Hereditary Prostate Cancer: Genes Related,Target Therapy and Prevention

Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary breast and ovarian cancer (HBOC) and Lynch syndromes (LS), are among the most important risk factors compared to age, race, ethnicity and environmental factors for PCa development. Hereditary prostate cancer (HPCa) has the highest heritability of any major cancer in men. The proportion of PCa attributable to hereditary factors has been estimated in the range of 5–15%. To date, the genes more consistently associated to HPCa susceptibility include mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, CHEK2). Additional genes are also recommended to be integrated into specific research, including HOXB13, BRP1 and NSB1. Importantly, BRCA1/BRCA2 and ATM mutated patients potentially benefit from Poly (ADP-ribose) polymerase PARP inhibitors, through a mechanism of synthetic lethality, causing selective tumor cell cytotoxicity in cell lines. Moreover, the detection of germline alterations in MMR genes has therapeutic implications, as it may help to predict immunotherapy benefits. Here, we discuss the current knowledge of the genetic basis for inherited predisposition to PCa, the potential target therapy, and the role of active surveillance as a management strategy for patients with low-risk PCa. Finally, the current PCa guideline recommendations are reviewed.     

Metabolic Profiling of VOCs Emitted by Bacteria Isolated from Pressure Ulcers and Treated with Different Concentrations of Bio-AgNPs

Considering the advent of antibiotic resistance, the study of bacterial metabolic behavior stimulated by novel antimicrobial agents becomes a relevant tool to elucidate involved adaptive pathways. Profiling of volatile metabolites was performed to monitor alterations of bacterial metabolism induced by biosynthesized silver nanoparticles (bio-AgNPs). Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae and Proteus mirabilis were isolated from pressure ulcers, and their cultures were prepared in the presence/absence of bio-AgNPs at 12.5, 25 and 50 µg mL⁻¹. Headspace solid phase microextraction associated to gas chromatography–mass spectrometry was the employed analytical platform. At the lower concentration level, the agent promoted positive modulation of products of fermentation routes and bioactive volatiles, indicating an attempt of bacteria to adapt to an ongoing suppression of cellular respiration. Augmented response of aldehydes and other possible products of lipid oxidative cleavage was noticed for increasing levels of bio-AgNPs. The greatest concentration of agent caused a reduction of 44 to 80% in the variety of compounds found in the control samples. Pathway analysis indicated overall inhibition of amino acids and fatty acids routes. The present assessment may provide a deeper understanding of molecular mechanisms of bio-AgNPs and how the metabolic response of bacteria is untangled.     

南水北调中线水源区浮游植物群落结构 及其生物多样性

为探究南水北调中线水源区丹江口水库浮游植物群落结构变化及其生物多样性，于 2014—2015 年对丹江 口水库进行为期 1 年的调查和分析。发现浮游植物共 8 门 76 属 101 种，其中，绿藻门、蓝藻门及硅藻门占总种数 90.10%，绿藻门种类数最多（45 种），其次是蓝藻门（26 种）和硅藻门（20 种）。浮游植物群落结构随季节变化有所 不同：夏秋季节生物量明显高于冬春季节；优势种在冬季以颗粒直链藻、颗粒直链藻极狭变种、铜绿微囊藻和小 环藻为主，春季以球衣藻、薄甲藻属及小环藻为主，夏季以简单颤藻、单胞衣藻原变种和球衣藻为主，秋季以类颤 藻鱼腥藻、简单颤藻、球衣藻和小环藻为主。应用 Shannon-Wiener 多样性指数 H′、Pielou 均匀度指数 J′、Margalef 丰富度指数 Dm评价水质结果表明：丹江口水库夏秋季水体营养化程度更高。典型对应分析表明：水温、透明度、 总氮、总磷等是影响浮游植物群落结构的主要环境因子，夏秋季受温度影响蓝藻、绿藻数量逐渐增多，一定程度 上增加了受水区生态变化风险。本研究可为南水北调中线水源区丹江口水库生态环境变化及生物迁移风险提供 数据支持。     

基于乙酰胆碱酯酶和氧化应激研究海胆酮对阿尔茨海默症的作用机制

海胆酮是一种酮式类胡萝卜素，主要从海胆及藻类等海洋生物中提取。本文研究海胆酮对乙酰胆碱酯酶（acetylcholinesterase，AChE）的抑制作用，应用酶动力学、荧光光谱、圆二色光谱和分子对接技术研究海胆酮对AChE的抑制机理，并用淀粉样β蛋白片段25～35（amyloid beta-peptide 25-35，Aβ25-35）诱导大鼠肾上腺嗜铬细胞瘤细胞（PC12细胞）建立阿尔茨海默症（Alzheimer’s disease，AD）模型，研究海胆酮对AD细胞模型氧化应激损伤的作用。结果表明，海胆酮有很强的AChE抑制活性，其半抑制质量浓度为（16.29±0.97）μg/mL，抑制常数Ki为3.82 μg/mL，表现为竞争性抑制；海胆酮可诱导AChE二级结构改变，更容易与AChE活性中心氨基酸Ser200、His440、Trp84和Tyr121结合，阻碍底物碘代硫代乙酰胆碱（acetylthiocholine iodide，ATCI）与酶结合，从而引起酶活力降低。海胆酮能有效抑制Aβ25-35诱导PC12细胞的AChE活力，降低丙二醛含量，增加超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活力，减轻Aβ25-35诱导的PC12细胞氧化应激损伤。本研究基于AChE和氧化应激阐明了海胆酮对AD的潜在作用机制，为海胆酮在功能食品、生物医药等领域的应用提供了数据支持和理论根据。     

解脂耶氏酵母作为微生物细胞工厂的应用研究进展

解脂耶氏酵母（Yarrowia lipolytica）是一种重要的工业微生物菌种，被公认为食品级安全微生物。近年来，随着合成生物学和基因编辑技术的快速发展，科学家们利用合成生物学及基因编辑技术已经成功构建出了能够生产生物化学品、生物燃料、香料、药物、工业酶和药用蛋白等多种高附加值工业产品的解脂耶氏酵母细胞工厂，使得该酵母在食品、药品和生化能源等领域均具有巨大的应用潜力。本文将重点介绍解脂耶氏酵母表达系统、合成生物学元件和基因编辑方法的最新研究进展和应用情况，并对近年来以解脂耶氏酵母作为微生物细胞工厂生产高附加值产品的应用实例进行总结，希望为研究人员进一步利用解脂耶氏酵母进行底盘细胞设计、构建和优化相关合成途径并最终实现目的产物的高效合成提供有用的信息。