Electron Spray Research Articles

Steroidal glycoside profile differences among primary roots system and adventitious roots in Solanum dulcamara

Main conclusionSolanum dulcamara primary and adventitious roots showed qualitative and quantitative differences in their steroidal glycosides profile. This opened new venues to evaluate the bioactivity of these molecules in belowground ecosystems.The Solanum genus is characterized by the presence of steroidal glycosides (SGs) that confer herbivore resistance and serve as drug precursors in the pharmaceutical industry. Solanum dulcamara is a self-compatible, sexually reproducing species that produces seeds after buzz-pollination. In addition, primordia on the stem facilitate clonal propagation via adventitious root (AR) formation. ARs contain aerenchyma being developmentally and morphologically different from primary roots (PRs). Therefore, we hypothesized that ARs and PRs have different SG profiles. Aiming to assess differences in SGs profiles in S. dulcamara roots in relation to their origins and morphologies, we used liquid chromatography coupled to electron spray ionization quadruple time of flight mass spectrometry (LC-ESI-qToF-MS) to profile SGs from PRs and ARs of seven S. dulcamara individuals. Mass fragmentation pattern analysis indicated the presence of 31 SG-type structures, including those with spirostans and furostans moieties. We assigned the 31 structures to 9 classes of steroidal aglycons (SAgls) that differ in hydroxylation and degree of unsaturation. We found that SAgls were conjugated with di-, tri- and tetra saccharides whereby one compound contained a malonylated sugar. Principle component analysis showed that SG profiles of PRs and ARs separated on the first principal component, supporting our hypothesis. Specifically, PRs contain higher number of SGs than ARs with some compounds exclusively present in PRs. Our results reveal a high level of novel chemodiversity in PRs and ARs of Solanum dulcamara. The knowledge gained will deepen our understanding of SGs biosynthesis and their functional role in plant-environment interactions.

Перспективні напрямки розробки засобів, що здатні підвищувати адаптаційні можливості організму людини в умовах негативного впливу середовища життєдіяльності

Abstract. The ever-increasing anthropogenic chemical load throughout the world prompts the search for sources of biologically active substances (BAS) capable of increasing the adaptive capabilities of a person exposed to the harmful effects of the environment. Aim. Scientific substantiation of the optimal composition of recipes and features of the production technology of products with immunomodulating and adaptogenic effects (dietary supplements, detoxification products for external use, including cosmetic preventive products for hand skin disinfection), based on technologically processed vegetable waste used in the production of pharmaceutical products Proteflazidum®". Material and Methods. The chemical composition of the ethanol extract of the plant raw material "Proteflazidum®" and the waste of its production - meal was studied. The mass fraction of flavonoid compounds aglycones of tricin, apigenin, luteolin, amino acids, sugars, carboxylic acids, natural polymers (pectin substances, chlorophylls and hemicellulose), ethanol (%, vol) was determined. The methods of ultra-high-performance high-speed liquid chromatography with diode-matrix detection (UPLCPDA, Waters, USA) were used; method of ultra-high-performance mass spectrometric high-speed liquid chromatography with electron spray ionization (UPLC-MC/MC, Waters, USA). A study of the dietary supplements "Immunoflazid Light" (syrup) and "Immunoflazid Pro" (capsules), manufactured in accordance with TU U 10.8-25589583-001:2020, was conducted according to safety indicators: the content of heavy metals, pesticides and radionuclides for compliance with the requirements of GN 4.4.8.073 -2001 "Temporary hygienic standards for the content of chemical and biological contaminants in biologically active supplements", approved by the resolution of the chief state sanitary doctor of Ukraine dated 04.20.2001. No. 131 and GN 6.6.1.1-130-2006 "Permissible levels of the content of radionuclides 137Cs, 90Sr in food and drinking water", approved by the order of the Ministry of Health of Ukraine dated 05.03.2006 under No. 256. A spectrometer was used to determine the content of lead, cadmium, and mercury atomic emission "SHIMADSU ICPE - 9820"; for the determination of radionuclides, the spectrometer "SEG-001", "AKP-S" and the spectrometer "SEB-01-70" were used. Methods of measuring pesticides according to DSTU EN 12393-1:2003, DSTU EN 12393-2:2003, DSTU EN 12393-3:2003 and GOST 30349-96. Results. The waste of vegetable raw materials, which is formed as a result of the production of the "Proteflazidum®", is a valuable source of BAS, which allows you to consider them as raw materials for creating recipes of products with an adaptogenic effect - dietary supplements and raw materials for the production of products for external use, including cosmetic prophylactic and means for hand skin disinfection. According to safety indicators, the new products belong to low-hazard substances when applied to the skin (hazard class 4), do not show skin-irritating, skin-resorptive and sensitizing properties, alcohol-free products do not irritate the mucous membrane of the eyes. Conclusions. Proteflazidum® production waste is a valuable raw material for the creation of a wide range of products with an adaptogenic effect (dietary supplements, raw materials for the production of products for external use, including cosmetic prophylactics and products for hand skin disinfection). Key Words: Proteflazidum®, Herba Deschampsia Сaespitosa L., Herba Calamagrostis Epigeios L., bioflavonoids, pectin substances.

Chemical constituents from the stem barks of polyscias serrata balf

Plants of the genus Polyscias (the family Araliaceae) are represented as perennial shrubs and are commonly cultivated in southeastern Asia and the Pacific regions. Pharmacological studies revealed that Polyscias crude extracts and their isolated compounds exhibited a variety of biological activity, such as antibacterial, antifungal, cytotoxic, immuno-stimulant, wound healing and anti-asthmatic activities. For the first time, phytochemical study on the methanol (MeOH) extract of the stem barks of Vietnamese species Polyscias serrata Balf. (locally named Dinh lang rang) resulted in the isolation and NMR (Nuclear Magnetic Resonance)-determination of six compounds 1-6. They include one nucleobase uracil (1), two nucleosides uridine (2) and adenosine (3), one alkaloid indole-3-carboxylic acid (4), one mono-phenol glucoside koaburside (5), and one saponin randianin (6). The chemical structures of these phytochemicals were elucidated by physicochemical, the 1D-NMR [1H, 13C-NMR, and DEPT (Distortionless Enhancement by Polarization Transfer)], the 2D-NMR [HSQC (heteronuclear single quantum coherence), HMBC (Heteronuclear Multiple Bond Correlation), and COSY (correlation spectroscopy)] spectral, and ESI-MS (Electron Spray Ionization-Mass Spectrum) data. This is the first time that compounds 2-6 have been obtained from the genus Polyscias. In agreement with various reports, the nitrogenous compounds and triterpene saponins can be seen as characteristic metabolites of genus Polyscia

Development of a Proton-Enhanced ESI UPLC-MS/MS Method for the Determination of Tetrodotoxin.

Tetrodotoxin (TTX) is a kind of low-molecular-weight non-protein neurotoxin. It is one of the most potent neurotoxins found in nature, and it is found in puffer fish and various marine biota. The low sensitivity of previous analytical methods limited their application in puffer fish organ samples. This study established a method for the accurate and fast determination of TTX by reversed ultra-performance liquid chromatography coupled with proton-enhanced electron spray ionization-tandem mass spectrometry. The method yields good peak shapes, high sensitivity and low coeluted interferences. The method was successfully applied to determine TTX in puffer fish tissue samples of about 0.2 g.

Synthesis of newer substituted chalcone linked 1,2,3-triazole analogs and evaluation of their cytotoxic activities

Abstract An innovative heterocyclic biologically active chalcone 1,2,3-triazole analogs (6a–j) were prepared to extract excellent yields by coupling the substituted aryl azides (5a–5j) and 5-ethynyl-1,2,3-trimethoxybenzene, by using the method of Huisgen azide–alkyne cycloaddition. The typically synthesized analogs were elucidated by IR, 1H-nuclear magnetic resonance (NMR), 13C-NMR, and Electron spray ionization (ESI)-mass spectroscopy and tested for their cytotoxicity effectiveness in MTT assays against the A549 lung cancer cells. The cytotoxic studies suggested that a few analogs showed moderate to good activities. The compounds 6i and 6c showed low cytotoxicity against the A549 cell line among 12 analogs, the values of IC50 were displayed in the range of 65.05 ± 1.12 and 71.56 ± 1.29 µM, respectively. The compound 6j showed slightly less cytotoxicity but showed good selectivity against A549 cell lines.

Pharmacokinetic Analysis of Diosgenin in Rat Plasma by a UPLC-MS/MS Approach.

Diosgenin, a steroidal sapogenin, has attracted attention worldwide owing to its pharmacological properties, including antitumor, cardiovascular protective, hypolipidemic, and anti-inflammatory effects. The current diosgenin analysis methods have the disadvantages of long analysis time and low sensitivity. The aim of the present study was to establish an efficient, sensitive ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach for pharmacokinetic analysis of diosgenin amorphous solid dispersion (ASD) using tanshinone IIA as an internal standard (IS). Male Sprague-Dawley rats were orally administered diosgenin ASD, and orbital blood samples were collected for analysis. Protein precipitation was performed with methanol-acetonitrile (50 : 50, v/v), and the analytes were separated under isocratic elution by applying acetonitrile and 0.03% formic acid aqueous solution at a ratio of 80 : 20 as the mobile phase. MS with positive electron spray ionization in multiple reaction monitoring modes was applied to determine diosgenin and IS with m/z 415.2⟶271.2 and m/z 295.2⟶277.1, respectively. This approach showed a low limit of quantification of 0.5 ng/ml for diosgenin and could detect this molecule at a concentration range of 0.5 to 1,500 ng/ml (r = 0.99725). The approach was found to have intra- and inter-day precision values ranging from 1.42% to 6.91% and from 1.25% to 3.68%, respectively. Additionally, the method showed an accuracy of -6.54 to 4.71%. The recoveries of diosgenin and tanshinone IIA were 85.81–100.27% and 98.29%, respectively, with negligible matrix effects. Diosgenin and IS were stable under multiple storage conditions. Pharmacokinetic analysis showed that the Cmax and AUC0⟶t of diosgenin ASD were significantly higher than those of the bulk drug. A sensitive, simple, UPLC-MS/MS analysis approach was established and used for the pharmacokinetic analysis of diosgenin ASD in rats after oral administration.

Fractionation and characterization of mucilage from Basil (Ocimum basilicum L.) seed

The study characterized physicochemical properties of basil seed mucilage (BSM) and the significance of research is discussed in context to exploit its polysaccharide nature for nutrition, food, and pharmaceutical applications. BSM was extracted, purified, and further fractionated to elaborate its biopolymer structure. Chemical analysis ascertained a decrease in impurities (protein, minerals, and alkaloids) after purification. Phytochemical behavior elucidated bioactivity due to presence of flavonoids. Uronic acid indicated polyelectrolyte behavior and polysaccharide fractions from BSM differed notably in monomer abundances and glycosidic linkages. BSM was extracted (BSM-20.49 % yield) and purified by alcoholic precipitation into basil seed gum-BSG (18.75 % yield). BSG was further fractionated into alcohol-insoluble fraction-F1 (13.70 % yield), alcohol-soluble fraction-F2 (6.80 % yield), and protein-free fraction-F3 (18.50 % yield). Colorimetric ‘L’ values (37.0–50.84) indicated light color. Bulk density (0.15–0.45 g/mL), wettability (0.06–3.5 min), solubility (3–30 %), antioxidant activity (27.01 %), polyphenols (11.76 mg GAE/100 g), and flavonoids (0.19 mg QE/100 g) were observed. BSM exhibited polyelectrolyte nature (3.10 % uronic acid) with 77.66 % carbohydrates. Fourier transform infrared spectroscopy (FTIR) revealed low intensity of hydroxyl and amide bond in F3. Electron spray-ionization Time-of-flight Mass spectrometry analysis (ESI-MS-TOF) showed presence of uronic acids, glycosidic linkages, and monomeric units (mannose, glucose, galactose, arabinose). X-Ray diffraction (XRD) revealed crystalline behavior of F3. The results give a better understanding of its potential use as a promising hydrocolloid in food and pharmaceutical applications.

3-Methoxy-5-methyl-12-phenylbenzacridinium Iodide

N-alkylacridinium derivatives are some of the most popular azo dye templates. Herein, we report the synthesis of 3-methoxy-5-methyl-12-phenylbenzacridinium iodide (MMPBAI) via N-alkylation. The structure of MMPBAI was elucidated using 1H Nuclear magnetic resonance (NMR), 13C NMR, Electronspray ionization mass spectrometry (ESI-MS), and Fourier-transform infrared spectroscopy (FT-IR). MMPBAI could not visualize double-stranded DNA in agarose gel, although the structural core would still be interesting as a template for new azo dyes.

A unique ternary Ce(III)-quercetin-phenanthroline assembly with antioxidant and anti-inflammatory properties

Quercetin is one of the most bioactive and common dietary flavonoids, with a significant repertoire of biological and pharmacological properties. The biological activity of quercetin, however, is influenced by its limited solubility and bioavailability. Driven by the need to enhance quercetin bioavailability and bioactivity through metal ion complexation, synthetic efforts led to a unique ternary Ce(III)-quercetin-(1,10-phenanthroline) (1) compound. Physicochemical characterization (elemental analysis, FT-IR, Thermogravimetric analysis (TGA), UV–Visible, NMR, Electron Spray Ionization-Mass Spectrometry (ESI-MS), Fluorescence, X-rays) revealed its solid-state and solution properties, with significant information emanating from the coordination sphere composition of Ce(III). The experimental data justified further entry of 1 in biological studies involving toxicity, (Reactive Oxygen Species, ROS)-suppressing potential, cell metabolism inhibition in Saccharomyces cerevisiae (S. cerevisiae) cultures, and plasmid DNA degradation. DFT calculations revealed its electronic structure profile, with in silico studies showing binding to DNA, DNA gyrase, and glutathione S-transferase, thus providing useful complementary insight into the elucidation of the mechanism of action of 1 at the molecular level and interpretation of its bio-activity. The collective work projects the importance of physicochemically supported bio-activity profile of well-defined Ce(III)-flavonoid compounds, thereby justifying focused pursuit of new hybrid metal-organic materials, effectively enhancing the role of naturally-occurring flavonoids in physiology and disease.

Novel trans iodo(2-(N-alkylsulfamoyl)phenyl)bis(-triphenylphosphine palladium) complexes: Synthesis, mass spectrometry, X-ray structural description, steric map, near infrared analyses and catalytic activities evaluation

2-iodo-N-ethylbenzenesulfonamide and 2-iodo-N-isopropylbenzenesulfonamide are used to prepare two novel palladium(II) complexes (4 and 5) by oxidative addition starting from Pd(PPh3)4. The desired complexes are fully characterized by 1H, 13C, 31P NMR and near infrared spectroscopy. Electron spray ionization mass spectrometry analyses showed identical fragmentation process of the complexes starting by the iodine cleavage. The molecular structures of the complexes 4 and 5 are confirmed by X-ray diffraction analysis. The crystal packing of these complexes are stabilized by the presence of hydrogen bonds established between oxygen and hydrogen atoms of the sulfonamide groups. In addition, Hirshfeld surface mapped over dnorm, Shape index and molecular electrostatic potential were used to describe the short interactions and electron reach domains. The analyses of molecular fingerprints reveal similar percentage of H···H (∼67%), H···C/C···H (∼23%), H···I/I···H (∼5%) and H···O/O···H (∼4.5%) contacts in 4 and 5. The valuation of the percentage of buried volume (%VBur) of these ligands shows that the N-ethyl- and N-isopropylbenzenesulfonamide substituents took around 30% share of the palladium coordination sphere. Finally, the catalytic activities of these new palladium complexes are evaluated in cyclopropanation of styrene and in atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA). The results showed that trans cyclopropane was obtained as major product independently to the tested catalyst. In polymerization reaction, the catalysts show moderate activity and did not induce a controlled polymerization of MMA.

A screening method for binding synthetic metallo-complexes to haem proteins

The introduction of a second coordination sphere, in the form of a protein scaffold, to synthetic catalysts can be beneficial for their reactivity and substrate selectivity. Here we present semi-native polyacrylamide gel electrophoresis (semi-native PAGE) as a rapid screening method for studying metal complex-protein interactions. Such a screening is generally performed using electron spray ionization mass spectrometry (ESI-MS) and/or UV–Vis spectroscopy. Semi-native PAGE analysis has the advantage that it does not rely on spectral changes of the metal complex upon protein interaction and can be applied for high-throughput screening and optimization of complex binding. In semi-native PAGE non-denatured protein samples are loaded on a gel containing sodium dodecyl sulphate (SDS), leading to separation based on differences in structural stability. Semi-native PAGE gel runs of catalyst-protein mixtures were compared to gel runs obtained with native and denaturing PAGE. ESI-MS was additionally realised to confirm protein-complex binding. The general applicability of semi-native PAGE was investigated by screening the binding of various cobalt- and ruthenium-based compounds to three types of haem proteins.

Bulky Thiolate-Protected Silver Nanocluster Ag 213 (Adm-S) 44 Cl 33 with Excellent Electrocatalytic Performance toward Oxygen Reduction

Bulky Thiolate-Protected Silver Nanocluster Ag ₂₁₃ (Adm-S) ₄₄ Cl ₃₃ with Excellent Electrocatalytic Performance toward Oxygen Reduction

Pharmacokinetics of tectorigenin, tectoridi, irigenin, and iridin in mouse blood after intravenous administration by UPLC-MS/MS

Abstract Tectorigenin, tectoridin, irigenin, and iridin are the four most predominant compounds present in She Gan. She Gan has been used in traditional Chinese medicine because of its anti-inflammatory, hepatoprotective, anti-tumor, antioxidant, phytoestrogen-like properties. In this paper, a UPLC-MS/MS method was developed to measure the pharmacokinetics of tectorigenin, tectoridin, irigenin, iridin after intravenous administration in mice. A UPLC BEH C18 (50 mm × 2.1 mm, 1.7 μm particle size) chromatographic column was utilized for separation of the four target analytes and internal standard (IS), and the analysis of blood plasma samples; the mobile phase consisted of an acetonitrile-water (w/0.1% formic acid) gradient elution. Electron spray ionization (ESI) positive-ion mode and multiple reaction monitoring (MRM) mode was used for quantitative analysis of the analytes and internal standard. The four compounds were administered intravenously (sublingual) at doses of 5 mg/kg. After blood sampling, samples were processed and then analyzed by UPLC-MS/MS. The linearity of the method was robust over the concentration range of 2–5,000 ng/mL. The intra-day precision of the analysis was within 15%, the inter-day precision was within 12%, and the accuracy was between 92% and 110%. The recoveries were 65–68%, and the matrix effect was 93–109%. The established UPLC-MS/MS detection method was then successfully applied to study the pharmacokinetics of tectorigenin, tectoridin, irigenin, iridin in mice.

Liquid extraction surface analysis-mass spectrometry: An advanced and environment-friendly analytical tool in modern analysis.

The liquid extraction surface analysis technique is a new high-throughput instrument for ambient mass spectrometry. The benefits of the liquid extraction surface analysis-mass spectrometry approach are the high throughput screening of samples and the absence of sample preparation. liquid extraction surface analysis-mass spectrometry also consumes less solvent for extraction, making it more environmentally friendly and there is no substrate restriction. It utilizes advanced instrumentation like the use of robotic pipettes, nanoelectrospray systems, electronspray ionization chips which makes it highly efficient. In recent years, liquid extraction surface analysis-mass spectrometry has seen widespread use in a variety of analytical fields including drug metabolite analysis, mapping drug distribution in tissues, protein and lipid characterization, etc. In this review, we have summarized the basic working principles of the liquid extraction surface analysis-mass spectrometry approach in detail along with a detailed description of the recently reported applications in the analysis of proteins, lipids, drugs and foods. The investigated analytes along with detection methodologies and significant outcomes of various research reports have been presented with the help of tables. This tool has also been utilized in clinical investigations of biological fluids, fingerprint analysis and authentication of agarwood.

Multi-component self-assembled heteroleptic Cu(I) complex with defective coordination site as a fluorescent probe to detect Zn2+

Heteroleptic copper(I)–phosphine complexes have attracted considerable attention due to their diverse structures and photophysical properties. In this work, a novel heteroleptic binuclear copper (I) complex C1·2BF4ˉ was designed and synthesized by using hexaazatriphenylene (L1) and 4, 5-Bis(diphenylphosphino)-9, 9-dimethylxanthene (dppd) as functional ligands. Such dinuclear structure with defective site was fully characterized by NMR, single-crystal X-ray diffraction analysis, and electron spray ionization mass spectrometry (ESI-MS). UV-vis and fluorescence spectrum revealed that the well-defined Cu(I) complex had a green emission at 518 nm in acetonitrile solution, and a red emission at 824 nm in the solid state. The DFT calculation demonstrated that the energy gap between LUMO and HOMO orbitals reached 1.20 eV. Furthermore, such heteroleptic Cu(I) complex showed high sensitivity and selectivity towards Zn2+ in acetonitrile solution in “turn-on” mode, which can be attributed to the coordination interaction between Zn2+ and defective binding site of probe C1·2BF4−. The LOD for Zn2+ was calculated to be 0.298 µM, and the reversible “on-off” fluorescence sensing behavior can be recovered by alternative treatment with EDTA tetrasodium and Zn2+ salts in solution. The Cu(I) complex probe C1·2BF4ˉ had reversible redox property with weak electrochemical responses towards Zn2+ ions.

Lignans and Other Compounds From the Roots of Pandanus tonkinensis and Their Lipid Peroxidation Inhibitory Activity

A new phenylpropane (1) and 9 known (2-10) compounds were isolated from the methanol extract of Pandanus tonkinensis roots. Their chemical structures were determined as (7 S)-2,6-dimethoxyphenyl-7,9-propanediol-1 -O-β-D-glucopyranoside (1), isorhapontigenin (2), pinoresinol-4,4′-di -O-β-D-glucoside (3), isoeucommin A (4), pinoresinol-4′ -O-β-D-glucoside (5), acanthoside B (6), eucommin A (7), urolignoside (8), benzyl O-α-L-arabinopyranosyl-(1→6) -β-D-glucopyranoside (9), and (6 S,9 S)-roseoside (10) by comprehensive analysis of high-resolution electron spray ionization mass spectrum and nuclear magnetic resonance spectral data, as well as by comparison of their spectral data with those reported in the literature. In addition, the stereochemistry of 1 was successfully determined by both theoretical and calculated CD spectra. All the isolates were tested for their lipid peroxidation inhibitory effects by in vitro assay. Compounds 2-7 exhibited significantly lipid peroxidation inhibitory effects with IC50 values of 21.3 ± 1.7, 61.9 ± 3.9, 57.5 ± 5.5, 10.4 ± 0.7, 28.9 ± 0.3, 54.2 ± 3.5 µM, respectively, compared to that of the positive control, trolox (31.4 ± 2.2 µM).

Elevated concentration and high Diversity of organophosphate esters (OPEs) were Discovered in Sediment from Industrial, and E-Waste Recycling Areas

Aquatic environments in industrial, and e-waste recycling areas might undergo severe contamination; however, there are few studies comprehensively assessing the pollution status of organophosphate esters (OPEs) in these two areas. Here, we applied both atmospheric pressure chemical ionization (APCI) and electron spray ionization (ESI) sources in our target, suspect, and functional group-dependent screening strategy, which enhanced the confidence for confirmation on precursor ions of OPEs. Then, n=53 sediment samples (30 from the industrial area, and 23 from the e-waste recycling area) were analyzed. Twenty-three out of 30 target OPEs were quantifiable in these analyzed samples. Total OPE concentrations (Σ30OPEs) in samples from e-waste recycling area range from 12.8 to 9250 ng/g dry weight (dw), that are statistically significantly greater (t-test, p < 0.001) than those from industrial area (25.1-5520 ng/g dw). Σ30OPEs in the sediments from industrial, or e-waste recycling area are statistically significantly greater (one-way ANOVA, p < 0.001) as compared to those (32.0-369 ng/g dw) from Taihu Lake in our previous study. In sediment from three areas, suspect and non-target analysis fully or tentatively identified other 20 OPEs. Four of them have not been recorded or registered in any of online chemical databases, and they are tentatively named as ((methoxy(phenoxy)phosphoryl)oxy)phenyl diphenyl phosphate (mPPODP), (tert-butyl)phenyl (ethyne-oxidane) bis(2,4-di-tert-butylphenyl) phosphate (TPBDTP), bis(dichlorophenyl) propane-1,3-diyl bis(hexylated phosphate) (BDCBHP), and bis(2-hexadecoxyethyl) ethyl phosphate (BHEPP). Overall, this study provided new insights regarding both analytical methodology and pollution status of OPEs, and highlights that elevated concentrations and high diversity of OPEs exist in sediments from industrial, and e-waste recycling areas.

Sera Protein Signatures of Endometrial Cancer Lymph Node Metastases.

The presence of lymph node metastases in endometrial cancer patients is a critical factor guiding treatment decisions; however, surgical and imaging methods for their detection are limited by morbidity and inaccuracy. To determine if sera can predict the presence of positive lymph nodes, sera collected from endometrial cancer patients with or without lymph node metastases, and benign gynecology surgical patients (N = 20 per group) were subjected to electron spray ionization mass spectrometry (ES-MS). Peaks that were significantly different among the groups were evaluated by leave one out cross validation (LOOCV) for their ability to differentiation between the groups. Proteins in the peaks were identified by MS/MS of five specimens in each group. Ingenuity Pathway Analysis was used to predict pathways regulated by the protein profiles. LOOCV of sera protein discriminated between each of the group comparisons and predicted positive lymph nodes. Pathways implicated in metastases included loss of PTEN activation and PI3K, AKT and PKA activation, leading to calcium signaling, oxidative phosphorylation and estrogen receptor-induced transcription, leading to platelet activation, epithelial-to-mesenchymal transition and senescence. Upstream activators implicated in these events included neurostimulation and inflammation, activation of G-Protein-Coupled Receptor Gβγ, loss of HER-2 activation and upregulation of the insulin receptor.

Synthesis of α-Hydroxy Acids via Dehydrogenative Cross-Coupling of a Sustainable C2 Chemical (Ethylene Glycol) with Alcohols.

Ir(NHC) (NHC, N-heterocyclic carbene)-catalyzed dehydrogenative coupling of sustainable ethylene glycol and various bioalcohols can produce industrially valuable α-hydroxy acids (AHAs). This study is the first to report the sustainable synthesis of higher Cn AHAs, in addition to glycolic acid (C2 AHA) and lactic acid (C3 AHA). This catalytic system can be recycled to the seventh cycle while maintaining good yields. A reaction mechanism, including facile dehydrogenation of each alcohol and fast cross-coupling of dehydrogenated aldehydes forming products, was proposed based on 18O- and 2H-labeling experiments and electron spray ionization-mass spectrometry (ESI-MS) and NMR spectral analyses.

Quantitation of Diclofenac, Tolbutamide, and Warfarin as Typical CYP2C9 Substrates in Rat Plasma by UPLC-MS/MS and Its Application to Evaluate Linderane-Mediated Herb-Drug Interactions.

Linderane (LDR), the main active and distinctive component of L. aggregate, is a mechanism-based inactivator of CYP2C9 in vitro, indicating the occurrence of herb-drug interactions. However, little is known about the changes of the pharmacokinetic properties of the common clinical drugs as CYP2C9 substrates after coadministration with LDR. In this study, a selective and rapid ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for the determination of diclofenac, tolbutamide, and warfarin as CYP2C9 substrates in rat plasma has been developed. Chlorzoxazone was employed as an internal standard (IS), and protein precipitation was used for sample preparation. Chromatographic separation was achieved on a UPLC BEH-C18 (2.1 × 50 mm, 1.7 µm) with 0.1% (v:v) formic acid in water (A) and acetonitrile (B) as the mobile phase with gradient elution. The total run time was only 3.8 min. MS analysis was performed under multiple reaction monitoring (MRM) with electron spray ionization (ESI) operated in the negative mode. The bioanalytical method was validated, and the selectivity, carryover effects, linearity, precision, accuracy, matrix effect, extraction recovery, and stability were acceptable. The validated method was then successfully applied for evaluating the potential pharmacokinetic interactions when LDR was used along with diclofenac, tolbutamide, and warfarin, respectively. Results showed that the Cmax of diclofenac in the treated group was 1287.82 ± 454.16 μg/L, which was about 5-fold of that in the control group (P < 0.01). The Cmax of tolbutamide in the treated group was 60.70 ± 10.70 mg/L, which was significantly decreased by about 25% when compared with the control group (P < 0.01). The Vd of warfarin in the treated group was obviously increased, which was about 1.4-fold of that in the control group (P < 0.01).