Diterpenoids with an unusual tricyclo[10.3.0.02,9]pentadecane skeleton from Pedilanthus tithymaloides as multidrug resistance modulators.

Three new diterpenoids with an unusual carbon skeleton, pedilanins A-C (1-3), and nine new jatrophane diterpenoids, pedilanins D-L (4-12), along with five known ones (13-17), were isolated from Pedilanthus tithymaloides. Compounds 1-3 characterize an unprecedented tricyclo[10.3.0.02,9]pentadecane skeleton. Compounds 4-8 are rare examples of the jatrophanes bearing a cyclic hemiketal substructure. Their structures were determined by an extensive analysis of HRESIMS, NMR, quantum-chemical calculation, DP4+ probability, and X-ray crystallographic data. In the bioassay, compounds 1-12 dramatically reversed multidrug resistance in cancer cells with the fold-reversals ranging from 17.9 to 396.8 at the noncytotoxic concentration of 10 µM. The mechanism results indicated that compounds 2 and 3 inhibited the P-glycoprotein (Pgp) transporter function, thus reversing the drug resistance.

Low microRNA150 expression is associated with activated carcinogenic pathways and a poor prognosis in patients with breast cancer.

Breast cancer is the most common type of cancer amongst women worldwide, and numerous microRNAs (miRNAs/miRs) are involved in the initiation and progression of breast cancer. The aim of the present study was to identify hub miRNAs and determine the underlying mechanisms regulated by these miRNAs in breast cancer. Breast invasive carcinoma transcriptome data (including mRNAs and miRNAs), and clinical data were acquired from The Cancer Genome Atlas database. Differential gene expression analysis, co­expression network analysis, gene set enrichment analysis (GSEA) and prognosis analysis were used to screen the hub miRNAs and explore their functions. Functional experiments were used to determine the underlying mechanisms of the hub miRNAs in breast cancer cells. The results revealed that low miR150 expression predicted a more advanced disease stage, and was associated with a less favorable prognosis. Through the combined use of five miRNA­target gene prediction tools, 31 potential miR150 target genes were identified. GSEA revealed that low miR150 expression was associated with the upregulation of several cancer­associated signaling pathways, and the downregulation of several tumor suppressor genes. Furthermore, miR150 independently affected overall survival in patients, and interacted with its target genes to indirectly affect overall and disease­free survival. Functional experiments demonstrated that miR150 positively regulated B and T lymphocyte attenuator (BTLA), and the downregulation of miR150 and BTLA combined promoted cell migration. In conclusion, the present study revealed that low miR150 expression was associated with less favorable clinical features, upregulation of several carcinogenic signaling pathways, and poor patient survival. Additionally, a miR150­BTLA axis was suggested to regulate cell viability and migration.

Protein-enriched fiber vegan meal promote satiety and suppress food intake in rats.

Dietary preferences were closely associated with the pathogenesis of numbers of metabolic disorders, in particularly, obesity. Dietary fiber was shown to be capable of preventing weight gain and excessive food intake mainly through stimulating chewing and saliva secretion, and promote satiety signals. In this study, we characterized the "Vitamin World® Vegan Meal" Formula of Feihe, a novel protein-enriched fiber dietary supplement contained potato protease inhibitor II (PI2) that developed. And we demonstrated that this particular fiber formula was effective in preventing weight gain, increasing satiety signals, and reducing food intake in rats in a dosage-dependent manner. Our study provides lines of evidence and would further bolster the use of this nutritious vegan meal in regulating satiety and food intake in clinics.

Calycosin Influences the Metabolism of Five Probe Drugs in Rats.

BACKGROUND: Calycosin (CAL), a type of O-methylated isoflavone extracted from the herb Astralagusmembranaceus (AM), is a bioactive chemical with antioxidative, antiphlogistic and antineoplastic activities commonly used in traditional alternative Chinese medicine. AM has been shown to confer health benefits as an adjuvant in the treatment of a variety of diseases. AIM: The main objective of this study was to determine whether CAL influences the cytochrome P450 (CYP450) system involved in drug metabolism. METHODS: Midazolam, tolbutamide, omeprazole, metoprolol and phenacetin were selected as probe drugs. Rats were randomly divided into three groups, specifically, 5% Carboxymethyl cellulose (CMC) for 8 days (Control), 5% CMC for 7 days + CAL for 1 day (single CAL) and CAL for 8 days (conc CAL), and metabolism of the five probe drugs evaluated using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: No significant differences were observed for omeprazole and midazolam, compared to the control group. T max and t1/2 values of only one probe drug, phenacetin, in the conc CAL group were significantly different from those of the control group (T max h: 0.50±0.00 vs 0.23±0.15; control vs conc CAL). C max of tolbutamide was decreased about two-fold in the conc CAL treatment group (conc vs control: 219.48 vs 429.56, P<0.001). CONCLUSION: Calycosin inhibits the catalytic activities of CYP1A2, CYP2D6 and CYP2C9. Accordingly, we recommend caution, particularly when combining CAL as a modality therapy with drugs metabolized by CYP1A2, CYP2D6 and CYP2C9, to reduce the potential risks of drug accumulation or ineffective treatment.

Unusual high-temperature reversible phase transition containing dielectric and nonlinear optical switches in host-guest supramolecular crown ether clathrates.

A novel high-temperature dielectric and quadratic nonlinear optical switching material, 3,4-difluoroanilinium 18-crown-6 perchlorate, was synthesized. It exhibits two successive structural phase transitions at 347 K and 240 K, respectively. Gradually increased SHG-active characteristics are also identified.

Effects of salidroside on rat CYP enzymes by a cocktail of probe drugs.

OBJECTIVES: In this study, we aimed to evaluate the effect of salidroside on the activities of the different drug-metabolizing enzymes CYP1A2, CYP2B6, CYP2C9, CYP2D6 and CYP3A4 in rats, in which a specific probe drug was used for each enzyme. MATERIALS AND METHODS: After pretreatment with salidroside, five probe drugs were simultaneously administered to rats by gavage. The given dose was 2.0 mg/kg for phenacetin (CYP1A2 activity), 4.0 mg/kg for bupropion (CYP2B6 activity), 2.0 mg/kg for losartan (CYP2C9 activity), 8.0 mg/kg for metoprolol (CYP2D6 activity) and 1.0 mg/kg for midazolam (CYP3A4 activity). Then, an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the concentrations of rats' blood, which were collected at different corresponding times. RESULTS: Our data showed that salidroside exhibited an inductive effect on CYP1A2, CYP2B6, CYP2C9 and CYP3A4 activities by changing the main pharmacokinetic parameters (t1/2, CL/F, Cmax and AUC(0-∞)) of the four probe drugs in rats. However, no significant changes in CYP2D6 activity were observed. CONCLUSION: In a word, the results displayed that salidroside could induce the activities of CYP1A2, CYP2B6, CYP2C9 and CYP3A4, which may influence the disposition of the drugs that are mainly metabolized by these pathways. Our research can provide the basis for the study of related herb-drug interactions in clinic.

Characterization of anthropogenic impacts in a large urban center by examining the spatial distribution of halogenated flame retardants.

Anthropogenic impacts have continuously intensified in mega urban centers with increasing urbanization and growing population. The spatial distribution pattern of such impacts can be assessed with soil halogenated flame retardants (HFRs) as HFRs are mostly derived from the production and use of various consumer products. In the present study, soil samples were collected from the Pearl River Delta (PRD), a large urbanized region in southern China, and its surrounding areas and analyzed for a group of HFRs, i.e., polybrominated diphenyl ethers (PBDEs), decabromodiphenyl ethane, bis(hexachlorocyclopentadieno)cyclooctane (DP) and hexabromobenzene. The sum concentrations of HFRs and PBDEs were in the ranges of 0.66-6500 and 0.37-5700 (mean: 290 and 250) ng g(-1) dry weight, respectively, around the middle level of the global range. BDE-209 was the predominant compound likely due to the huge amounts of usage and its persistence. The concentrations of HFRs were greater in the land-use types of residency, industry and landfill than in agriculture, forestry and drinking water source, and were also greater in the central PRD than in its surrounding areas. The concentrations of HFRs were moderately significantly (r(2) = 0.32-0.57; p < 0.05) correlated with urbanization levels, population densities and gross domestic productions in fifteen administrative districts. The spatial distribution of DP isomers appeared to be stereoselective as indicated by the similarity in the spatial patterns for the ratio of anti-DP versus the sum of DP isomers (fanti-DP) and DP concentrations. Finally, the concentrations of HFRs sharply decreased with increasing distance from an e-waste recycling site, indicating that e-waste derived HFRs largely remained in local soil.

The role of CYP2C9 genetic polymorphism in carvedilol O-desmethylation in vitro.

We aimed at investigating the role of CYP2C9 in carvedilol O-desmethylation and identifying the effect of 35 CYP2C9 allelic variants we found in Chinese Han population on the in vitro metabolism of carvedilol. Recombinant CYP2C9 and CYP2D6 microsomes of the wild type were used to test and verify the enzymes involved in carvedilol O-desmethylation. Recombinant CYP2C9 microsomes of distinguished genotypes were used to characterize the corresponding enzyme activity toward carvedilol. 2-100 µM carvedilol was incubated for 30 min at 37 °C. The products were detected using high-performance liquid chromatography. CYP2C9 plays a certain role in carvedilol metabolism. Compared with wild-type CYP2C9*1, the intrinsic clearance (V max/K m) values of all variants toward carvedilol O-desmethylation were significantly altered. The variants exhibited significantly decreased values (from 30 to 99.8 %) due to increased K m and/or decreased V max values. We conclude that recombinant system could be used to investigate the enzymes involved in drug metabolism and these findings complement the database where CYP2C9 polymorphism interacts with biotransformation of exogenous substances like drugs and toxins.

Assessing the effects of urbanization on the environment with soil legacy and current-use insecticides: a case study in the Pearl River Delta, China.

To evaluate the impacts of anthropogenic events on the rapid urbanized environment, the levels of legacy organochlorine pesticides (OCPs) and current-use insecticides (CUPs), i.e., dichlorodiphenyltrichloroethane and its metabolites (DDTs), hexachlorocyclohexanes (HCHs), pyrethroids and organophosphates in soil of the Pearl River Delta (PRD) and surrounding areas were examined. Spatial concentration distributions of legacy OCPs and CUPs shared similar patterns, with higher concentrations occurred in the central PRD with more urbanization level than that in the PRD's surrounding areas. Furthermore, relatively higher concentrations of OCPs and CUPs were found in the residency land than in other land-use types, which may be attributed to land-use change under rapid urbanization. Moderate correlations between gross domestic production or population density and insecticide levels in fifteen administrative districts indicated that insecticide spatial distributions may be driven by economic prosperity. The soil-air diffusive exchanges of DDTs and HCHs demonstrated that soil was a sink of atmospheric o,p'-DDE, o,p'-DDD, p,p'-DDD and o,p'-DDT, and was a secondary source of HCHs and p,p'-DDT to atmosphere. The soil inventories of DDTs and HCHs (100 ± 134 and 83 ± 70 tons) were expected to decrease to half of their current values after 18 and 13 years, respectively, whereas the amounts of pyrethroids and organophosphates (39 and 6.2 tons) in soil were estimated to decrease after 4 and 2 years and then increase to 87 and 1.0 tons after 100 years. In this scenario, local residents in the PRD and surrounding areas will expose to the high health risk for pyrethroids by 2109. Strict ban on the use of technical DDTs and HCHs and proper training of famers to use insecticides may be the most effective ways to alleviate the health effect of soil contamination.

[Fluoroimmunoassay and Magnetic Lateral Flow Immunoassay for the Detection of Ractopamine].

A fluoroimmunoassay based on quantum dots (QDs) and a lateral flow immunoassay system based on the magnetic beads (MB) were constructed to detect ractopamine (RAG) in urine samples. The monoclonal antibody (Ab1) against RAC was conjugated with QDs or MB as detector reagent, respectively. They apply a competitive format using an immobilized RAC conjugate and free RAC present in samples. That is to say, the concentration of RAC in the sample was negative related to the fluorescense intensity of QDs or the color density of MB. Results showed that the limit of detection (LOD) of fluorescence immunoassay method is 1 ng · mL⁻¹ and analysis time is 4 h, while the visual LOD was 10 ng · mL⁻¹ and analysis time was 15 min in magnetic lateral flow immunoassay system (MFLIS). Taken into consideration of the advantages and disadvantages of the two methods, it was suitable for the trace detection of RAC using fluoroimmunoassay while it was appropriate for point-of-care tesing of RAC by MFLIS.

[Fluorescent and Magnetic Relaxation Switch Immunosensor for the Detecting Foodborne Pathogen Salmonella enterica in Water Samples].

Fluoroimmunoassay based on quantum dots (QDs) and magnetic relaxation switch (MRS) immunoassay based on superparamagnetic nanoparticles (SMN) were constructed to detect Salmonella enterica (S. enterica) in water samples. In fluoroimmunoassay, magnetic beads was conjugated with S. enterica capture antibody (MB-Ab2) to enrich S. enterica from sample solution, then the QDs was conjugated with the S. enterica detection antibody (QDs-Ab1) to detect S. enterica based on sandwich immunoassay format. And the fluorescence intensity is positive related to the bacteria concentration of the sample. Results showed that the limit of detection (LOD) of this method was 102 cfu · mL⁻¹ and analysis time was 2 h. In MRS assay, magnetic nanoparticle-antibody conjugate (MN-Ab1) can switch their dispersed and aggregated state in the presence of the target. This state of change can modulate the spin-spin relaxation time (T2) of the neighboring water molecule. The change in T2(ΔT2) positively correlates with the amount of the target in the sample. Thus, AT can be used as a detection signal in MRS immunosensors. Results showed that LOD of MRS sensor for S. enterica was 10³ cfu · mL⁻¹ and analysis time was 0.5 h. Two methods were compared in terms of advantages and disadvantages in detecting S. enterica.

Global trends of research on emerging contaminants in the environment and humans: a literature assimilation.

Available literature data on five typical groups of emerging contaminants (EMCs), i.e., chlorinated paraffins (CPs), dechlorane plus and related compounds (DPs), hexabromocyclododecanes (HBCDs), phthalate esters, and pyrethroids, accumulated between 2003 and 2013 were assimilated. Research efforts were categorized by environmental compartments and countries, so that global trends of research on EMCs and data gaps can be identified. The number of articles on the target EMCs ranged from 126 to 1,379 between 2003 and 2013. The numbers of articles on CPs, DPs, HBCDs, and pyrethroids largely followed the sequence of biota > sediment ≥ air > water ≥ soil > human tissue, whereas the sequence for phthalate esters was water > sediment > soil > human tissue ≥ biota ≥ air. Comprehensive studies on the target EMCs in biological samples and human tissues have been conducted worldwide. However, investigations into the occurrence of the target EMCs in soil of background areas and water are still scarce. Finally, developed and moderately developed countries, such as the USA, China, Canada, Japan, and Germany, were the main contributors to the global research efforts on EMCs, suggesting that economic prosperity may be one of the main factors propelling scientific research on EMCs.

The complex jujube genome provides insights into fruit tree biology.

The jujube (Ziziphus jujuba Mill.), a member of family Rhamnaceae, is a major dry fruit and a traditional herbal medicine for more than one billion people. Here we present a high-quality sequence for the complex jujube genome, the first genome sequence of Rhamnaceae, using an integrated strategy. The final assembly spans 437.65 Mb (98.6% of the estimated) with 321.45 Mb anchored to the 12 pseudo-chromosomes and contains 32,808 genes. The jujube genome has undergone frequent inter-chromosome fusions and segmental duplications, but no recent whole-genome duplication. Further analyses of the jujube-specific genes and transcriptome data from 15 tissues reveal the molecular mechanisms underlying some specific properties of the jujube. Its high vitamin C content can be attributed to a unique high level expression of genes involved in both biosynthesis and regeneration. Our study provides insights into jujube-specific biology and valuable genomic resources for the improvement of Rhamnaceae plants and other fruit trees.

Association of soil polycyclic aromatic hydrocarbon levels and anthropogenic impacts in a rapidly urbanizing region: spatial distribution, soil-air exchange and ecological risk.

The occurrence of polycyclic aromatic hydrocarbons (PAHs) in soil of the Pearl River Delta (PRD) and surrounding areas was examined on a basis of six land-use types and four geographic regions, from which the impacts of anthropogenic events on the terrestrial environment were evaluated. No significant difference in the concentrations of Σ28PAH and Σ15PAH (sums of 28 and 15 PAHs, respectively) was found among the land-use types of industry, landfill and residency. On the other hand, higher soil PAH concentrations occurred in the central PRD characterized by dense population and high urbanization level, compared to other geographic regions. Source diagnostics implicated the combustions of coal and refined petroleum as the major input sources of anthropogenic PAHs. Furthermore, low molecular weight PAHs tended to volatilize from soil to air while the opposite was prevailing for high molecular weight PAHs. The mean annual diffusive flux of Σ15PAH (852 µg m(-2)yr(-1)) from the soil to the atmosphere in the central PRD was greater than those in the PRD's periphery (195 µg m(-2)yr(-1)), West region (322 µg m(-2)yr(-1)) and East region (84.9 µg m(-2)yr(-1)), suggesting that the central PRD may have become a secondary source of PAHs to the surrounding areas. Finally, ecological risk assessment based on the classification from Maliszewska-Kordybach showed that 3.5% of soil within the central PRD was heavily contaminated by PAHs and 5.2 million residents may be subjected to high health risk.

[Spatial distribution and risk assessment of insecticides in surface soil from a rapidly urbanizing region].

To examine the distribution patterns of organic contaminants in rapidly urbanizing regions, the levels and spatial distributions of 19 overlooked insecticides, i. e., phenyl-pyrazole class (fipronil), chlordane, endosulfan, nonachlor, hexachlorobenzene, heptachlor, dieldrin, aldrin, endrin, methoxychlor and their metabolites, were examined in 229 soil samples collected from the Pearl River Delta (PRD) and surrounding areas. The results indicated that higher insecticide levels distributed in the central PRD, while lower levels congested in the surrounding areas. The similar spatial patterns between the levels of insecticides and economic prosperity or population density demonstrated that social-economic factors may have dictated the spatial patterns of insecticides. In addition, the changing of land-use types during urbanization processes, e.g., historical plowlands have been converted into residential landscapes, resulted in high concentrations of banned insecticides in metropolis of the central PRD. Source diagnostics indicated that new inputs of technical chlordane products existed in the PRD and surrounding areas. Fipronil was degraded into fipronil sulfone and fipronil sulfide in most soil samples because of its low half-life in soil. Finally, a risk assessment of 19 insecticides in soil for human health suggested that six samples collected from the major administrative districts with dense population had potential cancer or non-cancer risk to human health. Therefore, these overlooked insecticides should be concerned in future environmental research.

A review of environmental and human exposure to persistent organic pollutants in the Pearl River Delta, South China.

Rapid economic growth in South China (including Guangdong Province, Hong Kong, and Macau), particularly within the Pearl River Delta region, has resulted in severe pollution of the natural eco-environment in the last three decades. Large amounts of monitoring data on organic pollution in the Pearl River Delta have been accumulated, which allows us to conduct a fairly comprehensive assessment of the state of the Pearl River Delta and elucidate spatial and temporal patterns of pollution on a regional scale. Of various causes for environmental deterioration, negative impact from persistent organic pollutants (POPs) is a global concern. This review examines the current levels and distribution patterns of several POPs, namely DDT (and its metabolites DDD and DDE), hexachlorocyclohexanes, and polybrominated diphenyl ethers, in various environmental compartments of South China. The general information on environmental occurrence, regional behaviors, ecological effects, and human exposure of these POPs in this region are reviewed.

[Study on the interaction between ICT fluorescence probe and bovine serum albumins].

The present article studied the interaction between intramolecular charge transfer fluorescence probe-1-keto-2-(p-dimethylaminobenzal)-tetrohydronaphthalene (KDTN) and bovine serum albumins (BSA). With the concentration of KDTN increasing, the fluorescence of BSA rapidly quenched and the fluorescence peak gradually blue-shifted. The result indicated that they were bound mainly by hydrophobic interaction. The binding sites is 0.94 (3 degrees C) and the equilibrium constant K is 3.27 x 10(4) L x mol(-1). Temperature increment is advantageous to the combination. It is a single static quenching process that the fluorescence of BSA quenches, which is induced by the combination of KDTN and BSA. Further study showed that different substances had different effects on the combination of KDTN and BSA.

[Study on the interaction of tetrabromofluorescein and DNA].

The interaction of tetrabramofluorescein (TBF) and DNA was studied by the fluorescence and SS-RTP. The effect of the ion strength and ethanol on the fluorescence spectra of TBF in the presence of DNA and absence of DNA was investigated. In addition, the effect of pH on the SS-RTP spectra of TBF was also examined. The quenched constant was 719.74 and 880.22 in the absence and presence of DNA respectively. Finally, the interaction mode between TBF and DNA was discussed from the fluorescence quenched and phosphorescence polarized experiments.