Kellylarson2899

The present study was designed to investigate the hepatoprotective potential of dimethyl fumarate (DMF) against thioacetamide (TAA)-induced liver damage. LY3009120 in vivo Wistar rats were treated with DMF (12.5, 25, and 50 mg/kg/day, orally) and TAA (200 mg/kg intraperitoneally, every third day) for 6 consecutive weeks. TAA exposure significantly reduced body weight, increased liver weight and index, and intervention with DMF did not ameliorate these parameters. DMF treatment significantly restored TAA-induced increase in the levels of aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, total bilirubin, uric acid, malondialdehyde, reduced glutathione, and histopathological findings such as inflammatory cell infiltration, deposition of collagen, necrosis, and bridging fibrosis. DMF treatment significantly ameliorated TAA-induced hepatic stellate cell activation, increase in inflammatory cascade markers (NACHT, LRR, and PYD domains-containing protein 3; NLRP3, apoptosis-associated speck like protein containing a caspase recruitment domain; ASC, caspase-1, nuclear factor-kappa B; NF-κB, interleukin-6), fibrogenic makers (α-smooth muscle actin; ɑ-SMA, transforming growth factor; TGF-β1, fibronectin, collagen 1) and antioxidant markers (nuclear factor (erythroid-derived 2)-like factor 2; Nrf2, superoxide dismutase-1; SOD-1, catalase). The present findings concluded that DMF protects against TAA-induced hepatic damage mediated through the downregulation of inflammatory cascades and upregulation of antioxidant status. © 2020 Wiley Periodicals, Inc.Enzymes in the cytochrome P450 family 1 (CYP1) catalyze metabolic activation of procarcinogens and deactivation of certain anticancer drugs. Inhibition of these enzymes is a potential approach for cancer chemoprevention and treatment of CYP1-mediated drug resistance. We characterized inhibition of human CYP1A1, CYP1A2, and CYP1B1 enzymes by the novel inhibitor N-(3,5-dichlorophenyl)cyclopropanecarboxamide (DCPCC) and α-naphthoflavone (ANF). Depending on substrate, IC50 values of DCPCC for CYP1A1 or CYP1B1 were 10-95 times higher than for CYP1A2. IC50 of DCPCC for CYP1A2 was 100-fold lower than for enzymes in CYP2 and CYP3 families. DCPCC IC50 values were 10-680 times higher than the ones of ANF. DCPCC was a mixed-type inhibitor of CYP1A2. ANF was a competitive tight-binding inhibitor of CYP1A1, CYP1A2, and CYP1B1. CYP1A1 oxidized DCPCC more rapidly than CYP1A2 or CYP1B1 to the same metabolite. Molecular dynamics simulations and binding free energy calculations explained the differences of binding of DCPCC and ANF to the active sites of all three CYP1 enzymes. We conclude that DCPCC is a more selective inhibitor for CYP1A2 than ANF. DCPCC is a candidate structure to modulate CYP1A2-mediated metabolism of procarcinogens and anticancer drugs. © 2020 John Wiley & Sons A/S.The purposes of this research were (1) to analyse the psychometric properties of the Inferential Confusion Questionnaire-Expanded Version (ICQ-EV) in a Spanish population; (2) to explore the role of inferential confusion in obsessive-compulsive disorder (OCD); and (3) to compare the inferential confusion construct in nonclinical and clinical samples. A sample of 342 nonclinical participants and 66 patients with OCD completed the ICQ-EV Spanish adaptation as well as a set of questionnaires. Results confirmed a good fit of the ICQ-EV Spanish version to the original unifactorial structure and excellent internal consistency and test-retest reliability. Moreover, results confirmed that the ICQ-EV predicts Obsessing, Checking, Washing, and Hoarding symptoms, independently of the contribution of dysfunctional beliefs. In addition, OCD patients scored significantly higher on the ICQ-EV than nonclinical participants. The Spanish version of the ICQ-EV is a reliable instrument to assess inferential confusion, and further support is provided for the relevance of the inferential confusion construct in OCD. © 2020 John Wiley & Sons, Ltd.BACKGROUND AND OBJECTIVE Placebo effects are considered to be learning phenomena. There is a growing body of evidence supporting the role of both classical conditioning and observational learning in the induction of placebo effects. However, the third basic learning process, operant conditioning, was not considered as a mechanism of placebo effects until very recently. Unlike classically conditioned responses, which are induced by stimuli that precede the behaviour, operant behaviours are shaped and maintained by their consequences. Thus, placebo effects may not only result from pairing an active intervention with the stimuli that accompany its administration (placebo) but also positive (e.g. the ability to perform a desired activity) or negative reinforcement (e.g. pain relief) of placebo administration may increase the frequency of taking placebos in the future. The paper reviews the evidence supporting the idea of operant conditioning as a mechanism of placebo effects and discusses it in the context of thetrolled trials. © 2020 European Pain Federation - EFIC®.A new generation of saturated benzene mimics - 2-oxabicyclo[2.1.1]hexanes, - was developed. These compounds were designed as analogues of bicyclo[1.1.1]pentane with an improved water solubility. Crystallographic analysis of 2-oxabicyclo[2.1.1]hexanes revealed that they occupy a novel chemical space, but at the same time resemble the fragment of meta -disubstituted benzenes. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.PURPOSE To reduce acquisition time and improve image quality and robustness of ventilation assessment in a single breath-hold using 1 H-guided reconstruction of fluorinated gas (19 F) MRI. METHODS Reconstructions constraining total variation in the image domain, L1 norm in the wavelet domain, and directional total variation between 19 F and 1 H images were compared in order to accelerate 19 F ventilation imaging using retrospectively undersampled data from a healthy volunteer. Using the optimal constrained reconstruction in 8 patients with chronic obstructive pulmonary disease (16-seconds breath-hold), ventilation maps of various acceleration factors (2-fold to 13-fold) were compared with maps of the full data set using the Dice coefficient, difference in volume defect percentage and overlap percentage, as well as hyperpolarized 129 Xe gas MRI. RESULTS The reconstruction constraining total variation and directional total variation simultaneously performed best in the healthy volunteer (RMS error = 0.07, structural similarity index = 0.