佛手化学成分研究

从佛手(Citrus medica L.var.sarcodactylis)乙醇提取物中分得3个化合物,经理化鉴定和光谱法确定其化学结构分别为柠檬内酯(Ⅰ),△~(5,22)-豆甾烯醇(Ⅱ)和棕榈酸(Ⅲ)。其中△~(5,22)-豆甾烯醇为首次从佛手中分离得到。     

2008年海南省霍乱暴发分离株的分析

目的 分析海南省2008年霍乱暴发菌株的分子分型成簇性,为疫情分析提供分离株的病原学特征,协助疫情判断.方法 从本次霍乱疫情患者中分离69株,外环境分离7株[其中患者家厕所1株,水样1株,患者家附近鱼(池)塘3株,患者上卫生所就诊时呕吐地面的涂抹拭子1株和海南大学食堂菜刀涂抹拭子1株]共76株,对分离株进行常规病原学检测,利用脉冲场凝胶电泳(PFGE)技术获取受试菌株的DNA分子指纹图谱并对其结果进行聚类分析,将PFGE图像应用BioNumerics(Version4.0)数据库软件(Applied Maths BVBA,Belium)进行处理,识别图像条带,自动生成得出相似系数.结果 2008年海南省暴发霍乱疫情中分离的76株霍乱菌株中,6月份分离到的5株分离菌株图谱相同,相似系数达100%;10-11月份自患者和环境水体中分离到的70株菌图谱完全一致,相似系数达100%,但与6月份分离株的图谱不同;1株在暴发中分离自食堂菜刀的菌株,其图谱与其他菌株差异较大,相似系数为79.7%.结论 海南2008年存在不同的霍乱暴发,10-11月出现在不同市县的疫情可能属于一起较大范围的流行,环境水体污染是传播的不可忽视的环节.     

Antimalarial and Structural Studies of Pyridine-Containing Inhibitors of 1-Deoxyxylulose-5-phosphate Reductoisomerase

d-xylulose-5-phosphate reductoisomerase (DXR) in the nonmevalonate isoprene biosynthesis pathway is a target for developing antimalarial drugs. Fosmidomycin, a potent DXR inhibitor, showed safety as well as efficacy against Plasmodium falciparum malaria in clinical trials. On the basis of our previous quantitative structure–activity relationship (QSAR) and crystallographic studies, several novel pyridine-containing fosmidomycin derivatives were designed, synthesized, and found to be highly potent inhibitors of P. falciparum DXR (PfDXR) having K_i values of 1.9–13 nM, with the best one being ∼11× more active than fosmidomycin. These compounds also potently block the proliferation of multidrug resistant P. falciparum with EC₅₀ values as low as 170 nM. A 2.3 Å crystal structure of PfDXR in complex with one of the inhibitors is reported, showing that the flexible loop of the protein undergoes conformational changes upon ligand binding and a hydrogen bond and favorable hydrophobic interactions between the pyridine group and the PfDXR account for the enhanced activity.     

Demonstration of two types of fatigue in subjects with chronic liver disease using factor analysis

Purpose

The purpose of this investigation was to determine if it was possible to separate fatigue self-reports into two distinct types of fatigue symptom clusters in research subjects with chronic liver disease (CLD). It was hypothesized that when items from the Medical Outcomes Study Short-Form (SF-36v2) are combined with items from the Fatigue Severity Scale (FSS), these distinct factors will emerge.

Methods

Confirmatory and exploratory factor analyses from data collected in a prospective, natural history study of CLD patients were conducted. Items were selected from the SF-36v2 and the FSS for entry into the factor analyses. In order to establish convergent and discriminant validity, derived factor scores were correlated with subscale scores of the Human Activity Profile (HAP), Mental Component Score (MCS) from the SF-36v2, and the Emotional Functioning Subscale of the Chronic Liver Disease Questionnaire (CLDQ-EF).

Results

106 participants with CLD were included (50% female; age: 51?±?10). Two factors were identified. The factors included one that clustered around questions addressing fatigue related to physical activity (peripheral fatigue) and the other to the questions addressing generalized fatigue that did not require physical tasks to produce the fatigue (central fatigue). The standardized factor loadings of all items were greater than 0.6 on their underlying constructs. Moreover, all factor loadings are significant at p?<?0.01. Peripheral fatigue was related to HAP (r?=?0.26, r?=?0.24, p?<?0.01), as was central fatigue (r?=??0.34, r?=??0.33, p?<?0.01). Central fatigue was related to MCS and CLDQ-EF (r?=??0.60; r?=??0.63, p?<?0.01), whereas peripheral fatigue was not (r?=?0.07, p?>?0.40). We then tested the original scales to determine if the newly created factors correlated better with the validity measures. The full FSS did not correlate as well as the newly created central fatigue scale, while the original peripheral fatigue scale (the SF-36v2 physical functioning) was more related to HAP than the newly created scale.

Conclusions

In individuals with CLD, two separate factors pertaining to fatigue were identified. This recognition of the multifaceted nature of fatigue may help increase the specificity of self-reports of fatigue and lead to treatments that can specifically address the underlying factors contributing to fatigue.

     

大鼠急性肝功能衰竭模型的建立及凝血功能的变化

目的：观察不同剂量D-氨基半乳糖（D-GalN）联合脂多糖（LPS）对大鼠急性肝衰竭模型的影响及凝血功能的变化,建立理想的急性肝衰竭大鼠模型。方法：SD大鼠随机分为正常组, D-GalN高、中、低剂量组,每组10只,除正常组外,其余各组注射不同剂量D-GalN联合LPS建立急性肝衰竭大鼠模型,观察大鼠的死亡率,检测大鼠0、12、24、48、72 h肝功能及凝血功能的水平;HE染色,观察肝脏病理的变化。结果：D-GalN高、中、低剂量组72 h内的死亡率分别为：60%、30%、10%;不同剂量组不同时间点血液中丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、总胆红素（TBIL）、凝血酶原时间（PT）、国际标准比率（INR）、血浆纤维蛋白原（FIB）含量与正常组比较均有明显差异（P<0.05）;但在高、中、低剂量组间比较,ALT、AST无统计学意义,TBIL、PT、INR、FIB均有统计学差异（P<0.05）。结论：凝血功能在肝衰竭模型建立中为更加稳定的检测指标,通过肝功能、凝血功能、病理形态综合诊断,中剂量D-GalN联合LPS腹腔注射48 h后建立的急性肝衰竭大鼠模型与临床肝衰竭症状比较一致,中剂量是理想的造模剂量。     

Two new quinones from the roots of <Emphasis Type="Italic">Juglans mandshurica</Emphasis>

Two new quinones, 1-hydroxy-5-pentyl-anthraquinone (1) and 4-(5-hydroxy-1,4-dioxo-1,4-dihydro-naphthalen-2-ylamino)-butyric acid methyl ester (2), together with two known quinones, 5-hydroxy-2-(2-hydroxy-ethylamino)-(1,4) naphthoquinone (3) and juglone (4) were isolated from the roots of Juglans mandshurica (Juglandaceae). Their structures were elucidated on the basis of spectral data. Compound 3 was isolated from the Juglans genus for the first time. Compounds 1–4 exhibited significant cytotoxicity towards cultured MDA-MB231, HepG2 and SNU638 cells with IC₅₀ values ranging from 4.46 to 88.47 μM.     

A polysaccharide from the stems of Rubus amabilis Focke and its immunological enhancement activity

A water-soluble polysaccharide (named RAP) was newly isolated from the stems of Rubus amabilis. Structural confirmation of the polysaccharide was provided by hydrolysis, periodate oxidation, Smith degradation, and methylation analysis, combined with nuclear magnetic resonance (NMR), capillary electrophoresis (CE), infrared spectroscopy (IR), and gas chromatography-mass spectra (GC-MS). In vitro immunological enhancement activity was characterized using the proliferative activity of spleen lymphocytes and phagocytic activity of peritoneal macrophages in mice. The polysaccharide was mainly composed of xylose, arabinose, glucose, rhamnose, galactose, mannose, glucuronic acid, and galactocuronic acid in the molar ratio of 1.0:6.9:0.8:1.1:6.9:0.3:0.5:3.3, with the average molecular weight of 26.2 kDa. The linkage types of netural monosaccharides were as follows: the arabinose was →2) Ara (1→ and galactose were Gal (1→, →3) Gal (1→, →3,6) Gal (1→, →2,3,6) Gal (1→ and →2,3,6) Gal_f (1→. Xyl (1→, →6) Glc (1→, →2) Glc (1→, →3) Rha (1→, Rha (1→ and Man (1→ were also found in the structure. RAP-B-2 could improve the proliferative activity of spleen T cells and B cells and boost phagocytic activity of peritoneal macrophages at the concentration of 50 μg/ml (p < 0.05, p < 0.01).     

iTRAQ-based proteomic profiling of human serum reveals down-regulation of platelet basic protein and apolipoprotein B100 in patients with hematotoxicity induced by chronic occupational benzene exposure

Benzene is an important industrial chemical and an environmental contaminant, but the pathogenesis of hematotoxicity induced by chronic occupational benzene exposure (HCOBE) remains to be elucidated. To gain an insight into the molecular mechanisms and developmental biomarkers for HCOBE, isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) were utilized. Identification and quantitation of differentially expressed proteins between HCOBE cases and healthy control were thus made. Expressions of selected proteins were confirmed by western blot and further validated by ELISA. A total of 159 unique proteins were identified (≥95% confidence), and relative expression data were obtained for 141 of these in 3 iTRAQ experiments, with fifty proteins found to be in common among 3 iTRAQ experiments. Plasminogen (PLG) was found to be significantly up-regulated, whereas platelet basic protein (PBP) and apolipoprotein B100 (APOB100) were significantly down-regulated in the serum of HCOBE cases. Additionally, the altered proteins were associated with the molecular functions of binding, catalytic activity, enzyme regulator activity and transporter activity, and involved in biological processes of apoptosis, developmental and immune system process, as well as response to stimulus. Furthermore, differential expressions of PLG, PBP and APOB100 were confirmed by western blot, and the clinical relevance of PBP and APOB100 with HCOBE was validated by ELISA. Overall, our results showed that lowered expression of PBP and APOB100 proteins served as potential biomarkers of HCOBE, and may play roles in the benzene-induced immunosuppressive effects and disorders in lipid metabolism.     

环孢素A对DSS结肠炎小鼠肠黏膜通透性影响及其机制的研究

目的探讨环孢素A(CsA)对葡聚糖硫酸钠(DSS)结肠炎小鼠肠黏膜通透性的影响及作用机制。方法 C57BL/6J小鼠(6～8周龄、体质量20 g±2 g、♂),实验分为正常对照组(饮用无菌蒸馏水+腹腔注射0.9%NS)、DSS模型组(DSS溶液+腹腔注射0.9%NS)、环孢素A组(DSS溶液+腹腔注射CsA)。小鼠自由饮用5%DSS溶液1周制备结肠炎模型,环孢素A(0.025 mg.g-1)腹腔注射给药,每天1次,共7 d。每日行DAI评分,实验结束后取结肠进行HE染色评分,结肠匀浆检测MPO活性、TNF-α、IFN-γ、IL-13和IL-17水平,另取小鼠小肠黏膜进行透射电镜检查和肌球蛋白轻链激酶(MLCK)活性测定,采用Evans blue和异硫氰酸荧光素-葡聚糖(FITC-D)方法检测小肠黏膜通透性。结果与正常对照组比较,模型对照组小鼠1周后出现明显体重减轻、便血和腹泻,DAI评分和HI评分增高,同时结肠黏膜MPO活性明显增高。电镜检查小鼠回肠黏膜上皮绒毛萎缩、排列不规则,细胞间连接复合体缩短、变宽,细胞间隙扩大,小肠黏膜通透性增高。小鼠结肠匀浆中TNF-α、IFN-γ、IL-13和IL-17水平均有不同程度增高,小肠黏膜中MLCK活性明显增高。与DSS模型组比较,环孢素A组小鼠DAI评分和HI评分明显降低,结肠黏膜MPO活性减低,回肠黏膜上皮细胞绒毛排列整齐,小肠黏膜通透性降低,小肠黏膜MLCK活性和结肠匀浆中TNF-α、IFN-γ、IL-13和IL-17水平均有不同程度降低。结论环孢素A具有明显的抗DSS小鼠结肠炎作用,机制可能与通过调控MLCK表达,改善肠黏膜通透性有关。     

Reframing climate change as a public health issue: an exploratory study of public reactions

Background  

Climate change is taking a toll on human health, and some leaders in the public health community have urged their colleagues to give voice to its health implications. Previous research has shown that Americans are only dimly aware of the health implications of climate change, yet the literature on issue framing suggests that providing a novel frame - such as human health - may be potentially useful in enhancing public engagement. We conducted an exploratory study in the United States of people's reactions to a public health-framed short essay on climate change.