• Mycobiology
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• v.45 no.4
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• pp.297-311
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• 2017

Saprolegniasis is one of the most devastating oomycete diseases in freshwater fish which is caused by species in the genus Saprolegnia including Saprolegnia parasitica. In this study, we isolated the strain of S. parasitica from diseased rainbow trout in Korea. Morphological and molecular based identification confirmed that isolated oomycete belongs to the member of S. parasitica, supported by its typical features including cotton-like mycelium, zoospores and phylogenetic analysis with internal transcribed spacer region. Pathogenicity of isolated S. parasitica was developed in embryo, juvenile, and adult zebrafish as a disease model. Host-pathogen interaction in adult zebrafish was investigated at transcriptional level. Upon infection with S. parasitica, pathogen/antigen recognition and signaling (TLR2, TLR4b, TLR5b, NOD1, and major histocompatibility complex class I), pro/anti-inflammatory cytokines (interleukin $[IL]-1{\beta}$, tumor necrosis factor ${\alpha}$, IL-6, IL-8, interferon ${\gamma}$, IL-12, and IL-10), matrix metalloproteinase (MMP9 and MMP13), cell surface molecules ($CD8^+$ and $CD4^+$) and antioxidant enzymes (superoxide dismutase, catalase) related genes were differentially modulated at 3- and 12-hr post infection. As an anti-Saprolegnia agent, plant based lawsone was applied to investigate on the susceptibility of S. parasitica showing the minimum inhibitory concentration and percentage inhibition of radial growth as $200{\mu}g/mL$ and 31.8%, respectively. Moreover, natural lawsone changed the membrane permeability of S. parasitica mycelium and caused irreversible damage and disintegration to the cellular membranes of S. parasitica. Transcriptional responses of the genes of S. parasitica mycelium exposed to lawsone were altered, indicating that lawsone could be a potential anti-S. parasitica agent for controlling S. parasitica infection.

• Journal of Oriental Neuropsychiatry
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• v.30 no.4
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• pp.357-369
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• 2019

Objectives: This study was designed to examine the effect of Hominis Placenta Pharmacopuncture on the change in behavior, sleep-related hormones, inflammatory cytokines, anti-oxidants, weight, blood, and serum on rats given chronic physical stress. Methods: Wistar rats older than age 10 weeks were used in this experiment. They were divided into six groups. The normal group was not given stress. The control group was given only chronic physical stress and no treatment. The positive control group was given chronic physical stress and treated with zolpidem. Three Hominis Placenta Pharmacopuncture (HPP) groups were given chronic physical stress, then treated with different concentrations of HPP; HPP-0.5× (0.5 times diluted), HPP-1× (undiluted) and HPP-2× (2 times condensed). The changes of values of Nestlet Shredding results, weight, Melatonin, Gamma-aminobutylic Acid (GABA), Tumor Necrosis Factor Alpha (TNF-α), Interleukin-6 (IL-6), Superoxide dismutase (SOD), glutathione peroxidase (GPx), AST, ALT, BUN, Creatinine, and leukocytes were observed during the experiment. Results: The changes in chronic physical stress of the rat model were as follow. The Nestlet Shredding result increased in the control group compared to the normal group (p<0.05), and decreased in the HPP-1× and HPP-2× compared to the control group (p<0.05). The amount of weight gain showed increasing tendency in the HPP-2× compared to the control group since the second week. The GABA increased (p<0.05) and Melatonin also showed certain increasing tendency in the HPP-1× and HPP-2× compared to the control group. The TNF-α and IL-6 increased in the control group compared to the normal group (p<0.01), and decreased in all the HPPs compared to the control group (p<0.05). The SOD level decreased in the control group compared to the normal group (p<0.01), and increased in all the HPPs compared to the control group (p<0.05). GPx, AST, ALT, Bun, Creatinine and leukocytes showed no noticeable difference among all groups. Conclusions: Hominis Placenta Pharmacopuncture was effective in increasing weight, GABA, Melatonin, SOD, and decreasing Nestlet Shredding and inflammatory cytokines, suggesting that it consequently facilitates in relieving physical stress.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.3
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• pp.445-451
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• 2016

This study demonstrated the immunological effects of methanol extracts from Doenjang added with wild plants (Pteridium aquilinum and Aster scaber) on bone-marrow derived macrophages and mouse splenocytes. Doenjang (DJ) and wild plant added Doenjang (WPDJ) extracts were treated to bone-marrow derived macrophages (BMDM) and splenocytes, and cell proliferation and cytokine production were measured. Cell proliferation of BMDM and splenocytes was more highly elevated in the WPDJ-treated group compared to the DJ-treated group. Cytokine [tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, IL-$1{\beta}$, IL-10, and IL-12] production in BMDM also significantly increased in the WPDJ-treated group. Similarly, in the case of cytokine production in splenocytes, WPDJ treatment highly increased production of Th 1 type cytokines [interferon (IFN)-${\gamma}$ and IL-2] but did not affect production of Th 2 type cytokines (IL-4). These results suggest that wild plants could improve the immunomodulatory activity of Doenjang and may be effective for the development Doenjang.

• Allergy, Asthma & Immunology Research
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• v.10 no.6
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• pp.628-647
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• 2018

Purpose: Obesity is associated with metabolic dysregulation, but the underlying metabolic signatures involving clinical and inflammatory profiles of obese asthma are largely unexplored. We aimed at identifying the metabolic signatures of obese asthma. Methods: Eligible subjects with obese (n = 11) and lean (n = 22) asthma underwent body composition and clinical assessment, sputum induction, and blood sampling. Sputum supernatant was assessed for interleukin $(IL)-1{\beta}$, -4, -5, -6, -13, and tumor necrosis factor $(TNF)-{\alpha}$, and serum was detected for leptin, adiponectin and C-reactive protein. Untargeted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolic profiles in sputum, serum and peripheral blood monocular cells (PBMCs) were analyzed by orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and pathway topology enrichment analysis. The differential metabolites were further validated by correlation analysis with body composition, and clinical and inflammatory profiles. Results: Body composition, asthma control, and the levels of $IL-1{\beta}$, -4, -13, leptin and adiponectin in obese asthmatics were significantly different from those in lean asthmatics. OPLS-DA analysis revealed 28 differential metabolites that distinguished obese from lean asthmatic subjects. The validation analysis identified 18 potential metabolic signatures (11 in sputum, 4 in serum and 2 in PBMCs) of obese asthmatics. Pathway topology enrichment analysis revealed that cyanoamino acid metabolism, caffeine metabolism, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, pentose phosphate pathway in sputum, and glyoxylate and dicarboxylate metabolism, glycerolipid metabolism and pentose phosphate pathway in serum are suggested to be significant pathways related to obese asthma. Conclusions: GC-TOF-MS-based metabolomics indicates obese asthma is characterized by a metabolic profile different from lean asthma. The potential metabolic signatures indicated novel immune-metabolic mechanisms in obese asthma with providing more phenotypic and therapeutic implications, which needs further replication and validation.

• Journal of Korean Medical Science
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• v.33 no.52
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• pp.336.1-336.12
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• 2018

Background: We aimed to investigate mucosal immunity related to forkhead box P3 ($FOXP3^+$) regulatory T (Treg) cells, T helper 17 (Th17) cells and cytokines in pediatric inflammatory bowel disease (IBD). Methods: Mucosal tissues from terminal ileum and colon and serum samples were collected from twelve children with IBD and seven control children. Immunohistochemical staining was done using anti-human FOXP3 and anti-$ROR{\gamma}t$ antibodies. Serum levels of cytokines were analyzed using a multiplex assay covering interleukin $(IL)-1{\beta}$, IL-4, IL-6, IL-10, IL-17A/F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon $(IFN)-{\gamma}$, soluble CD40L, and tumor necrosis factor-${\alpha}$. Results: $FOXP3^+$ Treg cells in the lamina propria (LP) of terminal ileum of patients with Crohn's disease were significantly (P < 0.05) higher than those in the healthy controls. $ROR{\gamma}t^+$ T cells of terminal ileum tended to be higher in Crohn's disease than those in the control. In the multiplex assay, serum concentrations (pg/mL) of IL-4 ($9.6{\pm}1.5$ vs. $12.7{\pm}3.0$), IL-21 ($14.9{\pm}1.5$ vs. $26.4{\pm}9.1$), IL-33 ($14.3{\pm}0.9$ vs. $19.1{\pm}5.3$), and $IFN-{\gamma}$ ($15.2{\pm}5.9$ vs. $50.2{\pm}42.4$) were significantly lower in Crohn's disease than those in the control group. However, serum concentration of IL-6 ($119.1{\pm}79.6$ vs. $52.9{\pm}39.1$) was higher in Crohn's disease than that in the control. Serum concentrations of IL-17A ($64.2{\pm}17.2$ vs. $28.3{\pm}10.0$) and IL-22 ($37.5{\pm}8.8$ vs. $27.2{\pm}3.7$) were significantly higher in ulcerative colitis than those in Crohn's disease. Conclusion: Mucosal immunity analysis showed increased $FOXP3^+$ T reg cells in the LP with Crohn's disease while Th17 cell polarizing and signature cytokines were decreased in the serum samples of Crohn's disease but increased in ulcerative colitis.

• Journal of Periodontal and Implant Science
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• v.51 no.5
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• pp.342-351
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• 2021

Purpose: The aim of this study was to compare the inflammatory and lipid profile of patients with and without peri-implantitis. Methods: A cross-sectional biochemical study was carried out in which blood samples were collected from 16 patients with peri-implantitis and from 31 subjects with healthy implants. Clinical peri-implant parameters were obtained from all subjects. Levels of tumor necrosis factor-alpha and interleukin-10 (IL-10) were measured in serum. Lipid fractions, glucose and creatinine levels, and complete blood count were also assessed. Results: After controlling for a history of periodontitis, statistically significant differences between peri-implantitis patients and controls were found for total cholesterol (estimated adjusted mean difference, 76.4 mg/dL; 95% confidence interval [CI], 39.6, 113.2 mg/dL; P<0.001), low-density lipoprotein (LDL) cholesterol (estimated adjusted mean difference, 57.7 mg/dL; 95% CI, 23.8, 91.6 mg/dL; P<0.001), white blood cells (WBC) (estimated adjusted mean difference, 2.8×10³/µL; 95% CI, 1.6, 4.0×10³/µL; P<0.001) and IL-10 (estimated adjusted mean difference, -10.4 pg/mL; 95% CI, -15.8, -5.0 pg/mL; P<0.001). The peri-implant probing pocket depth (PPD) was modestly positively correlated with total cholesterol (r=0.512; P<0.001), LDL cholesterol (r=0.463; P=0.001), and WBC (r=0.519; P<0.001). A moderate negative correlation was observed between IL-10 and PPD (r=0.609; P<0.001). Conclusions: Otherwise healthy individuals with peri-implantitis showed increased low-grade systemic inflammation and dyslipidemia.

• Herbal Formula Science
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• v.26 no.4
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• pp.295-306
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• 2018

Schisandra chinensis (SC) and Lycium chinense (LC) were widely distributed in Asia and the fruit has been used traditionally for medicinal herbs. The processing method was solid-state fermentation using Aspergillus oryzae for 48 h after stir-frying treatment at $220^{\circ}C$ for 12 min. In this study, in vitro the anti-inflammatory effect and in vivo hangover reduction were compared to unprocessed SC and LC water extract. Anti-inflammatory effects have been evaluated in pro-inflammatory mediators which were secreted by lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Nitric oxide (NO) was determined using Griess reaction. Proinflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$ and interleukin $(IL)-1{\beta}$ were measured by enzyme-linked immunosorbent assays (ELISA). Alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities were compared to processed SC or LC and mixtures thereof (1:1). In vivo study was compared to hangover relief in alcohol-fed mice. After administering a mixture of SC and LC (300 mg/kg) water extract (1:1), mice were fed 3 g/kg of ethanol. Serum was collected at 1, 3, and 5 h intervals to analyze ethanol and acetaldehyde levels using a colorimetric assay kit. The processed SC and LC water extracts compared to raw materials significantly inhibited LPS-induced NO and inflammatory cytokine production in RAW 264.7 cells. The results of the hangover mouse model are also consistent with anti-inflammatory effects. These results suggest that processed SC and LC extracts may be functional materials for the treatment of inflammation and hangover.

• Korean Journal of Radiology
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• v.19 no.6
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• pp.1089-1098
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• 2018

Objective: To investigate the diagnostic yield of contrast-enhanced computed tomography (CT) in Crohn's disease (CD) patients presenting with acute severe lower gastrointestinal bleeding (LGIB), and the role of CT in predicting the risk of rebleeding. Materials and Methods: A consecutive series of 110 CD patients presenting with acute severe LGIB between 2005 and 2016 were analyzed. Among them, 86 patients who had undergone contrast-enhanced CT constituted the study cohort. The diagnostic yield of CT for detecting contrast extravasation was obtained for the entire cohort and compared between different CT techniques. In a subgroup of 62 patients who had undergone CT enterography (CTE) and showed a negative result for extravasation on CTE, the association between various clinical and CTE parameters and the risk of rebleeding during subsequent follow-up was investigated using Cox regression analysis. Results: The diagnostic yield of CT was 10.5% (9 of 86 patients). The yield did not significantly differ between single-phase and multiphase examinations (p > 0.999), or between non-enterographic CT and CTE (p = 0.388). Extensive CD (adjusted hazard ratio [HR], 3.27; 95% confidence interval [CI], 1.09-9.80; p = 0.034) and bowel wall-to-artery enhancement ratio (adjusted HR, 2.81; 95% CI, 1.21-6.54; p = 0.016) were significantly independently associated with increased rebleeding risks, whereas anti-tumor necrosis factor-${\alpha}$ therapy after the bleeding independently decreased the risk of rebleeding (adjusted HR, 0.26; 95% CI, 0.07-0.95; p = 0.041). Conclusion: The diagnostic yield of contrast-enhanced CT was not high in CD patients presenting with acute severe LGIB. Nevertheless, even a negative CTE may be beneficial as it can help predict the risk of later rebleeding.

• Journal of Applied Biological Chemistry
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• v.62 no.3
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• pp.229-237
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• 2019

More effective treatments are needed for non-alcoholic fatty liver disease (NAFLD). We hypothesized that water extracts of blackberry fruits (BF) and leaves (BL) and their combinations (BFL) reduce fat deposition in HepG2 cells and modulate shor-tchain fatty acids (SCFA) and fecal bacteria in vitro. HepG2 cells were treated with BF, BL, BFL1:2, and BFL1:3 for 1 h, and 0.5 mM palmitate was added to the cells. Moreover, low ($30{\mu}g/mL$) and high doses ($90{\mu}g/mL$) of BL and BF were applied to fecal bacteria in vitro, and SCFA was measured by GC. BL, BF, BFL1:2, and BFL1:3 reduced triglyceride deposition in the cells in a dose-dependent manner, and BFL1:2 and BFL1:3 had a stronger effect than BF. The content of malondialdehyde, an index of oxidative stress, was also reduced in BL, BF, and BFL1:2 with increasing superoxide dismutase and glutathione peroxidase activities. The mRNA expression of acetyl CoA carboxylase, fatty acid synthase, and sterol regulatory element-binding protein-1c was reduced in BL, BF, BFL1:2, and BFL1:3 compared to the control, and BFL1:2 had the strongest effect. By contrast, the carnitine palmitolytransferase-1expression, a regulator of fatty acid oxidation, increased mostly in BFL1:2 and BFL1:3. Tumor necrosis factor-${\alpha}$ and interleukin-$1{\beta}$ expression was reduced in BL compared to that in BF and BFL1:2 in HepG2 cells. Interestingly, BL increased propionate production, and BF increased butyrate and propionate production and increased total SCFA content in fecal incubation. BF increased the contents of Bifidobacteriales and Lactobacillales and decreased those of Clostridiales, whereas BL elevated the contents of Bacteroidales and decreased those of Enterobacteriales. In conclusion, BFL1:2 and BFL1:3 may be potential therapeutic candidates for NAFLD.

• Journal of Ginseng Research
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• v.43 no.3
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• pp.377-384
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• 2019

Background: Inflammation is widespread in the clinical pathology and closely associated to the progress of many diseases. Triterpenoid saponins as a key group of active ingredients in Panax notoginseng (Burk.) F.H. Chen were demonstrated to show antiinflammatory effects. However, the chemical structures of saponins in the leaves and stems of Panax notoginseng (PNLS) are still not fully clear. Herein, the isolation, purification and further evaluation of the antiinflammatory activity of dammarane-type triterpenoid saponins from PNLS were conducted. Methods: Silica gel and reversed-phase C8 column chromatography were used. Furthermore, preparative HPLC was used as a final purification technique to obtain minor saponins with high purities. MS, NMR experiments, and chemical methods were used in the structural identifications. The antiinflammatory activities of the isolated saponins were assessed by measuring the nitric oxide production in RAW 264.7 cells stimulated by lipopolysaccharides. Real-time reverse transcription polymerase chain reaction was used to measure the gene expressions of inflammation-related gene. Results: Eight new minor dammarane-type triterpene oligoglycosides, namely notoginsenosides LK1-LK8 (1-8) were obtained from PNLS, along with seven known ones. Among the isolated saponins, gypenoside IX significantly suppressed the nitric oxide production and inflammatory cytokines including tumor necrosis $factor-{\alpha}$, interleukin 10, interferon-inducible protein 10 and $interleukin-1{\beta}$. Conclusion: The eight saponins may enrich and expand the chemical library of saponins in Panax genus. Moreover, it is reported for the first time that gypenoside IX showed moderate antiinflammatory activity.