• Title/Summary/Keyword: tumor necrosis factor-kappaB

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Effects of the cathepsin K inhibitor with mineral trioxide aggregate cements on osteoclastic activity

  • Kim, Hee-Sun;Kim, Soojung;Ko, Hyunjung;Song, Minju;Kim, Miri
    • Restorative Dentistry and Endodontics
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    • v.44 no.2
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    • pp.17.1-17.10
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    • 2019
  • Objectives: Root resorption is an unexpected complication after replantation procedures. Combining anti-osteoclastic medicaments with retrograde root filling materials may avert this resorptive activity. The purpose of this study was to assess effects of a cathepsin K inhibitor with calcium silicate-based cements on osteoclastic activity. Methods: MC3T3-E1 cells were cultured for biocompatibility analyses. RAW 264.7 cells were cultured in the presence of the receptor activator of nuclear factor-kappa B and lipopolysaccharide, followed by treatment with Biodentine (BIOD) or ProRoot MTA with or without medicaments (Odanacatib [ODN], a cathepsin inhibitor and alendronate, a bisphosphonate). After drug treatment, the cell counting kit-8 assay and Alizarin red staining were performed to evaluate biocompatibility in MC3T3-E1 cells. Reverse-transcription polymerase chain reaction, tartrate-resistant acid phosphatase (TRAP) staining and enzyme-linked immunosorbent assays were performed in RAW 264.7 cells to determine the expression levels of inflammatory cytokines, interleukin $(IL)-1{\beta}$, IL-6, tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and prostaglandin E2 (PGE2). Data were analyzed by one-way analysis of variance and Tukey's post hoc test (p < 0.05). Results: Biocompatibility results showed that there were no significant differences among any of the groups. RAW 264.7 cells treated with BIOD and ODN showed the lowest levels of $TNF-{\alpha}$ and PGE2. Treatments with BIOD + ODN were more potent suppressors of inflammatory cytokine expression (p < 0.05). Conclusion: The cathepsin K inhibitor with calcium silicate-based cement inhibits osteoclastic activity. This may have clinical application in preventing inflammatory root resorption in replanted teeth.

Renal protective effects of zingerone in a mouse model of sepsis

  • Lee, Bong-Seon;Lee, Changhun;Yang, Sumin;Ku, Sae-Kwang;Bae, Jong-Sup
    • BMB Reports
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    • v.52 no.4
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    • pp.271-276
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    • 2019
  • Zingerone (ZGR), a phenolic alkanone isolated from ginger, has been reported to possess pharmacological activities such as anti-inflammatory and anti-apoptotic effects. This study was initiated to determine whether ZGR could modulate renal functional damage in a mouse model of sepsis and to elucidate the underlying mechanisms. The potential of ZGR treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured by assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with ZGR resulted in elevated plasma levels of BUN and creatinine, and of protein in urine in mice with CLP-induced renal damage. Moreover, ZGR inhibited nuclear $factor-{\kappa}B$ activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. ZGR treatment also reduced the plasma levels of interleukin-6 and tumor necrosis $factor-{\alpha}$, reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. Our study showed renal suppressive effects of zingerone in a mouse model of sepsis, suggesting that ZGR protects mice against sepsis-triggered renal injury.

Hydrogen sulfide protects from acute kidney injury via attenuating inflammation activated by necroptosis in dogs

  • Wang, Shuang;Liu, XingYao;Liu, Yun
    • Journal of Veterinary Science
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    • v.23 no.5
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    • pp.72.1-72.14
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    • 2022
  • Background: The treatment of acute kidney injury (AKI), a common disease in dogs, is limited. Therefore, an effective method to prevent AKI in veterinary clinics is particularly crucial. Objectives: Hydrogen sulfide (H2S) is the third gaseous signal molecule involved in various physiological functions of the body. The present study investigated the effect of H2S on cisplatin-induced AKI and the involved mechanisms in dogs. Methods: Cisplatin-injected dogs developed AKI symptoms as indicated by renal dysfunction and pathological changes. In the H2S-treated group, 50 mM sodium hydrosulfide (NaHS) solution was injected at 1 mg/kg/h for 30 min before cisplatin injection. After 72 h, tissue and blood samples were collected immediately. We performed biochemical tests, optical microscopy studies, analysis with test kits, quantitative reverse-transcription polymerase chain reaction, and western blot analysis. Results: The study results demonstrated that cisplatin injection increased necroptosis and regulated the corresponding protein expression of receptor interacting protein kinase (RIPK) 1, RIPK3, and poly ADP-ribose polymerase 1; furthermore, it activated the expressions of inflammatory factors, including tumor necrosis factor-alpha, nuclear factor kappa B, and interleukin-1β, in canine kidney tissues. Moreover, cisplatin triggered oxidative stress and affected energy metabolism. Conversely, an injection of NaHS solution considerably reduced the aforementioned changes. Conclusions: In conclusion, H2S protects the kidney from cisplatin-induced AKI through the mitigation of necroptosis and inflammation. These findings provide new and valuable clues for the treatment of canine AKI and are of great significance for AKI prevention in veterinary clinics.

Anti-inflammatory Effects of Myrrh Ethanol Extract on Particulate Matter-induced Skin Injury (미세먼지로 인한 피부 각질 세포 손상에서 몰약 에탄올 추출물의 항염증 효과)

  • Young Hee Jung;Yeun Wha Roh;Myongsoo Chong
    • The Journal of Korean Medicine
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    • v.43 no.3
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    • pp.1-15
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    • 2022
  • Objectives: Myrrh have been used as a traditional remedy to treat infectious and inflammatory diseases. However, it is largely unknown whether myrrh ethanol extract could exhibit the inhibitory activities against particulate matter (PM)-induced skin injury on human keratinocytes, HaCaT cells. Therefore, this study was aimed to investigate the inhibitory activity of myrrh ethanol extract on PM-induced skin injury in HaCaT cells. Methods: To investigate the inhibitory effects of myrrh ethanol extract in HaCaT cells, the skin injury model of HaCaT cells was established under PM treatment. HaCaT keratinocyte cells were pre-treated with myrrh ethanol extract for 1 h, and then stimulated with PM. Then, the cells were harvested to measure the cell viability, reactive oxygen species (ROS), pro-inflammatory cytokines including interleukin (IL) 1-beta, IL-6, and tumor necrosis factor (TNF)-𝛼, hyaluronidase, collagen, MMPs. In addition, we examined the mitogen activated protein kinases (MAPKs) and inhibitory kappa B alpha (I𝜅-B𝛼) as inhibitory mechanisms of myrrh ethanol extract. Results: The treatment of myrrh ethanol extract inhibited the PM-induced cell death and ROS production in HaCaT cells. In addition, myrrh ethanol extract treatment inhibited the PM-induced elevation of IL-1beta, IL-6, and TNF-𝛼. Also, myrrh ethanol extract treatment inhibited the increase of hyaluronidase, MMP and decrease of collagen. Furthermore, myrrh ethanol extract treatment inhibited the activation of MAPKs and the degradation of I𝜅-B𝛼. Conclusions: Our result suggest that treatment of myrrh ethanol extract could inhibit the PM-induced skin injury via deactivation of MAPKs and nuclear factor (NF)-𝜅B in HaCaT cells. This study could suggest that myrrh ethanol extract could be a beneficial agent to prevent skin damage or inflammation.

Impact of peripheral blood mononuclear cells preconditioned by activated platelet supernatant in managing gastric mucosal damage induced by zinc oxide nanoparticles in rats

  • Darwish Badran;Ayman El-Baz El-Agroudy;Amira Adly Kassab;Khaled Saad El-Bayoumi;Zienab Helmy Eldken;Noha Ramadan Mohammed Elswaidy
    • Anatomy and Cell Biology
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    • v.57 no.1
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    • pp.105-118
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    • 2024
  • The world has witnessed tremendous advancements in nano-base applications. Zinc oxide nanoparticles (ZON) are widely used in food industry and medicine. Although their application is of important value, they may cause toxicity to body tissues. Peripheral blood mononuclear cells (PBMCs) proved its efficacy in tissue regeneration especially when it is preconditioned by activated platelet supernatant (APS). The aim of this study is to evaluate the effect of ZON on the gastric mucosa and the therapeutic role of the PBMCs preconditioned by APS in rats. Ten rats were donors and fifty rats were recipients. The recipients were divided into; control group, ZON group (10 mg/kg/day orally for five days) and preconditioned PBMCs group (1×107 once intravenously 24 hours after ZON). Gastric specimens were processed for histological, immunohistochemical, biochemical and quantitative real-time polymerase chain reaction studies. ZON group showed marked structural changes in the gastric mucosa. There was desquamation or deep ulceration of the epithelium. Cytoplasmic vacuoles and pyknotic nuclei were in glandular cells. Reduced proliferating cell nuclear antigen and increased tumor necrosis factor-α were in epithelial cells. There were significant elevation in malondialdahyde and reduction in glutathione, superoxide dismutase, and catalase. Enhancement in mRNA expression of nuclear factor kappa-B and cyclooxygenase-2 was detected. The preconditioned PBMCs group showed significant improvement of all parameters. So, ZON had cytotoxic effects on the gastric mucosa and the preconditioned PBMCs had a therapeutic effect on gastric mucosal damage after ZON.

Inhibitory Effect of Extract of Euonymus alatus (Thunb.) Sieb. on the Production of Inflammatory Cytokines (귀전우(鬼箭羽) 추출물의 염증성세포활성물질 억제효과)

  • Kim, Dae-Hyeon;Kim, Byung-Jin;Park, Kyung-Bae;Lee, Ju-Sung;Sung, Kang-Keyng;Park, Sung-Joo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.2
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    • pp.368-373
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    • 2009
  • The purpose of this study was to investigate the anti-inflammatory effects of water extract from Euonymus alatus (Thunb.) Sieb. (EAS) on the RAW 264.7 cells. To evaluate of anti-inflammatory of EAS, we examined the cytokine productions on lipopolysaccharide (LPS)-induced RAW 264.7 cells and also inhibitory mechanisms using Western blot. EAS reduced LPS-induced production of nitric oxide (NO), interleukin (IL)-1b, IL-6, IL-10 and tumor necrosis factor-a (TNF-a) in RAW 264.7 cells. EAS inhibited the activation of mitogen-activated protein kinases (MAPKs) such as p38, extracelluar signal-regulated kinase (ERK 1/2) and c-Jun NH2-terminal kinase (JNK) but not of inhibitory kappa B a (Ik-Ba) degradation in the LPS-stimulated RAW 264.7 cells. In conclusion, EAS down-regulated LPS-induced NO and cytokines production, which could provide a clinical basis.

Anti-inflammatory Effects of Gagamsoyosan (가감조요산(加減造遙散)의 항염(抗炎) 및 면역반응(免疫反應)에 대한 연구(硏究))

  • Kim, Joo-Yeon;Lee, Soon-Yee;Cho, Han-Baek;Kim, Song-Baeg;Choe, Chang-Min
    • The Journal of Korean Obstetrics and Gynecology
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    • v.21 no.4
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    • pp.17-35
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    • 2008
  • Purpose: It is the purpose of this study to investigate the anti-inflammatory effects of water extract from Gagamsoyosan(GGSYS) on the peritoneal macrophage. Methods: To evaluate anti-inflammatory effects of GGSYS. inflammatory cytokines were measured in lipopolysaccharide(LPS) -stimulated macrophages. Furthermore. the western blot has been done to look into the molecular mechanism. Results: GGSYS did not have any cytotoxicity in the peritoneal macrophages and suppressed production of LPS-induced NO. tumor necrosis factor-alpha (TNF-$\alpha$). interleukin(IL)-1$\beta$. IL-6. IL-12. GGSYS inhibited the activation of extracelluar signal-regulated kinase (ERK1/2). c-Jun N-terminal kinase(JNK), p38 kinase and the degradation of inhibitory kappa B-alpha($I_{k}B-\alpha$) in the LPS-stimulated peritoneal macro phages. GGSYS inhibited LPS-induced endotoxin shock and the production of TNF-$\alpha$. IL-l$\beta$. IL-6 in serum from LPS-stimulated mice. Conclusion: These results suggest that GGSYS may have the anti-inflammatory effect which can inhibit the production of NO and inflammatory cytokines. GGSYS is expected to protect against inflammatory diseases.

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Anti-Inflammatory Effects of Abalone (Haliotis discus hannai) Viscera via Inhibition of ROS Production in LPS-Stimulated RAW 264.7 Cells

  • Shin, Tai-Sun;Choi, Kap Seong;Chun, Jiyeon;Kho, Kang-Hee;Son, Seon Ah;Shim, Sun-Yup
    • Microbiology and Biotechnology Letters
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    • v.50 no.1
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    • pp.22-30
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    • 2022
  • Haliotis discus hannai called abalone, is the valuable marine mollusks and the by-products of abalone processing are viscera. Brownish abalone male viscera (AMV), which have not been reported as having anti-inflammatory effects, was extracted with acetone and fractionated by different six acetone/hexane ratios (0, 10, 20, 30, 40, and 100%) using a silica column via in vitro ABTS and DPPH radical and nitric oxide (NO) production assay-guided fractionation. Among the fractions, the acetone/hexane ratio 40%, A40 exhibited the most potent radical scavenging activities and inhibition of lipopolysaccharide (LPS)-induced NO production without cytotoxicity. A40 inhibited LPS-induced intracellular reactive oxygen species (ROS) production in a dose-dependent manner. Western blot analysis revealed that A40 down-regulated the activation of NF-κB, MAPK (ERK 1/2, p-38, and JNK), and inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. Moreover, this fraction inhibited the generation of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. These results suggested that AMV containing A40 with anti-inflammatory and anti-oxidantive effects, is the effective therapeutic and functional material for treating inflammatory disorders.

Bioactivity-Guided Fraction from Viscera of Abalone, Haliotis discus hannai Suppresses Cellular Basophils Activation and Anaphylaxis in Mice

  • Kap Seong Choi;Tai-Sun Shin;Ginnae Ahn;Shin Hye Kim;Jiyeon Chun;Mina Lee;Dae Heon Kim;Han-Gil Choi;Kyung-Dong Lee;Sun-Yup Shim
    • Journal of Microbiology and Biotechnology
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    • v.34 no.2
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    • pp.379-386
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    • 2024
  • Basophils and mast cells are specialized effector cells in allergic reactions. Haliotis discus hannai (abalone), is valuable seafood. Abalone male viscera, which has a brownish color and has not been previously reported to show anti-allergic activities, was extracted with acetone. Six different acetone/hexane fractions (0, 10, 20, 30, 40, and 100%) were obtained using a silica column via β-hexosaminidase release inhibitory activity-guided selection in phorbol myristate acetate and a calcium ionophore, A23187 (PMACI)-induced human basophils, KU812F cells. The 40% acetone/hexane fraction (A40) exhibited the strongest inhibition of PMACI-induced-β-hexosaminidase release. This fraction dose-dependently inhibited reactive oxygen species (ROS) production and calcium mobilization without cytotoxicity. Western blot analysis revealed that A40 down-regulated PMACI-induced MAPK (ERK 1/2, p-38, and JNK) phosphorylation, and the NF-κB translocation from the cytosol to membrane. Moreover, A40 inhibited PMACI-induced interleukin (IL)-1β, IL-6, and IL-8 production. Anti-allergic activities of A40 were confirmed based on inhibitory effects on IL-4 and tumor necrosis factor alpha (TNF-α) production in compound (com) 48/80-induced rat basophilic leukemia (RBL)-2H3 cells. A40 inhibited β-hexosaminidase release and cytokine production such as IL-4 and TNF-α produced by com 48/80-stimulated RBL-2H3 cells. Furthermore, it's fraction attenuated the IgE/DNP-induced passive cutaneous anaphylaxis (PCA) reaction in the ears of BALB/c mice. Our results suggest that abalone contains the active fraction, A40 is a potent therapeutic and functional material to treat allergic diseases.

Anti-inflammatory effect of barley leaf ethanol extract in LPS-stimulated RAW264.7 macrophage (LPS로 자극한 RAW264.7 대식세포에서 보리순 에탄올 추출물의 항염증 효과)

  • Kim, Mee-Kyung;Kim, Dae-Yong
    • Food Science and Preservation
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    • v.22 no.5
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    • pp.735-743
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    • 2015
  • This study investigated the anti-inflammatory activity of barley leaf extract in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and hairless mice. Pre-treatment with barley leaf extract significantly inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-II (COX-II) in a dose-dependent manner in LPS-stimulated RAW264.7 cells. Barley leaf extract also significantly inhibited the secretion of inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and interleukin-6 (IL-6). Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) were strongly suppressed by barley leaf extract in LPS-stimulated cells. In hairless mice, barley extract significantly decreased the pathological phenotypes of contact dermatitis, such as erythema, edema, and scabs. These results indicate that barley leaf extract has an anti-inflammatory effect and therefore a possible role in the treatment of inflammatory diseases or in functional cosmetics.