• Journal of Ginseng Research
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• 제42권3호
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• pp.343-351
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• 2018

Background: Red ginseng is a popularly used traditional medicine with antiaging effects in Asian countries. The present study aimed to explore the changes in protein expression underlying the mechanisms of life span extension and antiaging caused by red ginseng extract (RGE) in Drosophila melanogaster. Methods: A proteomic approach of two-dimensional polyacrylamide gel electrophoresis (2-DE) was used to identify the differential abundance of possible target proteins of RGE in D. melanogaster. The reliability of the 2-DE results was confirmed via Western blotting to measure the expression levels of selected proteins. Proteins altered at the expression level after RGE treatment (1 mg/mL) were identified by matrix-assisted laser desorption/ionization-time of flight tandem mass spectrometry and by searching against the National Center for Biotechnology nonredundant and Uniprot protein databases. The differentially expressed proteins were analyzed using bioinformatics methods. Results: The average survival life span of D. melanogaster was significantly extended by 12.60% with RGE treatment (1 mg/mL) compared to untreated flies. This followed increased superoxide dismutase level and decreased methane dicarboxylic aldehyde content. Based on the searching strategy, 23 differentially expressed proteins were identified (16 up-regulated and 7 down-regulated) in the RGE-treated D. melanogaster. Transduction pathways were identified using the Kyoto Encyclopedia of Genes and Genomes database, and included the hippo and oxidative phosphorylation pathways that play important roles in life span extension and antiaging process of D. melanogaster. Conclusion: Treatment with RGE in D. melanogaster demonstrated that mechanisms of life span extension and antiaging are regulated by multiple factors and complicated signal pathways.

• Journal of Ginseng Research
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• 제47권4호
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• pp.493-505
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• 2023

In recent years, an increasing number of reports have explored the wound healing mechanism of these two traditional Chinese herbal medicines- Panax ginseng and Panax notoginseng, but there is no systematic research on the related core functions and different mechanisms in the treatment of wound healing up to now. Based on network pharmacology and meta-analysis, the present work aimed to comprehensively review the commonality and diversity of P. ginseng and P. notoginseng in wound healing. In this study, a wound healing-related "ingredients-targets" network of two herbs was constructed. Thereafter, meta-analysis of the multiple target lists by Metascape showed that these two medicines significantly regulated blood vessel development, responses to cytokines and growth factors and oxygen levels, cell death, cell proliferation and differentiation, and cell adhesion. To better understand the discrepancy between these two herbs, it was found that common signaling pathways including Rap1, PI3K/AKT, MAPK, HIF-1 and Focal adhesion regulated the functions listed above. In parallel, the different pathways including renin-angiotensin system, RNA transport and circadian rhythm, autophagy, and the different metabolic pathways may also explained the discrepancies in the regulation of the above-mentioned functions, consistent with the Traditional Chinese Medicine theory about the effects of P. ginseng and P. notoginseng.

• Animal Bioscience
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• 제37권4호
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• pp.631-639
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• 2024

Objective: This study evaluates goat sperm motility in response to metabolic substrates and various inhibitors, aiming to assess the relative contribution of glycolysis and mitochondrial oxidation for sperm movement and adenosine triphosphate (ATP) production. Methods: In the present study, two main metabolic substrates; 0 to 0.5 mM glucose and 0 to 30 mM pyruvate were used to evaluate their contribution to sperm movements of goats. Using a 3-chloro-1,2-propanediol (3-MCPD), a specific inhibitor for glycolysis, and carbonyl cyanide 3-chlorophenylhydrazone as an inhibitor for oxidative phosphorylation, cellular mechanisms into ATP-generating pathways in relation to sperm movements and ATP production were observed. Data were analysed using one-way analysis of variance for multiple comparisons. Results: Sperm motility analysis showed that either glucose or pyruvate supported sperm movement during 0 to 30 min incubation. However, the supporting effects were abolished by the addition of a glycolysis inhibitor or mitochondrial uncoupler, concomitant with a significant decrease in ATP production. Although oxidative phosphorylation produces larger ATP concentrations than those from glycolysis, sperm progressivity in relation to these two metabolic pathways is comparable. Conclusion: Based on the present study, we suggest that goat sperm use glucose and pyruvate to generate cellular energy through glycolysis and mitochondrial respiration pathways to maintain sperm movement.

• Genomics & Informatics
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• 제5권2호
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• pp.77-82
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• 2007

Serotonin (5-HT), the endogenous nonselective 5-HT receptor agonist, activates the inositol-1,4,5-triphosphate/calcium $(InsP3/Ca^{2+})$ signaling pathway and exerts both stimulatory and inhibitory actions on cAMP production and neuromodulin secretion in rat hypothalamic neurons. Specific mRNA transcripts for 5-HT1A, 5-HT2C and 5-HT4 were identified in rat hypothalamic neurons. These experiments were supported by combined techniques such as cAMP and a $Ca^{2+}$ assays in order to elucidate the associated receptors and signaling pathways. The cAMP production and neuromodulin release were profoundly inhibited during the activation of the Gi-coupled 5-HT1A receptor. Treatment with a selective agonist to activate the Gq-coupled 5-HT2C receptor stimulated InsP3 production and caused $Ca^{2+}$ release from the sarcoplasmic reticulum. Selective activation of the Gs-coupled 5-HT4 receptor also stimulated cAMP production, and caused an increase in neuromodulin secretion. These findings demonstrate the ability of 5-HT receptor subtypes expressed in neurons to induce neuromodulin production. This leads to the activation of single or multiple G-proteins which regulate the $InsP3/Ca^{2+}/PLC-{\gamma}$ and adenyl cyclase / cAMP signaling pathways.

• BMB Reports
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• 제49권4호
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• pp.238-243
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• 2016

The efficacy of anticancer drugs depends on a variety of signaling pathways, which can be positively or negatively regulated. In this study, we show that SETDB1 HMTase is down-regulated at the transcriptional level by several anticancer drugs, due to its inherent instability. Using RNA sequence analysis, we identified FosB as being regulated by SETDB1 during anticancer drug therapy. FosB expression was increased by treatment with doxorubicin, taxol and siSETDB1. Moreover, FosB was associated with an increased rate of proliferation. Combinatory transfection of siFosB and siSETDB1 was slightly increased compared to transfection of siFosB. Furthermore, FosB was regulated by multiple kinase pathways. ChIP analysis showed that SETDB1 and H3K9me3 interact with a specific region of the FosB promoter. These results suggest that SETDB1-mediated FosB expression is a common molecular phenomenon, and might be a novel pathway responsible for the increase in cell proliferation that frequently occurs during anticancer drug therapy.

• 아동학회지
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• 제31권3호
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• pp.255-272
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• 2010

This study explored pathways from mothers' beliefs to children's subjective well-being through children's private after-school activities and stress levels. A sample of 230 6th grade elementary school students (125 boys and 105 girls) in Seoul completed questionnaires on children's stress and subjective well-being. Their mothers responded to questionnaires on mothers' beliefs and children's private after-school activities. Data were analyzed by means of Pearson's correlation coefficients and multiple regression analyses. Our results demonstrated that mothers' beliefs indirectly influenced children's subjective well-being through both children's private after-school activities and stress levels. Neither children's private after-school activities nor children's stress mediated between mothers' beliefs and children's subjective well-being. Mothers' beliefs also had a direct effect on children's subjective well-being. Significantly, both mothers' beliefs and children's stress played crucial roles in improving children's subjective well-being.

• 대한한의학방제학회지
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• 제28권3호
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• pp.243-254
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• 2020

Objectives : Network pharmacology analysis is commonly used to investigate the synergies and potential mechanisms of multiple compounds by analyzing complex, multi-layered networks. We used TCMSP and BATMAN-TCM databases to compare results of network pharmacological analysis between White Ginseng(WG) and Red Ginseng(RG). Methods : WG and RG were compared with components and their target molecules using TCMSP database, and compound-target-pathway/disease networks were compared using BATMAN-TCM database. Results : Through TCMSP, 104 kinds of target molecules were derived from WG and 38 kinds were derived from RG. Using the BATMAN-TCM database, target pathways and diseases were screened, and more target pathways and diseases were screened compared to RG due to the high composition of WG ingredients. Analysis of component-target-pathway/disease network using network analysis tools provided by BATMAN-TCM showed that WG formed more networks than RG. Conclusions : Network pharmacology analysis can be effectively performed using various databases used in system biology research, and although the materials that have been reported in the past can be used efficiently for research on diseases related to targets, the results are unreliable if prior studies are focused on limited or narrow research areas.

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.21-26
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• 2011

Ceramide is an important lipid mediator of extracellular signals that control various cellular functions, including apoptosis. In this study, we showed that ceramide induced apoptosis in U373MG human glioblastoma cells associated with G1 cell cycle arrest. Treatment of cells with ceramide increased proapoptotic Bax expression and inhibited the expression of antiapoptotic Bcl-2 and Bcl-xL Ceramide also downregulated cyclin E, cyclin D1, cdk 2, and cdk4 which are involved in regulating cell cycle. In addition, ceramide suppressed phosphorylation of Akt, Bad, p70 S6 kinase, and 4E-BP1, suggesting the involvement of Akt/mTOR signaling pathway. Additionally, okadaic acid, an inhibitor of protein phosphatase 2A, partially blocked the ceramide mediated inhibition of phosphorylation of Akt and 4E-BP1. These results suggest that ceramide induces apoptosis in U373MG glioblastoma cells by regulating multiple signaling pathways that involve cell cycle arrest associated with Akt signaling pathway.

• Environmental Analysis Health and Toxicology
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• 제18권4호
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• pp.255-269
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• 2003

The objective of this study was to estimate human exposure to benzo (a)pyrene through multimedia/multi-pathway exposure scenario. The human exposure scenario for benzo(a)pyrene was consisted of 12 multiple exposure pathways, and the multipathway human exposure model based on this scenario constituted. In this study, the multipathway human exposure model was used to estimate the concentrations in the exposure contact media, human intake factors and lifetime average daily dose (LAD $D_{model}$) of benzo(a)pyrene in the environment. Sensitivity analysis was performed to identify the important parameters and Monte-Carlo simulation was undertaken to examine the uncertainty of the model. The total LAD $D_{model}$ was estimated to be 5.52${\times}$10$^{-7}$ mg/kg-day (2.06${\times}$10$^{-7}$ -8.65${\times}$10$^{-7}$ mg/kg-day) using the multipathway human exposure model. The inhalation dose accounted for 78% of the total LADD, whereas ingestion and dermal contact intake accounted for 20.2% and 1.8% of the total exposure, respectively. Based on the sensitivity analysis, the most significant contributing input parameter was benzo (a)pyrene concentration of ambient air. Consequently, exposure via inhalation in outdoor/indoor air was the highest compared with the exposure via other medium/pathways.

• BMB Reports
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• 제53권1호
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• pp.56-63
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• 2020

The ubiquitin-proteasome system (UPS) and autophagy are two major degradative pathways of proteins in eukaryotic cells. As about 30% of newly synthesized proteins are known to be misfolded under normal cell conditions, the precise and timely operation of the UPS and autophagy to remove them as well as their tightly controlled regulation, is so important for proper cell function and survival. In the UPS, target proteins are labeled by small proteins called ubiquitin, which are then transported to the proteasome complex for degradation. Alternatively, many greatly damaged proteins are believed to be delivered to the lysosome for autophagic degradation. Although these autophagy and UPS pathways have not been considered to be directly related, many recent studies proposed their close link and dynamic interconversion. In this review, we'll focus on the several regulatory molecules that function in both UPS and autophagy and their crosstalk. Among the proposed multiple modulators, we will take a closer look at the so-called main connector of UPS-autophagy regulation, p62. Last, the functional role of p62 in the mitophagy and its implication for the pathogenesis of Parkinson's disease, one of the major neurodegenerative diseases, will be briefly reviewed.