基于网络药理学和分子对接技术探讨黄芪干预腹膜纤维化的机制

目的 运用网络药理学方法及分子对接技术探讨黄芪干预腹膜纤维化的可能机制。方法 利用中药系统药理学数据库及分析平台(TCMSP)检索黄芪的主要化学成分及靶点,并补充文献报道相关药理作用的成分作为潜在活性成分。以"peritoneal fibrosis"为关键词分别在OMIM、Genecards获取目前已知的与腹膜纤维化相关的疾病靶点,后取两者的交集靶点;对交集基因通过STRING数据库与Cytoscape 3.7.2软件构建"药物-成分-靶点-疾病"网络及蛋白互作(PPI)网络并筛选核心网络。基于R软件使用Bioconductor生物信息软件对核心靶点进行GO及KEGG富集分析,最终采用AutoDock软件将主要有效成分与核心靶点进行分子对接,得出其结合能力。结果 筛选出20个黄芪活性成分及文献报道有相关药理作用4个, 457药物作用靶点,与674个腹膜纤维化病靶点取交集,得到86个共同靶点。GO功能富集分析提示黄芪拮抗腹膜纤维化主要参与了蛋白激酶B信号转导的调节、细胞对化学的应激反应、炎症反应的调节等通路; KEGG通路富集分析主要涉及调控肿瘤、磷脂酰肌醇-3-羟激酶-蛋白激酶B(PI3K-Akt)、晚期糖基化终末产物/晚期糖基化终末产物受体(AGE-RAGE)、人类巨细胞病毒感染、HIF-1信号通路等;分子对接结果显示关键靶点与活性成分具有较好的结合能力。结论 黄芪治疗腹膜纤维化的分子机制,可能与抑制炎症及氧化应激反应、调节多种信号通路等相关。     

Effect of Tropicamide on Laser Flare Meter Measurements in Patients with Pseudoexfoliation

ABSTRACT

Purpose

To investigate the effect of 1% tropicamide on anterior chamber aqueous flare (ACAF) measurements acquired with laser flare meter in patients with pseudoexfoliation.     

Design and synthesis of novel organometallic complexes using boronated phenylalanine derivatives as potential anticancer agents

Drug design and discovery studies are important because of the prevalence of diseases without available medical cures. New anticancer agents are particularly urgent because of the high mortality rate associated with cancer. A series of mononuclear gold (III) and platinum (II) complexes based on boronated phenylalanine (BPA) were designed and synthesized using 4,4’-dimethyl-2,2’-dipyridyl (L1) or 1,10-phenanthroline-5,6-dion (L2) ligands to obtain promising anticancer drug candidates. Proton nuclear magnetic resonance, infrared, mass spectrometry, and elemental analyses were utilized for chemical characterizations. Cell viability, cancer cell colony formation, endothelial tube formation, and cytoskeleton staining assays were performed using A549 lung adenocarcinoma and human umbilical vein endothelial cells (HUVECs) to investigate preliminary pharmacological activities. L1-based platinum (II) complex (BPA-L1-Pt) was the most promising complex, and has similar activity with the approved chemotherapy drug cis-platinum. Half maximal inhibitory concentration values for BPA-L1-Pt were 9.15 µM on A549s and 16.61 µM on HUVECs; the values for cis-platinum were 5.24 µM on A549s and 23.14 µM on HUVECs. Consequently, further synthesis studies should be performed to boost the cancer cell selectivity feature of BPA by varying metal and ligand types.     

Using gas chromatography and mass spectrometry to determine 25-hydroxyvitamin D levels for clinical assessment of vitamin D deficiency

Vitamin D is responsible for multiple metabolic functions in humans. Rickets are the most common disease caused by vitamin D deficiency. It is caused by poor calcium intake resulting in poor serum-ionized calcium. The purpose of this study is to develop a rapid, sensitive, and feasible method to determine the 25-hydroxy-vitamin D3 (25(OH)D3) levels in blood samples for clinical assessment. In this study, gas chromatography coupled mass spectrometry with trimethylsilyl derivatization (TMS-GC-MS) is the most suitable protocol for quantitative analyses of 25(OH)D3. Performance of method was evaluated and compared with liquid chromatography and immunoassay. Method validation has been carried out with plasma specimens. The limit of quantitation of TMS-GC-MS method is 1.5 ppb with good linear correlation. Furthermore, the dietary intake and nutritional status of vegetarian and non-vegetarians in Taiwan were assessed by our validated method. As a result, this vitamin D nutrition survey demonstrates that most Taiwanese people have insufficient vitamin D. Due to dietary habits; the male vegans may have the highest risk of vitamin D deficiency.     

Evaluation of Tc-99m(V) DMSA for imaging inflammatory lesions: An experimental study

The present study evaluated^99mTc(V) DMSA as an agent for the visualization of inflammatory lesions in comparison to^99mTc(HI) DMSA and^99mTc-HIG. All three radiopharmaceuticals were prepared with commercial kits.^99mTc(V) DMSA was prepared at neutral pH by the addition of first bicarbonate and then pertechnetate to the kit contents. The labeling efficiency was 99% as determined by ITLC. Abscesses were induced by i.m. injection of 50 μl turpentine into the right thighs of 36 Swiss albino mice. Six days later 3.7 MBq of each radiopharmaceutical was i.v. administered to 12 mice. The mice were sacrificed at 1,3,6 and 24 h later. Scintigrams were obtained with a gamma camera. The abscesses were better visualized on scintigrams with^99mTc(V) DMSA compared to^99mTc(III) DMSA, starting at 1 h. The animals were dissected and the organs were removed, weighed and the radioactivity determined with a gamma counter. The abscess to other tissue ratios were higher with^99mTc(V) DMSA than the other radiopharmaceuticals. The max. abscess/muscle ratios were 9.46 ± 3.20 (24 h), 4.19 ± 1.39 (6 h) and 5.98 ± 1.17 (24 h) and max. abscess/blood ratios were 6.22 ± 1.41, 4.09 ± 0.84 and 0.914 ± 0.351 all at 24 h for^99mTc(V) DMSA,^99mTc(III) DMSA and^99mTc-HIG, respectively. Experimental arthritis was produced in 6 New Zealand white rabbits by intra-articular injection of ovalbumin. Four days later 37 MBq of^99mTc(V) DMSA and^99mTc-HIG were each i.v. administered to 3 rabbits. Scintigrams obtained at 1, 3, 6, and 24 h clearly demonstrated arthritic joints. ROFs over arthritic joints were compared to contralateral normal joints (A/C). The max. A/C ratios were 2.10 ± 0.31 (3 h) and 2.92 ± 0.99 (24 h) for^99mTc(V) DMSA and^99mTc-HIG, respectively. Our results indicated the feasibility of imaging inflammatory lesions with^99mTc(V) DMSA.     

Stoma Adjustable Silicone Gastric Banding versus Vertical Banded Gastroplasty for the Treatment of Morbid Obesity

Background: Among gastric restrictive operations, the procedure of choice is still controversial. The aim of this study is to compare the results of two different gastric restrictive procedures: vertical banded gastroplasty (VBG) and stoma adjustable silicone gastric banding (ASGB). Methods: Between 1991 and 1996, 51 patients were treated surgically for morbid obesity: 27 underwent VBG and 24 underwent ASGB. Preoperative body weight (BW), body mass index (BMI) and percentage of ideal body weight (% IBW) were (mean ± SD): 145.7 ± 45.3 kg; 53.9 ± 15.9 kg/m²; 249.1 ± 73.5% respectively in the VBG group. Corresponding figures for the ASBG group were 132.5 ± 22.7 kg; 46.9 ± 7.8 kg/m² and 207.2 ± 35.0%. Results: In the VBG group, the median follow-up period was 26 months (range: 7-47). Eighteen months after the operation BW, BMI, % IBW and percentage of excess weight loss (% EWL) were 85.5 ± 26.8 kg, 31.9 ± 9.8 kg/m², 145.4 ± 43.9% and 74 ± 1% respectively. Complications included incisional hernia (n = 1), and bowel obstruction (n = 1). One patient died of acute myocardial infarction on the third postoperative day. In the ASGB group, median follow-up time was 19.7 months (range: 18-26). At 18 months postoperation BW, BMI, % IBW and % EWL values were 86.6 ± 20.6 kg 30.6 ± 6.6 kg/m2 140.6 ± 29.3% and 64 ± 1% respectively. Gastric wall erosion occurred in two patients and the bands had to be removed. These patients underwent VBG 6 months later. Complications encountered in this group were incisional hernia (n = 1), outlet stenosis and reflux esophagitis (n = 1), reservoir leakage (n = 1) and gastrointestinal bleeding (n = 1). Two patients died of pulmonary embolism and acute gastrointestinal bleeding. Conclusions: Weight reduction was not statistically significant between the two groups. ASGB was easier to perform and less invasive than VBG.