Downregulation of Serum PTEN Expression in Mercury-Exposed Population and PI3K/AKT Pathway-Induced Inflammation.

Objective: This study investigated the impact of occupational mercury (Hg) exposure on human gene transcription and expression, and its potential biological mechanisms. Methods: Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA. Results: Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model (25 and 10 µmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression. Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels. Conclusion: This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.

Tailored Synthesis of Catalytically Active Cerium Oxide for N, N-Dimethylformamide Oxidation.

Cerium oxide nanopowder (CeOx) was prepared using the sol-gel method for the catalytic oxidation of N, N-dimethylformamide (DMF). The phase, specific surface area, morphology, ionic states, and redox properties of the obtained nanocatalyst were systematically characterized using XRD, BET, TEM, EDS, XPS, H2-TPR, and O2-TPO techniques. The results showed that the catalyst had a good crystal structure and spherelike morphology with the aggregation of uniform small grain size. The catalyst showed the presence of more adsorbed oxygen on the catalyst surface. XPS and H2-TPR have confirmed the reduction of Ce4+ species to Ce3+ species. O2-TPR proved the reoxidability of CeOx, playing a key role during DMF oxidation. The catalyst had a reaction rate of 1.44 mol g-1cat s-1 and apparent activation energy of 33.30 ± 3 kJ mol-1. The catalytic performance showed ~82 ± 2% DMF oxidation at 400 °C. This work's overall results demonstrated that reducing Ce4+ to Ce3+ and increasing the amount of adsorbed oxygen provided more suitable active sites for DMF oxidation. Additionally, the catalyst was thermally stable (~86%) after 100 h time-on-stream DMF conversion, which could be a potential catalyst for industrial applications.

DNA methylation loci identification for pan-cancer early-stage diagnosis and prognosis using a new distributed parallel partial least squares method.

Aberrant methylation is one of the early detectable events in many tumors, which is very promising for pan-cancer early-stage diagnosis and prognosis. To efficiently analyze the big pan-cancer methylation data and to overcome the co-methylation phenomenon, a MapReduce-based distributed and parallel-designed partial least squares approach was proposed. The large-scale high-dimensional methylation data were first decomposed into distributed blocks according to their genome locations. A distributed and parallel data processing strategy was proposed based on the framework of MapReduce, and then latent variables were further extracted for each distributed block. A set of pan-cancer signatures through a differential co-expression network followed by statistical tests was further identified based on their gene expression profiles. In total, 15 TCGA and 3 GEO datasets were used as the training and testing data, respectively, to verify our method. As a result, 22,000 potential methylation loci were selected as highly related loci with early-stage pan-cancer diagnosis. Of these, 67 methylation loci were further identified as pan-cancer signatures considering their gene expression as well. The survival analysis as well as pathway enrichment analysis on them shows that not only these loci may serve as potential drug targets, but also the proposed method may serve as a uniform framework for signature identification with big data.

Association between the HOTAIR Polymorphism and Susceptibility to Lead Poisoning in a Chinese Population.

This study explored the association between the lncRNA HOTAIR polymorphism and susceptibility to lead poisoning in a Chinese population. We speculated that lead poisoning caused elevated levels of oxidative stress, which, in turn, activate the HOTAIR gene to cause apoptosis. Three lncRNA HOTAIR tagSNPs (rs7958904, rs4759314, and rs874945) were genotyped by TaqMan genotyping technology in 113 lead-sensitive and 113 lead-resistant Chinese workers exposed to lead. Rs7958904 was significantly associated with susceptibility to lead poisoning (P = 0.047). The rs7958904 G allele had a protective effect compared with the C allele and reduced the risk of lead poisoning (P = 0.016). Rs7958904 may act as a potential biomarker for predicting the risk of lead poisoning and distinguishing lead-sensitive individuals from lead-resistant individuals.

Diallyl disulfide inhibits TGF­ß1­induced upregulation of Rac1 and ß­catenin in epithelial­mesenchymal transition and tumor growth of gastric cancer.

Transforming growth factor­ß1 (TGF­ß1) has been demonstrated to promote epithelial­mesenchymal transition (EMT), invasion and proliferation in tumors via the activation of Rac1 and ß­catenin signaling pathways. The present study investigated the effects of diallyl disulfide (DADS) on TGF­ß1­induced EMT, invasion and growth of gastric cancer cells. TGF­ß1 treatment augmented EMT and invasion, concomitantly with increased expression of TGF­ß1, Rac1 and ß­catenin in gastric cancer cells. DADS downregulated the expression levels of TGF­ß1, Rac1 and ß­catenin. DADS, TGF­ß1 receptor inhibitor as well as Rac1 inhibitor antagonized the upregulation of the TGF­ß1­induced expression of these genes, abolishing the enhanced effects of TGF­ß1 on EMT and invasion. Blocking the TGF­ß1 receptor through inhibition resulted in the decreased expression of Rac1 and ß­catenin. Rac1 inhibitor reduced the TGF­ß1­induced ß­catenin expression. In addition, DADS and the aforementioned inhibitors attenuated the TGF­ß1­induced tumor growth and the expression changes of E­cadherin, vimentin, Ki­67 and CD34 in nude mice. These data indicated that the blockage of TGF­ß1/Rac1 signaling by DADS may be responsible for the suppression of EMT, invasion and tumor growth in gastric cancer.

Analysis of plasma microRNA expression profiles in male textile workers with noise-induced hearing loss.

BACKGROUND: Circulating microRNAs (miRNAs) have attracted interests as non-invasive biomarkers of physiological and pathological conditions, which may be applied in noise-induced hearing loss (NIHL). However, no epidemiology studies have yet examined the potential effects of NIHL or noise exposure on miRNA expression profiles. OBJECTIVES: We sought to identify permanent NIHL-related miRNAs and to predict the biological functions of the putative genes encoding the indicated miRNAs. METHODS: In the discovery stage, we used a microarray assay to detect the miRNA expression profiles between pooled plasma samples from 10 noise-exposed individuals with normal hearing and 10 NIHL patients. In addition, we conducted a preliminary validation of six candidate miRNAs in the same 20 workers. Subsequently, three miRNAs were selected for expanded validation in 23 non-exposed individuals with normal hearing and 46 noise-exposed textile workers which including 23 noise-exposed workers with normal hearing and 23 NIHL patients. Moreover, we predicted the biological functions of the putative target genes using a Gene Ontology (GO) function enrichment analysis. RESULTS: In the discovery stage, compared with the noise exposures with normal hearing, 73 miRNAs demonstrated at least a 1.5-fold differential expression in the NIHL patients. In the preliminary validation, compared with the noise exposures, the plasma levels of miR-16-5p, miR-24-3p, miR-185-5p and miR-451a were all upregulated (P < 0.001) in the NIHL patients. In the expanded validation stage, compared with the non-exposures, the plasma levels of miR-24, miR-185-5p and miR-451a were all significantly downregulated (P < 0.001) in the exposures. And compared with the noise exposures, the plasma levels of miR-185-5p and miR-451a were slightly elevated (P < 0.001) in the NIHL patients, which were consistent with the results of preliminary validation and microarray analysis. CONCLUSION: The two indicated plasma miRNAs may be biomarkers of indicating responses to noise exposure. However, further studies are necessary to prove the causal association between miRNAs changes and noise exposure, and to determine whether these two miRNAs are clear biomarkers to noise exposure.