ALDH1A3 contributes to tumorigenesis in high-grade serous ovarian cancer by epigenetic modification.

High-grade serous ovarian cancer (HGSOC) is the most lethal histotype of ovarian cancer due to its unspecific symptoms in part. ALDH1A3 (aldehyde dehydrogenase 1 family member A3) is a key enzyme for acetyl-CoA production involving aggressive behaviors of cancers. However, ALDH1A3's effects and molecular mechanisms in HGSOC remain to be clarified. Using RNA-seq and publicly available datasets, ALDH1A3 was found to be highly expressed in HGSOC, and associated with poor survival. Knockdown of ALDH1A3 prevented HGSOC tumorigenesis and enhanced cell sensitivity to paclitaxel or cisplatin. ALDH1A3 expression in HGSOC cells was found to be increased by hypoxia, but decreased by HIF-1α inhibitor KC7F2. The dual-luciferase reporter assay showed that the increased transcriptional activity of ALDH1A3 induced by HIF-1α overexpression was reduced by KC7F2. In addition, PITX1 (paired like homeodomain 1) was identified to be inhibited by ALDH1A3 knockdown, and PITX1 depletion inhibited cell proliferation. The mechanistic studies showed that ALDH1A3 knockdown reduced the acetylation of histone 3 lysine 27 (H3K27ac). Treatment of exogenous acetate with NaOAc or inhibition of histone deacetylase with Pracinostat increased H3K27ac and PITX1 levels. CHIP assay demonstrated a significant enrichment of H3K27ac at the PITX1 promoter, and ALDH1A3 knockdown reduced the binding between H3K27ac and PITX1. Taken together, our data suggest that ALDH1A3, transcriptional activated by HIF-1α, promotes tumorigenesis and decreases chemosensitivity by increasing H3K27ac of PITX1 promoter in HGSOC.

ANXA3, associated with YAP1 regulation, participates in the proliferation and chemoresistance of cervical cancer cells.

BACKGROUND: Cervical cancer, as one of the most common cancers in women, remains a major health threat worldwide. Annexin A3 (ANXA3), a component of the annexin family, is upregulated in numerous cancers, with no explicit role in cervical cancer. OBJECTIVE: This study aims to investigate the function of ANXA3 in cervical cancer. METHODS: Differential expression genes between the cervical cancer tissues of patients and the controls were analyzed in The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) database. Using transfection approaches to either upregulate or downregulate ANXA3, its role in cell proliferation and chemosensitivity of human cervical cancer cell lines (HeLa and C33A) was evaluated. Furthermore, the binding activity between YAP1 and ANXA3 was also explored. RESULTS: Genomics analysis indicated that differential genes were mostly associated with cell cycle progression and DNA replication. ANXA3 was highly expressed in the cervical cancer tissues and closely linked to malignancy degree. Knockdown of ANXA3 in cervical cancer cells inhibited cell cycle progression. A similar result was observed in the reduction of cyclin D, CDK4, cyclin E, and CDK2 in cervical cancer cells with ANXA3 silencing. Cervical cancer cells obtained high sensitivity to cisplatin (DDP) when ANXA3 was downregulated. Conversely, these capabilities were the opposite in cervical cancer cells overexpressing ANXA3. Furthermore, the expression levels of ANXA3 and YAP1 were positively correlated. YAP1 upregulation was positively connected with malignant behaviors, which were reversed by ANXA3 downregulation. CONCLUSION: In light of our findings, targeting ANXA3 expressed in cervical cancer might contribute to more potential therapeutic strategies.

Development of nomogram to predict in-hospital death for patients with intracerebral hemorrhage: A retrospective cohort study.

Aim: This study aimed to investigate the association between systemic immune-inflammation (SII) and the risk of in-hospital death for patients with intracerebral hemorrhage (ICH) in the intensive care units (ICU) and to further develop a prediction model related to SII in predicting the risk of in-hospital death for patients with ICH. Methods: In this retrospective cohort study, we included 1,176 patients with ICH from the Medical Information Mart for Intensive Care III (MIMIC-III) database. All patients were randomly assigned to the training group for the construction of the nomogram and the testing group for the validation of the nomogram based on a ratio of 8:2. Predictors were screened by the least absolute shrinkage and selection operator (LASSO) regression analysis. A multivariate Cox regression analysis was used to investigate the association between SII and in-hospital death for patients with ICH in the ICU and develop a model for predicting the in-hospital death risk for ICU patients with ICH. The receiver operator characteristic curve was used to assess the predicting performance of the constructed nomogram. Results: In the training group, 232 patients with ICH died while 708 survived. LASSO regression showed some predictors, including white blood cell count, glucose, blood urea nitrogen, SII, the Glasgow Coma Scale, age, heart rate, mean artery pressure, red blood cell, bicarbonate, red blood cell distribution width, liver cirrhosis, respiratory failure, renal failure, malignant cancer, vasopressor, and mechanical ventilation. A prediction model integrating these predictors was established. The area under the curve (AUC) of the nomogram was 0.810 in the training group and 0.822 in the testing group, indicating that this nomogram might have a good performance. Conclusion: Systemic immune-inflammation was associated with an increased in-hospital death risk for patients with ICH in the ICU. A nomogram for in-hospital death risk for patients with ICH in the ICU was developed and validated.

Effects of salinity and particle size on radium desorption from river sediments in the Qinghai-Tibet Plateau.

Natural radium isotopes have been widely used to study groundwater discharge in different systems. Therefore, it is of great significance to understand the desorption behavior of radium isotopes on sediments to trace water-land exchange processes. However, there is very limited studies observing the desorption Ra isotopes to lake water of the brine lake. 224Ra desorption experiments with different salinities and particle sizes were carried out by collecting samples of brackish water from Qinghai Lake, brine from Dabuxun Lake and river sediments entering the lakes. The results show that the desorption activity of 224Ra from the river sediments to lake water of Qinghai Lake is 0.2 dpm/g when the salinity is 10.07‰. The maximum desorption activity of 224Ra from river sediments to lake water of Dabuxun Lake is 0.195 dpm/g at a salinity of 40.81‰. A salinity of 41.81‰ and particle size of 16.28 µm are the threshold points affecting the desorption behavior of Ra. When the salinity is less than 40.81‰, the desorption activity of Ra increases linearly with increasing salinity. When the salinity is greater than 40.81‰, the desorption activity of Ra decreases nonlinearly with increasing salinity and tends toward a stable low value. When the particle size is larger than 16.28 µm, the small particle size promotes desorption. The smaller the particle size is, the greater the desorption activity is. When the particle size is less than 16.28 µm, the small particle size inhibits desorption. The smaller the particle size is, the smaller the desorption activity. The co-precipitation of Ra2+ with supersaturated Ca2+, SO42- and other ions may be the main reason for the threshold point of salinity and particle size in Ra desorption process in salt lake system.