Quantitative determination of ondansetron in human plasma by enantioselective liquid chromatography-tandem mass spectrometry

A sensitive and enantioselective method was developed and validated for the determination of ondansetron enantiomers in human plasma using enantioselective liquid chromatography-tandem mass spectrometry. The enantiomers of ondansetron were extracted from plasma using ethyl acetate under alkaline conditions. HPLC separation was performed on an ovomucoid column using an isocratic mobile phase of methanol-5 mM ammonium acetate-acetic acid (20:80:0.02, v/v/v) at a flow rate of 0.40 mL/min. Acquisition of mass spectrometric data was performed in multiple reaction monitoring mode, using the transitions of m/z 294-->170 for ondansetron enantiomers, and m/z 285-->124 for tropisetron (internal standard). The method was linear in the concentration range of 0.10-40 ng/mL for each enantiomer using 200 microL of plasma. The lower limit of quantification (LLOQ) for each enantiomer was 0.10 ng/mL. The intra- and inter-assay precision was 3.7-11.6% and 5.6-12.3% for R-(-)-ondansetron and S-(+)-ondansetron, respectively. The accuracy was 100.4-107.1% for R-(-)-ondansetron and 103.3-104.9% for S-(+)-ondansetron. No chiral inversion was observed during the plasma storage, preparation and analysis. The method was successfully applied to characterize the pharmacokinetic profiles of ondansetron enantiomers in healthy volunteers after an intravenous infusion of 8 mg racemic ondansetron.     

麻类织物对须癣毛癣菌生长抑制作用的研究

目的通过分析汉麻、亚麻和苎麻对须癣毛癣菌生长的影响,探讨麻类织物对浅部真菌的抑制作用。方法实验采用振荡法。将3种麻类织物分别与须癣毛癣菌混合培养,对照组为棉布组,3d后分别取培养液稀释5倍后涂布培养皿,计算各自的菌落数和抑菌率并进行统计分析。结果麻类织物组菌落数明显少于对照组棉布组(P<0.01),3种麻类织物对须癣毛癣菌的抑菌率均高于60%,但3种麻类织物的抑菌率之间无明显差异(P<0.01)。结论3种麻类织物均可显著抑制须癣毛癣菌的生长,麻类织物有可能用来预防由须癣毛癣菌引起的足癣、股癣等浅部真菌病。     

Polycystin-1 induced apoptosis and cell cycle arrest in G0/G1 phase in cancer cells

Studies have shown that polycystin-1, encoded by PKD1, the major ADPKD, may have a central role in regulating both apoptosis and proliferation, which could prevent the malignant transformation of affected cells. However, as a putative tumor suppressor, direct studies on the possibility that polycystin-1 may play a role in cancer cells' biological properties have not yet been reported. We have demonstrated that the apoptosis of cancer cells was induced by overexpression of polycystin-1. After transfection with polycystin-1, three cancer cell lines, HepG2, A549, and SW480, showed significantly increased apoptosis compared with the respective control groups. This was accompanied by cell cycle arrest at G(0)/G(1) phase, whereas cell proliferation was not significantly affected. Overexpression of polycystin-1 induces apoptosis in cancer cells, at least partially, through Wnt and a caspase-dependent pathway.     

Measurement and modelling of ABA signalling in potato (Solanum tuberosum L.) during partial root-zone drying

The objective of this study was to develop a simple mechanistic model to predict the magnitude of ABA signalling ([X-ABA]) of potatoes (Solanum tuberosum L.) exposed to partial root-zone drying (PRD). Potatoes were grown in pots in a glasshouse with the roots split equally between two soil columns. At tuber initiation stage, plants were subjected to three irrigation treatments: (1) both soil columns were fully irrigated (FI) daily to a volumetric soil water content (θ) of 18.0%; (2) PRD, in which one soil column was irrigated daily to 18.0% while the other was allowed to dry, and the irrigation was shifted between columns when the θ of the drying soil column had decreased to 7–8%; (3) non-irrigation (NI), where irrigation was withheld after onset of treatments and lasted for 5 days until θ had decreased to 7%. In the PRD plants, the fraction of soil water extraction (FSWE) by the dry roots declined exponentially with declining soil water potential (Ψ_soil-dry); however, after shifting of irrigation, the previously dried roots immediately recovered the full capacity of water uptake. During the first PRD drying cycle, FI plants had the highest stomatal conductance (g_s), and followed by PRD plants and NI plants had the lowest g_s. Photosynthesis (A) was similar for FI and PRD plants, and was significantly lower for the NI plants only on 3–4 days after treatment. In the NI plants, a linear relationship between Ψ_soil and [X-ABA] was obtained. Based on these relationships, a simple model predicting [X-ABA] in the PRD plants ([X-ABA]_PRD) was developed. Assuming that a constant [X-ABA] of 115 nM (similar to that found in the FI plants) originated from the wet roots; the simulation results indicated that irrigation should be shifted between the two sides when Ψ_soil-dry had decreased to −80 kPa, and [X-ABA]_PRD had reached a peak of ca. 150 nM. However, the [X-ABA]_PRD predicted by the model was significantly lower than the measured value; whilst a simple average of [X-ABA] from the wet and the dry soil columns based on the [X-ABA]–Ψ_soil relationship better predicted [X-ABA]_PRD.     

Neurabin contributes to hippocampal long-term potentiation and contextual fear memory

Neurabin is a scaffolding protein that interacts with actin and protein phosphatase-1. Highly enriched in the dendritic spine, neurabin is important for spine morphogenesis and synaptic formation. However, less is known about the role of neurabin in hippocampal plasticity and its possible effect on behavioral functions. Using neurabin knockout (KO) mice, here we studied the function of neurabin in hippocampal synaptic transmission, plasticity and behavioral memory. We demonstrated that neurabin KO mice showed a deficit in contextual fear memory but not auditory fear memory. Whole-cell patch clamp recordings in the hippocampal CA1 neurons showed that long-term potentiation (LTP) was significantly reduced, whereas long-term depression (LTD) was unaltered in neurabin KO mice. Moreover, increased AMPA receptor but not NMDA receptor-mediated synaptic transmission was found in neurabin KO mice, and is accompanied by decreased phosphorylation of GluR1 at the PKA site (Ser845) but no change at the CaMKII/PKC site (Ser831). Pre-conditioning with LTD induction rescued the following LTP in neurabin KO mice, suggesting the loss of LTP may be due to the saturated synaptic transmission. Our results indicate that neurabin regulates contextual fear memory and LTP in hippocampal CA1 pyramidal neurons.     

Cimifugin suppresses allergic inflammation by reducing epithelial derived initiative key factors via regulating tight junctions

Cimifugin is a bioactive component of Saposhnikovia divaricata, a Chinese herb for treating allergy. Our previous studies demonstrated that cimifugin inhibited allergic inflammation efficiently. This study aims to determine the mechanism of cimifugin on epithelial cells in allergic inflammation. Mice were sensitized and challenged with FITC to establish type 2 atopic dermatitis (AD) model. The initial stage of AD model, in which mice were just sensitized with FITC, was established in vivo and immortalized human epidermal (HaCaT) cells were utilized in vitro. Initiative key cytokines, TSLP and IL‐33, were measured by ELISA, the junctions in ECs were observed by electron microscopy and TJs (CLDN‐1, occludin and CLDND1) were assessed by Western blot, immunohistochemistry and immunofluorescence. The results showed that TSLP and IL‐33 were inhibited significantly by cimifugin in the initial stage of AD model. Simultaneously, cimifugin reduced the separated gap among the epithelial cells and increased the expression of TJs. Similar effects on TSLP/IL‐33 and TJs were obtained in vitro. The effect of cimifugin on TSLP decreased significantly when expression of CLDN1 was interfered with siRNA and this implied cimifugin inhibits initiative cytokines through restoring TJs. Furthermore, cimifugin administered only in the initial stage obviously attenuated the ultimate allergic inflammation, which indicate that impacts of cimifugin in the initial stage on TSLP/IL‐33 and TJs are sufficient for suppressing allergic inflammation. This study not only revealed the mechanisms of cimifugin, but also indicated the possibility of initiative key cytokines and TJs as therapeutic targets.     

山西五鹿山自然保护区木贼麻黄群落优势种的种间关联性分析

为了探讨山西五鹿山自然保护区木贼麻黄群落的物种组成、群落结构和种间关联性,该研究基于2×2联列表,采用方差比率法、χ2检验、Pearson相关系数及Spearman秩相关系数检验等数量分析方法,对山西五鹿山自然保护区木贼麻黄群落中25个优势种、300个种对间进行了种间关联性分析。结果显示:(1)木贼麻黄群落优势种群间总体上呈正关联,表明该群落处于稳定的演替阶段。(2)χ2检验结果表明,正关联种对数有141对,负关联种对数有132对,正负关联比为1.07;Pearson相关系数检验中,正关联种对数有128对,负关联种对数有151对,正负关联比为0.85;Spearman秩相关系数检验中,正关联种对数有129对,负关联种对数有134对,正负关联比为0.96。(3)根据研究区25个优势种群对环境的适应方式和主导生态因素并结合PCA排序,可将25个优势种群划分为4个生态种组。研究表明,山西五鹿山自然保护区木贼麻黄群落物种组成相对稳定且群落结构处于发展阶段。     

Spatiotemporal variation of bacterial and archaeal communities in sediments of a drinking reservoir,Beijing, China

Bacterial and archaeal assemblages are one of the most important contributors to the recycling of nutrients and the decomposition of organic matter in aquatic sediments. However, their spatiotemporal variation and its driving factors remain unclear, especially for drinking reservoirs, which are strongly affected by human consumption. Using quantitative PCR and Illumina MiSeq sequencing, we investigated the bacterial and archaeal communities in the sediments of a drinking reservoir, the Miyun Reservoir, one of the most important drinking sources for Beijing City. The abundance of bacteria and archaea presented no spatiotemporal variation. With respect to community diversity, visible spatial and temporal differences were observed in archaea, whereas the bacterial community showed minor variation. The bacterial communities in the reservoir sediment mainly included Proteobacteria, Bacteroidetes, Nitrospirae, Acidobacteria, and Verrucomicrobia. The bacterial community structure showed obvious spatial variation. The composition of the bacterial operational taxonomic units (OTUs) and main phyla were dam-specific; the composition of samples in front of the dam were significantly different from the composition of the other samples. The archaeal communities were mainly represented by Woesearchaeota and Euryarchaeota. Distinctly spatial and seasonal variation was observed in the archaeal community structure. The sediment NH₄ ⁺–N, pH, and water depth were identified as the key driving factors of changes in the composition of the bacterial and archaeal communities. Water depth might have the greatest influence on the microbial community structure. The dam-specific community structure may be related to the greater water depth in front of the dam. This finding indicates that water depth might be the greatest contributor to the microbial community structure in the Miyun Reservoir.