BRMS1L confers anticancer activity in non-small cell lung cancer by transcriptionally inducing a redox imbalance in the GPX2-ROS pathway.

Low expression levels of breast cancer metastasis suppressor 1 like (BRMS1L) have been associated with the growth of cancer cells. However, the mechanisms underlying the role of BRMS1L as an antitumour transcription factor in the progression of NSCLC have not been explored. Herein, we reveal that BRMS1L plays a key role as a tumour suppressor in inhibiting NSCLC proliferation and metastasis. Mechanistically, BRMS1L overexpression results in the downregulation of glutathione peroxidase 2 (GPX2) expression and consequently causes abnormal glutathione metabolism and increased levels of reactive oxygen species (ROS) in cells, inducing oxidative stress injury and apoptosis. Furthermore, overexpression of GPX2 enhances the growth advantage and oxidative stress repair conferred by knockdown of BRMS1L. Importantly, we show that low expression of BRMS1L in NSCLC cells causes relatively high levels of antioxidant accumulation to maintain cell redox balance and renders cancer cells more sensitive to treatment with piperlongumine as an ROS inducer both in vitro and in vivo. These findings offer new insights into the role of BRMS1L as a transcriptional repressor in NSCLC and suggest that the BRMS1L expression level may be a potential biomarker for predicting the therapeutic response to small molecule ROS inducers, providing new ideas for targeted therapy.

A sialyltransferases-related gene signature serves as a potential predictor of prognosis and therapeutic response for bladder cancer.

BACKGROUND: Aberrant glycosylation, catalyzed by the specific glycosyltransferase, is one of the dominant features of cancers. Among the glycosyltransferase subfamilies, sialyltransferases (SiaTs) are an essential part which has close linkages with tumor-associated events, such as tumor growth, metastasis and angiogenesis. Considering the relationship between SiaTs and cancer, the current study attempted to establish an effective prognostic model with SiaTs-related genes (SRGs) to predict patients' outcome and therapeutic responsiveness of bladder cancer. METHODS: RNA-seq data, clinical information and genomic mutation data were downloaded (TCGA-BLCA and GSE13507 datasets). The comprehensive landscape of the 20 SiaTs was analyzed, and the differentially expressed SiaTs-related genes were screened with "DESeq2" R package. ConsensusClusterPlus was applied for clustering, following with survival analysis with Kaplan-Meier curve. The overall survival related SRGs were determined with univariate Cox proportional hazards regression analysis, and the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to generate a SRGs-related prognostic model. The predictive value was estimated with Kaplan-Meier plot and the receiver operating characteristic (ROC) curve, which was further validated with the constructed nomogram and decision curve. RESULTS: In bladder cancer tissues, 17 out of the 20 SiaTs were differentially expressed with CNV changes and somatic mutations. Two SiaTs_Clusters were determined based on the expression of the 20 SiaTs, and two gene_Clusters were identified based on the expression of differentially expressed genes between SiaTs_Clusters. The SRGs-related prognostic model was generated with 7 key genes (CD109, TEAD4, FN1, TM4SF1, CDCA7L, ATOH8 and GZMA), and the accuracy for outcome prediction was validated with ROC curve and a constructed nomogram. The SRGs-related prognostic signature could separate patients into high- and low-risk group, where the high-risk group showed poorer outcome, more abundant immune infiltration, and higher expression of immune checkpoint genes. In addition, the risk score derived from the SRGs-related prognostic model could be utilized as a predictor to evaluate the responsiveness of patients to the medical therapies. CONCLUSIONS: The SRGs-related prognostic signature could potentially aid in the prediction of the survival outcome and therapy response for patients with bladder cancer, contributing to the development of personalized treatment and appropriate medical decisions.

Alpha-2 Heremans Schmid Glycoprotein (AHSG) promotes the proliferation of bladder cancer cells by regulating the TGF-ß signalling pathway.

Bladder cancer (BC) is one of the most common urinary tract malignancies and is the tenth most common cancer globally. Alpha-2 Heremans Schmid Glycoprotein (AHSG) is a multifunctional protein that plays different roles in the progression of multiple tumors. However, the role and mechanism of AHSG in the development and progression of BC are unknown. AHSG expression was assessed in BC cells and tissues using western blot and immunohistochemistry. Using plasmid and siRNA, overexpressed and knocked down AHSG in BC cells were constructed. A series of functional experiments, including CCK8, plate clone formation, and flow cytometry, were performed to evaluate cell proliferation and cycle. AHSG was expressed higher in BC cells and tissues than in normal bladder epithelial cells and non-tumor tissues. Functionally, the overexpression of AHSG significantly increased the proliferation of BC cells and promoted the cell cycle from G1 to the S phase, whereas the knockdown of AHSG gave the opposite result.Additionally, western blot results revealed that AHSG expression level was negatively correlated with the phosphorylation level of Smad2/3 protein, a key downstream molecule of the traditional TGF-ß signaling pathway, suggesting that AHSG could antagonize the traditional TGF-ß signaling pathway. Finally, the expression level of AHSG in the urine of BC patients was significantly higher than that of healthy subjects by ELISA, with specificity. Our study concluded that AHSG might be a novel marker of BC that promotes the proliferation of BC cells by regulating the TGF-ß signaling pathway.

Glycolysis-Related Genes Serve as Potential Prognostic Biomarkers in Clear Cell Renal Cell Carcinoma.

Metabolic rearrangement is a marker of cancer that has been widely studied in recent years. One of the major metabolic characteristics of tumor cells is the high levels of glycolysis, even under aerobic conditions, a phenomenon that is called the "Warburg effect." We investigated the expression and copy number variation (CNV) frequency of all glycolysis-related genes in multiple cancer types and found many differentially expressed genes, particularly in clear cell renal cell carcinoma (ccRCC). Single nucleotide variants (SNVs) showed that the overall average mutation frequency for all genes was low. The purpose of this study was to establish a predictive model by studying glycolysis-related genes in ccRCC. We compared the expression of glycolysis-related genes in 539 ccRCC tissues and 72 normal renal tissues from The Cancer Genome Atlas dataset and identified 17 upregulated and 26 downregulated genes. Pathway analysis revealed that PSAT1 and SDHB could activate the cell cycle, RPIA could activate the DNA damage response, and HK3 could activate apoptosis and EMT signaling, while PDK2 could inhibit apoptosis. The results of the drug sensitivity analysis suggested that some of these differentially expressed genes were positively correlated with drug sensitivity. Thirteen genes were selected from the gene coexpression network and the LASSO regression analysis. The Kaplan-Meier overall survival curves showed that the expression of upregulated genes in ccRCC patients was associated with lower overall survival. We established a predictive model consisting of 13 genes (RPIA, G6PD, PSAT1, ENO2, HK3, IDH1, PDK4, PGM2, PGK1, FBP1, OGDH, SUCLA2, and SUCLG2). This predictive model correlated well with the development and progression of ccRCC. Thus, it is of great value in the diagnosis and prognostic evaluation of ccRCC and may aid the identification of potential prognostic biomarkers and drug targets.

Novel serum peptide model revealed by MALDI-TOF-MS and its diagnostic value in early bladder cancer.

BACKGROUND: Bladder cancer is the ninth most common cancer worldwide and has high morbidity and mortality. We aimed to search for potential serum peptide biomarkers and establish a diagnostic model for early bladder cancer. METHODS: A total of 67 bladder cancer patients and 64 healthy volunteers were randomly divided into a training set and testing set 1. There were 30 hematuria patients used as testing set 2. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry based on weak cation exchange magnetic beads was used to obtain and analyze the serum peptide profiles between bladder cancer patients and healthy volunteers in the training set. Serum peptide diagnostic model through a k-nearest neighbor algorithm, was established and validated, and significantly differentially expressed protein biomarkers were ultimately identified. RESULTS: We constructed a diagnostic model containing five peptides (m/z 1954.9, m/z 2081.0, m/z 3938.3, m/z 3946.5, and m/z 4268.8). In the training set, the area under the curve (AUC) value of the five-peptide model was 0.923, and the sensitivity and specificity was 93.75% and 96.77%, respectively. In testing set 1, the sensitivity and specificity was 91.43% and 90.91%, respectively, and the specificity of testing set 2 was 73.33%. For early-stage bladder cancer, the sensitivity and specificity was 92.31% and 93.75%, respectively; the sensitivity of early low-grade bladder cancer was 90.00%; and the AUC value was 0.944. CONCLUSION: The five-peptide diagnostic model established in this study had high sensitivity and specificity, especially in the diagnosis of early bladder cancer, and could differentiate between healthy volunteers and hematuria patients.

Effect of Tempering Conditions on Secondary Hardening of Carbides and Retained Austenite in Spray-Formed M42 High-Speed Steel.

In this study, the effect of tempering conditions on microstructure, grain size, and carbide phase compositions of spray-formed high-speed steel after quenching at 1180 °C was studied. The influence of carbide phase, size of carbides, and retained austenite content on secondary hardening of the steel was analyzed by field emission scanning electron microscope (FESEM), transmission electron microscope (TEM), electron backscattered diffraction (EBSD), and differential scanning calorimetry (DSC); the hardness, microhardness of carbide, and bending strength were tested. The results show that M3C, M6C, M7C3, and MC carbides may precipitate at different tempering temperatures and the transformation of the retained austenite can be controlled by tempering. The phase composition of carbides, microstructure, and retained austenite content strongly influences the performance characteristics of M42 high-speed steel after tempering. In contrast, the secondary carbides produced by tempering thrice at 540 °C are mainly M6C carbides rich in W and Mo elements, and the content of retained austenite is effectively reduced. At this stage, the Rockwell hardness reaches 67.2 HRC, bending strength reaches 3115 MPa, and the properties and microstructure are optimal.

Association of CT perfusion and postoperative cognitive dysfunction after off-pump coronary artery bypass grafting.

OBJECTIVE: To investigate the relationship between an abnormal CT perfusion scan and postoperative cognitive dysfunction, as measured by changes in MoCA and MMSE scores, after off-pump coronary artery bypass grafting (OPCABG). METHODS: Eight hundred and thirteen patients were selected who underwent OPCABG between August 2010 and September 2013. Cognitive function was assessed before operation and at seven days post-op. CT perfusion scan was obtained preoperatively and was used to divide patients into two groups: abnormal perfusion and normal perfusion groups. RESULTS: (1) Logistic regression analysis showed that perfusion abnormalities (OR, 3.012; 95% CI, 1.660-5.463; P < 0.05) were an independent risk factor for postoperative cognitive dysfunction (POCD). (2) 556 patients with CT perfusion scans were divided into normal perfusion and abnormal perfusion groups: incidence of POCD in the abnormal perfusion group is significantly higher than the control group (21.6 vs 8.6%, P < 0.05); MMSE scores were significantly lower in patients with abnormal perfusion before and after surgery. MoCA scores demonstrated a significant drop after surgery for all patients with abnormal perfusion (P < 0.05). The abnormal perfusion group had a significant reduction in the visuospatial/executive and naming scores in the MoCA as compared to normal perfusion (P < 0.05). CONCLUSION: Abnormal CT perfusion is a significant risk factor for postoperative cognitive dysfunction, and has the most impact on visuospatial/executive and naming functions.

A newly found cadmium accumulator--Malva sinensis Cavan.

Screening hyperaccumulators and accumulators is a key step in the phytoremediation of soils contaminated by heavy metals. A pot experiment was conducted involving a soil Cd concentration gradient (0, 50, 75, 100, 125, 150, 175, and 200 mg kg(-1)) to determine if Malva sinensis Cavan. from two lead-zinc mines in Kangding and Yajiang in western Sichuan, China, is a Cd-hyperaccumulator. The highest Cd concentrations in plant shoots from Kangding and Yajiang were 154.30 and 122.77 mg kg(-1), respectively, at a soil Cd concentration of 200 mg kg(-1). The largest amounts of accumulation in plant shoots from Kangding and Yajiang were 700.5 and 1403.2 microg pot(-1), respectively. The bioconcentration factors in shoots were 0.53-1.03 for Kangding and 0.69-1.25 for Yajiang. Moreover, all translocation factors of plants from the two sites were over 1.0. Therefore, M. sinensis can be classified as a Cd-accumulator or non-standard Cd-hyperaccumulator.