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Excessive host inflammation following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with severity and mortality in coronavirus disease 2019 (COVID-19). We recently reported that the SARS-CoV-2 spike protein S1 subunit (S1) induces pro-inflammatory responses by activating toll-like receptor 4 (TLR4) signaling in macrophages. ETAS(R)50, a standardized extract of Asparagus officinalis stem, is a unique functional food that elicits anti-photoaging effects by suppressing pro-inflammatory signaling in hydrogen peroxide- and ultraviolet B-exposed skin fibroblasts. To elucidate its potential in preventing excessive inflammation in COVID-19, we examined the effects of ETAS(R)50 on pro-inflammatory responses in S1-stimulated murine peritoneal exudate macrophages. Co-treatment of the cells with ETAS(R)50 significantly attenuated S1-induced secretion of interleukin (IL)-6 in a concentration-dependent manner without reducing cell viability. ETAS(R)50 also markedly suppressed the S1-induced transcription of IL-6 and IL-1{beta}. However, among the TLR4 signaling proteins, ETAS(R)50 did not affect the degradation of inhibitor {kappa}B, nuclear translocation of nuclear factor-{kappa}B p65 subunit, and phosphorylation of c-Jun N-terminal kinase p54 subunit after S1 exposure. In contrast, ETAS(R)50 significantly suppressed S1-induced phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) and Akt. Attenuation of S1-induced transcription of IL-6 and IL-1{beta} by the MAPK kinase inhibitor U0126 was greater than that by the Akt inhibitor perifosine, and the effects were potentiated by simultaneous treatment with both inhibitors. These results suggest that ETAS(R)50 attenuates S1-induced IL-6 and IL-1{beta} production by suppressing p44/42 MAPK and Akt signaling in macrophages. Therefore, ETAS(R)50 may be beneficial in regulating excessive inflammation in patients with COVID-19.

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BACKGROUND@#Heat shock protein 70 (HSP70) exhibits protective effects against ultraviolet (UV)-induced premature skin aging. A standardized extract of Asparagus officinalis stem (EAS) is produced as a novel and unique functional food that induces HSP70 cellular expression. To elucidate the anti-photoaging potencies of EAS, we examined its effects on HSP70 expression levels in UV-B-irradiated normal human dermal fibroblasts (NHDFs).@*METHODS@#NHDFs were treated with 1 mg/mL of EAS or dextrin (vehicle control) prior to UV-B irradiation (20 mJ/cm). After culturing NHDFs for different time periods, HSP70 mRNA and protein levels were analyzed using real-time polymerase chain reaction and western blotting, respectively.@*RESULTS@#UV-B-irradiated NHDFs showed reduced HSP70 mRNA levels after 1-6 h of culture, which were recovered after 24 h of culture. Treatment with EAS alone for 24 h increased HSP70 mRNA levels in the NHDFs, but the increase was not reflected in its protein levels. On the other hand, pretreatment with EAS abolished the UV-B irradiation-induced reduction in HSP70 expression at both mRNA and protein levels. These results suggest that EAS is capable to preserve HSP70 quantity in UV-B-irradiated NHDFs.@*CONCLUSIONS@#EAS exhibits anti-photoaging potencies by preventing the reduction in HSP70 expression in UV-irradiated dermal fibroblasts.

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Effects of environmental (cold) stress and aging on cells in monocyte/macrophage lineage were investigated. We demonstrated that immune suppressive states seen in acute cold-stressed mice (8-10 weeks of age) is attributable to FcγRII(bright) suppressor macrophages. Serum corticosterone levels were markedly increased in acute cold-stressed mice. In addition, expression of glucocorticoids (GC) receptor mRNA was observed in FcγRII(bright) cells from these mice. The increase of FcγRII(bright) cells in peritoneal exudate cells caused by acute cold stress was inhibited by adrenalectomy or administration of a saturating amount of the GC antagonist RU 38486 (mifepristone). On the contrary, administration of the GC agonist, dexamethasone, markedly increased the proportion of FcγRII(bright) cells in peritoneal exudate cells of control mice. These results suggest that the generation of FcγRII(bright) suppressor cells of monocyte/macrophage lineage by acute cold stress was mediated by action of GC through the GC receptor. We likewise found that the proportion of FcγRII(bright) suppressor macrophages is increased in aged mice (22-24 months of age). Meanwhile, activated macrophages which function as antigen presenting cells were decreased in aged rats. Both the basal corticosterone concentrations in serum and the expression of mRNA for GC receptor in peritoneal macrophages increased significantly in aged animals, suggesting that these populational and functional changes of macrophages in aged animals were mediated, in part, by the increased basal levels of GC. This is probably being responsible for immunosenescence.

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Effects of environmental (cold) stress and aging on cells in monocyte/macrophage lineage were investigated. We demonstrated that immune suppressive states seen in acute cold-stressed mice (8-10 weeks of age) is attributable to FcγRIIbright suppressor macrophages. Serum corticosterone levels were markedly increased in acute cold-stressed mice. In addition, expression of glucocorticoids (GC) receptor mRNA was observed in FcγRIIbright cells from these mice. The increase of FcγRIIbright cells in peritoneal exudate cells caused by acute cold stress was inhibited by adrenalectomy or administration of a saturating amount of the GC antagonist RU 38486 (mifepristone). On the contrary, administration of the GC agonist, dexamethasone, markedly increased the proportion of FcγRIIbright cells in peritoneal exudate cells of control mice. These results suggest that the generation of FcγRIIbright suppressor cells of monocyte/macrophage lineage by acute cold stress was mediated by action of GC through the GC receptor. We likewise found that the proportion of FcγRIIbright suppressor macrophages is increased in aged mice (22-24 months of age). Meanwhile, activated macrophages which function as antigen presenting cells were decreased in aged rats. Both the basal corticosterone concentrations in serum and the expression of mRNA for GC receptor in peritoneal macrophages increased significantly in aged animals, suggesting that these populational and functional changes of macrophages in aged animals were mediated, in part, by the increased basal levels of GC. This is probably being responsible for immunosenescence.

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From the viewpoint of atherosclerosis prevention, it is important to examine the effects of exercise on the lipoprotein fraction in the postprandial state. The purpose of this study was to investigate the effects of a single period of low-intensity exercise on serum lipoprotein triacylglycerol (TG) after an oral fat load (50g/body surface area) as exogenous TG. Seven normolipidemic men aged 23.1±1.1 years (mean ± SEM) took part in two trials. The subjects were all young students at a university graduate school. In the exercise trial (Ex), they exercised for 1.5 h on a bicycle ergometer at 35-40% of their maximal oxygen uptake, starting 2 h after ingestion of the fat, and then rested for a further 2 h. In the control trial (Co), they rested for 5.5 h after ingestion of the fat. Lipoprotein and lipid levels were measured in venous blood taken during the fasted state and at different intervals between the two trials for 5.5 h after the fat load. Serum total TG and high-density lipoprotein (HDL) TG decreased significantly in Ex from 3.5 to 5.5h (p<0.05, p<0.01) in comparison with Co. These results indicate that a single period of low-intensity exercise reduces exogenous serum total TG and HDL-TG.