Eukaryotic Initiation Translation Factor 2A activation by cannabidiolic acid alters the protein homeostasis balance in glioblastoma cells.

Eukaryotic Initiation Translation Factor 2A (EIF2A) is considered to be primarily responsible for the initiation of translation when a cell is subjected to stressful conditions. However, information regarding this protein is still incomplete. Using a combination of proteomic approaches, we demonstrated that EIF2A is the molecular target of the naturally occurring bioactive compound cannabidiolic acid (CBDA) within human glioblastoma cells. This finding allowed us to undertake a study aimed at obtaining further information on the functions that EIF2A plays in tumor cells. Indeed, our data showed that CBDA is able to activate EIF2A when the cells are in no-stress conditions. It induces conformational changes in the protein structure, thus increasing EIF2A affinity towards the proteins participating in the Eukaryotic Translation Machinery. Consequently, following glioblastoma cells incubation with CBDA we observed an enhanced neosynthesis of proteins involved in the stress response, nucleic acid translation and organization, and protein catabolism. These changes in gene expression resulted in increased levels of ubiquitinated proteins and accumulation of the autophagosome. Our results, in addition to shedding light on the molecular mechanism underlying the biological effect of a phytocannabinoid in cancer cells, demonstrated that EIF2A plays a critical role in regulation of protein homeostasis.

Recent update on COVID-19 in India: Is locking down the country enough?

BackgroundIndia is the second-largest population in the world, and it is not well equipped, hitherto, in the scenario of the global pandemic, SARS-CoV-2 could impart a devastating impact on the Indian population. Only way to respond against this critical condition is by practicing large-scale social distancing. India lock down for 21 days, however, till 7 April 2020, SARS- CoV-2 positive cases were growing exponentially, which raises the concerns if the number of reported and actual cases are similar. MethodsWe use Lasso Regression with = 0.12 and Polynomial features of degree 2 to predict the growth factor. Also, we predicted Logistic curve using the Prophet Python. Further, using the growth rate to logistic, and carrying capacity is 20000 allowed us to calculate the maximum cases and new cases per day. ResultsWe found the predicted growth factor with a standard deviation of 0.3443 for the upcoming days. When the growth factor becomes 1.0, which is known as Inflection point, it will be safe to state that the rate is no longer exponential. The estimated time to reach the inflection point is between 15-20 April. At that time, the estimated number of total positive cases will be over 12500, if lockdown remains continue. ConclusionsOur analysis suggests that there is an urgent need to take action to extend the period of lockdown and allocate enough resources, including personnel, beds, and intensive care facilities, to manage the situation in the next few days and weeks. Otherwise, the outbreak in India can reach the level of the USA or Italy or could be worse than these countries within a few days or weeks, given the size of the population and lack of resources.