Identification of novel dietary phytochemicals inhibiting the efflux transporter breast cancer resistance protein (BCRP/ABCG2)

Breast cancer resistance protein (BCRP/ABCG2) plays an important role in determining the absorption and disposition of consumed xenobiotics including various drugs and dietary phytochemicals and is also one of the prominent efflux transporters involved in multidrug resistance (MDR). In this study, we have investigated the interactions between ABCG2 and 56 naturally-occurring phytochemicals including phenolic acids, flavonoids, triterpenes and other common dietary phytochemicals, as well as two non plant-based compounds (hippuric acid and propyl gallate) using cell- and membrane-based transport inhibition assays. Of the non-flavonoid phytochemicals tested, berberine, celastrol, ellagic acid, limonin, oleanolic acid, propyl gallate, sinapic acid and ursolic acid demonstrated significant inhibition of ABCG2-mediated transport. Chrysoeriol, laricitrin, myricetin 3′,4′,5′-trimethylether, pinocembrin, quercitrin, tamarixetin, tricetin and tricetin 3′,4′,5′-trimethylether were also identified as novel flavonoid ABCG2 inhibitors. The identified inhibitory activity of dietary phytochemicals on ABCG2 provides a framework for further investigation of ABCG2-modulated phytochemical bioavailability, MDR, and possible food–drug interactions.     

Novel in vitro systems for prediction of veterinary drug residues in ovine milk and dairy products

A new in vitro tool was developed for the identification of veterinary substrates of the main drug transporter in the mammary gland. These drugs have a much higher chance of being concentrated into ovine milk and thus should be detectable in dairy products. Complementarily, a cell model for the identification of compounds that can inhibit the secretion of drugs into ovine milk, and thus reduce milk residues, was also generated. The ATP-binding cassette transporter G2 (ABCG2) is responsible for the concentration of its substrates into milk. The need to predict potential drug residues in ruminant milk has prompted the development of in vitro cell models over-expressing ABCG2 for these species to detect veterinary drugs that interact with this transporter. Using these models, several substrates for bovine and caprine ABCG2 have been found, and differences in activity between species have been reported. However, despite being of great toxicological relevance, no suitable in vitro model to predict substrates of ovine ABCG2 was available. New MDCKII and MEF3.8 cell models over-expressing ovine ABCG2 were generated for the identification of substrates and inhibitors of ovine ABCG2. Five widely used veterinary antibiotics (marbofloxacin, orbifloxacin, sarafloxacin, danofloxacin and difloxacin) were discovered as new substrates of ovine ABCG2. These results were confirmed for the bovine transporter and its Y581S variant using previously generated cell models. In addition, the avermectin doramectin was described as a new inhibitor of ruminant ABCG2. This new rapid assay to identify veterinary drugs that can be concentrated into ovine milk will potentially improve detection and monitoring of veterinary drug residues in ovine milk and dairy products.     

天然产物通过细胞自噬调节抑制癌症的研究进展

传统的化疗手段在抑制肿瘤细胞生长的同时也会损伤到正常细胞,所以其临床治疗效果受到很大限制。新型天然产物抗癌化合物基于其安全性和有效性,将会成为人工合成化合物的替代物。临床前和临床研究已经证实一些植物天然产物（如白藜芦醇、姜黄素、人参皂苷等）具有抗癌潜力。本文综述具有代表性的天然产物如何通过靶向细胞内自噬通路诱导肿瘤细胞死亡及其涉及到的信号通路,为其进一步开发应用于原发性和转移性肿瘤的治疗提供新的思路。     

三株植物乳杆菌降胆固醇机理的研究

测定了已筛选出的具有较高胆固醇去除能力和胆盐水解酶活性的3株植物乳杆菌(KLDS6.0330,KLDS6.0333,KLDS6.0335)的胆固醇同化作用,胆汁盐的去结合作用和胆固醇共沉淀作用。这3株植物乳杆菌能够同化较多的胆固醇(﹥43μg/mL);所有的菌株都表现出了对甘氨胆酸钠和牛磺胆酸钠的去结合作用,与牛磺胆酸钠相比,甘氨胆酸钠的去结合能够释放较多的胆酸;所有菌株都表现出了胆固醇与甘氨胆酸钠和牛磺胆酸钠去结合释放胆酸的共沉淀,与牛磺胆酸钠相比,甘氨胆酸钠去结合产生的胆酸表现出了与较多的胆固醇共沉淀;随着pH值的下降,解聚态的胆汁酸与胆固醇的共沉淀量增加,结合态胆盐与胆固醇的共沉淀量较少。结果表明这3株植物乳杆菌在体外可以通过3种机制去除胆固醇。     

酸菜来源植物乳杆菌体外去除胆固醇特性

对4株酸菜来源具有潜在益生特性的植物乳杆菌降胆固醇特性进行研究.研究发现其降胆固醇能力受胆盐浓度和胆盐种类的影响,当牛胆盐的添加浓度为3g/L时,降胆固醇能力达到最高(9.67mg/g～21.32mg/g[干重]);在培养基中添加不同种类的胆盐,降胆固醇能力不同,依次为牛磺胆酸钠＞混合胆盐＞甘氨胆酸钠.其产生的游离胆酸的量与胆固醇移除能力呈正相关,且以在牛磺胆酸钠存在下最佳.     

白藜芦醇葡萄糖苷的生物合成

为研究淀粉蔗糖酶催化白藜芦醇的性质,从中度嗜热菌Deinococcus geothermalis克隆淀粉蔗糖酶基因dgas并在大肠杆菌中诱导表达,纯化淀粉蔗糖酶DGAS。经SDS-PAGE检测DGAS的分子量为73.0 kDa。以蔗糖为葡萄糖基供体,白藜芦醇为受体,DGAS催化合成2个白藜芦醇葡萄糖苷。大规模培养表达制备淀粉蔗糖酶DGAS,催化白藜芦醇进行糖基化反应,经柱层析分离纯化得到2个化合物1和2。经NMR波谱解析化合物1和2分别鉴定为白藜芦醇-4’-O-α-D-吡喃葡萄糖苷和白藜芦醇-4’-O-α-D-吡喃葡萄糖基-(1→4)-O-α-D-吡喃葡萄糖苷。在室温条件下,白藜芦醇-4’-O-α-D-吡喃葡萄糖苷在水中溶解度为2.26 mg/mL。     

Invited review: Characterization of new probiotics from dairy and nondairy products—Insights into acid tolerance,bile metabolism and tolerance,and adhesion capability

The selection of potential probiotic strains that possess the physiological capacity of performing successfully in the gastrointestinal tract (GIT) is a critical challenge. Probiotic microorganisms must tolerate the deleterious effects of various stresses to survive passage and function in the human GIT. Adhesion to the intestinal mucosa is also an important aspect. Recently, numerous studies have been performed concerning the selection and evaluation of novel probiotic microorganisms, mainly probiotic bacteria isolated from dairy and nondairy products. Therefore, it would be crucial to critically review the assessment methods employed to select the potential probiotics. This article aims to review and discuss the recent approaches, methods used for the selection, and outcomes of the evaluation of novel probiotic strains with the main purpose of supporting future probiotic microbial assessment studies. The findings and approaches used for assessing acid tolerance, bile metabolism and tolerance, and adhesion capability are the focus of this review. In addition, probiotic bile deconjugation and bile salt hydrolysis are explored. The selection of a new probiotic strain has mainly been based on the in vitro tolerance of physiologically related stresses including low pH and bile, to ensure that the potential probiotic microorganism can survive the harsh conditions of the GIT. However, the varied experimental conditions used in these studies (different types of media, bile, pH, and incubation time) hamper the comparison of the results of these investigations. Therefore, standardization of experimental conditions for characterizing and selecting probiotics is warranted.     

应用体检套餐对女性乳腺癌、宫颈癌筛查结果的分析

目的:评价不同体检套餐对于女性乳腺癌、宫颈癌筛查的价值。方法:在女性健康体检中,应用临床检查、妇科检查、乳腺红外线检查及液基细胞学(TCT)等不同项目,乳腺癌、宫颈癌患者由专业医生依据阳性结果进行综合判断。结果:2007—2011年间,体检中心女性乳腺癌的平均检出率为435/10万,宫颈癌的平均检出率为155/10万,不同年龄段间乳腺癌的检出率均明显高于宫颈癌的检出率,差异随年龄的增加逐渐加大。采用常规体检方法能有效筛查乳腺癌、宫颈癌患者,且血清肿瘤标志物检测作为辅助手段对两癌的早期诊断、监测病情和判断预后也有重要意义。结论:体检中心应不断优化适宜女性的体检套餐,推广应用新的检查技术和手段,并在高危人群中有针对性地制定高发癌症的筛查计划。     

乳制品消费与癌症风险控制

乳制品是营养价值很高的食物,但近年来对于乳制品的健康意义有了质疑之声。本文综述了乳制品与结肠癌、乳腺癌、前列腺癌、卵巢癌4种癌症发生风险关系的营养流行病学研究,对近年"牛奶致癌论"作出客观评价。证据表明,乳制品与前列腺癌和卵巢癌可能有一定的正相关性,但研究结果并不一致;乳制品对结肠癌的预防具有益处,对乳腺癌的影响未有定论;尚无证据表明每日摄入200g以下会显著增加癌症的风险。