• BMB Reports
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• v.55 no.2
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• pp.81-86
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• 2022

Macrophages are a major cellular component of innate immunity and are mainly known to have phagocytic activity. In the tumor microenvironment (TME), they can be differentiated into tumor-associated macrophages (TAMs). As the most abundant immune cells in the TME, TAMs promote tumor progression by enhancing angiogenesis, suppressing T cells and increasing immunosuppressive cytokine production. N-myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene, whose expression is down-regulated in various cancers. However, the effect of NDRG2 on the differentiation of macrophages into TAMs in breast cancer remains elusive. In this study, we investigated the effect of NDRG2 expression in breast cancer cells on the differentiation of macrophages into TAMs. Compared to tumor cell-conditioned medium (TCCM) from 4T1-mock cells, TCCM from NDRG2-over-expressing 4T1 mouse breast cancer cells did not significantly change the morphology of RAW 264.7 cells. However, TCCM from 4T1-NDRG2 cells reduced the mRNA levels of TAM-related genes, including MR1, IL-10, ARG1 and iNOS, in RAW 264.7 cells. In addition, TCCM from 4T1-NDRG2 cells reduced the expression of TAM-related surface markers, such as CD206, in peritoneal macrophages (PEM). The mRNA expression of TAM-related genes, including IL-10, YM1, FIZZ1, MR1, ARG1 and iNOS, was also downregulated by TCCM from 4T1-NDRG2 cells. Remarkably, TCCM from 4T1-NDRG2 cells reduced the expression of PD-L1 and Fra-1 as well as the production of GM-CSF, IL-10 and ROS, leading to the attenuation of T cell-inhibitory activity of PEM. These data showed that compared with TCCM from 4T1-mock cells, TCCM from 4T1-NDRG2 cells suppressed the TAM differentiation and activation. Collectively, these results suggest that NDRG2 expression in breast cancer may reduce the differentiation of macrophages into TAMs in the TME.

• Molecules and Cells
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• v.45 no.3
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• pp.134-147
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• 2022

The anti-oxidant enzyme heme oxygenase-1 (HO-1) is known to exert anti-inflammatory effects. From a library of pyrazolo[3,4-d]pyrimidines, we identified a novel compound KKC080096 that upregulated HO-1 at the mRNA and protein levels in microglial BV-2 cells. KKC080096 exhibited anti-inflammatory effects via suppressing nitric oxide, interleukin1β (IL-1β), and iNOS production in lipopolysaccharide (LPS)-challenged cells. It inhibited the phosphorylation of IKK and MAP kinases (p38, JNK, ERK), which trigger inflammatory signaling, and whose activities are inhibited by HO-1. Further, KKC080096 upregulated anti-inflammatory marker (Arg1, YM1, CD206, IL-10, transforming growth factor-β [TGF-β]) expression. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinetreated mice, KKC080096 lowered microglial activation, protected the nigral dopaminergic neurons, and nigral damage-associated motor deficits. Next, we elucidated the mechanisms by which KKC080096 upregulated HO-1. KKC080096 induced the phosphorylation of AMPK and its known upstream kinases LKB1 and CaMKKbeta, and pharmacological inhibition of AMPK activity reduced the effects of KKC080096 on HO-1 expression and LPS-induced NO generation, suggesting that KKC080096-induced HO-1 upregulation involves LKB1/AMPK and CaMKKbeta/AMPK pathway activation. Further, KKC080096 caused an increase in cellular Nrf2 level, bound to Keap1 (Nrf2 inhibitor protein) with high affinity, and blocked Keap1-Nrf2 interaction. This Nrf2 activation resulted in concurrent induction of HO-1 and other Nrf2-targeted antioxidant enzymes in BV-2 and in dopaminergic CATH.a cells. These results indicate that KKC080096 is a potential therapeutic for oxidative stress-and inflammation-related neurodegenerative disorders such as Parkinson's disease.

• Sleep Medicine and Psychophysiology
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• v.26 no.2
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• pp.111-124
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• 2019

Objectives: Healthy sleep is important and can have a positive effect on resilience. The aim of the present study was to compare the differences in resilience between two group nurses in rotating shift and daytime fixed work schedules and to investigate stress perception, coping factors, social and psychological health, and sleep factors that may affect resilience. Methods: A total of 400 female nurses having rotating shift and daytime fixed work schedules at two hospitals was surveyed from June 12, 2017 to June 12, 2018. All participants completed perceived stress scale (PSS), stress coping short form (Brief COPE), psycho-social wellbeing Index short form (PWI-SF) or general health questionnaire-18 (GHQ-18), center for epidemiologic studies depression scale (CES-D), STAI-X-1 in state-trait anxiety inventory (STAI), Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), insomnia severity index (ISI), Conner Davidson resilience scale (CD-RISC). Independent t-test, paired t-test, Pearson correlation analysis, and multiple regression analysis were applied to the results of the final 373 questionnaires of 400 nurses in two general hospitals. Results: Comparing the variable statistics between the two groups of rotating shift and daytime fixed work nurses, showed statistically significant differences in all variables except perceived stress, sleep quality, and daytime sleepiness. Factors that had a significant correlation with resilience were stress coping strategies, depression, and insomnia severity (p < 0.001). In multiple regression analysis, larger positive reframing1 (β = 0.206, p < 0.001), severe less depression (β = -3.45, p < 0.001), and higher psychosocial health (β = 0.193, p < 0.001). As acceptance coping2 increased (β = 0.129, p < 0.05), as daytime sleepiness decreased (β = -1.17, p < 0.05), and as active coping2 increased (β = 0.118, p < 0.05), as the positive reframing2 increases (β = 0.110, p < 0.05), the resilience increased. Conclusion: This study, it was found that resilience was higher in daytime fixed workers than in shift workers. In addition, specific stress coping strategies, psycho-social health, sleep, and depression factors were associated with resilience.

• Korean Journal of Ichthyology
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• v.28 no.3
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• pp.200-206
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• 2016

The 7-week feeding experiment was conducted to investigate the effects of one experimental diet (ED) and five different commercial diets (CDs) on growth and body composition of juvenile olive flounder, Paralichthys olivaceus. An ED was formulated to contain 50.0% crude protein (CP) from fishmeal, casein, zein and wheat flour and 15.0% crude lipid (CL) from squid liver oil. Five CDs for seawater fish were two domestic E commercial diet (DECD) and C commercial diet (DCCD), three imported H commercial diet (IHCD), M commercial diet (IMCD) and O commercial diet (IOCD) containing 53.1~58.0% CP and 4.8~12.7% CL, respectively. Each diet was fed to triplicate groups of juvenile olive flounder initially weighing $29.1{\pm}0.8g/fish\;(mean{\pm}SD)$ in a flow-through seawater system with a water temperature of $23.4{\sim}28.0^{\circ}C$. Weight gain (WG) was significantly greatest in fish fed the IMCD; intermediate responses were observed for fish fed the DECD, DCCD, and IOCD, while the IHCD and the ED produced the lowest WG values. Feed efficiencies (FE) were similar to WG excluding fish fed the DCCD; FE was also greatest in fish fed the DCCD. Survival with no significant difference approached 100% for fish fed the all six diets in this experiment. Whole-body crude protein and ash contents were not affected excluding moisture and crude lipid by the different type of diets. Therefore, type of diets appeared to be important factor in influencing WG, FE and whole-body moisture and crude lipid of juvenile olive flounder; the best diet for juvenile olive flounder was determined to be the imported commercial M diets containing intermediate protein (55.9%) and lipid (12.7%) in natural seawater based on highest WG, and FE, respectively. This study indicates that the one commercially formulated diet containing intermediate protein and lipid used in this experiment could be a practical diet for juvenile olive flounder; these differences in growth performance between ED and CDs may be due to different dietary protein and lipid levels.

• Journal of Animal Science and Technology
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• v.49 no.1
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• pp.137-146
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• 2007

This study was conducted to determine fertilizer nutrient and pollutant production of Holstein dairy cattle by estimating manure characteristics. The moisture content of feces was 83.9% and 95.1% for urine. The pH of feces and urine were in the ranges of 7.0～7.4 and 7.5～7.8, respectively. The average BOD5, COD, SS, T-N, T-P concentrations of the dairy feces were 18,294, 52,765, 102,889, 2,575, and 457mg/ℓ, respectively. Dairy urine showed lower levels of BOD5(5,455mg/ℓ), COD(8,089mg/ℓ), SS(593mg/ℓ), T-N(3,401mg/l), and T-P(13mg/ℓ) than feces. The total daily produced pollutant amounts of a dairy cow were 924.1g(Milking cow), 538.8g(Dry cow), 284.4g(Heifer) of BOD5, 2,336.5g (Milking cow), 1,651.8g(Dry cow), 734.1g(Heifer) of COD and 4,210.1g(Milking cow), 2,417.1g(Dry cow), 1,629.1g(Heifer) of SS and 194.8g(Milking cow), 96.4g(Dry cow), 58.3g(Heifer) of T-N and 24.0g(Milking cow), 10.2g(Dry cow), 6.1g(Heifer) of T-P. The calculated amount of pollutants produced by a 450kg dairy cow for one year were 181.3kg of BOD5, 492.5kg of COD, 899.9kg of SS, 36.0kg of T-N and 4.1kg of T-P. The total yearly estimated pollutant production from all head(497,261) of dairy cattle in Korea is 90,149 tons of BOD5, 244,890 tons of COD, 447,491 tons of SS, 17,898 tons of T-N and 2,008 tons of T-P. The fertilizer nutrient concentrations of dairy feces was 0.26% N, 0.1% P2O5 and 0.14% K2O. Urine was found to contain 0.34% N, 0.003% of P2O5 and 0.31% K2O. The total daily fertilizer nutrients produced by dairy cattle were 197.4g (Milking cow), 97.4g(Dry cow), and 57.9g(Heifer) of Nitrogen, 54.2g(Milking cow), 22.2g(Dry cow), and 14.2g(Heifer) of P2O5 and 110.8g(Milking cow), 80.4g (Dry cow), and 39.5g(Heifer) of K2O. The total yearly estimated fertilizer nutrient produced by a 450kg dairy animal is 36.2kg of N, 8.8kg of P2O5, 24.6kg of K2O. The estimated yearly fertilizer nutrient production from all dairy cattle in Korea is 18,000 tons of N, 4,397 tons of P2O5, 12,206 tons of K2O. Dairy manure contains useful trace minerals for crops, such as CaO and MgO, which are contained in similar levels to commercial compost being sold in the domestic market. Concentrations of harmful trace minerals, such as As, Cd, Hg, Pb, Cr, Cu, Ni, Zn, met the Korea compost standard regulations, with some of these minerals being in undetected amounts.