Farooq A, Hoque R, Ouyang X, Farooq A, Ghani A, Ahsan K, Guerra M, Mehal WZ. Activation of N-methyl-D-aspartate receptor downregulates inflammasome activity and liver inflammation via a -arrestin-2 pathway. Am J Physiol Gastrointest Liver Physiol 307: G732-G740, 2014. First published August 7, 2014; doi:10.1152/ajpgi.00073.2014.-Activation of the cytosolic inflammasome machinery is responsible for acute and chronic liver inflammation, but little is known about its regulation. The N-methyl-Daspartate (NMDA) receptor families are heterotetrameric ligand-gated ion channels that are activated by a range of metabolites, including aspartate, glutamate, and polyunsaturated fatty acids. In the brain NMDA receptors are present on neuronal and nonneuronal cells and regulate a diverse range of functions. We tested the role of the NMDA receptor and aspartate in inflammasome regulation in vitro and in models of acute hepatitis and pancreatitis. We demonstrate that the NMDA receptor is present on Kupffer cells, and their activation on primary mouse and human cells limits inflammasome activation by downregulating NOD-like receptor family, pyrin domain containing 3 and procaspase-1. The NMDA receptor pathway is active in vivo, limits injury in acute hepatitis, and can be therapeutically further activated by aspartate providing protection in acute inflammatory liver injury. Downregulation of inflammasome activation by NMDA occurs via a -arrestin-2 NF-k and JNK pathway and not via Ca 2ϩ mobilization. We have identified the NMDA receptor as a regulator of inflammasome activity in vitro and in vivo. This has identified a new area of immune regulation associated by metabolites that may be relevant in a diverse range of conditions, including nonalcoholic steatohepatitis and total parenteral nutrition-induced immune suppression.aspartate
We present a case of severe acquired acrodermatitis enteropathica in a vegan adult female with multiple underlying comorbidities. Acquired acrodermatitis enteropathica or zinc-deficiency dermatitis is the most common diagnosis than many practitioners realize with up to 10% of the patients in developed nations with the risk of zinc deficiency. The condition can be difficult to diagnose due to many similarly-presenting conditions. Furthermore, comorbid conditions in the patients can serve as confounders to the diagnosis. The symptoms are often extremely distressing for the patients, though the treatment is simple and clinical improvement occurs rapidly with appropriate care. We recommend a high index of suspicion to practitioners as well as a low-threshold for initiating treatment in the patients with any clinical symptoms of the condition.
The basic purpose of this study is to identify a link concerning tourism, pecuniary expansion, and environmental protection in developing countries. The current research looks at the overall state of emerging economies as well as income comparisons. The study employs the 3sls model. Tourism benefits from economic growth as well. Tourism is attracted by economic prosperity, and tourism will increase tourism. According to the findings, economic growth has a negative impact on the environment, and the environment has an adverse effect on economic growth. As income activity accelerates, so will environmental emissions, and environmental emissions have a detrimental impact on economic growth? Further findings imply that tourism has a favorable impact on the environment, with an increase in tourism causing a depreciation of the ecosystem. Environmental pollution has a favorable effect on tourism, as the majority of people travel to other countries for business and religious reasons. This can be found in all models. The exchange rate has a negative influence on the overall and high-income groups, but a favorable effect in the reduced groups. In all models, the other variable, political instability, has a negative effect on tourism, while trade has a favorable effect. GDP is boosted by the literacy rate and gross capital formation Population increase, urbanization, and energy use all have a favorable impact on environmental emissions, according to the study. According to the findings, host nations should not only encourage tourism, but also guarantee that the environment is not harmed, therefore ecofriendly must be pushed to maintain a seamless and sustainable development process.
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