• Journal of Veterinary Science
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• v.24 no.3
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• pp.37.1-37.14
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• 2023

Background: Toll-like receptor (TLR) agonists have been used as adjuvants to modulate immune responses in both animals and humans. Objectives: The objective of this study was to evaluate the combined effects of the TLR 4 agonist monophosphoryl lipid A (MPL) and the TLR 3 agonist polyinosinic:polycytidylic acid (Poly I:C) on equine peripheral blood mononuclear cells (PBMCs), monocyte-derived dendritic cells (MoDCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs). Methods: The PBMCs, MoDCs, and BM-MSCs collected from three mixed breed horses were treated with MPL, Poly I:C, and their combination. The mRNA expression of interferon gamma (IFN-γ), interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-12p40, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1) was determined using real-time polymerase chain reaction. Results: The combination of MPL and Poly I:C significantly upregulated immunomodulatory responses in equine cells/ without cytotoxicity. The combination induced greater mRNA expression of pro-inflammatory cytokines IFN-γ and IL-6 than MPL or Poly I:C stimulation alone in PBMCs. In addition, the combination induced significantly higher mRNA expression of IL-1β, IL-6, and IL-12p40 in MoDCs, and IL-8, MCP-1, and VEGF in BM-MSCs compared to stimulation with a single TLR agonist. Conclusions: The combination of MPL and Poly I:C can be used as a potential adjuvant candidate for vaccines to aid in preventing infectious diseases in horses.

• Journal of Microbiology and Biotechnology
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• v.30 no.11
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• pp.1614-1625
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• 2020

A number of species of the genus Trichilia (Meliaceae) exhibit anti-inflammatory effects. However, the effect of Trichilia martiana C. DC. (TM) on lipopolysaccharide (LPS)-induced inflammation has not, to the best of our knowledge, yet been determined. Therefore, in the present study, the antiinflammatory effect of TM on LPS-stimulated RAW264.7 macrophages was evaluated. The ethanol extract of TM (TMEE) significantly inhibited LPS-induced nitric oxide (NO), prostaglandin 2 (PGE₂), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). TMEE also reduced the levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and IL-6. The upregulation of mitogen-activated protein kinases (MAPKs) and NF-κB activation was revealed to be downregulated following TMEE pretreatment. Furthermore, TMEE was indicated to lead to the nucleus translocation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1). In H292 airway epithelial cells, the pretreatment of TMEE significantly downregulated the production of LPS-stimulated IL-1β, and TMEE was indicated to increase the expression of HO-1. In animal models exhibiting LPS-induced acute lung injury (ALI), treatment with TMEE reduced the levels of macrophages influx and TNF-α production in the bronchoalveolar lavage fluid (BALF) of ALI mice. Additionally, TMEE significantly downregulated the activation of ERK, JNK and IκB, and upregulated the expression of HO-1 in the lungs of ALI mice. In conclusion, the results of the current study demonstrated that TMEE could exert a regulatory role in the prevention or treatment of the endotoxin-mediated inflammatory response.

• Microbiology and Biotechnology Letters
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• v.50 no.4
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• pp.574-583
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• 2022

Ficus vasculosa Wall. ex Miq. (FV) has been used as a herbal medicine in Southeast Asia and its antioxidant activity has been shown in previous studies. However, it has not yet been elucidated whether FV exerts anti-inflammatory effects on activated-macrophages. Thus, we aimed to evaluate the ameliorative property of FV methanol extract (FM) on lipopolysaccharide (LPS)-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 macrophages. The experimental results indicated that FM decreased the production of inflammatory mediators (NO/PGE2) and the mRNA/protein expression of iNOS and COX-2 in LPS-stimulated RAW264.7 cells. FM also reduced the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in LPS-stimulated RAW264.7 cells. Results also demonstrated that FM improved inflammatory response in LPS-stimulated A549 airway epithelial cells by inhibiting the production of cytokines, such as IL-1β, IL-6 and TNF-α. In addition, FM suppressed MAPK activation and NF-κB nuclear translocation induced by LPS. FM also upregulated the mRNA/protein expression levels of heme oxygenase-1 and the nuclear translocation of nuclear factor erythroid 2-related factor 2 in RAW264.7 cells. In an experimental animal model of LPS-induced acute lung injury, the increased levels of molecules in bronchoalveolar lavage (BAL) fluid were suppressed by FM administration. Collectively, it was founded that FM has anti-inflammatory properties on activated-macrophages by suppressing inflammatory molecules and regulating the activation of MAPK/NF-κB signaling.

• Journal of Life Science
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• v.33 no.12
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• pp.1062-1073
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• 2023

Although depression is a common psychiatric disorder that negatively affects individuals and societies, its exact pathogenesis is not well understood. Stress is a major risk factor for depression and is known to increase susceptibility by triggering inflammation. Indeed, many preclinical and clinical studies have suggested a strong link between depression and inflammation. Depression is associated with increased levels of pro-inflammatory cytokines, such as interleukin (IL-)1β, IL-6, IL-12, tumor necrosis factor-α, and interferon-γ, and decreased levels of the anti-inflammatory IL-4, IL-10, and transforming growth factor-β. Administering pro-inflammatory cytokines causes depression-like behaviors in rodents. Conversely, administering anti-inflammatory drugs appears to ameliorate depressive symptoms. Although the importance of inflammation as a mediator of depression has been demonstrated, the mechanisms by which inflammation is activated in depression remain unclear. To address this issue, recent studies have focused on the importance of stress-induced sterile inflammation. Sterile inflammation refers to the activation of inflammatory processes due to physical and/or psychological stress in the absence of pathogens. Stress promotes the release of endogenous factors known as damage-associated molecular patterns (DAMPs), thereby triggering sterile inflammation. In turn, DAMPs are recognized by pattern recognition receptors, leading to the production of pro-inflammatory cytokines. Here, we review the role of DAMPs in depression based on preclinical and clinical evidence on the dysregulation of sterile inflammation.

• Journal of Nutrition and Health
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• v.56 no.5
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• pp.455-468
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• 2023

Purpose: Abeliophyllum distichum (A.distichum) is a plant native to Korea. In this study, we investigated the mechanism of antioxidant and anti-inflammatory effects of the leaf extract of A.distichum. Methods: The antioxidant capacity of the A.distichum leaf extract was determined based on the total polyphenol content, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, and the ferric reducing antioxidant power (FRAP) assay. The anti-inflammatory effects of the A.distichum leaf extract were evaluated by measuring the production of nitric oxide (NO) and the expression levels of proinflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 using the enzyme-linked immunosorbent assay (ELISA) and reverse transcription quantitative real-time PCR (RT-qPCR). In addition, the expression of heme oxygenase-1 (HO-1), nuclear transcription factor-erythroid 2 related factor (Nrf2), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2), as well as the activation of nuclear factorkappa B (NF-ĸB) were examined using the western blot analysis. Results: The total polyphenol content of the A.distichum leaf extract was 329.89 ± 30.17 gallic acid equivalents mg/g and the DPPH and ABTS scavenging activities were 55% and 70%, respectively. Additionally, the FRAP value of the extract was 743.68 ± 116.59 mg/mL. After 12-hour treatment with the A.distichum leaf extract, there was a tendency for the Nrf2 expression to increase, and the expression of HO-1 was significantly elevated in the RAW264.7 cells. The A.distichum leaf extract treatment resulted in decreased levels of NO, TNF-α, IL-6, and IL-1β, as well as reduced expression of iNOS and COX-2, along with inhibition of NF-κB activation in lipopolysaccharide-stimulated RAW264.7 cells. Conclusion: These results suggest that the A.distichum leaf extract exerts antioxidative and anti-inflammatory effects by upregulating the expression of HO-1 and downregulating NF-κB activation.

• Journal of The Korean Society of Integrative Medicine
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• v.8 no.1
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• pp.159-168
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• 2020

Purpose : To provide data on exercise prescription for obesity management and prevention of cardiovascular disease in girl's high school and to prepare basic data for more effective exercise program for lifestyle improvement and prevention of lifestyle-related diseases. This study examines the effects on brain nerve growth factor and inflammatory factors, and the relationship between obesity factor and brain neuron cell production factor and inflammatory factor changes by complex exercise. Methods : The subjects of the study were obese students with a body fat percentage of 30 % or higher after obtaining body fat percentage of high school girls in C-city. Among them, 20 students who wanted to participate in the program of this study and did not participate in special exercise and diet therapy within the last 6 months were radio-sampled into groups of exercise group and control group, but attendance rate was low and The final exercise group (9) and control group (9) were measured, except for one student who did not respond. Results : Analysis of the range of variation in body composition, BMI, lean body mass, and the interaction between the groups showed significant differences (p<.05). TC, TG, HDL-C, and LDL-C as variables of blood lipids, TC and TG were not significantly different and TG was significantly different (p<.05) in interactions. HDL-C showed a significant difference (p<.01) in interactions, an increase in exercise group, and a significant decrease in control group (p<.05). There was a significant difference (p<.05) in BDNF interaction, an increase in the exercise group and a decrease in the control group, but no significant difference. NGF tended to increase in both exercise and control groups. IL-6 had a significant difference in timing (p<.05) and significantly decreased (p<.01) in the exercise group, and TNF-α interacted with timing (p<.05), and a significant increase in the control group. Conclusion : This study confirmed 12-week compound exercise program was effective in increasing the expression of basal fitness or CNS factor, but not enough to actually improve brain function. Fat mass and obesity are also affecting vascular inflammatory factors.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.6
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• pp.1500-1508
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• 2003

This study was performed to clarify the neurotoxic mechanism of nerve cells damage by brain ischemia. The cytotoxic effect of ischemia was determined by XTT assay, NR assay, superoxide dismutase(SOD) activity, amount of malondialdehyde(MDA), lactate dehydrogenase(LDH) activity, protein synthesis and tumor necrosis factor(TNF)-α activities after cerebral neurons derived from mouse were exposed to ischemia for 1∼30 minutes. In addition, the protective effect of extract of Daejo-whan(DJW) on ischemia-induced neurotoxicity was examined in these cultures. 1. Ischemia decreased cell number and viability by XTT assay or NR assay when cultured cerebral neurons were exposed to 95% N2/5% CO₂ for 1∼20 minutes in these cultures. 2. Ischemia decreased SOD and protein syntheses, but it increased amount of MDA and, LDH and TNF-α activities in these cultures. 3. In the neuroprotective effect of DJW extracts on cerebral neurons damaged by ischemia, DJW extracts increased SOD activity and protein synthesis. While, it decreased amount of MDA and, LDH and TNF-α activities after cerebral neurons preincubated with herb extracts. It suggests that brain ischemia has neurotoxicity on cultured mouse cerebral neurons, and the herb extract such as DJW was very effective in blocking the neurotoxicity induced by ischemia in cultured mouse cerebral neurons.

• Journal of Korean Medicine Rehabilitation
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• v.30 no.3
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• pp.57-69
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• 2020

Objectives The aim of this study was to investigate the inhibitory effect of ChondroT in indomethacin-induced gastric mucosal injury rat model. Methods Sprague-Dawley rats were randomly assigned to intact, control Joins, Celebrex, ChondroT50 and ChondroT200. Indomethacin (25 mg/kg) was used to induce damage to the gastric mucosal injury. ChondroT was administered by orally to inhibit the indomethacin-induced gastric mucosal injury. At the end of the experiment, pH level in stomach, stomach contents volume, tumor necrosis factor-α (TNF-α) level, interleukin-1β (IL-1β) level, prostaglandin E2 (PGE2) level, myeloperoxidase (MPO) activity, erythrocytes, and thrombocytes were measured. Ophthalmologic and histopathological examination was also analyzed. Results pH level in stomach and Stomach contents volume had no difference between Control, PC-Joins, PC-Cele, ChondroT50 and ChondroT200 group. TNF-α level was decreased in PC-Joins, PC-Cele, ChondroT50 and ChondroT200 group and there were no significant difference. IL-1β level was decreased in PC-Joins group and ChondroT200 group compared to control group. PGE2 level had no significant difference between Control, PC-Joins, PC-Cele, ChondroT50 and ChondroT200 group. MPO level and complete blood count level were decreased in PC-Joins, PC-Cele, ChondroT50 and ChondroT200. Symptom score of ophthalmologic examination was decreased in ChondroT50 and ChondroT200 group compared to control group. Conclusion Based on these results, It could be suggested that ChondroT was effective in reducing damage to the gastric mucosal injury. And further study is needed to conduct a rigorous clinical research.

• Journal of Korean Neurosurgical Society
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• v.64 no.5
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• pp.693-704
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• 2021

Objective : Endovascular mechanical thrombectomy (MT) has been regarded as one of the standard treatments for acute ischemic stroke caused by large vessel occlusion. Despite the wide use of stent retrievers for MT, arterial intimal damage caused when deployed stent is pulled has been a certain disadvantage. We hypothesized that statin could protect and stabilize vessel damage after endovascular MT using a stent retriever. In this animal study, we observed the protective effects of the statins towards MT-induced vessel wall injury. Methods : Twenty-eight carotid arteries of fourteen rabbits were used in the experiments with MT using stent retriever. We divided the rabbits into four groups as follows : group 1, negative control; group 2, positive control; group 3, statin before MT; and group 4, statin after MT. After MT procedures, we harvested the carotid arteries and performed histomorphological and immunohistochemical analyses. Results : In histomorphological analysis with hematoxylin and eosin and Masson's trichrome stain, significant intimal thickening (p<0.05) was observed in the positive control (group 2), compared to in the negative control (group 1). Intimal thickening was improved in the statin-administered groups (groups 3 and 4 vs. group 2, p<0.05). We also observed that statin administration after MT (group 4) resulted in a more effective decrease in intimal thickness than statin administration before MT (group 3) (p<0.05). We performed immunohistochemical analysis with the antibodies for tumor necrosis factor-alpha (TNF-α), cluster of differentiation (CD)11b, and CD163. In contrast to the negative control (group 1), the stained percentage areas of all immunological markers were markedly increased in the positive control (group 2) (p<0.05). Based on statin administration, the percentage area of TNF-α staining was significantly reduced (p<0.05) in group 3, compared to the positive control group (group 2). However, significant differences were not observed for CD11b and CD163 staining. In group 4, no significant differences were observed for TNF-α, CD11b, and CD163 staining (p≥0.05). The differences in the percentage areas of the different markers between the statin-administered groups (groups 3 and 4) were also not revealed. Conclusion : We presented that statin administration before and after MT exerted protective effects towards vessel wall injury. The efficacy of statins was greater post-administration than pre-administration. Thus, statin administration in routine prescriptions in the peri-procedural period is strongly advised.

• Korean Journal of Food Science and Technology
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• v.54 no.2
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• pp.147-154
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• 2022

The Mongolian lingonberry and blueberry are two essential food sources found in Mongolia. This study investigated the antioxidant and anti-inflammatory effects of methanol extracts from Mongolian lingonberry (LBE) and blueberry (BBE). Compared to the LBE, the BBE showed higher total phenolic, flavonoid, and anthocyanin contents, as well as antioxidant capacities. The LBE and BBE inhibited the mRNA expression of pro-inflammatory genes, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and cyclooxygenase (COX-2) in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. In addition, the LBE and BBE inhibited NADPH oxidase-2 (Nox2) mRNA expression, indicating that they have cellular antioxidant capacities. Anthocyanin derivatives of the LBE and BBE were analyzed using LC-QTOF/MS. Six anthocyanins were identified in the BBE, while one was detected in the LBE. Our findings demonstrate that the anthocyanin-rich LBE and BBE could be used as functional food sources in Mongolia.