IRE1α inhibitor enhances paclitaxel sensitivity of triple-negative breast cancer cells.

PURPOSE: Breast cancer is the most commonly diagnosed cancer in women, and triple-negative breast cancer (TNBC) accounts for approximately 15%-20% of all breast cancers. TNBC is highly invasive and malignant. Due to the lack of relevant receptor markers, the prognosis of TNBC is poor and the five-year survival rate is low. Paclitaxel is the first-line drug for the treatment of TNBC, which can inhibit cell mitosis. However, many patients develop drug resistance during treatment, leading to chemotherapy failure. Therefore, finding new therapeutic combinations to overcome TNBC drug resistance can provide new strategies for improving the survival rate of TNBC patients. METHODS: Cell viability assay, RT-qPCR, Colony formation assay, Western blot, and Xenogeneic transplantation methods were used to investigate roles and mechanisms of IRE1α/XBP1s pathway in the paclitaxel-resistant TNBC cells, and combined paclitaxel and IRE1α inhibitor in the treatment of TNBC was examined in vitro and in vivo. RESULTS: We found activation of UPR in paclitaxel-resistant cells, confirming that IRE1α/XBP1 promotes paclitaxel resistance in TNBC. In addition, we demonstrated that the combination of paclitaxel and IRE1α inhibitors can synergistically inhibit the proliferation of TNBC tumors both in vitro and in vivo,suggesting that IRE1α inhibitors combined with paclitaxel may be a new treatment option for TNBC. CONCLUSIONS: In this study, we demonstrated the important role of IRE1α signaling in mediating paclitaxel resistance and identified that combination therapies targeting IRE1α signaling could overcome paclitaxel resistance and enhance chemotherapy efficacy.

Urinary volatile organic compound metabolites and COPD among US adults: mixture, interaction and mediation analysis.

BACKGROUND: Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample. METHODS: We assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin. RESULTS: In the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers. CONCLUSIONS: Our findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk.

Exploring the antioxidant potential of nekemias species extracts on edible oils: In vitro assessment and lipid oxidation inhibition.

Synthetic antioxidants have long been used to protect edible oils from oxidation. However, concerns about their potential health risks and environmental impact have led to a growing interest in natural antioxidants. In this study, we explore the antioxidant properties of extracts from four Nekemias plant species: Nekemias grossedentata (AGR), Nekemias megalophylla (AME), Nekemias chaffanjonii (ACH), and Nekemias cantoniensis (ACA) by obtaining the values for different tests. We investigate their bioactive compound content and evaluate their antioxidant capabilities on six edible oils categorized into three lipid systems based on their fatty acid compositions: oleic acid, linoleic acid, and linolenic acid. Our findings demonstrate that AGR and AME extracts, rich in bioactive compounds, exhibit strong antioxidant activities in vitro, effectively inhibiting lipid oxidation, especially in oleic acid-rich oils like camellia oil. The antioxidant effects of these extracts are comparable to synthetic antioxidants such as TBHQ and superior to natural antioxidant Tea Polyphenols (TP). While the extracts also show antioxidant potential in linoleic and linolenic acid systems, the stability of their effects in these oils is lower than in oleic acid system. These results suggest that Nekemias species extracts have the potential to serve as natural additives for extending the shelf life of edible oils, contributing to the exploration of natural antioxidants.

Identification of SRSF10 as a promising prognostic biomarker with functional significance among SRSFs for glioma.

AIMS: The serine/arginine-rich splicing factor (SRSF) protein family members are essential mediators of the alternative splicing (AS) regulatory network, which is tightly implicated in cancer progression. However, the expression, clinical correlation, immune infiltration, and prognostic value of SRSFs in gliomas remain unclear. MATERIALS AND METHODS: Glioma samples were extracted from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets. Several databases, such as HPA, DAVID, UALCAN were used to comprehensively explore the roles of SRSFs. In addition, experimental validation of SRSF10 was also conducted. KEY FINDINGS: Here, we found the expression alterations of the SRSF family in glioma samples using data from the TCGA and CGGA_325 datasets. Among the 12 genes, most were found to be closely associated with glioma clinical features, which linked to poor prognosis in glioma patients. Interestingly, survival analysis identified only SRSF10 as a potential independent risk prognostic biomarker for glioma patients. Immune analysis indicated that glioma patients with high SRSF10 expression may respond well to immunotherapies targeting immune checkpoint (ICP) genes. Finally, knocking down SRSF10 reduced glioma cell viability, induced G1 cell cycle arrest, and induced the exclusion of bcl-2-associated transcription factor 1 (BCLAF1) exon 5a. SIGNIFICANCE: Overall, this study uncovers the oncogenic roles of most SRSF family members in glioma, with the exception of SRSF5, while highlighting SRSF10 as a potential novel independent prognostic biomarker for glioma.