Perssonnixon1045

Erythropoietin (EPO) is a hormone, which stimulates the production of red blood cells. Due to its performance-enhancing effect, it is prohibited by the World Anti-Doping Agency (WADA). In order to reduce the detection window of EPO doping, athletes have been applying low doses of recombinant EPO (e.g., less then 10 IU/kg body weight, daily or every second day) instead of larger doses twice or more per week (e.g., 30 IU/kg). Microdoses of Retacrit (epoetin zeta), an EPO biosimilar, were administered intravenously and subcutaneously to human males and females. Urine and serum samples were collected and analysed applying the new biotinylated clone AE7A5 EPO antibody and a further optimized sarcosyl polyacrylamide gel electrophoresis (SAR-PAGE) protocol. With the improved protocol, microdosed Retacrit (7.5 IU/kg body weight [BW]) was detectable for at least 52 h after intravenous administration. Detection windows were approximately the same for serum and urine and doubled after subcutaneous administration (~104 h). Previous studies applying different electrophoretic techniques and the not further optimized SAR-PAGE protocol revealed considerably shorter detection windows for recombinant human erythropoietin (rhEPO) microdoses. Because the new biotinylated antibody performed significantly more sensitive than the nonbiotinylated version, the new protocol will improve the sensitivity and hence detectability of recombinant EPO in doping control.Mitogen-activated protein kinases (MAPKs) play a key role in complex cellular processes such as proliferation, development, differentiation, transformation and apoptosis. Mammals express at least four distinctly regulated groups of MAPKs which include extracellular signal-related kinases (ERK)-1/2, p38 proteins, Jun amino-terminal kinases (JNK1/2/3) and ERK5. p38 MAPK is activated by a wide range of cellular stresses and modulates activity of several downstream kinases and transcription factors which are involved in regulating cytoskeleton remodeling, cell cycle modulation, inflammation, antiviral response and apoptosis. In viral infections, activation of cell signalling pathways is part of the cellular defense mechanism with the basic aim of inducing an antiviral state. However, viruses can exploit enhanced cell signalling activities to support various stages of their replication cycles. Kinase activity can be inhibited by small molecule chemical inhibitors, so one strategy to develop antiviral drugs is to target these cellular signalling pathways. In this review, we provide an overview on the current understanding of various cellular and viral events regulated by the p38 signalling pathway, with a special emphasis on targeting these events for antiviral drug development which might identify candidates with broad spectrum activity.Osteoarthritis (OA) is a heterogeneous disease that is extremely hard to cure owing to its complex regulation network of pathogenesis, especially cartilage degeneration. FBXO21 is a subunit of ubiquitin E3 ligases that degrades P-glycoprotein and EID1 by ubiquitination and activates the JNK and p38 pathways; however, its role in OA remains unknown. Here, the main objective of this study was to evaluate the potential effects and mechanism of FBXO21 in OA degeneration, we revealed that FBXO21 is upregulated in the cartilage of patients with OA, aging, and monosodium iodoacetate-induced OA rats, and chondrocytes treated with interleukin-1β, tumor necrosis factor-α, and lipopolysaccharide. Moreover, the in vivo and in vitro knockdown of FBXO21 suppressed OA-related cartilage degeneration, as evidenced by activated autophagy, upregulated anabolism, alleviated apoptosis, and downregulated catabolism. In contrast, its overexpression promoted OA-related cartilage degeneration. In addition, using mass spectrometry and co-immunoprecipitation assay, we demonstrated that the downstream mechanism of FBXO21 inhibits autophagy by interacting with and phosphorylating ERK. Furthermore, FBXO21 alleviated anabolism and enhanced apoptosis and catabolism by inhibiting autophagy in rat chondrocytes. Interestingly, for its upstream mechanism, JUNB promoted FBXO21 expression by directly targeting the FBXO21 promoter, thus further accelerating cartilage degeneration in SW1353 cells and rat chondrocytes. Overall, our findings reveal that the JUNB-FBXO21-ERK axis regulates OA apoptosis and cartilage matrix metabolism by inhibiting autophagy. Therefore, FBXO21 is an attractive target for regulating OA pathogenesis, and its knockdown may provide a novel targeted therapy for OA.A new extraction procedure based on combination of a solvent extraction and deep eutectic solvent based dispersive liquid-liquid microextraction has been introduced for the extraction of aflatoxin M1 from cheese samples. In this method, acetonitrile, deionized water, and n-hexane are added onto the sample and vortexed. Owning to different affinities of the substances in cheese toward the mentioned solvents, an efficient and selective extraction of the analyte is done in the acetonitrile phase. After centrifugation, the acetonitrile phase is removed and mixed with a new hydrophobic deep eutectic solvent prepared from N,N-diethanol ammonium chloride and carvacrol as an extraction solvent. The mixture is injected into deionized water, and a cloudy solution is obtained. Eventually, an aliquot of the organic phase is injected into high-performance liquid chromatography-fluorescence detection. After optimizing the effective parameters with the response surface methodology and a quadratic model, limits of detection and quantification were 0.74 and 2.56 ng/kg, respectively. The obtained extraction recovery and enrichment factor were 94% and 94, respectively. Also, intra- (n = 6) and interday (n = 4) precisions were less than or equal to 8.6% at a concentration of 5 ng/kg. The suggested method was applied to determine aflatoxin M1 in different cheese samples.Storage of solar energy as hydrogen provides a platform towards decarbonizing our economy. One emerging strategy for the production of solar fuels is to use photocatalytic biohybrid systems that combine the high catalytic activity of non-photosynthetic microorganisms with the high light-harvesting efficiency of metal semiconductor nanoparticles. However, few such systems have been tested for H2 production. We investigated light-driven H2 production by three novel organisms, Desulfovibrio desulfuricans, Citrobacter freundii, and Shewanella oneidensis, self-photosensitized with cadmium sulfide nanoparticles, and compared their performance to Escherichia coli. selleck kinase inhibitor All biohybrid systems produced H2 from light, with D. desulfuricans-CdS demonstrating the best activity overall and outperforming the other microbial systems even in the absence of a mediator. With this system, H2 was continuously produced for more than 10 days with a specific rate of 36 μmol gdcw -1  h-1 . High apparent quantum yields of 23 % and 4 % were obtained, with and without methyl viologen, respectively, exceeding values previously reported.