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Silver nanoparticles (AgNPs) have been widely used in a variety of biomedical applications. Previous studies demonstrated that AgNPs significantly enhanced bone cell mineralization and differentiation in MC3T3-1 cells, a model in vitro system, when compared to several other NPs. This increased bone deposition was evaluated by phenotypic measurements and assessment of the expression of miRNAs associated with regulation of bone morphogenic proteins. In the present study, we used RNA-seq technology, a more direct measurement of gene expression, to investigate further the mechanisms of bone differentiation induced by AgNP treatment. Key factors associated with the osteoclast pathway were significantly increased in response to AgNP exposure including Bmp4, Bmp6 and Fosl1. In addition, genes of metabolism and toxicity pathways were significantly regulated as well. Although this study suggests the potential for AgNPs to influence bone morphogenesis in injury or disease applications, further investigation into the efficacy and safety of AgNPs in bone regeneration is warranted. [ABSTRACT FROM AUTHOR]

1. As a potential new drug candidate for cardiovascular protection and antitumor treatment, the physicochemical properties, gastrointestinal (GI) absorption behaviors and mechanisms of S-propargyl-cysteine (SPRC) were investigated in this study. 2. SPRC exhibited favorable solubility in aqueous media. The log P and log D values were low (≤1.93 ± 0.08). The p Ka in the acidic and basic regions was 2.08 ± 0.02 and 8.72 ± 0.03, respectively. The isoelectric point was 5.40 ± 0.02. SPRC was stable in the rat GI fluids, and showed no obvious adsorption and metabolism in the rat GI tract. 3. SPRC displayed poor gastric absorption and favorable intestinal absorption in the rat in situ GI perfusion model. Absorption rate constants ( ka), hourly absorption percentage ( P) and apparent permeability coefficient ( Papp) of SPRC in the small intestine were ≥0.77 ± 0.06 h−1, 59.25 ± 4.02% and (7.99 ± 0.88) × 10−5 cm/s, respectively. Absorption of SPRC exhibited a certain dependence on physiological pH and absorption region. Absorption of SPRC was not inhibited by l-methionine and 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid. 4. SPRC showed favorable oral absorption. It can be categorized as a BCS class I drug. The membrane pore transport appeared to be one of the predominant absorption modes for SPRC. [ABSTRACT FROM AUTHOR]

ABSTRACT Leonurine (SCM-198), an alkaloid from Herba Leonuri, has been suggested as a novel cardiovascular agent by pharmacology studies in preclinical stage. In present study, we report a simple, rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry method (HPLC-MS/MS) for determination of leonurine in rat plasma. Leonurine and its internal standard (IS) n-benzoyl- l-arginine ethyl ester (BAEE) were extracted from plasma samples by one-step protein precipitation with perchloric acid. Chromatographic separation was performed on an Agilent Zorbax SB-C18 column (150 × 2.1 mm, 5 µm) using an isocratic elution with acetonitrile-ammonium acetate buffer (10 m m, pH 4.0; 25:75, v/v) as mobile phase at a flow rate of 0.2 mL/min. Analytes were detected by tandem mass spectrometry in positive electrospray ionization (ESI) mode using multiple reaction monitoring (MRM) with the transitions of m/ z 312.3 → 181.1 for leonurine and m/ z 307.2 → 104.6 for IS. The calibration curves were linear over the range of 4-256 ng/mL with a lower limit of quantitation (LLOQ) of 4 ng/mL. The intra- and inter-day assay precision (as relative standard deviation) were <15%, except which at LLOQ were <20%, with accuracy in the range 98.73-105.42%. The validated HPLC-MS/MS method was successfully applied to the pharmacokinetic study in rats following oral administration of leonurine. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

As a novel hydrogen sulfide-modulated agent, S-propargyl-L-cysteine (SPRC) is proven to be a potent cardioprotective candidate. Bioavailability and pharmacokinetics of SPRC (20 mg/kg) in beagle dogs after oral and intravenous administrations were investigated in this study. Plasma concentrations of SPRC were measured by a LC-MS/MS method. Intravenous administration of SPRC (single dose) to beagle dogs gave a mean plasma half-life of 14.7 h, mean clearance of 0.4 ml min−1 kg−1 and mean apparent volume of distribution of 0.56 L/kg. Single oral administration was completely, fast absorbed (Tmax= 0.33 ± 0.20 h) with a mean absolute availability of 112% and mean plasma half-life of 16.5 h. Multiple oral administration (once daily for 10 consecutive days) of SPRC to dogs resulted in steady state plasma drug concentration being reached after seven doses and didn't cause obvious accumulation. No significant difference was found between the single and multiple pharmacokinetic parameters. [ABSTRACT FROM AUTHOR]

P 2 -type Ca 2+ ATPases are responsible for cellular Ca 2+ transport, which plays an important role in plant development and tolerance to biotic and abiotic stresses. However, the role of P 2 -type Ca 2+ ATPases in stress response and stomatal regulation is still elusive in soybean. In this study, a total of 12 P 2 -type Ca 2+ ATPases genes ( GmACAs and GmECAs ) were identified from the genome of Glycine max . We analyzed the evolutionary relationship, conserved motif, functional domain, gene structure and location, and promoter elements of the family. Chlorophyll fluorescence imaging analysis showed that vegetable soybean leaves are damaged to different extents under salt, drought, cold, and shade stresses. Real-time quantitative PCR (RT-qPCR) analysis demonstrated that most of the GmACAs and GmECAs are up-regulated after drought, cold, and NaCl treatment, but are down-regulated after shading stress. Microscopic observation showed that different stresses caused significant stomatal closure. Spatial location and temporal expression analysis suggested that GmACA8, GmACA9, GmACA10, GmACA12, GmACA13 , and GmACA11 might promote stomatal closure under drought, cold, and salt stress. GmECA1 might regulate stomatal closure in shading stress. GmACA1 and GmECA3 might have a negative function on cold stress. The results laid an important foundation for further study on the function of P 2 -type Ca 2+ ATPase genes GmACAs and GmECAs for breeding abiotic stress-tolerant vegetable soybean., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Fu, Zhang, Chen, Li, Shangguan, Zheng, Xu, Chen and Xu.)

The lack of samples for generating standardized DNA datasets for setting up a sequencing pipeline or benchmarking the performance of different algorithms limits the implementation and uptake of cancer genomics. Here, we describe reference call sets obtained from paired tumor-normal genomic DNA (gDNA) samples derived from a breast cancer cell line-which is highly heterogeneous, with an aneuploid genome, and enriched in somatic alterations-and a matched lymphoblastoid cell line. We partially validated both somatic mutations and germline variants in these call sets via whole-exome sequencing (WES) with different sequencing platforms and targeted sequencing with >2,000-fold coverage, spanning 82% of genomic regions with high confidence. Although the gDNA reference samples are not representative of primary cancer cells from a clinical sample, when setting up a sequencing pipeline, they not only minimize potential biases from technologies, assays and informatics but also provide a unique resource for benchmarking 'tumor-only' or 'matched tumor-normal' analyses., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Leonurine, a major bioactive component from Herba Leonuri, shows therapeutic potential for cardiovascular disease and stroke prevention in some preclinical experiments. The aim of this study is to characterize metabolites of leonurine in rats using high performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS). The chromatographic separation was performed on an Agilent ZORBAX SB-C18 column using a gradient elution with acetonitrile/ammonium acetate buffer (10 mM, pH 4.0) solvent system. An information dependent acquisition (IDA) method was developed for screening and identifying metabolites of leonurine under positive ion mode. Compared with control, the interesting compound in the extracted ion chromatogram (XIC) of the in vivo samples was chosen and further identified by analyzing their retention times, changes in observed mass (Δm/z), and spectral patterns of product ion utilizing advanced software tool. For the first time, a total of three metabolites were identified, including two phase II metabolites generated by glucuronidation (M1) and sulfation (M2) and one phase I metabolite formed by O-demethylation (M3). Finally, the lead metabolite M1 was isolated from urine and its structure was characterized as leonurine-10-O- β-D-glucuronide by NMR spectroscopy (¹H, ¹³C, HMBC, and HSQC).