EXOSC2 Mediates the Pro-tumor Role of WTAP in Breast Cancer Cells via Activating the Wnt/ß-Catenin Signal.

BC (breast cancer) is the leading cause of cancer death in women. Exosome component 2 (EXOSC2), an RNA exosome component, is elevated in BC tissues and may relate to BC carcinogenesis. In this work, the high EXOSC2 expression was correlated with TNM (Tumor Node Metastasis) stage. Moreover, overexpression of EXOSC2 enhanced tumorigenic capacity of BC cells via facilitating cell proliferation and cell cycle progression, increasing migration and angiogenesis, as well as exacerbating xenograft formation in vivo. Whereas, EXOSC2 knockdown showed anti-cancer effects, including inhibition of cell proliferation and angiogenesis. Mechanistically, EXOSC2 activated the wnt/ß-catenin pathway, which was also abolished by EXOSC2 knockdown. In addition, there were m6A methylation modification sites in the mRNA of EXOSC2. WTAP (Wilms tumor 1-associated protein) bound to EXOSC2 mRNA and increased its m6A methylation, resulting in extending the half-life of EXOSC2 mRNA. Luciferase data also confirmed that WTAP enhanced EXOSC2 mRNA stability through binding with the 3'-UTR containing m6A sites. Furthermore, WTAP silencing exhibited cancer-inhibiting effects on cell viability, cell cycle progression and tube formation, which was effectively reversed by EXOSC2 overexpression. In conclusion, our results demonstrate that EXOSC2 promotes the malignant behaviors of BC cells via activating the wnt/ß-catenin pathway. In addition, EXOSC2 mediates the function of WTAP which contributes to the m6A modification of EXOSC2. Totally, this study suggested that EXOSC2 mediated the pro-tumor role of WTAP via activating the wnt/ß-catenin signal.

Synthesis of ZnO nanoparticle-anchored biochar composites for the selective removal of perrhenate, a surrogate for pertechnetate, from radioactive effluents.

Pertechnetate (TcO4-) is a component of low-activity waste (LAW) fractions of legacy nuclear waste, and the adsorption removal of TcO4- from LAW effluents would greatly benefit the site remediation process. However, available adsorbent materials lack the desired combination of low cost, radiolytic stability, and high selectivity. In this study, a ZnO nanoparticle-anchored biochar composite (ZBC) was fabricated and applied to potentially separate TcO4- from radioactive effluents. The as-synthesized material exhibited γ radiation resistance and superhydrophobicity, with a strong sorption capacity of 25,916 mg/kg for perrhenate (ReO4-), which was used in this study as a surrogate for radioactive pertechnetate (TcO4-). Additionally, the selectivity for ReO4- exceeded that for the competing ions I-, NO2-, NO3-, SO42-, PO43-, Cu2+, Fe3+, Al3+, and UO22+. These unique features show that ZBC is capable of selectively removing ReO4- from Hanford LAW melter off-gas scrubber simulant effluent. This selectivity stems from the synergistic effects of both the superhydrophobic surface of the sorbent and the inherent nature of sorbates. Furthermore, density functional theory (DFT) calculations indicated that ReO4- can form stable complexes on both the (100) and (002) planes of ZnO, of which, the (002) complexes have greater stability. Electron transfer from ReO4- on (002) was greater than that on (100). These phenomena may be because (002) has a lower surface energy than (100). Partial density of state (PDOS) analysis further confirms that ReO4- is chemisorbed on ZBC, which agrees with the findings of the Elovich kinetic model. This work provides a feasible pathway for scale-up to produce high-efficiency and cost-effective biosorbents for the removal of radionuclides.

The effect of air pollution on hospitalization of individuals with respiratory and cardiovascular diseases in Jinan, China.

To analyze the short-term effects of air pollution on the hospitalization rates of individuals with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), stroke, and myocardial infarction (MI) after adjusting for confounding factors including weather, day of the week, holidays, and long-term trends in Jinan, China.Hospitalization information was extracted based on data from the primary class 3-A hospitals in Jinan from 2013 to 2015. The concentrations of PM2.5, PM10, SO2, NO2, and O3 were obtained from Jinan Environment Monitoring Center. The relative risk and 95% confidence intervals of AECOPD, stroke, and MI were estimated using generalized additive models with quasi-Poisson distribution in the mgcv package, using R software, version 1.0.136.The incremental increased concentrations of particulate pollutants including PM2.5 and PM10 were significantly associated with increased risk of hospitalization of AECOPD, stroke, and MI, and the adverse influences of PM2.5 on these diseases were generally stronger than that of PM10. The incremental increased concentrations of gaseous pollutants including SO2, NO2, and O3 were significantly associated with increased risk of hospitalization of stroke and MI in this population.Air pollution has significant adverse effects on hospitalization rates of individuals with AECOPD, stroke, and MI in Jinan, China.

The impact of airborne particulate matter on pediatric hospital admissions for pneumonia among children in Jinan, China: A case-crossover study.

This study aims to examine the effect of short-term changes in the concentration of particulate matter of diameter ≤2.5 µm (PM2.5) and ≤10 µm (PM10) on pediatric hospital admissions for pneumonia in Jinan, China. It explores confoundings factors of weather, season, and chemical pollutants. Information on pediatric hospital admissions for pneumonia in 2014 was extracted from the database of Jinan Qilu Hospital. The relative risk of pediatric hospital admissions for pneumonia was assessed using a case-crossover approach, controlling weather variables, day of the week, and seasonality. The single-pollutant model demonstrated that increased risk of pediatric hospital admissions for pneumonia was significantly associated with elevated PM2.5 concentrations the day before hospital admission and elevated PM10 concentrations 2 days before hospital admission. An increment of 10 µg/m3 in PM2.5 and PM10 was correlated with a 6% (95% CI 1.02--1.10) and 4% (95% CI 1.00-1.08) rise in number of admissions for pneumonia, respectively. In two pollutant models, PM2.5 and PM10 remained significant after inclusion of sulfur dioxide or nitrogen dioxide but not carbon monoxide. This study demonstrated that short-term exposure to atmospheric particulate matter (PM2.5/PM10) may be an important determinant of pediatric hospital admissions for pneumonia in Jinan, China. IMPLICATIONS: This study demonstrated that short-term exposure to atmospheric particulate matter (PM2.5/PM10) may be an important determinant of pediatric hospital admissions for pneumonia in Jinan, China, and suggested the relevance of pollutant exposure levels and their effects. As a specific group, children are sensitive to airborne particulate matter. This study estimated the short-term effects attribute to other air pollutants to provide references for relevant studies.

Urotensin II contributes to collagen synthesis and up-regulates Egr-1 expression in cultured pulmonary arterial smooth muscle cells through the ERK1/2 pathway.

AIM: The objective of this study was to investigate the effects of urotensin II (UII) treatment on the proliferation and collagen synthesis of cultured rat pulmonary arterial smooth muscle cells (PASMCs) and to explore whether these effects are mediated by mitogen-activated protein kinase (MAPK) signaling pathways and early growth response 1 (Egr-1). METHODS: The proliferation of cultured PASMCs stimulated with different doses of UII was detected by BrdU incorporation. The mRNA expression levels of procollagen I (procol I), procollagen III (procol III), extracellular regulated protein kinase 1/2 (ERK1/2), stress-stimulated protein kinase (Sapk), p38 MAPK (p38), and Egr-1 mRNA in cultured PASMCs after treatment with UII, the UII-specific antagonist urantide, and the ERK1/2 inhibitor PD98059 were detected by real-time polymerase chain reaction (PCR), and the protein expression levels of procol I, procol III, phosphorylated (p)-ERK1/2, p-Sapk, p-p38, and Egr-1 were detected by Western blotting. RESULTS: Treatment with UII increased the proliferation of cultured PASMCs in a dose-dependent manner (P<0.05). However, treatment with urantide and PD98059 inhibited the promoting effect of UII on PASMC proliferation (P<0.05). Real-time PCR analysis showed that UII up-regulated the expression of procol I, procol III, ERK1/2, Sapk, and Egr-1 mRNA (P<0.05), but not p38 mRNA. However, the up-regulating effect of UII was inhibited by PD98059 and urantide. Western blotting analysis showed that UII increased the synthesis of collagen I, collagen III, p-ERK1/2, p-Sapk, and Egr-1, and these effects also were inhibited by PD98059 and urantide (P<0.05). CONCLUSIONS: Egr-1 participates in the UII-mediated proliferation and collagen synthesis of cultured rat PASMCs via activation of the ERK1/2 signaling pathway.

Protease-activated receptor-2 induces expression of vascular endothelial growth factor and cyclooxygenase-2 via the mitogen-activated protein kinase pathway in gastric cancer cells.

Protease-activated receptor-2 (PAR-2) has shown strong pro-angiogenesis activity physiologically and pathologically. This study aimed to explore PAR-2 regulation of pro-angiogenesis gene expression and the underlying molecular pathways in gastric cancer cells. MKN28 human gastric cancer cells were treated with trypsin, a PAR-2 activator, and subjected to real-time reverse transcription polymerase chain reaction (qRT-PCR), western blotting and ELISA for gene expression analyses. ERK1/2 phosphorylation and p38 MAP kinase inhibitors (PD98059 and SB203580, respectively) were used to block their gene activities. PAR-2 mRNA and protein were expressed in MKN-28 cells and activated by trypsin treatment. Trypsin-activated PAR-2 protein significantly enhanced expression of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) mRNA and protein in gastric cancer cells in a dose- and time-dependent manner. PAR-2 activation also induced the phosphorylation of ERK1/2 and p38 MAP kinase, but the ERK1/2 and p38 inhibitors blocked the activated PAR-2-induced VEGF and COX-2 expression in gastric cancer cells. PAR-2-induced expression of VEGF and COX-2 mRNA and protein in gastric cancer MKN28 cells was mediated by activation of an ERK1/2- and p38 MAP kinase-dependent pathway. Thus, PAR-2 may serve as a promising target for anti-angiogenesis therapy to treat gastric cancer.

Effects of environmental hypothermia on hemodynamics and oxygen dynamics in a conscious swine model of hemorrhagic shock.

BACKGROUND: Hypothermia is associated with poor outcome in trauma patients; however, hemorrhagic shock (HS) model with anesthetized swine was different from that of clinical reality. To identify the effects of environmental hypothermia on HS, we investigated hemodynamics and oxygen dynamics in an unanesthetized swine model of HS under simulating hypothermia environment. METHODS: Totally 16 Bama pigs were randomly divided into ambient temperature group (group A) and low temperature group (group B), 8 pigs in each group. Venous blood (30 mL/kg) was continuously withdrawn for more than 15 minutes in conscious swine to establish a hemorrhagic shock model. Pulmonary arterial temperature (Tp), heart rate (HR), mean arterial pressure (MAP), pulmonary arterial pressure (PAP), pulmonary arterial wedge pressure (PAWP), central venous pressure (CVP), cardiac output (CO), hemoglobin (Hb), saturation of mixed venous blood (SvO2) and blood gas analysis were recorded at the baseline and different hemorrhagic shock time (HST). The whole body oxygen delivery indices, DO2I and VO2I, and the O2 extraction ratio (O2ER) were calculated. RESULTS: Core body temperature in group A decreased slightly after the hemorrhagic shock model was established, and environmental hypothermia decreased in core body temperature. The mortality rate was significantly higher in group B (50%) than in group A (0%). DO2I and VO2I decreased significantly after hemorrhage. No difference was found in hemodynamics, DO2I and VO2I between group A and group B, but the difference in pH, lactic acid and O2ER was significant between the two groups. CONCLUSION: Environmental hypothermia aggravated the disorder of oxygen metabolism after hemorrhagic shock, which was associated with poor prognosis.