Introduction: Differentially expressed genes (DEGs) biomarkers have the potential to aid in the diagnosis and monitoring of diseases, as well as determining the most effective treatments. However, ...due to the complex nature of Myelodysplastic neoplasm (MDS), it is challenging to assess the impact and variations of DEGs between CD34+ HSC (hematopoietic stem cells) and primary bone marrow cells (PBMC) in MDS pathogenesis. Consequently, this aspect remains largely unknown. Objective: The aim was to investigate the divergences in differential gene expression patterns between these two cell types as potential pathogenic biomarkers for MDS. Materials and Methods: To understand the transcriptome differential expression in MDS pathogenesis, we employed two groups: first, four datasets (GSE18366, GSE19429, GSE30195 and GSE58831) from CD34+ HSC samples were obtained to analyze expression profiles of 392 MDS patients and 44 healthy individuals; second, four other datasets (GSE41130, GSE97064, GSE107400 and GSE114869) from PBMC samples were obtained to analyze expression profiles of 700 MDS patients and 47 healthy individuals. All databases were based on Affymetrix GeneChip Human Transcriptome Array. We employed bioinformatic analysis of microarray to investigate significant abnormal differentially expressed genes (DEGs) in MDS and health individuals on every microarray dataset for both types of samples based on Transcriptome Analysis Console (TAC) Software algorithm. Heatmaps, Volcano and Scatter plots were performed in TAC software based in R algorithm. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were conducted to clarify the functional roles of DEGs. Enriched functional categories of gene–ontology associations were performed using the R software and the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Results: Our analysis initially revealed a disparity of 7117 expressed transcripts between PBMC (n = 40,165) and CD34+ HSC (n = 33,048). Furthermore, we identified 240 DEGs in CD34+ HSC samples and 2948 DEGs in PBMC samples. Among them, it was notable that there is no common pattern of gene expression between upregulated or downregulated transcripts in both samples. In this study, we conducted GO enrichment and KEGG pathway analyses to investigate the functional roles of DEGs in Myelodysplastic Syndrome (MDS) pathobiology. We categorized the DEGs of CD34+ HSC and PBMC into functional categories using GO analysis. In CD34+ HSC, the most enriched pathways were signal transduction, negative regulation of transcription, and immune response. In PBMC, the immune response, signal transduction, and innate immune response pathways were significantly activated. We also performed KEGG pathway analysis for upregulated and downregulated DEGs in both CD34+ HSC and PBMC samples. In CD34+ HSC, the top pathways were involved in hematopoietic cell lineage, cell receptor signaling, and primary immunodeficiency. These pathways were also identified in PBMC, along with cancer and cell cycle pathways. Discussion and Conclusion: To summarize, our study uncovered disparities in DEGs between CD34+ HSC and PBMC cell types in MDS. However, we also observed a certain degree of similarity in the activated pathways of both cell samples based on Gene Ontology and KEGG pathways enrichment analyses. Of particular importance in our study was the role of the immune system and the activation of hematopoietic cell lineage pathways as the most activated in MDS, regardless of the cell type evaluated. These findings provide novel insights into DEGs biomarkers associated with MDS pathogenesis, holding clinical significance.
To support the development and characterization of chromophores with targeted photophysical properties, excited-state electronic structure calculations should rapidly and accurately predict how ...derivatization of a chromophore will affect its excitation and emission energies. This paper examines whether a time-independent excited-state density functional theory (DFT) approach meets this need through a case study of BODIPY chromophore photophysics. A restricted open-shell Kohn–Sham (ROKS) treatment of the S1 excited state of BODIPY dyes is contrasted with linear-response time-dependent density functional theory (TDDFT). Vertical excitation energies predicted by the two approaches are remarkably different due to overestimation by TDDFT and underestimation by ROKS relative to experiment. Overall, ROKS with a standard hybrid functional provides the more accurate description of the S1 excited state of BODIPY dyes, but excitation energies computed by the two methods are strongly correlated. The two approaches also make similar predictions of shifts in the excitation energy upon functionalization of the chromophore. TDDFT and ROKS models of the S1 potential energy surface are then examined in detail for a representative BODIPY dye through molecular dynamics sampling on both model surfaces. We identify the most significant differences in the sampled surfaces and analyze these differences along selected normal modes. Differences between ROKS and TDDFT descriptions of the S1 potential energy surface for this BODIPY derivative highlight the continuing need for validation of widely used approximations in excited state DFT through experimental benchmarking and comparison to ab initio reference data.
Background: Helicobacter pylori has been established as a risk factor for gastric carcinoma (GCa). Since before the discovery of H. pylori, atrophic gastritis and intestinal metaplasia have been ...linked to GCa, especially the intestinal-type tumor. The prevalence of H. pylori infection and atrophic gastritis increase with age. Thus, analysis of H. pylori infection in young patients with GCa could help clarify the role of this bacterium in the development of GCa. Accordingly, we investigated the relationship between H. pylori infection, GCa, and histologic gastritis in patients less than 30 years old. Methods: Fifty GCa patients less than 30 years (mean, 26.4 years) and 100 sex- and age-matched controls (mean, 26.8 years) were examined for the presence of H. pylori infection and histologic gastritis. Results: The prevalence of H. pylori infection was significantly higher in GCa patients than in controls (94% versus 40%, P < 0.01). Its prevalence was not associated with tumor location, tumor stage, or histologic type. Gastritis, atrophy, and intestinal metaplasia significantly increased the risk of GCa. By means of multiple logistic regression analysis, the odds ratio for the risk of GCa in H. pylori-positive subjects was found to be 23.5 (95% confidence interval, 6.84-80.7). Conclusions: We confirmed a strong association between H. pylori infection and GCa in young patients. Along with H. pylori infection, histologic gastritis might play an important role in the pathogenesis of GCa in these patients.
The effect of prior polymer concentration on solution-crystallized morphologies in ultra-high molecular weight polyethylene has been characterized by transmission electron microscopy (TEM) and X-ray ...analysis. Molecular motion in crystalline and amorphous phases was evaluated by nuclear magnetic resonance (NMR) techniques. The series of solution-crystallized mats was prepared from different polymer concentrations. TEM results indicate these samples consist of lamellae aligned parallel to the mat surface. The observed high order scattering of small-angle X-ray scattering (SAXS) patterns indicate a regular stacking of lamellae. The long period was ∼11nm, independent of prior polymer concentration. Wide-angle X-ray diffraction analysis also revealed the same level of crystallinity for these solution-crystallized samples, well coincident with 1H-NMR results. These indicate that the thickness of crystal/amorphous layers was constant, which was also confirmed by layer thickness distribution analysis for this series of samples, based on direct TEM observation. However, the SAXS peak gradually grew and sharpened with increasing prior polymer concentration. 1H-NMR results also indicate amorphous chain mobility was restricted for the sample prepared from lower polymer concentration in spite of unchanged crystallinity and relaxation characteristics for crystalline chains. Morphological and relaxation characteristics information demonstrates that lower prior polymer concentration might prefer formation of tie molecules which connect tightly crystalline layers. In contrast, the higher concentration could trap loosely entangled chains in amorphous layers, providing for an ease of chain relaxation estimated by 1H-NMR analysis.
New μ-opioid receptor (MOR) agonists containing piperazine and homopiperazine moieties in the structures were synthesized and their affinities to and agonist potencies on MOR were evaluated. Among ...the synthesized compounds, 4-4-(2-methoxyphenyl)piperazin-1-yl-N,N-dimethyl-2,2-diphenylbutanamide (20Aa) showed the highest affinity to the human MOR expressed in Chinese hamster ovary (CHO)-K1 cells, and the highest agonist potency on the MOR in isolated guinea-pig ileum preparation.
In order to pursue a possibility of application of radiopaque polymer hydrogels to vascular embolization, studies were done on synthesis of iodine-containing copolyanions and properties of their ...hydrogels with polycation via formation of polyion complexes. Acrylamide derivatives having triiodophenyl and carboxyl groups were synthesized and copolymerized with sodium styrene sulfonate at various molar ratios of initiator to monomer and temperatures. Hydrogels were prepared by mixing aqueous solutions of the obtained radiopaque copolyanions and polyallylamine. Embolization was examined by injection of these hydrogels into vein of a removed porcine kidney as a preliminary test for transcatheter arterial embolization (TAE) for hepatocellular carcinoma. It was found that the hydrogels prepared from the copolycation obtained under particular conditions give high X-ray contrasts of the vein and remained there, though copolycations with low molecular weights had a tendency to drain through the capillaries to the peripheral tissues. It is therefore concluded that the hydrogels examined in the present study are promising for vascular embolization.
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