• Korean Journal of Clinical Laboratory Science
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• v.55 no.3
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• pp.174-183
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• 2023

Antioxidant, cytotoxic, and anti-inflammatory assays were conducted to determine the commercial viability of Brachythecium populeum. The antioxidant activity was assessed by performing the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. This was followed by the quantification of polyphenols and flavonoids. Results of the DPPH and ABTS assay showed that antioxidant activities of the ethanol extract of B. populeum were 3.7 and 3.6 times higher than water extract, respectively. The polyphenol concentration was also determined to be 4.1 times higher and the flavonoid concentration was 5.3 times higher than the water extract. The cell-based experiments, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay and nitric oxide assay, were performed using RAW 264.7. Results of the MTT assay revealed that both extracts exerted no cytotoxicity on the cells (based on 80% viability). In the nitric oxide (NO) production inhibition experiment, inhibition of NO production was determined to be 15.42% more when exposed to ethanol extract as compared to water extract. Furthermore, the ethanol extract exerted greater inhibition of inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α production (9.39%, 11.87%, and 14.49% more, respectively) when compared to the water extract. Due to the good antioxidant activity and potential for inhibiting NO and inflammatory cytokine production, B. populeum ethanol extracts are prospective sources of anti-inflammatory compounds.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.1
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• pp.44-52
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• 2023

Objective: The DNA integrity of spermatozoa that attach to fallopian tube (FT) cells is higher than spermatozoa that do not attach. FT epithelial cells can distinguish normal and abnormal sperm chromatin. This study investigated the effects of sperm with a high-DNA fragmentation index (DFI) from men with unexplained repeated implantation failure (RIF) on the Toll-like receptor (TLR) signaling pathway in human FT cells in vitro. Methods: Ten men with a RIF history and high-DFI and 10 healthy donors with low-DFI comprised the high-DFI (>30%) and control (<30%) groups, respectively. After fresh semen preparation, sperm were co-cultured with a human FT epithelial cell line (OE-E6/E7) for 24 hours. RNA was extracted from the cell line and the human innate and adaptive immune responses were tested using an RT2 profiler polymerase chain reaction (PCR) array. Results: The PCR array data showed significantly higher TLR-1, TLR-2, TLR-3, TLR-6, interleukin 1α (IL-1α), IL-1β, IL-6, IL-12, interferon α (IFN-α), IFN-β, tumor necrosis factor α (TNF-α), CXCL8, GM-CSF, G-CSF, CD14, ELK1, IRAK1, IRAK2, IRAK4, IRF1, IRF3, LY96, MAP2K3, MAP2K4, MAP3K7, MAP4K4, MAPK8, MAPK8IP3, MYD88, NFKB1, NFKB2, REL, TIRAP, and TRAF6 expression in the high-DFI group than in the control group. These factors are all involved in the TLR-MyD88 signaling pathway. Conclusion: The MyD88-dependent pathway through TLR-1, TLR-2, and TLR-6 activation may be one of the main inflammatory pathways activated by high-DFI sperm from men with RIF. Following activation of this pathway, epithelial cells produce inflammatory cytokines, resulting in neutrophil infiltration, activation, phagocytosis, neutrophil extracellular trap formation, and apoptosis.

• Journal of Marine Bioscience and Biotechnology
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• v.15 no.1
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• pp.1-11
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• 2023

In the present study, the antioxidant and anti-inflammatory activities of ethanolic extracts from Lathyrus japonicus at concentrations of 50, 100, and 200 ㎍/mL were investigated in LPS-stimulated, RAW264.7 cells. Antioxidant properties were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays and ferric reducing antioxidant power assay. In addition, the production of reactive oxygen species (ROS) was measured using the 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe by flow cytometry. To examine the anti-inflammatory activity of the extracts of L. japonicus, their effects on the levels of nitric oxide (NO); production of cytokines such as interleukin (IL)-1β, IL-10, and tumor necrosis factor-α (TNF-α); and the activities of enzymes such as inducible NOS (iNOS) and cyclooxygenase-2 (COX-2) were assessed. The IC₅₀ values of the DPPH and ABTS radical scavenging assays were 476.09 ± 1.50 and 34.91 ± 0.37 ㎍/mL, respectively. In addition, L. japonicus extracts not only inhibited ROS production, but also the production of NO, IL-1β, and IL-10, and the activity of iNOS in a dose-dependent manner. In summary, the ethanolic extracts of L. japonicus could be used as a functional food additive and an anti-inflammatory agent owing to their antioxidant and anti-inflammatory activities

• Journal of Veterinary Science
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• v.24 no.4
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• pp.52.1-52.13
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• 2023

Background: Mesenchymal stem cells (MSCs) have been investigated as therapeutic agents for inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and companion animals. Objectives: This study aimed to assess the therapeutic effect of tumor necrosis factor (TNF)-α-stimulated feline adipose tissue-derived MSCs (fAT-MSCs) in a dextran sulfate sodium (DSS)-induced colitis mouse model. Methods: Colitis mice was made by drinking water with 3% DSS and fAT-MSCs were injected intraperitoneally. Colons were collected on day 10. The severity of the disease was evaluated and compared. Raw 264.7 cells were cultured with the conditioned medium to determine the mechanism, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: TNF-α-stimulated fAT-MSCs more improved severity of DSS-induced colitis in disease activity, colon length, histologic score, and inflammatory cytokine. In sectionized colon tissues, the group comprising TNF-α-stimulated fAT-MSCs had higher proportion of CD11b⁺CD206⁺ macrophages than in the other groups. In vitro, TNF-α-stimulation increased cyclooxygenase-2 (COX-2) expression and prostaglandin E₂ (PGE₂) secretion from fAT-MSCs. The conditioned medium from TNF-α-stimulated fAT-MSCs enhanced the expression of interleukin-10 and arginase-1 in LPS-activated Raw 264.7 cells. Conclusions: These results represent that TNF-α-stimulated fat-mscs ameliorate the inflamed colon more effectively. Furthermore, we demonstrated that the effectiveness was interlinked with the COX-2/PGE₂ pathway.

• Journal of the Korean Applied Science and Technology
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• v.40 no.5
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• pp.988-1000
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• 2023

Hesperetin(HT) is a potent antioxidant flavonoid aglycone derived from hesperidin(HD). The antioxidant, anti-inflammatory, and antimicrobial activities of HT and its cyclodextrin(CD) inclusion complexes were compared in vitro. HT was prepared by enzymatic hydrolysis of HD, and HT/CD complexes were prepared using 𝛽-cyclodextrin(𝛽-CD) and hydroxypropyl-𝛽-cyclodextrin(HP-𝛽-CD) by solvent co-evaporation method. The solubility of the HT/HP-𝛽-CD inclusion complex increased 93.5-fold compared to HT, and the solubility of HT/𝛽-CD increased 22.5-fold. The HT/HP-𝛽-CD inclusion complex showed a similar effect as HT on radical scavenging activity in antioxidant assays, whereas the HT/𝛽-CD inclusion complex showed slightly lower activity than HT. Cytotoxicity was low in the following order; HT/HP-𝛽-CD, HT/𝛽-CD, and HT in murine macrophage RAW264.7 cells. Treatment with HT and HT/CD inclusion complexes reduced the levels of inflammatory mediators such as nitric oxide(NO), tumor necrosis factor-𝛼(TNF-𝛼) and interleukin-6(IL-6) in the cells. HT and HT/HP-𝛽-CD inclusion complex were more effective than HT/𝛽-CD inclusion complex at relatively low concentrations. Inhibitory effects were tested on skin-pathogenic bacteria, Staphylococcus aureus and Pseudomonas aeruginosa, and they showed an antimicrobial effect on S. aureus in the order of HT = HT/HP-𝛽-CD > HT/𝛽-CD, but they did not show any significant inhibitory effect on P. aeruginosa. In conclusion, HT, the aglycone form of HD, and its CD inclusion complexes showed various biological activities. HT/HP-𝛽-CD inclusion complex, which is the highly soluble form of HT, showed relatively higher activity compared to HT/𝛽-CD inclusion complex.

• Korean Journal of Radiology
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• v.21 no.6
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• pp.746-755
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• 2020

Objective: To identify predictors of pulmonary fibrosis development by combining follow-up thin-section CT findings and clinical features in patients discharged after treatment for COVID-19. Materials and Methods: This retrospective study involved 32 confirmed COVID-19 patients who were divided into two groups according to the evidence of fibrosis on their latest follow-up CT imaging. Clinical data and CT imaging features of all the patients in different stages were collected and analyzed for comparison. Results: The latest follow-up CT imaging showed fibrosis in 14 patients (male, 12; female, 2) and no fibrosis in 18 patients (male, 10; female, 8). Compared with the non-fibrosis group, the fibrosis group was older (median age: 54.0 years vs. 37.0 years, p = 0.008), and the median levels of C-reactive protein (53.4 mg/L vs. 10.0 mg/L, p = 0.002) and interleukin-6 (79.7 pg/L vs. 11.2 pg/L, p = 0.04) were also higher. The fibrosis group had a longer-term of hospitalization (19.5 days vs. 10.0 days, p = 0.001), pulsed steroid therapy (11.0 days vs. 5.0 days, p < 0.001), and antiviral therapy (12.0 days vs. 6.5 days, p = 0.012). More patients on the worst-state CT scan had an irregular interface (59.4% vs. 34.4%, p = 0.045) and a parenchymal band (71.9% vs. 28.1%, p < 0.001). On initial CT imaging, the irregular interface (57.1%) and parenchymal band (50.0%) were more common in the fibrosis group. On the worst-state CT imaging, interstitial thickening (78.6%), air bronchogram (57.1%), irregular interface (85.7%), coarse reticular pattern (28.6%), parenchymal band (92.9%), and pleural effusion (42.9%) were more common in the fibrosis group. Conclusion: Fibrosis was more likely to develop in patients with severe clinical conditions, especially in patients with high inflammatory indicators. Interstitial thickening, irregular interface, coarse reticular pattern, and parenchymal band manifested in the process of the disease may be predictors of pulmonary fibrosis. Irregular interface and parenchymal band could predict the formation of pulmonary fibrosis early.

• Journal of Nutrition and Health
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• v.57 no.1
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• pp.88-104
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• 2024

Purpose: High-sensitivity C-reactive protein (hs-CRP) is primarily synthesized in the liver upon stimulation of infectious disease cytokines, such as interleukin-6 (IL-6), and is used as a biological marker of systemic inflammation. Previous studies reported that hs-CRP is closely related to diet and abdominal obesity. Furthermore, a dietary score favoring the consumption of vegetables, fruits, and whole grains over meat and saturated fat reduced inflammation and decreased the prevalence of obesity and abdominal obesity. Nevertheless, no studies have examined whether hs-CRP mediates the relationship between dietary scores and abdominal obesity, and research on the Korean Healthy Eating Index (KHEI) is lacking. Therefore, the present study examined the association between the KHEI and abdominal obesity and the mediating effect of hs-CRP. Methods: In total, 17,770 adults aged ≥19 years were included in the study using the Korea National Health and Nutrition Examination Survey 2015-2018. KHEI was developed to assess the overall diet quality of Korean adults. Multivariable linear and logistic regression analyses assessed the relationship between KHEI, hs-CRP, and abdominal obesity. The mediation analysis with the bootstrapping method was performed using SAS MACRO. Results: Among women, the odds ratio (OR) of abdominal obesity prevalence was lower in the highest KHEI compared to the lowest KHEI after adjusting for age, body mass index, educational level, income level, occupational status, marital status, household type, region type, alcohol consumption, smoking status, physical activity, total energy intake, and hsCRP (OR 0.744, 95% confidence interval 0.598-0.926). The association between KHEI and abdominal obesity was partially mediated via hs-CRP, and the mediated proportion was 68.7% in men and 38.1% in women. Conclusion: A substantial relationship was observed between the KHEI and abdominal obesity among females. Moreover, according to the KHEI, abdominal obesity may be mediated partially by hs-CRP.

• Journal of Life Science
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• v.28 no.2
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• pp.207-215
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• 2018

Inflammatory response and oxidative stress play critical roles in the development and progression of many human diseases. Therefore, a great deal of attention has been focused on finding functional materials that can control inflammation and oxidative stress simultaneously. The purpose of this study was to investigate the effects of Socheongja and Socheong 2, Korean black seed coat soybean varieties, on the inflammatory and oxidative stress induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages. Our data indicated that the extracts of Socheongja (SCJ) and Socheong 2 (SC2) significantly suppressed LPS-induced production of nitrite oxide (NO) and prostaglandin $E_2$, key pro-inflammatory mediators, by suppressing the expression of inducible NO synthase and cyclooxygenase-2. It was also found that SCJ and SC2 reduced the LPS-induced secretion of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$, which was concomitant with a decrease in the protein levels. In addition, SCJ and SC2 markedly diminished LPS-stimulated intracellular reactive oxygen species accumulation, and effectively enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase (HO)-1 expression. Furthermore, LPS-induced activation of mitogen-activated protein kinases (MAPKs) was abrogated by SCJ and SC2. Taken together, these data suggest that SCJ and SC2 may offer protective roles against LPS-induced inflammatory and oxidative responses in RAW 264.7 macrophages through attenuating MAPKs pathway, and these effects are mediated, at least in part, through activating Nrf2/HO-1 pathway. Given these results, we propose that SCJ and SC2 have therapeutic potential in the treatment of inflammatory and oxidative disorders caused by over-activation of macrophages.

• Korean Journal of Medicinal Crop Science
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• v.16 no.5
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• pp.349-355
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• 2008

Anticancer and immuno-modulatory activities of methanol extracts from different parts, bark, wood and leaf, of Cornus macrophylla Wall. were investigated in this study. All extracts at a concentration of 1.0mg/ml showed relativity low cytotoxicities on human normal kidney cell (HEK293) by approximately 25%. Bark extract of C. macrophylla showed the highest anticancer activity on human lung cancer cell line (A549) and human breast cancer cell line (MCF-7) by 57.4% and 58.7%, respectively, at a concentration of 1.0mg/ml. All extracts enhanced the growth of human B and T cells, showing 38.7% and 65.9% increase compared to control, respectively, by 5 days incubation with bark extract. The secretions of interleukin 6 (IL6) and tumor necrosis factor alpha (TNF-$\alpha$) from human B and T cells were significantly increased by extracts, especially bark extract. B or T cell medium, which contains cytokines (IL 6 and TNF-$\alpha$) secreted by bark extract treatment for 5 days, time-dependently enhanced the growth of NK-92MI cells with the maximal effect at 5th day of incubation. These results suggest that C. macrophylla, especially bark, has the potential for anticancer and immuno-modulatory activities.

• Journal of Life Science
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• v.26 no.1
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• pp.50-58
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• 2016

The root bark of Ulmus macrocarpa has been used in traditional medicine for the treatment of various diseases such as edema, infection and inflammation. Nevertheless, the biological activities and underlying mechanisms of the immunomodulatory effects remain unclear. In this study, as part of our ongoing screening program to evaluate the immunomodulatory potential of new compounds from traditional medicinal resources, we investigated the effects of U. macrocarpa water extract (UME) on immune modulation in a murine RAW 264.7 macrophage model. As immune response parameters, the productions of as nitric oxide (NO) and cytokines such tumor necrotic factor (TNF)-α, interleukin (IL)-1β and IL-10 were evaluated. Although the release of IL-1β remained unchanged in UME-treated RAW 264.7 macrophages, the productions of NO, TNF-α and IL-10 were significantly increased, along with the increased expression of inducible NO synthase, TNF-α and IL-10 expression at concentrations with no cytotoxicity. UME treatment also induced the nuclear translocation of nuclear factor κB (NF-κB), and phosphorylation of Akt and mitogen-activated protein kinases (MAPKs) indicating that UME activated macrophages through the activation of NF-κB, phosphoinositide-3-kinase (PI3K)/Akt and MAPKs signaling pathways in RAW 264.7 macrophages. Furthermore, pre-treatment with UME significantly attenuated the production of NO, but not TNF-α, IL-1β and IL-10, in lipopolysaccharide-stimulated RAW 264.7 cells suggesting that UME may be useful in preventing inflammatory diseases mediated by excessive production of NO. These findings suggest that the beneficial therapeutic effects of UME may be attributed partly to its ability to modulate immune functions in macrophages.