Synthesis and biological evaluation of halogenated phenoxychalcones and their corresponding pyrazolines as cytotoxic agents in human breast cancer

Novel halogenated phenoxychalcones 2a–f and their corresponding N-acetylpyrazolines 3a–f were synthesised and evaluated for their anticancer activities against breast cancer cell line (MCF-7) and normal breast cell line (MCF-10a), compared with staurosporine. All compounds showed moderate to good cytotoxic activity when compared to control. Compound 2c was the most active, with IC₅₀ = 1.52 µM and selectivity index = 15.24. Also, chalcone 2f showed significant cytotoxic activity with IC₅₀ = 1.87 µM and selectivity index = 11.03. Compound 2c decreased both total mitogen activated protein kinase (p38α MAPK) and phosphorylated enzyme in MCF-7 cells, suggesting its ability to decrease cell proliferation and survival. It also showed the ability to induce ROS in MCF-7 treated cells. Compound 2c exhibited apoptotic behaviour in MCF-7 cells due to cell accumulation in G2/M phase and elevation in late apoptosis 57.78-fold more than control. Docking studies showed that compounds 2c and 2f interact with p38alpha MAPK active sites.     

Mechanical stretch regulates the expression of specific miRNA in extracellular vesicles released from lung epithelial cells

The underlying mechanism of normal lung organogenesis is not well understood. An increasing number of studies are demonstrating that extracellular vesicles (EVs) play critical roles in organ development by delivering microRNAs (miRNA) to neighboring and distant cells. miRNAs are important for fetal lung growth; however, the role of miRNA–EVs (miRNAs packaged inside the EVs) during fetal lung development is unexplored. The aim of this study was to examine the expression of miRNA–EVs in MLE-12, a murine lung epithelial cell line subjected to mechanical stretch in vitro with the long-term goal to investigate their potential role in the fetal lung development. Both cyclic and continuous mechanical stretch regulate miRNA differentially in EVs released from MLE-12 and intracellularly, demonstrating that mechanical signals regulate the expression of miRNA–EVs in lung epithelial cells. These results provide a proof-of-concept for the potential role that miRNA–EVs could play in the development of fetal lung.     

HIRA directly targets the enhancers of selected cardiac transcription factors during in vitro differentiation of mouse embryonic stem cells

Molecular Biology Reports - HIRA is a histone chaperone known to modulate gene expression through the deposition of H3.3. Conditional knockout of Hira in embryonic mouse hearts leads to...     

Effect of a rye dwarfing gene on plant height,heading stage,and Fusarium head blight in triticale (×Triticosecale Wittmack)

Key message

The rye-derived dwarfing gene Ddw1 on chromosome 5R acts in triticale in considerably reducing plant height, increasing FHB severity and delaying heading stage.

Abstract

Triticale, an amphiploid hybrid between durum wheat and rye, is an European cereal mainly grown in Germany, France, Poland, and Belarus for feeding purposes. Dwarfing genes might further improve the genetic potential of triticale concerning lodging resistance and yield. However, they might have pleiotropic effects on other, agronomically important traits including Fusarium head blight. Therefore, we analyzed a population of 199 doubled haploid (DH) lines of the cross HeTi117-06 × Pigmej for plant height, heading stage, and FHB severity across 2 locations and 2 years. The most prominent QTL was detected on chromosome 5R explaining 48, 77, and 71 % of genotypic variation for FHB severity, plant height, and heading stage, respectively. The frequency of recovery in cross validation was ≥90 % for all three traits. Because the markers that detect dwarfing gene Ddw1 in rye are also in our population the most closely linked markers, we assume that this major QTL resembles Ddw1. For FHB severity two, for plant height three, and for heading stage five additional QTL were detected. Caused by the considerable genetic variation for heading stage and FHB severity within the progeny with the dwarfing allele, short-strawed, early heading and FHB-resistant lines can be developed when population size is large enough.     

Patient and Healthcare Provider Barriers to Hypertension Awareness,Treatment and Follow Up: A Systematic Review and Meta-Analysis of Qualitative and Quantitative Studies

Background

Although the importance of detecting, treating, and controlling hypertension has been recognized for decades, the majority of patients with hypertension remain uncontrolled. The path from evidence to practice contains many potential barriers, but their role has not been reviewed systematically. This review aimed to synthesize and identify important barriers to hypertension control as reported by patients and healthcare providers.

Methods

Electronic databases MEDLINE, EMBASE and Global Health were searched systematically up to February 2013. Two reviewers independently selected eligible studies. Two reviewers categorized barriers based on a theoretical framework of behavior change. The theoretical framework suggests that a change in behavior requires a strong commitment to change [intention], the necessary skills and abilities to adopt the behavior [capability], and an absence of health system and support constraints.

Findings

Twenty-five qualitative studies and 44 quantitative studies met the inclusion criteria. In qualitative studies, health system barriers were most commonly discussed in studies of patients and health care providers. Quantitative studies identified disagreement with clinical recommendations as the most common barrier among health care providers. Quantitative studies of patients yielded different results: lack of knowledge was the most common barrier to hypertension awareness. Stress, anxiety and depression were most commonly reported as barriers that hindered or delayed adoption of a healthier lifestyle. In terms of hypertension treatment adherence, patients mostly reported forgetting to take their medication. Finally, priority setting barriers were most commonly reported by patients in terms of following up with their health care providers.

Conclusions

This review identified a wide range of barriers facing patients and health care providers pursuing hypertension control, indicating the need for targeted multi-faceted interventions. More methodologically rigorous studies that encompass the range of barriers and that include low- and middle-income countries are required in order to inform policies to improve hypertension control.     

Synthesis,Biological Evaluation,Molecular Docking,ADME Predictions and QSAR Studies of Novel 1,2-Diazet and Pyrrole Derivatives as Anti-Inflammatory Agents

Russian Journal of Bioorganic Chemistry - Here we synthesized novel 1, 2-diazet and pyrrole derivatives and screened for their anti-inflammatory activity. In vivo anti-inflammatory evaluation...