关键词： Longitudinal dietary intervention   Anthocyanins   Flavanones   UHPLC-ESIQqQ-MS   MS   Maqui berry   Citrus  

摘要： The comparison of non-caloric sweeteners (stevia and sucralose) and sucrose, on the plasma concentration and cumulative effects of phenolic compounds, was achieved. A long-term intervention, consisting of the daily intake of 330 mL of healthy citrus-maqui soft drinks, for 60 days, by 138 healthy overweight adults, was followed. A total of 24 bioavailable metabolites derived from caffeic acid, 3,4-di-hydroxyphenylacetic acid, eriodictyol, homoeriodictyol, hippuric acid, naringenin, 2,4,6-tri-hydroxybenzaldehyde, and vanillic acid were detected in peripheral blood plasma. A similar augment of bioactive compounds in plasma concentrations were found for the three beverages, in the range 12.3% (day 0)-85.3% (day 60), depending on the analyte considered. Due to this, the present study highlights sucralose and stevia as valuable alternatives to sucrose, providing and non significantly different plasma concentration and cumulative effect in the plasma, thus contributing to prevent a diversity of metabolic disorders and health constraints.

关键词： alternative splicing   chromatin   histone modifications   H3K27   CRISPR   epigenome editing   epithelial-to-mesenchymal transition   EMT  

摘要： Histone modifications impact final splicing decisions. However, there is little evidence of the driving role of these marks in inducing cell-specific splicing changes. Using CRISPR epigenome editing tools, we show in an epithelial-to-mesenchymal cell reprogramming system (epithelial-to-mesenchymal transition [EMT]) that a single change in H3K27ac or H3K27me3 levels right at the alternatively spliced exon is necessary and sufficient to induce a splicing change capable of recapitulating important aspects of EMT, such as cell motility and invasiveness. This histone-mark-dependent splicing effect is highly dynamic and mediated by direct recruitment of the splicing regulator PTB to its RNA binding sites. These results support a role for H3K27 marks in inducing a change in the cell's phenotype via regulation of alternative splicing. We propose the dynamic nature of chromatin as a rapid and reversible mechanism to coordinate the splicing response to cell-extrinsic cues, such as induction of EMT.

摘要： Alternatively spliced RNA isoforms are a hallmark of tumors, but their nature, prevalence, and clinical implications in gastric cancer have not been comprehensively characterized. We systematically profiled the splicing landscape of 83 gastric tumors and matched normal mucosa, identifying and experimentally validating eight splicing events that can classify all gastric cancers into three sub-types: epithelial-splicing (EpiS), mesenchymal-splicing (MesS), and hybrid-splicing. These subtypes were associated with distinct molecular signatures and epithelial-mesenchymal transition mar-kers. Subtype-specific splicing events were enriched in motifs for splicing factors RBM24 and ESRP1, which were upregulated in MesS and EpiS tumors, respectively. A simple classifier based only on RNA levels of RBM24 and ESRP1, which can be readily imple-mented in the clinic, was sufficient to distinguish gastric cancer subtypes and predict patient survival in multiple independent patient cohorts. Overall, this study provides insights into alternative splicing in gastric cancer and the potential clinical utility of splicing-based patient classification. Significance: This study presents a comprehensive analysis of alternative splicing in the context of patient classification, molecular mechanisms, and prognosis in gastric cancer.

关键词： Plant-based alternative foods   Food system transformations   Dietary trends   United Kingdom   Sustainable food systems  

摘要： A global transformation towards sustainable food systems is crucial for delivering on climate change mitigation targets worldwide. In high-and middle-income settings, plant-based meat and dairy alternatives present potential substitutes for animal sourced foods, and a pathway to transition to more sustainable diets. We examined plant-based alternative foods (PBAF) consumption trends in the UK by analysing repeated cross-sectional food consumption data from the National Diet and Nutrition Survey 2008-2019. Dietary data for 15,655 individuals aged 1.5 years and over were analysed to assess aggregate change in intake of PBAF and six other food groups that play a role in transformative dietary change. Characteristics associated with consumption of PBAF were explored using logistic regression, and consumption patterns in high and low meat consumers were explored by examining intake of potential animal product substitute food groups. The proportion of individuals reporting consumption of any PBAFs increased from 6.7% in 2008-2011, to 13.1% in 2017-2019 (p < 0.01). Compared to 2008-2011 PBAF consumption rose by 115% in 2017-2019 (p < 0.01). Females were 46% more likely than males to report consumption of PBAF (p < 0.01). Millennials (age 24-39 years) were the most likely generation to report PBAF consumption (p < 0.01 compared to generation Z (age 11-23 years) and traditionalists (age 75+ years)), as were individuals of the highest income tertile (p < 0.01). Among "low meat consumers", PBAF consumption was on average higher than "high meat consumers" (18.6 g versus 4.8 g PBAF per day, p < 0.01). Our results support the hypothesis of a pivotal role of PBAF in the transition towards sustainable food systems in the UK, by demonstrating they are becoming increasingly popular among UK consumers. This highlights the ur-gent need to assess in detail the environmental and health impacts of large scale and population-wide consump-tion of PBAF in comparison to their animal-based equ

关键词： Trypanosome alternative oxidase inhibitor   Trypanosoma brucei   benzamidine   imidazoline   glycolysis  

摘要： The trypanosome alternative oxidase (TAO), a mitochondrial enzyme involved in the respiration of the blood-stream form trypomastigotes of Trypanosoma brucei, is a validated drug target against African trypanosomes. Earlier series of TAO inhibitors having a 2,4-dihydroxy-6-methylbenzoic acid scaffold ("head") and a triphenylphosphonium or quinolin-1-ium cation as a mitochondrion-targeting group ("tail") were shown to be nanomolar inhibitors in enzymatic and cellular assays. We investigated here the effect of different mitochondrion-targeting cations and other scaffold modifications on the in vitro activity of this class of inhibitors. Low micromolar range activities were obtained, and the structure-activity relationship studies showed that modulation of the tail region with polar substituents is generally detrimental to the enzymatic and cellular activity of TAO inhibitors.

关键词： Dipyridamole   DNA binding   Genotoxicity   Cytotoxicity   Anti-cancer  

摘要： The molecular mechanism behind the anti-cancer potential of dipyridamole, an antiplatelet drug was investigated by examining the interaction of dipyridamole with DNA as well as the genotoxicity and cytotoxicity associated with dipyridamole . Interaction of dipyridamole with calf thymus DNA (Ct-DNA) was determined in order to ascertain the strength and mode of binding as well as the thermodynamic parameters involved. Dipyridamole interacts with Ct-DNA through a groove binding mechanism. Furthermore, a preliminary assessment of the genotoxic effect of dipyridamole was performed in vitro using the plasmid nicking assay and comet assay. Genotoxicity was also confirmed through DAPI nuclear staining of HeLa and HCT-116 cells. Cytotoxicity was assessed in vitro on HeLa, HCT-116 as well as HEK293 cells using the MTT assay as well as through inverted microscopy. Dipyridamole was selectively more toxic towards cancer cells. Dipyridamole demonstrated induction of micronucleus and chromosomal aberrations only at high concentrations in bone marrow cells of male Wistar rats, suggesting its safe usage at clinically relevant concentrations. These results indicated the existence of an intrinsic genotoxic potential of dipyridamole which may be contributing to its anti-cancer properties . (c) 2021 Elsevier B.V. All rights reserved.

关键词： Alternative preservatives   Cosmetic products   Gas chromatography-mass spectrometry   Hydroxylated compounds   Ultrasound-assisted leaching  

摘要： Some hydroxylated compounds commonly used in cosmetic formulations including short chain glycols, benzylic alcohols, and organic acids show antimicrobial activity, although they are not considered as preservatives according to the existing European legislation. These 'alternative preservatives' are not exempt of potential side-effects for cosmetics users. The aim of this work is to develop a simple and affordable analytical method useful for the simultaneous and green determination of fourteen compounds used as 'alternative preservatives' in cosmetic samples with different matrices. The proposed method allows a rapid sample preparation by simple dissolution or dispersion of the sample in ethanol using ultrasound-assisted leaching of the analytes from the cosmetic matrix. Gas chromatography coupled to mass spectrometry (GC-MS) is used for the analysis of the samples. Working conditions for the instrumental measure and the quantification of analytes were studied. The method was found to have high sensitivity and good precision (relative standard deviation below 13%) as well as low limits of detection (i.e., 0.01.10(-3)-2.14.10(-3)% w/w) and quantification (i.e., 0.04.10(-3)-7.14.10(-3)% w/w). The method was successfully applied to five commercial cosmetic samples of different composition. Recovery values near 100% were obtained. Each sample was found to contain at least three of the analytes of the study and their concentrations were determined with low standard deviations. The analytical features of the proposed method and the obtained results agree with the principles of Green Analytical Chemistry and make it a useful tool for controlling these alternative preservatives in the cosmetic industry in order to guarantee quality and safety of the products. (C) 2021 The Authors. Published by Elsevier B.V.

关键词： alternative splicing   pluripotency   RNA-binding protein   ZFP207   Zinc finger protein  

摘要： The pluripotent state is not solely governed by the action of the core transcription factors OCT4, SOX2, and NANOG, but also by a series of co-transcriptional and post-transcriptional events, including alternative splicing (AS) and the interaction of RNA-binding proteins (RBPs) with defined subpopulations of RNAs. Zinc Finger Protein 207 (ZFP207) is an essential transcription factor for mammalian embryonic development. Here, we employ multiple functional analyses to characterize its role in mouse embryonic stem cells (ESCs). We find that ZFP207 plays a pivotal role in ESC maintenance, and silencing of Zfp207 leads to severe neuroectodermal differentiation defects. In striking contrast to human ESCs, mouse ZFP207 does not transcriptionally regulate neuronal and stem cell-related genes but exerts its effects by controlling AS networks and by acting as an RBP. Our study expands the role of ZFP207 in maintaining ESC identity, and underscores the functional versatility of ZFP207 in regulating neural fate commitment.

关键词： 益生菌   替抗产品   肉鸡   联合应用技术  

摘要： 抗生素使用在肉鸡养殖业中起到了不可替代的作用,而其耐药性的产生、对环境的污染已引起全行业人的重视,新抗生素的研发速度远远落后于耐药菌进化速率,不得不让人类发展与应用能够规避其缺陷的产品。肉鸡业是全球增长速度较快行业之一,伴随我国饲料禁抗令的频布与实施,许多的替抗产品应运而生,但效果不一。为了保障经济效益和高质量需求,不同替抗产品之间的联合应用技术开始不断地探索与尝试。本文综述了国内外益生菌与其他替抗产品在肉鸡上联合应用技术,以期为生产提供理论借鉴。