AM1638, a GPR40-Full Agonist, Inhibited Palmitate-Induced ROS Production and Endoplasmic Reticulum Stress, Enhancing HUVEC Viability in an NRF2-Dependent Manner

Background G protein-coupled receptor 40 (GPR40) is a key molecule in diabetes and fatty liver, but its role in endothelial dysfunction remains unclear. Our objective in this study was to determine whether GPR40 agonists protect endothelial cells against palmitatemediated oxidative stress. Methods Human umbilical vein endothelial cells (HUVECs) were used to investigate effects of various GPR40 agonists on vascular endothelium. Results In HUVECs, AM1638, a GPR40-full agonist, enhanced nuclear factor erythroid 2–related factor 2 (NRF2) translocation to the nucleus and heme oxygenase-1 (HO-1) expression, which blocked palmitate-induced superoxide production. Those antioxidant effects were not detected after treatment with LY2922470 or TAK875, GPR40-partial agonists, suggesting that GPR40 regulates reactive oxygen species (ROS) removal in a ligand-dependent manner. We also found that palmitate-induced CCAAT/enhancer‐binding protein homologous protein expression; X-box binding protein-1 splicing, nuclear condensation, and fragmentation; and caspase-3 cleavage were all blocked in an NRF2-dependent manner after AM1638 treatment. Both LY2922470 and TAK875 also improved cell viability independent of the NRF2/ROS pathway by reducing palmitate-mediated endoplasmic reticulum stress and nuclear damage. GPR40 agonists thus have beneficial effects against palmitate in HUVECs. In particular, AM1638 reduced palmitate-induced superoxide production and cytotoxicity in an NRF2/HO-1 dependent manner. Conclusion GPR40 could be developed as a good therapeutic target to prevent or treat cardiovascular diseases such as atherosclerosis

The Biological Assessment and Rehabilitation of the World’s Rivers: An Overview

The biological assessment of rivers i.e., their assessment through use of aquatic assemblages, integrates the effects of multiple-stressors on these systems over time and is essential to evaluate ecosystem condition and establish recovery measures. It has been undertaken in many countries since the 1990s, but not globally. And where national or multi-national monitoring networks have gathered large amounts of data, the poor water body classifications have not necessarily resulted in the rehabilitation of rivers. Thus, here we aimed to identify major gaps in the biological assessment and rehabilitation of rivers worldwide by focusing on the best examples in Asia, Europe, Oceania, and North, Central, and South America. Our study showed that it is not possible so far to draw a world map of the ecological quality of rivers. Biological assessment of rivers and streams is only implemented officially nation-wide and regularly in the European Union, Japan, Republic of Korea, South Africa, and the USA. In Australia, Canada, China, New Zealand, and Singapore it has been implemented officially at the state/province level (in some cases using common protocols) or in major catchments or even only once at the national level to define reference conditions (Australia). In other cases, biological monitoring is driven by a specific problem, impact assessments, water licenses, or the need to rehabilitate a river or a river section (as in Brazil, South Korea, China, Canada, Japan, Australia). In some countries monitoring programs have only been explored by research teams mostly at the catchment or local level (e.g., Brazil, Mexico, Chile, China, India, Malaysia, Thailand, Vietnam) or implemented by citizen science groups (e.g., Southern Africa, Gambia, East Africa, Australia, Brazil, Canada). The existing large-extent assessments show a striking loss of biodiversity in the last 2–3 decades in Japanese and New Zealand rivers (e.g., 42% and 70% of fish species threatened or endangered, respectively). A poor condition (below Good condition) exists in 25% of South Korean rivers, half of the European water bodies, and 44% of USA rivers, while in Australia 30% of the reaches sampled were significantly impaired in 2006. Regarding river rehabilitation, the greatest implementation has occurred in North America, Australia, Northern Europe, Japan, Singapore, and the Republic of Korea. Most rehabilitation measures have been related to improving water quality and river connectivity for fish or the improvement of riparian vegetation. The limited extent of most rehabilitation measures (i.e., not considering the entire catchment) often constrains the improvement of biological condition. Yet, many rehabilitation projects also lack pre-and/or post-monitoring of ecological condition, which prevents assessing the success and shortcomings of the recovery measures. Economic constraints are the most cited limitation for implementing monitoring programs and rehabilitation actions, followed by technical limitations, limited knowledge of the fauna and flora and their life-history traits (especially in Africa, South America and Mexico), and poor awareness by decision-makers. On the other hand, citizen involvement is recognized as key to the success and sustainability of rehabilitation projects. Thus, establishing rehabilitation needs, defining clear goals, tracking progress towards achieving them, and involving local populations and stakeholders are key recommendations for rehabilitation projects (Table 1). Large-extent and long-term monitoring programs are also essential to provide a realistic overview of the condition of rivers worldwide. Soon, the use of DNA biological samples and eDNA to investigate aquatic diversity could contribute to reducing costs and thus increase monitoring efforts and a more complete assessment of biodiversity. Finally, we propose developing transcontinental teams to elaborate and improve technical guidelines for implementing biological monitoring programs and river rehabilitation and establishing common financial and technical frameworks for managing international catchments. We also recommend providing such expert teams through the United Nations Environment Program to aid the extension of biomonitoring, bioassessment, and river rehabilitation knowledge globally