The 2019-2020 SARS-related coronavirus-2 (SARS-CoV-2) pandemic has brought unprecedented challenges to healthcare sectors around the world. As of November 2020, there have been over 64 million confirmed cases and approaching 2 million deaths globally. Despite the large number of positive cases, there are very limited established standards of care and therapeutic options available. To date, there is still no Food and Drug Administration (FDA) approved vaccine for COVID-19, although there are several options in various clinical trial stages. Herein, we have performed a global review evaluating the roles of age and sex on COVID-19 hospitalizations, ICU admissions, deaths in hospitals, and deaths in nursing homes. We have identified a trend in which elderly and male patients are significantly affected by adverse outcomes. There is evidence suggesting that sex hormone levels can influence immune system function against SARS-CoV-2 infection, thus reducing the adverse effects of COVID-19. Since older adults have lower levels of these sex hormones, we therefore speculate, within rational scientific context, that sex steroids, such as estrogen and progesterone, needs further consideration for use as alternative therapeutic option for treating COVID-19 elderly patients. To our knowledge, this is the first comprehensive article evaluating the significance of sex hormones in COVID-19 outcomes in older adults.

This report analyzes nuclear receptor (NR) subfamily 4A’s potential role in treating those diagnosed with breast cancer. Here we reviewed the current literature on NR4 family members. We also examined the relative gene expression of the NR4A receptor subfamily in the basal, HER2 (human epidermal growth factor receptor 2) positive, luminal A, and luminal B subtypes using data from tumor samples in The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). These data showed a positive link between NR4A1-NR4A3 expression and increased overall survival and relapse-free survival in breast cancer patients. In addition, we observed that high expression of NR4A1, NR4A2, and NR4A3 led to better survival. Furthermore, NR4A family genes seem to play an essential regulatory role in glycolysis and oxidative phosphorylation in breast cancer. The novel prognostic role of the NR4A1–NR4A3 receptors implicates these receptors as important mediators controlling breast cancer metabolic reprograming and its progression. The review establishes a strong clinical basis for the investigation of the cellular, molecular, and physiological roles of NR4A genes in breast cancer.

Background: Breast cancer is the most prevalent female cancer. Emerging evidence suggests that the unique serum miRNAs can assist in the early detection and diagnosis of breast cancer. Cell-free circulating miRNAs (about 22 nucleotides) are potential diagnostic tools and minimally invasive biomarkers for breast cancer detection. This study aimed to identify specific microRNAs in the serum of patients with breast cancer, which may serve as promising diagnostic and prognostic biomarkers and therapeutic targets. Material and methods: Next-generation sequencing and quantitative real-time PCR (qRT-PCR) array analyses of microRNAs in sera from different subtypes of breast cancer patients and normal female individuals were performed. The differentially expressed microRNAs were verified in serum samples from 100 breast cancer patients. The predictive values of the selected microRNAs were statistically analyzed, determined by the correlation between microRNA expression and tumor parameters. Datasets were graphed using GraphPad Prism Software 8.0. and analysis was done using one-way ANOVA with unpaired two-tailed Student’s t-test. Result: High serum levels of miR-125a-3p and miR-451a were found to be associated with breast cancer tumor subtype, size, and lymph node metastasis. Further functional in vitro experiments and enrichment analysis showed that overexpression and knockdown of miR-451 might significantly affect tumorigenic signaling pathways in TNBC cells. Conclusion: Altogether, our data suggested that serum levels of microRNAs miR-125a-3p and miR-451a can potentially serve as liquid biopsy biomarkers in breast cancer. Citation Format: Hassan Yousefi, Steven C. Eastlack, Jordyn T Fong, Samuel C. Okpechi, Jovanny Zabaleta, Lyndsey R. Buckner, Donnalee N Trapani, Erin Sims, Alison McDaniel McDaniel, Heather Scuderi, Meredith A. Lakey, John T. Cole, Suresh K. Alahari. Circulating miR-125a-3p and miR-451a may be liquid biopsy biomarkers for the diagnosis of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1477.