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Search results for: METABOLIZM
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Mass spectrometry based identification of geometric isomers during metabolic stability study of a new cytotoxic sulfonamide derivatives supported by quantitative structure-retention relationships
PublicationA set of 15 new sulphonamide derivatives, presenting antitumor activity have been subjected to a metabolic stability study. The results showed that besides products of biotransformation, some additional peaks occurred in chromatograms. Tandem mass spectrometry revealed the same mass and fragmentation pathway, suggesting that geometric isomerization occurred. Thus, to support this hypothesis, quantitative structure-retention relationships...
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Metabolic transformation of antitumor acridinone C-1305 but not C-1311 via selective cellular expression of UGT1A10 increases cytotoxic response: implications for clinical use.
PublicationThe acridinone derivates C-1305 and C-1311 are promising antitumor agents with high activity against several experimental cellular and tumor models and which are under evaluation in pre-clinical and early phase clinical trials. Recent evidence from our laboratories has indicated that both compounds were conjugated by several UGT isoforms with the most active being extrahepatic UGT1A10. The present studies were designed to test...
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Adenylate Kinase 4—A Key Regulator of Proliferation and Metabolic Shift in Human Pulmonary Arterial Smooth Muscle Cells via Akt and HIF-1α Signaling Pathways
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The overexpression of CPR and P450 3A4 in pancreatic cancer cells changes the metabolic profile and increases the cytotoxicity and pro-apoptotic activity of acridine antitumor agent, C-1748
PublicationDrug resistance is one of the major cause of pancreatic cancer treatment failure. Thus, it is still imperative to develop new active compounds and novel approach to improve drug efficacy. Here we present 9-amino-1-nitroacridine antitumor agent, C-1748, developed in our laboratory, as a candidate for pancreatic cancer treatment. We examined (i) the cellular response of pancreatic cancer cell lines: Panc-1, MiaPaCa-2, BxPC-3 and...
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Novel 2-(2-alkylthiobenzenesulfonyl)-3-(phenylprop-2-ynylideneamino)guanidine derivatives as potent anticancer agents – Synthesis, molecular structure, QSAR studies and metabolic stability
PublicationA series of new 2-(2-alkylthiobenzenesulfonyl)-3-(phenylprop-2-ynylideneamino)guanidine derivatives have been synthesized and evaluated in vitro by MTT assays for their antiproliferative activity against cell lines of colon cancer HCT-116, cervical cancer HeLa and breast cancer MCF-7. The obtained results indicated that these compounds display prominent cytotoxic effect. The best anticancer properties have been observed for derivatives...
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MRI assessment of ectopic fat accumulation in pancreas, liver and skeletal muscle in patients with obesity, overweight and normal BMI in correlation with the presence of central obesity and metabolic syndrome
PublicationPurpose: Obesity, defined as a body mass index (BMI) exceeding 30 kg/m2, is a serious health problem, which can be called an epidemic on a global scale and is one of the most important causes of preventable death. The aim of this study was to assess ectopic fat accumulation in pancreas, liver and skeletal muscle in patients with obesity, overweight and normal BMI in correlation with metabolic syndrome (MetS). Patients and methods:...
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Drug-drug interaction potential of antitumor acridine agent C-1748: The substrate of UDP-glucuronosyltransferases 2B7, 2B17 and the inhibitor of 1A9 and 2B7
PublicationBackground The compound 9-(2′-hydroxyethylamino)-4-methyl-1-nitroacridine (C-1748), the promising antitumor agent developed in our laboratory was determined to undergo phase I metabolic pathways. The present studies aimed to know its biotransformation with phase II enzymes – UDP-glucuronosyltransferases (UGTs) and its potential to be engaged in drug-drug interactions arising from the modulation of UGT activity. Methods UGT-mediated...
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The role of intestine and liver in glucuronidation of the imidazo- and triazoloacridinone antitumor agents, C-1311 and C-1305: High affinity substrates for UGT1A10
PublicationCelem przeprowadzonych badań było określenie roli poszczególnych izoform UDP-glukuronylotransferazy (UGT)oraz mikrosomów jelita(HIM)i wątroby (HLM) wyizolowanych od różnych pacjentów w metabolizmie pochodnych akrydonu, związków C-1311 i C-1305. Wykazano, że rodziną UGT katalizującą przemiany C-1305 i C-1311 jest UGT1A, z najwyższą aktywnością wykazywaną przez pozawątrobowy izoenzym UGT1A10. Rozkład aktywności frakcji mikrosomalnych...
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Novel 5-Substituted 2-(Aylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides: Synthesis, Molecular Structure, Anticancer Activity, Apoptosis-Inducing Activity and Metabolic Stability
PublicationA series of novel 5-substituted 2-(arylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl) benzenesulfonamide derivatives 27–60 have been synthesized by the reaction of aminoguanidines with an appropriate phenylglyoxal hydrate in glacial acetic acid. A majority of the compounds showed cytotoxic activity toward the human cancer cell lines HCT-116, HeLa and MCF-7, with IC50 values below 100 M. It was found that for the analogues 36–38...
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Glukuronidacja leków przeciwnowotworowych – detoksyfikacja, mechanizm oporności czy sposób na formę proleku?*
PublicationKsenobiotyki podlegają w organizmie biotransformacji I i II fazy, której celem jest ich detoksyfikacja i ułatwienie wydalania. UDP-glukuronylotransferazy (UGT) – enzymy należące do II fazy metabolizmu katalizują przyłączenie kwasu glukuronowego do lipofilowego substratu zawierającego nukleofilową grupę funkcyjną. Nadrodzina UGT składa się z izoenzymów o różnej swoistości substratowej oraz odmiennym profilu ekspresji w poszczególnych tkankach....
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T cell Activation Is Driven by an ADP-Dependent Glukosinase Linking Enhanced Glycolysis with Mitochondrial Reactive Oxygen Species Generation
PublicationMitochondria-originating reactive oxygen species control T cell receptor (TCR)-induced gene expression. Here, we show that TCR-triggered activation of ADP-dependent glucokinase (ADPGK), an alternative, glycolytic enzyme typical for Archaea, mediates generation of the oxidative signal. We also show that ADPGK is localized in the endoplasmic reticulum and suggest that its active site protrudes toward the cytosol. The ADPGK-driven...
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Synthesis, molecular structure, and metabolic stability of new series of N' -(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-1-(5-phenyl-1 H -pyrazol-1-yl)amidine as potential anti-cancer agents
PublicationA series of new N'-(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-1-(5-phenyl-1H-pyrazol-1-yl)amidine derivatives have been synthesized and evaluated in vitro by MTT assays for their antiproliferative activity against cell lines of colon cancer HCT-116, cervical cancer HeLa and breast cancer MCF-7. The studied compounds display selective activity mainly against HCT-116 and HeLa cells. Thus, five compounds show selective cytotoxic...
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Nutritional properties of mussels Mytilus galloprovincialis
PublicationCelem badań było oznaczenie jakości markerów oraz oszacowanie wpływu diety wzbogaconej w małże pochodzące z zanieczyszczonych i niezanieczyszczonych obszarów na wybrane markery metabolizmu białek i lipidów u szczurów, których pokarm zawierał różne dawki cholesterolu. Obszerny zakres przeprowadzonych testów w warunkach in vitro wykazał, że małże pochodzące z zanieczyszczonych terenów charakteryzują się wyższą zawartością białek,...
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Pregnane X receptor dependent up-regulation of CYP2C9 and CYP3A4 in tumor cells by antitumor acridine agents, C-1748 and C-1305, selectively diminished under hypoxia
PublicationInduction of proteins involved in drug metabolism and in drug delivery has a significant impact on drug-drug interactions and on the final therapeutic effects. Two antitumor acridine derivatives selected for present studies, C-1748 (9-(2’-hydroxyethylamino)-4-methyl-1-nitroacridine) and C-1305 (5-dimethylaminopropylamino-8-hydroxy-triazoloacridinone), expressed high and low susceptibility to metabolic transformations with liver...
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In Vitro and In Vivo Imaging-Based Evaluation of Doxorubicin Anticancer Treatment in Combination with the Herbal Medicine Black Cohosh
PublicationAs a substitution for hormone replacement therapy, many breast cancer patients use black cohosh (BC) extracts in combination with doxorubicin (DOX)-based chemotherapy. In this study, we evaluated the viability and survival of BC- and DOX-treated MCF-7 cells. A preclinical model of MCF-7 xenografts was used to determine the influence of BC and DOX administration on tumor growth and metabolism. The number of apoptotic cells after...
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Determination of phenol biodegradation pathways in three psychrotolerant yeasts, Candida subhashii A011, Candida oregonensis B021 and Schizoblastosporion starkeyi-henricii L012, isolated from Rucianka peatland
PublicationIn this study, three psychrotolerant phenol-degrading yeast strains Candida subhashii (strain A011), Candida oregonenis (strain B021) and Schizoblastosporion starkeyi-henricii (strain L012) isolated from Rucianka peatland were examined to determine which alternative metabolic pathway for phenol biodegradation is used by these microorganisms. All yeast strains were cultivated in minimal salt medium supplemented with phenol at 500,...
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How pesticides affect neonates? - Exposure, health implications and determination of metabolites
PublicationThis review covers key information related to the effects of pesticides on fetal and child health. All humans are exposed to environmental toxicants, however child's health, due to their high vulnerability, should be of special concern. They are continuously exposed to environmental xenobiotics including a wide variety of pesticides, and other pollutants. These compounds can enter the child's body through various routes, both during...
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Determination of bromhexine and its metabolites in equine serum samples by liquid chromatography – Tandem mass spectrometry: Applicability to the elimination study after single oral dose
PublicationBromhexine (BH), expectorant used in the treatment of respiratory disorders associated with viscid or excessive mucus, is not permitted for use in the competing horse by many authorities in horseracing and Olympic disciplines. Metabolic studies are of the great importance in anti-doping field because they allow for updating the selection of the most appropriate markers for prohibited substances, such as metabolites present at higher...
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Bioactivities of Phenolic Compounds from Kiwifruit and Persimmon
PublicationFruit used in the common human diet in general, and kiwifruit and persimmon particularly, displays health properties in the prevention of heart disease. This study describes a combination of bioactivity, multivariate data analyses and fluorescence measurements for the differentiating of kiwifruit and persimmon, their quenching and antioxidant properties. The metabolic differences are shown, as well in the results of bioactivities...
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Modulation of mRNA and protein levels of CYP1A1, 1A2, and 1B1 in nontumorigenic breast epithelial cells (MCF10A) by cabbage juice and its active components
PublicationZbadano wpływ soków z kapusty oraz występujących w nich pochodnych indolowych i sulforafanu na poziom ekspresji enzymów odpowiedzialnych za metabolizm ksenobiotyków w tym estrogenów. Wykazano, że soki z kapusty i izolowane substancje mają podobny wpływ na poziom mRNA i białek enzymatycznych.
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Lifestyle changes in patients with morbid obesity and type 2 diabetes mellitus during the COVID-19 pandemic
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The cellular response of human hepatoma cells with different expression of CYP3A4 isoenzyme to treatment with triazoloacridinone derivative C-1305
PublicationCelem badań było określenie w jaki sposób ekspresja enzymów odpowiedzialnych za metabolizm pochodnej triazoloakrydonu C-1305 wpływa na odpowiedź komórek ludzkiego raka wątroby HepG2 i Hep3A4. W komórkach HepG2 triazoloakrydon C-1305 indukuje proces starzenia, podczas gdy w przypadku linii Hep3A4, komórki ulegają apoptozie oraz nekrozie.
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Heat and mass transfer in air-fed pressurised suits
PublicationOpisano konieczność modelowania transportu masy i ciepła w kombinezonach ochronnych. Omówiono różne sposoby modelowania wymiany ciepła, łącznie ze sprzężoną wymianą ciepła. Uwzględniono również ludzki metabolizm i turbulentne mechanizmy wymiany masy i ciepła. Publikacja opisuje również sposób modelowanie turbulentnych przepływów wieloskładnikowych. Pokazano również porównanie obliczeń z eksperymentem.
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Heat and mass transfer in air-fed pressurised suits
PublicationOpisano konieczność modelowania transportu masy i ciepła w kombinezonach ochronnych. Omówiono różne sposoby modelowania wymiany ciepła, łącznie ze sprzężoną wymianą ciepła. Uwzględniono również ludzki metabolizm i turbulentne mechanizmy wymiany masy i ciepła. Publikacja opisuje również sposób modelowanie turbulentnych przepływów wieloskładnikowych. Pokazano również porównanie obliczeń z eksperymentem.
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Transcriptomic Effects of Estrogen Starvation and Induction in the MCF7 Cells. The Meta-analysis of Microarray Results
PublicationEstrogen is one of the most important signaling molecules which targets a number of genes. Estrogen levels regulate cell proliferation and a plethora of metabolic processes, which may interfere with a range of medical conditions and drug metabolism. The MCF7 breast cancer cell line, expressing the estrogen receptor α, is a well-studied model of cellular answer to estrogen. The aim of this study was to characterize transcriptomic...
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Feasibility Study of Biohydrogen Production from Acid Cheese Whey via Lactate-Driven Dark Fermentation
PublicationThe high loading of lactic acid bacteria (LAB) present in cheese whey still limits its use as hydrogen feedstock. This study aims to investigate the feasibility of producing hydrogen from acid cheese whey via lactate-driven dark fermentation (LD-DF). Mesophilic batch fermentations were performed with delipidated acid cheese whey at a fixed pH of 5.8 and driven by an acidogenic bacterial culture containing LAB and lactate-oxidizing...
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Metody oznaczania właściwości przeciwutleniających fitozwiązków w systemach komórkowych z wykorzystaniem zjawiska fluorescencji/luminescencji.
PublicationOd czasu odkrycia roli reaktywnych form tlenu (RFT) w etiologii tzw. chorób cywilizacyjnych, obejmujących nieinfekcyjne chroniczne choroby, takie jak nowotwory, cukrzyca czy nadciśnienie tętnicze oraz możliwości wykorzystania związków o charakterze przeciwutleniaczy w walce z tymi chorobami, naukowcy opracowali wiele metod służących do oznaczania aktywności przeciwutleniającej , zarówno czystych związków chemicznych, jak i ekstraktów...
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Integration of the sulfate reduction and anammox processes for enhancing sustainable nitrogen removal in granular sludge reactors
PublicationThe Anammox and Sulfate Reduction Ammonium Oxidation processes were compared in two granular sequencing batch reactors operated for 160 days under anammox conditions. It was hypothesized that increasing the concentration of SO42− may positively influence the rate of N removal under anaerobic conditions and it was tested whether SO42− reduction and anammox occur independently or are related to each other. The cooperation of N-S...
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Design optimisation of air-fed full pressurised suits
PublicationOpisano szczegóły złożoności zjawisk cieplno-przepływowych pomiędzy wewnętrzną powierzchnią kombinezonu ochronnego i zewnętrznego ubioru. Komplikacja polega na jednoczesnym rozważaniu wymiany masy i ciepła wraz z realistycznymi, trójwymiarowymi geometriami. Dodatkowo rozważany jest ludzki metabolizm. Zrozumienie tych zjawisk i umiejętnośćich symulacji jest konieczna w celu właściwych prac projektowych nad nowymi typami kombinezonów...
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Oxylipin profiling for clinical research: Current status and future perspectives
PublicationOxylipins are potent lipid mediators with increasing interest in clinical research. They are usually measured in systemic circulation and can provide a wealth of information regarding key biological processes such as inflammation, vascular tone, or blood coagulation. Although procedures still require harmonization to generate comparable oxylipin datasets, performing comprehensive profiling of circulating oxylipins in large studies...
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The antitumor derivatives, C1305 and C1748, were different in effects on CYP3A4 expression and catalytic activity in HepG2 cells
PublicationCytochromy P450 (CYP) należą do grupy enzymów biorących udział w 70-80% metabolizmu fazy I większości stosowanych klinicznie leków. Z tego powodu oddziaływanie leków z enzymami cytochromu P450 stało się istotnym elementem w projektowaniu chemoterapeutyków, szczególnie tych, które są stosowane w terapii wielolekowej. Znajomość substratów, induktorów i inhibitorów poszczególnych izoenzymów P450, nie tylko może obniżać częstość występowania...
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Comparison of nitrogen and VFA removal pathways in autotrophic and organotrophic anammox reactors
PublicationOrganotrophic anammox is a promising process for treating both nitrogen and organic containing wastewater than that of the traditional autotrophic anammox for sole nitrogen removal. However pathways of nitrogen removal particularly at metagenomic level in both processes are still unknown. Here we report, metabolic pathways of nitrogen removal in two lab-scale sequencing batch reactors (SBR), one autotrophic and another organotrophic...
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Genetic Determinants of Vitamin D-Related Disorders; Focus on Vitamin D Receptor
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Evidence for sex differences in the determinants of homocysteine concentrations
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Genistein: a lysosomal stimulator for treatment of various lysosomal diseases
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The molecular mechanism of genistein action in lysosomal storage diseases: A transcriptomic approach
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Amphotericin B and Its New Derivatives - Mode of Action
PublicationAmphotericin B (AmB) is a well known antifungal and antiprotozoal antibiotic used in the clinic for several decades. Clinicalapplications of AmB, however, are limited by its nephrotoxicity and many other acute side effects which are not acceptable by patientswhen their life is not threaten. In order to improve the therapeutic index of this drug, lipid formulations have been introduced and manyefforts have been made to obtain less...
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Disposition of Drugs of Abuse and Their Metabolites in Wastewater as a Method of the Estimation of Drug Consumption
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Biotransformation of abused synthetic cannabinoids, JWH-018 and JWH-073, by human cytochromes P450 and UDP-glucuronosyltransferases
PublicationZwiązki oznaczone symbolami JWH-018 i JWH-073 są syntetycznymi pochodnymi kanabinoidów, obecnymi w preparatach o działaniu psychoaktywnym (K2/Spice). Wcześniejsze badań wykazały, że u osób przyjmujących tzw. ''legalną marihuanę'', głównymi produktami biotransformacji obecnymi w moczu były hydroksylowe pochodne obu związków, jak również ich glukuronidy. W związku z tym celem prowadzonych badań było określenie roli poszczególnych...
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Hyperproteic diet modifies microbiota composition and associated metabolites in rats
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Role of Human UDP-Glucuronosyltransferases in the Biotransformation of the Triazoloacridinone and Imidazoacridinone Antitumor Agents C-1305 and C-1311 : Highly Selective Substrates for UGT1A10
Publication5-Diethylaminoethylamino-8-hydroxyimidazoacridinone, C-1311 (NSC-645809), is an antitumor agent shown to be effective against breast cancer in phase II clinical trials. A similar compound, 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone, C-1305, shows high activity against experimental tumors and is expected to have even more beneficial pharmacological properties than C-1311. Previously published studies showed that these...
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Analytical techniques in studies of the environmental fate of pharmaceuticals and personal-care products
PublicationW pracy przedstawiono dane literaturowe odnośnie źródeł emisji, dróg transportu, przemian i metabolizmu, pomiomu stężeń ksenobiotyków z grupy farmaceutyków i środków higieny osobistej w próbkach pobranych z różnych elementów środowiska (woda, gleba, osady denne) oraz próbek bioty. Szczególną uwagę zwrócono na techniki analityczne wykorzystywane w badaniach losu środowiskowego w/w zanieczyszczeń.
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C-1305 inactivation of recombinant human cytochrome P450, CYP1A2 and CYP3A4, is due to mechanism-based inhibition
PublicationPodjęto próbę określenia mechanizmu obserwowanej inhibicji izoenzymów CYP1A2 i CYP3A4 przez pochodną triazoloakrydonu C-1305.W pierwszym kroku stwierdzono, że hamowanie aktywnosci obu enzymów jest procesem nieodwracalnym. W kolejnych etapach badań wykazano między innymi, że obecność NADPH zwiększa istotnie stopień obserwowanej inhibicji, co wskazało, że mamy do czynienia z inhibicją samobójczą opartą na mechanizmie działania (ang....
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Antibacterial activity of the secondary metabolites from in vitro cultures of Drosera aliciae
PublicationRośliny owadożerne (D. aliciae) metabolity wtórne farmakologicznie czynne substancje. Na wzrost akumulacji tychże substancji w tkankach roślin owadożernych ma wpływ dodatek elicytora. Końcowego oznaczenia zawartości metabolitów w ekstraktach roślinnych dokonano techniką chromatografii cieczowej.
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Modulation of CYP1A1, CYP1A2 and CYP1B1 expression by cabbage juices and indoles in human breast cell lines
PublicationEpidemiological studies have shown that consumption of cab- bage and sauerkraut is connected with significant reduction of breast cancer incidences. Estrogens are considered a major breast cancer risk factor and their metabolism by P450 enzymes substan- tially contributes to carcinogenic activity. The aim of this study was to investigate the effect of cabbage and sauerkraut juices of differ- ent origin on the expression profile...
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Adipokine and cytokine levels in non-functioning adrenal incidentalomas (NFAI)
PublicationDue to the fact that overweight or obesity is accompanied by hormonally active adrenal tumors: Cushing Syndrome-(CS) and Subclinical Cushing Syndrome (SCS), it is of high interest the correlation between different adipokines and cytokines secreted by adipose tissue, with metabolic disorders and hormonal activity in this group. Even in non-functioning adrenal incidentalomas (NFAI) elevated risk for cardiovascular disease and metabolic...
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Microbiological corossion of metallic products as a result of biofilm
PublicationWarunkiem do pojawienia się korozji mikrobiologicznej jest utworzenie na powierzchni metalu biofilmu. Zawiera on biologicznie czynne mikroorganizmy wraz z produktami ich przemian metabolicznych. Biofilm ogranicza dyfuzję produktów metabolizmu wytwarzanych przez poszczególne komórki mikrokolonii. Powoduje to, że produkty uboczne tych przemian gromadzą się w bezpośrednim sąsiedztwie metalu. Gdy powierzchnia metalu nie jest odporna...
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Induction of napthoquinone and flavonoid production in Dionaea muscipula and Drosera capensis
PublicationMetabolity (naftochinony: plumbagina i ramantaceon, flawonoidy: mirecytyna i kwercetyna) z roślin Droseraceae: Dionaea muscipula i Drosera capensis są używane jako leki przeciwnowotworowe i przeciwkurczowe. Przedstawiono zdolności indukowania produkcji tych metabolitów, przez odpowiednie warunki elicytacji w hodowli in vitro.
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In vivo imaging of the human eye using a two-photon excited fluorescence scanning laser ophthalmoscope
PublicationBACKGROUND. Noninvasive assessment of metabolic processes that sustain regeneration of human retinal visual pigments (visual cycle) is essential to improve ophthalmic diagnostics and to accelerate development of new treatments to counter retinal diseases. Fluorescent vitamin A derivatives, which are the chemical intermediates of these processes, are highly sensitive to UV light; thus, safe analyses of these processes in humans...
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Plasma free amino acid profiling as metabolomic diagnostic and prognostic biomarker in paediatric cancer patients: a follow‑up study
PublicationAmino acids (AAs) play a crucial role in cancer cell metabolism. Levels of 22 plasma AAs at the time of diagnosis and after treatment were established among 39 pediatric cancer patients and 33 healthy children. Glutamic acid levels decreased and tryptophan levels increased during treatment. Cancer patients presented significantly lower levels of glutamine and leucine post-treatment while levels of 12 other AAs were higher comparing...