• Clinical and Experimental Pediatrics
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• v.60 no.5
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• pp.145-150
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• 2017

Purpose: The gut microbiota can influence several diseases through immune modulation; however, the exact role of microbes such as Clostridium difficile and the relationship between microbiota colonization and allergic diseases are not well known. This study aimed to determine the relationship between C. difficile colonization and/or infection (CDCI) during infancy and allergic diseases during early childhood. Methods: Infants 1-12 months of age presenting changes in bowel habits for more than 2 weeks were enrolled in this study. After dividing them into 2 groups according to the presence and absence of C. difficile, the risk of allergic disease development during childhood was identified and compared. Results: Sixty-five patients were included in this study; 22 (33.8%) were diagnosed with CDCI. No significant differences were observed in baseline characteristics between the C. difficile-positive and-negative groups except for antibiotic exposure (22.7% vs. 60.5%, P=0.004). Compared to the C. difficile-negative group, the risk of developing at least one allergic disease was higher in the C. difficile-positive group after adjusting other variables (adjusted odds ratios, 5.61; 95% confidence interval, 1.52-20.74; P=0.007). Furthermore, food allergies were more prevalent in the C. difficile-positive group (P=0.03). Conclusion: CDCI during infancy were associated with a higher risk of developing allergic diseases during early childhood. These results suggest that CDCI during infancy might reflect the reduced diversity of the intestinal microbiota, which is associated with an increased risk of allergic sensitization. To identify the underlying mechanism, further investigation and a larger cohort study will be needed.

• Food Science of Animal Resources
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• v.21 no.4
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• pp.374-382
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• 2001

Lactoferrin(Lf) has the function of modulation in the host defense systems, including cytokine production and immune responses. We have tested the effect of Lf and Lf ydrolysates(Lf-H) on the productions of tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) and nitric oxide(NO) in macrophage cells. Lf from Korean native cattle(K-Lf) and hydrolyzed K-Lf(K-Lf-H) increased the production of TNF-${\alpha}$ in RAW264.7 cells with dose-dependency. Bovine Lf(B-Lf), human Lf(H-Lf), and its hydrolysates did not induce either TNF-${\alpha}$ production or NO production. On the other hand those didn\`t affect on the production of TNF-${\alpha}$ in lipopolysaccharide(LPS)-stimulated RAW264.7 cells. K-Lf induced the production of NO similar to its role on the TNF-${\alpha}$ production.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.1
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• pp.16-22
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• 2016

The intestinal environment plays a critical role in maintaining swine health. Many factors such as diet, microbiota, and host intestinal immune response influence the intestinal environment. Intestinal alkaline phosphatase (IAP) is an important apical brush border enzyme that is influenced by these factors. IAP dephosphorylates bacterial lipopolysaccharides (LPS), unmethylated cytosine-guanosine dinucleotides, and flagellin, reducing bacterial toxicity and consequently regulating toll-like receptors (TLRs) activation and inflammation. It also desphosphorylates extracellular nucleotides such as uridine diphosphate and adenosine triphosphate, consequently reducing inflammation, modulating, and preserving the homeostasis of the intestinal microbiota. The apical localization of IAP on the epithelial surface reveals its role on LPS (from luminal bacteria) detoxification. As the expression of IAP is reported to be downregulated in piglets at weaning, LPS from commensal and pathogenic gram-negative bacteria could increase inflammatory processes by TLR-4 activation, increasing diarrhea events during this phase. Although some studies had reported potential IAP roles to promote gut health, investigations about exogenous IAP effects or feed additives modulating IAP expression and activity yet are necessary. However, we discussed in this paper that the critical assessment reported can suggest that exogenous IAP or feed additives that could increase its expression could show beneficial effects to reduce diarrhea events during the post weaning phase. Therefore, the main goals of this review are to discuss IAP's role in intestinal inflammatory processes and present feed additives used as growth promoters that may modulate IAP expression and activity to promote gut health in piglets.

• Restorative Dentistry and Endodontics
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• v.25 no.4
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• pp.606-618
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• 2000

Dental pulp infection is most commonly caused by extensive dental caries, and some bacterial species invade root canals; bacterial components and products are thought to be associated with the pathogenesis of periapical periodontitis. A principle driving force behind pulpal disease response appears to lie in the host immune system's to bacteria and their products. We examined the production of interleukin $1{\beta}$ (IL-$1{\beta}$) and tumor necrosis factor ${\alpha}$(TNF-${\alpha}$) from human peripheral mononuclear cells, lymphocytes and monocytes stimulated by heat-killed Acitnobacillus actinomycetemcomitans (ATCC 29523), Porphyromonas gingivalis (ATCC 33277) and Prevotella intermedia (ATCC 25611), and also by their sonicated bacterial extracts (SBE), respectively. The effects of three strains of heat-killed bacteria and their SBEs on the morphology of cultured blood cell lines HL-60 (KCLB 10240) and J774A.1 (KCLB 40067) were observed under the inverted microscope. Ultrastructural changes of J774A.1 exposed to heat-killed P. intermedia and its SBE were investigated using transmission electron microscopy. Production of IL-$1{\beta}$ was reduced in human peripheral mononuclear cells after stimulation by sonic bacterial extracts of A. actinomycetemcomitans, P. gingivalis, and P. intermedia. Heat-killed and sonic extract of P. gingivalis inhibited the production of TNF-${\alpha}$ in peripheral mononuclear cells. Production of TNF-${\alpha}$ was inhibited in peripheral monocytes after stimulation by sonic extracts of A. actinomycetemcomitans, P. gingivalis, and P. intermedia. HL-60 and J 774A.1 cells showed granular degeneration after treatment with heat-killed and sonic extracts of A. actinomycetemcomitans, P. gingivalis, and P. intermedia Chromatin margination and shrinkage were observed in 774A.1 treated with heat-killed P. intermedia. Cell wall structure and organelles were destroyed and vacuoles were formed in cytoplasm in J774A.1 treated with P. intermedia sonic extract. These results suggest that A actinomycetemcomitans, P gingivalis and P intermedia may have an important role in the formation and progression of pulpal diseases via both modulation of production of IL-$1{\beta}$ and TNF-${\alpha}$ from blood mononuclear cells and cytopathic effects.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2002.10a
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• pp.170-170
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• 2002

College of Pharmacy, Ewha womans University, Seoul, 120-750, Korea 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A1. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity, immune suppression, and reproductive and developmental toxicity. Dramatic differences in dioxin toxicity have been observed between the sexes of some animal species, suggesting hormonal modulation of dioxin action. Many studies have been reported and propose several mechanisms of anti-estrogenic effects of TCDD. In contrast, the effect of estrogen on the regulation of CYP1A1 are not clear at present. There are several reports showing conflicting results. It seems that induction/inhibition of CYP1A1 may be dependent on cell-type and concentration. The purpose of this study was to investigate the regulation of TCDD-induced CYP1A1 gene expression by estradiol and its metabolites. We examined whether estradiol and its metabolites altered TCDD-mediated induction of CYP1A1 enzyme activity. 17 ${\beta}$ estradiol and 16 ${\alpha}$ estriol at non cytotoxic concentrations caused a significant concentration dependent decline of TCDD-induced EROD activity To determine whether reduced EROD activity reflected altered CYP1A1 mRNA expression, we measured CYP1A1 mRNA level by RT-PCR. And to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level, we also peformed transient transfection with an AhR responsive reporter plasmid containing the 5' flanking region of the human CYP1A1 gene to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.1
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• pp.39-44
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• 2006

Type I diabetes (T1D) is an organ-specific autoimmune disease caused by the T cell-mediated destruction of the insulin-producing ${\beta}$ cells in the pancreatic islets. The onset of T1D is the consequence of a progressive destruction of islet ${\beta}$ cells mediated by an imbalance between effector $CD4^+$ T helper (Th)1 and regulatory $CD4^+$ Th2 cell function. Since interferon-alpha (IFN-${\alpha}$) has been known to modulate immune function and autoimmunity, we investigated whether administration of adenoviralmediated IFN-${\alpha}$ gene would inhibit the diabetic process in NOD mice. The development of diabetes was significantly inhibited by a single injection of adenoviral-mediated IFN-${\alpha}$ gene before 8 weeks of age. Next, we examined the hypothesis that Th2-type cytokines are associated with host protection against autoimmune diabetes, whereas Th1-type cytokines are associated with pathogenesis of T1D. The expression of IFN-${\alpha}$ induced increase of serum IL-4 and IL-6 (Th2 cytokines) levels and decrease of serum IL-12 and IFN-${\gamma}$ (Th1 cytokines) levels. Therefore, overexpression of IFN-${\alpha}$ by adenoviralmediated delivery provides modulation of pathogenic progression and protection of NOD mice from T1D.

• The Journal of Internal Korean Medicine
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• v.25 no.4
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• pp.9-17
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• 2004

Objective : Mesangial cell proliferation and excessive accumulation of extracellular matrix (ECM) proteins is the common pathologic feature of glomerulosclerosis, and platelet-derived growth factor (PDGF) BB-chain, transforming growth factor betal $(TGF-{\beta}1)$, cyclin dependent kinases (CDK) and CDK inhibitors mediated in these pathophysiological processes. Bupleurum falcatum which is one of the most widely used components in traditional oriental medicines, has multiple pharmacological effects, such as antipyretic, analgesic, immune modulating, anti-inflammatory, anti-allergic, anti-thrombotic, anti-atherosclerotic, and antitussive effects. Methods : In this study, we evaluated the influence of Bupleurum falcatum on mesangial cell proliferation, DNA synthesis and expression of PDGF-BB chain, $TGF-{\beta}1$, CDKI, CDK2, CDK4, p21 and p27 in fetal bovine serum (FBS)-activated human mesangial cell. Results : Bupleurum falcatum reduced the mesangial cell proliferation and DNA synthesis more than control and captopril. And in the ELISA analysis of $TGF-{\beta}1$, and RT-PCR of PDGF-BB chain, CDK1, CDK2, CDK4, p21, and p27, Bupleurum falcatum inhibited the expression of $TGF-{\beta}1$ protein and PDGF-BB, CDK1, CDK2 gene and promoted that of p21 gene in a dose-dependent manner in comparing with control and captopril. Conclusions: These results suggest that Bupleurum falcatum may inhibit the mesangial cell proliferation and DNA synthesis by regulation of PDGF-BB and $TGF-{\beta}1$ expressions, and by modulation of CDK1, CDK2 and p21 expression.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.210-217
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• 2018

Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer's disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3',4'-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3',4'-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin $E_2$ and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor $(NF)-{\kappa}B$ activation. This indicates that the anti-inflammatory activities of 3',4'-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and $NF-{\kappa}B$ signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3',4'-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.

• Journal of Pharmacopuncture
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• v.20 no.3
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• pp.158-172
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• 2017

Nigella sativa (N. sativa, family Ranunculaceae) is a medicinal plant that has been widely used for centuries throughout the world as a natural remedy. A wide range of chemical compounds found in N. sativa expresses its vast therapeutic effects. Thymoquinone (TQ) is the main component (up to 50%) in the essential oil of N. sativa. Also, pinene (up to 15%), p-cymene (40%), thymohydroquinone (THQ), thymol (THY), and dithymoquinone (DTQ) are other pharmacologically active compounds of its oil. Other terpenoid compounds, such as carvacrol, carvone, 4-terpineol, limonenes, and citronellol, are also found in small quantities in its oil. The main pharmacological characteristics of this plant are immune system stimulatory, anti-inflammatory, hypotensive, hepatoprotective, antioxidant, anti-cancer, hypoglycemic, anti-tussive, milk production, uricosuric, choleretic, anti-fertility, and spasmolytic properties. In this regard, we have searched the scientific databases PubMed, Web of Science, and Google Scholar with keywords of N. sativa, anti-cancer, apoptotic effect, antitumor, antioxidant, and malignancy over the period from 2000 to 2017. The effectiveness of N. sativa against cancer in the blood system, kidneys, lungs, prostate, liver, and breast and on many malignant cell lines has been shown in many studies, but the molecular mechanisms behind that anti-cancer role are still not clearly understood. From among the many effects of N. sativa, including its anti-proliferative effect, cell cycle arrest, apoptosis induction, ROS generation, anti-metastasis/anti-angiogenesis effects, Akt pathway control, modulation of multiple molecular targets, including p53, p73, STAT-3, PTEN, and $PPAR-{\gamma}$, and activation of caspases, the main suggestive anti-cancer mechanisms of N. sativa are its free radical scavenger activity and the preservation of various anti-oxidant enzyme activities, such as glutathione peroxidase, catalase, and glutathione-S-transferase. In this review, we highlight the molecular mechanisms of apoptosis and the anti-cancer effects of N. sativa, with a focus on its molecular targets in apoptosis pathways.

• Journal of Dental Anesthesia and Pain Medicine
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• v.17 no.3
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• pp.163-181
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• 2017

In the field of orofacial surgery, a red blood cell transfusion (RBCT) is occasionally required during double jaw and oral cancer surgery. However, the question remains whether the effect of RBCT during the perioperative period is beneficial or harmful. The answer to this question remains challenging. In the field of orofacial surgery, transfusion is performed for the purpose of oxygen transfer to hypoxic tissues and plasma volume expansion when there is bleeding. However, there are various risks, such as infectious complications (viral and bacterial), transfusion-related acute lung injury, ABO and non-ABO associated hemolytic transfusion reactions, febrile non-hemolytic transfusion reactions, transfusion associated graft-versus-host disease, transfusion associated circulatory overload, and hypersensitivity transfusion reaction including anaphylaxis and transfusion-related immune-modulation. Many studies and guidelines have suggested RBCT is considered when hemoglobin levels recorded are 7 g/dL for general patients and 8-9 g/dL for patients with cardiovascular disease or hemodynamically unstable patients. However, RBCT is occasionally an essential treatment during surgeries and it is often required in emergency cases. We need to comprehensively consider postoperative bleeding, different clinical situations, the level of intra- and postoperative patient monitoring, and various problems that may arise from a transfusion, in the perspective of patient safety. Since orofacial surgery has an especially high risk of bleeding due to the complex structures involved and the extensive vascular distribution, measures to prevent bleeding should be taken and the conditions for a transfusion should be optimized and appropriate in order to promote patient safety.