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The current study provides new information regarding the metabolic profiles of ponatinib and would be helpful in understanding the effectiveness and toxicity of ponatinib, especially the mechanism of hepatotoxicity. © 2020 John Wiley & Sons, Ltd.BACKGROUND Short-chain fatty acids (SCFAs) are fermented dietary components that regulate immune responses, promote colonic health and suppress mast cell-mediated diseases. However, the effects of SCFAs on human mast cell function, including the underlying mechanisms, remain unclear. Here, we investigated the effects of the SCFAs acetate, propionate and butyrate on mast cell-mediated pathology and human mast cell activation, including the molecular mechanisms involved. METHOD Precision-cut lung slices (PCLS) of allergen-exposed guinea pigs were used to assess the effects of butyrate on allergic airway contraction. Human and mouse mast cells were co-cultured with SCFAs and assessed for degranulation after IgE- or non-IgE-mediated stimulation. The underlying mechanisms involved were investigated using knockout mice, small molecule inhibitors/agonists, and genomics assays. RESULTS Butyrate treatment inhibited allergen-induced histamine release and airway contraction in guinea pig PCLS. Propionate and butyrate, but not acetate, inhibited IgE and non-IgE-mediated human or mouse mast cell degranulation in a concentration-dependent manner. Notably, these effects were independent of the stimulation of SCFA receptors GPR41, GPR43 or PPAR, but instead were associated with inhibition of histone deacetylases. Transcriptome analyses revealed butyrate-induced downregulation of the tyrosine kinases BTK, SYK and LAT, critical transducers of FcεRI-mediated signals that are essential for mast cell activation. Epigenome analyses indicated that butyrate redistributed global histone acetylation in human mast cells, including significantly decreased acetylation at the BTK, SYK and LAT promoter regions. CONCLUSION Known health benefits of SCFAs in allergic disease can, at least in part, be explained by epigenetic suppression of human mast cell activation. This article is protected by copyright. All rights reserved.Folium Camelliae Nitidissimae (jinhuacha in Chinese, JHC) is a kind of caffeine-less tea with antioxidant, antitumor and antibacterial effects. Studies on the chemical profiles and hepatoprotective effects of JHC extracts have not been systematically conducted so far. This study comprehensively investigated the compound profiles of JHC extract by ultrafast liquid chromatography with quadrupole time-of-flight tandem mass spectrometry. We also determined JHC's hepatoprotective effects against CCl4 -induced liver injury in mice. A JHC extract was administered orally to mice at 1.95 and 7.80 g/kg body weight once daily for 14 consecutive days prior to CCl4 treatment. Eighty-four compounds including flavonoids, organic acids, catechins, coumarins, phenylpropanol, amino acids, anthraquinones, saponins and nucleosides in JHC extract were authentically identified or tentatively identified by comparing MS information and retention times with those of authentic standards or available references. JHC administration significantly decreased elevated levels of aspartate aminotransferase and alanine aminotransferase in mouse serum, inhibited hepatic malondialdehyde formation and enhanced glutathione and superoxide dismutase activities in the liver of CCl4 -treated mice. The histological observations also further supported the results. These results demonstrate that JHC contains various chemical compounds and its hepatoprotective effects against CCl4 -induced liver injury correlated with decreasing lipid oxidation are significant. © 2020 John Wiley & Sons, Ltd.Imatinib was the first BCR-ABL inhibitor used in clinical practice to treat chronic myeloid leukemia (CML) and significantly improve the life expectancy of CML patients in the chronic phase. However, a portion of CML patients are resistant to imatinib. This study aimed to determine whether menadione (Vitamin K3) can improve imatinib efficacy in CML and to thoroughly explore the combination regimen mechanism between imatinib and menadione. Menadione improved imatinib efficacy in K562 cells by downregulating ABCB1 expression and increased the intracellular concentration of imatinib, which confirmed that this combination regimen is more effective than imatinib monotherapy. The results demonstrate that menadione and imatinib combination therapy may be a promising approach to refractory CML. This article is protected by copyright. All rights reserved.Increasing temperatures resulting from climate change dramatically impact rice crop production in Asia. Bemcentinib Depending on the specific stage of rice development, heat stress reduces tiller/panicle number, decreases grain number per plant and lower grain weight, thus negatively impacting yield formation. Hence improving rice crop tolerance to heat stress in terms of sustaining yield stability under high day temperature (HDT), high night temperature (HNT), or combined high day and night temperature (HDNT) will bolster future food security. In this review article, we highlight the phenological alterations caused by heat and the underlying molecular-physiological and genetic mechanisms operating under different types of heat conditions (HDT, HNT, and HDNT) to understand heat tolerance. Based on our synthesis of HDT, HNT, and HDNT effects on rice yield components, we outline future breeding strategies to contribute to sustained food security under climate change. © 2020 John Wiley & Sons Ltd.Estrogen is an important risk factor for cholesterol gallstone disease because women are twice as likely as men to form gallstones. The classical estrogen receptor α (ERα), but not ERβ, in the liver plays a critical role in the formation of estrogen-induced gallstones in female mice. The molecular mechanisms underlying the lithogenic effect of estrogen on gallstone formation have become more complicated with the identification of the G protein-coupled receptor 30 (GPR30), a novel estrogen receptor. We investigated the biliary and gallstone phenotypes in ovariectomized female GPR30 (-/-), ERα (-/-), and wild-type mice injected intramuscularly with the potent GPR30-selective agonist G-1 at 0 or 1 μg/day and fed a lithogenic diet for 8 weeks. The activation of GPR30 by G-1 enhanced cholelithogenesis by suppressing expression of cholesterol 7α-hydroxylase, the rate-limiting enzyme for the classical pathway of bile salt synthesis. These metabolic abnormalities led to an increase in biliary cholesterol concentrations in company with hepatic hyposecretion of biliary bile salts, thereby inducing cholesterol-supersaturated gallbladder bile and accelerating cholesterol crystallization.