Novel neuroactive insecticides are discovered/registered differently, have a lower value in use, and exert their physiological actions in manners distinct from neuroactive pharmaceuticals, but there are clear similarities in their biochemical modes of action. Insecticides are generally discovered using whole pest insect screens, and this eases difficulties in 'translational science' from laboratory to field, as opposed to pharmaceutical translation from biochemical or cell-based targets to animal models to human clinical trials to registered drug. This paper examines recent trends in pharmaceutical science and identifies some technologies which may represent complementary approaches to insecticide discovery screening and mode of action determination beyond the sound processes in common practice today. Examples will be drawn from nanoparticle delivery of neuroactives, unique ligand-polymer conjugates, proposed advances in insect cell culture following from pharmaceutical cell biology, and laboratory or organ-on-a-chip approaches. It is hoped that these concepts will stimulate novel thinking which may enable discovery of efficacious new neuroactive insecticides. © 2020 Society of Chemical Industry.Detection of amplification of the MYCN gene is essential for determining optimal treatment and estimating prognosis of patients with neuroblastoma (NB). DNA FISH with neuroblastoma tissues or patient-derived bone marrow cells is the standard clinical practice for the detection of MYCN amplification. As tumor cells may often be unavailable, we developed a method to detect MYCN amplification in the plasma of patients with neuroblastoma. Taking single-copy NAGK DNA as reference, we used real-time quantitative PCR (qPCR) to determine the MYCN/NAGK ratio in the plasma of 115 patients diagnosed with NB. An increased MYCN/NAGK ratio in the plasma was consistent with MYCN amplification as assessed by DNA FISH. The AUC for a MYCN/NAGK ratio equal to 6.965 was 0.943, with 86% sensitivity and 100% specificity.  https://www.selleckchem.com/products/dexketoprofen-trometamol.html  Beyond the threshold of 6.965, the MYCN/NAGK ratio correlated with a heavier tumor burden. Event-free and overall survival of two years were significantly shortened in stage 4 patients with a MYCN/NAGK ratio higher than 6.965. Plasma MYCN/NAGK ratios increased in patients with progressive disease and relapse. Thus, we conclude that the determination of the plasma MYCN/NAGK ratio by qPCR is a noninvasive and reproducible method to measure MYCN amplification in patients with NB.Norcantharidin (NCTD), the demethylated analog of cantharidin isolated from Mylabris, is known to inhibit renal fibrosis. However, the underlying mechanism is largely unknown. The present study investigates whether NCTD exerts this effect through regulation of the protein phosphatase 2A catalytic subunit (PP2Ac)-Smad3 pathway. HK-2 human renal proximal tubule cells exposed to transforming growth factor (TGF)-β1 were used as an in vitro model of renal fibrosis. The levels of total Smad3, C-terminal-phosphorylated Smad3 (p-Smad3), PP2Ac, and fibronectin (Fn) were evaluated by Western blotting. A PP2Ac overexpression plasmid and the PP2Ac inhibitor okadaic acid (OA) were used for functional analyses. The subcellular localization of Smad3 was visualized by immunofluorescence labeling. The results showed that PP2Ac overexpression increased Smad3 phosphorylation and nuclear translocation in HK-2 cells, while pharmacologic inhibition of PP2Ac with OA had the opposite effect. NCTD suppressed Fn and p-Smad3 expression and TGF-β1-induced nuclear entry of Smad3, but these effects were abrogated by inhibition of PP2Ac. Thus, the anti-renal interstitial fibrosis effect of NCTD is exerted through inhibition of PP2Ac-mediated C-terminal phosphorylation of Smad3. These findings highlight the therapeutic potential of NCTD for the treatment of renal interstitial fibrosis.
  Bacillus velezensis and other Bacillus species are known for the production of bioactive secondary metabolites that are active against plant pathogenic fungi. In view of this, a study was undertaken to investigate the antifungal potential of B. velezensis AR1 culture supernatant.
 
  The butanol extract concentrate of B. velezensis AR1 was separated into different fractions by column chromatography. A fraction eluted by 91 chloroform methanol caused 25.8-70.2% and 25.2-56.3% growth inhibition of Monilinia fructicola and Colletotricum goeosporioides, respectively. This fraction was subjected to solid-phase extraction using a Strata SI-1 column and further purified by prep-TLC to obtain a pure metabolite showing a single peak on high performance liquid chromatography. On the basis of the nuclear magnetic resonance (NMR 
  H, 
  C, HH COSY, HSQC and HMBC) analysis, the metabolite was identified as 5-N-tyrosinylornithine. The compound exhibited antifungal activity against two plant pathogenic fungi.
 
  5-N-tyrosinylornithine, the secondary metabolite isolated from the culture supernatant of B. velezensis AR1 exhibited significant antifungal activity against two plant pathogenic fungi.
 5-N-tyrosinylornithine, the secondary metabolite isolated from the culture supernatant of B. velezensis AR1 exhibited significant antifungal activity against two plant pathogenic fungi.Continuous Subcutaneous Insulin Infusion (CSII) is superior to conventional insulin therapy as it improves glycemic control thus reducing the probability of diabetic complications. Notwithstanding CSII's benefits, insulin dependent diabetic patients rarely achieve optimal glucose control. Moreover, CSII is only FDA approved for 3 days and often fails prematurely for reasons that have not been fully elucidated. We hypothesize that phenolic compounds, such as m-cresol and phenol, which are present in all commercial insulin formulations are responsible for the tissue reaction occurring at the insulin infusion site. This hypothesis was examined with in vitro cell cultures and a mouse air-pouch model to determine cellular and tissue reactions following infusions with saline, phenolic compounds, (i.e., commercial diluent), and insulin. We demonstrated that diluent and insulin were cytotoxic to cells in culture at sub-clinical concentrations (e.g., >110 of commercial insulin). Air pouch studies demonstrated that infusion of either diluted insulin or diluent itself induced three to five-fold level of recruited leukocytes as compared to saline.