High Incidence of Morphological Myelodysplasia and Apoptotic Bone Marrow Cells in Behçet’s Disease

Beh?et's disease (BD) is a systemic inflammatory disorder of unknown etiology, and rarely complicated with myelodysplastic syndrome (MDS). In the present study, we investigated the morphological myelodysplasia and apoptotic rate of bone marrow cells in 15 patients with BD in comparison with MDS patients. Morphological myelodysplasia of bone marrow cells was detected in 53.3% of BD, but none showed chromosomal abnormalities. The apoptotic rate in BD patients (26.1 +/- 8.4%) was significantly higher in normal controls (11.3 +/- 2.4%; p < 0.005) and significantly lower in patients with MDS (50.8 +/- 14.0%; p < 0.0001). These findings suggest that myelodysplasia in patients with BD is more frequent than expected, and possibly due to excess induction of apoptosis of bone marrow cells in BD. However, the rate of apoptotic bone marrow cells is lower than MDS, which may explain the slight peripheral cytopenia in BD, distinct from that in MDS.     

Recent advances in fluorescent labeling techniques for fluorescence microscopy

Tremendous progress in recent computer-controlled systems for fluorescence and laser-confocal microscopy has provided us with powerful tools to visualize and analyze molecular events in the cells. Various fluorescent staining and labeling techniques have also been developed to be used with these powerful instruments. Fluorescent proteins such as green fluorescent protein (GFP) allow us to directly label particular proteins of interest in living cells. This technique has been extended over a large area of cell biology, and a variety of fluorescent protein-derived techniques have been developed to visualize the functions and conditions of the molecules within living cells. In this review, we summarize the techniques for fluorescent staining and labeling for recent fluorescence microscopy.     

Making All Medications Gluten Free

Gluten is found in food containing wheat, rye, and barley, and it may be introduced into medicines through the use of starch or any modified form of starch derived from these grains. The ingestion of gluten poses serious health hazards to people with celiac disease and non-celiac gluten sensitivity, and they must avoid the oral ingestion of gluten. In 2011, the Food and Drug Administration solicited information and public comments on ‘gluten in drug products.’ However, the ‘final rule’ that the Agency issued in 2013 involved only the voluntary ‘gluten-free’ labeling of food, and it did not include drug products. In this commentary, we are proposing that all drug products can and should be made gluten free. This is especially important since there is currently a global trade in medicines, and patients and health care providers do not know whether a product is gluten free or not unless they are labeled as such. All drug products can be made gluten free as there are many alternatives to gluten-containing starch that can be used as excipients during their formulation. Global collaborative efforts of regulatory agencies, pharmaceutical companies, and excipient manufacturers will be needed to implement a gluten-free medication policy and new regulatory guidelines.     

Synthesis of obeticholic acid,a farnesoid X receptor agonist,and its major metabolites labeled with deuterium

Simple and facile methods for the synthesis of deuterium‐labeled obeticholic acid and its 2 metabolites, glycine and taurine conjugates of obeticholic acid, are described herein. The 3 deuterated compounds were applicable for use as internal standards in drug development.     

Nutrition Facts Use in Relation to Eating Behaviors and Healthy and Unhealthy Weight Control Behaviors

Objective

Investigate the relationship between use of Nutrition Facts labels on packaged foods and weight-related behaviors.

The relationship between DNA adduct formation by benzo[a]pyrene and expression of its activation enzyme cytochrome P450 1A1 in rat

Benzo[a]pyrene (BaP) is a human carcinogen requiring metabolic activation prior to reaction with DNA. Cytochrome P450 (CYP) 1A1 is the most important hepatic and intestinal enzyme in both BaP activation and detoxification. CYP1A2 is also capable of oxidizing BaP, but to a lesser extent. The induction of CYP1A1/2 by BaP and/or β-naphthoflavone in liver and small intestine of rats was investigated. Both BaP and β-naphthoflavone induced CYP1A expression and increased enzyme activities in both organs. Moreover, the induction of CYP1A enzyme activities resulted in an increase in formation of BaP–DNA adducts detected by ³²P-postlabeling in rat liver and in the distal part of small intestine in vivo. The increases in CYP1A enzyme activity were also associated with bioactivation of BaP and elevated BaP–DNA adduct levels in ex vivo incubations of microsomes of both organs with DNA and BaP. These findings indicate a stimulating effect of both compounds on BaP-induced carcinogenesis.     

Monomethylarsonous acid inhibited endogenous cholesterol biosynthesis in human skin fibroblasts

Human exposure to arsenic in drinking water is a widespread public health concern, and such exposure is known to be associated with many human diseases. The detailed molecular mechanisms about how arsenic species contribute to the adverse human health effects, however, remain incompletely understood. Monomethylarsonous acid [MMA(III)] is a highly toxic and stable metabolite of inorganic arsenic. To exploit the mechanisms through which MMA(III) exerts its cytotoxic effect, we adopted a quantitative proteomic approach, by coupling stable isotope labeling by amino acids in cell culture (SILAC) with LC-MS/MS analysis, to examine the variation in the entire proteome of GM00637 human skin fibroblasts following acute MMA(III) exposure. Among the ~ 6500 unique proteins quantified, ~ 300 displayed significant changes in expression after exposure with 2 μM MMA(III) for 24 h. Subsequent analysis revealed the perturbation of de novo cholesterol biosynthesis, selenoprotein synthesis and Nrf2 pathways evoked by MMA(III) exposure. Particularly, MMA(III) treatment resulted in considerable down-regulation of several enzymes involved in cholesterol biosynthesis. In addition, real-time PCR analysis showed reduced mRNA levels of select genes in this pathway. Furthermore, MMA(III) exposure contributed to a distinct decline in cellular cholesterol content and significant growth inhibition of multiple cell lines, both of which could be restored by supplementation of cholesterol to the culture media. Collectively, the present study demonstrated that the cytotoxicity of MMA(III) may arise, at least in part, from the down-regulation of cholesterol biosynthesis enzymes and the resultant decrease of cellular cholesterol content.     

RGD功能化多肽纳米纤维的制备及其体内肿瘤靶向性研究

目的 制备肿瘤靶向RGD多肽纳米纤维,研究其体内分布和肿瘤靶向性.方法 通过多肽固相合成法制备靶向多肽Nap-GFFYGRGD(RGD-肽)和对照多肽Nap-GFFYGRGE(RGE-肽),利用核磁和质谱对多肽的分子结构进行表征.多肽溶液经煮沸后冷却可自组装形成纳米纤维(RGD-纤维和RGE-纤维),通过透射电镜(TEM)对纳米纤维的微观形貌进行观察.采用氯胺-T法对多肽进行125I标记,利用放射性HPLC对标记多肽进行分离纯化.建立BALB/c小鼠皮下乳腺癌肿瘤模型,125I标记的多肽自组装形成纳米纤维后经尾静脉注射,分别于注射后1、3、6、12 h进行眼球取血并处死小鼠,取肿瘤、心、肝、脾、肺、肾、胃、大肠、小肠、肌肉和脑等,用γ计数仪测量各组织放射性信号强度.结果 RGD-肽和RGE-肽均可自组装形成直径约为10～ 20 nm的纳米纤维.RGD-纤维和RGE-纤维在注射后各个时间点在体内主要脏器的分布规律相似,主要分布于胃中,其次是肠.但2者在肿瘤组织的分布规律存在显著性差异,RGD-纤维注射后6h内在肿瘤组织中呈现出一个逐渐积累的过程,而RGE-纤维在3h时达最高浓度,在6h2者差异达到最大,分别为6.25％ ID/g和2.79％ ID/g(P ＜0.01).结论 肿瘤靶向肽RGD能明显提高多肽纳米纤维在体内的肿瘤靶向分布,为该载体作为抗肿瘤药物载体用于肿瘤靶向治疗提供了强有力的数据支持.