Anti-metastatic and differential effects on protein expression of epigallocatechin-3-gallate in HCCLM6 hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third highest cause of cancer-related mortality in humans. Epigallocatechin-3-gallate (EGCG) has been shown to inhibit the metastatic activity of certain cancer cells. The aim of this study was to determine the effects and molecular mechanism(s) of action of EGCG in human HCC cells. A migration and invasion assay for the metastatic behavior of HCCLM6 cells was performed. The anti-metastatic effects of EGCG were investigated by RT-PCR and gelatin zymography. A total cellular protein profile was obtained using 2-dimensional gel electrophoresis (2-DE), followed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) analyses of proteins with significant differences in expression following treatment with EGCG. The results revealed that EGCG induced apoptosis and inhibited the metastasis of HCCLM6 cells. The anti-metastatic effects of EGCG were associated with the inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 activity. The expression levels of far upstream element (FUSE) binding protein 1 (FUBP1), heat shock protein beta 1 (HSPB1), heat shock 60 kDa protein 1 (chaperonin) (CH60) and nucleophosmin (NPM) proteins, which are associated with metastasis, were significantly altered in the EGCG-treated HCCLM6 cells. The data from the present study suggest that EGCG has potential as a therapeutic agent for the treatment of HCC

Sequential gene expression analysis of myelodysplastic syndrome transformation identifies HOXB3 and HOXB7 as the novel targets for mesenchymal cells in disease

Abstract Background Myelodysplastic syndrome (MDS) is known to arise through the pathogenic bone marrow mesenchymal stem cells (MSC) by interacting with hematopoietic stem cells (HSC). However, due to the strong heterogeneity of MDS patients, it is difficult to find common targets in studies with limited sample sizes. This study aimed to describe sequential molecular changes and identify biomarkers in MSC of MDS transformation. Methods Multidimensional data from three publicly available microarray and TCGA datasets were analyzed. MDS-MSC was further isolated and cultured in vitro to determine the potential diagnostic and prognostic value of the identified biomarkers. Results We demonstrated that normal MSCs presented greater molecular homogeneity than MDS-MSC. Biological process (embryonic skeletal system morphogenesis and angiogenesis) and pathways (p53 and MAPK) were enriched according to the differential gene expression. Furthermore, we identified HOXB3 and HOXB7 as potential causative genes gradually upregulated during the normal-MDS-AML transition. Blocking the HOXB3 and HOXB7 in MSCs could enhance the cell proliferation and differentiation, inhibit cell apoptosis and restore the function that supports hematopoietic differentiation in HSCs. Conclusion Our comprehensive study of gene expression profiling has identified dysregulated genes and biological processes in MSCs during MDS. HOXB3 and HOXB7 are proposed as novel surrogate targets for therapeutic and diagnostic applications in MDS

The composition of the blood microbiota and its relationship to osteoporosis-related clinical parameters

Osteoporosis, a systemic bone disease, is characterized by decreased bone mass, deterioration of skeletal structure, and increased bone susceptibility. Age, environment, hormone levels, nutrition, and immunity are all factors that influence bone mass. Currently, intestinal flora has been recently recognized as a key regulator of bone mass. The blood's microbiome role in bone health and in the pathogenesis of osteoporosis remains unknown. In this study, the abundance of various blood's microbial taxa in osteoporosis patients were analyzed. We investigated the associations between prominent bacterial taxa and other clinical indicators (i.e. biochemical, blood cell counts and CT scan). DNA was extracted from the whole blood samples of patients with degenerative bone diseases with or without osteoporosis (i.e. n = 8; ST and n = 12, T group) and healthy controls (n = 4, N group). The 16S rRNA gene sequencing technique was utilized to characterize the blood microbiome taxaThe Shannon–Winner and dilution curves revealed that all the characterized species in the sample and the sequencing data were reliable. The number of bacterial taxa in blood and annotated operational taxonomic units were positively correlated with neutrophils. This support that bacteria exist within or adhere to the neutrophil's membrane. The abundance of Yersinia ruckeri, Rhodanobacter_uncultured bacterium, Enterobacter spp., and Raoultella spp increased in the ST group as compared with the N group. Hence, indicate their potential role in the onset and progression of osteoporosis. These findings provide new insights into the association between blood microbiota and bone health. This study could open a new horizon in exploring the clinical application of blood microbiome to improve bone health

Transcriptional profiling and biological pathway analysis of human equivalence PCB exposure in vitro: Indicator of disease and disorder development in humans.

BACKGROUND AND AIMS: Our earlier gene-expression studies with a Slovak PCBs-exposed population have revealed possible disease and disorder development in accordance with epidemiological studies. The present investigation aimed to develop an in vitro model system that can provide an indication of disrupted biological pathways associated with developing future diseases, well in advance of the clinical manifestations that may take years to appear in the actual human exposure scenario. METHODS: We used human PBMC (Primary Blood Mononuclear Cells) and exposed them to a mixture of human equivalence levels of PCBs (PCB-118,138,153,170,180) as found in the PCBs-exposed Slovak population. The microarray studies of global gene expression were conducted on the Affymetrix platform using Human Genome U133 Plus 2.0 Array along with Ingenuity Pathway Analysis (IPA) to associate the affected genes with their mechanistic pathways. High-throughput qRT-PCR Taqman Low Density Array (TLDA) was done to further validate the selected 6 differentially expressed genes of our interest, viz., ARNT, CYP2D6, LEPR, LRP12, RRAD, TP53, with a small population validation sample (n=71). RESULTS: Overall, we revealed a discreet gene expression profile in the experimental model that resembled the diseases and disorders observed in PCBs-exposed population studies. The disease pathways included Endocrine System disorders, Genetic disorders, Metabolic diseases, Developmental disorders, and Cancers, strongly consistent with the evidence from epidemiological studies. INTERPRETATION: These gene finger prints could lead to the identification of populations and subgroups at high risk for disease, and can pose as early disease biomarkers well ahead of time, before the actual disease becomes visible

Additional file 1 of Effect of crude polysaccharide from seaweed, Dictyopteris divaricata (CDDP) on gut microbiota restoration and anti-diabetic activity in streptozotocin (STZ)-induced T1DM mice

Additional file 1: Figure S1. High performance liquid chromatography (HPLC) analysis of crude polysaccharide (CDDP) from seaweed, Dictyopteris divaricata.; Figure S2. Box-plot of Shannon index (0.0231), Simpson index (0.0154) and Chao1 (0.0456) was plotted to observe the changes in species richness and evenness; Figure S3. Heatmap of different taxa at genus level. Data represents the degree of similarity among the groups in the form of cluster and dissimilarity arranged individually. Data is a representative of twenty-four samples; Table S1. The body weight of the mice in the experimental study. Table S2. List of qPCR primers; Table S3. The relative abundance (%) of all the phyla at phylum level; Table S4. The differences (%) between the proportion of bacteria at family level; Table S5. Representation of bacterial microbial community (%) at genus level

Effects of epigallocatechin gallate on the cell-wall structure of <i>Mycobacterial smegmatis</i> mc²155

<div><p>Epigallocatechin gallate (EGCG) is the main component of green tea extracts that inhibits the growth of <i>Mycobacterial smegmatis</i> mc²155, and the mechanism is not clear. This study showed the effects of EGCG on the growth of mc²155. The content and the structure of EGCG in LB medium with mc²155 were identified by HPLC and LC/MS. Transmission electron microscopy was utilised to identify the cell envelope structure. As a result, the optional inhibition concentration was determined to be 20 μg mL^− 1. Most of EGCG was transferred into its isomeride in LB medium, but the inhibition effects against mc²155 had yet been maintained. The changes of cell envelope structure were showed after EGCG treatment for 18 h. The cell wall appeared to have a less electron-translucent zone, turn rougher and thicker. The results show that EGCG impacts the integrity of mycobacterial cell wall and is likely be a better prophylactic agent against tuberculosis.</p></div