Cancer Cell Response to Anthracyclines Effects: Mysteries of the Hidden Proteins Associated with These Drugs

A comprehensive proteome map of T-lymphoblastic leukemia cells and its alterations after daunorubicin, doxorubicin and mitoxantrone treatments was monitored and evaluated either by paired comparison with relevant untreated control and using multivariate classification of treated and untreated samples. With the main focus on early time intervals when the influence of apoptosis is minimized, we found significantly different levels of proteins, which corresponded to 1%–2% of the total amount of protein spots detected. According to Gene Ontology classification of biological processes, the highest representation of identified proteins for all three drugs belong to metabolic processes of proteins and nucleic acids and cellular processes, mainly cytoskeleton organisation and ubiquitin-proteasome pathway. Importantly, we observed significant proportion of changes in proteins involved in the generation of precursor metabolites and energy typical for daunorubicin, transport proteins participating in response to doxorubicin and a group of proteins of immune system characterising response to mitoxantrone. Both a paired comparison and the multivariate evaluation of quantitative data revealed daunorubicin as a distinct member of the group of anthracycline/anthracenedione drugs. A combination of identified drug specific protein changes, which may help to explain anti-cancer activity, together with the benefit of blocking activation of adaptive cancer pathways, presents important approaches to improving treatment outcomes in cancer.     

Universities of the Kyrgyz Republic on the Web: accessibility and usability

Universal Access in the Information Society - Today the Internet is the easiest way to find information about any kind of organization, and the first impression about an organization is almost...     

Hyperbaric storage at and above room temperature of a highly perishable food

Hyperbaric storage at naturally variable room temperature (RT) conditions (18–21 °C) and above (30 °C) was evaluated as a possible new food preservation method, regardless of temperature. Preservation of watermelon juice (used as a case study of a highly perishable food) at RT and 5 °C at atmospheric pressure was compared to preservation under 100 MPa at RT. After 8 h of hyperbaric storage at 100 MPa, the initial microbial loads of the watermelon juice were reduced by 1 log unit for total aerobic mesophiles, and 1–2 log units for Enterobacteriaceae and yeasts and moulds, to levels of about 3 log units for the former and below the detection limit for the latter, and remained thereafter unchanged up to 60 h. Similar results were obtained at 30 °C at 100 MPa after 8 h. At atmospheric pressure at RT (24 h) and 30 °C (8 h), microbial levels were already above quantification limits and unacceptable for consumption. Furthermore, pressure attenuated the increase in titratable acidity verified at atmospheric pressure, but caused higher colour changes, especially a higher lightness and a lower browning degree. Post-hyperbaric storage at 5 °C revealed an extended shelf life, as an additional benefit of hyperbaric storage. These results show that hyperbaric storage is a very promising food preservation methodology.     

ANP and BNP Exert Anti-Inflammatory Action via NPR-1/cGMP Axis by Interfering with Canonical,Non-Canonical,and Alternative Routes of Inflammasome Activation in Human THP1 Cells

Dysregulated inflammasome activation and interleukin (IL)-1β production are associated with several inflammatory disorders. Three different routes can lead to inflammasome activation: a canonical two-step, a non-canonical Caspase-4/5- and Gasdermin D-dependent, and an alternative Caspase-8-mediated pathway. Natriuretic Peptides (NPs), Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP), binding to Natriuretic Peptide Receptor-1 (NPR-1), signal by increasing cGMP (cyclic guanosine monophosphate) levels that, in turn, stimulate cGMP-dependent protein kinase-I (PKG-I). We previously demonstrated that, by counteracting inflammasome activation, NPs inhibit IL-1β secretion. Here we aimed to decipher the molecular mechanism underlying NPs effects on THP-1 cells stimulated with lipopolysaccharide (LPS) + ATP. Involvement of cGMP and PKG-I were assessed pre-treating THP-1 cells with the membrane-permeable analogue, 8-Br-cGMP, and the specific inhibitor KT-5823, respectively. We found that NPs, by activating NPR-1/cGMP/PKG-I axis, lead to phosphorylation of NLRP3 at Ser295 and to inflammasome platform disassembly. Moreover, by increasing intracellular cGMP levels and activating phosphodiesterases, NPs interfere with both Gasdermin D and Caspase-8 cleavage, indicating that they disturb non-canonical and alternative routes of inflammasome activation. These results showed that ANP and BNP anti-inflammatory and immunomodulatory actions may involve the inhibition of all the known routes of inflammasome activation. Thus, NPs might be proposed for the treatment of the plethora of diseases caused by a dysregulated inflammasome activation.     

Weissella cibaria short-fermented liquid sourdoughs based on quinoa or amaranth flours as fat replacer in focaccia bread formulation

Production of the traditional Italian Focaccia bread (FcBread) requires reformulation to meet the new rules for healthier foods. We tested the applicability of a short-fermented (15 h) liquid sourdough (LS) (dough yield, DY, 250), obtained using quinoa (Q) or amaranth (Am) flour fermented with a Weissella cibaria strain (C43-11) producing exopolysaccharides (EPS) as fat replacer in yeast-leavened FcBread. The LSs were applied during the FcBread-making process at industrial pilot plant, reducing the added fat amount by 20% (FcBread-QLS and FcBread-AmLS) and products were compared with reference samples not containing EPS. All the products were analysed for physico-chemical properties (pH, TTA, organic acids, protein content and profile, instrumental colour), textural properties, sensory quality and glycemic index. The application of both pseudo-cereal-based W. cibaria LSs in FcBread allowed obtaining products with a reduced amount of fat, increased protein amount, mainly due to the albumin and glutenin/glutelin fractions, reduced glycemic index, improved texture and preserved in the traditional sensory profile of ‘focaccia’.