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.

[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.

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.

[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.

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.

[Study on interaction of caffeine and theophylline with bovine serum albumins].

The interation of caffeine and theophylline with bovine serum albumins has been studied by fluorescence spectroscopy. The results indicated that enoxacin could bind with BSA strongly at molar ratio 1:1 and the equilibrium constants were Kc = 1.673 x 10(4) L x mol(-1) and Kt = 6.802 x 10(3) L x mol(-1), respectively. Good linear Stern-Volmer lines were observed on the fluorescence of BSA quenched by enoxacin of different concentration, indicating that the combination reaction of enoxacin with BSA is a single static quenching process.

[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.

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.

Fabrication of a hydrogen peroxide biosensor based on a self-assemble composite oxide film.

A titania film with horseradish peroxidase (HRP) was immobilized on indium tin oxide (ITO) electrodes to act as a biosensor of hydrogen peroxide via the self-assembling and sol-gel route. The film was characterized by the atomic functional microscopy, electrochemical and UV-vis spectroscopy methods. The resulting biosensor exhibited fast amperometric response and good stability to hydrogen peroxide (H2O2). The linear range for H2O2 determination was from 2 x10(-6) to 1.45 x 10(-3) M, with a detection limit of 4 x10(-6) M based on S/N=3. The apparent Michaelis-Menten constant of the biosensor to H2O2 was estimated to be 1.5 mM, showing the HRP on the films had the higher biologic activities.

Study for luminescence performance of three methyl xanthine derivatives.

In this paper, the low-temperature phosphorescence (LTP), the low-temperature fluorescence (LTF), the paper substrate room-temperature phosphorescence (PS-RTP) and the room fluorescence (RTF) properties of caffeine (CF), theophylline (TP), and theobromine (TB) are investigated and compared, and some rules are found out: their maximal excitation wavelength and emission wavelength are in the range of 270-300 nm and 395-445 nm, respectively. And the PS-RTP characters of lifetime, polarization and quanta yield are also investigated and compared. It is found that their lifetimes of PS-RTP are all in the level of 0.1s. They belong to long-life phosphorescence and their PS-RTP spectra are incompletely polarized.

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.

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.

Study on inclusion complex of cyclodextrin with methyl xanthine derivatives by fluorimetry.

The inclusion complexes of beta-cyclodextrin (beta-CD) and HP-beta-cyclodextrin (HP-beta-CD) with caffeine, theophylline and theobromine were investigated by fluorimetry. Various factors affecting the formation of inclusion complexes were discussed in detail including forming time, pH effect and temperature. The results indicate that inclusion process was affected seriously by laying time and pH. The forming time of beta-CD inclusion complexes is much longer than that of HP-beta-CD. The optimum pH range is about 7-12 for caffeine, 8-10 for TP, 10.5-12 for TB. The intensities of their fluorescence increase with the decreasing of temperature. Their maximum excitation wavelengths are all in the range of 280-290 nm. The emission wavelength of caffeine and theophylline are both in the range of 340-360 nm, and that of theobromine is about 325 nm. The fluorescence signals are intensified with the increasing concentration of CD. The stoichiometry of the inclusion complexes of CD with these three methyl xanthine derivatives are all 1:1 and the formation constant are all calculated.

[A study on inclusion complexes of cyclodextrin with three anticancer xanthines by fluorescence].

The inclusion complexes of beta-Cyclodextrin (beta-CD) and HP-beta-Cyclodextrin (HP-beta-CD) with 6-Mercaptopurine (6-MP), Azathioprine (BAN) and 8-Azaguanine (Azan) were investigated by fluorescence. Various factors affecting the formation of inclusion complexes were discussed in detail including formation time and pH effect. The formation constants of their inclusion complexes were determined. The results indicated that their inclusion was affected significantly by laying time and pH. The formation time of beta-CD inclusion complexes is much longer than that of HP-beta-CD. The optimum pH is about pH = 7.7-12. Their maximum excitation wavelengths are all in the range of 276-285 nm and the maximum emission wavelengths are all in the range of 328-353 nm. The fluorescence signals are intensified with increasing concentration of CD. The stoichiometries of the inclusion complexes of CD with these three anticancer xanthines are all 1:1 and the formation constants are calculated.