• The Korean Journal of Physiology and Pharmacology
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• 제24권3호
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• pp.249-257
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• 2020

The aim of the present study was to investigate the pathophysiological etiology of osteoarthritis that is mediated by the apoptosis of chondrocytes exposed to 25-hydroxycholesterol (25-HC), an oxysterol synthesized by the expression of cholesterol-25-hydroxylase (CH25H) under inflammatory conditions. Interleukin-1β induced the apoptosis of chondrocytes in a dose- dependent manner. Furthermore, the production of 25-HC increased in the chondrocytes treated with interleukin-1β through the expression of CH25H. 25-HC decreased the viability of chondrocytes. Chondrocytes with condensed nucleus and apoptotic populations increased by 25-HC. Moreover, the activity and expression of caspase-3 were increased by the death ligand-mediated extrinsic and mitochondria-dependent intrinsic apoptotic pathways in the chondrocytes treated with 25-HC. Finally, 25-HC induced not only caspase-dependent apoptosis, but also induced proteoglycan loss in articular cartilage ex vivo cultured rat knee joints. These data indicate that 25-HC may act as a metabolic pathophysiological factor in osteoarthritis that is mediated by progressive chondrocyte death in the articular cartilage with inflammatory condition.

• Journal of Ginseng Research
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• 제42권1호
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• pp.98-106
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• 2018

Panax ginseng has been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginseng have focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng, it still remains unclear how multiple active ingredients of P. ginseng interact with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases. In order to decipher the systems-level mechanism of multiple ingredients of P. ginseng, a novel approach is needed beyond conventional reductive analysis. We aim to review the systems-level mechanism of P. ginseng by adopting novel analytical framework-network pharmacology. Here, we constructed a compound-target network of P. ginseng using experimentally validated and machine learning-based prediction results. The targets of the network were analyzed in terms of related biological process, pathways, and diseases. The majority of targets were found to be related with primary metabolic process, signal transduction, nitrogen compound metabolic process, blood circulation, immune system process, cell-cell signaling, biosynthetic process, and neurological system process. In pathway enrichment analysis of targets, mainly the terms related with neural activity showed significant enrichment and formed a cluster. Finally, relative degrees analysis for the target-disease association of P. ginseng revealed several categories of related diseases, including respiratory, psychiatric, and cardiovascular diseases.

• BMB Reports
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• 제57권3호
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• pp.143-148
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• 2024

Pulmonary fibrosis is a serious lung disease that occurs predominantly in men. Genistein is an important natural soybean-derived phytoestrogen that affects various biological functions, such as cell migration and fibrosis. However, the antifibrotic effects of genistein on pulmonary fibrosis are largely unknown. The antifibrotic effects of genistein were evaluated using in vitro and in vivo models of lung fibrosis. Proteomic data were analyzed using nano-LC-ESI-MS/MS. Genistein significantly reduced transforming growth factor (TGF)-β1-induced expression of collagen type I and α-smooth muscle actin (SMA) in MRC-5 cells and primary fibroblasts from patients with idiopathic pulmonary fibrosis (IPF). Genistein also reduced TGF-β1-induced expression of p-Smad2/3 and p-p38 MAPK in fibroblast models. Comprehensive protein analysis confirmed that genistein exerted an anti-fibrotic effect by regulating various molecular mechanisms, such as unfolded protein response, epithelial mesenchymal transition (EMT), mammalian target of rapamycin complex 1 (mTORC1) signaling, cell death, and several metabolic pathways. Genistein was also found to decrease hydroxyproline levels in the lungs of BLM-treated mice. Genistein exerted an anti-fibrotic effect by preventing fibroblast activation, suggesting that genistein could be developed as a pharmacological agent for the prevention and treatment of pulmonary fibrosis.

• Applied Biological Chemistry
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• 제35권6호
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• pp.485-489
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• 1992

식물은 자극이 큰 환경적 stress에 반응 외견상의 변모 뿐 아니라 내적으로 생리적 생화학적인 변화가 있게 되며, 특히 체내의 단백질 합성계는 그러한 stress에 더욱 급격하게 반응한다. 여러가지 stress하에서 유묘기 벼의 단백질 수준이 어떻게 변화되는 가를 일차적으로 조사하기 위하여 NaCl, 한발 및 온도를 각각 달리 처리하여 이에 따른 폴리펩티드의 변이 양상을 전기영동에 의하여 비교하여 보았다. 환경 변화에 내성이 다소 강한 벼의 경우에도 stress 처리에 따라 다수의 폴리펩티드가 변화되었으며, 새로운 폴리펩티드의 생성도 관찰 되었다. 또한 기존의 1차 대사과정을 위한 단백질의 감소도 각각의 처리에 따라서 달리 표현되는 것이 확인되었다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.3993-4003
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• 2013

Scientific evidence for the primary prevention of cancer caused by physical activity of regular moderate-intensity or greater is rapidly accumulating in this field. About 300 epidemiologic studies on the association between physical activity and cancer risk have been conducted worldwide. The objectives of this paper were three-fold: (i) to describe briefly the components of physical activity and its quantification; (ii) to summarize the most important conclusions available from comprehensive reports, and reviews of the epidemiologic individual and intervention studies on a role physical activity in cancer prevention; (iii) to present proposed biological mechanisms accounting for effects of activity on cancer risk. The evidence of causal linked physical activity and cancer risk is found to be strong for colon cancer - convincing; weaker for postmenopausal breast and endometrium cancers - probable; and limited suggestive for premenopausal breast, lung, prostate, ovary, gastric and pancreatic cancers. The average risk reductions were reported to be 20-30%. The protective effects of physical activity on cancer risk are hypothesized to be through multiple interrelated pathways: decrease in adiposity, decrease in sexual and metabolic hormones, changes in biomarkers and insulin resistance, improvement of immune function, and reduction of inflammation. As there are several gaps in the literature for associations between activity and cancer risk, additional studies are needed. Future research should include studies dealing with limitations in precise estimates of physical activity and of a lack of consensus on what defines sedentary behavior of individuals and those linked with the proposed biomarkers to cancer risk and controlled exercise intervention trials.

• Molecules and Cells
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• 제38권10호
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• pp.843-850
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• 2015

The1hepatic cell death induced by acetaminophen (APAP) is closely related to cellular adenosine triphosphate (ATP) depletion, which is mainly caused by mitochondrial dysfunction. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of low energy status. AMPK regulates metabolic homeostasis by stimulating catabolic metabolism and suppressing anabolic pathways to increase cellular energy levels. We found that the decrease in active phosphorylation of AMPK in response to APAP correlates with decreased ATP levels, in vivo. Therefore, we hypothesized that the enhanced production of ATP via AMPK stimulation can lead to amelioration of APAP-induced liver failure. A769662, an allosteric activator of AMPK, produced a strong synergistic effect on AMPK Thr172 phosphorylation with APAP in primary hepatocytes and liver tissue. Interestingly, activation of AMPK by A769662 ameliorated the APAP-induced hepatotoxicity in C57BL/6N mice treated with APAP at a dose of 400 mg/kg intraperitoneally. However, mice treated with APAP alone developed massive centrilobular necrosis, and APAP increased their serum alanine aminotransferase and aspartate aminotransferase levels. Furthermore, A769662 administration prevented the loss of intracellular ATP without interfering with the APAP-mediated reduction of mitochondrial dysfunction. In contrast, inhibition of glycolysis by 2-deoxy-glucose eliminated the beneficial effects of A769662 on APAP-mediated liver injury. In conclusion, A769662 can effectively protect mice against APAP-induced liver injury through ATP synthesis by anaerobic glycolysis. Furthermore, stimulation of AMPK may have potential therapeutic application for APAP overdose.

• Genes and Genomics
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• 제40권12호
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• pp.1287-1300
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• 2018

Hydrogen sulfide ($H_2S$), a small bioactive gas, has been proved functioning in plant growth and development as well as alleviation of abiotic stresses, which including promoting seed germination, accelerating embryonic root growth, regulating flower senescence, inducing stomatal closure, and defending drought, heat, heavy metals and osmotic stresses etc. However, the molecular functioning mechanism of $H_2S$ was still unclear. The primary objective of this research was to analyze the transcriptional differences and functional genes involved in the $H_2S$ responses. In details, 4-week-old plantlets in tissue culture of grapevine (Vitis vinifera L.) cultivar 'Zuoyouhong' were sprayed with 0.1 mM NaHS for 12 h, and then transcriptome sequencing and qRT-PCR analysis were used to study the transcriptional differences and functional genes involved in the $H_2S$ responses. Our results indicated that 650 genes were differentially expressed after $H_2S$ treatment, in which 224 genes were up-regulated and 426 genes were down-regulated. The GO enrichment analysis and KEGG enrichment analysis results indicated that the up-regulated genes after $H_2S$ treatment focused on carbon metabolism, biosynthesis of amino acids, and glycolysis/gluconeogenesis, and the down-regulated genes were mainly in metabolic pathways, biosynthesis of secondary metabolites, and plant hormone signal transduction. Analyzing the transcription factor coding genes in details, it was indicated that 10 AP2/EREBPs, 5 NACs, 3 WRKYs, 3 MYBs, and 2 bHLHs etc. transcription factor coding genes were up-regulated, while 4 MYBs, 3 OFPs, 3 bHLHs, 2 AP2/EREBPs, 2 HBs etc. transcription factor coding genes were down-regulated. Taken together, $H_2S$ increased the productions in secondary metabolites and a variety of defensive compounds to improve plant development and abiotic resistance, and extend fruits postharvest shelf life by regulating the expression of AP2/EREBPs, WRKYs, MYBs, CABs, GRIP22, FERRITINs, TPSs, UGTs, and GHs etc.