoA-limited autophagy in osteocytes, and disruption leads to a bone fragility independent of bone mass.
A novel ANAMMOX biofilm reactor that combines the advantages of conventional biofilm reactors and membrane bioreactors (MBRs) was developed in an attempt to decrease the levels of nitrogen in the ...reactor filtrate. In this reactor, nonwoven fabric modules served as both biofilm carriers and membrane-like separators, and the biofilm acted as a permeable reactive barrier for the removal of nitrogen species from the bulk liquid. Long-term monitoring suggests that the nitrogen removal rates (NRR) of the reactor reached ca. 1.6 kg-N/(m3 d). Interestingly, large fractions of the ammonium (ca. 27%) and nitrite (ca. 48%) remaining in the bulk liquid were removed during their transport through the biofilm; thus, the reactive barrier process of the biofilm contributed ca. 11% to the total NRR. With an increase in the imposed flux, the contribution of the reactive barrier process to the removal of nitrogen from the reactor bulk liquid increased significantly, e.g., it contributed 26% to the NRR at 17.4 L/(m2 h). Additionally, the nonwoven modules could retain free bacteria effectively; they maintained a non-fouling state during the entire operation period of approximately 400 days. Sequence analysis shows that Candidatus Kuenenia-like species dominated the ANAMMOX bacteria in the reactor. These results clearly demonstrate that this innovative reactor holds great promise for improving the ANAMMOX process, thus decreasing nitrogen levels in the effluent.
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•A novel ANAMMOX biofilm reactor using biofilm as reactive barriers was developed.•The reactive barrier can improve N removal, but depends on operating conditions.•Unlike conventional MBRs, this reactor achieved a non-fouling operation state.•Candidatus Kuenenia-like species dominated the ANAMMOX bacteria.
Endometrial carcinoma (EC) is the sixth most frequent malignancy in women and is often linked to high estrogen exposure. Polycystic ovarian syndrome (PCOS) is a known risk factor for EC, but the ...underlying mechanisms remain unclear.
We investigated shared gene signals and potential biological pathways to identify effective therapy options for PCOS- and EC-related malignancies. Weighted gene expression network analysis (WGCNA) was used to identify genes associated with PCOS and EC using gene expression data from the Gene Expression Omnibus (GEO) and Cancer Genome Atlas (TCGA) datasets. Enrichment analysis using Cluego software revealed that the steroid hormone biosynthetic process was a critical feature in both PCOS and EC. A predictive signature encompassing genes involved in steroid hormone production was developed using multivariate and least absolute shrinkage and selection operator (LASSO) regression analysis to predict the prognosis of EC. Then, we conducted further experimental verification.
Patients in the TCGA cohort with high predictive scores had poorer outcomes than those with low scores. We also investigated the relationship between tumor microenvironment (TME) features and predictive risk rating and found that patients with low-risk scores had higher levels of inflammatory and inhibitory immune cells. Also, we found that immunotherapy against anti-CTLA4 and anti-PD-1/PD-L1 was successful in treating individuals with low risk. Low-risk individuals were more responsive to crizotinib therapy, according to further research performed using the "pRRophetic" R package. We further confirmed that IGF2 expression was associated with tumor cell migration, proliferation, and invasion in EC cells.
By uncovering the pathways and genes linking PCOS and EC, our findings may provide new therapeutic strategies for patients with PCOS-related EC.
Selenium (Se) is an essential trace element in human. Recent studies of Se supplementation on the effect of Hashimoto’s thyroiditis (HT) have been reported, but the exact benefit is unclear as well ...as the underlying immunologic mechanism. We aimed to evaluate the clinical effect of Se supplement in patients with HT, and explore the potential mechanism against thyroid autoimmunity. A prospective, randomized‑controlled study was performed in patients with HT assigned to two groups. Se‐treated group (n = 43) received selenious yeast tablet (SYT) for 6 months, whereas no treatment in control group (n = 47). The primary outcome is the change of thyroid peroxidase antibody (TPOAb) or thyroglobulin antibody (TGAb). Second, thyroid function, urinary iodine, Se, Glutathione peroxidase3 (GPx3), and Selenoprotein P1 (SePP1) levels were measured during the SYT treatment. Meanwhile, regulatory T cells (Tregs) and their subsets activated Tregs (aTregs), resting Tregs, and secreting Tregs, as well as Helios and PD‐1 expression on these cells were also detected. The results showed that SYT treatment significantly decreased TPOAb, TGAb, and thyroid stimulating hormone (TSH) levels, accompanied with the increased Se, GPx3, and SePP1, compared with the control group. Subgroup analysis revealed that subclinical HT may benefit more from this treatment in the decrease of TSH levels by interaction test. Moreover, the percentage of aTregs, Helios/Tregs, and Helios/aTregs were significantly higher in the Se‐treated group than control. In conclusion, Se supplementation may have a beneficial effect on thyroid autoantibodies and thyroid function by increasing the antioxidant activity and upregulating the activated Treg cells.
Background:
Exercise improves function, reduces disability, maintains independence, and improves quality of life for low-grade glioma (LGG) patients. Exercise can also improve the effectiveness of ...cancer treatment. The goal of this research was to find potential exercise related genes that may be used to predict exercise levels and may be used as a biomarker for cancer outcomes.
Methods:
The GSE111551 database was thoroughly examined in this research, and the resulting conclusion of exercise-related genes was reached. The protein interaction network (PPI) was used to examine the differentially expressed genes (DEGs). Then the exercise-related gene TLR1 was chosen. The expression, methylation degree, prognosis, and immune relevance of TLR1 were investigated using bioinformatics. In addition, we verified the role of TLR1 in Glioma cell lines.
Results:
LGG patients with reduced TLR1 expression and hypermethylation had a better overall survival (OS) and progression free survival (PFS), using the TCGA database. Low TLR1 expression and hypermethylation of TLR1 were found to be independent biomarkers for OS using Cox regression. Furthermore, the CGGA database was used to confirm the prognostic function of TLR1 in this cancer. Finally, most methylation sites of TLR1 were strongly correlated with immune infiltration and immune checkpoint. Then, reducing TLR1 expression substantially slowed the cell cycle and decreased LGG cell proliferation, emigration, and infiltration
in vitro
.
Conclusions:
Exercise-related gene TLR1 has the potential to be a useful prognostic biomarker, and it is thought to be involved in immune cell infiltration and immunotherapy in LGG.
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