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The phenylpropenes α-asarone and β-asarone are widely spread in the marsh plant Acorus calamus. BLZ945 price Both isomers are classified as carcinogenic in rodents. However, the respective genotoxic mechanisms are not elucidated so far. The present study gives deeper insights into the genotoxic effects of asarone isomers as well as their known oxidative phase I metabolites, (E)-3′-oxoasarone and asarone epoxide. We show that asarone metabolites highly increase DNA strand breaks after one hour of incubation, markedly metabolic activation contributes to their carcinogenic mode of action. All test compounds act as aneugens and potently enhance the amounts of micronuclei in binuclear cells. However, a prolonged incubation time until 24 h results in a decrease in DNA damage. This work suggests that asarone metabolites also induce DNA double strand breaks (DSB), why we put a strong focus on homologous recombination (HR) and nonhomologous end-joining. The obtained results herein indicate that asarone epoxide-induced DNA strand breaks are repaired via a homologous repair pathway.The “co-use” patterns of cosmetics would be critical for accurate aggregate exposure assessment. The Korean national representative exposure factor database, which includes simultaneous usage patterns of 31 cosmetics by 1001 subjects, was used to analyze the co-use patterns by Koreans. Three analytical methods were applied to determine the co-use patterns. Cohen’s kappa coefficient was used to analyze the correlation between pairs. This method revealed an effect of gender on the cosmetics co-use pattern. Hierarchical clustering analysis was performed using the binary linkage distance method. The clusters were divided into one large cluster and small clusters of one or two cosmetics. Frequent pattern mining was performed using the eclat algorithm. The number of cosmetics used and co-use pattern were influenced by gender and age of the population. The co-use patterns exhibited an additive property in that new cosmetics were added to previous cosmetic combinations. A co-use scenario was proposed using the rank of occurrence frequency in co-use patterns and percentile values of the number of cosmetics used. The 16 co-use scenarios represented to the 25th, 50th, 75th, and 95th percentiles of the co-use patterns for four gender-age groups. These could be applied to aggregate exposure assessment as exposure scenarios.Hypoxia-inducible factors (HIFs) are the force which drives hypoxic cancer cells to a more aggressive and resistant phenotype in a number of solid tumors, including colorectal and breast cancer. Results from recent studies suggest a role for HIF-1 in immune evasion and cancer stem cell phenotype promotion, establishing HIF-1 as a potential therapeutic target. Thus, identifying new compounds that might inhibit HIF1 activity, or at least exert antiproliferative effects that are unaffected by HIF1-dependent adaptations, is an attractive goal for the management of hypoxic tumors. Here we show that the flavonoid luteolin exerts a significant cytotoxic effect on the colon cancer cell line HCT116 and the breast adenocarcinoma cell line MDA-MB231, by inducing both apoptotic and necrotic cell death, and that this effect is not impaired by HIF-1 activation. In these cells, luteolin also stimulates autophagy; however this seems to be part of a protective response, rather than contribute to the cytotoxic effect. Interestingly, luteolin induces a decrease in HIF-1 transcriptional activity. This is accompanied by a decrease in the levels of protein markers of stemness and invasion, and by a reduction of migratory capacity of the cells. Taken together, our results suggest that luteolin could be developed into a useful therapeutic agent aimed at hypoxic tumors.Non-alcoholic fatty liver disease is emanating as a global cataclysm. This study was designed to investigate the antioxidative, anti-inflammatory and fat metabolism-regulating potential of berbamine (BBM), a natural bis-benzylisoquinoline alkaloid. BBM attenuated intracellular lipid accumulation in oleic-acid exposed HepG2 cells (0.5 mM) by inhibiting fatty acid uptake, lipogenesis, and promoting fatty acid β-oxidation by activating AMP-activated kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR)-α. Berbamine (5 μM) induced AMPK activation (P less then 0.001) via LKB1 (Ser-428) and elevated AMPATP ratio (P less then 0.001). AMPK activation negatively regulated mTOR and also constrained the nuclear translocation of SREBP-1c and inhibited the lipogenic proteins, stearoyl-CoA desaturase-1 (SCD-1) and fatty acid synthase (FAS) (P less then 0.001). BBM stimulated nuclear translocation of redox-sensitive nuclear factor erythroid-2-related factor-2 (Nrf2) and increased hepatic expression of Nrciation to ameliorate oxidative stress/proinflammatory response.Owing to a broad spectrum of functions performed by neuropeptides, this class of signaling molecules attracts an increasing interest. One of the key steps in the regulation of biological activity of neuropeptides is proteolytic conversion or degradation by proteinases that change or terminate biological activity of native peptides. These enzymes, in turn, are regulated by inhibitors, which play integral role in controlling many metabolic pathways. Thus, the search for selective inhibitors and detailed knowledge on the mechanisms of binding of these substances to enzymes, could be of importance for designing new pharmacological approaches. The aim of this review is to summarize the current knowledge on the inhibitors of enzymes that convert selected groups of neuropeptides, such as dynorphins, enkephalins, substance P and NPFF fragments. The importance of these substances in pathophysiological processes involved in pain and drug addiction, have been discussed.Cobra venom factor (CVF) is the complement-activating protein in cobra venom. CVF is a structural and functional analog of complement component C3. CVF, like C3b, forms a convertase with factor B. This bimolecular complex CVF, Bb is an enzyme that cleaves C3 and C5. However, CVF, Bb exhibits significantly different functional properties from C3b,Bb. Whereas both, CVF, Bb and C3b, Bb exhibit spontaneous decay-dissociation into the respective subunits, thereby eliminating the enzymatic activity, the CVF, Bb convertase is physico-chemically far more stable, decaying with a half-life that is more than two orders of magnitude slower than that of C3b,Bb. In addition, CVF, Bb is completely resistant to inactivation by Factors H and I. These two properties of CVF, Bb allow continuous activation of C3 and C5, and complement depletion in serum. In order to understand the structural basis for the physico-chemical stability of CVF,Bb, we have created recombinant hybrid proteins of CVF and human C3, based on structural differences between CVF and human C3b in the C-terminal C345C domain.