Poly lactic-co-glycolic acid-alginate nanocarrier for efficient drug delivery to liver cancer cells.

Efficient drug delivery systems (DDSs) can potentially replace with conventional modalities in cancer therapy, like liver cancer. In this study, a novel folic acid (FA)-functionalised and alginate (Alg)-modified poly lactic-co-glycolic acid (PLGA) nanocomposite was developed for delivery of doxorubicin (Dox) to HepG2 and Huh7 liver cancer cells. After synthesising the nanocarrier, several analytical devices, including FT-IR, DLS, TGA, and TEM, were employed for its characterisation. Nano-metric size (55 and 85 nm in diameter), close to neutral surface charge, semi-spherical morphology, and successful synthesis were approved. Dox entrapment efficiency was determined near 1%, and sustained and pH-sensitive drug release behaviours of nanocarrier were ascertained for DDS. Afterwards, the cell viability test was carried out to study the HepG2 and Huh7 cells suppression capability of FA-PLGA-Dox-Alg. About 12% and 10% cell viabilities were observed in HepG2 and Huh7 cancer cells after 24 h treatment with 400 nM concentration of FA-PLGA-Dox-Alg nanocarrier respectively. The IC50 value was observed for 100 nM after 24 h of treatment in cancer cells. These data have indicated that fabricated nanocarrier could be promising DDS against liver cancer and replace with conventional approaches in cancer treatment, like chemotherapy.

PI3K/Akt/mTOR signaling pathway in cancer stem cells.

Cancer stem cells (CSCs) as a small subpopulation in tumor bulk are believed to initiate tumor formation and are responsible for the resistance to cancer therapy. The proliferation and differentiation of CSCs result in heterogeneity in a tumor which increases the chance of tumor survival and invasion. Many signaling pathways are abnormally activated or repressed in CSCs. Understanding these pathways and the metabolisms in CSCs may help targeted therapy in drug-resistant tumors. The PI3K/Akt/mTOR pathway is one of the major signaling pathways in CSCs involved in the maintenance of stemness, proliferation, differentiation, epithelial to mesenchymal transition (EMT), migration, and autophagy. Thus, suppressing the PI3K/Akt/mTOR pathway with inhibitors might be a promising strategy for targeted cancer therapy. Although the pathway is well-recognized and reviewed in tumor bulks, the functions in CSCs have not been well focused. Here, we reviewed the PI3K/Akt/mTOR signaling pathway and its functions in CSCs and addressed the potential therapeutic applications in drug-resistant tumors.

The effects of curcumin on the prevention of atrial and ventricular arrhythmias and heart failure in patients with unstable angina: A randomized clinical trial.

OBJECTIVE: Inflammation along with oxidative stress has an important role in the pathophysiology of unstable angina which leads to acute myocardial infarction, arrhythmias and eventually heart failure. Curcumin has anti-inflammatory and anti-oxidant effects and thereby, it may reduce cardiovascular complications. This randomized controlled trial aimed to investigate the effects of curcumin on the prevention of atrial and ventricular arrhythmias and heart failure in patients with unstable angina. MATERIALS AND METHODS: Forty patients with unstable angina who met the trial inclusion and exclusion criteria, participated in this double-blind randomized clinical trial. The patients were randomized into two groups: curcumin (80 mg/day for 5days) and placebo (80 mg/day for 5days). Cardiac function was evaluated by two-dimensional echocardiography devices at baseline (immediately after hospitalization) and 5 days after the onset of the trial. Atrial and ventricular arrhythmias were recorded by Holter monitors in cardiology ward, Ghaem academic hospital, Mashhad, Iran. Progression to heart failure, myocardial infarction, and pulmonary and cardiopulmonary resuscitation events as well as mortality were recorded daily throughout the study. RESULTS: There were no significant differences between the two groups in atrial and ventricular arrhythmias (p=0.2), and other echocardiographic parameters (Ejection fraction, E, A, E/A ratio, Em, and pulmonary artery pressure) at baseline and five days after the start of the trial. CONCLUSION: Nanocurcumin administered at the dose of 80 mg/day for five days had no effect in the incidence of cardiovascular complications in patients with unstable angina.