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  • Broe posted an update 8 months, 4 weeks ago

    The hepatotoxic potential of drugs is one of the main reasons why a number of drugs never reach the market or have to be withdrawn from the market. Therefore, the evaluation of the hepatotoxic potential of drugs is an important part of the drug development process. The aim of this work was to evaluate the relative abilities of different supervised self-organizing algorithms in classifying the hepatotoxic potential of drugs. Two modifications of standard counter-propagation training algorithms were proposed to achieve good separation of clusters on the self-organizing map. A series of optimizations were performed using genetic algorithm to select models developed with counter-propagation neural networks, X-Y fused networks, and the two newly proposed algorithms. The cluster separations achieved by the different algorithms were evaluated using a simple measure presented in this paper. Both proposed algorithms showed a better formation of clusters compared to the standard counter-propagation algorithm. The X-Y fused neural network confirmed its high ability to form well-separated clusters. Nevertheless, one of the proposed algorithms came close to its clustering results, which also resulted in a similar number of selected models.Lipidomics provides an overview of lipid profiles in biological systems. Although blood is commonly used for lipid profiling, cerebrospinal fluid (CSF) is more suitable for exploring lipid homeostasis in brain diseases. However, whether an individual’s background affects the CSF lipid profile remains unclear, and the association between CSF and plasma lipid profiles in heathy individuals has not yet been defined. Herein, lipidomics approaches were employed to analyze CSF and plasma samples obtained from 114 healthy Japanese subjects. Results showed that the global lipid profiles differed significantly between CSF and plasma, with only 13 of 114 lipids found to be significantly correlated between the two matrices. Additionally, the CSF total protein content was the primary factor associated with CSF lipids. LBH589 nmr In the CSF, the levels of major lipids, namely, phosphatidylcholines, sphingomyelins, and cholesterolesters, correlated with CSF total protein levels. These findings indicate that CSF lipidomics can be applied to explore changes in lipid homeostasis in patients with brain diseases.In this study, two metal oxide nanoparticles NiO and MnO2 were synthesized from green sources Mentha spicata (M. spicata) extract and Malus domestica (M. domestica) peel extract, respectively. The optical and physical properties of the synthesized nanoparticles were characterized using spectroscopic and microscopic techniques. Simple, precise, and new spectrophotometric probes were suggested for the determination of three cephalosporin antibiotics, including levofloxacin (LVX), cephalexin (CPX), and cefotaxime sodium (CTX) in their pure form and commercial products. The spectrophotometric detection of the selected drugs is based on the catalytic enhancement of NiO and MnO2 nanoparticles (NPs) due to their unique optical properties. Linear relationships with main correlation coefficients 0.999 were obtained at 0.1-20, 1.0-80, and 0.001-100 µg mL-1 for the three drugs in the presence of NiONPs, whereas 0.01-60, 0.1-160, and 0.01-80 µg mL-1 were obtained in the presence of MnO2NPs at absorption wavelengths 290, 262, and 235 nm for LVX, CPX and CTX, respectively. The analytical methods were validated and successfully used for determination of the instigated drugs in their bulk and commercial dosage forms.Obesity has become a worldwide health problem, and many significant inflammatory markers have been associated with the risk of side effects of obesity and obesity-related diseases. After a normal diet or high-fat diet with high-fructose water (HFHF) for 8 weeks, male Wistar rats were divided randomly into four experimental groups according to body weight. Next, for 8 weeks, a normal diet, HFHF diet, and HFHF diet with L. plantarum strains ATG-K2 or ATG-K6 were administered orally. Compared to the control group, the HFHF diet group showed significantly increased visceral fat, epididymal fat, and liver weight. The mRNA and protein expression levels of FAS and SREBP-1c were higher in the HFHF diet group than in the HFHF diet with L. plantarum strains ATG-K2 and ATG-K6. The HFHF diet with L. plantarum strain ATG-K2 showed significantly decreased inflammatory cytokine expression in the serum and small intestine compared to the HFHF diet group. Furthermore, histological morphology showed minor cell injury, less severe infiltration, and longer villi height in the small intestine ileum of the HFHF diet with L. plantarum strains groups than in the HFHF diet group. These results suggest that L. plantarum strains K2 and K6 may help reduce intestinal inflammation and could be used as treatment alternatives for intestinal inflammatory reactions and obesity.Complaints of cognitive functions (CCFs), defined as subjective cognitive dysfunction, affect social function; additionally, for workers, this condition is an important factor in presenteeism and mediates the effect of depressive symptoms on presenteeism. This study aimed to investigate whether CCFs mediate the relationships among insomnia, state anxiety (SA), and presenteeism. Participants were 471 Japanese adult workers evaluated using the Athens Insomnia Scale, State-Trait Anxiety Inventory (Form Y), Cognitive Complaints in Bipolar Disorder Rating Assessment, and Work Limitations Questionnaire 8 to assess insomnia, SA, CCFs, and presenteeism, respectively. Path analysis was used to evaluate the correlations between variables. CCFs significantly mediated the associations among insomnia, SA, and presenteeism. To address the presenteeism associated with insomnia and SA, it may be useful to assess the mediating roles of CCFs.G protein-coupled receptors (GPCRs) bind a broad array of extracellular molecules and transmit intracellular signals that initiate physiological responses. The signal transduction functions of GPCRs are inherently related to their structural plasticity, which can be experimentally observed by spectroscopic techniques. Nuclear magnetic resonance (NMR) spectroscopy in particular is an especially advantageous method to study the dynamic behavior of GPCRs. The success of NMR studies critically relies on the production of functional GPCRs containing stable-isotope labeled probes, which remains a challenging endeavor for most human GPCRs. We report a protocol for the production of the human histamine H1 receptor (H1R) in the methylotrophic yeast Pichia pastoris for NMR experiments. Systematic evaluation of multiple expression parameters resulted in a ten-fold increase in the yield of expressed H1R over initial efforts in defined media. The expressed receptor could be purified to homogeneity and was found to respond to the addition of known H1R ligands.

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