The Polymethoxy Flavonoid Sudachitin Inhibits Interleukin-1β-Induced Inflammatory Mediator Production in Human Periodontal Ligament Cells

Sudachitin, which is a polymethoxylated flavonoid found in the peel of Citrus sudachi, has some biological activities. However, the effect of sudachitin on periodontal resident cells is still uncertain. The aim of this study was to examine if sudachitin could decrease the expression of inflammatory mediators such as cytokines, chemokines, or matrix metalloproteinase (MMP) in interleukin- (IL-) 1β-stimulated human periodontal ligament cells (HPDLC). Sudachitin inhibited IL-1β-induced IL-6, IL-8, CXC chemokine ligand (CXCL)10, CC chemokine ligand (CCL)2, MMP-1, and MMP-3 production in HPDLC. On the other hand, tissue inhibitor of metalloproteinase- (TIMP-) 1 expression was increased by sudachitin treatment. Moreover, we found that the nuclear factor- (NF-) κB and protein kinase B (Akt) pathways in the IL-1β-stimulated HPDLC were inhibited by sudachitin treatment. These findings indicate that sudachitin is able to reduce inflammatory mediator production in IL-1β-stimulated HPDLC by inhibiting NF-κB and Akt pathways

TGF-β1 and IL-4 induce CCL11 production

Transforming growth factor (TGF)-β1 is a multifunctional cytokine, which can control certain functions of various kinds of cells. However, it is unclear whether TGF-β1 affects T-cell migration in periodontal lesions. The aim of this study was to examine the effects of TGF-β1 on the production of C-C chemokine ligand (CCL)11, which is a T-helper 2-type chemokine, in human periodontal ligament cells (HPDLC). Interleukin (IL)-4 induced CCL11 production, but TGF-β1 did not, in HPDLC. However, TGF-β1 enhanced CCL11 production in IL-4-stimulated HPDLC. Western blot analysis showed that the signal transducer and activator of transcription 6 (STAT6) pathway was highly activated in HPDLC that had been stimulated with both IL-4 and TGF-β1. Mitogen-activated protein kinase activation did not differ between the HPDLC treated with a combination of IL-4 and TGF-β1 and those treated with IL-4 or TGF-β1 alone. Moreover, a STAT6 inhibitor significantly inhibited CCL11 production in HPDLC that had been stimulated with IL-4 and TGF-β1. The current study clearly demonstrated that TGF-β1 enhanced IL-4-induced CCL11 production in HPDLC. The STAT6 pathway is important for CCL11 production in IL-4- and TGF-β1-treated HPDLC

Nobiletin Inhibits Inflammatory Reaction in Interleukin-1β-Stimulated Human Periodontal Ligament Cells

The immune response in periodontal lesions is involved in the progression of periodontal disease. Therefore, it is important to find a bioactive substance that has anti-inflammatory effects in periodontal lesions. This study aimed to examine if nobiletin, which is found in the peel of citrus fruits, could inhibit inflammatory responses in interleukin (IL)-1β-stimulated human periodontal ligament cells (HPDLCs). The release of cytokines (IL-6, IL-8, CXCL10, CCL20, and CCL2) and matrix metalloproteinases (MMP-1 and MMP-3) was assessed by ELISA. The expression of cell adhesion molecules (ICAM-1and VCAM-1) and the activation of signal transduction pathways (nuclear factor (NF)-κB, mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt)) in HPDLCs were detected by Western blot analysis. Our experiments revealed that nobiletin decreased the expression of inflammatory cytokines, cell adhesion molecules, and MMPs in IL-1β-stimulated HPDLCs. Moreover, we revealed that nobiletin treatment could suppress the activation of the NF-κB, MAPKs, and Akt pathways. These findings indicate that nobiletin could inhibit inflammatory reactions in IL-1β-stimulated HPDLCs by inhibiting multiple signal transduction pathways, including NF-κB, MAPKs, and Akt

Observation of finite excess noise in the voltage-biased quantum Hall regime as a precursor for breakdown

We performed noise measurements in a two-dimensional electron gas to investigate the nonequilibrium quantum Hall effect (QHE) state. While excess noise is perfectly suppressed around the zero-biased QHE state reflecting the dissipationless electron transport of the QHE state, considerable finite excess noise is observed in the breakdown regime of the QHE. The noise temperature deduced from the excess noise is found to be of the same order as the energy gap between the highest occupied Landau level and the lowest empty one. Moreover, unexpected finite excess noise is observed at a finite source-drain bias voltagesmaller than the onset voltage of the QHE breakdown, which indicates finite dissipation in the QHE state and may be related to the prebreakdown of the QHE.Comment: 8 pages, 8 figure

IL-27 Modulates Chemokine Production in Oral Epithelial Cells

Background/Aims: Interleukin-27 (IL-27) is a cytokine which belongs to the IL-12 family. However, the role of IL-27 in the pathogenesis of periodontal disease is uncertain. The aim of this study was to examine the effect of IL-27 on chemokine production in TNF-α-stimulated human oral epithelial cells (TR146). Methods: We measured chemokine production in TR146 by ELISA. We used western blot analysis to detect the phosphorylation levels of signal transduction molecules, including STAT1 and STAT3 in TR146. We used inhibitors to examine the role of STAT1 and STAT3 activation. Results: IL-27 increased CXCR3 ligands production in TNF-α-stimulated TR146. Meanwhile, IL-27 suppressed IL-8 and CCL20 production induced by TNF-α. STAT1 phosphorylation level in IL-27 and TNF-α-stimulated TR146 was enhanced in comparison to TNF-α-stimulated TR146. STAT3 phosphorylation level in IL-27-treated TR146 did not change by TNF-α. Both STAT1 inhibitor and STAT3 inhibitor decreased CXCR3 ligands production. STAT1 inhibitor overrode the inhibitory effect of IL-27 on IL-8 and CCL20 production in TNF-α-stimulated TR146. Meanwhile, STAT3 inhibitor did not modulate IL-8 and CCL20 production. Conclusion: IL-27 might control leukocyte migration in periodontal lesion by modulating chemokine production from epithelial cells

Comparison of Conventional 2D CC (Cranio-Caudal) + MLO (Medio-Lateral Oblique) Bi-Directional Photography and 2D-MLO + DBT-MLO (Digital Breast Tomosynthesis) in Mammography Examination

Introduction: Mammography (MMG) is an excellent examination for breast cancer detection and is widely used in both screening and clinical practice. However, the breast thickness and background the concentration of the mammary gland is large among individuals, and the mammary gland and cancer may overlap and it may not be possible to point out a lesion. In recent years, digital breast tomosynthesis (hereinafter referred to as DBT) has been introduced to solve these problems, and its usefulness has been reported in clinical practice. Therefore, in anticipation of a higher cancer detection rate etc., we compared the conventional 2D CC + MLO 2-way MMG examination with 2DMLO + DBTMLO 2-way MMG examination.Materials and Methods: The combination of 2D CC + MLO and 2DMLO + DBTMLO was read for 95 cases of breast cancer taking 2D CC and MLO and DBT MLO from May 2016 to October 2017. It was judged that the category 3 or more required detailed examination, cancer detection, and cancer detection rates were compared. Subjects were 28 to 87 years of age (median: 55 years), breast composition: high concentration 15.8% (15 cases), heterogeneous high concentration 47.4% (45 cases), mammary gland 28.4% (27 cases), Fatty was 8.4% (8 cases).Results: The cancer detection rate was 87% for the 2D CC + MLO combination and 94% for the 2DMLO + DBTMLO combination in 95 cases of breast cancer. The interpretation time was 95 minutes for the 2D CC + MLO combination and 110 minutes for the 2DMLO + DBTMLO combination.The breast cancer detected only by the combination of 2D CC + MLO was scattered in 1 case and was classified as Category 3 by FAD. Breast cancer detected only by the combination of 2DMLO + DBTMLO: 8 cases with uneven distribution of breast composition, 3 cases with scattered mammary gland, 3 cases with 5 cases with disordered construction, Category 4 with 3 cases with FAD was.Conclusion: Both 2D CC + MLO combination and 2DMLO + DBTMLO combination are considered useful for screening MMG examination. In particular, we would like to consider the introduction to medical examinations for the addition of MMG in DBT, but the issue of the amount of image information, the problem of exposure to radiation, the direction of imaging, the establishment of interpretation methods etc. are future issues

IL-4 Modulates Chemokine Productions in Fibroblast

Background/Aims: IL-4 is a multifunctional cytokine that is related with the pathological conditions of periodontal disease. However, it is uncertain whether IL-4 could control T cells migration in periodontal lesions. The aim of this study was to examine the effects of IL-4 on CCL11, which is a Th2-type chemokine, and CCL20, which is related with Th17 cells migration, productions from human periodontal ligament cells (HPDLCs). Methods: CCL20 and CCL11 productions from HPDLCs were monitored by ELISA. Western blot analysis was performed to detect phosphorylations of signal transduction molecules in HPDLCs. Results: IL-1β could induce both CCL11 and CCL20 productions in HPDLCs. IL-4 enhanced CCL11 productions from IL-1β-stimulated HPDLCs, though IL-4 inhibited CCL20 production. Western blot analysis showed that protein kinase B (Akt) and signal transducer and activator of transcription (STAT)6 pathways were highly activated in IL-4/IL-1β-stimulated HPDLCs. Akt and STAT6 inhibitors decreased CCL11 production, but enhanced CCL20 production in HPDLCs stimulated with IL-4 and IL-1β. Conclusions: These results mean that IL-4 enhanced Th2 cells migration in periodontal lesion to induce CCL11 production from HPDLCs. On the other hand, IL-4 inhibits Th17 cells accumulation in periodontally diseased tissues to inhibit CCL20 production. Therefore, IL-4 is positively related with the pathogenesis of periodontal disease to control chemokine productions in periodontal lesions

genipinはTNF-αが誘導するヒト歯根膜細胞のMMP-1およびMMP-3産生を抑制する

Genipin, the aglycon of geniposide found in gardenia fruit has long been considered for treatment of inflammatory diseases in traditional oriental medicine. Genipin has recently been reported to have some pharmacological functions, such as antimicrobial, antitumor, and anti-inflammatory effects. The aim of this study was to examine whether genipin could modify matrix metalloproteinase (MMP)-1 and MMP-3, which are related to the destruction of periodontal tissues in periodontal lesion, expression in tumor necrosis factor (TNF)-a-stimulated human periodontal ligament cells (HPDLCs). Genipin prevented TNF-a- mediated MMP-1 and MMP-3 productions in HPDLCs. Moreover, genipin could suppress not only extracellular signal-regulated kinase (ERK) and Jun-N-terminal kinase (JNK) phosphorylations but also AMP-activated protein kinase (AMPK) phosphorylation in TNF-a-stimulated HPDLCs. Inhibitors of ERK and AMPK could inhibit both MMP-1 and MMP-3 productions. Moreover, we revealed the ERK inhibitor suppressed AMPK phosphorylation in TNF-a-stimulated HPDLCs. These data provide a new mechanism through which genipin could be used for the treatment of periodontal disease to prevent MMPs expression in periodontal lesion