Paclitaxel (PTX) is widely used as a front-line chemotherapy for breast cancer treatment. However, its clinical applications are limited by the development of chemoresistance. The objective of this study was to investigate the reversal effects of ursolic acid (UA) on PTX resistance and the possible mechanisms in breast cancer. The role of miRNA-149-5p/MyD88 in the regulation of PTX resistance was investigated by the transfection of breast cancer cells with MDA-MB-231 (231) and MDA-MB-231/PTX-resistance (231/PTX) with lentiviruses carrying the MyD88 gene, shRNA specific for MyD88, the miR-149-5p gene, and shRNA specific for miR-149-5p. The PTX sensitivity was assessed by a CCK-8 assay. qRT-PCR and Western blot analyses were used to detect changes in the mRNA and protein levels. Flow cytometry was used to measure the rate of cell apoptosis. A luciferase activity assay was used to detect the binding site of miR-149-5p on the 3′UTR of MyD88. 231/PTX cells were injected into the flanks of female athymic nude mice, and the mice were randomly divided into the five following groups: PBS, PTX (low), PTX (high), UA, and PTX+UA. Our data show that UA reversed the resistance of breast cancer 231/PTX cells to PTX
in vitro
and
in vivo
. UA treatment significantly increased the expression of miR-149-5p, which was lower in 231/PTX cells than in 231 cells. Furthermore, the overexpression of miR-149-5p increased the sensitivity of 231/PTX cells to PTX treatment, whereas the knockdown of the miR-149-5p gene attenuated the effects of UA on the regulation of PTX sensitivity. A luciferase assay demonstrated that miR-149-5p could directly regulate the transcriptional activity of MyD88, a known PTX-resistance gene, by targeting the 3′UTR of MyD88. Meanwhile, the downregulation of MyD88 through the overexpression of miR-149-5p or UA treatment inhibited the activation of the Akt signaling pathway in 231/PTX cells. Thus, our data indicate that UA can reverse PTX resistance by targeting the miRNA-149-5p/MyD88 axis in breast cancer cells.
Developing a rapid antibody-based detection method is of great importance for preventing and controlling the spread of coronavirus disease 2019 (COVID-19). Among the antibody-based methods for point-of-care (POC) detection, lateral flow immunoassay (LFIA) is the most widely used. However, LFIA still has the disadvantage of low sensitivity. In this work, an ReSe 2 nanosheet with a thickness of 10−20 nm was prepared by liquid exfoliation and applied as the label in a photothermal LFIA due to its high photothermal conversion efficiency and high photothermal stability. An integrated detection device was introduced for rapid, on-site, and highly sensitive assay of the human antisevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike (S) protein IgG antibodies. The device mainly included a rhenium diselenide (ReSe 2 ) nanosheet-based photothermal LFIA, a portable laser, and a smartphone with a portable thermal imager, which was used to record and analyze the thermal signal of the LFIA test zone. The human anti-SARS-COV-2 S protein IgG antibodies in buffer solution can be detected in a portable box within 10 min, with a thermal signal detection limit of 0.86 ng mL −1 , which was 108-fold lower than that of the colorimetric signal. The integrated device can detect values as low as 2.76 ng mL −1 of the human anti-SARS-COV-2 S protein IgG antibodies in 50% serum. The integrated device showed great potential for rapid and home self-testing diagnosis of COVID-19.
Rapid and sensitive detection of foodborne pathogenic bacteria is particularly important for the prevention and control of foodborne diseases. The lateral flow strip biosensor (LFSB) is one of the most promising point-of-care detection tools and has been widely used in food safety monitoring. This review introduces recent advances in the detection of foodborne pathogenic bacteria using LFSBs. According to different bacterial biomarkers, we summarize the direct and indirect sensing strategies of bacterial LFSBs. The direct sensing strategies for whole bacterial cells are divided into antibodies, antibody alternatives, and label-free according to the recognition elements. The indirect sensing strategies refer to the detection of bacterial nucleic acids and metabolites. Next, we compare and discuss the applications of direct and indirect sensing strategies. Finally, the existing challenges, future perspectives, and development directions are discussed, which will facilitate the theoretical innovation and practical application for bacterial LFSBs.
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