67 research outputs found
Physyological role of t-PMET in erythrocytes redox homeostasis: influence of flavonoids
No full textPHYSYOLOGICAL ROLE OF t-PMET IN ERYTHROCYTES REDOX HOMEOSTASIS:INFLUENCE OF FLAVONOIDS
D. Di Majo1, M. La Guardia2, M. Crescimanno1, C. Flandina1, G. Leto1, M. Giammanco1
1Unità Didattico Scientifica di Fisiologia e Farmacologia, Dip. DIGSPO, Università di Palermo;
2Dip. STEBICEF, Università degli Studi di Palermo.
Corresponding author: Danila Di Majo, Unità Didattico Scientifica di Fisiologia e Farmacologia, Dip. DIGSPO,Università degli Studi di Palermo.
e-mail. [email protected], phone +390916236405
Background
In the last decade the trans-Plasma Membrane Electron Transport (t-PMET) has been subject to more research. Ever growing evidence has demonstrated that t-PMET occurs in all types of organisms, including bacteria, yeast plants and animals (1). This system regulates distinct cellular functions and its malfunction relates to some diseases such as cancer, cardiovascular diseases, aging, obesity, neurodegenerative diseases, pulmonary fibrosis, asthma (1). The activity of t-PMET is critical to redox homeostasis in blood. In particular, a close link between t-PMET and metabolic status of erythrocytes has been reported (2). In hypoxic condition the activation of t-PMET may serve to compensate the impaired pentose phosphate pathway, thus ensuring a functional reducing capacity; in this conditions t-PMET may use ascorbic acid or polyphenols as electron donator, since NADH derived from enhanced glycolysis is preferentially utilized by meta-hemoglon reductase (3).Some authors have found a relationship between the dietary flavonoids and trans- plasma membrane oxidoreductase activity, suggesting an additional mechanism whereby dietary flavonoids may exert beneficial effects in human (4).
Aim of this work was evaluate whether some of flavonoids, enclosed in sub-class of flavonols (Quercetin and Kaempherol) and phenolic acids, are able to modify the erythrocytes redox homeostasis. Quercetin has been used as control because other authors had previously described its activity to enter erythrocytes and donate electrons to the PMOR system (4).
Methods
Human venous blood from different healthy volunteers of both sexes between the ages of 25-50 years was obtained by venipuncture in heparin after an over-night fast and centrifuged. The plasma and buffy coat and the upper 15% of the packed red blood cells (RBC) have been removed. The antioxidant capacity of plasma was analyzed by crocin bleaching assay (5) and FRAP. A stock solution (20mM) of each flavonoid was prepared in dimethyl sulfoxide and then diluted 1:2 with PBS. Packed RBC (10%v/v) were incubated in PBS containing 5mM glucose at 37°C for 10 minutes with a 50 μM concentration of each flavonoids. After this time the suspensions was centrifuged, the RBC were washed and then analyzed. The extracellular concentration of the flavonoids was measured in the medium at the end of the incubation period with the compounds (4). The assay was performed spectrophometrically by measuring the absorbance at the wavelength corresponding to the maximal absorption spectrum. The flavonoids intracellular content was measured on the erythrocytes lysate after extraction three times with ethyl acetate and they have been quantified spectrophometrically. The activity of the erythrocyte plasma membrane redox system (PMRS) was estimated by reduction of ferricyanide according to Fiorani method (4). The catalase activity was measured by catalase assay kit purchased from the SIGMA-ALDRICH.
Results
All compounds were taken up by the erythrocytes and displaying significant FIC-reducing activity. Their ability to act as intracellular substrates of PMOR is structure-dependence.
In physiologic condition the catalase activity varies from 28.6 mU/g protein to 40,6 mU/g protein. Catalase activity decreased with increasing concentration of flavonoid and related compounds. The activity of catalase after incubation in the presence of luteolin is lower by 30% than control (erythrocytes without luteolin). This results is not dose-dependence. In fact, no-significance difference has been observed at both luteolin concentrations (10 and 100μM). Not any correlation has been found between catalase and plasma antioxidant capacity.
Conclusions
This study shows that the flavonoids are able to form stable complexes with the erythrocytes and to influence the intracellular redox homeostasis. Therefore, it could affirm that the polyphenols are able to increase the defence of erythrocytes against ROS. This work underlines that the RBC plays a pivotal role in the distribution and bioavailability of circulating polyphenols which contribute to the defence against injury induced by ROS in various clinical disorders.
References
[1] Del Principe D, Avigliano L., Savini I., Catani M.V. 2011. Trans-Plasma Membrane Electron Transport in Mammals: Functional Significance in Health and Disease. Antioxid. Redox Signal 11: 2289-2318;
[2] Kennett EC. and Kuchel PW. 2006. Plasma membrane oxidoreductase: effects on erythrocyte metabolism and redox homeostasis. Antioxid. Redox Signal 8:1241-1247
[3] Rogers SC, Said A, Corcuera DD, McLaughlin D, Kelly P, Doctor A. 2009. Hypoxia limits antioxidant capacity in red blood cells by altering glycolytic pathway dominance. FASEB J. 23: 3159-3170.
[4] Fiorani M and Accorsi A. 2005. Dietary flavonoids as intracellular substrates for erythrocyte trans-plasma membrane oxidoreductase activity. Br. J. Nutr. 94:338-345
[5] Tubaro F, Ghiselli A, Rapuzzi P,Maiorino M, Ursini F.1998.Analysis of plasma antioxidant capacity by competition kinetics. Free Rad. Biol. Med. 24:1228-34
Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies
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GENRE АND POETICS OF I.S. SHMELYOV AUTOBIOGRAPHIC ESSAYS
No full textThe article is devoted to researching of genre nature of I.S. Shmelyov’s autobiographic essays «Leto Gospodne» and «Bogomolye». The main thing is a «soulbuilding» of young man. So one can define the genre as «psychological novel» or «psychological short novel». And also they are «pedagogical novels»: the «ideal tutor», Gorkin, uses the pedagogics of love and virtue founded on Christian doctrines. The author describes also the poetics of Shmelyov’s works based on child’s world outlook connected with colour and sound sensations
Metformin improves lipid metabolism disorders through reducing the expression of microsomal triglyceride transfer protein in OLETF rats
No full textObjective: This study aimed to investigate the role of MTP on lipid metabolism disorders in insulin-resistant rats and the potential mechanism through which metformin can improve lipid metabolism disorders. Methods: 30 OLETF rats served as research subjects and 18 LETO rats of the same strain served as the control group (LETO group). After the first oral glucose tolerance test (at 8-week- old), 6 rats were randomly killed from each group. The remaining 24 OLETF rats were randomly divided into untreated group (OLETF group) and treated group (OLETF/M group, cured with metformin). By the end of the 10th and 20th week of treatment, MTP in the liver was measured for all rats in the study. Results: All OLETF rats exhibited diabetic phenotypes at 18-week-old, with their triglyceride level higher than in LETO rats at the same age. In OLETF rats, MTP level in the liver was higher than in LETO rats at 18-week-old, and the difference was significant at 28-week-old [(13.79 +/- 1.47) vs. (8.20 +/- 1.14), p < 0.05]. Treatment with metformin for 20 weeks decreased triglyceride [(1.06 +/- 0.23) vs. (2.20 +/- 0.62) mmol/L, p < 0.05] and total cholesterol [(1.90 +/- 0.19) vs. (2.36 +/- 0.14) mmol/L, p < 0.05] in OLETF rats. Metformin also decreased MTP level in the liver [(7.65 +/- 1.31) vs. (13.79 +/- 1.47), p < 0.01]. Conclusions: MTP may be associated with the lipid metabolism disorder in OLETF rats and metformin could improve lipid metabolism through reducing the expression of MTP. (C) 2016 Elsevier Ireland Ltd. All rights reserved.'Beijing Natural Science Foundation', Beijing, China [7082092, 7122187]SCI(E)[email protected]
Author response image 1. Author response
No full textObesity produces a chronic inflammatory state involving the NFκB pathway, resulting in persistent elevation of the noncanonical IκB kinases IKKε and TBK1. In this study, we report that these kinases attenuate β-adrenergic signaling in white adipose tissue. Treatment of 3T3-L1 adipocytes with specific inhibitors of these kinases restored β-adrenergic signaling and lipolysis attenuated by TNFα and Poly (I:C). Conversely, overexpression of the kinases reduced induction of Ucp1, lipolysis, cAMP levels, and phosphorylation of hormone sensitive lipase in response to isoproterenol or forskolin. Noncanonical IKKs reduce catecholamine sensitivity by phosphorylating and activating the major adipocyte phosphodiesterase PDE3B. In vivo inhibition of these kinases by treatment of obese mice with the drug amlexanox reversed obesity-induced catecholamine resistance, and restored PKA signaling in response to injection of a β-3 adrenergic agonist. These studies suggest that by reducing production of cAMP in adipocytes, IKKε and TBK1 may contribute to the repression of energy expenditure during obesity. DOI: http://dx.doi.org/10.7554/eLife.01119.001
DEVELOPMENT OF CONTENT ON DEMAND SYSTEM ON XBMC PLATFORM
No full textV diplomski nalogi predstavljamo razvoj sistema vsebin na zahtevo na XBMC platformi. V nalogi predstavimo infrastrukturo sistema IPTV, pripadajoče storitve ter module sistema. Za sistem UMB-SmartTV smo razvili tudi nov XBMC vtičnik za pregled lastnih vsebin. Vtičnik omogoča pregled in predvajanje različnih vsebin na sistemu UMB SmartTV, ki jih lahko uporabnik dodaja v bazo sistema. Podatke o vsebinah je mogoče pregledovati glede na želene kategorije: žanr, leto nastanka, režiser, igralci, avtor itd. Poudarek pri razvoju sistema smo namenili čim hitrejšemu iskanju vsebin, kar smo dosegli tudi z razvrščanjem vsebin v kategorije.The purpose of the diploma thesis is to introduce the development of a Content-on-Demand system on the XBMC platform. The thesis deals with the architecture of the IPTV system, the services that are delivered through this system and its modules. Furthermore we have developed a new XBMC plugin for the content review for the UMB-SmartTV system. The plugin allows the user to view and play various contents that can be added to the system’s database on the UMB-SmartTV system. The user is able to review the information about the content by selecting between different categories like genre, director, actors, author etc. The main goal was to develop a system that provides fast search for specific content and the classification of the content into categories that can help us to access it
Effective drug combinations in breast, colon and pancreatic cancer cells
No full textCombinations of anti-cancer drugs can overcome resistance and provide new treatments1,2. The number of possible drug combinations vastly exceeds what could be tested clinically. Efforts to systematically identify active combinations and the tissues and molecular contexts in which they are most effective could accelerate the development of combination treatments. Here we evaluate the potency and efficacy of 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines. We show that synergy between drugs is rare and highly context-dependent, and that combinations of targeted agents are most likely to be synergistic. We incorporate multi-omic molecular features to identify combination biomarkers and specify synergistic drug combinations and their active contexts, including in basal-like breast cancer, and microsatellite-stable or KRAS-mutant colon cancer. Our results show that irinotecan and CHEK1 inhibition have synergistic effects in microsatellite-stable or KRAS–TP53 double-mutant colon cancer cells, leading to apoptosis and suppression of tumour xenograft growth. This study identifies clinically relevant effective drug combinations in distinct molecular subpopulations and is a resource to guide rational efforts to develop combinatorial drug treatments.Pattern Recognition and Bioinformatic
Slovaški tisk v poznem 19. in zgodnjem 20. stoletju sposebnim poudarkom na slovaško-ameriškem tisku
No full textThe founders of the Slovak press in the United States were Jan Slovensky and Julius Wolf who in 1885 launched the Amerikanszko-Szlovenszke Noviny (American-Slovak News) weekly. Between 1885 and 1918 as many as 121 newspapers and reviews were launched, more than a half of them having lived less then one year. Of those established between 1885 and 1891, only three survived until 1918. The author outlines the development and orientation of these publications and compares them to the press in the homeland.Ustanovitelja prvega slovaškega časopisa v ZDA sta bila Jan Slovensky in Julius Wolf, ki sta 1886 začela izdajati tednik z naslovom Amerikanszko-Szlovenszke Noviny (Ameriškoslovaške novice). Med leti 1885 in 1918 se jih je pojavilo kar 121, vendar jih je polovica od njih izhajala manj kot leto dni. Samo trije, ustanovljeni med 1885 in 1891, so preživeli do leta 1918. Avtor prikazuje razvoj in usmeritev teh časopisov in jih primerja s slovaškim tiskom v matični domovini
Abstract 309: Targeting anti-apoptotic reprogramming to counteract drug tolerance in EGFR-inhibited colorectal tumors
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