• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.522-529
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• 2019

M1/M2 polarization of immune cells including microglia has been well characterized. It mediates detrimental or beneficial roles in neuroinflammatory disorders including cerebral ischemia. We have previously found that sphingosine 1-phospate receptor subtype 1 ($S1P_1$) in post-ischemic brain following transient middle cerebral artery occlusion (tMCAO) can trigger microglial activation, leading to brain damage. Although the link between $S1P_1$ and microglial activation as a pathogenesis in cerebral ischemia had been clearly demonstrated, whether the pathogenic role of $S1P_1$ is associated with its regulation of M1/M2 polarization remains unclear. Thus, this study aimed to determine whether $S1P_1$ was associated with regulation of M1/M2 polarization in post-ischemic brain. Suppressing $S1P_1$ activity with its functional antagonist, AUY954 (5 mg/kg, p.o.), attenuated mRNA upregulation of M1 polarization markers in post-ischemic brain at 1 day and 3 days after tMCAO challenge. Similarly, suppressing $S1P_1$ activity with AUY954 administration inhibited M1-polarizatioin-relevant $NF-{\kappa}B$ activation in post-ischemic brain. Particularly, $NF-{\kappa}B$ activation was observed in activated microglia of post-ischemic brain and markedly attenuated by AUY954, indicating that M1 polarization through $S1P_1$ in post-ischemic brain mainly occurred in activated microglia. Suppressing $S1P_1$ activity with AUY954 also increased mRNA expression levels of M2 polarization markers in post-ischemic brain, further indicating that $S1P_1$ could also influence M2 polarization in post-ischemic brain. Finally, suppressing $S1P_1$ activity decreased phosphorylation of M1-relevant ERK1/2, p38, and JNK MAPKs, but increased phosphorylation of M2-relevant Akt, all of which were downstream pathways following $S1P_1$ activation. Overall, these results revealed $S1P_1$-regulated M1/M2 polarization toward brain damage as a pathogenesis of cerebral ischemia.

• Journal of Physiology & Pathology in Korean Medicine
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• v.38 no.1
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• pp.32-37
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• 2024

The aim of this study was to investigate the role of Daesiho-tang (Da Chai Hu-Tang) water extract (DSTE) in regulating chronic stress-induced cancer progression, focusing on its activity in modulating tumor-associated macrophages (TAMs). Different stimuli can polarize TAMs into immune-stimulating M1 macrophages or immunosuppressive M2 macrophages. During cancer progression, M2 phenotype increases and supports tumor growth, angiogenesis and metastasis. Notably, chronic stress-induced catecholamines promote M2 macrophage polarization. In this study, we investigated whether DSTE regulates norepinephrine (NE)-induced M2 macrophage polarization in RAW 264.7 mouse macrophage cells. Even though NE itself did not increase the expression of M2 markers, the conditioned media of NE-treated 4T1 mouse breast cancer cells (NE CM) significantly up-regulated M2 markers in RAW 264.7 cells, suggesting that NE-regulated cancer cell secretome stimulated M2 polarization. However, such increase was abrogated by DSTE. NE CM also induced phosphorylation of signal transducer and activator of transcription 6 (STAT6) in RAW 264.7 cells, which was clearly reversed by pretreatment with DSTE, demonstrating that DSTE inhibited M2 polarization by inactivating STAT6. Finally, M2-polarized RAW264.7 cells by NE CM markedly increased the migration of 4T1 cells. However, such increase was completely reversed by co-treating RAW264.7 cells with NE CM and DSTE, indicating that DSTE attenuated cancer cell migration by blocking M2 polarization. Taken together, our results suggest a probable use of DSTE for cancer patients under chronic stress by regulating M2 macrophage polarization.

• Journal of Pharmacopuncture
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• v.22 no.4
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• pp.253-259
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• 2019

Objectives: It is reported that tumor-associated macrophages (TAMs) contribute to cancer progression by promoting tumor growth and metastasis. The purpose of this study is to investigate the effect of different fractions of Adenophora triphylla var. japonica (AT) on the polarization of macrophages into the M2 phenotype, a major phenotype of TAMs. Methods: We isolated hexane, ethyl acetate, and butanol fractions from crude ethanol extract of AT. The cytotoxicity of AT in RAW264.7 cells was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RAW264.7 cells were polarized into the M2 phenotype by treatment with interleukin (IL)-4 and IL-13. The expression of M2 macrophage marker genes was detected by reverse transcription polymerase chain reaction (RT-PCR). The phosphorylation level of signal transducer and activator of transcription 6 (STAT6) was investigated by western blot analysis. The migration of Lewis lung carcinoma (LLC) cells was examined by transwell migration assay using conditioned media (CM) collected from RAW264.7 cells as a chemoattractant. Results: Among various fractions of AT, the ethyl acetate fraction of AT (EAT) showed the most significant suppressive effect on the mRNA expression of M2 macrophage markers, including arginase-1, interleukin (IL)-10 and mannose receptor C type 1 (MRC-1), up-regulated by treatment of IL-4 and IL-13. In addition, EAT suppressed the phosphorylation of STAT6, a critical regulator of IL-4 and IL-13-induced M2 macrophage polarization. Finally, the increased migration of Lewis lung carcinoma (LLC) cells by CM from M2-polarized RAW264.7 cells was reduced by CM from RAW264.7 cells co-treated with EAT and M2 polarization inducers. Conclusion: We demonstrated that EAT attenuated cancer cell migration through suppression of macrophage polarization toward the M2 phenotype. Additional preclinical or clinical researches are needed to evaluate its regulatory effects on macrophage polarization and anti-cancer activities.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.437-448
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• 2023

Diabetic ulcer is usually seen in people with uncontrolled blood sugar. Reportedly, many factors such as impaired glucose metabolism, and macrovascular and microvascular diseases caused angiogenesis disorders and delayed the healing of diabetic ulcers, thus affecting the body's metabolism, nutrition, and immune function. This study aimed to explore the effect of paeonol on skin wound healing in diabetic rats and the related mechanism. A rat model of diabetic ulcer was established. High glucose-treated mouse skin fibroblasts were co-cultured with M1 or M2-polarized macrophages treated with or without paeonol. H&E and Masson staining were used to reveal inflammatory cell infiltration and collagen deposition, respectively. Immunohistochemistry visualized the expression of Ki67, CD31, and vascular endothelial growth factor (VEGF). Western blot was used to detect interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, IL-10, CD31, VEGFA, and collagen I/III. The expression of iNOS and arginase 1 was revealed by immunofluorescence staining. Paeonol treatment augmented collagen deposition and the expression of Ki67, CD31, VEGF, and macrophage M2 polarization markers (IL-4 and IL-10) and reduced wound area, inflammatory cell infiltration, and macrophage M1 polarization markers (IL-1β and TNF-α) in the ulcerated area. In vitro, paeonol treatment promoted M2-polarization and repressed M1-polarization in macrophages, thereby improving the repair of cell damage induced by high glucose. Paeonol accelerates the healing of diabetic ulcers by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization.

• Archives of Plastic Surgery
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• v.50 no.4
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• pp.432-442
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• 2023

Background Macrophages play a major role in wound healing and prevent infection from the outside. Polarization conversion of macrophages regulates aspects of inflammation, and two macrophages, M1 (classically activated) and M2 (alternatively activated), exist at both ends of broad-spectrum macrophage polarization. Thus, we aimed to investigate whether macrophage polarization can be artificially regulated. To this end, MgSO4 and small-interfering RNA (siRNA) targeting magnesium transport 1 (MAGT1) were used to investigate the effects of intracellular magnesium (Mg2+) concentrations on the differentiation of macrophages in vitro. Methods THP-1 derived macrophages maintained in a culture medium containing 5 mM MgSO4 and siRNA to inhibit the expression of MAGT1. As comparative groups, THP-1 derived macrophages polarized into M1 and M2 macrophages by treatment with M1, M2 inducer cytokine. The polarization status of each group of cells was confirmed by cell surface antigen expression and cytokine secretion. Results We found that MgSO4 treatment increased CD163 and CD206, similar to the effect noted in the M2 group. The expression of CD80 and HLA-DR was increased in the group treated with MAGT1 siRNA, similar to the effect noted in the M1 group. Functional assays demonstrated that the group treated with MgSO4 secreted higher levels of IL-10, whereas the MAGT1 siRNA-treated group secreted higher levels of IL-6 cytokines. Additionally, the conditional medium of the Mg2+ treated group showed enhanced migration of keratinocytes and fibroblasts. Conclusion Mg2+ can help to end the delay in wound healing caused by persistent inflammation in the early stages.

• Journal of Fisheries and Marine Sciences Education
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• v.18 no.1
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• pp.58-64
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• 2006

In order to examine the effect of humidity on hydrogen embrittlement of STS 444 weld zone for boiler with dry and wet welding conditions, this paper was carried out the accelerated hydrogen osmosis test and the electrochemical Tafel polarization test. In 0.5M $H_2SO_4$ + 0.01M $As_20_3$ solution, this test is added to load of $1400kg/cm^2$ together with hydrogen osmosis by current of $50 {mA/cm^2}$ for 60 min.. The electrochemical Tafel polarization test was carried out in 0.5M $H_2SO_4$ + 0.01M $As_20_3$ solution. Therefore, the effect of humidity on hydrogen embrittlement of STS 444 was considered. The main results are as following: On the basis of hydrogen embrittlement mechanism, that is, integrated electrochemical polarization characteristics with the established mechanism of hydrogen embrittlement, the reduction rate of corrosion current density of weld zone in the wet weld condition is larger than in the dry condition. We can nondestructively predict the degree of hydrogen embrittlement of STS 444 weld zone for boiler through the reduction rate of electrochemical corrosion current density.

• Electrical & Electronic Materials
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• v.10 no.2
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• pp.156-165
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• 1997

D-E hysteresis loops have been measured for the 65/35 mole % copolymer of vinylidene fluoride and trifluoroethylene over wide temperature range. The remanent polarization and the coercive field at room temperature were estimated to be 75 mC/m$^{2}$ and 55 MV/m respectively. D-E hysteresis loops were observed even below the glass transition temperature(-20.deg. C) and the remanent polarization and the coercive field were larger, as the temperature lower. It seems that the remanent polarization and the coercive field depend on the amorphous region as well as crystalline region in this copolymer. And the ferroelectric-to-paraelectric phase transition was observed at 90.deg. C on heating and 80'C on cooling. Double hysteresis loops were observed at the temperature(85.deg. C) of paraelectric phase.

• Journal of The Korean Astronomical Society
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• v.40 no.4
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• pp.113-118
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• 2007

Recently far infra-red (FIR) polarization of the $850{\mu}m$ continuum emission from T Tauri disks has been detected. The observed degree of polarization is around 3 %. Since thermal emission from dust grains dominates the spectral energy distribution at the FIR regime, dust grains might be the cause of the polarization. We explore alignment of dust grains by radiative torque in T Tauri disks and provide predictions for polarized emission for disks viewed at different wavelengths and viewing angles. In the presence of magnetic field, these aligned grains produce polarized emission in infrared wavelengths. When we take a Mathis-Rumpl-Nordsieck-type distribution with maximum grain size of $500-1000{\mu}m$, the degree of polarization is around 2-3 % level at wavelengths larger than ${\sim}100{\mu}m$. Our study indicates that multifrequency infrared polarimetric studies of protostellar disks can provide good insights into the details of their magnetic structure.

• Journal of the Korean Magnetic Resonance Society
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• v.21 no.4
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• pp.114-118
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• 2017

Here, I report solid state Dynamic Nuclear Polarization (DNP) of $^1H$ nuclear spins at 0.3 T and 4.2 K. The DNP polarizer was developed based on a commercial X-band Electron Spin Resonance (ESR) modified for DNP, in combination with a NMR console and a liquid-Helium cryostat. By detuning magnetic field, DNP spectrum was measured to find the optimal condition. At +3 mT detuned from on-resonance field, $^1H$ NMR signal of 60:40 glycerol/water frozen solution doped with 20 mM perdeuterated-Tempone was amplified 43 times. The $^1H$ spin polarization obtained at 4.2 K is over 3100 times higher than that at 300 K. The width of the DNP spectrum, which is five times broader than ESR spectrum, is inconsistent with solid effect or thermal mixing, and presumably suggests a different DNP mechanism.

• Journal of The Korean Astronomical Society
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• v.56 no.1
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• pp.1-9
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• 2023

The Crab nebula is widely used as a polarization angle calibrator for single-dish radio observations because of its brightness, high degree of linear polarization, and well-known polarization angle over a wide frequency range. However, the Crab nebula cannot be directly used as a polarization angle calibrator for single-dish observations with the Korean VLBI Network (KVN), because the beam size of the telescopes is smaller than the size of the nebula. To determine the polarization angle of the Crab nebula as seen by KVN, we use 3C 286, a compact polarized extragalactic radio source whose polarization angle is well-known, as a reference target. We observed both the Crab nebula and 3C 286 with the KVN from 2017 to 2021 and find that the polarization angles at the total intensity peak of the Crab nebula (equatorial coordinates (J2000) R.A. = 05^h34^m32.3804^s and Dec = 22°00'44.0982'') are 154.2° ± 0.3°, 151.0° ± 0.2°, 150.0° ± 1.0°, and 151.3° ± 1.1° at 22, 43, 86, and 94 GHz, respectively. We also find that the polarization angles at the pulsar position (RA = 05^h34^m31.971^s and Dec = 22°00'52.06'') are 154.4° ±0.4°, 150.7° ±0.4°, and 149.0° ± 1.0° for the KVN at 22, 43, and 86 GHz. At 129 GHz, we suggest to use the values 149.0° ± 1.6° at the total intensity peak and 150.2° ± 2.0° at the pulsar position obtained with the Institute for Radio Astronomy in the Millimeter Range (IRAM) 30-meter Telescope. Based on our study, both positions within the Crab nebula can be used as polarization angle calibrators for the KVN single-dish observations.