Metabolism and Metabolic Inhibition of Xanthotoxol in Human Liver Microsomes

Cytochrome p450 (CYP450) enzymes are predominantly involved in Phase I metabolism of xenobiotics. In this study, the CYP450 isoforms involved in xanthotoxol metabolism were identified using recombinant CYP450s. In addition, the inhibitory effects of xanthotoxol on eight CYP450 isoforms and its pharmacokinetic parameters were determined using human liver microsomes. CYP1A2, one of CYP450s, played a key role in the metabolism of xanthotoxol compared to other CYP450s. Xanthotoxol showed stronger inhibition on CYP3A4 and CYP1A2 compared to other isoenzymes with the IC50 of 7.43 μM for CYP3A4 and 27.82 μM for CYP1A2. The values of inhibition kinetic parameters (Ki) were 21.15 μM and 2.22 μM for CYP1A2 and CYP3A4, respectively. The metabolism of xanthotoxol obeyed the typical monophasic Michaelis-Menten kinetics and Vmax, Km, and CLint values were calculated as 0.55 nmol·min−1·mg−1, 8.46 μM, and 0.06 mL·min−1·mg−1. In addition, the results of molecular docking showed that xanthotoxol was bound to CYP1A2 with hydrophobic and π-π bond and CYP3A4 with hydrogen and hydrophobic bond. We predicted the hepatic clearance (CLh) and the CLh value was 15.91 mL·min−1·kg−1 body weight. These data were significant for the application of xanthotoxol and xanthotoxol-containing herbs

The Analysis of Gravity on Tourism Resource of Shijiazhuang with Anion, Hebei

AbstractThis paper analyzes the decisive factor of The Shijiazhuang coastal economic zone's tourist resource from the perspective of the actual data by adopting Gravity model; meanwhile, presents an overall aspect of Shijiazhuang city, its current development of the tourism industry, and the advantages and characteristics as well. Further proposal is also produced to contribute to the tourist development based on the analysis of the model data

City-level water withdrawal in China:Accounting methodology and applications

In the context of the freshwater crisis, accounting for water withdrawal could help planners better regulate water use in different sectors to combat water scarcity. However, the water withdrawal statistics in China are patchy, and the water data across all sectors at the city level appear to be relatively insufficient. Hence, we develop a general framework to, for the first time, estimate the water withdrawal of 58 economic–social–environmental sectors in cities in China. This methodology was applied because only inconsistent water statistics collected from different data sources at the city level are available. We applied it to 18 representative Chinese cities. Different from conventional perceptions that agriculture is usually the largest water user, industrial and household water withdrawal may also occupy the largest percentages in the water-use structure of some cities. The discrepancy among annual household water use per capita in the urban areas of different cities is relatively small (as is the case for rural areas), but that between urban and rural areas is large. As a result, increased attention should be paid to controlling industrial and urban household water use in particular cities. China should specifically prepare annual water accounts at the city level and establish a timetable to tackle water scarcity, which is a basic step toward efficient and sustainable water crisis mitigation

Activity of T-type calcium channels is independent of CRMP2 in sensory neurons

Amongst the regulators of voltage-gated ion channels is the collapsin response mediator protein 2 (CRMP2). CRMP2 regulation of the activity and trafficking of NaV1.7 voltage-gated sodium channels as well as the N-type (CaV2.2) voltage-gated calcium channel (VGCC) has been reported. On the other hand, CRMP2 does not appear to regulate L- (CaV1.x), P/Q- (CaV2.1), and R- (CaV2.3) type high VGCCs. Whether CRMP2 regulates low VGCCs remains an open question. Here, we asked if CRMP2 could regulate the low voltage-gated (T-type/CaV3.x) channels in sensory neurons. Reducing CRMP2 protein levels with short interfering RNAs yielded no change in macroscopic currents carried by T-type channels. No change in biophysical properties of the T-type currents was noted. Future studies pursuing CRMP2 druggability in neuropathic pain will benefit from the findings that CRMP2 regulates only the N-type (CaV2.2) calcium channels.Guangdong Medical Research Foundation [A2017047]; National Institute of Neurological Disorders and Stroke [R01NS098772]; National Institute on Drug Abuse [R01DA042852]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Effects of different nutrient solutions on the acclimatisation of in vitro Caladium plantlets using a simplified hydroponic system

An efficient acclimatisation protocol is critical to improve the survival rate and promote growth of in vitro plantlets. Herein, tissue-cultured plantlets of ‘Red Flash’ caladium (Caladium × hortulanum Birdsey) were treated with deionised water and three nutrient solutions including Japanese garden formula (JG), South China Agriculture University formula B for leafy vegetables (SCAU-B) and Hoagland solution in a simplified hydroponic system under indoor environmental conditions. The results showed that all the plantlets survived after 30 days of hydroponic culture, and the three nutrient solutions showed significant positive effects on the plant growth and the content of chlorophyll a, chlorophyll b, total chlorophyll, carotenoid, soluble sugar and soluble protein compared to the deionised water treatment. No significant difference was recorded for the other growth parameters except the average leaf number per plantlet among the nutrient solution treatments. For the analysed physiological parameters, the plantlets treated by SCAU-B contained significantly higher content than those of the Hoagland treatment except the protein content. No significant difference was found between the JG and the SCAU-B treatment except the carotenoid content, and between the JG and the Hoagland treatment except the protein content. The plantlets acclimatised in the nutrient solutions also had a good performance when transferred to plastic pots. These results implied that water alone was not capable of maintaining healthy growth of in vitro caladium plantlets, and hydroponics approach using the three nutrient solutions could be a feasible method for acclimatisation of the plantlets

City-level water-energy nexus in Beijing-Tianjin-Hebei region

Water-energy nexus in a city can either prompt or undermine its development. Yet in China, the relevant research is rarely found. This study accounts the city-level water-energy nexus in Beijing-Tianjin-Hebei region in 2012 from both production and consumption perspectives, where input-output analysis based on city-level input-output tables are applied to conduct consumption-based accounts. Regarding water for energy, Beijing, Tianjin and Tangshan occupy the largest amounts of water for production in the energy sector, at 203 million tonnes (Mt), 148 Mt and 118 Mt, and they also consume most water for energy, at 6690 Mt, 1328 Mt and 1476 Mt. In terms of energy for water, Shijiazhuang and Tianjin have the largest amounts of CO2 emissions for production and consumption respectively, at 28 thousand tonnes (Kt) and 1746 Kt. Furthermore, local authorities should prioritise electricity sector as it holds 69% and 72% of the total water amounts for production and consumption in the energy sector. Besides, integrated management is crucial for cities with low water and energy efficiency (Baoding and Zhangjiakou), and for large CO2 emitters in Hebei province in order to ensure their water and energy sustainability without stunting their economic growth

Evaluating the effect of lactic acid bacteria fermentation on quality, aroma, and metabolites of chickpea milk

Legumes are an attractive choice for developing new products since their health benefits. Fermentation can effectively improve the quality of soymilk. This study evaluated the impact of Lactobacillus plantarum fermentation on the physicochemical parameters, vitamins, organic acids, aroma substances, and metabolites of chickpea milk. The lactic acid bacteria (LAB) fermentation improved the color, antioxidant properties, total phenolic content, total flavonoid content, lactic acid content, and vitamin B6 content of raw juice. In total, 77 aroma substances were identified in chickpea milk by headspace solid-phase microextraction with gas chromatography/mass spectrometry (HS-SPME-GC-MS); 43 of the 77 aroma substances increased after the LAB fermentation with a significant decrease in beany flavor content (p < 0.05), improving the flavor of the soymilk product. Also, a total of 218 metabolites were determined in chickpea milk using non-targeted metabolomics techniques, including 51 differentially metabolites (28 up-regulated and 23 down-regulated; p < 0.05). These metabolites participated in multiple metabolic pathways during the LAB fermentation, ultimately improving the functional and antioxidant properties of fermented soymilk. Overall, LAB fermentation can improve the flavor, nutritional, and functional value of chickpea milk accelerating its consumer acceptance and development as an animal milk alternative