Chandwani, M. N. | bioRxiv Science

bioRxiv2023

Effect of homotypic vs. heterotypic interactions on the cellular uptake of extracellular vesicles

Extracellular vehicles (EVs) are an emerging class of drug carriers and are primarily reported to be internalized into recipient cells via a combination of endocytic routes such as clathrin-mediated, caveolae-mediated and macropinocytosis pathways. In this work, (1) we investigated potential effects of homotypic vs. heterotypic interactions by studying the cellular uptake of homologous EVs (EV donor cells and recipient cells of the same type) vs. heterologous EVs (EV donor cells and recipient cells of different types) and (2) determined the route of EV internalization into low pinocytic/hard-to-deliver cell models such as brain endothelial cells (BECs). We used BECs and macrophages as low-pinocytic and phagocytic cell models, respectively, to study the effect of homotypic vs. heterotypic interactions on EV uptake in the recipient cells. Homotypic interactions led to a greater extent of uptake into the recipient BECs compared to heterotypic interactions. However, we did not see a complete reduction in EV uptake into recipient BECs when endocytic pathways were blocked using pharmacological inhibitors. Our results suggest that EVs primarily use membrane fusion to enter low-pinocytic recipient BECs instead of relying on endocytosis. Lipophilic PKH67 dye-labeled EVs but not intravesicular esterase-activated calcein ester-labeled EVs severely reduced particle uptake into BECs while phagocytic macrophages internalized both types of EV-labeled particles to comparable extents. Our results also highlight the importance of carefully choosing labeling dye chemistry to study EV uptake, especially in the case of low pinocytic cells such as BECs. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=171 HEIGHT=200 SRC="FIGDIR/small/563628v2_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@d5cb50org.highwire.dtl.DTLVardef@172d1dorg.highwire.dtl.DTLVardef@192caf6org.highwire.dtl.DTLVardef@4b16ba_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

Long weekend sleep is linked to stronger academic performance in male but not female pharmacy students

Introduction Poor sleep hygiene portends loss of physical and mental stamina. Therefore, maintaining a regular sleep/wake schedule on both weekdays and weekends is highly recommended. However, this advice runs contrary to the habits of university students, who may only experience recovery sleep if they sleep late on weekends. Pharmacy students at Duquesne University sit for frequent examinations, typically commencing at 7:30 AM, and they complain about fatigue. Here, we tested the central hypothesis that longer sleep durations on weekdays and weekends are linked to stronger academic performance in Pharmacy students.Methods Students in their first professional year were administered three surveys to collect data on sleep habits and factors that might influence sleep, such as roommates, long commute times, and sleep interruptions. GPAs were collected from the Dean’s office, with permission from the students.Results Longer weekend—but not weekday—sleep durations were significantly correlated with higher cumulative GPAs in men and not in women. Women achieved slightly higher cumulative GPAs than men. Students who fell asleep within 15 minutes of going to bed had higher professional-phase GPAs than those who fell asleep after an hour or more.Conclusion Our observations cannot establish causal links, but, given the body of prior evidence on the salutary properties of sleep, men in this cohort may reap benefit from recovery sleep on weekends. Rather than recommending that students force themselves awake early on weekends in an attempt to maintain a consistent sleep routine, the real-life habits of students should be given consideration.View Full Text

scientific communication and education↗