• Journal of Chest Surgery
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• v.57 no.3
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.1
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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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• v.14 no.12
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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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• v.15 no.24
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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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• v.37 no.2
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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.

• Journal of Life Science
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• v.21 no.1
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• pp.22-30
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• 2011

Apolipoprotein A-I (apoA-I) has anti-inflammatory and anti-oxidative properties. This study was designed to investigate whether apoA-I affects apoptosis and cytokine production of human blood neutrophils in an in vitro culture system. Spontaneous apoptosis of neutrophils was significantly delayed by apoA-I. In addition, high density lipoprotein containing apoA-I also delayed apoptosis of neutrophils. Apoptosis of neutrophils was inhibited by anti-scavenger receptor type B-I antibodies. The amounts of interleukin-8, interferon (IFN)-inducible protein 10 (IP-10), and tumor necrosis factor-$\alpha$ (TNF-$\alpha$) in the supernatants of cultured neutrophils treated with apoA-I were significantly increased. Combined treatment of neutrophils with IFN-$\gamma$ and apoA-I produced higher amounts of IP-10 and TNF-$\alpha$ than did treatment with IFN-$\gamma$ or apoA-I alone. The present study reveals that apoA-I activates neutrophils to produce cytokines and delays spontaneous apoptosis of neutrophils. These findings suggest that apoA-I, although a well-known negative acute-phase protein, has a pro-inflammatory effect in neutrophils.

• Journal of dental hygiene science
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• v.19 no.4
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• pp.254-260
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• 2019

Background: The primary aims of periodontal disease treatment is to remove dental plaque and calculus, the main causes of tooth loss, and restore periodontal tissue destroyed by inflammation. Periodontal disease treatment should also help maintain the alveolar bone, alleviate inflammation, and promote periodontal ligament cell proliferation, which is essential for tissue regeneration. Conventional antibiotics and anti-inflammatories have adverse side effects, especially during long-term use, so there is a need for adjunct treatment agents derived from natural products. The purpose of this study was to investigate whether the herbal flavone baicalein has the osteogenic activity under inflammatory conditions, and assess the involvement of osteoblast immediate early response 3 (IER3) expression. Methods: Human osteoblastic MG-63 cells were cultured with the pro-inflammatory cytokines tumor necrosis factor α and interleukin 1β in the presence and absence of baicalein. Proliferation was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and expression of IER3 mRNA was assessed using real-time polymerase chain reaction. The expression of IER3 protein levels and activation of associated signal transduction pathways were assessed using western blotting. Results: Baicalein increased IER3 mRNA and protein expression synergistically. In addition, baicalein reversed the suppression of cell proliferation, and the downregulation of osteogenic transcription factor runt-related transcription factor 2 and osterix induced by pro-inflammatory cytokines. Baicalein also upregulated the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK 1/2). The upregulation of IER3 by pro-inflammatory cytokines was blocked by pretreatment with inhibitors of AKT, p38, JNK, and ERK 1/2. Conclusion: Baicalein mitigates the deleterious responses of osteoblasts to pro-inflammatory cytokines. Further, IER3 enhanced the effect of baicalein via activation of AKT, p38, JNK, and ERK pathways.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.1
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• pp.27-37
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• 2020

Neuroinflammation is an important process underlying a wide variety of neurodegenerative diseases. Carvacrol (CAR) is a phenolic monoterpene commonly used as a food additive due to its antibacterial properties, but it has also been shown to exhibit strong antioxidative, anti-inflammatory, and neuroprotective effects. Here, we sought to investigate the effects of CAR on inflammation in the hippocampus and prefrontal cortex, as well as the molecular mechanisms underlying these effects. In our study, lipopolysaccharide was injected into the lateral ventricle of rats to induce memory impairment and neuroinflammation. Daily administration of CAR (25, 50, and 100 mg/kg) for 21 days improved recognition, discrimination, and memory impairments relative to untreated controls. CAR administration significantly attenuated expression of several inflammatory factors in the brain, including interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2. In addition, CAR significantly increased expression of brain-derived neurotrophic factor (BDNF) mRNA, and decreased expression of Toll-like receptor 4 (TLR4) mRNA. Taken together, these results show that CAR can improve memory impairment caused by neuroinflammation. This cognitive enhancement is due to the anti-inflammatory effects of CAR medicated by its regulation of BDNF and TLR4. Thus, CAR has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases.

• Journal of Microbiology and Biotechnology
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• v.25 no.7
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• pp.1047-1055
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• 2015

For the search of a potent first-in-class compound to inactivate macrophages responsible for inflammatory responses, in the present study, we investigated the anti-nflammatory effects of YH-1118, a novel synthetic compound, in a lipopolysaccharide (LPS)-stimulated mouse macrophage cell line, Raw 264.7. YH-1118 inhibited LPS-induced nitric oxide (NO) production and inducible NO synthase (iNOS) expression at both the protein and mRNA levels. The suppression of LPS-induced iNOS expression by YH-1118 was mediated via nuclear factor kappa B (NF-κB), but not activator protein-1 (AP-1) transcription factor. This was supported by the finding that YH-1118 attenuated the phosphorylation of inhibitor of κBα (IκBα) and nuclear translocation and DNA binding activity of NF-κB. Through the mechanisms that YH-1118 inhibited the activation of IκB kinases (IKKs), upstream activators of NF-κB, or p38 MAPK, YH-1118 significantly suppressed LPS-induced production of pro-inflammatory cytokines, tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 (p < 0.05). In conclusion, our results suggest that YH-1118 inhibits LPS-induced inflammatory responses by blocking IKK and NF-κB activation in macrophages, and may be a therapeutic candidate for the treatment of various inflammatory diseases.

• Biomolecules & Therapeutics
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• v.21 no.6
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• pp.435-441
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• 2013

Emodin, a naturally occurring anthraquinone derivative isolated from Polygoni cuspidati radix, has several beneficial pharmacologic effects, which include anti-cancer, anti-diabetic, and anti-inflammatory activities. In this study, the authors examined the effect of emodin on the production of proinflammatory cytokines, such as, tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6, in mouse bone marrow-derived mast cells (BMMCs) stimulated with phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187. To investigate the mechanism responsible for the regulation of pro-inflammatory cytokine production by emodin, the authors assessed its effects on the activations of transcriptional factor nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and mitogen-activated protein kinases (MAPKs). Emodin attenuated the nuclear translocation of (NF)-${\kappa}B$ p65 and its DNA-binding activity by reducing the phosphorylation and degradation of $I{\kappa}B{\alpha}$ and the phosphorylation of $I{\kappa}B$ kinase B (IKK). Furthermore, emodin dose-dependently attenuated the phosphorylations of MAPKs, such as, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAP kinase, and the stress-activated protein kinases (SAPK)/c-Jun-N-terminal kinase (JNK). Taken together, the findings of this study suggest that the anti-inflammatory effects of emodin on PMA plus A23187-stimulated BMMCs are mediated via the inhibition of NF-${\kappa}B$ activation and of the MAPK pathway.