No abstract

No abstract

Drug resistance in breast cancer (BC) cells continues to be a stern obstacle hindering BC treatment. Adriamycin (ADR) is a frequently employed chemotherapy agent used to treat BC. The exosomal transfer of microRNAs (miRNAs) has been reported to enhance the drug-resistance of BC cells. Herein, we first sought to elucidate the possible role of the exosomal transfer of miR-221-3p in the drug resistance of MCF-7 cells to ADR. Differentially expressed genes (DEGs) were initially screened through microarray analysis in BC drug resistance-related datasets. Next, the expression of miR-221-3p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was quantified in ADR-resistant MCF-7 (MCF-7/ADR) and ADR-sensitive MCF-7 (MCF-7/S) cell lines, after which exosomes were separated and identified in each cell line. Target relationship between miR-221-3p and PIK3R1 was validated by a dual-luciferase reporter assay. Next, the expression of miR-221-3p and PIK3R1 was altered to clarify their effects on the resistance of MCF-7 cells to ADR in vitro and in vivo. PIK3R1 was identified as a BC drug resistance-related DEG, with the regulatory miR-221-3p subsequently obtained. Moreover, the MCF-7/ADR cells exhibited a low expression of PIK3R1 and a high expression of miR-221-3p. Notably, PIK3R1 was identified as a target gene of miR-221-3p. The overexpression of miR-221-3p in MCF-7/ADR cell-derived exosomes promoted ADR resistance in MCF-7/S cells via the PI3K/AKT signaling pathway. The in vitro results were reproducible in in vivo assays. Taken together, drug-resistant BC cell-derived exosomal miR-221-3p can promote the resistance of BC cells to ADR by targeting PIK3R1 via the PI3K/AKT signaling pathway in vitro and in vivo. These findings provide encouraging insights and provide perspectives for further investigation into the BC drug resistance mechanism.

No abstract

BackgroundPatients with type 2 diabetes mellitus (T2DM) are at increased risk for COVID-19 related morbidity and mortality. Antibody response to COVID-19 vaccine in T2DM patients is not very clear. The present work aims to evaluate the antibody response to the inactivated SARS-CoV-2 vaccine in this population.MethodsTwo groups of subjects with no history of SARS-CoV-2 infection were included: 63 T2DM patients and 56 non-T2DM controls. Each participant received two doses of inactivated COVID-19 vaccine. IgG antibodies against the nucleocapsid (N) and spike (S) proteins of SARS-CoV-2 (anti-N/S IgG) and receptor binding domain (RBD) proteins (anti-RBD IgG) were quantitatively evaluated by the electrochemiluminescence immunoassays, respectively.ResultsIt was observed that the positive rates and titers of anti-N/S IgG and anti-RBD IgG in T2DM patients were significantly lower than those in controls, respectively (anti-N/S: 85.7 vs. 98.2%, P = 0.034; 25.48 vs. 33.58 AU/ml P = 0.011; anti-RBD: 85.7 vs. 96.4%, P = 0.044; 15.45 vs. 22.25 AU/ml, P = 0.019). Compared to non-T2DM subjects, T2DM patients with uncontrolled glycemia showed lower positive antibody rates and titers (anti-N/S IgG: 75% and 13.30 AU/ml; anti-RBD IgG: 75% and 11.91 AU/ml, respectively, all P < 0.05), while T2DM patients with controlled glycemia had similar positive antibody rates and titers (anti-N/S IgG: 94.3% and 33.65 AU/ml; and anti-RBD IgG: 94.3% and 19.82 AU/ml, respectively, all P > 0.05).ConclusionIn the analysis performed, the data indicate that T2DM patients with uncontrolled glycemia showed a lower level of IgG antibodies compared to non-diabetic controls and individuals with controlled glycemia when immunized with the inactivated COVID-19 vaccine.