Background: Breast cancer is the most occurring cancer in women with high incidence rates both in developed and developing countries. Among different types of breast cancers, Triple Negative Breast Cancer (TNBC) is the most aggressive type as it lacks receptors of Estrogen, Progesterone and Human Epidermal Growth Factor Receptor 2, common diagnostic biomarkers for the disease. Since early detection of TNBC can save thousands of lives, there is a dire need to discover and develop effective and affordable methods for early detection. Different Post Translational Modifications (PTMs) have been proposed as potential biomarker for various clinical conditions. Ubiquitination is a type of PTM involved in the stability and regulation of cellular proteins.
Objective: It is hypothesized that reticence of ubiquitination may lead to cell death. Current study focuses on the inhibition of Ubiquitin Specific Protease (USP), USP2 using its inhibitor, ML364 in HTB- 132 triple negative breast cancer cell line to induce cell death. The aim of the current study was to evaluate anticancer property of ML364 that might be a promising novel therapeutic agent for TNBC. Furthermore, current investigations focus on USP2 and their focal stabilizing substrates i.e. Fatty acid Synthase (FAS) and Cyclin D1 could be potential prognostic markers for the disease.
Methods: Quantitative PCR of CyclinD1, USP2, MDM2, and Fatty Acid Synthase (FAS) was performed to identify the deubiquitination effect of ML364 in breast cancer cells, which complemented our results with studies on normal and breast cancerous tissue samples.
Results: Expression of USP2 and its substrates Cyclin D1and FAS was found to be down regulated in ML364 treated breast cancer cell line whereas higher expression was observed in breast cancer tissue, indicating therapeutic potential of USP2 inhibitor.
Background: The essential trace element and micronutrient selenium exerts most of its biological actions through incorporation into selenoproteins as selenocysteine. Two further types of Se-containing proteins exist, including those that have selenomethionine incorporated instead of methionine, and the group of selenium-binding proteins. We previously described an ortholog of selenium-binding protein 1 (SELENBP1) in the nematode Caenorhabditis elegans, Y37A1B.5, and demonstrated that it confers resistance to toxic selenite concentrations while impairing general stress resistance and life expectancy of C. elegans.
Objective: We tested for the effect of selenite on Y37A1B.5 expression, and we analyzed whether Y37A1B.5 also shows a lifespan-modulating effect when the nematodes are deficient in the selenoenzyme thioredoxin reductase-1 (TRXR-1).
Methods: C. elegans expressing a translational reporter construct encoding GFP-tagged Y37A1B.5 under the control of the Y37A1B.5 promoter were exposed to selenite, followed by fluorescence microscopic analysis of GFP levels. Lifespan analyses and RNA interference experiments were performed in trxr-1-deficient worms.
Results: We here demonstrate that selenite at toxic concentrations stimulates the expression of the translational Y37A1B.5 reporter. The lifespan-extending effect of Y37A1B.5 deficiency was preserved upon the deletion of the only selenoprotein in C. elegans, TRXR-1.
Conclusion: These data suggest that (1) Y37A1B.5 may serve as a selenite-responsive buffer against high environmental selenium concentrations and that (2) lifespan extension elicited by Y37A1B.5 knockdown does not require functional TRXR-1. To read out more, please visit:https://www.eurekaselect.com/179267/article
Task-specific ionic liquids (TSILs) have received increased attention over the past few years as a Green Catalysts and Solvents for a large number of organic transformations. The present review article aims to provide an introduction, types of task-specific ionic liquids, preparation/synthesis, physical properties, characterization, use of TSILs as solvent and catalyst in organic synthesis. To read out more, please visit:http://www.eurekaselect.com/178331/article
Scientific interest in mycobacteria has been sparked by the medical importance of Mycobacterium tuberculosis (Mtb) that is known to cause severe diseases in mammals, i.e. tuberculosis and by properties that distinguish them from other microorganisms which are notoriously difficult to treat. The treatment of their infections is difficult because mycobacteria fortify themselves with a thick impermeable cell envelope. Channel and transporter proteins are among the crucial adaptations of Mycobacterium that facilitate their strength to combat against host immune system and anti-tuberculosis drugs. In previous studies, it was investigated that some of the channel proteins contribute to the overall antibiotic resistance in Mtb. Moreover, in some of the cases, membrane proteins were found responsible for virulence of these pathogens. Given the ability of M. tuberculosis to survive as an intracellular pathogen and its inclination to develop resistance to the prevailing anti-tuberculosis drugs, its treatment requires new approaches and optimization of anti-TB drugs and investigation of new targets are needed for their potential in clinical usage. Therefore, it is imperative to investigate the survival of Mtb. in stressed conditions with different behavior of particular channel/ transporter proteins. Comprehensive understanding of channel proteins and their mechanism will provide us direction to find out preventive measures against the emergence of resistance and reduce the duration of the treatment, eventually leading to plausible eradication of tuberculosis. To read out more, please visit:http://www.eurekaselect.com/180061/article