Abstract: Metabolomics has become a rising field of research
for various diseases, particularly cancer. Increases or decreases in
metabolite concentrations in the human body are indicative of various
cancers. Further elucidation of metabolic pathways and their
significance in cancer research may greatly spur medicinal discovery.
We analyzed the metabolomics profiles of lung cancer. Thirty-three
metabolites were selected as significant. These metabolites are
involved in 37 metabolic pathways delivered by MetaboAnalyst
software. The top pathways are glyoxylate and dicarboxylate
pathway (its hubs are formic acid and glyoxylic acid) along with
Citrate cycle pathway followed by Taurine and hypotaurine pathway
(the hubs in the latter are taurine and sulfoacetaldehyde) and Glycine,
serine, and threonine pathway (the hubs are glycine and L-serine). We
studied interactions of the metabolites with the proteins involved in
cancer-related signaling networks, and developed an approach to
metabolomics biomarker use in cancer diagnostics. Our analysis
showed that a significant part of lung-cancer-related metabolites
interacts with main cancer-related signaling pathways present in this
network: PI3K–mTOR–AKT pathway, RAS–RAF–ERK1/2 pathway,
and NFKB pathway. These results can be employed for use of
metabolomics profiles in elucidation of the related cancer proteins
signaling networks.
Abstract: The MyD88 is an evolutionarily conserved host-expressed adaptor protein that is essential for proper TLR/ IL1R immune-response signaling. A previously identified complete cDNA (1626 bp) of OfMyD88 comprised an ORF of 867 bp encoding a protein of 288 amino acids (32.9 kDa). The gDNA (3761 bp) of OfMyD88 revealed a quinquepartite genome organization composed of 5 exons (with the sizes of 310, 132, 178, 92 and 155 bp) separated by 4 introns. All the introns displayed splice signals consistent with the consensus GT/AG rule. A bipartite domain structure with two domains namely death domain (24-103) coded by 1st exon, and TIR domain (151-288) coded by last 3 exons were identified through in silico analysis. Moreover, homology modeling of these two domains revealed a similar quaternary folding nature between human and rock bream homologs. A comprehensive comparison of vertebrate MyD88 genes showed that they possess a 5-exonic structure.In this structure, the last three exons were strongly conserved, and this suggests that a rigid structure has been maintained during vertebrate evolution.A cluster of TATA box-like sequences were found 0.25 kb upstream of cDNA starting position. In addition, putative 5'-flanking region of OfMyD88 was predicted to have TFBS implicated with TLR signaling, including copies of NFkB1, APRF/ STAT3, Sp1, IRF1 and 2 and Stat1/2. Using qPCR technique, a ubiquitous mRNA expression was detected in liver and blood. Furthermore, a significantly up-regulated transcriptional expression of OfMyD88 was detected in head kidney (12-24 h; >2-fold), spleen (6 h; 1.5-fold), liver (3 h; 1.9-fold) and intestine (24 h; ~2-fold) post-Fla challenge. These data suggest a crucial role for MyD88 in antibacterial immunity of teleosts.
Abstract: NFκB is a transcription factor regulating many
function of the vessel wall. In the normal condition , NFκB is
revealed diffuse cytoplasmic expressionsuggesting that the system is
inactive. The presence of activation NFκB provide a potential
pathway for the rapid transcriptional of a variety of genes encoding
cytokines, growth factors, adhesion molecules and procoagulatory
factors. It is likely to play an important role in chronic inflamatory
disease involved atherosclerosis. There are many stimuli with the
potential to active NFκB, including hyperlipidemia. We used 24 mice
which was divided in 6 groups. The HFD given by et libitum
procedure during 2, 4, and 6 months. The parameters in this study
were the amount of NFKB activation ,H2O2 as ROS and VCAM-1 as
a product of NFKB activation. H2O2 colorimetryc assay performed
directly using Anti Rat H2O2 ELISA Kit. The NFKB and VCAM-1
detection obtained from aorta mice, measured by ELISA kit and
imunohistochemistry. There was a significant difference activation of
H2O2, NFKB and VCAM-1 level at induce HFD after 2, 4 and 6
months. It suggest that HFD induce ROS formation and increase the
activation of NFKB as one of atherosclerosis marker that caused by
hyperlipidemia as classical atheroschlerosis risk factor.
Abstract: NFκB activation plays a crucial role in anti-apoptotic responses in response to the apoptotic signaling during tumor necrosis factor (TNFa) stimulation in Multiple Myeloma (MM). Although several drugs have been found effective for the treatment of MM by mainly inhibiting NFκB pathway, there are no any quantitative or qualitative results of comparison assessment on inhibition effect between different single drugs or drug combinations. Computational modeling is becoming increasingly indispensable for applied biological research mainly because it can provide strong quantitative predicting power. In this study, a novel computational pathway modeling approach is employed to comparably assess the inhibition effects of specific single drugs and drug combinations on the NFκB pathway in MM, especially the prediction of synergistic drug combinations.