用正交法探讨过氧乙酸含量测定的影响因素

目的探讨过氧乙酸含量测定的影响因素.方法用正交法设计影响因素,碘量法测定其含量.结果高锰酸钾放置时间是影响过氧乙酸含量测定的主要因素.结论当滴加高锰酸钾液使供试液呈微红色时应迅速地完成实验操作.     

远志的化学成分研究Ⅱ

目的 :研究远志的化学成分。方法 :采用多种色谱方法进行分离 ,利用光谱数据结合理化分析进行结构鉴定。结果 :从远志根皮的正丁醇层中分离得到 4个蔗糖酯类化合物 ,分别鉴定为 :sibiricoseA₅(1) ,sibiricoseA₆(2 ) ,tenuifolisideA(3)和 3′ ,6 disinapoylsucrose(4 )。结论 :化合物 1和 2为首次从该植物中分离得到。     

神经甾体的合成和代谢及其对神经系统作用

神经甾体是指存在于中枢和外周神经系统，不需依赖于内分泌腺体的甾体激素，包括孕烯醇酮、孕酮、别孕烯醇酮、脱氢表雄酮等，由胆固醇或其前体在相应酶的作用下在神经系统合成。神经甾体可以通过作用于GABAA受体、NMDA受体和σ受体发挥作用。它们对记忆、睡眠、惊厥、细胞兴奋性毒性等产生相应的作用，为某些疾病的治疗指明方向。     

Amelioration of Endotoxin-Induced Uveitis in Rabbit by Topical Administration of Tacrolimus Proglycosome Nano-Vesicles

This work was aimed to improve the efficacy of tacrolimus in the treatment of endotoxin-induced uveitis (EIU) using propylene glycol modified lipid vesicles termed as proglycosome nano-vesicles (PNVs). PNVs were prepared by modified film hydration method. Experimental uveitis in rabbit eye was induced by an intravitreal injection of 20 μL of the endotoxin solution containing 100 ng of lipopolysaccharide endotoxin. In vivo efficacy of PNVs was determined by studying clinical symptoms of uveitis using slit lamp examination and by quantitatively measuring levels of tumor necrosis factor-alpha, interleukin-6, leukocytes and total proteins in aqueous humor, 24 h after intravitreal injection of endotoxin. Comparison was made with healthy, untreated and tacrolimus solution treated eyes. PNVs developed were nano-sized, deformable and showed sustained release of tacrolimus over period of 12 h. In vivo results indicated statistically significant difference between the effects of PNVs in the treatment of EIU compared to tacrolimus. PNV treatment not only subsides clinical symptoms of uveitis but also prevented breakdown of blood aqueous barrier. Tacrolimus loaded PNVs are potential new topical treatment for uveitis.     

Determination of testosterone esters in the hair of male greyhound dogs using liquid chromatography–high resolution mass spectrometry

The doping of greyhound dogs with testosterone is done in an attempt to improve their athletic performance, but such doping cannot easily be confirmed, especially in male dogs owing to the natural presence of endogenous testosterone. As testosterone is usually administered as its esters, their direct detection in hair would provide confirmatory evidence of the administration of a pharmaceutical product. This article demonstrates that the use of a liquid chromatography–high resolution mass spectrometry method with heated electrospray ionisation (HESI) combined with the use of amino solid‐phase extraction (SPE) cartridges for sample clean‐up, is suitable for the sensitive determination of propionate, phenyl propionate, isocaproate, decanoate, and enanthate esters of testosterone in greyhound hair. The method is linear over the range, 0.1 μg/kg–10 μg/kg, for all the testosterone esters analysed. The limits of detection (LOD) are 0.05 μg/kg for testosterone phenyl propionate, isocaproate, and decanoate, 0.025 μg/kg for testosterone propionate, and 0.25 μg/kg for testosterone enanthate. This method was applied to hair samples collected from male greyhounds before and after a single administration of a product containing several testosterone esters, each of which could be detected up to 100 days post‐administration. The study also demonstrates that tail hair is the specimen of choice for the analysis of testosterone in dog hair and that washing of dogs does not impact the analysis of testosterone esters in hair. This method may be useful in racing regulation for the detection of illegitimate use of testosterone in all species.     

Nose-to-brain delivery of temozolomide-loaded PLGA nanoparticles functionalized with anti-EPHA3 for glioblastoma targeting

Glioblastoma is the most common malignant brain tumor. Efficient delivery of drugs targeting glioblastomas remains a challenge. Ephrin type-A receptor 3 (EPHA3) tyrosine kinase antibody-modified polylactide-co-glycolide (PLGA) nanoparticles (NPs) were developed to target glioblastoma via nose-to-brain delivery. Anti-EPHA3-modified, TBE-loaded NPs were prepared using an emulsion-solvent evaporation method, showed a sustained in vitro release profile up to 48 h and a mean particle size of 145.9 ± 8.7 nm. The cellular uptake of anti-EPHA3-modified NPs by C6 cells was significantly enhanced compared to that of nontargeting NPs (p < .01). In vivo imaging and distribution studies on the glioma-bearing rats showed that anti-EPHA3-modified NPs exhibited high fluorescence intensity in the brain and effectively accumulated to glioma tissues, indicating the targeting effect of anti-EPHA3. Glioma-bearing rats treated with anti-EPHA3-modified NPs resulted in significantly higher tumor cell apoptosis (p < .01) than that observed with other formulations and prolonged the median survival time of glioma-bearing rats to 26 days, which was 1.37-fold longer than that of PLGA NPs. The above results indicated that anti-EPHA3-modified NPs may potentially serve as a nose-to-brain drug carrier for the treatment of glioblastoma.     

Plasmodium falciparum synthetic LbL microparticle vaccine elicits protective neutralizing antibody and parasite-specific cellular immune responses

Epitopes of the circumsporozoite (CS) protein of Plasmodium falciparum, the most pathogenic species of the malaria parasite, have been shown to elicit protective immunity in experimental animals and human volunteers. The mechanisms of immunity include parasite-neutralizing antibodies that can inhibit parasite motility in the skin at the site of infection and in the bloodstream during transit to the hepatocyte host cell and also block interaction with host cell receptors on hepatocytes. In addition, specific CD4+ and CD8+ cellular mechanisms target the intracellular hepatic forms, thus preventing release of erythrocytic stage parasites from the infected hepatocyte and the ensuing blood stage cycle responsible for clinical disease. An innovative method for producing particle vaccines, layer-by-layer (LbL) fabrication of polypeptide films on solid CaCO₃ cores, was used to produce synthetic malaria vaccines containing a tri-epitope CS peptide T1BT* comprising the antibody epitope of the CS repeat region (B) and two T-cell epitopes, the highly conserved T1 epitope and the universal epitope T*. Mice immunized with microparticles loaded with T1BT* peptide developed parasite-neutralizing antibodies and malaria-specific T-cell responses including cytotoxic effector T-cells. Protection from liver stage infection following challenge with live sporozoites from infected mosquitoes correlated with neutralizing antibody levels. Although some immunized mice with low or undetectable neutralizing antibodies were also protected, depletion of T-cells prior to challenge resulted in the majority of mice remaining resistant to challenge. In addition, mice immunized with microparticles bearing only T-cell epitopes were not protected, demonstrating that cellular immunity alone was not sufficient for protective immunity. Although the microparticles without adjuvant were immunogenic and protective, a simple modification with the lipopeptide TLR2 agonist Pam₃Cys increased the potency and efficacy of the LbL vaccine candidate. This study demonstrates the potential of LbL particles as promising malaria vaccine candidates using the T1BT* epitopes from the P. falciparum CS protein.     

苄基膦酸二乙酯乙酰胺类熊果酸衍生物的合成及其体外抗肝癌活性研究

目的 考察新型熊果酸衍生物的体外抗肝癌活性及其作用机制。方法 依据"Topliss决策法"将熊果酸与不同取代的苄基膦酸二乙酯片段通过取代反应得到目标化合物,并采用MTT法考察其体外抗肝癌活性;通过分子对接试验分析化合物可能的作用靶点并通过Western blotting试验加以验证。结果 目标化合物4a~4e的化学结构经过¹H-NMR﹑ ¹³C-NMR以及HRMS的联合确证;化合物4b及4e对BEL-7402及HepG2 2种肝癌细胞株的抑制活性优于熊果酸及阳性对照药5-氟尿嘧啶,同时对正常肝细胞L02的毒性显著降低;化合物4e呈浓度依赖性下调p-AKT蛋白的表达。结论 化合物4e的体外抗肝癌活性最为理想(针对HepG2的IC₅₀值为2.69 μmol·L^-1),可作为AKT蛋白抑制剂进行深入研究。     

A Ca2+ chelator ameliorates chromium (VI)-induced hepatocyte L-02 injury via down-regulation of voltage-Dependent anion channel 1 (VDAC1) expression

Hexavalent chromium could result in cell malfunctions. Intracellular Ca²⁺ ([Ca²⁺]_i) content and VDAC1 expression are both important features related to cell survial. This study aimed to explore the mechanism of cell injury induced by Cr(VI) and tentatively offer clues to repairing this cell damage using [Ca²⁺]_i and VDAC1. L-02 hepatocytes were treated with Cr(VI)/BAPTA, and the levels of [Ca²⁺]_i and cell injury associated with Cr(VI) were determined in addition to the effect of BAPTA. The expression of VDAC1 in Cr(VI)-induced cells was evaluated. The results showed a dose-dependent elevation of the level of VDAC1 and the mRNA level of the VDAC1 biogenesis-related gene Sam50. BAPTA could ameliorate less severe damage induced by 4 μM Cr(VI) via reducing VDAC1 and Sam50. Additionally, cell injury caused by less than 4 μM Cr(VI) could be ameliorated by VDAC1 knockdown. Taken together, the findings of this study suggest that inhibition of intracellular Ca^2± overload could protect cells from damage and that VDAC1 plays a considerable role in Cr(VI)-induced liver injury.