Plant natural products: from traditional compounds to new emerging drugs in cancer therapy

Natural products are chemical compounds or substances produced naturally by living organisms. With the development of modern technology, more and more plant extracts have been found to be useful to medical practice. Both micromolecules and macromolecules have been reported to have the ability to inhibit tumour progression, a novel weapon to fight cancer by targeting its 10 characteristic hallmarks. In this review, we focus on summarizing plant natural compounds and their derivatives with anti‐tumour properties, into categories, according to their potential therapeutic strategies against different types of human cancer. Taken together, we present a well‐grounded review of these properties, hoping to shed new light on discovery of novel anti‐tumour therapeutic drugs from known plant natural sources.     

陕西洛川旱塬苹果园地深层土壤水分和养分特征

测定了陕西洛川旱塬11、15、20、25和43龄苹果园地0～1500 cm土层土壤湿度和0～300 cm土层土壤有机质、全氮、全磷、全钾、速效氮、速效磷、速效钾含量,分析了测定深度范围内土壤干燥化情况、各养分指标丰缺状况及其随种植年限和土层深度的变化特征.结果表明： 11、15、20、25和43龄苹果园地0～1500 cm土层土壤湿度依次为18.6%、13.7%、170％、11.5%和13.1%,随树龄增加果园土壤湿度总体呈降低趋势,有补灌果园土壤尚未发生干燥化,而旱作果园均发生了轻度或中度干燥化,0～300 cm土层土壤湿度高于麦田.0～300 cm土层土壤有机质、全氮和碱解氮含量分别小于10 g·kg^-1、0.75 g·kg^-1和50 mg·kg^-1,均处于亏缺状态;速效磷含量介于3.30～6.42 mg·kg^-1,总体表现为浅层适宜、深层亏缺状态,速效钾含量介于78.09～98.31 mg·kg^-1,尚未亏缺.果园0～100 cm土层有机质和氮、磷、钾含量均高于100～300 cm土层.随果树种植年限增加,土壤有机质、全氮、碱解氮含量及土壤养分指数（SNI）均表现为先增加后降低趋势;除全钾外,随土层深度增加,各养分含量在0～100 cm土层范围内快速降低,之后维持相对稳定.土壤有机质、全氮、碱解氮、全磷、速效磷和速效钾含量之间呈极显著正相关,而全钾与其他6个养分指标之间的相关性不显著.     

UNC51‐like kinase 1, autophagic regulator and cancer therapeutic target

Autophagy, the cell process of self‐digestion, plays a pivotal role in maintaining energy homoeostasis and protein synthesis. When required, it causes degradation of long‐lived proteins and damaged organelles, indicating that it may play a dual role in cancer, by both protecting against and promoting cell death. The autophagy‐related gene (Atg) family, with more than 35 members, regulates multiple stages of the process. Serine/threonine protein kinase Atg1 in yeast, for example, can interact with other ATG gene products, functioning in autophagosome formation. One mammalian homologue of Atg1, UNC‐51‐like kinase 1 (ULK1) and its related complex ULK1–mAtg13–FIP200 can mediate autophagy under nutrient‐deprived conditions, by protein–protein interactions and post‐translational modifications. Although specific mechanisms of how ULK1 and its complex transduces upstream signals to the downstream central autophagy pathways is not fully understood, past studies have indicated that ULK1 can both suppress and promote tumour growth under different conditions. Here, we summarize some properties of ULK1 which can regulate autophagy in cancer, which may shed new light on future cancer therapy strategies, utilizing ULK1 as a potential new target.     

尿囊素在肉苁蓉属植物分类中的应用

以尿囊素作为鉴别试剂,对肉苁蓉属中的管花肉苁蓉与同属的其它品种植物进行鉴别.采用HPLC法,在以下色谱条件下(Hypersil ODS-2色谱柱4.6 mm×250 mm,5 μm,流动相为乙腈-7.5%二氧六环水溶液1:99,流速0.5 mL/min,柱温25℃,检测波长224 nm)绘制肉苁蓉属植物不同品种的色谱图.在盐生肉苁蓉或荒漠肉苁蓉的HPLC色谱图中,与对照品尿囊素色谱峰相应的位置处,显示保留时间相同的色谱峰,而在管花肉苁蓉供试品的HPLC色谱图中,无尿囊素色谱峰,提示不含尿囊素的肉苁蓉为管花肉苁蓉.该鉴别方法简便、灵敏,能快速、准确地将管花肉苁蓉与同属其它品种植物鉴别开来.     

An innovative prognostic model based on autophagy-related long noncoding RNA signature for low-grade glioma

Autophagy is a highly conserved lysosomal degradation process essential in tumorigenesis. However, the involvement of autophagy-related long noncoding RNAs (lncRNAs) in low-grade glioma (LGG) remains unclear. In this study, we established an autophagy-related lncRNA prognostic signature for patients with LGG and assess its underlying functions. We used univariate Cox, least absolute shrinkage and selection operator and multivariate Cox regression models to establish an autophagy-related lncRNA prognostic signature. Kaplan–Meier survival analysis, receiver operating characteristic curve, nomogram, C-index, calibration curve and clinical decision-making curve were used to assess the predictive capability of the identified signature. A signature comprising nine autophagy-related lncRNAs (AL136964.1, ARHGEF26-AS1, PCED1B-AS1, AS104072.1, PRKCQ-AS1, LINC00957, AS125616.1, PSMB8-AS1 and AC087741.1) was identified as a prognostic model. Patients with LGG were divided into the high- and low-risk cohorts based on the median model-based risk score. The survival analysis revealed a 10-year survival rate of 9.3% (95% CI 1.91–45.3%) and 13.48% (95% CI 4.52–40.2%) in high-risk patients in the training and validation sets, respectively, and 48.4% (95% CI 24.7–95.0%) and 48.4% (95% CI 28.04–83.4%) in low-risk patients in the training and validation sets, respectively. This finding suggested a relatively low survival in high-risk patients. In addition, the lncRNA signature was independently prognostic and potentially associated with the progression of LGG. Therefore, the 9-autophagy-related-lncRNA signature may play a crucial role in the diagnosis and treatment of LGG, which may offer new avenues for tumour-targeted therapy.

     

Key autophagic targets and relevant small‐molecule compounds in cancer therapy

Autophagy is a highly conserved lysosomal degradation process which can recycle unnecessary or dysfunctional cell organelles and proteins, thereby playing a crucial regulatory role in cell survival and maintenance. It has been widely accepted that autophagy regulates various pathological processes, among which cancer attracts much attention. Autophagy may either promote cancer cell survival by providing energy during unfavourable metabolic circumstance or can induce individual cancer cell death by preventing necrosis and increasing genetic instability. Thus, dual roles of autophagy may determine the destiny of cancer cells and make it an attractive target for small‐molecule drug discovery. Collectively, key autophagy‐related elements as potential targets, oncogenes mTORC1, class I PI3K and AKT, as well as tumour suppressor class III PI3K, Beclin‐1 and p53, have been discussed. In addition, some small molecule drugs, such as rapamycin and its derivatives, rottlerin, PP242 and AZD8055 (targeting PI3K/AKT/mTORC1), spautin‐1, and tamoxifen, as well as oridonin and metformin (targeting p53), can modulate autophagic pathways in different types of cancer. All these data will shed new light on targeting the autophagic process for cancer therapy, using small‐molecule compounds, to fight cancer in the near future.     

HEART与GRACE危险评分对急性冠脉综合征患者危险分层的对比研究

目的:探讨HEART与GRACE危险评分对急性冠脉综合症(ACS)患者主要心血管不良事件(MACE)发生的预测应用价值。方法:回顾性分析自2015年6月至2018年6月就诊于我院急诊入院的ACS患者591例,分别使用HEART与GRACE危险评分对研究对象进行危险分层(低危组,中危组,高危组),随访患者发病后90天MACE发生情况,分析不同危险分层ACS患者发病后90天MACE发生情况与评分之间的关系,并比较两种评分对ACS患者90天发生MACE事件的预测能力。结果:本研究纳入371例患者,其中男性324例(87.3%),女性47例(12.7%),年龄(58±11.70)岁;167患者(45.1%)在3个月内发生MACE。随着HEART和GRACE危险评分越高,发病90天发生MACE事件的发生率显著增加(P<0.05),HEART评分中高危组预测MACE准确性较GRACE评分高,GRACE评分低危险组预测MACE准确性较HEART评分高。HEART和GRACE评分对ACS患者预测MACE敏感性分别为76.51%,64.73%,特异性分别为96.71%,96.25%。HEART评分具有良好的预测价值,其ROC曲线下面积为0.908(95%CI 0.846~0.974),与GRACE评分ROC曲线下面积的0.801相比,差异有统计学意义(P<0.05)。结论:HEART和GRACE评分都可以应用于ACS患者的危险分层,预后评估和预测MACE发生,但HEART危险评分更可靠。     

Screening of crude drug extracts for prolyl endopeptidase inhibitory activity.

Prolyl endopeptidase (PEP, EC 3.4.21.26) is an enzyme to play a role in metabolism of proline-containing neuropeptides, such as vasopressin, substance P and thyrotropin-releasing hormone (TRH), which were suggested to be involved with learning and memory processes. Then, specific inhibitor of PEP is expected to have antiamnesic effects, and thus we screened forty-six water- and methanol-extracts from crude drugs selected on the basis of traditional Chinese medicine theory, for Flavobacterium prolyl endopeptidase inhibition. Among them, the water-extracts of Rhodiola sacra (IC50, 0.77 microgram/ml) and the methanol-extracts of Lycopodium clavatum (IC50, 1.3 micrograms/ml), Paeonia lactiflora var. trichocarpa (IC50, 5.7 micrograms/ml), Paeonia veitchii (IC50, 2.4 micrograms/ml) and Rhodiola sacra (IC50, 0.67 microgram/ml) showed strong inhibitory activity. In addition, we also examined the PEP inhibitory activity of eleven compounds from Salvia deserta, and found that in addition to a catechol group alpha-hydroxy-para-quinone group may be related to the PEP inhibition.