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A risk assessment on the aquatic toxicity of the plant biostimulant strigolactone mimic (2-(4-methyl-5-oxo-2,5-dihydro-furan-2-yloxy)-benzo[de]isoquinoline-1,3-dione (SL-6) was performed using a suite of standardised bioassays representing different trophic groups and acute and chronic endpoints. In freshwater, three trophic groups of algae, crustacea and fish were used. Whilst in seawater, algae (unicellular and macroalgae), Crustacea and Mollusca were employed. In addition, the genotoxicity of SL-6 was determined with the comet assessment performed on unicellular marine algae, oysters, and fish embryos. This was the first time ecotoxicity tests have been performed on SL-6. In freshwater, the lowest LOEC was measured in the unicellular algae at 0.31 mg/L SL-6. Although, similar LOEC values were found for embryo malformations and impacts on hatching rate in zebrafish (LOEC 0.31–0.33 mg/L). Consistent malformations of pericardial and yolk sac oedemas were identified in the zebrafish embryos at 0.31 mg/L. In marine species, the lowest LOEC was found for both Tisbe battagliai mortality and microalgae growth at an SL-6 concentration of 1.0 mg/L. Significant genotoxicity was observed above control levels at 0.0031 mg/L SL-6 in the unicellular algae and 0.001 mg/L SL-6 in the oyster and zebrafish larvae. When applying the simple risk assessment, based on the lowest NOECs and appropriate assessment factors, the calculated predicted no effect concentration (PNEC), for the ecotoxicity and the genotoxicity tests were 1.0 µg/L and 0.01 µg/L respectively.

Abstract Background Metabolic syndrome (MetS) is characterized by a cluster of signs of metabolic disturbance and has caused a huge burden on the health system. The study aims to explore the prevalence and characteristics of MetS defined by different criteria in the Chinese population. Methods Using the data of the China Hypertension Survey (CHS), a nationally representative cross-sectional study from October 2012 to December 2015, a total of 28,717 participants aged 35 years and above were included in the analysis. The MetS definitions of the International Diabetes Federation (IDF), the updated US National Cholesterol Education Program Adult Treatment Panel III (the revised ATP III), and the Joint Committee for Developing Chinese Guidelines (JCDCG) on Prevention and Treatment of Dyslipidemia in Adults were used. Multivariable logistic regression was used to identify factors associated with MetS. Results The prevalence of MetS diagnosed according to the definitions of IDF, the revised ATP III, and JCCDS was 26.4%, 32.3%, and 21.5%, respectively. The MetS prevalence in men was lower than in women by IDF definition (22.2% vs. 30.3%) and by the revised ATP III definition (29.2% vs. 35.4%), but the opposite was true by JCDCG (24.4%vs 18.5%) definition. The consistency between the three definitions for men and the revised ATP III definition and IDF definition for women was relatively good, with kappa values ranging from 0.77 to 0.89, but the consistency between the JCDCG definition and IDF definition (kappa = 0.58) and revised ATP III definition (kappa = 0.58) was poor. Multivariable logistic regression showed that although the impact and correlation intensity varied with gender and definition, area, age, education, smoking, alcohol use, and family history of cardiovascular disease were factors related to MetS. Conclusions The prevalence and characteristics of the MetS vary with the definition used in the Chinese population. The three MetS definitions are more consistent in men but relatively poor in women. On the other hand, even if estimated according to the definition of the lowest prevalence, MetS is common in China.

Acquired drug resistance and metastasis in breast cancer (BC) are coupled with epigenetic deregulation of gene expression. Epigenetic drugs, aiming to reverse these aberrant transcriptional patterns and sensitize cancer cells to other therapies, provide a new treatment strategy for drug-resistant tumors. Here we investigated the ability of DNA methyltransferase (DNMT) inhibitor decitabine (DAC) to increase the sensitivity of BC cells to anthracycline antibiotic doxorubicin (DOX). Three cell lines representing different molecular BC subtypes, JIMT-1, MDA-MB-231 and T-47D, were used to evaluate the synergy of sequential DAC + DOX treatment in vitro. The cytotoxicity, genotoxicity, apoptosis, and migration capacity were tested in 2D and 3D cultures. Moreover, genome-wide DNA methylation and transcriptomic analyses were employed to understand the differences underlying DAC responsiveness. The ability of DAC to sensitize trastuzumab-resistant HER2-positive JIMT-1 cells to DOX was examined in vivo in an orthotopic xenograft mouse model. DAC and DOX synergistic effect was identified in all tested cell lines, with JIMT-1 cells being most sensitive to DAC. Based on the whole-genome data, we assume that the aggressive behavior of JIMT-1 cells can be related to the enrichment of epithelial-to-mesenchymal transition and stemness-associated pathways in this cell line. The four-week DAC + DOX sequential administration significantly reduced the tumor growth, DNMT1 expression, and global DNA methylation in xenograft tissues. The efficacy of combination therapy was comparable to effect of pegylated liposomal DOX, used exclusively for the treatment of metastatic BC. This work demonstrates the potential of epigenetic drugs to modulate cancer cells' sensitivity to other forms of anticancer therapy.

Introduction microRNAs (miRs) have been reported as blood-based noninvasive indicators for the diagnosis of various diseases. However, the utility of whole blood-based miRs in the diagnosis of intracranial aneurysm (IA) is still not clear. The present study aimed to examine miR expression profiling in the peripheral whole blood of IA patients and healthy controls. Material and methods Seventy-three IA patients, including 34 unruptured and 39 ruptured, and 28 healthy subjects, were recruited for diagnostic analysis. microRNA (miR) expression profiling in whole blood from healthy controls and IA patients was evaluated using miRNA microarray assay. RT-qPCR was used to evaluate miR expression. Receiver operating characteristics (ROC) curves and the area under the ROC curves (AUC) were used to calculate the diagnostic power of miRs in whole blood of IA. Results We observed significantly higher miR-21 and miR-92 expression levels in aneurysmal tissues and whole blood of IA patients as compared to healthy subjects. miR-21 expression level was significantly positively correlated with miR-92 in IA tissues and whole blood of IA patients. ROC analysis revealed that miR-21 (AUC = 0.843, sensitivity = 0.849, specificity = 0.750) and miR-92 (AUC = 0.892, sensitivity = 0.945, specificity = 0.786) were promising in diagnosis of IA with high detectability. Intriguingly, miR-21 combined with miR-92 markedly improved the diagnostic power of IA (AUC = 0.920, sensitivity = 1.000, specificity = 0.786). Conclusions miR-21 combined with miR-92 could be considered as a potential biomarker for IA screening.

Metabolic syndrome (MetS) is associated with cardiovascular risk, and there are various definitions, but which is most predictive of future cardiovascular disease (CVD) in the Chinese population is still unclear. MetS was defined with the revised ATP III (Third Adult Treatment Panel Report), International Diabetes Federation (IDF), and the Joint Committee for Developing Chinese Guidelines (JCDCG) definitions. Cox regression was used to estimate the hazard risk of cardiovascular disease among 20,888 participants using the Chinese Hypertension Survey (CHS) data. Sensitivity, specificity, and receiver operating characteristic (ROC) curve distance were used to test the ability of three MetS criteria to identify CVD. During an average follow-up of 4.89 years of 20,888 participants, 925 CVD events occurred (stroke, 560; coronary heart disease, 275; and other cardiovascular events, 119). The revised ATP III criteria identified the most individuals with MetS and had the highest prevalence of MetS. In addition, MetS was associated with a high risk of CVD in both men and women, according to three criteria. The highest diagnostic specificity was for IDF in men and JCDCG in women. The revised ATP III criteria had the highest sensitivity and shortest ROC curve distance in both men and women. Although the MetS definitions, including the revised ATP III, IDF, and JCDCG, are all related to the increased risks of CVD, overall, the revised ATP III performs best and is the most recommended for the Chinese population.

Introduction: microRNAs (miRs) have been reported as blood-based noninvasive indicators for the diagnosis of various diseases. However, the utility of whole blood-based miRs in the diagnosis of intracranial aneurysm (IA) is still not clear. The present study aimed to examine miR expression profiling in the peripheral whole blood of IA patients and healthy controls. Material and methods: Seventy-three IA patients, including 34 unruptured and 39 ruptured, and 28 healthy subjects, were recruited for diagnostic analysis. microRNA (miR) expression profiling in whole blood from healthy controls and IA patients was evaluated using miRNA microarray assay. RT-qPCR was used to evaluate miR expression. Receiver operating characteristics (ROC) curves and the area under the ROC curves (AUC) were used to calculate the diagnostic power of miRs in whole blood of IA. Results: We observed significantly higher miR-21 and miR-92 expression levels in aneurysmal tissues and whole blood of IA patients as compared to healthy subjects. miR-21 expression level was significantly positively correlated with miR-92 in IA tissues and whole blood of IA patients. ROC analysis revealed that miR-21 (AUC = 0.843, sensitivity = 0.849, specificity = 0.750) and miR-92 (AUC = 0.892, sensitivity = 0.945, specificity = 0.786) were promising in diagnosis of IA with high detectability. Intriguingly, miR-21 combined with miR-92 markedly improved the diagnostic power of IA (AUC = 0.920, sensitivity = 1.000, specificity = 0.786). Conclusions: miR-21 combined with miR-92 could be considered as a potential biomarker for IA screening. [ABSTRACT FROM AUTHOR]