Project description:Scope: Soy flour diet (MS) prevented isoflavones from stimulating MCF-7 tumor growth in athymic nude mice, indicating that other bioactive compounds in soy can negate the estrogenic properties of isoflavones. The underlying signal transduction pathways to explain the protective effects of soy flour consumption were studied here. Methods and results: Ovariectomized athymic nude mice inoculated with MCF-7 human breast cancer cells were fed either MS or purified isoflavone mix (MI), both with equivalent amounts of genistein. Positive controls received estradiol pellets and negative controls received sham pellets. GeneChip-Human-Genome-U133 Plus-2.0 Array platform was used to evaluate gene expressions, and results were analyzed using bioinformatics approaches. Tumors in MS-fed mice exhibited higher expression of tumor-growth-suppressing genes ATP2A3 and BLNK, and lower expression of oncogene MYC. Tumors in MI-fed mice expressed higher level of oncogene MYB and lower level of MHC-I and MHC-II, allowing tumor cells to escape immunosurveillance. MS-induced gene expression alterations were predictive of prolonged survival among estrogen-receptor-positive breast cancer patients, whilst MI-induced gene changes were predictive of shortened survival. Conclusion: Our findings suggest dietary soy flour affects gene expression differently than purified isoflavones, which may explain why soy foods prevent isoflavones-induced stimulation of MCF-7 tumor growth in athymic nude mice.
Project description:Genome-wide association studies in multiple sclerosis (MS) identified a polymorphism (rs6897932) located in the coding region of the alpha chain of the cytokine receptor interleukin 7 receptor (IL7R) as a component that increases susceptibility to develop the disease. This single nucleotide polymorphism (SNP) affects the splicing of the primary transcript leading to genotype-defined transcript ratios encoding either a full length membrane spanning form or a soluble receptor chain. Genotyping at the IL7R locus reveals that the region can be described by four haplotypes. Interestingly, only one out of three haplotypes harbouring the associated SNP is positively associated with MS whereas the other two do not show association. The minor allele containing haplotype shows a reduced susceptibility to develop MS. We hypothesized that additional functional or phenotypic differences exist between individuals homozygous for haplotypes shown to have either positive, negative, or neutral effect, on susceptibility to develop MS. Gene expression profiles of CD4+ T cells from MS individuals before and after stimulation with IL7 were recorded. Haplotype-specific gene signatures were found indicating small alterations in IL7/IL7R signal processing/sensitivity through JAK/STAT and p38/MAPK14. We can not exclude that the obtained signatures result from differences within the CD4+ T cell compartment that, in fact, should be seen as a consequence of systemic haplotype-specific processing of homeostatic and proliferation signals transmitted through IL7/IL7R. Samples of CD4+ cells were obtained from 7 MS patients (homozygous for Hap1 (3), Hap2 (2), Hap3 (2)). CD4+ cells were collected from peripheral blood, frozen and stored in liquid nitrogen. All samples were thawed and CD4+ cells were purified by magnetic bead separation. Purity and viability of cells was analyzed by Fluorescence Activated Cell Sorter (FACS). Total cellular RNA were extracted with TRIzol reagent and analyzed with the Human Gene 1.0 ST Array (affymetrix). IL7R haplotypes and susceptibility to develop MS: Hap1 homozygous <-> Risk <-> positive effect on MS susceptibility Hap2 homozygous <-> Hap2 <-> neutral effect on MS susceptibility Hap3 homozygous <-> Prot <-> neutral effect on MS susceptibility [Note: Haplotype nomenclature subject to revision.]
Project description:The cytostatic compounds palbociclib (CDK4/6 inhibitor, 2 uM) and pimasertib (MEK inhibitor, 0.5 uM) were added to the growth media of HT-1080 fibrosarcoma cells for 48 hours. Then, RNA was collected from the samples and sequenced.
Project description:Excessive MS is known to result in disappearance of the alveolar hard line, enlargement of thePDL space, and destruction of alveolar bone, leading to occlusal traumatism. The regulatory role of MS is believed to play a critical role in the process of alveolar bone remodeling. However, little is known about the effect of excessive MS on expression of osteoclastogenesis-related genes in human PDL cells. Human PDL cells were cultured in silicon chambers, which was attached to a stretching apparatus (STB-140; Strex Co. Ltd., Osaka, Japan) The cells were allowed to attach to the chamber base for 48 hours, after which uniaxial sinusoidal stretching (conditions: 60 sec/returns, resting time; 29 sec, stretch length; 1.6 mm, stretch ratio; 105%) was applied at 37°C, 5% CO2. We compared to the genes expression between 0 and 48 hours after MS stimulation.
Project description:ITDR MS-CETSA was conducted on MMV compounds-treated live parasites and lysate of P. falciparum trophozoites in order to identify potential drug protein targets. MMV compounds: MMV007127, MMV665886.
Project description:Grape volatiles include a great number of compounds, among which monoterpenes, alcohols,esters and carbonyls were found.Grape may be divided into aromatic and non-aromatic varieties. ‘Shine Muscat’ belongs to the aromatic cultivar. The most abundant free compounds detected in Muscat grape were linalool, geraniol, citronellol, nerol. Grapevine (Vitis vinifera L.) is an economically important and widely cultivated fruit crop. Grape quality is important for its market value and is largely decided by its taste and aroma.Gas-chromatograph mass-spectrometry (GC-MS) was performed to observe changes of the volatile compounds.
Project description:ITDR MS-CETSA was conducted on MMV compounds-treated live parasites and lysate of P. falciparum trophozoites in order to identify potential drug protein targets. MMV compounds: MMV020885, MMV665806, MMV665864.
Project description:LC-MS lipidomics analysis of two MDCK monoclonal cell lines, C59 and C113, at 24, 48, and 72 hour post infection, including the purified influenza virus from each clone.