Determination of phytosterols in oenological matrices by liquid chromatography-atmospheric pressure chemical ionization and ion-trap mass spectrometry

The aim of the present study is the identification of plant sterols and the development of an analytical method that allows for the quantification of such family of compounds in oenological matrices. The application of liquid chromatography-atmospheric pressure chemical ionization ion-trap mass spectrometry (LC-APCI-ITMS) to sterol characterization is a useful tool and was selected to perform this research. Sterol separation was achieved using a C8 column with a mobile phase consisting of water and acetonitrile under gradient conditions and column temperature of 35 °C, which leads to analyte elution in less than 25 min. Retention times, precursor ions and MRM transitions of analytes allowed for the identification and sensitive quantitative determination of phytosterols in oenological matrices at trace levels. The method showed a dynamic linear range over the concentration ranges from 0.02 to 320 mg kg⁻¹ for the different parts of grapes and from 8 to 100 ng mL⁻¹ in case of wine. The most abundant phytosterol in all samples was β-sitosterol. The seeds are the richest source of phytosterols having a great amount of β-sitosterol, 314 mg kg⁻¹ fresh berry mass, followed by stigmasterol, fucosterol and campesterol at much lower concentrations (ranging from 3 to 10 mg kg⁻¹).     

早期空间爬行运动训练对子鼠心理行为的影响

目的观察早期空间爬行运动训练对子鼠心理行为的影响,为0~3岁婴幼儿运动方式促进心理行为发展提供理论依据。方法 25只新生鼠随机分为对照组(n=13)和运动组(n=12)。运动组进行早期空间运动训练4周。应用动物行为学平台(转棒仪和旷场试验)对36~37日龄子鼠进行心理行为测定。结果 1)运动组子鼠降落的潜伏期非常明显长于对照组(t=3.031,P0.01);2)运动组子鼠跨格次数少于对照组(t=3.710,P0.01);中心区域活动时间明显短于对照组(t=4.259,P0.01);中心区域活动距离少于对照组(t=3.437,P0.01);周边区域活动时间长于对照组(t=3.018,P0.01);3)5min时间分段分析显示运动组子鼠中心区域活动距离少表现在首5 min,活动时间短表现在后5min。结论早期空间爬行运动可使子鼠对新环境认知能力增加、情绪稳定和运动协调性明显增加。     

Augmentation in patients with restless legs syndrome receiving pramipexole therapy: a retrospective study in a single center from China

Sleep and Breathing - Augmentation is a major complication of long-term pramipexole treatment of restless legs syndrome (RLS). However, there have been no studies on augmentation in Chinese...     

Is the required therapeutic effect always achieved by racemic switch of proton-pump inhibitors？

Many of the drugs currently used in medical practice are racemates. The enantiomers of a racemic drug differ in pharmacodynamics and/or pharmacokinetics, thus in some cases it is preferable to develop pure enantiomers by racemic switch. In a recent study by Pai et al, dexrabeprazole [R（＋）-rabeprazole] （10 mg） was found to be more effective than rabeprazole （20 mg） in the treatment of gastroesophageal reflux disease. We read with great interest in this study and discussed whether such racemic switch would be applicable to other proton-pump inhibitors （PPIs）. A literature review indicates that stereoselective pharmacokinetics, rather than stereoselective pharmacological activity, is the main cause of differences in clinical efficacy between pure enantiomer and racemic PPI. Racemic switches of PPI provide the therapeutic advantages such as reducing metabolic load on the body, simplifying pharmacokinetics, providing benefit to the non-responders to standard dose of racemate, more homogenous response to treatment and better efficacy with equal safety. Further studies in quantitative structure-activity relationships （QSARs） are needed to address the fact that the preferred enantiomer of PPI is not always in the same absolute configuration, i.e., S-form is for omeprazole, pantoprazole and tenatoprazole whereas R-form is for lansoprazole and rabeprazole.     

Self-aggregated nanoparticles of linoleic acid-modified glycol chitosan conjugate as delivery vehicles for paclitaxel: preparation,characterization and evaluation

A series of linoleic acid-modified glycol chitosan (LAGC) conjugates were synthesized and characterized by FTIR and ¹H NMR. The effect of the amount of linoleic acid (LA) on the physicochemical properties of LAGC conjugates was investigated. The mean diameters of three LAGC nanoparticles determined by dynamic light scattering ranged from 204 to 289 nm. The critical aggregation concentration values of LAGC conjugates in aqueous solution were 0.0148, 0.0348, and 0.0807 mg/ml, respectively. Paclitaxel (PTX) was physically loaded into the LAGC nanoparticles by a dialysis method. The drug loading content and encapsulation efficiency of PTX-loaded LAGC (PTX-LAGC) nanoparticles increased with an increasing ratio of the hydrophobic LA to hydrophilic glycol chitosan in the conjugates. PTX-LAGC nanoparticles were almost spherical in shape observed by transmission electron microscopy. In vitro release revealed that PTX release from the nanoparticles was reduced as the LA substitution degree of LAGC conjugates increased. Compared with the commercial formulation Taxol, PTX-LAGC-1 nanoparticles exhibited comparable cellular uptake and cytotoxicity against HepG2 cells in vitro. Importantly, PTX-LAGC-1 nanoparticles demonstrated the stronger antitumor efficacy against hepatic H22 tumor-bearing mice than Taxol (p < 0.05). Therefore, glycolipid-like LAGC nanoparticles had a potential as delivery vehicles for tumor therapy.     

神经元树突非典型运输途径的微结构和功能的研究进展

细胞中蛋白质的合成和运输是复杂而严格调控的过程,在结构高度特异化的神经元细胞更是如此。神经元树突中存在着不同于其他细胞的独立于胞体运输途径的非典型运输途径,其构成主要有树突mRNA、树突内质网（dER）和树突“外驻”高尔基体(Golgi outposts)。关于这
些细胞微结构的形态分布,其非典型运输的功能以及相关病理学研究近几年有重要的进展。     

Soybean glycinin- and β-conglycinin-induced intestinal immune responses in a murine model of allergy

Glycinin and β-conglycinin are major soybean allergens involved in food hypersensitivity. The study was aimed to investigate the soybean protein-induced intestinal immune responses and its possible mechanism. Balb/c mice were sensitised intragastrically with glycinin and β-conglycinin without an adjuvant for five weeks. Results showed that the sensitised mice displayed diarrhoea symptoms and jejunal morphological changes, including decreased villous height and thickened crypt depth. Both the histamine and immunoglobulin A levels in jejunum were increased in soybean allergen-sensitised mice. Moreover, the number of IgA+B cells and CD4+T cells in the jejunal lamina propria of sensitised mice were significantly increased. The expression levels of interleukin-4 and interferon-γ were increased, whereas the levels of IL-10 and transforming growth factor-β (TGF-β) were decreased in the jejunum mucosa. In conclusion, glycinin and β-conglycinin induce a mixed Th1/Th2 immune response. The suppression of IL-10 and TGF-β may play important roles in the development of intestinal allergic reactions.     

多肽C16/Ang1联合胎盘间充质干细胞对视神经脊髓炎大鼠的保护作用

目的:评价多肽C16/血管生成素1(Ang1)联合胎盘来源间充质干细胞(PDMSCs)治疗大鼠视神经脊髓炎(NMO)的效果。方法:分离培养大鼠PDMSCs,通过脑室及脊髓蛛网膜下腔注射水通道蛋白4(APQ4)抗体与人补体C5蛋白诱导大鼠NMO模型,将大鼠分为5组,即正常组、NMO模型组、PDMSCs组、C16/Ang1组以及C16/Ang1+PDMSCs组。对治疗后大鼠进行8周的神经行为学评分,采用免疫组化观察脊髓炎症因子CD48的表达,神经丝蛋白200及髓磷脂碱性蛋白免疫荧光双染评价脱髓鞘和轴索缺失,Nissl染色计数脊髓神经元数量,Evans blue染色评估血管通透性,ELISA检测血清中白细胞介素1β(IL-1β)、IL-8、IL-10和肿瘤坏死因子α(TNF-α)的含量变化,Western blot检测胶质细胞原纤维酸性蛋白(GFAP)、AQP4以及caspase-3表达水平。结果:C16/Ang1+PDMSCs组神经行为学评分高峰出现延后,并在8周时评分出现显著性下降(P<0.05);炎症细胞的实质浸润和脊髓神经元丢失减少(P<0.05),腰段脊髓的脱髓鞘和轴索缺失评分下降(P<0.05)及血管通透性降低;促炎因子IL-1β、IL-8和TNF-α的表达降低(P<0.05),抗炎因子IL-10的表达升高(P<0.05);脊髓组织中GFAP和APQ4的表达上升(P<0.05),caspase-3则下调(P<0.05)。结论:C16/Ang1联合PDMSCs能够有效延缓NMO的疾病进程,其通过抑制炎症细胞浸润及内源性细胞凋亡,促进神经功能的修复。     

The inhibitor effect of RKIP on inflammasome activation and inflammasome-dependent diseases

Aberrant inflammasome activation contributes to the pathogenesis of various human diseases, including atherosclerosis, gout, and metabolic disorders. Elucidation of the underlying mechanism involved in the negative regulation of the inflammasome is important for developing new therapeutic targets for these diseases. Here, we showed that Raf kinase inhibitor protein (RKIP) negatively regulates the activation of the NLRP1, NLRP3, and NLRC4 inflammasomes. RKIP deficiency enhanced caspase-1 activation and IL-1β secretion via NLRP1, NLRP3, and NLRC4 inflammasome activation in primary macrophages. The overexpression of RKIP in THP-1 cells inhibited NLRP1, NLRP3, and NLRC4 inflammasome activation. RKIP-deficient mice showed increased sensitivity to Alum-induced peritonitis and Salmonella typhimurium-induced inflammation, indicating that RKIP inhibits NLRP3 and NLRC4 inflammasome activation in vivo. Mechanistically, RKIP directly binds to apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and competes with NLRP1, NLRP3, or NLRC4 to interact with ASC, thus interrupting inflammasome assembly and activation. The depletion of RKIP aggravated inflammasome-related diseases such as monosodium urate (MSU)-induced gouty arthritis and high-fat diet (HFD)-induced metabolic disorders. Furthermore, the expression of RKIP was substantially downregulated in patients with gouty arthritis or type 2 diabetes (T2D) compared to healthy controls. Collectively, our findings suggest that RKIP negatively regulates NLRP1, NLRP3, and NLRC4 inflammasome activation and is a potential therapeutic target for the treatment of inflammasome-related diseases.