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The Biological Clues about the particular Inclination towards Flu Contamination throughout Jr Rodents by simply Comprehensive Evaluation of lncRNA Information.
Serotonin (5-hydroxytryptamine, 5-HT) is readily secreted in patients with carcinoid tumors, especially arising from the midgut. Although serotonin assay in human plasma or whole blood has been extensively studied, serotonin assay in human serum by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has received much less attention. In this study, a simple and reliable LC-MS/MS method based on one step protein precipitation for sample pretreatment was developed for clinical assay of serum serotonin. Namely, 150 μL of serum was mixed with 50 μL of internal standard (IS) and 200 μL of 4 wt.% 5-sulfosalicylic acid (SSA) solution for protein precipitation. The supernatant after centrifugation was analyzed directly without further treatment. This method was validated for consistent linearity from 0.94 to 240 ng/mL with CVs ≤ 11.7%, good recovery in the range of 87.5%-104%, excellent analyte stability and low carryover. No obvious matrix effect was observed. Intra- and inter-day imprecision were below 8.03% and 11.5% respectively. Dilution linearity was verified with satisfying linearly dependent coefficients (r2 = 0.9937). The reference interval of serotonin was established from 126 results derived from subjects without carcinoid tumors. Halofuginone Therefore, apart from development of a serum serotonin assay by the LC-MS/MS method, the reference interval (RI) of 5-HT has also been established for clinical testing in patients with carcinoid tumors. In addition, this method has been successfully used in our laboratory, indicating that this robust LC-MS/MS assay with simple sample preparation and short analysis time could offer inspiring potential for clinical testing of 5-HT in routine clinical laboratories.Treatment of multidrug-resistant tuberculosis (MDR-TB) is challenging due to high treatment failure rate and adverse drug events. This study aimed to develop and validate a simple LC-MS/MS method for simultaneous measurement of five TB drugs in human plasma and to facilitate therapeutic drug monitoring (TDM) in MDR-TB treatment to increase efficacy and reduce toxicity. Moxifloxacin, levofloxacin, prothionamide, pyrazinamide and ethambutol were prepared in blank plasma from healthy volunteers and extracted using protein precipitation reagent containing trichloroacetic acid. Separation was achieved on an Atlantis T3 column with gradient of 0.1% formic acid in water and acetonitrile. Drug concentrations were determined by dynamic multiple reaction monitoring in positive ion mode on a LC-MS/MS system. The method was validated according to the United States' Food and Drug Administration (FDA) guideline for bioanalytical method validation. The calibration curves for moxifloxacin, levofloxacin, prothionamide, pyraziod is robust and sample preparation is simple, it can easily be implemented to facilitate TDM in programmatic MDR-TB treatment.Residue chemists who analyse pesticides in vegetables or veterinary drugs in animal-based food are currently facing a situation where there is a requirement to detect more and more compounds at lower and lower concentrations. Conventional tandem quadrupole instruments provide sufficient sensitivity, but speed and selectivity appear as future limitations. This will become an even larger issue when there is a need to not only detect active compounds but also their degradation products and metabolites. This will likely lead to a situation in which the conventional targeted approach must be expanded or augmented by a certain non-targeted strategy. High-resolution mass spectrometry provides such capabilities, but it frequently requires an additional degree of selectivity for the unequivocal confirmation of analytes present at trace levels in highly complex and variable food matrices. The hyphenation of ultrahigh performance liquid chromatography with ion mobility and high-resolution mass spectrometry provides analytical chemists with a new tool for performing such a demanding multiresidue analysis. The objective of this paper is to investigate the benefits of the added ion mobility dimension as well as to critically discuss the current limitations of this commercially available technology.This study presents the development and validation of a fast and simple bioanalytical ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) method intended for quantifying the anti-inflammatory candidate 5'-methoxynobiletin (5'-MeONB) in rat plasma. Standard of 5'-MeONB was purified from A. conyzoides extract by using preparative HPLC. After a pretreatment of plasma samples with acetonitrile, chromatographic separations were efficiently achieved with a C18 column using a 9 min gradient system of 0.1% aqueous formic acid and acetonitrile as eluent. Drug candidate 5'-MeONB and chrysin (internal standard, IS) detection were carried out using ESI+ through the extracted ion chromatograms approach, monitored at m/z 433.1494 (for 5'-MeONB, tR1.78 min) and m/z 255.0657 (for IS, tR1.57 min). Method was validated according to US FDA guidelines, presenting linearity (R2 > 0.999) over concentration range of 30-750 ng/mL. Relative standard deviation (RSD) of repeatability and intermediary precision respectively ranged between 1.93-3.65% and 2.16-7.54%, considering lower limit of quantitation (30 ng/mL) and quality control (90, 360 and 600 ng/mL) samples, while accuracy was between 82.51 and 109.44%. Moreover, no interference from plasma endogenous substances, no carryover effect, and no influence of extraction method even in hemolyzed blood samples were observed. Sample stability in auto-sampler and long-term -80 °C storage, as well as matrix effect were within acceptable limits. For the first time, using the validated UPLC-MS bioanalytical method, the plasma pharmacokinetics of 5'-MeONB following 2 mg/kg intravenous bolus dosing to Wistar rats was characterized allowing the determination of the parameters describing drug distribution and elimination.The conjoining of salient pharmacophoric properties directing the development of prominent cytotoxic agents was executed by constructing thiadiazolo-carboxamide bridged β-carboline-indole hybrids. On the evaluation of in vitro cytotoxic potential, 12c exhibited prodigious cytotoxicity among the synthesized new molecules 12a-k, with an IC50 less then 5 μM in all the tested cancer cell lines (A549, MDA-MB-231, BT-474, HCT-116, THP-1) and the best cytotoxic potential was expressed in lung cancer cell line (A549) with an IC50 value of 2.82 ± 0.10 μM. Besides, another compound 12a also displayed impressive cytotoxicity against A549 cell line (IC50 3.00 ± 1.40 μM). Further target-based assay of these two compounds 12c and 12a revealed their potential as DNA intercalative topoisomerase-IIα inhibitors. Additionally, the antiproliferative activity of compound 12c was measured in A549 cells by traditional apoptosis assays revealing the nuclear, morphological alterations, and depolarization of membrane potential in mitochondria and externalization of phosphatidylserine in a concentration-dependent manner.
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