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Transfection of a miR-143-3p mimic into PBMCs downregulated FOSL2 expression, leading to an upregulation of IL-2 and TNF-α expression and a downregulation of IL-6 expression. When silencing FOSL2 while inhibiting miR-143-3p in PBMCs, there was no significant change in expression of the FOSL2 mRNA, protein and cytokines.

The expression of miR-143-3p in PBMCs from ADM patients is upregulated. miR-143-3p could function in the pathogenesis of ADM by modulating the inflammatory reaction through FOSL2.

The expression of miR-143-3p in PBMCs from ADM patients is upregulated. miR-143-3p could function in the pathogenesis of ADM by modulating the inflammatory reaction through FOSL2.The epidermal growth factor receptors EGFR and HER2 are the main targets for tyrosine kinase inhibitors (TKIs). The quinazoline derivative lapatinib (LAP) is used since 2007 as dual TKI in the treatment of metastatic breast cancer and currently, it is used as an oral anticancer drug for the treatment of solid tumors such as breast and lung cancer. Although hepatotoxicity is its main side effect, it makes sense to investigate the ability of LAP to induce photosensitivity reactions bearing in mind that BRAF (serine/threonine-protein kinase B-Raf) inhibitors display a considerable phototoxic potential and that afloqualone, a quinazoline-marketed drug, causes photodermatosis. Metabolic bioactivation of LAP by CYP3A4 and CYP3A5 leads to chemically reactive N-dealkylated (N-LAP) and O-dealkylated (O-LAP) derivatives. In this context, the aim of the present work is to explore whether LAP and its N- and O-dealkylated metabolites can induce photosensitivity disorders by evaluating their photo(geno)toxicity through in vitro studies, including cell viability as well as photosensitized protein and DNA damage. As a matter of fact, our work has demonstrated that not only LAP, but also its metabolite N-LAP have a clear photosensitizing potential. They are both phototoxic and photogenotoxic to cells, as revealed by the 3T3 NRU assay and the comet assay, respectively. By contrast, the O-LAP does not display relevant photobiological properties. Remarkably, the parent drug LAP shows the highest activity in membrane phototoxicity and protein oxidation, whereas N-LAP is associated with the highest photogenotoxicity, through oxidation of purine bases, as revealed by detection of 8-Oxo-dG.Quantum chemical theoretical computation was performed on gaseous molecular reaction systems to simulate parallel synthesis of energetic primary explosive precursor 4,6-dinitrobenzofuroxan (4,6-DNBF) and its isomeric derivatives. Related polarized continuum model (PCM) and Materials Studio (MS/forcite) energies were collected via kinetic rate and thermodynamic equilibrium analyses, enabling comparison of and suggestions as to suitable reaction conditions (reaction temperature, reagent concentration, mixed acid ratio) together with feasible pathways to obtain a high production yield of the research target. In summary, at a low reaction temperature of 278 K, 1.0 M 4-nitrobenzofuroxan (or 5,6-nitrobenzofuroxan) could be nitrated using concentrated nitric acid/sulfuric acid at a 1 to 2 volume ratio to efficiently and rapidly produce 4,6-dinitro-benzofuroxan (or 5,6-dinitrobenzofuroxan), in agreement with the experimental results reported in the literature. Graphical abstract.The rapidly increasing population of urban centers leads to the increasing need for greenspaces. Sodding of turfgrass provides instant greenspace, but it removes soil from sod farms. The extent of such removal has not been widely quantified. The amount quantity of soil and organic matter lost with sod harvest and the associated cost of nutrients lost from six sod farms in the Marmara region of Turkey were determined. Soil loss ranged from 166 to 243 Mg ha-1 year-1, while the associated organic matter loss ranged from 1 to 6 Mg ha-1 year-1. The amount of soil loss increased with increases in gravimetric water, clay, and silt contents, and duration under sod harvest, while it decreased with an increase in sand content. Tacrolimus Annual nutrient lost ranged from 117 to 449 kg ha-1 for N, from 2 to 18 kg ha-1 for P2O5, and from 21 to 175 kg ha-1 for K2O. Replacing the nutrient lost would cost about $134 ha-1 year-1 for sandy soils and $444 ha-1 year-1 for fine-textured soils. Soil lost with sod harvest was 134 times higher than that from agricultural lands by erosion in the region, although the area under sod production is much smaller than that under croplands. Similarly, organic matter loss was 4 to 5 times higher than the accumulation rate under established turfgrass in golf courses and lawns in locations with similar climate. Overall, sod harvesting results in significant and costly soil, organic matter, and nutrient loss, which, although small in area, can be an important component of total soil erosion.Inconsistency of the results regarding the genetic variability within genes coding for receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) in rheumatoid arthritis (RA) prompted us to study the RANK and RANKL polymorphisms as potential biomarkers associated with disease predisposition and response to anti-TNF treatment in a group of Polish patients with RA. This study enrolled 318 RA patients and 163 controls. RANK (rs8086340, C > G; rs1805034, C > T) and RANKL (rs7325635, G > A; rs7988338 G > A) alleles were determined by real-time PCR with melting curve analysis and related with clinical parameters. In addition, RANKL serum levels were measured by ELISA. The RANK rs8086340-G allele was overrepresented among patients as compared to controls (OD = 1.777, p = 0.038). C-reactive protein (CRP) levels were significantly (p  less then  0.05) associated with RANK rs8086340 polymorphism and were higher in the CC-homozygotes at the baseline while lower in the GG-carriers at the 12th week of the treatment. At the latter time point RANKL rs7325635-GG-positive patients also showed significantly lower CRP concentrations. Higher alkaline phosphatase levels before induction of anti-TNF therapy were observed in RANK rs8086340 and RANK rs1805034 CC homozygotes (p = 0.057 and p = 0.035, respectively). The GG homozygosity of both RANKL single nucleotide polymorphisms was significantly associated with the number of swollen joints (rs7988338 and rs7325635, before and at the 12th week of therapy, respectively, p  less then  0.05 in both cases). These results imply that polymorphisms within the RANK and RANKL genes affect RA susceptibility and anti-TNF treatment outcome.