Small Extracellular Vesicles (sEVs) are 50–200 nm in diameter vesicles delimited by a lipid bilayer, formed within the endosomal network or derived from the plasma membrane. They are secreted in various biological fluids, including airway nasal mucus. The goal of this work was to understand the role of sEVs present in the mucus (mu‐sEVs) produced by human nasal epithelial cells (HNECs) in SARS‐CoV‐2 infection. We show that uninfected HNECs produce mu‐sEVs containing SARS‐CoV‐2 receptor ACE2 and activated protease TMPRSS2. mu‐sEVs cleave prefusion viral Spike proteins at the S1/S2 boundary, resulting in higher proportions of prefusion S proteins exposing their receptor binding domain in an ‘open’ conformation, thereby facilitating receptor binding at the cell surface. We show that the role of nasal mu‐sEVs is to complete prefusion Spike priming performed by intracellular furin during viral egress from infected cells. This effect is mediated by vesicular TMPRSS2 activity, rendering SARS‐CoV‐2 virions prone to entry into target cells using the ‘early’, TMPRSS2‐dependent pathway instead of the ‘late’, cathepsin‐dependent route. These results indicate that prefusion Spike priming by mu‐sEVs in the nasal cavity plays a role in viral tropism. They also show that nasal mucus does not protect from SARS‐CoV‐2 infection, but instead facilitates it.

Prostate cancer (PCa) is the second most frequent cancer and the fifth leading cause of cancer death among men worldwide. At first, advanced PCa is treated by androgen deprivation therapy with a good initial response. Nevertheless, recurrences occur, leading to Castrate-Resistance Prostate Cancer (CRPC). During the last decade, new therapies based on inhibition of the androgen receptor pathway or taxane chemotherapies have been used to treat CRPC patients leading to an increase in overall survival, but the occurrence of resistances limits their benefits. Numerous studies have demonstrated the implication of extracellular vesicles (EVs) in different cancer cellular mechanisms. Thus, the possibility to isolate and explore EVs produced by tumor cells in plasma/sera represents an important opportunity for the deciphering of those mechanisms and the discovery of biomarkers. Herein, we summarized the role of EVs in therapeutic resistance of advanced prostate cancer and their use to find biomarkers able to predict these resistances.

In early 2020, the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, and rapidly propagated worldwide causing a global health emergency. SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) protein for cell entry, followed by proteolytic cleavage of the Spike (S) protein by the transmembrane serine protease 2 (TMPRSS2), allowing fusion of the viral and cellular membranes. Interestingly, TMPRSS2 is a key regulator in prostate cancer (PCa) progression which is regulated by androgen receptor (AR) signaling. Our hypothesis is that the AR signaling may regulate the expression of TMPRSS2 in human respiratory cells and thus influence the membrane fusion entry pathway of SARS-CoV-2. We show here that TMPRSS2 and AR are expressed in Calu-3 lung cells. In this cell line, TMPRSS2 expression is regulated by androgens. Finally, pre-treatment with anti-androgen drugs such as apalutamide significantly reduced SARS-CoV-2 entry and infection in Calu-3 lung cells but also in primary human nasal epithelial cells. Altogether, these data provide strong evidence to support the use of apalutamide as a treatment option for the PCa population vulnerable to severe COVID-19.

Background/Objectives: Carvedilol is an adrenergic blocker FDA-approved to improve outcomes in heart failure with reduced ejection fraction. Clinical trials examining whether carvedilol may be cardioprotective in the setting of cancer therapy-induced heart failure have generated mixed results that may depend on the cancer regimen, tumor, or comorbidities. Methods: To investigate the therapeutic potential of carvedilol to mitigate doxorubicin cardiotoxicity in cardiomyocytes, myocardial tissue, and in vivo, independent of confounding factors in clinical studies, we utilized disease-free cardiac slices and cardiomyocytes from mice, dogs, and human in vitro, and in wildtype mice injected with doxorubicin in vivo. We further evaluated the impact of carvedilol in dogs with cancer receiving doxorubicin. Results: In primary canine and murine cardiac slices, carvedilol treatment restored autophagy and prevented apoptosis from doxorubicin. Carvedilol restored mitochondrial energetics in human, canine, and murine models. In wildtype mice challenged with doxorubicin, carvedilol prevented declines in cardiac function and alterations in cardiac structure. In pet dogs with cancer and undergoing doxorubicin treatment, carvedilol was beneficial in preserving cardiac function and structure. Conclusions: Carvedilol activates cardioprotective autophagy, arrests doxorubicin-induced cell death, and improves energetics and cardiac structure and function across species.