• 대한본초학회지
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• 제32권5호
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• pp.7-12
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• 2017

Objectives : Recently, numerous studies reported that excessive generation of advanced glycation end products (AGEs) stimulated expression of skin wrinkle related proteins. This study aimed to evaluate inhibits skin wrinkle formation effect of Mori Folium (MF) through decreased AGEs. Methods : To evaluate the skin wrinkle inhibition effect of MF, SD-rats were divided into three groups; normal rats (Nor), AGEs-induced rats (Con), AGEs-induce rats treated with MF at dose of 100mg/kg body weight (MF). To induced AGEs, streptozotocin (50mg/kg) was injected intraperitoneally, and after 3 days, 100mM methyl glyoxal was administered orally for 3 weeks. After the experiment, the animal's dorsal skin tissues and serum were separated and tested. Results : The oral administration of MF suppressed the AGEs level in serum. Also, the AGEs in skin tissues was significantly reduced through treatment of MF compared with control group. Moreover, the expressions of AGEs related proteins such as polyclonal anti-$N^e$-(carboxymethyl) lysine (CML), anti-$N^e$-(carboxyethyl)lysine (CEL), AGE receptors (RAGE) were reduced in MF group compared with the control group in kidney and skin tissues. The matrix metallo proteinase-1 (MMP-1) reduced by MF treatment with the result that collagen type 1 alpha 2 (COL1A2) was improved that reduced by accumulation of AGEs. Conclusion : The evidence of this study indicate that oral administration of MF reduces the levels of AGEs in serum, skin, and kidney tissues. In conclusion, MF inhibit skin wrinkle formation, suggesting the potential of anti-wrinkle material.

• 대한본초학회지
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• 제32권4호
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• pp.53-60
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• 2017

Objectives : Collagen decrease of Skin appears through various path ways. One of causes may be the Advanced glycation endproducts (AGEs) that combine formation of glucose and protein. The aim of this study was to explore the prevent wrinkle formation of Paeoniae radix (PR) and heated Paeoniae radix (HPR) via AGEs path way. Methods : AGEs formation inhibitory activities of PR and HPR measured using bovine serum albumin, glucose, and fructose. To evaluate the protective effects of PR and HPR in diabetic rats induced with streptozotocin (STZ) and methyl glyoxal (MGO), SD rat were distributed into four groups. Normal rats (Nor), AGEs-induced rats (Con), AGEs-induced rats treated with 100 mg/kg PR(PR), AGEs-induced rats treated with 100 mg/kg HPR (HPR). To induce AGEs, streptozotocin (50 mg/kg) was administered intraperitoneally and after 3 days administrated 100mM methyl glyoxal for 3 weeks. Results : The oral administration of HPR inhibited AGEs in skin tissues compared with PR. The increased reactive oxygen species (ROS) levels in the serum were diminished by HPR treatment. The analyses of kidney and skin tissues proteins indicated that HPR treatment effectively reduced AGEs related protein levels as compared to that by PR treatment. Also, HPR decreased anti-oxidant related protein levels in skin tissues such as catalase, glutathione peroxidase. Moreover, it inhibited the reduction of COL1A2 by decreasing MMP-1. Conclusion : Based on these results, it was suggested that PR and HPR could have Improving effects on wrinkle formation. These evidences provide useful information for the development wrinkle formation treated agent.

• Biomolecules & Therapeutics
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• 제31권1호
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• pp.97-107
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• 2023

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

• 한국환경보건학회지
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• 제48권6호
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• pp.315-323
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• 2022

Background: Socioeconomical disadvantaged communities are more vulnerable to environmental chemical exposure and associated health effects. However, there is limited information on chemical exposure among vulnerable populations in Korea. Objectives: This study investigated chemical exposure among underprivileged populations. We measured urinary metabolites of phthalates in urban disadvantaged communities and investigated their correlations with residential environment factors and relative socioeconomic vulnerability. Methods: Urine samples were collected from 64 residents in a disadvantaged community in Seoul. A total of eight phthalate metabolites were analyzed by liquid chromatography-mass spectroscopy. Analytical method used by the Korean National Environmental Health Survey (KoNEHS) was employed. Covariate variance analysis and general linear regression adjusted with age, sex and smoking were performed. Results: Several phthalate metabolites, namely monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-n-butyl phthalate (MnBP) had higher levels than those reported in the adults of 4th KoNEHS. Notably, the MnBP level was higher in the lower socioeconomic group (geometric mean [GM]=47.3 ㎍/g creatinine) compared to non-recipients (GM=31.9 ㎍/g creatinine) and the national reference level (GM=22.0, 28.2 and 32.2 ㎍/g creatinine for adults, 60's and 70's, respectively.). When age, sex and smoking were adjusted, MEP and MnBP were significantly increased the lower socioeconomic group than non-recipients (p=0.014, p=0.023). The lower socioeconomic group's age of flooring were higher than non-recipients, not statistically significant. Conclusions: These results suggest that a relatively low income and aged flooring could be considered as risk factors for increased levels of phthalate metabolites in socioeconomic vulnerable populations.

• Molecules and Cells
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• 제45권3호
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• pp.122-133
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• 2022

The aim of this study was to investigating whether lncRNA H19 promotes myocardial fibrosis by suppressing the miR-29a-3p/miR-29b-3p-VEGFA/TGF-β axis. Patients with atrial fibrillation (AF) and healthy volunteers were included in the study, and their biochemical parameters were collected. In addition, pcDNA3.1-H19, si-H19, and miR-29a/b-3p mimic/inhibitor were transfected into cardiac fibroblasts (CFs), and proliferation of CFs was detected by MTT assay. Expression of H19 and miR-29a/b-3p were detected using real-time quantitative polymerase chain reaction, and expression of α-smooth muscle actin (α-SMA), collagen I, collagen II, matrix metalloproteinase-2 (MMP-2), and elastin were measured by western blot analysis. The dual luciferase reporter gene assay was carried out to detect the sponging relationship between H19 and miR-29a/b-3p in CFs. Compared with healthy volunteers, the level of plasma H19 was significantly elevated in patients with AF, while miR-29a-3p and miR-29b-3p were markedly depressed (P < 0.05). Serum expression of lncRNA H19 was negatively correlated with the expression of miR-29a-3p and miR-29b-3p among patients with AF (r_s = -0.337, r_s = -0.236). Moreover, up-regulation of H19 expression and down-regulation of miR-29a/b-3p expression facilitated proliferation and synthesis of extracellular matrix (ECM)-related proteins. SB431542 and si-VEGFA are able to reverse the promotion of miR-29a/b-3p on proliferation of CFs and ECM-related protein synthesis. The findings of the present study suggest that H19 promoted CF proliferation and collagen synthesis by suppressing the miR-29a-3p/miR-29b-3p-VEGFA/TGF-β axis, and provide support for a potential new direction for the treatment of AF.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2023년도 임시총회 및 춘계학술대회
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• pp.50-50
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• 2023

Prostaglandin E2(PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because PGE2 functions by signaling through PGE2 receptors (Eps), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting Eps. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibititing the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinases (MMP)-9 as well as the down-regulation of COX-2 expression and PGE2 production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells. Through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

• 한국응용과학기술학회지
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• 제40권5호
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• pp.925-935
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• 2023

PPARα activator가 고지방 사료를 섭취한 운동하지 않은 쥐에 비해 고지방 사료를 섭취한 운동 쥐에서 백색지방조직의 혈관신생을 보다 효과적으로 억제하는지를 조사하였다. 수컷 쥐는 무작위로 PPARα activator인 fenofibrate와 운동을 모두 처리하지 않은 대조군(Con), fenofibrate 단독처리군(FF), 운동 단독처리군(Ex) 및 fenofibrate와 운동의 조합처리군(Ex+FF)으로 나누어 8주간 고지방 사료를 섭취시켰다. 백색지방조직의 무게와 백색지방세포의 크기는 Con에 비해 FF, Ex 및 Ex+FF 모두 감소하였으며, Ex+FF는 FF에 비해 더욱 감소하였다. 백색지방조직에서 MMPs와 혈관신생 인자의 유전자 발현은 Con에 비해 FF, Ex 및 Ex+FF 모두 감소하였으며, Ex+FF는 FF에 비해 더욱 감소하였다. 그러나 혈관신생 억제인자의 유전자 발현은 Con에 비해 FF, Ex 및 Ex+FF 모두 증가하였고, Ex+FF는 FF에 비해 더욱 증가하였다. 따라서 본 연구는 fenofibrate 단독처리보다는 fenofibrate와 운동의 조합처리가 효과적으로 백색지방조직의 혈관신생을 억제함으로써 백색지방조직의 증가를 감소시키고 복부비만을 억제한다는 것을 밝혔다.

• IMMUNE NETWORK
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• 제22권4호
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• pp.34.1-34.19
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• 2022

Osteoarthritis (OA) is the most common form of arthritis associated with ageing. Vitamin D has diverse biological effect on bone and cartilage, and observational studies have suggested it potential benefit in OA progression and inflammation process. However, the effect of vitamin D on OA is still contradictory. Here, we investigated the therapeutic potential of vitamin D in OA. Six-week-old male Wistar rats were injected with monosodium iodoacetate (MIA) to induce OA. Pain severity, cartilage destruction, and inflammation were measured in MIA-induced OA rats. Autophagy activity and mitochondrial function were also measured. Vitamin-D (1,25(OH)₂D3) and celecoxib were used to treat MIA-induced OA rats and OA chondrocytes. Oral supplementation of vitamin D resulted in significant attenuations in OA pain, inflammation, and cartilage destruction. Interestingly, the expressions of MMP-13, IL-1β, and MCP-1 in synovial tissues were remarkably attenuated by vitamin D treatment, suggesting its potential to attenuate synovitis in OA. Vitamin D treatment in OA chondrocytes resulted in autophagy induction in human OA chondrocytes and increased expression of TFEB, but not LC3B, caspase-1 and -3, in inflamed synovium. Vitamin D and celecoxib showed a synergistic effect on antinociceptive and chondroprotective properties in vivo. Vitamin D showed the chondroprotective and antinociceptive property in OA rats. Autophagy induction by vitamin D treatment may be a promising treatment strategy in OA patients especially presenting vitamin D deficiency. Autophagy promoting strategy may attenuate OA progression through protecting cells from damage and inflammatory cell death.

• International Journal of Stem Cells
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• 제16권1호
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• pp.52-65
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• 2023

Background and Objectives: Epithelial-Mesenchymal transition (EMT) is one of the origins of myofibroblasts in renal interstitial fibrosis. Mesenchymal stem cells (MSCs) alleviating EMT has been proved, but the concrete mechanism is unclear. To explore the mechanism, serum-free MSCs conditioned medium (SF-MSCs-CM) was used to treat rat renal tubular epithelial cells (NRK-52E) fibrosis induced by transforming growth factor-β1 (TGF-β1) which ameliorated EMT. Methods and Results: Galectin-3 knockdown (Gal-3 KD) and overexpression (Gal-3 OE) lentiviral vectors were established and transfected into NRK-52E. NRK-52E fibrosis model was induced by TGF-β1 and treated with the SF-MSCs-CM for 24 h after modelling. Fibrosis and autophagy related indexes were detected by western blot and immunocytochemistry. In model group, the expressions of α-smooth muscle actin (α-SMA), fibronectin (FN), Galectin-3, Snail, Kim-1, and the ratios of P-Akt/Akt, P-GSK3β/GSK3β, P-PI3K/PI3K, P-mTOR/mTOR, TIMP1/MMP9, and LC3B-II/I were obviously increased, and E-Cadherin (E-cad) and P62 decreased significantly compared with control group. SF-MSCs-CM showed an opposite trend after treatment compared with model group. Whether in Gal-3 KD or Gal-3 OE NRK-52E cells, SF-MSCs-CM also showed similar trends. However, the effects of anti-fibrosis and enhanced autophagy in Gal-3 KD cells were more obvious than those in Gal-3 OE cells. Conclusions: SF-MSCs-CM probably alleviated the EMT via inhibiting Galectin-3/Akt/GSK3β/Snail pathway. Meanwhile, Gal-3 KD possibly enhanced autophagy via inhibiting Galectin-3/Akt/mTOR pathway, which synergistically ameliorated renal fibrosis. Targeting galectin-3 may be a potential target for the treatment of renal fibrosis.

• BMB Reports
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• 제36권1호
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• pp.82-94
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• 2003

Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-${\kappa}B$ binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-${\kappa}B$ binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-$\gamma$, RANTES, TNF-$\alpha$, TNFR p75, IL-$1{\beta}$ in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric/cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.