silverdonna80
silverdonna80
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Gene silencing induced by RNAi represents a promising antiviral development strategy. This review will summarise the current state of RNAi therapeutics for treating acute and chronic human virus infections. The gene silencing pathways exploited by RNAi therapeutics will be described and include both classic RNAi, inducing cytoplasmic mRNA degradation post-transcription and novel RNAi, mediating epigenetic modifications at the transcription level in the nucleus. Finally, the challenge of delivering gene modifications via RNAi will be discussed, along with the unique characteristics of respiratory versus systemic administration routes to highlight recent advances and future potential of RNAi antiviral treatment strategies.The application of the Quality by Design (QbD) principles in developing a new ultra high performance liquid chromatography method for the analysis of formoterol/budesonide and related substances using Fusion QbD® software is explored. The effect of various chromatographic parameters including, column stationary phase, pH, temperature, flow rate, and gradient time on separations were systematically investigated. Results show that optimal separations of these compounds in a standard solution can be achieved using a BEH C18 column (2.1 × 1.7 μm × 10 cm) applying a pH of 8.2, a temperature of 35 °C, a flow rate of 0.35 mL min-1 and a gradient time of 25 min. Furthermore, the results show that the main parameters affecting the performance of the method were the mobile phase pH, gradient time, and the temperature. For example, the most important factor for peak tailing was the pH of the mobile phase and the critical factors affecting resolution of the analytes were the gradient time and the temperature. As an application, the method was further used to analyze budesonide and formoterol in a sample obtained from a Symbicort® metered dose inhaler and it was found to provide similar separations to those obtained with the standard solution. These findings indicate that applying the QbD principles in analytical method development can be very advantageous not only in obtaining deep understanding of the effect of input parameters but also potential regulatory flexibility.Ginseng has been used for prevention and treatment of disease for thousands of years in China and many other Asian countries. Phytochemical studies have indicated that ginsenosides, polysaccharides, alkaloids, and phenolic acids are the active constituents of ginseng. Main and branch roots of ginseng exhibit distinct bioactive behavior. Furthermore, the bioactive behavior of ginseng depends on its age. Traditional analysis is complex preparation and provides inadequate of chemical information of the original distribution of analytes. Therefore, in this study, ultraperformance liquid chromatography quadrupole/time of flight-mass spectrometry (UPLC-QTOF MS) and desorption electrospray ionization mass spectrometry imaging (DESI-MSI) combined with orthogonal partial least squares discriminant analysis were used to discriminate ginseng in different age and parts of ginseng, and profiled distribution of selected markers. The results indicated that UPLC-QTOF-MS and DESI-MSI could be used to determine the parts and age of ginseng. Fifteen variables including five of protopanaxatriol (PPT), four of protopanaxadiol (PPD), and six of other types were assumed as markers for different parts of ginseng. Moreover, four variables of PPT, four of PPD, and ten of other types were used to determine the age of ginseng samples. An analysis of localization of markers indicated that malonyl ginsenoside, including malonyl-ginsenoside Rb1, Rb2, Rc, and Rd was mainly distributed in the corks. Neutral ginsenoside Rg1, yesanchinoisde D, and chikusetsusaponin Iva were mainly distributed in the cork and phloem. Non-ginsenoside castanoside H, 20(S)-protopanaxatriol, unknown 2, saponin III and cistanoside C were distributed in all tissues. Ethyloleate, unknown 1 and monolinolein were distributed in the cork.Huanglong cough oral liquid (HL), an important traditional Chinese medicine prescription for treating pediatric cough variant asthma (CVA) in Nanjing hospital of traditional Chinese medicine for many years. In this study, a selective, accurate and sensitive ultra fast liquid chromatography extreme resolution coupled with mass spectrometer (UFLC-MS/MS) method was established and validated for the simultaneous determination of nine constituents including morusin, ephedrine, praeruptorin A, praeruptorin B, luteolin, rosmarinic acid, quercetin, amygdalin, caffeic acid in CVA rat plasma sensitized and challenged with ovalbumin and cinnamaldehyde. Plasma samples were prepared by protein precipitation with four-fold amount of methanol. UFLC separation was performed on a Thermo Scientific AcclaimTM RSLC 120 C18 column (2.1 mm × 100 mm, 2.2 μm) with mobile phase containing methanol and 0.1% formic acid-water by gradient elution in 8.1 min at total flow of 0.3 mL/min. The determination of target compounds in plasma was operated by multiple reaction monitoring (MRM) mode with positive and negative electrospray ionization (ESI) source. The correlation coefficients (r) of all compounds were from 0.9930 to 0.9994 in the linear range. Lower limit of quantification (LLOQ, ng/mL) was 0.81, 2.01, 2.11, 1.17, 1.04, 0.89, 0.67, 1.45 and 0.59 for morusin, ephedrine, praeruptorin A, praeruptorin B, luteolin, rosmarinic acid, quercetin, amygdalin and caffeic acid, respectively. Intra- and inter-day accuracy and precision, extraction recovery, matrix effect, carryover effect, dilution integrity, and stability were within the limits specified. The established method was effectively applied to a pharmacokinetic study of the nine compounds in CVA rat plasma following oral administration HL exact (7.5, 15, 30 g/kg).Fibromyalgia is characterized by the amplification of central nervous system pain with concomitant fatigue, sleep, mood disorders, depression, and anxiety. It needs extensive pharmacological therapy. In the present study, Swiss mice were treated with reserpine (0.25 mg/kg, s.c.) over three consecutive days, in order to reproduce the pathogenic process of fibromyalgia. https://www.selleckchem.com/products/a2ti-1.html On day 4, the administrations of the Tx3-3 toxin produced significant antinociception in the mechanical allodynia (87.16% ±12.7%) and thermal hyperalgesia (49.46% ± 10.6%) tests when compared with the PBS group. The effects produced by the classical analgesics (duloxetine 30 mg/kg, pramipexole 1 mg/kg, and pregabalin 30 mg/kg, p.o., respectively) in both of the tests also demonstrated antinociception. The administrations were able to increase the levels of the biogenic amines (5-HTP and DE) in the brain. The treatments with pramipexole and pregabalin, but not duloxetine, decreased the immobility time in the FM-induced animals that were submitted to the forced swimming test; however, the Tx3-3 toxin (87.

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