Effects of statins on outcomes in Hispanic patients with COVID-19.

The Hispanic population is regarded among those who are at greater risk of adverse prognoses due to higher rates of diabetes and obesity in the USA during the COVID-19 pandemic. Statin medications are speculated to help treat the infection by decreasing inflammation caused by COVID-19. In this retrospective, observational study, outcomes of statin use were assessed among Hispanic patients with COVID-19 by screening all patients hospitalized between March, 2020 and March, 2021 at a tertiary care hospital in El Paso, Texas, resulting in a total of 1039 patients. The patients were categorized into a group of either being on statins or not. The considered outcomes were mechanical ventilation, intensive care unit (ICU) hospitalization, oxygen supplementation at discharge, hospital length of stay, and mortality. Patients receiving statins were observed to be older with more comorbidities. In the propensity-scores adjusted analysis, no association was found between statin use and: mortality (adjusted risk ratio (aRR)=0.96, p=0.754), mechanical ventilation (aRR=0.91, p=0.503), ICU transfer (aRR=0.96, p=0.395), and O2 supplementation at discharge (aRR=1.03, p=0.729). These outcomes were also evaluated in patients who had myocardial infarction and stroke with COVID-19. Among these patients, association was found between statin use and: a reduced risk of mortality (aRR=0.61, p=0.005), mechanical ventilation (aRR=0.53, p=0.012) and ICU transfers (aRR=0.81, p=0.005). These results may not give us a reason to start patients on statins for the specific treatment of COVID-19, but it may be sufficient evidence to suggest statins should not be discontinued during hospitalization due to COVID-19.

Crosstalk between progesterone receptor membrane component 1 and estrogen receptor α promotes breast cancer cell proliferation.

Progesterone (P4) and estradiol (E2) have been shown to stimulate and regulate breast cancer proliferation via classical nuclear receptor signaling through progesterone receptor (PR) and estrogen receptor α (ERα), respectively. However, the basis of communication between PR/ERα and membrane receptors remains largely unknown. Here, we aim to identify classical and nonclassical endocrine signaling mechanisms that can alter cell proliferation through a possible crosstalk between PR, ERα, and progesterone receptor membrane component 1 (PGRMC1), a membrane receptor frequently observed in breast cancer cells. While P4 and E2 treatment increased cell proliferation of ER+/PR+/PGRMC1 overexpressing breast cancer cells, silencing ERα and PR or treatment with selective estrogen receptor modulator (SERM) tamoxifen, or (PR-antagonist) RU-486 decreased cell proliferation. All four treatments rapidly altered PGRMC1 mRNA levels and protein expression. Furthermore, P4 and E2 treatments rapidly activated EGFR a known interacting partner of PGRMC1 and its downstream signaling. Interestingly, downregulation of ERα by tamoxifen and ERα silencing decreased the expression levels of PGRMC1 with no repercussions to PR expression. Strikingly PGRMC1 silencing decreased ERα expression irrespective of PR. METABRIC and TCGA datasets further demonstrated that PGRMC1 expression was comparable to that of ERα in Luminal A and B breast cancers. Targeting of PR, ERα, and PGRMC1 confirmed that a crosstalk between classical and nonclassical signaling mechanisms exists in ER+ breast cancer cells that could enhance the growth of ER+/PR+/PGRMC1 overexpressing tumors.