Preparation and application of 3-(methylene-bis(1',4'-phenylene)dicarbamate-2,3-bis(3,5-dimethylphenylcarbamate)-amylose)-2-hydroxylpropoxy-propylsilyl-appended silica particles as chiral stationary phase for HPLC.

3-(Methylene-bis(1',4'-phenylene) dicarbamate-2,3-bis(3,5-dimethylphenylcarbamate)-amylose)-2-hydroxylpropoxy-propylsilyl-appended silica particles (DMP-AM-HPS), a new type of 2, 3-regioselectively substituted amylose-immobilized chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC), have been prepared by treatment of 3-(2,3-dihydroxyl-propoxy)-propylsilyl silica particles with 2,3-bis(3,5-dimethylphenylcarbamate)-amylose and 4,4'-diphenylmethane diisocyanate. The chemical characterization of the bonded particles DMP-AM-HPS has been carried out by elemental analysis and Fourier transform infrared spectroscopic analysis. The chromatographic performance of the DMP-AM-HPS has been evaluated in HPLC under multi-mode conditions including normal phase, reversed phase, and polar organic mobile phase conditions.

Green and enhanced extraction of coumarins from Cortex Fraxini by ultrasound-assisted deep eutectic solvent extraction.

Green and enhanced extraction of bioactive ingredients from medicinal plants has become a hot research field, and deep eutectic solvents have been considered as a novel kind of sustainable solvents in the extraction process. In this study, hydrogen bond acceptor (choline chloride, etc.) and hydrogen bond donor (l-malic acid, etc.

Sitagliptin ameliorates diabetic nephropathy by blocking TGF-β1/Smad signaling pathway.

Diabetic nephropathy (DN) is the leading cause of end-stage failure of the kidney, but the efficacy of current strategies available for the prevention of DN remains unsatisfactory. The purpose of this study was to assess whether sitagliptin (SIT) has therapeutic potential for prevention of DN and to investigate its possible mechanism. The effects of SIT on DN were investigated in rats with type 2 diabetes mellitus (T2DM) and rat mesangial cells (MCs) induced by high glucose.

Application of Partially Substituted 3,5-Dimethylphenylcarbamate-(3-(2-O-β-Cyclodextrin)-2-Hydroxypropoxy)-Propylsilyl-Appended Silica Particles as Chiral Stationary Phase for Multi-mode High-performance Liquid Chromatography.

A new type of partially substituted 3,5-dimethylphenylcarbamate-(3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles (MP-CD-HPS) have been prepared by a convenient post-immobilization derivazition procedure. The MP-CD-HPS has been successfully used as chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC) under normal phase, reversed phase and polar organic mobile phase conditions. The chromatographic evaluation results show that the MP-CD-HPS has excellent selectivity for the separation of aromatic positional isomers and enantiomers of some chiral compounds.

Disturbance of Mammary UDP-Glucuronosyltransferase Represses Estrogen Metabolism and Exacerbates Experimental Breast Cancer.

The progression of breast cancer is closely related to the levels of estrogens within the body. UDP-glucuronosyltransferase (UGT) is an important class of phase II metabolizing enzymes, playing a pivotal role in detoxifying steroid hormone. In the present study, we aim at uncovering the potential dysregulation pattern of UGT and its role in estrogen metabolism and in the pathogenesis of breast cancer.

Investigation of uterotonic properties of Ananas comosus extracts.

Ethnopharmacological Relevance: In folklore medicine Ananas comosus (pineapple) is reputed to act as an abortifacient and in expectant women as a means of inducing labor. Several reports have claimed abortifacient property of A. comosus fruit (ripe or unripe).

Simultaneous determination of multiple androgens in mice organs with liquid chromatography tandem mass spectrometry.

Prostate cancer (PCa) is the most commonly diagnosed cancer in men worldwide. It is essentially dependent on potent androgens, such as testosterone (T) and dihydrotestosterone (DHT). The precursors of T and DHT, which includes androstenedione (A4) and dihydroepiandrosterone (DHEA), and also the metabolites of DHT, 5α-androstane-3α,17β-diol (3α-Diol) and 5α-androstane-3β,17β-diol (3β-Diol) are able to affect the development of PCa.

Serum estrogen receptor beta mediated bioactivity correlates with poor outcome in lung cancer patients.

Objectives: The role of estrogen signaling in lung cancer remains unresolved. We investigate the influence of serum estrogenic compounds and estrogen receptor (ERα and ERβ) mediated bioactivity on lung cancer outcomes.

Materials And Methods: Serum samples were collected from 222 postmenopausal Chinese patients diagnosed with lung cancer in five Singapore hospitals.

Phytoplankton blooms: an overlooked marine source of natural endocrine disrupting chemicals.

Background: We had previously reported high androgenic and estrogenic activities in seawaters in confined clusters close to Singapore. Further investigations revealed a hitherto unsuspected link between estrogenic/androgenic activity and net phytoplankton count.

Objective: The primary objective of this study was to investigate the cause of a correlation between net phytoplankton and endocrine activity, and corroborate this observation, and rule out other possible confounding factors.

Serum estrogen receptor bioactivity and breast cancer risk among postmenopausal women.

The estrogen levels of Asian women are different from those of Western women, and this could affect estrogen receptor (ER) bioactivity and breast cancer risk. We conducted a case-control study in 169 postmenopausal breast cancer cases and 426 matched controls nested within a population-based prospective cohort study, the Singapore Chinese Health Study, to evaluate the serum levels of estrogens and their receptor (ERα and ERβ)-mediated estrogenic activities in relation to breast cancer risk. Breast cancer cases had higher levels of estrogens and ER-mediated bioactivities in baseline serum than the controls.

Selective estrogen receptor modulator effects of epimedium extracts on breast cancer and uterine growth in nude mice.

Epimedium is popularly used in traditional Chinese medicine to treat sexual dysfunction, menstrual irregularity, and osteoporosis. The estrogenic effects of the prenylated flavonoids of Epimedium make it an attractive alternative for hormone replacement therapy. Here, we examined the therapeutic potential of the estrogenic herb extract of Epimedium brevicornum as an alternative to hormone replacement therapy in a breast cancer mouse model.

Preparation and characterization of 4-isopropylcalix[4]arene-capped (3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles as chiral stationary phase for high-performance liquid chromatography.

A new type of 4-isopropylcalix[4]arene-capped (3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)propylsilyl-appended silica particles (IPC4CD-HPS) has been prepared by treatment of bromoacetate-substituted (3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)propylsilyl-appended silica particles (BACD-HPS) with 4-isopropylcalix[4]arene oxyanions in anhydrous N-methyl-2-pyrrolidone. The bonded silica IPC4CD-HPS has been successfully used as chiral stationary phase (CSP) in high-performance liquid chromatography (HPLC) for the first time. The synthetic stationary phase was characterized by means of elemental analysis and Fourier transform infrared spectroscopy.

Determination of androgen receptor degradation enhancer ASC-J9(®) in mouse sera and organs with liquid chromatography tandem mass spectrometry.

A novel androgen receptor (AR) degradation enhancer ASC-J9(®) has displayed beneficial effects during the in vitro and in vivo studies for treatment of prostate cancer, liver cancer, bladder cancer and spinal and bulbar muscular atrophy (SBMA). It works mainly via the degradation of AR with minimal side effects on the tested mice. Here we developed a fast, robust and more sensitive method for the quantification of ASC-J9(®) in 100μL of mouse serum by using liquid chromatography tandem mass spectrometry (LC-MS/MS).

Serum free estradiol and estrogen receptor-α mediated activity are related to decreased incident hip fractures in older women.

There is paucity of data from Asian women on the association between serum estrogens and osteoporotic hip fracture risk. We conducted a case-control study nested within a population-based prospective cohort, The Singapore Chinese Health Study, to evaluate serum estrogens levels, ERα-mediated estrogenic activity and hip fracture risk in postmenopausal Asian women. Among 35,298 women who were recruited between 1993 and 1998, 15,410 women donated blood for research between 1999 and 2004.

Identification and mechanism of 10-carbon fatty acid as modulating ligand of peroxisome proliferator-activated receptors.

Peroxisome proliferator-activated receptors (PPARα, -β/δ, and -γ) are a subfamily of nuclear receptors that plays key roles in glucose and lipid metabolism. PPARγ is the molecular target of the thiazolidinedione class of antidiabetic drugs that has many side effects. PPARγ is also activated by long chain unsaturated or oxidized/nitrated fatty acids, but its relationship with the medium chain fatty acids remains unclear even though the medium chain triglyceride oils have been used to control weight gain and glycemic index.

Preparation and application of methylcalix[4]resorcinarene-bonded silica particles as chiral stationary phase in high-performance liquid chromatography.

Two new types of methylcalix[4]resorcinarene-bonded stationary phases, (3-(C-methylcalix[4]resorcinarene)-2-hydroxypropoxy)-propylsilyl-appended silica particles (MCR-HPS) and bromoacetate-substituted MCR-HPS particles (BAMCR-HPS), have been synthesized and used as chiral stationary phases for high-performance liquid chromatography (HPLC) for the first time. The synthetic stationary phases are characterized by means of elemental analysis and Fourier-transform infrared spectroscopy. The chromatographic behavior of MCR-HPS and BAMCR-HPS was studied with several disubstituted benzenes and some chiral drug compounds under both normal phase and reversed-phase conditions.

Preparation and application of rifamycin-capped (3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles as chiral stationary phase for high-performance liquid chromatography.

Rifamycin-capped (3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles (RCD-HPS), a new type of substituted β-cyclodextrin-bonded chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC), have been synthesized by the treatment of bromoacetate-substituted-(3-(2-O-β-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles (BACD-HPS) with rifamycin SV in anhydrous acetonitrile. The stationary phase is characterized by means of elemental analysis and Fourier-transform infrared spectroscopy. This new CSP has a chiral selector with two recognition sites: rifamycin and β-cyclodextrin (β-CD).

Application of bromoacetate-substituted beta-CD-bonded silica particles as chiral stationary phase for HPLC.

Bromoacetate-substituted [3-(2-O-beta-cyclodextrin)-2-hydroxypropoxy]propylsilyl-appended silica particles (BACD-HPS), an important and useful synthetic intermediate for preparation of novel types of macrocycles-capped beta-CD-bonded silica particles including crown ether/cyclam/calix[4]arene-capped beta-CD-bonded silica particles, have been prepared and used as chiral stationary phase for HPLC. This synthetic stationary phase is characterized by means of elemental analysis. For the first time, the chromatographic behavior of BACD-HPS was systematically evaluated with several disubstituted benzenes and some chiral drug compounds under both normal and RP conditions in HPLC.

Determination of breviflavone A and B in Epimedium herbs with liquid chromatography-tandem mass spectrometry.

Two new types of minor flavonoids, breviflavone A and B, have been recently isolated and identified from Epimedium brevicornu in our previous research. Breviflavone B is a novel flavonoid with potent and specific estrogen receptor (ER) bioactivity. Its positional isomer, breviflavone A, is not ER active.

Preparation and evaluation of calix[4]arene-capped beta-cyclodextrin-bonded silica particles as chiral stationary phase for high-performance liquid chromatography.

Calix[4]arene-capped [3-(2-O-beta-cyclodextrin)-2-hydroxypropoxy]propylsilyl-appended silica particles (C4CD-HPS), a new type of substituted beta-cyclodextrin-bonded chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC), have been synthesized by treatment of bromoacetate-substituted [3-(2-O-beta-cyclodextrin)-2-hydroxypropoxy]propylsilyl-appended silica particles (BACD-HPS) with calix[4]arene oxyanions in anhydrous N-methyl-2-pyrrolidone. The synthetic stationary phase is characterized by means of elemental analysis. This new type of CSP has a chiral selector with two recognition sites: calix[4]arene and beta-cyclodextrin (beta-CD).

Trace analysis of icariin in human serum with dansyl chloride derivatization after oral administration of Epimedium decoction by liquid chromatography tandem mass spectrometry.

Epimedium herbs are a type of complex traditional Chinese medicine (TCM) with high estrogenic bioactivity. The Epimedium herbal decoction mixture contains many compounds including icariin that can exert potent effects on numerous physiological processes related to human health. An ultrasensitive liquid chromatography tandem mass spectrometric (LC-MS/MS) method has been developed to determine trace levels of icariin in human serum with dansyl chloride derivatization after oral administration of the Epimedium herbal decoctions.

Ultrasensitive cell-based bioassay for the measurement of global estrogenic activity of flavonoid mixtures revealing additive, restrictive, and enhanced actions in binary and higher order combinations.

Flavonoids present in food, botanicals, and body fluids occur as complex mixtures, and data on their combinatorial estrogenic effects are sparse. Human cell lines that permanently express estrogen receptor (ER) alpha and ERbeta proteins were developed for the measurement of the global estrogenicity of flavonoids in such complex mixtures. The presence of estrogenic ligands, known and unknown, in these mixtures can be detected by activation of an ER-driven luciferase reporter gene.

New estrogenic prenylflavone from Epimedium brevicornum inhibits the growth of breast cancer cells.

Estrogens maintain female sexual health. The hormone also drives the growth of estrogen receptor (ER) positive breast tumors, and ER modulators, like tamoxifen, are used to reduce tumor recurrence. To identify phytoestrogens with possible health benefits, we screened several Traditional Chinese Medicines and encountered an extract from the leaves of Epimedium brevicornum (EB), with strong (EC50: 1.

Androgenic and estrogenic response of green mussel extracts from Singapore's coastal environment using a human cell-based bioassay.

In the last decade, evidence of endocrine disruption in biota exposed to environmental pollutants has raised serious concern. Human cell-based bioassays have been developed to evaluate induced androgenic and estrogenic activities of chemical compounds. However, bioassays have been sparsely applied to environmental samples.

Clustering of sex hormone disruptors in Singapore's marine environment.

Abnormal sexual differentiation and other reproductive abnormalities in marine animals indicate the presence in seawater of endocrine-disrupting compounds (EDCs) that perturb the function of the sex hormone signaling pathways. However, most studies to date have reported on EDC effects in freshwater and sewage samples, and there is a paucity of bioassay data on the effects of EDCs in marine waters. Our aims in this study were to devise robust methodologies suitable for extracting potential EDCs and to measure their summated effects on activities of androgen receptors (ARs) and estrogen receptors (ER-alpha and ER-beta) in marine samples from Singapore's coastal waters.