Daidzein and genistein but not their glucosides are absorbed from the rat stomach

AbstractAbsorption of isoflavone aglycones and glucosides was compared in rats. Daidzein, genistein, daidzin and genistin were orally administered at a dose of 7.9 μmol/kg in 25 mM Na2CO3 and next their metabolite concentration in blood plasma was monitored for 30 min. After isoflavone glucosides administration, their metabolites appeared in plasma with a few minutes delay as compared to aglycones, which suggested that aglycones, but not glucosides, were absorbed already in the rat stomach. This observation was confirmed when absorption site was restricted solely to the stomach and absorption was shown to be independent of the vehicle pH used for administration

Estimation of the Lin-Yang bound of the least static energy of the Faddeev model

Lin and Yang's upper bound E_Q <= cQ^(3/4) of the least static energy E_Q of the Faddeev model in a sector with a fixed Hopf index Q is investigated. By constructing an explicit trial configuration for the Faddeev field n, a possible value of the coefficient c is obtained numerically, which is much smaller than the value obtained quite recently by analytic discussions.Comment: 11 pages, 2 figure

Iscador Qu inhibits doxorubicin-induced senescence of MCF7 cells

Chemotherapy in patients with inoperable or advanced breast cancer inevitably results in low-dose exposure of tumor-cell subset and senescence. Metabolically active senescent cells secrete multiple tumor promoting factors making their elimination a therapeutic priority. Viscum album is one of the most widely used alternative anti-cancer medicines facilitating chemotherapy tolerance of breast cancer patients. The aim of this study was to model and investigate how Viscum album extracts execute additive anti-tumor activity with low-dose Dox using ER + MCF7 breast cancer cells. We report that cotreatment of MCF7 with Viscum album and Dox abrogates G2/M cycle arrest replacing senescence with intrinsic apoptotic program. Mechanistically, this switch was associated with down-regulation of p21, p53/p73 as well as Erk1/2 and p38 activation. Our findings, therefore, identify a novel mechanistic axis of additive antitumor activity of Viscum album and low dose-Dox. In conclusion, ER + breast cancer patients may benefit from addition of Viscum album to low-dose Dox chemotherapy due to suppression of cancer cell senescence and induction of apoptosis

Alkyne-Tag Raman Imaging for Visualization of Mobile Small Molecules in Live Cells

Alkyne has a unique Raman band that does not overlap with Raman scattering from any endogenous molecule in live cells. Here, we show that alkyne-tag Raman imaging (ATRI) is a promising approach for visualizing nonimmobilized small molecules in live cells. An examination of structure–Raman shift/intensity relationships revealed that alkynes conjugated to an aromatic ring and/or to a second alkyne (conjugated diynes) have strong Raman signals in the cellular silent region and can be excellent tags. Using these design guidelines, we synthesized and imaged a series of alkyne-tagged coenzyme Q (CoQ) analogues in live cells. Cellular concentrations of diyne-tagged CoQ analogues could be semiquantitatively estimated. Finally, simultaneous imaging of two small molecules, 5-ethynyl-2′-deoxyuridine (EdU) and a CoQ analogue, with distinct Raman tags was demonstrated

Alkyne-Tag SERS Screening and Identification of Small-Molecule-Binding Sites in Protein

Identification of small-molecule-binding sites in protein is important for drug discovery and analysis of protein function. Modified amino-acid residue(s) can be identified by proteolytic cleavage followed by liquid chromatography–mass spectrometry (LC–MS), but this is often hindered by the complexity of the peptide mixtures. We have developed alkyne-tag Raman screening (ATRaS) for identifying binding sites. In ATRaS, small molecules are tagged with alkyne and form covalent bond with proteins. After proteolysis and HPLC, fractions containing the labeled peptides with alkyne tags are detected by means of surface-enhanced Raman scattering (SERS) using silver nanoparticles and sent to MS/MS to identify the binding site. The use of SERS realizes high sensitivity (detection limit: ∼100 femtomole) and reproducibility in the peptide screening. By using an automated ATRaS system, we successfully identified the inhibitor-binding site in cysteine protease cathepsin B, a potential drug target and prognostic marker for tumor metastasis. We further showed that the ATRaS system works for complex mixtures of trypsin-digested cell lysate. The ATRaS technology, which provides high molecular selectivity to LC–MS analysis, has potential to contribute in various research fields, such as drug discovery, proteomics, metabolomics and chemical biology