Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer

PURPOSE: MicroRNAs (miRNAs) play an essential role in breast malignant tumor development and progression. The development of clinically validated biomarkers for primary breast cancer (BC) has remained an insurmountable task despite other advances in the field of cancer molecular biology. The objective of this study is to investigate the differential expression of miRNAs and the potential of circulating microRNAs as novel primary breast cancer biomarkers. METHODS: Our analyses were performed on 48 tissue and 100 serum samples of patients with primary BC and a set of 20 control samples of healthy women, respectively. The relative expression of ten candidate miRNAs (miR-106b, miR-125b, miR-17, miR-185, miR-21, miR-558, miR-625, miR-665, miR-92a, and miR-93) from the results of four bioinformatics approaches and literature curation was measured by real-time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The level of miR-92a was significantly lower, while miR-21 was higher, as previous reports, in tissue and serum samples of BC than that of healthy controls (p < 0.001). Logistic regression and receiver operating characteristic curve analyses revealed the significant and independent value (p < 0.001) of the miR-92a and miR-21 expression quantification in serums. Moreover, the comparison with the clinicopathologic data of the BC patients showed that decreased levels of miR-92a and increased levels of miR-21 were associated with tumor size and a positive lymph node status (p < 0.001). CONCLUSIONS: These findings suggest that many miRNAs expressions are altered in BC, whose expression profiling may provide a useful clue for the pathophysiological research. Circulating miR-92a has potential use as novel breast cancer biomarker, which is comparable to miR-21

Selectively fluorinated citronellol analogues support a hydrogen bonding donor interaction with the human OR1A1 olfactory receptor

Authors thank the Chinese Scholarship Council for funding a Studentship (No. 202008060063) at the University of St. Andrews, U.K.C-2 fluorinated and methylated stereoisomers of the fragrance citronellol 1 and its oxalate esters were prepared from (R)-pulegone 11 and explored as agonists of the human olfactory receptor OR1A1 and assayed also against site-specific mutants. There were clear isomer preferences and C-2 difluorination as in 18 led to the most active compound suggesting an important hydrogen bond donor role for citronellol 1. C-2 methylation and the corresponding oxalate ester analogues were less active.Publisher PDFPeer reviewe

Activation of GATA4 gene expression at the early stage of cardiac specification

The exclusionary protected area-based approach to biodiversity conservation has succeeded at several places,but at a significant social cost and conflict, especially in the developing country tropics.More inclusive approaches, including community-based conservation (CBC), its subset enterprise-based conservation(EBC), and payments-based conservation (PES) programs, have been tried in the past 15 years. A brief summary of the literature on socio-economic impacts of the exclusionary approach suggests that, although detailed studies and documentation is missing,impacts are significant, and the ethical argument against forced displacement quite strong. We then examine the potential of non exclusionary approaches from a broader perspective that values biodiversity gains as well as socio-economic ones. Our review suggests that (a) comprehensive socio–ecological and comparative studies of such initiatives are surprisingly scarce, (b) enterprise-based conservation offers some potential if design flaws, poor implementation, assumptions about homogeneous communities, and inattention to tenurial change and security are addressed, (c) payments-based programs require caution because of their focus on economic efficiency, and simplified assumptions regarding the nature of rights, biological information,monitoring costs, and state interventions, and (d) the alternatives to exclusion have often not been given adequate state support and space to function, nor is the ongoing neoliberalization of the political-economic system conducive to giving them that space, except when they fit the direction of this larger process

Nutlin-3 overcomes arsenic trioxide resistance and tumor metastasis mediated by mutant p53 in Hepatocellular Carcinoma

Background: Arsenic trioxide has been demonstrated as an effective anti-cancer drug against leukemia and solid tumors both in vitro and in vivo. However, recent phase II trials demonstrated that single agent arsenic trioxide was poorly effective against hepatocellular carcinoma (HCC), which might be due to drug resistance. Methods: Mutation detection of p53 gene in arsenic trioxide resistant HCC cell lines was performed. The therapeutic effects of arsenic trioxide and Nutlin-3 on HCC were evaluated both in vitro and in vivo. A series of experiments including MTT, apoptosis assays, co-Immunoprecipitation, siRNA transfection, lentiviral infection, cell migration, invasion, and epithelial-mesenchy-mal transition (EMT) assays were performed to investigate the underlying mechanisms. Results: The acquisition of p53 mutation contributed to arsenic trioxide resistance and enhanced metastatic potential of HCC cells. Mutant p53 (Mutp53) silence could re-sensitize HCC resistant cells to arsenic trioxide and inhibit the metastatic activities, while mutp53 overexpression showed the opposite effects. Neither arsenic trioxide nor Nutlin-3 could exhibit obvious effects against arsenic trioxide resistant HCC cells, while combination of them showed significant effects. Nutlin-3 can not only increase the intracellular arsenicals through inhibition of p-gp but also promote the p73 activation and mutp53 degradation mediated by arsenic trioxide. In vivo experiments indicated that Nutlin-3 can potentiate the antitumor activities of arsenic trioxide in an orthotopic hepatic tumor model and inhibit the metastasis to lung. Conclusions: Acquisitions of p53 mutations contributed to the resistance of HCC to arsenic trioxide. Nutlin-3 could overcome arsenic trioxide resistance and inhibit tumor metastasis through p73 activation and promoting mutant p53 degradation mediated by arsenic trioxide

The specification and use of 18F-FES PET in breast cancer

Estrogen receptor (ER) is overexpressed in approximately 2/3 of breast cancer patients’ lesions. Noninvasive detection of ER in vivo and dynamic monitoring of ER are crucial for individualized treatment decision-making. 16α-18F-17β-fluoroestradiol (18F-FES) positron emission tomography (PET) has been used in a variety of preclinical and clinical studies to detect ER expression. However, there is still a lack of technical specifications in China. This technical specification was jointly written by domestic experts who had experience of 18F-FES PET imaging and was formed through consultation based on their own experience and research progress in this field both domestically and internationally. This technical specification introduced the synthesis method and quality control requirements of 18F-FES, recommended its clinical application scenarios, and classified them. In addition, experts’ suggestions were provided throughout the entire process systemically and detailly, including pre-imaging preparation, imaging process, image analysis (normal biological distribution, determination of ER positive and negative, lesion detection, influencing factors, false negative and false positive, report requirements), and the limitations of this imaging technique were proposed. The future application prospects were also discussed. This specification aimed to promote the standardized application of 18F-FES PET in China, achieve repeatability and comparability, and provide important molecular imaging technical support for accurate diagnosis and treatment of breast cancer

Research on anti-time dimension randomization method based on TSDM

Time-domain randomization makes side channel attacks difficult to align side information by inserting random delays, redundant operations, and variable frequency clocks, thereby reducing the efficiency. Aiming at the problem of time-domain misalignment of energy traces caused by time-dimensional randomization technology, this paper proposes an anti-time-domain randomization method based on Trend Series Dynamic Matching (TSDM). This method analyzes the distribution of attack interest points, and describes the shape feature of the energy trace, compresses the dimension of the energy trace, preserves the sensitive information of energy attacks, suppresses the negative impact of noise, realizes the dynamic alignment of data, and improves the efficiency of side channel attacks. This paper, conducts method verification and performance analysis for three typical time randomization techniques. Compared with various classical alignment methods, this method has better data alignment effect in different noise environments, and the number of energy traces required for the success rate of energy attack to reach 100% respectively decreased by 23.8%, 24.2%, 11.3%