ABSTRACT

The majority of patients find that the oral route of drug administration is the most convenient, easy to follow, non- invasive, and physician-preferred method. However, oral biologic administration is not as beneficial as other routes because of mucosal permeability and various gastrointestinal barriers that limit the systemic absorption of complex macromolecules after ingestion. Patients tend to prefer taking medicines orally as tends to be more convenient; however, oral administration is not currently possible for biologics. The physiological role of the gastrointestinal tract presents multiple barriers that limit the systemic absorption of complex macromolecules after ingestion. Biologics are not only highly sensitive to the harsh environment of the gastrointestinal tract, but, as very large molecules, their permeability across the intestinal mucosa is extremely poor. Research in the area of oral delivery of biologics has a long and rich history and the proliferation of biologics in recent decades has further accelerated the research activity. This article summarizes the main physiological barriers to oral delivery of biologics and discuss different research strategies to enable or improve oral delivery of biologics.

Keywords: Absorption enhancers; biologics; drug delivery; gastrointestinal barriers; insulin; micro needle pill.

ABSTRACT

Adrenocortical cancer poses a significant clinical challenge due to its aggressiveness and limited treatment options. Herein, we investigated the role of NR2F1, as a potential dormancy factor, and its relationship with glutamine-dependency of adrenocortical cancer cells. Materials and Methods: NR2F1 expression was evaluated in adrenocortical cancer, in publicly available databases. H295R adrenocortical cancer cells and HAdCC normal adrenocortical cells transfected to overexpress NR2F1, were analyzed for cell viability, lysosome function, and protein expression of cell-cycle regulators, as well as for cell-cycle distribution. Kaplan-Meier analyses of publicly available databases showed a marginal positive association of NR2F1 expression with OS in adrenocortical cancer. Transient overexpression of NR2F1 in H295R cells resulted in suppressed proliferation and increased lysosome function. In normal human AdCC adrenocortical cells, lysosome activity was increased in glucose- and glutamine- deprived state, only when the cells were confluent. On the contrary, in H295R cells, lysosome activity was reduced in glucose- and glutamine- deprived states, only when the cells were confluent. Western blot analyses showed that the expression of NR2F1 was induced by confluency. Confluency also induced a marked increase in CDK1 and CDKN1A expression, which was significantly reduced by glutamine deprivation in H295R cells. Our findings provide new insights into the molecular mechanisms underlying the role of NR2F1 in cellular dormancy, as well as the expression patterns of CDK1 and CDKN1A in response to confluency and glutamine dependency, suggesting an interdependence of these pathways as potential therapeutic targets in adrenocortical cancer.

Keywords: Adrenocortical cancer, NR2F1, dormancy, glutamine deprivation.

ABSTRACT

The COVID-19 pandemic had a severe global impact. A range of campaigns and activities, including vaccines, are being implemented to counteract this pandemic. Using observational data, the goal of this scoping review is to identify adverse events connected with COVID-19 vaccinations. We conduct a scoping study and searched three databases from the start of the COVID-19 pandemic in 2020 through June 2022. Based on our criteria and searched keywords, the review included eleven papers in total, with the majority of the studies being conducted in developed countries. The study populations varied and included general community populations, healthcare professionals, military forces, and patients with systemic lupus and cancer. This study includes vaccines from Pfizer-BioNTech, Oxford-AstraZeneca, Sinopharm, and Moderna. The COVID-19 vaccine-related adverse events were classified into three types: local side effects, systemic side effects, and other side effects such as allergies. The adverse reactions to COVID-19 vaccines are mild to moderate in severity, with no significant influence or interference in individual daily activities and no unique patterns in cause of death among vaccine-related deaths. According to the findings of these investigations, the COVID-19 vaccine is safe to administer and induces protection. It is vital to convey accurate information to the public about vaccination side effects, potential adverse responses, and the safety level of the vaccines supplied. Multiple strategies must be implemented at the individual, organizational, and population levels to eliminate vaccine hesitance. Future studies could investigate the vaccine’s effect on people of various ages and medical conditions.

Keywords: COVID-19, vaccination, immune system, blood cells