• Title/Summary/Keyword: inhibiting factor

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Anthocyanins Inhibits Oxidative Injury in Human Retinal Pigment Epithelial ARPE-19 Cells via Activating Heme Oxygenase-1

  • Cheol Park;Hyun Hwangbo;Sung Ok Kim;Jeong Sook Noh;Shin-Hyung Park;Su Hyun Hong;Sang Hoon Hong;Gi-Young Kim;Yung Hyun Choi
    • Journal of Microbiology and Biotechnology
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    • v.34 no.3
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    • pp.596-605
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    • 2024
  • Anthocyanins belong to phenolic pigments and are known to have various pharmacological activities. This study aimed to investigate whether anthocyanins could inhibit hydrogen peroxide (H2O2)-induced oxidative damage in human retinal pigment epithelial ARPE-19 cells. Our results indicated that anthocyanins suppressed H2O2-induced genotoxicity, while inhibiting reactive oxygen species (ROS) production and preserving diminished glutathione. Anthocyanins also suppressed H2O2-induced apoptosis by reversing the Bcl-2/Bax ratio and inhibiting caspase-3 activation. Additionally, anthocyanins attenuated the release of cytochrome c into the cytosol, which was achieved by interfering with mitochondrial membrane disruption. Moreover, anthocyanins increased the expression of heme oxygenase-1 (HO-1) as well as its activity, which was correlated with the phosphorylation and nuclear translocation of nuclear factor-erythroid-2 related factor 2 (Nrf2). However, the cytoprotective and anti-apoptotic effects of anthocyanins were significantly attenuated by the HO-1 inhibitor, demonstrating that anthocyanins promoted Nrf2-induced HO-1 activity to prevent ARPE-19 cells from oxidative stress. Therefore, our findings suggest that anthocyanins, as Nrf2 activators, have potent ROS scavenging activity and may have the potential to protect ocular injury caused by oxidative stress.

Protein tyrosine phosphatase PTPN21 acts as a negative regulator of ICAM-1 by dephosphorylating IKKβ in TNF-α-stimulated human keratinocytes

  • Cho, Young-Chang;Kim, Ba Reum;Cho, Sayeon
    • BMB Reports
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    • v.50 no.11
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    • pp.584-589
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    • 2017
  • Intercellular adhesion molecule-1 (ICAM-1), which is induced by tumor necrosis factor (TNF)-${\alpha}$, contributes to the entry of immune cells into the site of inflammation in the skin. Here, we show that protein tyrosine phosphatase non-receptor type 21 (PTPN21) negatively regulates ICAM-1 expression in human keratinocytes. PTPN21 expression was transiently induced after stimulation with TNF-${\alpha}$. When overexpressed, PTPN21 inhibited the expression of ICAM-1 in HaCaT cells but PTPN21 C1108S, a phosphatase activity-inactive mutant, failed to inhibit ICAM-1 expression. Nuclear factor-${\kappa}B$ (NF-${\kappa}B$), a key transcription factor of ICAM-1 gene expression, was inhibited by PTPN21, but not by PTPN21 C1108S. PTPN21 directly dephosphorylated phospho-inhibitor of ${\kappa}B$ ($I{\kappa}B$)-kinase ${\beta}$ ($IKK{\beta}$) at Ser177/181. This dephosphorylation led to the stabilization of $I{\kappa}B{\alpha}$ and inhibition of NF-${\kappa}B$ activity. Taken together, our results suggest that PTPN21 could be a valuable molecular target for regulation of inflammation in the skin by dephosphorylating p-$IKK{\beta}$ and inhibiting NF-${\kappa}B$ signaling.

Suppression of the TRIF-Dependent Signaling Pathway of Toll-Like Receptors by Isoliquiritigenin in RAW264.7 Macrophages

  • Park, Se-Jeong;Song, Ho-Yeon;Youn, Hyung-Sun
    • Molecules and Cells
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    • v.28 no.4
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    • pp.365-368
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    • 2009
  • Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens and initiating innate immune responses. The stimulation of TLRs by microbial components triggers the activation of myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-${\beta}$ (TRIF)-dependent downstream signaling pathways. Isoliquiritigenin (ILG), an active ingredient of Licorice, has been used for centuries to treat many chronic diseases. ILG inhibits the MyD88-dependent pathway by inhibiting the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether ILG inhibits the TRIF-dependent pathway. To evaluate the therapeutic potential of ILG, we examined its effect on signal transduction via the TRIF-dependent pathway of TLRs induced by several agonists. ILG inhibited nuclear factor-${\kappa}B$ and interferon regulatory factor 3 activation induced by lipopolysaccharide or polyinosinic-polycytidylic acid. ILG inhibited the lipopolysaccharide-induced phosphorylation of interferon regulatory factor 3 as well as interferon-inducible genes such as interferon inducible protein-10, and regulated activation of normal T-cell expressed and secreted (RANTES). These results suggest that ILG can modulate TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression.

The Anti-inflammatory Mechanism of Pu-erh Tea via Suppression the Activation of NF-κB/HIF-1α in LPS-stimulated RAW264.7 Cells

  • Su-Jin Kim
    • Biomedical Science Letters
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    • v.29 no.2
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    • pp.58-65
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    • 2023
  • Pu-erh tea, a popular and traditional Chinese tea, possesses various health-promoting effects, including inhibiting tumor cell progression and preventing type II diabetes and neurodegenerative disorders. However, the precise anti-inflammatory mechanisms are not well understood. In present study, we elucidated the anti-inflammatory mechanism of Pu-erh tea in lipopolysaccharide (LPS)-activated RAW264.7 cells. We explored the effects of Pu-erh tea on the levels of inflammatory-related genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) in LPS-activated RAW264.7 cells. Moreover, we investigated its regulatory effects on nuclear factor-kappa B (NF)-κB and hypoxia-inducible-factor (HIF)-1α activation. The findings of this study demonstrated that Pu-erh tea inhibited the LPS-increased inflammatory cytokines and PGE2 release, as well as COX-2 and iNOS expression. Moreover, we confirmed that the anti-inflammatory mechanism of Pu-erh tea occurs via the inhibition of NF-κB and HIF-1α activation. Conclusively, these findings provide experimental evidence that Pu-erh tea may be useful candidate in the treatment of inflammatory-related diseases.

Recent Updates on Acetaminophen Hepatotoxicity: The Role of Nrf2 in Hepatoprotection

  • Gum, Sang Il;Cho, Min Kyung
    • Toxicological Research
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    • v.29 no.3
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    • pp.165-172
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    • 2013
  • Acetaminophen (APAP) known as paracetamol is the main ingredient in Tylenol, which has analgesic and anti-pyretic properties. Inappropriate use of APAP causes major morbidity and mortality secondary to hepatic failure. Overdose of APAP depletes the hepatic glutathione (GSH) rapidly, and the metabolic intermediate leads to hepatocellular death. This article reviews the mechanisms of hepatotoxicity and provides an overview of current research studies. Pharmacokinetics including metabolism (activation and detoxification), subsequent transport (efflux)-facilitating excretion, and some other aspects related to toxicity are discussed. Nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated gene battery plays a critical role in the multiple steps associated with the mitigation of APAP toxicity. The role of Nrf2 as a protective target is described, and potential natural products inhibiting APAP toxicity are outlined. This review provides an update on the mechanism of APAP toxicity and highlights the beneficial role of Nrf2 and specific natural products in hepatoprotection.

Licochalcone B Exhibits Anti-inflammatory Effects via Modulation of NF-κB and AP-1

  • Kim, Jin-Kyung;Jun, Jong-Gab
    • Biomedical Science Letters
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    • v.21 no.4
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    • pp.218-226
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    • 2015
  • The present study investigated the mechanisms of licochalcone B (LicB)-mediated inhibition of the inflammatory response in murine macrophages. RAW264.7 murine macrophages were cultured in the absence or presence of lipopolysacharide (LPS) with LicB. LicB suppressed the generation of nitric oxide and the pro-inflammatory cytokines interleukin (IL)-$1{\beta}$, IL-6 and tumor necrosis factor-${\alpha}$. LicB also inhibited the expression of mRNA for inducible nitric oxide synthase and pro-inflammatory cytokines induced by LPS. Moreover, LicB inhibited nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and activator protein-1 translocation into the nucleus in a dose-dependent manner. Thus, LicB mainly exerts its anti-inflammatory effects by inhibiting the LPS-induced NF-${\kappa}B$ and activator protein-1 signaling pathways in macrophages, which subsequently diminishes the expression and release of various inflammatory mediators. LicB shows promise as a therapeutic agent in inflammatory diseases.

Green Employee Empowerment? Driving and Inhibiting Factors for Green Employee Performance

  • ADI, Nyoman Rasmen;MULYADI, Made;SETINI, Made;ASTAWA, Nengah Dasi
    • The Journal of Asian Finance, Economics and Business
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    • v.8 no.5
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    • pp.293-302
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    • 2021
  • Being able to survive during the Covid19 pandemic is a big task for a company, as such, empowerment of employees is a must. The sample in this study was 300 employees who worked in Spas throughout Bali. The sampling technique was purposive sampling. Data analysis was using SEM and SMARTS as data processing. The results showed that green communication, namely communication that occurs between employees, superiors, and the environment, has a very good influence on the sustainability of employee performance. To become green management, a green organizational commitment that cares about the safety of employee health and the environment is an important factor as motivation in green dedication or positive employee productivity, but communication between work actors and justice is also a motivating factor. Work safety and job security for employees empower employees (which is a green line), especially for freelance work organizations so that further research in subsequent studies can make samples in a more varied industrial sector.

Inhalation of panaxadiol alleviates lung inflammation via inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells

  • Yifan Wang;Hao Wei;Zhen Song;Liqun Jiang;Mi Zhang;Xiao Lu;Wei Li;Yuqing Zhao;Lei Wu;Shuxian Li;Huijuan Shen;Qiang Shu;Yicheng Xie
    • Journal of Ginseng Research
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    • v.48 no.1
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    • pp.77-88
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    • 2024
  • Background: Lung inflammation occurs in many lung diseases, but has limited effective therapeutics. Ginseng and its derivatives have anti-inflammatory effects, but their unstable physicochemical and metabolic properties hinder their application in the treatment. Panaxadiol (PD) is a stable saponin among ginsenosides. Inhalation administration may solve these issues, and the specific mechanism of action needs to be studied. Methods: A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophage inflammation model, and a coculture model of epithelial cells and macrophages were used to study the effects and mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy and mechanism were verified in a human BALF cell model. Results: Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, including inflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose of inhalation was much lower than that of intragastric administration under the same therapeutic effect, which may be related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysis and verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibiting TNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosis and promote proliferation. Conclusion: PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lung inflammation.

Effect of Atrial Natriuretic Factor on the Renal Function and Renin Release in Unanesthetized Rabbit (무마취 가토 신장기능에 미치는 Atrial Natriuretic Factor의 영향)

  • Lee, June-K.;Cho, Kyung-W.
    • The Korean Journal of Physiology
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    • v.20 no.1
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    • pp.103-124
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    • 1986
  • Since it has been suggested that atrial receptor may be involved in the mechanism of extracellular volume regulation, it was shown that the granularity of atrial cardiocytes can be changed by water and salt depletion, and that an extract of cardiac atrial tissue, when injected intravenously into anesthetized rats, was shown to cause a large and rapid increase in renal excretion of sodium. Various natriuretic peptides were isolated and synthetized, and the effects were investigated by many workers. Most studies, however, have been carried out under anesthesia and there have teen some controversies over direct effect of the factor on the renal function. Therefore, it was attempted in this study to access the effects of an atrial extract and a synthetic natriuretic factor in unanesthetized rabbits. Intrarenal arterial infusion of atrial extract caused a rapid increase of urinary volume and excretion of sodium. Glomerular filtration rate and renal plasma flow were both increased with no change in filtration fraction. The ventricular extract produced no change in urinary excretion of electrolytes, nor in renal hemodynamics. Intrarenal infusion of synthetic atrial natriuretic factor caused increases of renal excretory rate of sodium, chloride and potassium, and $FE_{Na}$. Glomerular filtration rate, renal plasma flow increased. And free water clearance also increased. Accentuated excretory function correlated well with increased glomerular filtration rate and renal plasma flow during infusion and for 10 minutes following the cessation of the infusion. Renin secretion rate decreased during constant infusion of atrial natriuretic factor. However, no correlation was found with the changes in glomerular filtration rate, renal plasma flow, or urinary excretion of sodium. These results suggest that atrial extract or atrial natriuretic factor induces changes in renal hemodynamics, as in excretion of electrolytes either indirectly through hemodynamic changes or directly by inhibiting tubular reabsorption. At the same time, renin secretory function is affected by the factor possibly through an unknown mechanism.

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Sensitivity of Colletotrichum spp. Isolated from Red-pepper to Sterol Biosynthesis Inhibiting-Fungicides and Their Field Fitness (고추에서 분리한 탄저병균의 스테롤 생합성 저해 살균제에 대한 감수성 반응과 포장 적응력)

  • Park, Sung-Woo;Kim, Joon-Tae;Kim, Jae-Jung;Kim, Seung-Tae
    • Research in Plant Disease
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    • v.8 no.4
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    • pp.239-244
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    • 2002
  • Among 34 isolates of Colletotrichum spp., 20 from red pepper and 14 from apple, only one isolate 2001-45 was identified as the isolate resistant to sterol biosynthesis inhibiting fungicides. EC$_{50}$ values of the isolate 2001-45 were 153.5, 42.7, 34.0, and 17.1 $\mu\textrm{g}$/ml for myclobutanil, tebuconazole, hexaconazole and nuarimol, respectively, The resistance factor of the isolate 2001-45 against the other isolate 2001-44 to 4 above fungicides was ranged from 17 to 57. However, EC$_{50}$ value of the 2001-45 for prochloraz was 0.07 $\mu\textrm{g}$/ml, which was lower than those of the 2001-44 and the isolate JC24. For the fitness test of the 2001-45, mycelial growth, sporulation on PDA and pathogenicity on fruits were investigated. No difference in mycelial growth was found between 2001-45 and 2001-44, but great difference in sporulation. No symptom was developed by 2001-45 even by wound inoculation of pepper fruit. Therefore, this study indicated that the isolate 2001-45 was inferior to the other isolates in the fitness, although the isolate 2001-45 was highly resistant to sterol biosynthesis inhibiting fungicides.