Silica nanoparticles with iron on their surface cause the production of oxidants and stimulate an inflammatory response in macrophages. Nuclear factor erythroid-derived 2 –like factor 2 (Nrf2) signaling and its regulated antioxidant genes play critical roles in maintaining redox homeostasis. In this study we investigated the regulation of four representative Nrf2-regulated antioxidant genes; i.e., glutamate cysteine ligase (GCL) catalytic subunit (GCLC), GCL modifier subunit (GCLM), heme oxygenase 1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO-1), by iron-coated silica nanoparticles (SiO2-Fe) in human THP-1 macrophages. We found that the expression of these four antioxidant genes was modified by SiO2-Fe in a time-dependent manner. At 6 h, their expression was unchanged except for GCLC, which was reduced compared with controls. At 18 h, the expression of these antioxidant genes was significantly increased compared with controls. In contrast, the Nrf2 activator sulforaphane induced all antioxidant genes at as early as 3 h. The nuclear translocation of Nrf2 occurred later than that for NF-κB p65 protein and the induction of proinflammatory cytokines (TNFα and IL-1β). NF-κB inhibitor SN50 prevented the reduction of GCLC at 6 h and abolished the induction of antioxidant genes at 18 h by SiO2-Fe, but did not affect the basal and sulforaphane-induced expression of antioxidant genes, suggesting that NF-κB signaling plays a key role in the induction of Nrf2-mediated genes in response to SiO2-Fe. Consistently, SN50 inhibited the nuclear translocation of Nrf2 caused by SiO2-Fe. In addition, Nrf2 silencing decreased the basal and SiO2-induced expression of the four reprehensive antioxidant genes. Taken together, these data indicated that SiO2-Fe induced a delayed response of Nrf2-regulated antioxidant genes, likely through NF-κB-Nrf2 interactions.
How macrophages maintain redox homeostasis in the inflammatory process, in which a large amount of oxidants are produced, remains elusive. In this study, we investigated the temporal changes in the intracellular glutathione (GSH), the master antioxidant, and the expression of glutamate cysteine ligase (GCL), the rate-limiting enzyme for GSH biosynthesis, in the inflammatory response of human macrophages (THP1 cells) to lipopolysaccharide. Intracellular GSH concentration was decreased significantly in the early phase (∼6 h) of LPS exposure, and then gradually went back to the basal level in the late phase (9∼24 h). The expression level of the catalytic subunit of GCL (GCLC) followed a similar pattern of change as GSH: its mRNA and protein levels were reduced in the early phase and then back to basal level in the late phase. In contrast, the expression of the modifier subunit of GCL (GCLM) was significantly increased in the phase of LPS exposure. Activation Nrf2, the transcription factor involved in the induction of both GCLC and GCLM, occurred at as early as 3 h after LPS exposure; whereas the activation of NF-κB occurred at as early as 30 min. Inhibition of NF-κB signaling with SN50 prevented the decrease of GCLC and inhibited Nrf2 activation in response to LPS. These data demonstrate time-dependent changes in the expression of GCL and Nrf2 signaling during the inflammatory response, and that the regulation of GCLC and GCLM might be through different pathways in this process.
The results indicate that individuals with ID do have a partial to full understanding of the concepts of death. The culture of Hong Kong is one that considers death to be a taboo or unlucky subject. Therefore, the results mirror the the lack of understanding of universality and inevitability concepts as it is forbidden to speak of these concepts. An open and honest environment is encouraged to educate individuals with ID about death and bereavement.
Background
Special Olympics International (SOI) has provided eye assessments at no cost to athletes participating in competitions through the Special Olympics Lions Clubs International Foundation Opening Eyes (OE) programme. Access to vision services is crucial given the high rates of eye abnormalities found in studies collected at OE programmes in other countries. As of 2022, no studies covering vision data have been published on SOI athletes specifically from the USA. Therefore, this multiple cross‐sectional study hopes to investigate the vision profile of US athletes over three national games, detecting any changes in vision and ocular health outcomes over an 8‐year period.
Methods
Vision assessments were conducted in the US national games of 2010, 2014 and 2018. Demographic and clinical data from 1427 vision assessments were used in this study. Prevalence of vision and ocular health abnormalities were compared across national games.
Results
In our cohort of 1427 assessments with athletes' mean age ± SD of 29.8 ± 11.5 years, 85.3% (n = 1170) had an abnormal vision result with at least one of the following findings: decreased visual acuity of 20/40 or worse (31.0%, n = 442), refractive error including myopia (52.8%, n = 754), hypermetropia (15.7%, n = 224), and astigmatism (35.0%, n = 499), ocular misalignment distant (16.2%, n = 224) or near (17.2%, n = 239), or ocular abnormality (19.1%, n = 273).
Conclusions
This study demonstrates the burden of vision defects and ocular disease in US SOI athletes over the past decade. While continued effort must be made to train eye providers in caring for patients with ID to increase eyecare accessibility outside of SOI, vision assessments at national games can continue providing opportunities for improved ocular health in children and adults with ID.
How macrophages maintain redox homeostasis in the inflammatory process, in which a large amount of oxidants are produced, remains elusive. In this study, we investigated the temporal changes in the intracellular glutathione (GSH), the master antioxidant, and the expression of glutamate cysteine ligase (GCL), the rate-limiting enzyme for GSH biosynthesis, in the inflammatory response of human macrophages (THP1 cells) to lipopolysaccharide. Intracellular GSH concentration was decreased significantly in the early phase (∼6 h) of LPS exposure, and then gradually went back to the basal level in the late phase (9∼24 h). The expression level of the catalytic subunit of GCL (GCLC) followed a similar pattern of change as GSH: its mRNA and protein levels were reduced in the early phase and then back to basal level in the late phase. In contrast, the expression of the modifier subunit of GCL (GCLM) was significantly increased in the phase of LPS exposure. Activation Nrf2, the transcription factor involved in the induction of both GCLC and GCLM, occurred at as early as 3 h after LPS exposure; whereas the activation of NF-κB occurred at as early as 30 min. Inhibition of NF-κB signaling with SN50 prevented the decrease of GCLC and inhibited Nrf2 activation in response to LPS. These data demonstrate timedependent changes in the expression of GCL and Nrf2 signaling during the inflammatory response, and that the regulation of GCLC and GCLM might be through different pathways in this process.
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