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Long-term exposure to arsenic, a widely distributed environmental toxicant, may result in damage to various organs, including the liver. Mice exposed chronically to arsenite developed hepatic damage, inflammation, and fibrosis, as well as increased levels of microRNA-21 (miR-21) and hypoxia-inducible factor (HIF)-1α. The levels of miR-21 and HIF-1α were also enhanced in primary hepatocytes and L-02 cells exposed to arsenite. The culture media from these cells induced the activation of hepatic stellate cells (HSCs), as demonstrated by up-regulation of the protein levels of α-smooth muscle actin (α-SMA) and collagen1A2 (COL1A2) and by increased activity in gel contractility assays. For L-02 cells, knockdown of miR-21 blocked the arsenite-induced up-regulation of HIF-1α and vascular endothelial growth factor (VEGF), which prevented the activation of LX-2 cells induced by medium from arsenite-exposed L-02 cells. However, these effects were reversed by down-regulation of von Hippel Lindau protein (pVHL). In arsenite-treated L-02 cells, miR-21 knockdown elevated the levels of ubiquitination and accelerated the degradation of HIF-1α via pVHL. In the livers of miR-21-/- mice exposed chronically to arsenite, there were less hepatic damage, lower fibrosis, lower levels of HIF-1α and VEGF, and higher levels of pVHL than for wild-type mice. In summary, we propose that miR-21, acting via the HIF-1α/VEGF signaling pathway, is involved in arsenite-induced hepatic fibrosis through mediating aberrant cross-talk of hepatocytes and HSCs. The findings provide evidence relating to the pathogenesis of hepatic fibrosis induced by exposure to arsenic.Lake Ziway, a freshwater lake located in Ethiopia, is under the pressure of pesticide and nutrient pollution due to agricultural activity and urbanization. This study has analysed concentrations of insecticides, fungicides and nutrients in water and sediment samples of Lake Ziway taken in the wet and dry season at 13 sites expected to be under different environmental stress and assessed their expected ecological impacts. PMX-53 Malathion, dimethoate, metalaxyl, diazinon, chlorpyrifos, fenitrothion and endosulfan were detected in more than half of the water samples, while diazinon, α-cypermethrin and endosulfan were frequently detected (>25%) in sediment samples. Higher levels of physicochemical parameters were observed at sample locations proximate to agricultural and urban activities. Risk quotients (RQ) and multi-substance Potentially Affected Fraction (msPAFRA) were calculated to assess the ecological risk of individual and mixture of pesticides, respectively. The majority of the pesticides detected in the water of the lake showed a potential acute risk (RQ > 1), specifically the insecticides chlorpyrifos, λ-cyhalothrin and α-cypermethrin for which high potential acute risks were calculated using a 2nd tier risk assessment. Levels of pesticides in sediment showed low ecological risks. Arthropods and fishes are expected to be highly affected by mixtures of pesticides (msPAFRA = less then 1-80%) detected at locations that are proximate to smallholders' farms, and receive largescale farms' wastewater and at sites where inflow rivers join the lake. Macroinvertebrates based redundancy analysis showed the effectiveness of EPT richness to assess ecological status of the lake. Training for smallholder farmers on pesticides safety and usage, and implementation of improved effluent management mechanisms by floriculture farms are urgently needed intervention measures to reduce the pollution.Sandy soils in Florida are vulnerable to toxic metal pollution, and it is necessary to identify desirable amendments for the remediation of metal contaminated soils. Sorption and incubation experiments were conducted to compare the effectiveness of dolomite phosphate rock (DPR), humic acid activated dolomite phosphate rock (ADPR) and biochar (BC) in immobilizing Cd2+ and Pb2+ in two representative agricultural soils in south Florida (Alfisol-Riviera and Spodosol -Ankona series). The results showed that the soils had a low sorption capacity for metals with maximum sorption of 0.767-3.30 mg/g. Application of amendments increased the maximum sorption by 4.2-4.8 times for Pb2+ and 1.5-2.2 times for Cd2+ in Alfisol soil, and 7.1-7.9 times for Pb2+ and 1.7-3.1 times for Cd2+ in Spodosol soil. ADPR was the most effective amendment for increasing the soil's sorption capacity for Cd2+ and Pb2+. 0.01 M CaCl2 extractable metals in the contaminated soils were significantly decreased by all the amendments, especially ADPR, which reduced extractable Cd2+ and Pb2+by 87.2 and 76.0% in Alfisol and 91.3 and 76.3% in Spodosol soil as compared to control. The amounts of extractable Cd2+ and Pb2+ were negatively correlated with soil pH and available P, indicating that the change of soil characteristics by amendments was the dominant mechanism for enhanced immobilization of metals in the contaminated soils. These results indicate that ADPR has great potential for remediating toxic levels of Cd2+ and Pb2+ in contaminated soils.Venom geographical variation is common among venomous animals. This phenomenon presents problems in the development of clinical treatments and medicines against envenomation. The venomous giant jellyfish Nemopilema nomurai, Scyphozoan, is a blooming jellyfish species in the Yellow Sea and the East China Sea that causes numerous jellyfish sting cases every year. Metalloprotease and phospholipase A2 (PLA2) are the main components in Nemopilema nomurai venom and may activate many toxicities, such as hemolysis, inflammation and lethality. Geographical variation in the content and activity of these enzymes may cause different symptoms and therapeutic problems. For the first time, we verified metalloprotease and PLA2 geographical variation in Nemopilema nomurai venom by performing a comparative analysis of 31 venom samples by SDS-PAGE, analyzing protease zymography, enzymatic activity, and drawing contour maps. Band locations and intensities of SDS-PAGE and protease zymograms showed geographical differences. The enzymatic activities of both metalloprotease and PLA2 showed a trend of geographic regularity. The distribution patterns of these activities are directly shown in contour maps. Metalloproteinase activity was lower near the coast. PLA2-like activity was lower in the Southern Yellow Sea. We surmised that metalloproteinase and PLA2-like activities might be related to venom ontogeny and species abundance respectively, and influenced by similar environmental factors. This study provides a theoretical basis for further ecological and medical studies of Nemopilema nomurai jellyfish venom.
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