• 한국축산식품학회지
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• 제43권4호
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• pp.703-711
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• 2023

As an initial study to elucidate the molecular mechanism of how probiotics modulate macrophage activity, we monitored mRNA expression patterns in peritoneal macrophages (PMs) treated with two different strains of probiotics. After treatment with either Weissella cibaria WIKIM28 or Latilactobacillus sakei WIKIM50, total RNAs from PMs were isolated and subjected into gene chip analyses. As controls, mRNAs from vehicle (phosphate-buffered saline, PBS)-treated PMs were also subjected to gene chip analysis. Compared to vehicle (PBS)-treated PMs, WIKIM28-treated and WIKIM50-treated PMs exhibited a total of 889 and 432 differentially expressed genes with expression differences of at least 4 folds, respectively. Compared to WIKIM28-treated PMs, WIKIM50-treated PMs showed 25 up-regulated genes and 21 down-regulated genes with expression differences of more than 2 folds. Interestingly, mRNA transcripts of M2 macrophage polarization marker such as anxa1, mafb, and sepp1 were increased in WIKIM50-treated PMs comparing to those in WIKIM28-treated PMs. Reversely, mRNA transcripts of M1 macrophage polarization marker such as hdac9, ptgs2, and socs3 were decreased in WIKIM50-treated PMs comparing to those in WIKIM28-treated PMs. In agreement with these observations, mRNA expression levels of tumor necrosis factor-α and interleukin-1α were significantly reduced in WIKIM50-treated macrophages compared to those in WIKIM28-treated macrophages. These results may indicate that probiotics can be classified as two different types depending on their ability to convert macrophages into M1 or M2 polarization.

• 운동영양학회지
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• 제23권4호
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• pp.14-22
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• 2019

[Purpose] Here, we aimed to determine the effect of Polygonum cuspidatum stem extract (PSE) on exorbital lacrimal gland-excised rat models and hyperosmotic stress-stimulated human conjunctival cells (HCCs). [Methods] Seven week old male Wistar rats were divided into six groups. Only the rats in the control group (NOR, n=5) did not undergo surgery. Three days after the surgery, the exorbital lacrimal gland-excised rats were randomly allocated to five groups: (1) vehicle-treated dry-eyed rats (DED, n=5); (2) PSE (10 mg/kg) treated DED rats (PSE-10, n=5); (3) PSE (100 mg/kg) treated DED rats (PSE-100, n=5); and (4) PSE (250 mg/kg) treated DED rats (PSE-250, n=5). In addition, the HCC line was co-treated with hyperosmolar media (528 mOsm) and PSE (1-100 μg/ml). [Results] PSE treatment restored the tear volume and goblet cell density by inhibiting severe corneal irregularities and damage. The treatment with PSE significantly attenuated the hyperosmolar stress-induced inflammation and cell death through the suppression of mRNA expression levels of Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and Interferon-γ (IFN-γ), and the expression of Bcl-2-associated X protein (Bax) as well as the activation of caspase-3 in vitro. [Conclusion] The inhibitory effects of PSE treatment on dry eye disease indicate the potential of nutritional intervention by PES against inflammatory diseases without adverse effects.

• Journal of Dairy Science and Biotechnology
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• 제41권3호
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• pp.113-125
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• 2023

In this study, we explored the synergistic effects of whey protein concentrate (WPC) and soybean protein components after fermentation with lactic acid bacteria isolated from kimchi, and identified several peptides with desirable physiological functions, proteolysis, and immune effects. Antioxidant activity was determined using 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid, 1,1-diphenyl-2-picrylhydrazyl, ferric-reducing antioxidant power, and hydroxyl radical scavenging assays, followed by cross-validation of the four antioxidant activities. These assays revealed that samples with a 8:2 and 9:1 whey to soy ratio possessed higher antioxidant activity than the control samples. Antibacterial potency testing revealed high antibacterial activity in the 9:1 and 8:2 samples. Cytotoxicity testing of samples using 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide revealed that only the 10:0, 1:9, and 0:10 samples had <80% viable cells, indicating no significant cytotoxicity. Nitric oxide (NO) assays revealed that NO expression was reduced in 8:2, 5:5, and 0:10 protein ratio fermentations, indicating low inflammatory reaction stimulatory potential. Cytokine expression was confirmed using an enzyme-linked immunosorbent assay kit. The 8:2 sample had the lowest inflammatory cytokine (interleukin [IL]-1α, IL-6, and tumor necrosis factor-α) levels compared with the lipopolysaccharide-treated group. Amino acid profiling of the 8:2 sample identified 17 amino acids. These results suggest that inoculating and fermenting Lactobacillus plantarum DK203 and Lactobacillus paracasei DK209 with an 8:2 mixture of WPC and soybean protein releases bioactive peptides with excellent anti-inflammatory and antioxidant properties, making them suitable for functional food development.

• Journal of Acupuncture Research
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• 제40권4호
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• pp.356-367
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• 2023

Background: The aim of this study is to determine the antioxidant and anti-inflammatory effects of Dusokohwaeum (DOE). Methods: To measure the antioxidant and anti-inflammatory effects of DOE, the total flavonoid and polyphenol contents and radical scavenging activity were measured. Furthermore, reactive oxygen species (ROS), nitric oxide, and cytokine production were measured by treating lipopolysaccharide-induced RAW264.7 cells with DOE, and gene expression levels of inducible cyclooxygenase-2, nitric oxide synthase, and cytokines were evaluated. Results: Radical scavenging experiments revealed a significant concentration-dependent increase in scavenging capacity. The production of ROS, nitric oxide, and cytokines in the cells showed a significant concentration-dependent decrease when compared with the control group. The gene expression levels of inducible cyclooxygenase-2, nitric oxide synthase, and cytokines also showed a significant concentration-dependent decrease when compared with the control group. Conclusion: Interestingly, the antioxidant and anti-inflammatory effects of DOE were 23.42 ± 0.64 mg GAE/g and 20.83 ± 0.98 mg QE/g, respectively. The administration of DOE resulted in a concentration-dependent increase in scavenging ability in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging ability experiments. The production of intracellular ROS and nitric oxide was significantly reduced in the presence of DOE. The production of inflammatory cytokines (prostaglandin E2, tumor necrosis factor-alpha [TNF-α], interleukin-1 beta [IL-1β], and IL-6) was significantly reduced in the presence of DOE. Finally, the expression levels of inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, IL-1β, and IL-6 were significantly decreased in the presence of DOE.

• Journal of Veterinary Science
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• 제25권1호
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• pp.11.1-11.16
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• 2024

Background: Canine parvoviral enteritis (CPE) is a fatal disease worldwide. The treatment of CPE is based mainly on supportive and symptomatic treatment. Antiviral addition to the treatment may result in a higher survival. Objectives: This study evaluated the effects of antiviral treatments with a standardized treatment (ST) on the clinical and inflammatory response of dogs with naturally occurring CPE. Methods: Twenty-eight dogs with CPE caused by canine parvovirus type 2 were divided randomly into treatment groups. The ST group received fluid, antibiotic, antiemetic, and deworming treatments. The antiviral treatment groups received the same ST with an additional antiviral drug, recombinant feline interferon omega (rFeIFN-ω), oseltamivir (OSEL) or famciclovir (FAM). Results: Compared to the healthy control, the tumor necrosis factor-α, interleukin-1β, interferon (IFN)-α, IFN-γ, haptoglobin, and C-reactive protein values were high (p < 0.05) on day zero. At presentation, mild lymphopenia, neutropenia, and a high neutrophil to lymphocyte (LYM) ratio (NLR) were also observed. Adding rFeIFN-ω to the ST produced the best improvement in the clinical score with a decreased NLR, while leucocytes remained low and inflammatory markers stayed high on day three. The survival rates of the groups were 85.7% in ST+IFN, 71.4% in ST+OSEL, 71.4% in ST+FAM, and 57.1% in ST groups on day seven. Conclusions: Antiviral drugs may be valuable in treating CPE to improve the clinical signs and survival. In addition, the decrease in NLR in favor of LYM may be an indicator of the early prognosis before the improvement of leukocytes, cytokines, and acute phase proteins in CPE.

• Journal of Chest Surgery
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• 제57권3호
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• pp.263-271
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• 2024

Background: Delirium is a recognized neurological complication following cardiac surgery and is associated with adverse clinical outcomes, including elevated mortality and prolonged hospitalization. While several clinical risk factors for post-cardiac surgery delirium have been identified, the pathophysiology related to the immune response remains unexamined. This study was conducted to investigate the immunological factors contributing to delirium in patients after thoracic aortic surgery. Methods: We retrospectively evaluated 43 consecutive patients who underwent thoracic aortic surgery between July 2017 and June 2018. These patients were categorized into 2 groups: those with delirium and those without it. All clinical characteristics were compared between groups. Blood samples were collected and tested on the day of admission, as well as on postoperative days 1, 3, 7, and 30. Levels of helper T cells (CD4), cytotoxic T cells (CD8), B cells (CD19), natural killer cells (CD56+CD16++), and monocytes (CD14+CD16-) were measured using flow cytometry. Results: The median patient age was 71 years (interquartile range, 56.7 to 79.0 years), and 21 of the patients (48.8%) were male. Preoperatively, most immune cell counts did not differ significantly between groups. However, the patients with delirium exhibited significantly higher levels of interleukin-6 and lower levels of tumor necrosis factor-alpha (TNF-α) than those without delirium (p<0.05). Multivariate analysis revealed that lower TNF-α levels were associated with an increased risk of postoperative delirium (p<0.05). Conclusion: Postoperative delirium may be linked to perioperative changes in immune cells and preoperative cytokine levels. Additional research is required to elucidate the pathophysiological mechanisms underlying delirium.

• 동의생리병리학회지
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• 제18권1호
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• pp.114-121
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• 2004

We investigated the effects of healthful decoction utilizing Phellinus linteus(HDPL) for suppression in the process of carbon tetrachloride (CCl₄4)-induced inflammation(50% CCl₄ : olive oil=1:1, 1 ㎖/KgㆍB.W.) of rat using biochemical, Western, histological and immunohistochemical analysis. Biochemical analysis of serum showed that the level of aspartate aminotransferase, alanine aminotransferase, lactate Dehydrogenase, alkaline phosphatase and triglyceride were significantly decreased by pretreatment of HDPL, but albumin and nitric oxide were increased. Immunoblot analysis of the liver showed that CCl₄-induced expression of interleukin-1β(IL-1β) and inducible nitric oxide synthase(iNOS) was inhibited by pretreatment of HDPL. More severe histopathological changes of the liver such as Kupffer cell reaction, inflammatory cell infiltration and focal necrosis were demonstrated in the rats challenged with CCl₄ compared with normal. Fewer scores of these changes were observed in the HDPL pretreated rats. Immunohistochemical analysis of the liver showed that while the expression of IL-1β, iNOS, tumor necrosis factor-α, COX(cyclooxygenase)-1 and COX-2 tended to increase, a decline of these immunoreaction of HDPL pre-treated groups were observed in the hepatocytes, especially in the focal necrotic sites. These results suggest that HDPL may act as a therapeutic agent for liver disease through a regulation of inflammation-related proteins.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7243-7249
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• 2013

Numerous studies have been conducted regarding association between TNF-${\alpha}$ and oral cancer risk, but the results remain controversial. The present meta-analysis is performed to acquire a more precise estimation of relationships. Databases of Pubmed, the Cochrane library and the China National Knowledge Internet (CNKI) were retrieved until August 10, 2013. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated with fixed- or random-effect models. The heterogeneity assumption was assessed by I-squared test. Among the eight included case-control studies, all were focused on TNF-${\alpha}$-308G>A and four also concerned the TNF-${\alpha}$-238G>A polymorphism. It was found that oral cancer risk were significant decreased with the TNF-${\alpha}$-308G>A polymorphism in the additive genetic model (GG vs. AA, OR=0.19, 95% CI: [0.04, 1.00], P=0.05, I2=68.9%) and the dominant genetic model (GG+GA vs. AA, OR=0.22, 95% CI: [0.06, 0.82], P=0.03, I2=52.4%); however, no significant association was observed in allele contrast (G vs. A, OR=0.70, 95% CI: [0.23, 2.16], P=0.54, I2=95.9%) and recessive genetic models (GG vs. GA+AA, OR=0.72, 95% CI: [0.33, 1.57], P=0.41, I2=93.1%). For the TNF-${\alpha}$-238G>A polymorphism, significant associations with oral cancer risk were found in the allele contrast (G vs. A, OR=2.75, 95% CI: [1.25, 6.04], P=0.01, I2=0.0%) and recessive genetic models (GG vs. GA+AA, OR=2.23, 95%CI: [1.18, 4.23], P=0.01, I2=0.0%). Conclusively, this meta-analysis indicates that TNF-${\alpha}$ polymorphisms may contribute to the risk of oral cancer. Allele G and the GG+GA genotype of TNF-${\alpha}$-308G>A may decrease the risk of oral cancer, while allele G and the GG genotype of TNF-${\alpha}$-238G>A may cause an increase.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10879-10882
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• 2015

Objective: To investigate the effect of intraoperative glucose fluctuation and postoperative interlukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), C-reactive protein (CRP) levels on the short-term prognosis of patients with intracranial supratentorial neoplasms. Materials and Methods: Eighty-six patients undergoing intracranial excision were selected in The Second Hospital of Jilin University. According to the condition of glucose fluctuation, the patients were divided into group A (glucose fluctuation <2.2 mmol/L, n=57) and group B (glucose fluctuation ${\geq}2.2mmol/L$, n=29). Glucose was assessed by drawing 2 mL blood from internal jugular vein in two groups in the following time points, namely fasting blood glucose 1 d before operation ($T_0$), 5 min after anesthesia induction ($T_1$), intraoperative peak glucose ($T_2$), intraoperative lowest glucose ($T_3$), 5 min after closing the skull ($T_4$), immediately after returning to intensive care unit (ICU) ($T_5$) and 2 h after returning to ICU ($T_6$). 1 d before operation and 1, 3 and 6 d after operation, serum IL-6 and TNF-${\alpha}$ levels were detected with enzyme-linked immunosorbent assay (ELISA), and CRP level with immunoturbidimetry. Additionally, postoperative adverse reactions were monitored. Results: There was no statistical significance between two groups regarding the operation time, anesthesia time, amount of intraoperative bleeding and blood transfusion (P>0.05). The glucose levels in both groups at $T_1{\sim}T_6$ went up conspicuously compared with that at $T_0$ (P<0.01), and those in group B at $T_2$, $T_4$, $T_5$ and $T_6$ were significantly higher than in group A (P<0.01). Serum IL-6, TNF-${\alpha}$ and CRP levels in both groups 1, 3 and 6 d after operation increased markedly compared with 1 d before operation (P<0.01), but the increased range in group A was notably lower than in group B (P<0.05 or P<0.01). Postoperative incidences of hypoglycemia, hyperglycemia and myocardial ischemia in group A were significantly lower than in group B (P<0.05), and respiratory support time obviously shorter than in group B (P<0.01). Conclusions: The glucose fluctuation of patients undergoing intracranial excision is related to postoperative IL-6, TNF-${\alpha}$ and CRP levels and those with small range of glucose fluctuation have better prognosis.

• BMB Reports
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• 제37권2호
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• pp.185-191
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• 2004

Tissue transglutaminase (tTGase) regulates various biological processes, including extracellular matrix organization, cellular differentiation, and apoptosis. Here we report the protective role of tTGase in the cell death that is induced by the tumor necrosis factor $\alpha$ (TNF-$\alpha$) and ceramide, a product of the TNF-$\alpha$ signaling pathway, in human neuroblastoma SH-SY5Y cells. Treatment with retinoic acid (RA) induced the differentiation of the neuroblastoma cells with the formation of extended neurites. Immunostaining and Western blot analysis showed the tTGase expression by RA treatment. TNF-$\alpha$ or $C_2$ ceramide, a cell permeable ceramide analog, induced cell death in normal cells, but cell death was largely inhibited by the RA treatment. The inhibition of tTGase by the tTGase inhibitors, monodansylcadaverine and cystamine, eliminated the protective role of RA-treatment in the cell death that is caused by TNF-$\alpha$ or $C_2$-ceramide. In addition, the co-treatment of TNF-$\alpha$ and cycloheximide ecreased the protein level of tTGase and cell viability in the RA-treated cells, supporting the role of tTGase in the protection of cell death. DNA fragmentation was also induced by the co-treatment of TNF-$\alpha$ and cycloheximide. These results suggest that tTGase expressed by RA treatment plays an important role in the protection of cell death caused by TNF-$\alpha$ and ceramide.