• Molecules and Cells
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• v.45 no.6
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• pp.376-387
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• 2022

Extracellular vesicles (EVs) play an essential role in the communication between cells and the tumor microenvironment. However, the effect of tumor-derived EVs on the growth and metastasis of lung adenocarcinoma (LUAD) remains to be explored. This study aimed to elucidate the role of miR-153-3p-EVs in the invasion and migration capabilities of LUAD cells and explore its mechanism through in vivo and in vitro experiments. We found that miR-153-3p was specifically and highly expressed in LUAD and its secreted EVs. Furthermore, the expression of BANCR was negatively regulated by miR-153-3p and identified as a target gene of miR-153-3p using luciferase reporter assays. Through further investigation, we found that the downregulation of BANCR activates the PI3K/AKT pathway and accelerates the process of epithelial-mesenchymal transition (EMT), which ultimately leads to the aggravation of LUAD. The orthotopic xenograft mouse model was established to illustrate the effect of miR-153-3p-EVs on LUAD. Animal studies showed that miR-153-3p-EVs accelerated tumor growth in mice. Besides, we found that miR-153-3p-EVs could damage the respiratory ability of mice and produce a mass of inflammatory cells around the lung tissue of mice. Nevertheless, antagomir-153-3p treatment could inhibit the deterioration of respiratory function and inhibit the growth of lung tumors in mice. In conclusion, our study reveals the potential molecular mechanism of miR-153-3p-EVs in the development of LUAD and provides a potential strategy for the treatment of LUAD.

• Parasites, Hosts and Diseases
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• v.60 no.5
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• pp.309-315
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• 2022

Inflammatory bowel disease (IBD) is a chronic and recurrent illness of the gastrointestinal tract. Treatment of IBD traditionally involves the use of aminosalicylic acid and steroids, while these drugs has been associated with untoward effects and refractoriness. The absence of effective treatment regimen against IBD has led to the exploration of new targets. Parasites are promising as an alternative therapy for IBD. Recent studies have highlighted the use of parasite-derived substances, such as excretory secretory products, extracellular vesicles (EVs), and exosomes, for the treatment of IBD. In this report, we examined whether EVs secreted by Giardia lamblia could prevent colitis in a mouse model. G. lamblia EVs (GlEVs) were prepared from in vitro cultures of Giardia trophozoites. Clinical signs, microscopic colon tissue inflammation, and cytokine expression levels were detected to assess the effect of GlEV treatment on dextran sulfate sodium (DSS)-induced experimental murine colitis. The administration of GlEVs prior to DSS challenge reduced the expression levels of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 beta, and interferon gamma. Our results indicate that GlEV can exert preventive effects and possess therapeutic properties against DSS-induced colitis.

• Archives of Plastic Surgery
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• v.48 no.4
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• pp.440-447
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• 2021

Background Brown adipose tissue (BAT) is a potential target for anti-obesity treatments. Previous studies have shown that BAT activation causes an acute metabolic boost and reduces adiposity. Furthermore, BAT and BAT-derived cell transplantation reportedly help treat obesity by regulating glucose and fatty acid metabolism. However, since BAT transplantation leads to whole-body weight loss, we speculated that earlier approaches cause a generalized and unnecessary fat tissue loss, including in breast and hip tissues. Methods We transplanted white adipose tissue-derived or BAT-derived preadipocytes prepared from C57BL/6 mice into one side of the inguinal fat pads of an obese mouse model (db/db mice) to examine whether it would cause fat loss at the peri-transplant site (n=5 each). The same volume of phosphate-buffered saline was injected as a control on the other side. Six weeks after transplantation, the inguinal fat pad was excised and weighed. We also measured the concentrations of glucose, triglycerides, fatty acids, and total cholesterol in the peripheral blood. Results BAT-derived preadipocytes showed abundant mitochondria and high levels of mitochondrial membrane uncoupling protein 1 expression, both in vivo and in vitro, with a remarkable reduction in weight of the inguinal fat pad after transplantation (0.17±0.12 g, P=0.043). Only free fatty acid levels tended to decrease in the BAT-transplanted group, but the difference was not significant (P=0.11). Conclusions Our results suggest that brown adipocytes drive fat degradation around the transplantation site. Thus, local transplantation of BAT-derived preadipocytes may be useful for treating obesity, as well as in cosmetic treatments.

• Nutrition Research and Practice
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• v.15 no.3
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• pp.279-293
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• 2021

BACKGROUND/OBJECTIVES: The steamed ginger has been shown to have antioxidative effects and a protective effect against obesity. In the present study, we investigated the effects of ethanolic extract of steamed ginger (SGE) on adipogenesis in 3T3-L1 preadipocytes and diet-induced obesity (DIO) mouse model. MATERIALS/METHODS: The protective effects of SGE on adipogenesis were examined in 3T3-L1 adipocytes by measuring lipid accumulations and genes involved in adipogenesis. Male C57BL/6J mice were fed a normal diet (ND, 10% fat w/w), a high-fat diet (HFD, 60% fat w/w), and HFD supplemented with either 40 mg/kg or 80 mg/kg of SGE for 12 weeks. Serum chemistry was measured, and the expression of genes involved in lipid metabolism was determined in the adipose tissue. Histological analysis and micro-computed tomography were performed to identify lipid accumulations in epididymal fat pads. RESULTS: In 3T3-L1 cells, SGE significantly decreased lipid accumulation, with concomitant decreases in the expression of adipogenesis-related genes. SGE significantly attenuated the increase in body, liver, and epididymal adipose tissue weights by HFD. Serum total cholesterol and triglyceride levels were significantly lower in SGE fed groups compared to HFD. In adipose tissue, SGE significantly decreased adipocyte size than that of HFD and altered adipogenesis-related genes. CONCLUSIONS: In conclusion, steamed ginger exerted anti-obesity effects by regulating genes involved in adipogenesis and lipogenesis in 3T3-L1 cell and epididymal adipose tissue of DIO mice.

• Nutrition Research and Practice
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• v.15 no.3
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• pp.319-328
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• 2021

BACKGROUND/OBJECTIVES: Curcuma zedoaria R. (Zingiberaceae) has been used to treat headache, fever, and hypertension-related symptoms in Asian countries, including Korea, China, and Japan. We investigated whether dietary intake of a C. zedoaria extract (CzE) affected atherosclerosis in vivo. MATERIALS/METHODS: Apolipoprotein E-deficient (ApoE^-/-) mice (n = 32) were fed a normal diet (ND), a high-cholesterol diet (HCD), an HCD containing CzE (100 mg/kg/day), or an HCD containing simvastatin (10 mg/kg/day) for 12 weeks. The anti-atherosclerotic effects were evaluated by observing changes in fatty streak lesions, immunohistochemical analysis, ex vivo fluorescence imaging, lipid profiles, and western blot analysis. RESULTS: The CzE-fed group showed a 41.6% reduction of atherosclerosis. Furthermore, CzE significantly reduced the levels of serum triglyceride, high-density lipoprotein, the chemokine (C-X3-C-motif ) ligand 1, the adhesion molecules vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin; down-regulation of tumor necrosis factor-α, interleukin-6, high mobility group box-1, and cathepsin levels in the aortic sinuses and aortas of ApoE^-/- mice were also observed. CONCLUSIONS: The results suggest that the inclusion of a water extract of C. zedoaria in a HCD is closely correlated with reducing the risk of vascular inflammatory diseases in an ApoE mouse model.

• Journal of Veterinary Science
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• v.21 no.1
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• pp.9.1-9.15
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• 2020

Regenerative therapy holds great promise in the development of cures of some untreatable diseases such as cardiovascular diseases, and pluripotent stem cells (PSCs) including induced PSCs (iPSCs) are the most important regenerative seed cells. Recently, differentiation of human PSCs into functional tissues and cells in vitro has been widely reported. However, although porcine reports are rare they are quite essential, as the pig is an important animal model for the in vitro generation of human organs. In this study, we reprogramed porcine embryonic fibroblasts into porcine iPSCs (piPSCs), and differentiated them into cluster of differentiation 31 (CD31)-positive endothelial cells (ECs) (piPSC-derived ECs, piPS-ECs) using an optimized single-layer culture method. During differentiation, we observed that a combination of GSK3β inhibitor (CHIR99021) and bone morphogenetic protein 4 (BMP4) promoted mesodermal differentiation, resulting in higher proportions of CD31-positive cells than those from separate CHIR99021 or BMP4 treatment. Importantly, the piPS-ECs showed comparable morphological and functional properties to immortalized porcine aortic ECs, which are capable of taking up low-density lipoprotein and forming network structures on Matrigel. Our study, which is the first trial on a species other than human and mouse, has provided an optimized single-layer culture method for obtaining ECs from porcine PSCs. Our approach can be beneficial when evaluating autologous EC transplantation in pig models.

• Journal of Veterinary Science
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• v.21 no.4
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• pp.59.1-59.12
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• 2020

Background: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. To understand AD, there have been many trials establishing AD animal models. Although various trials to establish AD animal models have been existed, even the mechanisms of AD in animal models are not enough clarified. Objectives: This study assessed AD characteristics induced in Nishiki-nezumi Cinnamon/Nagoya (Nc/Nga) mice following trinitrochlorobenzene (TNCB) treatment for different periods and house dust mite (HDM) treatment to compare each model's immunological patterns, especially with cytokine antibody array tool. Methods: In this study, we exposed Nc/Nga mice to TNCB or HDM extract to induce AD. Nc/Nga mice were divided into 4 groups: control, TNCB 2 weeks-treated, TNCB 8 weeks-treated, and HDM-treated groups. After AD induction, all mice were evaluated by serum immunoglobulin E (IgE) concentration and serum cytokine antibody assays, scoring of skin lesions, scoring of scratching frequency, and histological analysis. Results: The results showed significant differences between groups in serum IgE concentration, skin lesion scores, and scratching frequency. The analysis results for serum cytokine antibody arrays showed that in the TNCB 8 weeks- and HDM-treated groups, but not in the TNCB 2 weeks-treated group, expressions of genes related to the immune response were enriched. Among the histological results, the skin lesions in the HDM-treated group were most similar to those of AD. Conclusions: We confirmed that immunological pattern of AD mice was markedly different between HDM and TNCB treated groups. In addition, the immunological pattern was quietly different dependent on TNCB treated duration.

• Herbal Formula Science
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• v.30 no.4
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• pp.293-304
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• 2022

Objectives : Sagunja-Tang is a famous prescription used in Korean medicine for the purpose of promoting vital energy, and there are few studies using Sagunja-Tang on cerebrovascular diseases yet. As previous studies confirmed that Sagunja-tang is highly likely to be used effectively for stroke, this study was intended to predict the mechanism through which Sagunja-tang would act effectively on stroke. Methods : In this study, a network pharmacology analysis method was used, and oral bioavailability (OB), drug likeness (DL), Caco-2 and BBB permeability were utilized to select compounds with potential activity. For the values of each variable used in this study, OB ≥ 30%, DL ≥ 0.18, Caco-2 ≥ 0, and BBB ≥ 0.3 were applied. Using the above variables, the relations between target genes and diseases that are presumed to be involved in the selected bioavailable compounds were constructed in a network format, and proteins thought to play a major role were identified. Results : Among the compounds included in Sagunja-Tang, 26 bioavailable compounds were selected and it was confirmed that these compounds can be effectively used in cerebrovascular diseases such as Alzheimer's disease and stroke. These compounds are considered to act on proteins related in cell death and growth. The most important mechanism of action was predicted to be apoptosis, and the protein that is thought to play the most key action in this mechanism was caspase-3. Conclusions : In our future study, Sagunja-Tang will be used in an ischemic stroke mouse model, and the mechanism of action will be explored focusing on apoptosis and cell proliferation.

• Journal of Marine Bioscience and Biotechnology
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• v.14 no.2
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• pp.61-68
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• 2022

This study aimed to investigate the hepatoprotective activities of the sea cucumber products, including extracts and hydrolysates, in vitro and in vivo. Dried sea cucumber, produced on the western coast of Korea, was boiled in water or 70% ethanol at 85℃ or 100℃ for 18 or 24 h, respectively, to extract bioactive compounds. The enzymatic hydrolysates were prepared by reacting the dried sea cucumber with pepsin or neutral protease (PNL) under optimal enzyme conditions. The anti-inflammatory effect of the samples was investigated using RAW 264.7 cells treated with lipopolysaccharide (LPS). The amount of nitric oxide (NO) was produced from the cells treated with LPS and each sample was compared. Therefore, the pepsin hydrolysate treatment decreased NO production compared to LPS sole treatment. Furthermore, the effects of the samples on cell injury in the hepatic cell line and bisphenolA-induced hepatic injury mouse model were investigated. The water extracts and the pepsin hydrolysates of sea cucumber significantly inhibited cell injury generated in the hepatocytes without cytotoxicity (p < 0.05), whereas the ethanol extracts were cytotoxic. However, these results indicate that the extracts and the enzymatic hydrolysates derived from sea cucumber can be used as beneficial materials for inhibiting liver damage.

• Journal of Animal Science and Technology
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• v.64 no.6
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• pp.1245-1258
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• 2022

This study was conducted to determine the effect of natural ingredient seasoning on the reduction of heterocyclic amine (HCA) production that may occur when pork belly is cooked at a very high temperature for a long time. Pork belly seasoned with natural ingredients, such as natural spices, blackcurrant, and gochujang, was cooked using the most common cooking methods, such as boiling, pan fry, and barbecue. HCAs in pork belly were extracted through solid-phase extraction and analyzed via high-performance liquid chromatography. For short-term toxicity, a mouse model was used to analyze weight, feed intake, organ weight, and length; hematology and serology analysis were also performed. Results revealed that HCAs formed only when heating was performed at a very high temperature for a long time, not under general cooking conditions. Although the toxicity levels were not dangerous, the method showing the relatively highest toxicity among various cooking methods was barbecue, and the natural material with the highest toxicity reduction effect was blackcurrant. Furthermore, seasoning pork belly with natural materials containing a large amount of antioxidants, such as vitamin C, can reduce the production of toxic substances, such as HCAs, even if pork belly is heated to high temperatures.