• 제목/요약/키워드: Release mechanism

검색결과 899건 처리시간 0.032초

Oxymatrine inhibits the pyroptosis in rat insulinoma cells by affecting nuclear factor kappa B and nuclear factor (erythroid-derived 2)-like 2 protein/heme oxygenase-1 pathways

  • Gao, Jingying;Xia, Lixia;Wei, Yuanyuan
    • The Korean Journal of Physiology and Pharmacology
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    • 제26권3호
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    • pp.165-174
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    • 2022
  • As the mechanism underlying glucose metabolism regulation by oxymatrine is unclear, this study investigated the effects of oxymatrine on pyroptosis in INS-1 cells. Flow cytometry was employed to examine cell pyroptosis and reactive oxygen species (ROS) production. Cell pyroptosis was also investigated via transmission electron microscopy and lactate dehydrogenase (LDH) release. Protein levels were detected using western blotting and interleukin (IL)-1β and IL-18 secretion by enzyme-linked immunosorbent assay. The caspase-1 activity and DNA-binding activity of nuclear factor kappa B (NF-κB) and nuclear factor (erythroid-derived 2)-like 2 protein (Nrf2) were also assessed. In the high glucose and high fat-treated INS-1 cells (HG + PA), the caspase-1 activity and LDH content, as well as Nod-like receptor family pyrin domain containing 3, Gsdmd-N, caspase-1, apoptosis-associated speck-like protein containing a CARD, IL-1β, and IL-18 levels were increased. Moreover, P65 protein levels increased in the nucleus but decreased in the cytoplasm. Oxymatrine attenuated these effects and suppressed high glucose and high fat-induced ROS production. The increased levels of nuclear Nrf2 and heme oxygenase-1 (HO-1) in the HG + PA cells were further elevated after oxymatrine treatment, whereas cytoplasmic Nrf2 and Keleh-like ECH-associated protein levels decreased. Additionally, the elevated transcriptional activity of p65 in HG + PA cells was reduced by oxymatrine, whereas that of Nrf2 increased. The results indicate that the inhibition of pyroptosis in INS-1 cells by oxymatrine, a key factor in its glucose metabolism regulation, involves the suppression of the NF-κB pathway and activation of the Nrf2/HO-1 pathway.

SKF96365 impedes spinal glutamatergic transmission-mediated neuropathic allodynia

  • Qiru Wang;Yang Zhang;Qiong Du;Xinjie Zhao;Wei Wang;Qing Zhai;Ming Xiang
    • The Korean Journal of Physiology and Pharmacology
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    • 제27권1호
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    • pp.39-48
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    • 2023
  • Spinal nerve injury causes mechanical allodynia and structural imbalance of neurotransmission, which were typically associated with calcium overload. Storeoperated calcium entry (SOCE) is considered crucial elements-mediating intracellular calcium homeostasis, ion channel activity, and synaptic plasticity. However, the underlying mechanism of SOCE in mediating neuronal transmitter release and synaptic transmission remains ambiguous in neuropathic pain. Neuropathic rats were operated by spinal nerve ligations. Neurotransmissions were assessed by whole-cell recording in substantia gelatinosa. Immunofluorescence staining of STIM1 with neuronal and glial biomarkers in the spinal dorsal horn. The endoplasmic reticulum stress level was estimated from qRT-PCR. Intrathecal injection of SOCE antagonist SKF96365 dose-dependently alleviated mechanical allodynia in ipsilateral hind paws of neuropathic rats with ED50 of 18 ㎍. Immunofluorescence staining demonstrated that STIM1 was specifically and significantly expressed in neurons but not astrocytes and microglia in the spinal dorsal horn. Bath application of SKF96365 inhibited enhanced miniature excitatory postsynaptic currents in a dosage-dependent manner without affecting miniature inhibitory postsynaptic currents. Mal-adaption of SOCE was commonly related to endoplasmic reticulum (ER) stress in the central nervous system. SKF96365 markedly suppressed ER stress levels by alleviating mRNA expression of C/ EBP homologous protein and heat shock protein 70 in neuropathic rats. Our findings suggested that nerve injury might promote SOCE-mediated calcium levels, resulting in long-term imbalance of spinal synaptic transmission and behavioral sensitization, SKF96365 produces antinociception by alleviating glutamatergic transmission and ER stress. This work demonstrated the involvement of SOCE in neuropathic pain, implying that SOCE might be a potential target for pain management.

관상동맥이완과 혈소판응집에 대한 GS283과 GS386의 약리작용기전에 관한 연구 (Pharmacological Mechanism of Action of GS283 and GS386 on Human Platelet and Pig Coronary Artery)

  • 장기철;이회영;이균우;구의본;강영진;이영수
    • Biomolecules & Therapeutics
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    • 제5권3호
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    • pp.239-245
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    • 1997
  • Trimetoquinol (TMQ) and its analogs are known to have thromboxane $A_2$ antagonistic action. We also reported that GS389, chemically similar to TMQ, has competitive antagonistic action in rat aorta and human platelets. In the present study, we investigated the pharmacological characteristics of GS283 and GS 386, analogs of GS389, using vascular smooth muscle, human platelets and rat brain homogenates. In isolated pig coronary artery (PCA), both of GS283 and GS386 relaxed U46619-contracted rings in concentration dependent manner. Pretreatment with several concentrations of GS283 and GS386 shifted the dose-response curves to the right, and reduced of maximum contration dose-dependently. Furthermore, GS283 and GS386 strongly inhibited $Ca^{2+}$ -induced contraction in the PCA. In human platelets, U46619- and A23187-induced platelet aggregation was inhibited by GS283 and GS386, concentration-dependently. Anti-platelet aggregation was related to the compound\`s ability to inhibit ATP release at each stimulation. In rat brain homogenates, receptor-binding assay resulted that both GS283 and GS386 have a relative affinity to $\alpha$-adrenergic receptor. Taken together. we concluded that the mechamism of action of GS283 and GS86 is not related with in TXA$_2$ receptor but concerned with calcium antagonistic action and a-blocking action.n.

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Ovastacin: An oolemma protein that cleaves the zona pellucida to prevent polyspermy

  • Inyoung Kang;Myoungjoo Koo;Hyejin Yoon;Beom Seok Park;Jin Hyun Jun;Jaewang Lee
    • Clinical and Experimental Reproductive Medicine
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    • 제50권3호
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    • pp.154-159
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    • 2023
  • Monospermy occurs in the process of normal fertilization where a single sperm fuses with the egg, resulting in the formation of a diploid zygote. During the process of fertilization, the sperm must penetrate the zona pellucida (ZP), the outer layer of the egg, to reach the egg's plasma membrane. Once a sperm binds to the ZP, it undergoes an acrosomal reaction, which involves the release of enzymes from the sperm's acrosome that help it to penetrate the ZP. Ovastacin is one of the enzymes that is involved in breaking down the ZP. Studies have shown that ovastacin is necessary for the breakdown of the ZP and for successful fertilization to occur. However, the activity of ovastacin is tightly regulated to ensure that only one sperm can fertilize the egg. One way in which ovastacin helps to prevent polyspermy (the fertilization of an egg by more than one sperm) is by rapidly degrading the ZP after a sperm has penetrated it. This makes it difficult for additional sperm to penetrate the ZP and fertilize the egg. Ovastacin is also thought to play a role in the block to polyspermy, a mechanism that prevents additional sperm from fusing with the egg's plasma membrane after fertilization has occurred. In summary, the role of ovastacin in monospermic fertilization is to help ensure that only one sperm can fertilize the egg, while preventing polyspermy and ensuring successful fertilization.

The Semiconductor Industry and High-Quality Economic Development: An International Perspective

  • Eun-Young Nam;Xiao-Long Wang
    • Journal of Korea Trade
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    • 제26권7호
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    • pp.77-92
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    • 2022
  • Purpose - This paper is an empirical investigation of the mediation effect of innovation activity in industry transformation considering the relationship between the semiconductor industry and high-quality economic development. The research questions are whether the semiconductor industry drives high-quality economic development and if so, what is the semiconductor industry's role in high-quality development? We found that the semiconductor industry has clearly improved the quality of economic development, and its comparative advantage has significantly increased per capita national incomes. Furthermore, innovation activity proved to be an intermediary factor for the semiconductor industry to promote high-quality economic development. The world economy should aim to reasonably develop the international semiconductor industry and cultivate innovation markets. Design/methodology - Our empirical model considers the relationship between the semiconductor industry, innovation activity, and high-quality economic development. We constructed an analysis framework based on data from 199 World Bank economies between 1995 and 2019, and we used a mediation effect method to calculate the total effect of the semiconductor industry on promoting high-quality economic development, the indirect effect of the semiconductor industry on promoting innovation activity, and the mediation effect of these innovation activities on the promotion of high-quality economic development. Findings - The results show that the semiconductor industry has significantly promoted high-quality economic development. This is true even after the robustness test of grouping and alternative variables was applied. An analysis of the mechanism shows that promoting patents, scientific research, efficient government, and urban management innovation are important mechanisms for the semiconductor industry to release high-quality development dividends. Originality/value - Although it has been shown that specific industries like semiconductors can affect high-quality economic development through industrial upgrading, few researchers have attempted to empirically test the impact of the semiconductor industry on high-quality economic development. In this paper, we use a mediation effect model, alternative variables and a grouping test to find the internal mechanisms of the comparative advantage of the semiconductor industry in high-quality economic development from the perspective of innovation activity.

육미지황탕가감방(六味地黃湯加減方)이 멜라닌 생성 및 유전자발현에 미치는 영향 (The Effect of Yukmijihwangtang -gagambang (YMG) on Melanin Synthesis and Gene Expression)

  • 김진경;유동열
    • 대한한방부인과학회지
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    • 제22권3호
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    • pp.66-82
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    • 2009
  • Purpose: This study was performed to elucidate the inhibitory effect of Yukmijihwangtang-gagambang (YMG) on melanin synthesis in B16F10 mouse melanoma cell. Methods: To demonstrate the inhibitory effects of YMG on melanin synthesis, we measured the amount of released and produced melanin in B16F10 melanoma cell. Also, we evaluated tyrosinase-activity in vitro as well as in B16F10 melanoma cell. And to investigate the action mechanism we assessed the gene expressions of tyrosinase, TRP-1, TRP-2, MMP-2, PKA, PKC${\beta}$, ERK-1 ERK-2, AKT-1 and MITF in B16F10 melanoma cells. Results: 1. YMG decreased the release and production of melanin in B16F10 melanoma cells. 2. YMG decreased tyrosinase activity in vitro and in B16F10 melanoma cells. 3. YMG decreased the expression of tyrosinase, TRP-1, TRP-2, PKA, PKC${\beta}$ and MMP-2 in B16F10 melanoma cells. 4. YMG increased the expression of ERK-1, ERK-2, and AKT-1 in B16F10 melanoma cells. 5. YMG decreased the expression of MITF in B16F10 melanoma cells. Conclusion: From these results, we suggest that YMG inhibit melanin synthesis via tyrosinase inhibition and regulation of the gene expression in B16F10 melanoma cells.

육미지황탕합이지환가감방(六味地黃湯合二至丸加減方)이 멜라닌 생성과 관련 유전자 발현에 미치는 영향 (The Effect of Yukmijihwangtanghapyijihwangagambang on Melanin Synthesis and Related Gene Expressions in B16F10 Mouse Melanoma Cell)

  • 신선미;유동열
    • 대한한방부인과학회지
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    • 제22권4호
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    • pp.28-45
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    • 2009
  • Purpose: This study was performed to elucidate the inhibitory effect of Yukmijihwangtanghapyijihwangagambang (YM) on melanin synthesis in B16F10 melanoma cells. Methods: To demonstrate the inhibitory effects of YM on melanin synthesis, we measured the amount of released and produced melanin in B16F10 melanoma call. Also, we evaluated tyrosinase-activity in vitro as well as in B16F10 melanoma call. And to investigate the action mechanism, we assessed the gene expression of tyrosinase, TRP-1, TRP-2, PKA, $PKC{\beta}$, ERK-1 ERK-2, AKT-1 and MITF in B16F10 melanoma call. Results: 1. YM decreased the release and production of melanin in B16F10 melanoma cells. 2. YM decreased tyrosinase activity in vitro and in B16F10 melanoma cells. 3. YM decreased the expression of tyrosinase, TRP-1, TRP-2 in B16F10 melanoma cells. 4. YM decreased the expression of PKA, $PKC{\beta}$ in B16F10 melanoma cells. 5. YM increased the expression of ERK-1, ERK-2 and AKT-1 in B16F10 melanoma cells. 6. YM decreased the expression of MITF in B16F10 melanoma cells. Conclusion: From these results, it may be concluded that YM has antimelanogenetic effects.

Estimation of GHG emissions and footprint from Daecheong Reservoir using G-res Tool

  • Min, Kyeongseo;Kim, Dongmin;Chung, Sewoong
    • 한국수자원학회:학술대회논문집
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    • 한국수자원학회 2022년도 학술발표회
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    • pp.209-209
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    • 2022
  • Reservoirs play a key role in the carbon cycle between terrestrial and marine systems and are pathways that release greenhouse gases(GHGs), CO2, CH4, and N2O, into the atmosphere by decomposing organic matters. Developed countries have been actively conducting research on carbon emission assessment of dam reservoirs for over 10 years under the leadership of UNESCO/IHA, but associated research is very rare in Korea. In particular, the GHGs footprint evaluation, which calculates the change in net carbon emission considering the watershed environment between pre- and post- impoundment, is very important in evaluating the carbon emission of hydroelectric dams. The objective of this study was to estimate the GHG emissions and footprints in Daecheong Reservoir using the G-res Tool, an online platform developed by UNESCO/IHA. The G-res Tool estimates CO2 and CH4 emissions in consideration of diverse pathway fluxes of GHGs from the reservoir and characterizes changes in GHG fluxes over 100 years based on the expected lifetime of the dam. The input required to use the G-res Tool include data related to watersheds, reservoirs, and dams, and most were collected through the government's public portal. As a result of the study, the GHG footprint of Daecheong Reservoir was estimated to be 93 gCO2eq/m2/yr, which is similar to that of other reservoirs around the world in the same climate zone. After impoundment, the CH4 diffusion emission from the reservoir was 73 gCO2eq/m2/yr, also similar to those of the overseas reservoirs, but the CH4 bubbling emission, degassing emission, and CO2 diffusion emissions were 44, 34, 252 gCO2eq/m2/yr, respectively, showing a rather high tendency. Since the dam reservoir carbon footprint evaluation is essential for the Clean Development Mechanism evaluation of hydroelectric power generation, continuous research is needed in the future. In particular, experimental studies that can replace the emission factors obtained from the overseas dam reservoirs currently used in the G-res Tool should be promoted.

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Chemical signalling within the rumen microbiome

  • Katie Lawther;Fernanda Godoy Santos;Linda B Oyama;Sharon A Huws
    • Animal Bioscience
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    • 제37권2_spc호
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    • pp.337-345
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    • 2024
  • Ruminants possess a specialized four-compartment forestomach, consisting of the reticulum, rumen, omasum, and abomasum. The rumen, the primary fermentative chamber, harbours a dynamic ecosystem comprising bacteria, protozoa, fungi, archaea, and bacteriophages. These microorganisms engage in diverse ecological interactions within the rumen microbiome, primarily benefiting the host animal by deriving energy from plant material breakdown. These interactions encompass symbiosis, such as mutualism and commensalism, as well as parasitism, predation, and competition. These ecological interactions are dependent on many factors, including the production of diverse molecules, such as those involved in quorum sensing (QS). QS is a density-dependent signalling mechanism involving the release of autoinducer (AIs) compounds, when cell density increases AIs bind to receptors causing the altered expression of certain genes. These AIs are classified as mainly being N-acyl-homoserine lactones (AHL; commonly used by Gram-negative bacteria) or autoinducer-2 based systems (AI-2; used by Gram-positive and Gram-negative bacteria); although other less common AI systems exist. Most of our understanding of QS at a gene-level comes from pure culture in vitro studies using bacterial pathogens, with much being unknown on a commensal bacterial and ecosystem level, especially in the context of the rumen microbiome. A small number of studies have explored QS in the rumen using 'omic' technologies, revealing a prevalence of AI-2 QS systems among rumen bacteria. Nevertheless, the implications of these signalling systems on gene regulation, rumen ecology, and ruminant characteristics are largely uncharted territory. Metatranscriptome data tracking the colonization of perennial ryegrass by rumen microbes suggest that these chemicals may influence transitions in bacterial diversity during colonization. The likelihood of undiscovered chemicals within the rumen microbial arsenal is high, with the identified chemicals representing only the tip of the iceberg. A comprehensive grasp of rumen microbial chemical signalling is crucial for addressing the challenges of food security and climate targets.

Toxoplasma gondii IST suppresses inflammatory and apoptotic responses by inhibiting STAT1-mediated signaling in IFN-γ/TNF-α-stimulated hepatocytes

  • Seung-Hwan Seo;Ji-Eun Lee;Do-Won Ham;Eun-Hee Shin
    • Parasites, Hosts and Diseases
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    • 제62권1호
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    • pp.30-41
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    • 2024
  • The dense granule protein of Toxoplasma gondii, inhibitor of signal transducer and activator of transcription 1 (IST) is an inhibitor of signal transducer and activator of transcription 1 (STAT1) transcriptional activity that binds to STAT1 and regulates the expression of inflammatory molecules in host cells. A sterile inflammatory liver injury in pathological acute liver failures occurs when excessive innate immune function, such as the massive release of IFN-γ and TNF-α, is activated without infection. In relation to inflammatory liver injury, we hypothesized that Toxoplasma gondii inhibitor of STAT1 transcription (TgIST) can inhibit the inflammatory response induced by activating the STAT1/IRF-1 mechanism in liver inflammation. This study used IFN-γ and TNF-α as inflammatory inducers at the cellular level of murine hepatocytes (Hepa-1c1c7) to determine whether TgIST inhibits the STAT1/IRF-1 axis. In stable cells transfected with TgIST, STAT1 expression decreased with a decrease in interferon regulatory factor (IRF)-1 levels. Furthermore, STAT1 inhibition of TgIST resulted in lower levels of NF-κB and COX2, as well as significantly lower levels of class II transactivator (CIITA), iNOS, and chemokines (CLXCL9/10/11). TgIST also significantly reduced the expression of hepatocyte proapoptotic markers (Caspase3/8/9, P53, and BAX), which are linked to sterile inflammatory liver injury. TgIST also reduced the expression of adhesion (ICAM-1 and VCAM-1) and infiltration markers of programmed death-ligand 1 (PD-L1) induced by hepatocyte and tissue damage. TgIST restored the cell apoptosis induced by IFN-γ/TNF-α stimulation. These results suggest that TgIST can inhibit STAT1-mediated inflammatory and apoptotic responses in hepatocytes stimulated with proinflammatory cytokines.