• 제목/요약/키워드: Mechanistic study

검색결과 298건 처리시간 0.024초

Formosanin C attenuates lipopolysaccharide-induced inflammation through nuclear factor-κB inhibition in macrophages

  • Yin, Limin;Shi, Chaohong;Zhang, Zhongchen;Wang, Wensheng;Li, Ming
    • The Korean Journal of Physiology and Pharmacology
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    • 제25권5호
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    • pp.395-401
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    • 2021
  • Extended inflammation and cytokine production pathogenically contribute to a number of inflammatory disorders. Formosanin C (FC) is the major diosgenin saponin found in herb Paris formosana Hayata (Liliaceae), which has been shown to exert anti-cancer and immunomodulatory functions. In this study, we aimed to investigate anti-inflammatory activity of FC and the underlying molecular mechanism. RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS) or pretreated with FC prior to being stimulated with LPS. Thereafter, the macrophages were subjected to analysis of the expression levels of pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E2 (PGE), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, as well as two relevant enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The analysis revealed that FC administration blunted LPS-induced production of NO and PGE in a dose-dependent manner, while the expression of iNOS and COX-2 at both mRNA and protein levels was inhibited in LPS-stimulated macrophages pre-treated with FC. Moreover, LPS stimulation upregulated mRNA expression and medium release of TNF-α, IL-1β, and IL-6, whereas this effect was blocked upon FC pre-administration. Mechanistic studies showed that inhibitory effects of FC on LPS-induced inflammation were associated with a downregulation of IκB kinase, IκB, and p65/NF-κB pathway. Taken together, these data suggest that FC possesses an inflammation-suppressing activity, thus being a potential agent for the treatment of inflammation-associated disorders.

Mechanistic investigations on emission characteristics from g-C3N4, gC3N4@Pt and g-C3N4@Ag nanostructures using X-ray absorption spectroscopy

  • Sharma, Aditya;Varshney, Mayora;Chae, Keun Hwa;Won, Sung Ok
    • Current Applied Physics
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    • 제18권11호
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    • pp.1458-1464
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    • 2018
  • An improved method for the preparation of g-$C_3N_4$ is described. Currently, heating (> $400^{\circ}C$) of urea is the common method used for preparing the g-$C_3N_4$. We have found that sonication of melamine in $HNO_3$ solution, followed by washing with anhydrous ethanol, not only reduce the crystallite size of g-$C_3N_4$ but also facilitate intriguing electronic structure and photoluminescence (PL) properties. Moreover, loading of metal (Pt and Ag) nanoparticles, by applying the borohydride reduction method, has resulted in multicolor-emission from g-$C_3N_4$. With the help of PL spectra and local electronic structure study, at C K-edge, N K-edge, Pt L-edge and Ag K-edge by X-ray absorption spectroscopy (XAS), a precise mechanism of tunable luminescence is established. The PL mechanism ascribes the amendments in the transitions, via defect and/or metal states assimilation, between the ${\pi}^*$ states of tris-triazine ring of g-$C_3N_4$ and lone pair states of nitride. It is evidenced that interaction between the C/N 2p and metal 4d/5d orbitals of Ag/Pt has manifested a net detraction in the ${\delta}^*{\rightarrow}LP$ transitions and enhancement in the ${\pi}^*{\rightarrow}LP$ and ${\pi}^*{\rightarrow}{\pi}$ transitions, leading to broad PL spectra from g-$C_3N_4$ organic semiconductor compound.

통증과 우울증의 병합 동물모델에 대한 최신 연구 동향 분석 (A Review on the Pain and Depression Comorbidity Animal Models)

  • 송지혜;국혜정;박병진;김송이;박지연
    • Korean Journal of Acupuncture
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    • 제38권2호
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    • pp.75-99
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    • 2021
  • Objectives : The purpose of this study is to analyze animal behavioral changes and related neurobiological mechanisms in recent studies using animal models with pain and depression. Methods : We conducted database search in Pubmed, NDSL, and EMBASE up to January 2021. Included studies were classified as depression-like behavior observed in pain model, pain-like behavior observed in depression model, and pain and depression comorbidity model. The results of pain- and depression-like behaviors, the changes of neurobiological mechanisms, and the treatment methods such as drugs, natural substance-derived chemicals, or acupuncture were analyzed. Results : We included 124 studies (81 studies in depression-like behavior observed in pain model, 19 studies in pain-like behavior observed in depression model, and 24 studies in pain and depression comorbidity model). Pain and depression comorbidity animal models were induced using various methods by drugs or surgery. Von frey test, a method for evaluating mechanical allodynia was the most commonly used for measuring pain-like behavior and the forced swimming test was the most commonly used for measuring depression-likes behavior. The changes of neurobiological factors, such as decrease of 5-hydroxytryptamine and increase of oxidative stress and pro-inflammation cytokines were generally changed in the frontal cortex, hippocampus, thalamus, and spinal cord in all types of models. For treating pain and depression-like behaviors, various types of drugs such as antidepressant, tranquilizer, analgesic, and natural substance-derived chemicals were used. Acupuncture treatment was used in 4 studies. Conclusions : In the future, more diverse studies on the combined model of pain and depression need to be conducted. In addition, it is necessary to establish a mechanistic basis for the development of various treatments by identifying the common mechanisms of pain and depression.

Anti-nociceptive and anti-inflammatory activities of the essential oil isolated from Cupressus arizonica Greene fruits

  • Fakhri, Sajad;Jafarian, Safoora;Majnooni, Mohammad Bagher;Farzaei, Mohammad Hosein;Mohammadi-Noori, Ehsan;Khan, Haroon
    • The Korean Journal of Pain
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    • 제35권1호
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    • pp.33-42
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    • 2022
  • Background: Cupressus arizonica Greene is a coniferous tree with great importance in fragrance and pharmaceutical industries. Essential oils from C. arizonica (EC) have shown potential antioxidant, and anti-microbial activities. This study aimed at investigating the anti-nociceptive and anti-inflammatory effects/mechanisms of EC. Methods: The EC was evaluated for anti-nociceptive and anti-inflammatory activities on male Wistar rats using a formalin test and carrageenan-induced paw edema, respectively. Also, we pre-treated some of the animals with naloxone and flumazenil in the formalin test to find out the possible contributions of opioid and benzodiazepine receptors to EC anti-nociceptive effects. Finally, gas chromatography/mass spectrometry (GC/MS) analysis was used to identify the EC's constituents. Results: EC in intraperitoneal doses of 0.5 and 1 g/kg significantly decrease the nociceptive responses in both early and late phases of the formalin test. From a mechanistic point of view, flumazenil administration 20 minutes before the most effective dose of EC (1 g/kg) showed a meaningful reduction in the associated anti-nociceptive responses during the early and late phases of the formalin test. Naloxone also reduced the anti-nociceptive role of EC in the late phase. Furthermore, EC at the doses of 1, 0.5, and 0.25 g/kg significantly reduced paw edema from 0.5 hours after carrageenan injection to 4 hours. GC/MS analysis showed that isolated EC is a monoterpene-rich oil with the major presence of α-pinene (71.92%), myrcene (6.37%), δ-3-carene (4.68%), β-pinene (3.71%), and limonene (3.34%). Conclusions: EC showed potent anti-nociceptive and anti-inflammatory activities with the relative involvement of opioid and benzodiazepine receptors.

죽력의 3T3-L1 지방전구세포에서 지방축적 억제 효과 (Suppression of Lipid Accumulation in Differentiating 3T3-L1 Preadipocytes by a Standardized Commercial Juknyeok)

  • 장병철
    • 한방비만학회지
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    • 제22권1호
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    • pp.38-46
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    • 2022
  • Objectives: Juknyeok (JN) is natural liquor extracted from bamboo stems (Phyllostachys bambusoides) and has been used as a traditional Korean medicine for improving vascular function, blood glucose, and treating stroke. Until now, the JN's lipid-lowering effect and underlying mechanism in adipocytes are poorly understood. The aim of this study was to scrutinize the effect of a standardized commercial JN on lipid accumulation during the differentiation of 3T3-L1 preadipocytes. Methods: Lipid and triglyceride (TG) accumulation in differentiating 3T3-L1 preadipocytes were measured by Oil Red O staining and AdipoRed assay, respectively. Cell count analysis was used to ascertain 3T3-L1 cytotoxicity. Immunoblotting and Reverse transcription polymerase chain reaction analysis were used to assess protein and messenger RNA (mRNA) expression levels in 3T3-L1 cells, respectively. Results: Treatment with JN at 25 𝜇l/ml after pH calibration with 6.35 significantly reduced lipid and TG accumulation in differentiating 3T3-L1 preadipocytes without significant cytotoxicity. On mechanistic levels, JN markedly suppressed protein expression levels of CCAAT/enhancer-binding protein (C/EBP)-𝛽 and fatty acid synthase (FAS) during the differentiation of 3T3-L1 preadipocytes. However, JN did not affect the protein expression levels of C/EBP-𝛼, peroxisome proliferator-activated receptor-𝛽/𝛾, and phosphorylation levels of signal transducer and activator of transcription-3/5 in differentiating 3T3-L1 preadipocytes. JN also reduced leptin mRNA expression levels in differentiating 3T3-L1 preadipocytes. Conclusions: JN at 25 𝜇l/ml lowers lipid accumulation and TG content in differentiating 3T3-L1 cells, mediated through the reduced expression levels of C/EBP-𝛽 and FAS.

Hepatitis C Virus Nonstructural Protein 5A Interacts with Immunomodulatory Kinase IKKε to Negatively Regulate Innate Antiviral Immunity

  • Kang, Sang-Min;Park, Ji-Young;Han, Hee-Jeong;Song, Byeong-Min;Tark, Dongseob;Choi, Byeong-Sun;Hwang, Soon B.
    • Molecules and Cells
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    • 제45권10호
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    • pp.702-717
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    • 2022
  • Hepatitis C virus (HCV) infection can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV employs diverse strategies to evade host antiviral innate immune responses to mediate a persistent infection. In the present study, we show that nonstructural protein 5A (NS5A) interacts with an NF-κB inhibitor immunomodulatory kinase, IKKε, and subsequently downregulates beta interferon (IFN-β) promoter activity. We further demonstrate that NS5A inhibits DDX3-mediated IKKε and interferon regulatory factor 3 (IRF3) phosphorylation. We also note that hyperphosphorylation of NS5A mediates protein interplay between NS5A and IKKε, thereby contributing to NS5A mediated modulation of IFN-β signaling. Lastly, NS5A inhibits IKKε-dependent p65 phosphorylation and NF-κB activation. Based on these findings, we propose NS5A as a novel regulator of IFN signaling events, specifically by inhibiting IKKε downstream signaling cascades through its interaction with IKKε. Taken together, these data suggest an additional mechanistic means by which HCV modulates host antiviral innate immune responses to promote persistent viral infection.

백악기 중기 해양 무산소 사건 2 동안의 생지화학적 순환 (Biogeochemical Cycles during the mid-Cretaceous Oceanic Anoxic Event 2)

  • 주영지
    • 한국지구과학회지
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    • 제43권5호
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    • pp.569-578
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    • 2022
  • 백악기 중기, 세노마눔절-투로니아절에 발생한 해양 무산소 사건인 Oceanic Anoxic Event 2 (OAE2)는 다량의 유기물을 포함한 흑색셰일이 전세계적으로 퇴적된 단기간의 탄소 순환 교란 사건이다. 백악기 후기의 온실 지구의 환경(높은 CO2농도, 고해수면, 해양의 무산소 환경 확장)은 탄소, 황 및 여타 주요 원소의 생지화학 순환의 교란과 밀접하게 상호 작용하였다. 1970년대 최초 명명 이후 동위원소를 포함한 화학적 지시자 연구가 활발하게 진행되었으며, 그 결과 화산 활동과 해양 표층의 유기물 생산 증가가 무산소 환경 발달의 주된 원인으로 여겨진다. 본 논평에서는 OAE2의 기작을 탄소 및 황, 미량 금속원소의 순환을 중심으로 살펴보고자 한다.

Cordycepin from Medicinal Fungi Cordyceps militaris Mitigates Inflammaging-Associated Testicular Damage via Regulating NF-κB/MAPKs Signaling in Naturally Aged Rats

  • Kopalli, Spandana Rajendra;Cha, Kyu-Min;Cho, Jae Youl;Kim, Si-Kwan;Koppula, Sushruta
    • Mycobiology
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    • 제50권1호
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    • pp.86-95
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    • 2022
  • Inflammaging in male reproductive organs covers a wide variety of problems, including sexual dysfunction and infertility. In this study, the beneficial effects of cordycepin (COR), isolated from potential medicinal fungi Cordyceps militaris, in aging-associated testicular inflammation and serum biochemical changes in naturally aged rats were investigated. Male Sprague Dawley rats were divided into young control (YC), aged control (AC), and COR (5, 10, and 20 mg/kg) treated aged rat groups. Aging-associated serum biochemical changes and inflammatory parameters were analyzed by biochemical assay kits, Western blotting, and real-time RT-PCR. Results showed a significant (p < 0.05) alteration in the total blood cell count, lipid metabolism, and liver functional parameters in AC group when compared with YC group. However, COR-treated aged rats ameliorated the altered biochemical parameters significantly (p < 0.05 and p < 0.01 at 5, 10, and 20 mg/kg, respectively). Furthermore, the increase in the expression of inflammatory mediators (COX-2, interleukin (IL)-6, IL-1β, and tissue necrosis factor-alpha) in aged rat testis was significant (p < 0.05) when compared with YC group. Treatment with COR at 20 mg/kg to aged rats attenuated the increased expression of inflammatory mediators significantly (p < 0.05). Mechanistic studies revealed that the potential attenuating effects exhibited by COR in aged rats was mediated by regulation of NF-κB activation and MAPKs (c-Jun N-terminal kinase, extracellular signal-regulated kinase 1/2, and p38) signaling. In conclusion, COR restored the altered serum biochemical parameters in aged rats and ameliorated the aging-associated testicular inflammation proving the therapeutic benefits of COR targeting inflammaging-associated male sexual dysfunctions.

Anti-inflammatory Effect of the Hedgehog Skin Extracts on LPS-Stimulated RAW 264.7 Cells

  • Kim, Tae Yeon;Jo, Na Young;Leem, Kang Hyun
    • 대한본초학회지
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    • 제33권3호
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    • pp.19-24
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    • 2018
  • Objectives : Hedgehog skin is one of the animal medicines in Traditional Korean Medicine for hematochezia and hemorrhoids. In this study, we examined cytotoxicity and anti-inflammatory effects. Methods : Cytotoxicity of hedgehog skin extracts was measured by MTT assay in vitro. We investigated the inhibition of lipopolysaccharide (LPS) stimulated nitric oxide (NO) production in RAW 264.7 cells. The phosphorylation of mitogen-activated protein kinases (MAPKs) was measured by western blot. And we observed the effect of hedgehog skin extracts on the expression of IL-6 genes using real time PCR. Results : As a result of MTT assay for cytotoxicity, there were no significant differences between non-treatment group and hedgehog skin extracts treatment groups. $500{\mu}g/m{\ell}$ of hedgehog skin extracts treatment significantly decreased nitric oxide production in comparison with non-treatment in LPS-induced RAW 264.7 cells. In measurement of the phosphorylation of MAPKs using western blot analysis, LPS stimulation increased the phosphorylation of MAPKs and $500{\mu}g/m{\ell}$ of hedgehog skin extracts treatment decreased the phosphorylation of ERK1, ERK2 and p38 significantly. But there were no significant differences the phosphorylation of JNK1 and JNK2. As a result of confirmation of the IL-6 mRNA gene expression using real time PCR, IL-6 mRNA gene expressions were significantly decreased in $50{\mu}g/m{\ell}$, $100{\mu}g/m{\ell}$ and $500{\mu}g/m{\ell}$ hedgehog skin extracts treated groups by comparison with non-treatment group. Conclusion : These results could provide a mechanistic explanation for the anti-inflammatory effects of the hedgehog skin.

Bitter taste receptors protect against skin aging by inhibiting cellular senescence and enhancing wound healing

  • Chung, Min Gi;Kim, Yerin;Cha, Yeon Kyung;Park, Tai Hyun;Kim, Yuri
    • Nutrition Research and Practice
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    • 제16권1호
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    • pp.1-13
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    • 2022
  • BACKGROUND/OBJECTIVES: Bitter taste receptors are taste signaling pathway mediators, and are also expressed and function in extra-gustatory organs. Skin aging affects the quality of life and may lead to medical issues. The purpose of this study was to better understand the anti-skin aging effects of bitter taste receptors in D-galactose (D-gal)-induced aged human keratinocytes, HaCaT cells. MATERIALS/METHODS: Expressions of bitter taste receptors in HaCaT cells and mouse skin tissues were examined by polymerase chain reaction assay. Bitter taste receptor was overexpressed in HaCaT cells, and D-gal was treated to induce aging. We examined the effects of bitter taste receptors on aging by using β-galactosidase assay, wound healing assay, and Western blot assay. RESULTS: TAS2R16 and TAS2R10 were expressed in HaCaT cells and were upregulated by D-gal treatment. TAS2R16 exerted protective effects against skin aging by regulating p53 and p21, antioxidant enzymes, the SIRT1/mechanistic target of rapamycin pathway, cell migration, and epithelial-mesenchymal transition markers. TAS2R10 was further examined to confirm a role of TAS2R16 in cellular senescence and wound healing in D-gal-induced aged HaCaT cells. CONCLUSIONS: Our results suggest a novel potential preventive role of these receptors on skin aging by regulating cellular senescence and wound healing in human keratinocyte, HaCaT.