Boron neutron capture therapy (BNCT) for cancer is on the rise worldwide due to recent developments of in-hospital neutron accelerators which are expected to revolutionize patient treatments. There is an urgent need for improved boron delivery agents, and herein we have focused on studying the biochemical foundations upon which a successful GLUT1-targeting strategy to BNCT could be based. By combining synthesis and molecular modeling with affinity and cytotoxicity studies, we unravel the mechanisms behind the considerable potential of appropriately designed glucoconjugates as boron delivery agents for BNCT. In addition to addressing the biochemical premises of the approach in detail, we report on a hit glucoconjugate which displays good cytocompatibility, aqueous solubility, high transporter affinity, and, crucially, an exceptional boron delivery capacity in the in vitro assessment thereby pointing toward the significant potential embedded in this approach.

Edema and insufficient blood perfusion are common problems in reconstructive surgery. The blood vasculature is reconstructed in microvascular flaps, whereas lymphatic vessel function is lost after surgical incision. Here, we demonstrate that vascular endothelial growth factor C (VEGF-C) gene transfer can be used to reconstruct a lymphatic vessel network severed by incision of skin flaps. We used adenoviral VEGF-C gene transfer at the edges of epigastric skin flaps in mice. Our results show that VEGF-C gene expression results in the formation of anastomoses between the lymphatic vessels of the skin flap and the surrounding lymphatic vasculature. Some spontaneous lymphangiogenesis also took place in the control mice, but the lymphatic vessels generated remained nonfunctional even 2 months postoperatively. In contrast, the VEGF-C treated mice demonstrated persistent lymphatic vessel function during the 2 month follow-up despite the transient nature of the adenoviral VEGF-C gene expression. The restoration of lymphatic function by VEGF-C in skin flaps provides new tools to promote vascular perfusion and to reduce tissue edema in skin and muscle flaps. These results have important implications for the prevention and treatment of surgically induced secondary lymphedema.

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Probabilistic Latent Semantic Analysis (PLSA) is an information retrieval technique proposed to improve the problems found in Latent Semantic Analysis (LSA). We have applied both LSA and PLSA in our system for grading essays written in Finnish, called Automatic Essay Assessor (AEA). We report the results comparing PLSA and LSA with three essay sets from various subjects. The methods were found to be almost equal in the accuracy measured by Spearman correlation between the grades given by the system and a human. Furthermore, we propose methods for improving the usage of PLSA in essay grading.

Our report represents a comprehensive review on the antibacterial activity of inorganic nanomaterials and antimicrobial peptides, and how concomitant use of the two can effectively tackle a range of bacterial infections which is a rapidly escalating issues in public health care worldwide. We believe this is of particular current interest with regard to "antimicrobial resistance" being declared one of the top-10 global health threats in 2019 by the WHO.In this group of authors, we have teamed up within the NordForsk-funded university hub Nordic POP (Patient Oriented Products), which we wish to showcase with this contribution. We are currenlty carrying out joint research supported by this network within the topic of the review, so we view this a valuable contribution also within the dissemination of Nordic POP activities.

Scoparone, a major constituent of the Chinese herbal medicine Yin Chen Hao, expresses beneficial effects in experimental models of various diseases. The intrinsic doses and effects of scoparone are dependent on its metabolism, both in humans and animals. We evaluated in detail the metabolism of scoparone in human, mouse, rat, pig, dog, and rabbit liver microsomes in vitro and in humans in vivo. Oxidation of scoparone to isoscopoletin via 6-O-demethylation was the major metabolic pathway in liver microsomes from humans, mouse, rat, pig and dog, whereas 7-O-demethylation to scopoletin was the main reaction in rabbit. The scoparone oxidation rates in liver microsomes were 0.8 – 1.2 µmol/(min*g protein) in mouse, pig, and rabbit, 0.2 – 0.4 µmol/(min*g protein) in man and dog, and less than 0.1 µmol/(min*g) in rat. In liver microsomes of all species, isoscopoletin was oxidized to 3-[4-methoxy-ρ-(3, 6)-benzoquinone]-2-propenoate and esculetin, which was formed also in the oxidation of scopoletin. Human CYP2A13 exhibited the highest rate of isoscopoletin and scopoletin oxidation, followed by CYP1A1 and CYP1A2. Glucuronidation of isoscopoletin and scopoletin was catalyzed by the human UGT1A1, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, and UGT2B17. Dog was most similar to man in scoparone metabolism. Isoscopoletin glucuronide and sulfate conjugates were the major scoparone in vivo metabolites in humans, and they were completely excreted within 24 h in urine. Scoparone and its metabolites did not activate key nuclear receptors regulating CYP and UGT enzymes. These results outline comprehensively the metabolic pathways of scoparone in man and key preclinical animal species.

A series of 7‐(2‐oxoalkoxy)coumarins have been synthesized by conjugating substituted 7‐hydroxycoumarins with different chloroketones. The anti‐inflammatory properties of 7‐(2‐oxoalkoxy)coumarins were studied in LPS‐induced inflammatory response in J774 macrophages. Western blot was used to determine the expression of iNOS and COX‐2, NO was determined by measuring its metabolite nitrite by Griess reaction and IL‐6 was measured by ELISA. Seventeen of the studied compounds inhibited NO and IL‐6 production over 50% at 100 μM concentrations. IC50 values of the best inhibitors were 21 μM/24 μM (NO/IL‐6) for compound 12 and 30 μM/10 μM (NO/IL‐6) for compound 20. The main result was that the substitution with 7‐(2‐oxoalkoxy) group improved the anti‐inflammatory properties of most of the investigated 7‐hydroxycoumarins.

in Wiley Online Library (wileyonlinelibrary.com).As a continuum to our work with coumarins, 12 psoralens were synthesized and evaluated for their anti-inflammatory activity. Psoralens were prepared in three steps; at first, 7-hydroxycoumarins were synthesized by von Pechmann condensation and then converted to 7-(2-oxopropoxy)coumarins. In the final step, a fused furan ring was introduced in an intramolecular ring-formation reaction. Based on a SciFinder search, two out of the 12 synthesized psoralen derivatives (compounds 9 and 12) were found to be novel. The derivatives displayed anti-inflammatory activity by suppressing iNOS and IL-6 expression, but their mechanism of action seemed to be dependent on the substitution. Compound 6 with propyl side chain inhibited NF-κB mediated transcription, while compound 10 with a phenyl substituent down-regulated iNOS expression in a posttranscriptional manner. The results introduce psoralen derivatives as promising anti-inflammatory compounds with potential for treatment of conditions involving iNOS and/or IL-6-mediated adverse responses. J. Heterocyclic Chem., 55, 2590 (2018. and on the production of inflammatory mediators NO and IL-6 in activated macrophages. RESULTS AND DISCUSSIONChemistry. Psoralens 1-12 were synthesized according to Scheme 1. Substituted 7-(2-oxopropoxy)coumarins were prepared previously from 7-hydroxycoumarins, as described in our earlier publications [2,3]. In general, 7-hydroxycoumarins were prepared by mixing ethyl acetoacetate and substituted resorcinol in perchloric acid at room temperature or by refluxing resorcinol and ethyl propiolate in 1,4-dioxane with a catalytic amount of aluminum chloride. The prepared 7-hydroxycoumarins were then refluxed in dry acetone with chloroacetone and potassium carbonate to yield 7-(2-oxopropoxy) coumarins.Psoralens were prepared by mixing substituted 7-(2-oxopropoxy)coumarin (4.5 mmol) into 45 mL of 1 M aqueous NaOH and refluxing for 16 h under a nitrogen atmosphere. This inert gas was used to prevent the formation of undesired angular isoforms, angelicins. After refluxing, the reaction mixture was cooled to room temperature and made slightly acidic to precipitate the product. In most published methods, a small portion (e.g., 5 mL) of orthophosphoric acid has been used for acidifying the mixture. However, some psoralens did not precipitate while using phosphoric acid but instead formed an unfilterable paste. To avoid this problem, we