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Objectives:The aim of the study is (1) to assess the extent to which omnivores are willing to stop or reduce their consumption of red and processed meat in response to evidence-based information regarding the possible reduction of cancer mortality and incidence achieved by dietary modification; (2) to identify socio-demographic categories associated with higher willingness to change meat consumption and (3) to understand the motives facilitating and hindering such a change.Design:During an initial computer-assisted web interview, respondents were presented with scenarios containing the estimates of the absolute risk reduction in overall cancer incidence and mortality tailored to their declared level of red and processed meat consumption. Respondents were asked whether they would stop or reduce their average meat consumption based on the information provided. Their dietary choices were assessed at 6-month follow-up. Additionally, we conducted semi-structured interviews to better understand the rationale for dietary practices and the perception of health information.Participants:The study was conducted among students and staff of three universities in Krakow, Poland.Results:Most of the 513 respondents were unwilling to change their consumption habits. We found gender to be a significant predictor of the willingness. Finally, we identified four themes reflecting key motives that determined meat consumption preferences: the importance of taste and texture, health consciousness, the habitual nature of cooking and persistence of omnivorous habits.Conclusions:When faced with health information about the uncertain reduction in the risk of cancer mortality and incidence, the vast majority of study participants were unwilling to introduce changes in their consumption habits.

The large and significant increase in carbon dioxide concentration in the Earth’s atmosphere is a serious problem for humanity. The amount of CO2 is increasing steadily which causes a harmful greenhouse effect that damages the Earth’s climate. Therefore, one of the current trends in modern chemistry and chemical technology are issues related to its utilization. This work includes the analysis of the possibility of chemical consumption of CO2 in Diels-Alder processes under non-catalytic and catalytic conditions after prior activation of the C=O bond. In addition to the obvious benefits associated with CO2 utilization, such processes open up the possibility of universal synthesis of a wide range of internal carboxylates. These studies have been performed in the framework of Molecular Electron Density Theory as a modern view of the chemical reactivity. It has been found, that explored DA reactions catalyzed by Lewis acids with the boron core, proceeds via unique stepwise mechanism with the zwitterionic intermediate. Bonding Evolution Theory (BET) analysis of the molecular mechanism associated with the DA reaction between cyclopentadiene and carbon dioxide indicates that it takes place thorough a two-stage one-step mechanism, which is initialized by formation of C–C single bond. In turn, the DA reaction between cyclopentadiene and carbon dioxide catalysed by BH3 extends in the environment of DCM, indicates that it takes place through a two-step mechanism. First path of catalysed DA reaction is characterized by 10 different phases, while the second by eight topologically different phases.

The structure of tetraphosphetane zirconium complex C52H100N8OP10Zr2 was determined by single crystal X-ray diffraction analysis. The crystal belongs to the monoclinic system, space group P21/c, with a = 19.6452(14), b = 17.8701(12), c = 20.7963(14) Å, alfa = gamma = 90º, beta = 112.953(7), V = 6722.7(8)Å3, Z = 4. The electronic structure of the organometallic complex has been characterized within the framework of Quantum Chemical Topology. The topology of the Electron Localization Function (ELF) and the electron density according to the Quantum Theory of Atoms in Molecules (QTAIM) show no covalent bonds involving the Zr atom, but rather dative, coordinate interactions between the metal and the ligands. This is the first reported case of a Zr complex stabilized by an oxide anion, anionic cyclopentadienyl ligands and rare tetraphosphetane anions.

Background Hepatic enzymes involved in drug metabolism vary markedly in expression, abundance and activity, which affects individual susceptibility to drugs and toxicants. The present study aimed to compare mRNA expression and protein abundance of the most pharmacologically relevant drug-metabolizing enzymes in two main sources of the control liver samples that are used as the reference, i.e. organ donor livers and non-tumorous tissue from metastatic livers. An association analysis of the most common genetic variants with mRNA and protein levels was also performed. Methods The CYP450 and UGT enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, UGT1A1, UGT1A3, UGT2B7 and UGT2B15) were analyzed for mRNA (qPCR) and protein abundance (LC–MS/MS) in healthy donors (n = 11) and metastatic (n = 13) livers. Genotyping was performed by means of TaqMan assays and pyrosequencing. Results Significantly higher protein abundance in the metastatic livers was observed in case of CYP2C9, CYP2D6, and UGT2B7, and for UGT1A3 the difference was only significant at mRNA level. For all the enzymes except CYP2E1 some significant correlation between mRNA and protein content was observed, and for UGT1A1 an inverse correlation with age was noted. CYP2C19, CYP3A5 and CYP2D6 were significantly affected by genotype. Conclusion The selection of a control group for the study on drug-metabolizing enzymes (e.g. in pathological states) may possibly affect its conclusions on differences in mRNA and protein content. Genotyping for common functional variants of CYP450 enzymes should be performed in all studies on drug-metabolizing enzymes.

Background Wilson’s disease is a genetic disorder inherited in a recessive manner, caused by mutations in the copper-transporter ATP7B. Although it is a well-known disease, currently available treatments are far from satisfactory and their efficacy varies in individual patients. Due to the lack of information about drug-metabolizing enzymes and drug transporters profile in Wilson’s disease livers, we aimed to evaluate the mRNA expression and protein abundance of selected enzymes and drug transporters in this liver disorder. Methods We analyzed gene expression (qPCR) and protein abundance (LC–MS/MS) of 14 drug-metabolizing enzymes and 16 drug transporters in hepatic tissue from Wilson’s disease patients with liver failure (n = 7, Child–Pugh class B and C) and metastatic control livers (n = 20). Results In presented work, we demonstrated a downregulation of majority of CYP450 and UGT enzymes. Gene expression of analyzed enzymes ranged between 18 and 65% compared to control group and significantly lower protein content of CYP1A1, CYP1A2, CYP2C8, CYP2C9, CYP3A4 and CYP3A5 enzymes was observed in Wilson’s disease. Moreover, a general decrease in hepatocellular uptake carriers from SLC superfamily (significant at protein level for NTCP and OATP2B1) was observed. As for ABC transporters, the protein abundance of BSEP and MRP2 was significantly lower, while levels of P-gp and MRP4 transporters were significantly higher in Wilson’s disease. Conclusions Altered hepatic expression of drug‐metabolizing enzymes and drug transporters in Wilson’s disease patients with liver failure may result in changes of drug pharmacokinetics in that group of patients.

Environmental factors contribute to autoimmune disease manifestation, and as regarded today, AhR has become an important factor in studies of immunomodulation. Besides immunological aspects, AhR also plays a role in pharmacological, toxicological and many other physiological processes such as adaptive metabolism. In recent years, epigenetic mechanisms have provided new insight into gene regulation and reveal a new contribution to autoimmune disease pathogenesis. DNA methylation, histone modifications, chromatin alterations, microRNA and consequently non-genetic changes in phenotypes connect with environmental factors. Increasing data reveals AhR cross-roads with the most significant in immunology pathways. Although study on epigenetic modulations in autoimmune diseases is still not well understood, therefore future research will help us understand their pathophysiology and help to find new therapeutic strategies. Present literature review sheds the light on the common ground between remodeling chromatin compounds and autoimmune antibodies used in diagnostics. In the proposed review we summarize recent findings that describe epigenetic factors which regulate AhR activity and impact diverse immunological responses and pathological changes.

Membrane monocarboxylate transporter 1 (SLC16A1/MCT1) plays an important role in hepatocyte homeostasis, as well as drug handling. However, there is no available information about the impact of liver pathology on the transporter levels and function. The study was aimed to quantify SLC16A1 mRNA (qRT-PCR) and MCT1 protein abundance (liquid chromatography&ndash, tandem mass spectrometry (LC&shy, &shy, &ndash, MS/MS)) in the livers of patients diagnosed, according to the standard clinical criteria, with hepatitis C, primary biliary cirrhosis, primary sclerosing hepatitis, alcoholic liver disease (ALD), and autoimmune hepatitis. The stage of liver dysfunction was classified according to Child&ndash, Pugh score. Downregulation of SLC16A1/MCT1 levels was observed in all liver pathology states, significantly for ALD. The progression of liver dysfunction, from Child&ndash, Pugh class A to C, involved the gradual decline in SLC16A1 mRNA and MCT1 protein abundance, reaching a clinically significant decrease in class C livers. Reduced levels of MCT1 were associated with significant intracellular lactate accumulation. The MCT1 transcript and protein did not demonstrate significant correlations regardless of the liver pathology analyzed, as well as the disease stage, suggesting posttranscriptional regulation, and several microRNAs were found as potential regulators of MCT1 abundance. MCT1 membrane immunolocalization without cytoplasmic retention was observed in all studied liver pathologies. Overall, the study demonstrates that SLC16A1/MCT1 is involved in liver pathology, especially in ALD.

Despite on-going medical advances, ovarian cancer survival rates have stagnated. In order to improve IP delivery of platinum-based antineoplastics, we aimed to develop a sustained drug delivery system for carboplatin (CPt). Toward this aim, we pursued a double emulsion process for obtaining CPt-loaded microcapsules composed of poly(ethylene terephthalate-ethylene dilinoleate) (PET-DLA) copolymer. We were able to obtain PET-DLA microspheres in the targeted size range of 10&ndash, 25 &micro, m (median: 18.5 &micro, m), to reduce intraperitoneal clearance by phagocytosis and lymphoid transit. Empty microspheres showed the lack of toxicity in vitro. The double emulsion process yielded 2.5% w/w CPt loading and obtained microcapsules exhibited sustained (&gt, 20 day) zero-order release. The encapsulated CPt was confirmed to be bioavailable, as the microcapsules demonstrated efficacy against human ovarian adenocarcinoma (SK-OV-3) cells in vitro. Following intraperitoneal injection in mice, we did not observe adhesions, only mild, clinically-insignificant, local inflammatory response. Tissue platinum levels, monitored over 14 days using atomic absorption spectroscopy, revealed low burst and reduced systemic uptake (plasma, kidney), as compared to neat carboplatin injection. Overall, the results demonstrate the potential of the developed microencapsulation system for long-term intraperitoneal sustained release of carboplatin for the treatment of ovarian cancer.

The domino sequence of pseudocyclic reactions involving 4-methoxybenzonitrile N-oxide and trans-2-phenyl-1-cyano-1-nitroethene proceeding in mild (r.t.; atm. pressure) non-catalytic (without participation of palladium or other transition metals (TM)) conditions yielded a bis-heterobiarylic molecular system containing an oxadiazole moiety with an almost 40% yield. The presented methodology represents therefore an evident contrast to the existing methods of preparation of bis-heterobiarylic systems, which require the presence of TMs. This reaction should be considered stereochemically “clean” and contains a stage of cycloaddition to the C N bond. It should be underlined that this is the first case of non-catalyzed [3 + 2] cycloaddition involving the nitrile C N bond. Our comprehensive study shows that the described protocol can be applied as a general methodology for preparation of a wide group of bis-heterobiarylic molecules. The self-adjusted cascade of transformations, which is unique and valuable from the practical point of view, leads to formation of a single isomeric product (from many possible) as a consequence of three pseudocyclic tandem reactions performed in agreement with the fundamental principles of green chemistry and sustainable development with a maximal level of atom economy and good overall yields. A self-adjustment phenomenon observed in the studied smart technology leading to production of a material with special properties was explained by it deep quantum nature confirmed undoubtedly by the modern Molecular Electron Density Theory.

5-(Nitromethyl)-3-phenyl-4,5-dihydroisoxazole was obtained as a product of a high-yielding [3 + 2] cycloaddition reaction of in situ-generated benzonitrile N-oxide and 3-nitroprop-1-ene. For the first time, the regiochemistry of this reaction was unambiguously proven by X-ray structural analysis. The quantum-chemical calculation performed at the M06-2X/6-31G(d) (PCM) theoretical level affords a basis for explaining the course of reaction as well as the nature of transition states. Next, further DFT calculations together with spectral data shed light on structural aspects of the product. The research was carried out with the equipment purchased thanks to the financial support of the European Regional Development Fund in the framework of the Operational Program Development of Eastern Poland 2007–2013 (Contract no. UDA-POIG.02.01.00-06-212/09-03, ECOTECH Complex—Man, Environment, Production). The authors also thank the Polish Ministry of Science and High Education for financial support (Grant no. C-2/171/2017/DS).

Purpose New-onset diabetes after transplantation (NODAT) is a major complication after kidney transplantation. The risk factors for NODAT include the use of calcineurin inhibitors as part of the immunosuppressive regimen, among which tacrolimus has the most pronounced diabetogenic effect. Both NODAT and type 2 diabetes mellitus (T2DM) share several risk factors. Recent studies have identified a number of common genetic variants associated with increased risk of T2DM. Here we report the results of our study on the potential effect of single nucleotide polymorphisms (SNPs) previously associated with T2DM on the risk of NODAT in kidney transplant patients medicated with tacrolimus. Methods Seven SNPs in six genes known to increase the risk of T2DM in Caucasians were genotyped by means of TaqMan assays in 235 kidney transplant patients medicated with tacrolimus: rs4402960 and rs1470579 in IGF2BP2; rs1111875 in HHEX; rs10811661 upstream of CDKN2A/B; rs13266634 in SLC30A8; rs1801282 in PPARG; rs5215 in KCNJ11. The TCF7L2 rs7903146 SNP was also included in the multivariate analysis. Results None of the analyzed SNPs was significantly associated with the risk of NODAT. However, the IGF2BP2 rs4402960 T allele was present significantly more frequently among patients diagnosed with NODAT more than 2 weeks after transplantation (p = 0.048). Mean (± standard deviation) number of the analyzed alleles tended to be lower in patients without NODAT (6.19 ± 1.71) than in NODAT patients (6.58 ± 1.1.95; p = 0.09) and significantly lower compared to late-onset NODAT patients (7.03 ± 1.88; p = 0.018). Multivariate analysis confirmed the significance of ‘diabetogenic’ allele number in late-onset NODAT development [odds ratio (OR) 1.37, 95 % confidence interval (CI) 1.05–1.78; p = 0.017]. Additionally, individuals carrying >7 of the analyzed ‘diabetogenic’ alleles were at a significantly higher risk of NODAT (OR 2.17, 95 % CI 1.18–3.99; p = 0.015). Conclusions Complex analysis of genotypes increasing the risk of diabetes may lead to the identification of NODAT susceptibility predictors.

The synthesis, characterization, and toxicity of graphene oxide and reduced graphene oxide are reported. Prior to the cytocompatibility tests the stability of the suspensions in a wide range of concentrations (3.125-100 μg/mL) of three different dispersants is studied. Polyethylene glycol (PEG), polyethylene glycol-polypropylene glycol-polyethylene glycol (Pluronic P123), and sodium deoxycholate (DOC) are investigated as the dispersants. The toxicity depends on the type of dispersant and concentration of the nanomaterials in the suspensions. Detailed analysis suggests that graphene oxide functionalized with PEG in the concentration range between 3125 μg/mL and 25 μg/mL exhibits the best biocompatibility with mice fibroblast cells (line L929).

In the title compound, [Zr(C(5)H(5))(C(13)H(9))(2)Cl]·C(7)H(8), the Zr(IV) atom is coordinated by a Cl atom, a cyclo-penta-dienyl (Cp) ligand [Zr-centroid (Cp) = 2.199 (3) Å] and two fluorenyl ligands (Fl) [Zr-centroid (Fl) = 2.273 (2) Å and Zr-CH from fluorenyl = 2.355 (2) Å] in a distorted tetra-gonal geometry. The dihedral angles between the mean planes of the fluorenyl ring systems and the Cp ring are 36.62 (6)° for the η(1)-coordinated fluorenyl and 52.85 (6)° for the η(5)-coordinated fluorenyl, while the dihedral angle between the mean planes of the two fluorenyl ring systems is 76.18 (7)°.