Systematic implications of flavonoids and sesquiterpene lactones in species of Vernonia

Systematic and evolutionary interpretations based upon the distributional data for 27 flavonoids from 39 species and 9 sesquiterpene lactones from 38 species are presented for species of Vernonia mostly from the New World.     

MiR-221/222 promote chemoresistance to cisplatin in ovarian cancer cells by targeting PTEN/PI3K/AKT signaling pathway

Cisplatin resistance is one of the main limitations in the treatment of ovarian cancer, and its mechanism has not been fully understood. The objectives of this study were to determine the role of miR-221/222 and its underlying mechanism in chemoresistance of ovarian cancer. We demonstrated that miR-221/222 expression levels were higher in A2780/CP cells compared with A2780 S cells. An in vitro cell viability assay showed that downregulation of miR-221/222 sensitized A2780/CP cells to cisplatin-induced cytotoxicity. Moreover, we found that knockdown of miR-221/222 by its specific inhibitors promoted the cisplatin-induced apoptosis in A2780/CP cells. Using bioinformatic analysis and luciferase reporter assay, miR-221/222 were found to directly target PTEN. Moreover, knockdown of miR-221/222 in A2780/CP cells significantly upregulated PTEN and downregulated PI3KCA and p-Akt expression. In conclusion, our results demonstrated that miR-221/222 induced cisplatin resistance by targeting PTEN mediated PI3K/Akt pathway in A2780/CP cells, suggesting that miR-221/222/PTEN/PI3K/Akt may be a promising prognostic and therapeutic target to overcome cisplatin resistance and treat ovarian cancer in the future.     

The role of sphingosine 1 phosphate in coronary artery disease and ischemia reperfusion injury

Coronary artery disease (CAD) is a common cause of morbidity and mortality worldwide. Atherosclerotic plaques, as a hallmark of CAD, cause chronic narrowing of coronary arteries over time and could also result in acute myocardial infarction (AMI). The standard treatments for ameliorating AMI are reperfusion strategies, which paradoxically result in ischemic reperfusion (I/R) injury. Sphingosine 1 phosphate (S1P), as a potent lysophospholipid, plays an important role in various organs, including immune and cardiovascular systems. In addition, high-density lipoprotein, as a negative predictor of atherosclerosis and CAD, is a major carrier of S1P in blood circulation. S1P mediates its effects through binding to specific G protein-coupled receptors, and its signaling contributes to a variety of responses, including cardiac inflammation, dysfunction, and I/R injury protection. In this review, we will focus on the role of S1P in CAD and I/R injury as a potential therapeutic target.     

New Arylazo-Based (Chromene-Thiazole) Hybrids as Potential MRSA Inhibitors

A three-component protocol was established to efficiently synthesize (chromene-thiazole) and related arylazo analogs in good to excellent yields. The desired products were prepared by reacting the appropriate salicylaldehydes, 2-cyanothioacetamide, and chloroacetone or hydrazonyl chlorides. Using piperidine as a mediator in ethanol at 80 °C for 4–6 h, the three-component protocol produce the target hybrids in 87–96 % yields. The newly synthesized products showed a broad range of antibacterial activity. The addition of an arylazo unit at the chromene-C6 position significantly improved the antibacterial activity, while the impact of adding an arylazo group at the thiazole-C5 position varied based on the electronic characteristics of the para-substituted arene unit. Generally, series that is linked to two arylazo units, one at chromene-C6 and the other at thiazole-C5, showed the best activity. Some new hybrids showed effective antibacterial activity than ciprofloxacin with MIC/MBC values up to 1.9/3.9 μM against S. aureus and E. coli. Additionally, they demonstrated better effectiveness against MRSA ATCC:33591 and ATCC:43300 compared to linezolid, with MIC/MBC values up to 4.0/16.1 and 3.9/15.6 μM, respectively. The data predicted for the physicochemical properties, lipophilicity, pharmacokinetics, and drug-likeness of new arylazo-based chromene-thiazole hybrids evaluated by SwissADME. As a result of the above, products that are linked to two arylazo units can be considered drug-like scaffolds.     

Evaluation of cytokeratin 19 as a prognostic tumoral and metastatic marker with focus on improved detection methods

In the last few years, there has been a growing interest in Cytokeratin 19 (CK19) studies in the cancer research field. CK19 belongs to the Type I CKs, serves as a useful research tool in prognosis, diagnosis, and management of the tumors. In this paper, we dissect the metastatic potential of CK19, its relation with cancer stem cells and retinal epithelial cells behavior, its application as a tumor marker and its role among 30 cancers such as thyroid, thoracic, lung, pancreatic, cervical, colorectal, and so forth. CK19 expressed in several cancer types because of its metastatic potential. This paper also presents modified detection methods of CK19 in disseminated tumor cells.