Tilleywestergaard8311

Background Paclitaxel (PTX) resistance is a major obstacle in the treatment of triple-negative breast cancer (TNBC). Previously, we have reported that interleukin-1 receptor-associated kinase 1 (IRAK1) and its downstream pathways are associated with PTX resistance in TNBC cells. In this study, we sought to investigate the combination treatment of ginsenoside panaxatriol (GPT), one of the main active components in Panax ginseng, with PTX on viability and apoptosis of TNBC PTX resistant cells, and explore the role of IRAK1 mediated signaling pathways in the therapeutic effects. Methods CellTiter-Glo and colony formation assays were used to assess cell viability. Flow cytometry was used to analyze subG1 and apoptosis. Western blot was used to detect expressions of proteins involved in apoptosis and the IRAK1/NF-κB and ERK pathways. The mRNA expression of inflammatory cytokines, S100A7/8/9 and cancer stem cell (CSC)-related genes were examined by qPCR. Stem cells were identified by tumor sphere assay. Brr2 Inhibitor C9 DNA inhibitor Cell invasion ability was examined by transwell assay. Results We show that GPT inhibits MDA-MB-231 PTX resistant (MB231-PR) cell viability in a dose-dependent manner. When combined with PTX, GPT synergistically causes more cell death, induces subG1 accumulation and cell apoptosis. Besides, up-regulation of BAX/BCL-2 ratio, and down-regulation of MCL-1 are also observed. Moreover, this combination inhibits IRAK1, NF-κB and ERK1/2 activation, and leads to down-regulation of inflammatory cytokines (IL6, IL8, CXCL1, CCL2), S100A7/9 and CSC-related genes (OCT4, SOX2, NANOG, ALDH1, CD44) expression. In addition, the combination treatment suppresses MB231-PR cell invasion ability, and impairs tumor sphere growth both in MB231-PR and SUM159 PTX resistant (SUM159-PR) cells. Conclusion Our study demonstrates that GPT can resensitize TNBC PTX resistant cells to PTX by inhibiting the IRAK1/NF-κB and ERK pathways and reducing stem cell characteristics.Background Highly sensitive real-time reverse transcription polymerase chain reaction (RT-qPCR) methods have been developed for the detection of SARS-CoV-2. However, they are costly. Loop-mediated isothermal amplification (LAMP) assay has emerged as a novel alternative isothermal amplification method for the detection of nucleic acid. Methods A rapid, sensitive and specific real-time reverse transcription LAMP (RT-LAMP) assay was developed for SARS-CoV-2 detection. Results This assay detected one copy/reaction of SARS-CoV-2 RNA in 30 min. Both the clinical sensitivity and specificity of this assay were 100%. The RT-LAMP showed comparable performance with RT-qPCR. Combining simplicity and cost-effectiveness, this assay is therefore recommended for use in resource resource-limited settings.Cardiovascular factors are associated with the pathophysiological features and risk of sudden sensorineural hearing loss (SSNHL). However, little is known about the link between carotid intima-media thickness (IMT), SSNHL risk, and their respective treatment outcomes. In this study, we retrospectively reviewed 47 SSNHL cases and 33 control subjects from a single medical center and compared their demographic data and clinical characteristics, including their carotid IMT and audiological data. Of the 80 enrolled subjects, the proportion of those with high carotid IMT was greater in the SSNHL group (53.2%) than in the control group (21.2%), with an odds ratio (OR) of 4.22 (95% confidence interval (CI) [1.53-11.61], P = 0.004). Notably, high carotid IMT was more common in female SSNHL patients than females in the control group (54.2% vs. 12.5%; OR, 8.27 (95% CI [1.53-44.62]), P = 0.008), particularly in female patients ≥50 years of age (75% vs. 25%; OR, 9.0 (95% CI [1.27-63.9]), P = 0.032). The multivariate regression analyses showed the association between high carotid IMT and SSNHL with an adjusted OR of 4.655 (95% CI [1.348-16.076], P = 0.015), particularly in female SSNHL patients (adjusted OR, 9.818 (95% CI [1.064-90.587], P = 0.044). The carotid IMT was not associated with the treatment outcomes of SSNHL. Our results indicate that early-stage atherosclerosis may be associated with SSNHL, particularly in female patients more than 50 years old.Background Carbon (C), nitrogen (N) and phosphorus (P) stoichiometric ratios are important indicators of ecosystem function and productivity. However, few studies have assessed the nutrient relationship between plant, litter and soil, and the nutrient stock in different secondary mixed forest types. Methods We investigated the C, N and P concentrations and stoichiometric ratios in trees, understory plants, litter and soil layers in three different secondary mixed forest types (broadleaf mixed forests (BM), broadleaf-conifer mixed forests (BCM) and coniferous mixed forests (CM)) in the Qinling Mountains. Results The results showed that significant differences in CNP stoichiometry were detected in multiple organs in the vegetation layers in the different forest types. Trees, shrubs and herbs all allocated more N and P in leaves and had a higher NP ratio in leaves than in other organs. The C concentrations, CN ratios and CP ratios of all tree organs showed a decreasing order BM CM. For litter and soil, BM had generally higher N and P concentrations than those of BCM and CM. The highest N and P stock was in tree branches-not in the stem, which had the highest biomass (except for P in CM). Compared with other forest types, CM stored more nutrients in the labile litter layer, while BM stored more nutrients in the stable soil layer. The net ecosystem nutrient element stock in BM was generally higher than that in BCM and CM. The C, N and P concentrations and stoichiometry in the plant organs, litter and soil were significantly correlated. Conclusion Our findings demonstrate that nutrient concentrations in plant organs, litter and soil are tightly linked in secondary mixed forests.Background Melanoma is a highly invasive malignant skin tumor. While melanoma may share some similarities with that of melanocytic nevi, there also exist a number of distinct differences between these conditions. An analysis of these differences may provide a means to more effectively evaluate the etiology and pathogenesis of melanoma. In particular, differences in aberrant methylation expression may prove to represent a critical distinction. Methods Data from gene expression datasets (GSE3189 and GSE46517) and gene methylation datasets (GSE86355 and GSE120878) were downloaded from the GEO database. GEO2R was used to obtain differentially expressed genes (DEGs) and differentially methylation genes (DMGs). Function and pathway enrichment of selected genes were performed using the DAVID database. A protein-protein interaction (PPI) network was constructed by STRING while its visualization was achieved with use of cytoscape. Primary melanoma samples from TCGA were used to identify significant survival genes. Results There was a total of 199 genes in the hypermethylation-low expression group, while 136 genes in the hypomethylation-high expression group were identified.