Hypoxic 3D in vitro culture models reveal distinct resistance processes to TKIs in renal cancer cells

The aim of this study is to determine the effect of hypoxia on axitinib and sorafenib-treated renal cell carcinoma (RCC) cells. Hypoxia is a crucial factor influencing transcription process via protein modulation, which was shown i.e. in pancreatic cancer. Until now, hypoxia has been defined as associated with poorer outcome and inducing chemotherapy resistance in solid tumors. The unique phenomenon of pseudo-hypoxia connected with vhl mutation was observed in clear-cell, but not in papillary RCC, and the treatment of this subtype of cancer is still challenging. Despite the introduction of new antiangiogenic targeted therapies (inter alia tyrosine kinase inhibitors, TKIs), patients still develop both primary and acquired resistance. Overcoming resistance to TKIs, also in papillary RCC, may be possible by finding significantly modified protein expression. To do this, hypoxic 3D in vitro models must be developed to mimic both molecular pathways typical for low oxygen tension and cell–cell dynamics in tumor-like spatial structures

Hypoxic 3D in vitro culture models reveal distinct resistance processes to TKIs in renal cancer cells

The aim of this study is to determine the effect of hypoxia on axitinib and sorafenib-treated renal cell carcinoma (RCC) cells. Hypoxia is a crucial factor influencing transcription process via protein modulation, which was shown i.e. in pancreatic cancer. Until now, hypoxia has been defined as associated with poorer outcome and inducing chemotherapy resistance in solid tumors. The unique phenomenon of pseudo-hypoxia connected with vhl mutation was observed in clear-cell, but not in papillary RCC, and the treatment of this subtype of cancer is still challenging. Despite the introduction of new antiangiogenic targeted therapies (inter alia tyrosine kinase inhibitors, TKIs), patients still develop both primary and acquired resistance. Overcoming resistance to TKIs, also in papillary RCC, may be possible by finding significantly modified protein expression. To do this, hypoxic 3D in vitro models must be developed to mimic both molecular pathways typical for low oxygen tension and cell–cell dynamics in tumor-like spatial structures

Nursing diagnoses and care assessed by the patients treated with percutaneous coronary intervention due to acute coronary syndrome

At present, the most effective method of treatment for acute coronary syndromes (ACS) is the promptest possible canalisation of the infarct-related vessel by means of the percutaneous coronary intervention method (PCI), which also affects the mode of nursing procedure. There is currently no functional model of care with regard to post-PCI patients, while previous attempts at implementing it have failed to include verification of patients' opinions. The purpose of the work was to indicate what problems of biopsychosocial nature occurred among post-PCI patients and to what extent they were resolved by the nurses. 100 ACS-affected patients treated with the PCI method were subjected to the study. The study utilised data collected on the basis of a survey questionnaire, medical records, and direct observation. It follows from the obtained data that the major problems occurring among post-PCI patients included: pain complaints, dyspnea, difficult urination, weakness, increased thirst, disturbed sleep rhythm, fear and anxiety, insufficient knowledge relating to disease risk factors. The patients were satisfied with nursing care involving the fulfillment of their biological needs, while significantly less with emotional and value-oriented support. 88% of the subjects reported an absence of health-related information and education. Among the patients treated with the PCI method due to the ACS causes, a high level of satisfaction was found with regard to nursing activities aimed at resolving biological problems. Improvements in the areas of emotional support, information, and health education are required

An Ultrasensitive Biosensor for Detection of Femtogram Levels of the Cancer Antigen AGR2 Using Monoclonal Antibody Modified Screen-Printed Gold Electrodes.

The detection of cancer antigens is a major aim of cancer research in order to develop better patient management through early disease detection. Many cancers including prostate, lung, and ovarian secrete a protein disulfide isomerase protein named AGR2 that has been previously detected in urine and plasma using mass spectrometry. Here we determine whether a previously developed monoclonal antibody targeting AGR2 can be adapted from an indirect two-site ELISA format into a direct detector using solid-phase printed gold electrodes. The screen-printed gold electrode was surface functionalized with the anti-AGR2 specific monoclonal antibody. The interaction of the recombinant AGR2 protein and the anti-AGR2 monoclonal antibody functionalized electrode changed its electrochemical impedance spectra. Nyquist diagrams were obtained after incubation in an increasing concentration of purified AGR2 protein with a range of concentrations from 0.01 fg/mL to 10 fg/mL. In addition, detection of the AGR2 antigen can be achieved from cell lysates in medium or artificial buffer. These data highlight the utility of an AGR2-specific monoclonal antibody that can be functionalized onto a gold printed electrode for a one-step capture and quantitation of the target antigen. These platforms have the potential for supporting methodologies using more complex bodily fluids including plasma and urine for improved cancer diagnostics

Inhibition of protein disulfide isomerase induces differentiation of acute myeloid leukemia cells

Acute myeloid leukemia is a malignant disease of immature myeloid cells. Despite significant therapeutic effects of differentiation-inducing agents in some acute myeloid leukemia subtypes, the disease remains incurable in a large fraction of patients. Here we show that SK053, a thioredoxin inhibitor, induces differentiation and cell death of acute myeloid leukemia cells. Considering that thioredoxin knock-down with short hairpin RNA failed to exert antiproliferative effects in one of the acute myeloid leukemia cell lines, we used a biotin affinity probe-labeling approach to identify potential molecular targets for the effects of SK053. Mass spectrometry of proteins precipitated from acute myeloid leukemia cells incubated with biotinylated SK053 used as a bait revealed protein disulfide isomerase as a potential binding partner for the compound. Biochemical, enzymatic and functional assays using fluorescence lifetime imaging confirmed that SK053 binds to and inhibits the activity of protein disulfide isomerase. Protein disulfide isomerase knockdown with short hairpin RNA was associated with inhibition of cell growth, increased CCAAT enhancer-binding protein α levels, and induction of differentiation of HL-60 cells. Molecular dynamics simulation followed by the covalent docking indicated that SK053 binds to the fourth thioredoxin-like domain of protein disulfide isomerase. Differentiation of myeloid precursor cells requires the activity of CCAAT enhancer-binding protein α, the function of which is impaired in acute myeloid leukemia cells through various mechanisms, including translational block by protein disulfide isomerase. SK053 increased the levels of CCAAT enhancer-binding protein α and upregulated mRNA levels for differentiation-associated genes. Finally, SK053 decreased the survival of blasts and increased the percentage of cells expressing the maturation-associated CD11b marker in primary cells isolated from bone marrow or peripheral blood of patients with acute myeloid leukemia. Collectively, these results provide a proof-of-concept that protein disulfide isomerase inhibition has potential as a therapeutic strategy for the treatment of acute myeloid leukemia and for the development of small-molecule inhibitors of protein disulfide isomerase

Bioaccumulation of Macronutrients in Edible Mushrooms in Various Habitat Conditions of NW Poland—Role in the Human Diet

Recently, the interest in mushroom consumption has been growing, since their taste and low calorific value are appreciated, but also due to their nutritional value. In determining the usefulness of mushrooms in the human diet, it is important to consider the conditions of their occurrence to perform the assessment of bioaccumulation of minerals. The aim of the study was: (a) to determine the content of selected macronutrients (P, K, Ca, Mg, Na) in fruiting bodies of Boletus edulis, Imleria badia, Leccinum scabrum and the soils, (b) to determine their bioaccumulation potential taking into account the habitat conditions, and (c) an attempt to estimate their role in covering the requirement for macronutrients of the human organism. The research material was obtained in the NW of Poland: Uznam and Wolin, the Drawa Plain and the Ińsko Lakeland. In the soil, we determined the content of organic matter, pH, salinity and the content of absorbable and general forms of macronutrients. The content of macronutrients in mushrooms was also determined. Chemical analyses were performed using the generally accepted test methods. The study showed that in NW Poland, B. edulis grew on the acidic soils of Arenosols, and I. badia and L. scabrum grew on Podzols. The uptake of K, Mg and Ca by the tested mushrooms was positively, and P and Na negatively correlated with the content of these elements in the soil. The acidity of the soil affected the uptake of K and Mg by mushrooms. There was no effect of the amount of organic matter in the soil noticed on the content of macronutrients (except sodium) in mushrooms. Among the studied macronutrients, none of the mushrooms accumulated Ca, while P and K were generally accumulated in the highest amounts, regardless of the species. Each of the other elements was usually accumulated at a similar level in the fruiting bodies of the species we studied. The exception was I. badia, which accumulated higher amounts of Mg compared to B. edulis and L. scabrum. Mushrooms can enrich the diet with some macronutrients, especially in P and K

Effects of Ozone Dissolved in Water on the Physicochemical Properties of Activated Carbons Applied in Drinking Water Treatment

The results of treating commercial granulated activated carbons with ozone, both gaseous and dissolved in water, were analyzed. The original carbons (Filtrasorb-300 and Carbsorb-38) were carefully flushed with distilled water to remove any water-soluble impurities. For comparison, each of the washed activated carbons was treated separately with aqueous hydrogen peroxide. The following procedures were applied to assess the effects of contact between each carbon and the oxidizing agents: thermogravimetry, alkalimetry, voltammetry, EDX and FT-IR methods to illustrate changes in the surface chemistry, and nitrogen low-temperature adsorption to show up any possible changes in the porous structure. Ozone dissolved in water exhibited the lowest oxidative strength — EDX and FT-IR spectroscopy revealed only a slight oxidation of the Filtrasorb-300 surface layer. Despite its smaller specific area, this carbon surface exhibited greater roughness and was more susceptible to oxidation. The liquid-phase adsorption isotherms of p -chlorophenol from aqueous solution onto this carbon showed that surface oxygen reduced the extent of adsorption. The experimental data were best fitted by the Langmuir isotherm model

Nursing diagnoses and care assessed by the patients treated with percutaneous coronary intervention due to acute coronary syndrome

Wstęp. Obecnie najskuteczniejszym sposobem leczenia ostrych zespołów wieńcowych (OZW) jest jak najszybsze udrożnienie naczynia dozawałowego metodą przezskórnej angioplastyki tętnic wieńcowych (PCI), co zmienia także sposób postępowania pielęgniarskiego. Dotychczas nie funkcjonuje model opieki nad chorym po PCI, a podejmowane próby wdrożenia go w życie nie uwzględniały weryfikacji opinii pacjentów. Cel pracy. Celem pracy było wskazanie, jakie problemy w sferze biopsychospołecznej wystąpiły u chorych po PCI i w jakim stopniu były one rozwiązane przez pielęgniarki. Materiał i metody. Badaniu poddano 100 pacjentów z OZW leczonych metodą PCI. W badaniu wykorzystano dane zebrane na podstawie kwestionariusza ankiety, dokumentacji i obserwacji bezpośredniej. Wyniki. Z uzyskanych danych wynika, że głównymi problemami występującymi u pacjentów po PCI były: dolegliwości bólowe, duszność, trudności w oddawaniu moczu, osłabienie, wzmożone pragnienie, zaburzony rytm snu, uczucie lęku i niepokoju, niedostateczna wiedza na temat czynników ryzyka choroby. Pacjenci byli zadowoleni z opieki pielęgniarskiej w zakresie zaspokajania potrzeb biologicznych, rzadziej ze wsparcia emocjonalnego i wartościującego. Brak informacji oraz edukacji zdrowotnej zgłosiło 88% badanych. Wnioski. Wśród pacjentów leczonych PCI z powodu OZW stwierdzono wysoki poziom satysfakcji z działań pielęgniarskich zmierzających do rozwiązania problemów biologicznych. Poprawy wymagają obszary wsparcia, informacji i edukacji zdrowotnej.Introduction. At present, the most effective method of treatment for acute coronary syndromes (ACS) is the promptest possible canalisation of the infarct-related vessel by means of the percutaneous coronary intervention method (PCI), which also affects the mode of nursing procedure. There is currently no functional model of care with regard to post-PCI patients, while previous attempts at implementing it have failed to include verification of patients’ opinions. Aim. The purpose of the work was to indicate what problems of biopsychosocial nature occurred among post-PCI patients and to what extent they were resolved by the nurses. Material and methods. 100 ACS-affected patients treated with the PCI method were subjected to the study. The study utilised data collected on the basis of a survey questionnaire, medical records, and direct observation. Results. It follows from the obtained data that the major problems occurring among post-PCI patients included: pain complaints, dyspnea, difficult urination, weakness, increased thirst, disturbed sleep rhythm, fear and anxiety, insufficient knowledge relating to disease risk factors. The patients were satisfied with nursing care involving the fulfillment of their biological needs, while significantly less with emotional and value-oriented support. 88% of the subjects reported an absence of health-related information and education. Conclusions. Among the patients treated with the PCI method due to the ACS causes, a high level of satisfaction was found with regard to nursing activities aimed at resolving biological problems. Improvements in the areas of emotional support, information, and health education are required

The Role in the Human Diet of Bioaccumulation of Selenium, Copper, Zinc, Manganese and Iron in Edible Mushrooms in Various Habitat Conditions of NW Poland—A Case Study

The aim of the study was to determine the contents of microelements in Boletus edulis, Imleria badia and Leccinum scabrum, taking into account the soil conditions in selected forest areas of Northwest Poland and the bioaccumulation capacity of these fungi and their role in the human diet. Se, Cu, Zn, Mn and Fe contents were determined in the soil (organic and mineral layers) and mushrooms. The study showed that the soils on which fruiting bodies grew did not differ significantly in the contents of these trace elements. The concentrations of microelements in mushrooms in NW Poland were mostly at the lower range of the contents reported for these species in other regions of Poland and Europe. The uptake of microelements by the studied mushrooms was influenced by soil reaction, organic matter content, and bioavailable and total forms of the elements. B. edulis contained significantly more Se than other mushroom species and, together with I. badia, was much more abundant in Cu and Zn than L. scabrum. Fruiting bodies bioaccumulated Se (most strongly by B. edulis; BCF = 120.6), Cu and Zn. The contents of microelements in the tested mushrooms may be supplementary elements in the human diet

O profesor Marii Wojtak

Rozmowa z prof. Teresą Dobrzyńską (Instytut Badań Literackich PAN, Warszawa), prof. Ewą Malinowską (Uniwersytet Opolski), prof. Bożeną Witosz (Uniwersytet Śląski), prof. Janem Mazurem (Uniwersytet Marii Curie-Skłodowskiej), prof. Terézią Rončákovą (Katolícka univerzita v Ružomberku) oraz z prof. Danutą Kępą-Figurą (Uniwersytet Marii Curie-Skłodowskiej) na temat wkład prof. Marii Wojtak w rozwój badań dotyczących stylistyki, genologii lingwistycznej, języka religii