Emerging evidence points towards an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While pre-existing diabetes is associated with severe COVID-19 , it is unclear if COVID-19 severity is a cause or consequence of diabetes . To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β-cells can be infected by SARS-CoV-2 and cause β-cell depletion. We found that the SARS-CoV-2 receptor, ACE2 and related entry factors (TMPRSS2, NRP1, TRFC) are expressed in β-cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic β-cells in patients who succumbed to COVID-19 and selectively infects human islet β-cells in vitro . We demonstrated SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion, and induces β-cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic β-cell signaling, similar to that observed in Type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce β-cell killing.

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Preeclampsia (PE) is a major cause of maternal mortality and morbidity worldwide. Although there has been great progress in the understanding of PE, the exact cause for the disease development is still unclear. Recently, studies showed that genetic deletion of ELABELA (ELA, also known as APELA) could induce PE-like symptoms in mice. However, the role of ELA in the disease development of PE remains elusive. Our objective was to measure the changes of ELA levels in maternal serum, urine, and placenta from preeclamptic pregnant women and healthy pregnant women and evaluate the correlation between ELA levels and the occurrence of PE. Additionally, we investigated the effect of ELA on the migration and proliferation of human trophoblast cells. ELA levels are significantly decreased in late-onset PE pregnancies compared with normal pregnancies. The mRNA and protein expressions of ELA and the apelin receptor (APLNR or APJ) in late-onset PE placental tissues are also decreased. Furthermore, our in vitro study showed that the addition of ELA significantly increased the invasion ability and proliferation of trophoblast cells, which were inhibited by the APJ-specific antagonist ML221. Our study identified ELA as significantly decreased in late-onset PE; therefore, it might play an important role in the pathogenesis of late-onset PE.

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Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.

IMPORTANCE Breast cancer is the most commonly diagnosed cancer and the leading cause of death in women worldwide. Yet the racial/ethnic disparity in incidences and distributions of breast cancer remains largely unknown. OBJECTIVE To examine the racial/ethnic patterns associated with the incidence of the subtypes of breast cancer and distribution of patients across clinicopathological variables. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, which collected data from 18 SEER cancer registries that identified patients with breast cancer in the US diagnosed between January 1, 2010, and December 31, 2015. The inclusion criteria were (1) female patients with primary unilateral breast cancer who underwent surgical treatment; (2) record of estrogen receptor, progesterone receptor, and ERBB2 status; (3) record of medical history and histological subtype of the specified tumor location; and (4) data on patient race/ethnicity, lateral tumor position, tumor size, tumor TNM stage, and number of tumors. Incidence and distribution rates were identified and compared for different molecular subtypes, histological grades, pathological patterns, T stages, TNM stages, and tumor sites of breast cancers for each racial/ethnic group. Patient race/ethnicity was classified as follows: non-Hispanic White, Hispanic White, Black, Asian/Pacific Islander, American Indian/Alaskan Native, and unknown. Data were analyzed from January 1, 2010, to December 31, 2015. MAIN OUTCOMES AND MEASURES Incidence rates of 4 molecular subtypes: hormone receptor (HR)-positive and ERBB2-negative, HR-positive and ERBB2-positive, HR-negative and ERBB2positive, and triple-negative breast cancer (TNBC). Data on distribution by histological grades (grades 1-4 and unknown), pathological patterns, T stages, TNM stages, and tumor sites was also extracted. Annual age-standardized incidence rates and incidence rate ratios (IRRs) were calculated with 95% CIs. Race/ethnicity case-to-case odds ratios were estimated using polytomous regression. RESULTS A total of 239 211 women with breast cancer were analyzed (median [interquartile range]) age, 60 [50-69] years). The annual incidence rate of all breast cancers was 31.3 (95% CI, 31.2-31.5) per 100 000 people in non-Hispanic White women (the reference group), which was higher compared with the incidence among Black women