• Journal of Veterinary Clinics
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• v.39 no.6
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• pp.302-310
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• 2022

Recently, in human medicine and veterinary medicine, interest in synthetic bone graft is increasing. Among them, bone morphogenic protein (BMP) is currently being actively researched and applied to clinical trials. However, BMP has the disadvantage of being expensive and easily absorbed into surrounding tissues. Therefore, BMP requires the use of small amounts and rhBMP (recombinant human bone morphogenetic protein)-2 carriers that can be released slowly. Hydrogel has the property of swelling a large amount of water inside when it is aqueous solution, and when it is, it consists of more than 90 percent water. Using these properties, hydrogels are often used as rhBMP-2 carrier. The scaffold used in this study is a hydrogel made from which keratin is extracted using human hair and based on it. In this study, we wanted to see the effect of bone formation in the calvarial defect model by using keratin-based hydrogel made with human hair as a scaffold. The experiment was conducted by dividing 3 groups a total of 12 mice. Calvarial bone defect is set to all 4 mm diameters. Bone formation was evaluated by using gross evaluation, micro-computed tomography (micro-CT), immunohistochemistry. Groups using keratin-based hydrogel were significantly observed compared to Group 1s, and the most bone formations were found when rhBMP-2 and hydrogel were used. This represents the superiority of the functions of the rhBMP-2 carrier by a new material, keratin-based hydrogel. Through gross evaluation, micro-CT, and immunohistochemistry, we can confirm that keratin-based hydrogel is a useful rhBMP-2 carrier.

• Genomics & Informatics
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• v.21 no.1
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• pp.8.1-8.19
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• 2023

Cancer of the stomach is the second most frequent cancer-related death worldwide. The survival rate of patients with gastric cancer (GC) remains fragile. There is a requirement to discover biomarkers for prognosis approaches. Helicobacter pylori in the stomach is closely associated with the progression of GC. We identified the genes associated with poor/favorable prognosis in H. pylori-induced GC. Multivariate statistical analysis was applied on the Gene Expression Omnibus (GEO) dataset GSE54397 to identify differentially expressed miRNAs (DEMs) in gastric tissues with H. pylori-induced cancer compared with the H. pylori-positive with non-cancerous tissue. A protein interaction map (PIM) was built and subjected to DEMs targets. The enriched pathways and biological processes within the PIM were identified based on substantial clusters. Thereafter, the most critical genes in the PIM were illustrated, and their prognostic impact in GC was investigated. Considering p-value less than 0.01 and |Log2 fold change| as >1, five microRNAs demonstrated significant changes among the two groups. Gene functional analysis revealed that the ubiquitination system, neddylation pathway, and ciliary process are primarily involved in H. pylori-induced GC. Survival analysis illustrated that the overexpression of DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, and TXNIP was associated with poor prognosis, while increased MRPS5 expression was related to a favorable prognosis in GC patients. DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, TXNIP, and MRPS5 may be considered prognostic biomarkers for H. pylori-induced GC. However, experimental validation is necessary in the future.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.619-628
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• 2023

In the modern era, chronic kidney failure due to diabetes has spread across the globe. Prunetin (PRU), a component of herbal medicines, has a broad variety of pharmacological activities; these may help to slow the onset of diabetic kidney disease. The anti-nephropathic effects of PRU have not yet been reported. The present study explored the potential nephroprotective actions of PRU in diabetic rats. For 28 days, nephropathic rats were given oral doses of PRU (20, 40, and 80 mg/kg). Body weight, blood urea, creatinine, total protein, lipid profile, liver marker enzymes, carbohydrate metabolic enzymes, C-reactive protein, antioxidants, lipid peroxidative indicators, and the expression of insulin receptor substrate 1 (IRS-1) and glucose transporter 2 (GLUT-2) mRNA genes were all examined. Histological examinations of the kidneys, liver, and pancreas were also performed. The oral treatment of PRU drastically lowered the blood glucose, HbA1c, blood urea, creatinine, serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, lipid profile, and hexokinase. Meanwhile, the levels of fructose 1,6-bisphosphatase, glucose-6-phosphatase, and phosphoenol pyruvate carboxykinase were all elevated, but glucose-6-phosphate dehydrogenase dropped significantly. Inflammatory marker antioxidants and lipid peroxidative markers were also less persistent due to this administration. PRU upregulated the IRS-1 and GLUT-2 gene expression in the nephropathic group. The possible renoprotective properties of PRU were validated by histopathology of the liver, kidney, and pancreatic tissues. It is therefore proposed that PRU (80 mg/kg) has considerable renoprotective benefits in diabetic nephropathy in rats.

• Journal of Ginseng Research
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• v.48 no.2
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• pp.181-189
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• 2024

Background: Cigarette smoke is generally accepted as a major contributor to chronic obstructive pulmonary disease (COPD), which is characterized by emphysematous lesions. In this study, we investigated the protective effects of Korean Red Ginseng (KRG) against cigarette smoke condensate (CSC)-induced emphysema. Methods: Mice were instilled with 50 mg/kg of CSC intranasally once a week for 4 weeks, KRG was administered to the mice once daily for 4 weeks at doses of 100 or 300 mg/kg, and dexamethasone (DEX, positive control) was administered to the mice once daily for 2 weeks at 3 mg/kg. Results: KRG markedly decreased the macrophage population in bronchoalveolar lavage fluid and reduced emphysematous lesions in the lung tissues. KRG suppressed CSC-induced apoptosis as revealed by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining and Caspase 3 immunohistochemistry. Additionally, KRG effectively inhibited CSC-mediated activation of Bcl-2-associated X protein/Caspase 3 signaling, followed by the induction of cell survival signaling, including vascular endothelial growth factor/phosphoinositide 3-kinase/protein kinase B in vivo and in vitro. The DEX group also showed similar improved results in vivo and in vitro. Conclusion: Taken together, KRG effectively inhibits macrophage-mediated emphysema induced by CSC exposure, possibly via the suppression of pro-apoptotic signaling, which results in cell survival pathway activation. These findings suggest that KRG has therapeutic potential for the prevention of emphysema in COPD patients.

• Journal of Ginseng Research
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• v.48 no.3
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• pp.323-332
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• 2024

Background: Studies have reported that the combination of two or more therapeutic compounds at certain ratios has more noticeable pharmaceutical properties than single compounds and requires reduced dosage of each agent. Red ginseng and velvet antler have been extensively used in boosting immunity and physical strength and preventing diseases. Thus, this study was conducted to elucidate the skin-protective potentials of red ginseng extract (RGE) and velvet antler extract (VAE) alone or in combination on ultraviolet (UVB)-irradiated human keratinocytes and SKH-1 hairless mice. Methods: HaCaT cells were preincubated with RGE/VAE alone or in combination for 2 h before UVB (30 mJ/cm²) irradiation. SKH-1 mice were orally given RGE/VAE alone or in combination for 15 days before exposure to single dose of UVB (600 mJ/cm²). Treated cells and treated skin tissues were collected and subjected to subsequent experiments. Results: RGE/VAE pretreatment alone or in combination significantly prevented UVB-induced cell death, apoptosis, reactive oxygen species production, and DNA damage in keratinocytes and SKH-1 mouse skins by downregulating mitogen-activated protein kinases/activator protein 1/nuclear factor kappa B and caspase signaling pathways. These extracts also strengthened the antioxidant defense systems and skin barriers in UVB-irradiated HaCaT cells and SKH-1 mouse skins. Furthermore, RGE/VAE co-administration appeared to be more effective in preventing UVB-caused skin injury than these extracts used alone. Conclusion: Overall, these findings suggest that the consumption of RGE/VAE, especially in combination, offers a protective ability against UVB-caused skin injury by preventing inflammation and apoptosis and enhancing antioxidant capacity.

• Nutrition Research and Practice
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• v.18 no.2
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• pp.194-209
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• 2024

BACKGROUND/OBJECTIVES: High levels of plasma low-density lipoprotein (LDL) cholesterol are an important determinant of atherosclerotic lesion formation. The disruption of cholesterol efflux or reverse cholesterol transport (RCT) in peripheral tissues and macrophages may promote atherogenesis. The aim of the current study was to examine whether bioactive ellagic acid, a functional food component, improved RCT functionality and high-density lipoprotein (HDL) function in diet-induced atherogenesis of apolipoproteins E (apoE) knockout (KO) mice. MATERIALS/METHODS: Wild type mice and apoE KO mice were fed a high-cholesterol Paigen diet for 10 weeks to induce hypercholesterolemia and atherosclerosis, and concomitantly received 10 mg/kg ellagic acid via gavage. RESULTS: Supplying ellagic acid enhanced induction of apoE and ATP-binding cassette (ABC) transporter G1 in oxidized LDL-exposed macrophages, facilitating cholesterol efflux associated with RCT. Oral administration of ellagic acid to apoE KO mice fed on Paigen diet improved hypercholesterolemia with reduced atherogenic index. This compound enhanced the expression of ABC transporters in peritoneal macrophages isolated from apoE KO mice fed on Paigen diet, indicating increased cholesterol efflux. Plasma levels of cholesterol ester transport protein and phospholipid transport protein involved in RCT were elevated in mice lack of apoE gene, which was substantially reduced by supplementing ellagic acid to Paigen diet-fed mice. In addition, ellagic acid attenuated hepatic lipid accumulation in apoE KO mice, evidenced by staining of hematoxylin and eosin and oil red O. Furthermore, the supplementation of 10 mg/kg ellagic acid favorably influenced the transcriptional levels of hepatic LDL receptor and scavenger receptor-B1 in Paigen diet-fed apoE KO mice. CONCLUSION: Ellagic acid may be an athero-protective dietary compound encumbering diet-induced atherogenesis though improving the RCT functionality.

• Korean Circulation Journal
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• v.54 no.1
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• pp.43-56
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• 2024

Background and Objectives: The therapeutic strategy for inflammation and degenerative calcification is of utmost importance for bioprosthetic heart valve (BHV) implanted patients. The purpose of this study was to compare the anti-inflammatory and anti-calcification effects of Entelon150^® (grape seed extract), losartan, and rosuvastatin, in a rabbit model of intravascular BHV leaflet implantation in bovine pericardium. Methods: A total of 28 rabbits were implanted with BHV leaflet in the external jugular veins. The Entelon150^® group was administered 7.7 mg/kg Entelon150^® twice daily for 6 weeks after surgery. The losartan and rosuvastatin groups received 5.14 mg/kg and 1 mg/kg, respectively, once per day. The control group received 1 ml of saline once daily. And then, calcium concentration was measured in the implanted BHV, and histological and molecular analyses were performed on the surrounding tissues. Results: The calcium content of the implanted tissue in the Entelon150^® group (0.013±0.004 mg/g) was lower than that in the control group (0.066±0.039 mg/g) (p=0.008). The losartan (0.024±0.016 mg/g, p=0.032) and rosuvastatin (0.022±0.011 mg/g, p=0.032) groups had lower calcium content than the control group, and higher tendency than the Entelon150^® group. Immunohistochemistry revealed that the expressions of bone morphogenic protein 2 (BMP2), S-100, and angiotensin II type 1 receptor in the Entelon150^® group showed lower tendency than those in the control group. The protein expression levels of BMP2 were reduced in the Entelon150^® group compared with those in the control group. Conclusions: Entelon150^® exhibited a significant effect, similar to other drugs, in reducing calcification and inflammation in the intravascular bovine pericardium.

• International Journal of Oncology
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• v.56 no.2
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• pp.618-629
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• 2020

Bcl2l10, also known as Diva, Bcl-b and Boo, is a member of the Bcl2 family of proteins, which are involved in signaling pathways that regulate cell apoptosis and autophagy. Previously, it was demonstrated that Bcl2l10 plays a crucial role in the completion of oocyte meiosis and is a key regulator of Aurora kinase A (Aurka) expression and activity in oocytes. Aurka is overexpressed in several types of solid tumors and has been considered a target of cancer therapy. Based on these previous results, in the present study, the authors aimed to investigate the regulatory role of Bcl2l10 in A2780 and SKOV3 human ovarian cancer cells. The protein expression of Bcl2l10 was examined in human cancer tissues and cell lines, including the ovaries, using a tissue microarray and various human ovarian cancer cell lines. It was found that Bcl2l10 regulated the protein stability and activities of Aurka in ovarian cancer cells. Although apoptosis was not affected, the cell cycle was arrested at the G0/G1 phase by Bcl2l10 knockdown. Of note, cell viability and motility were markedly increased by Bcl2l10 knockdown. On the whole, the findings of this study suggest that Bcl2l10 functions as tumor suppressor gene in ovarian cancer.

• Korean Journal of Ichthyology
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• v.26 no.3
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• pp.171-178
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• 2014

Myogenesis is the formation process of multinucleated myofiber with a contractile capacity from muscle satellite cell (MSCs) during life. This process is tightly controlled by several transcription factors such as Pax3 and Pax7 (paired box protein 3 and 7), MEF2C (myocyte enhancer factor 2) and MRFs (myogenic regulatory factors) etc. On the contrary, myostatin (MSTN) is a transforming growth factor-${\beta}$ superfamily, which functions as a negative regulator of skeletal muscle development and growth. Carnosic acid (CA) is a major phenolic component in rosemary (Rosmarinus officinalis) and have been reported various biological activities such as anticancer, antioxidant, antimicrobial and therapeutic agents for amnesia, dementia, alzheimer's disease. This study was confirmed to effects of CA on muscle cell line and muscle tissue alteration of zebrafish by intramuscular injection or feeding methods. $10{\mu}M$ CA showed a non-cytotoxic on myoblast and a complete inhibition effect against myostatin activity on luciferase assay. In intramuscular injection experiment, the total protein and triglyceride amount of $10{\mu}M/kg$ of CA injected group increased by 11% and decreased by 13% compared to these of the no injected group. In histology analysis of muscle tissues by hematoxylin/eosin staining, the number of muscle fiber of $10{\mu}M/kg$ of CA injected group decreased by 29% and fiber area increased 40% compared to these of no injected group. In feeding experiment, the total protein and triglyceride amount no significance difference compared to these of the normal feeding group. In histology analysis, the number of muscle fiber of 1% CA fed group decreased by 35% and fiber area increased 56% compared to these of normal fed group. We identified that CA have an effect on hypertrophy of muscle fiber in adult zebrafish and the results of this study are considered as the basic data that can reveal the mechanisms of muscle formation via gene and protein level analysis.

• KSBB Journal
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• v.21 no.5
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• pp.376-383
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• 2006

Pine needle(Pinus densiflora sieb, et zucc) extract has been used to improve cardiovascular disorders, detoxification of nicotine, the infirmities of age and curing diseases of unidentified symptoms. It has various useful components including amino acids, vitamin C, terpenoids and chlorophyll. In this study we have identified 8 different yeast strains that are developed spontaneously causing self fermentation in the extract. The self-fermented pine extract(SFPE) inhibited the growth of some bacterial strains like E. coli, Bacillus subtilis and Staphylococcus aureus. The SFPE($0.2{\mu}{\ell}/ml{\sim}0.3{\mu}{\ell}/ml$) showed 90% NBT superoxide scavenging activities which is similar for all tested samples of different ages. The 7 years old SFPE(0.15 mg/ml and 0.3 mg/ml) caused relaxation of spontaneous contraction and relaxation rhythm of thoracic arterial tissues from rat. Therefore, SFPE has useful effects such as antibacterial, antioxidant and improved blood circulation and could be a good source of functional food development.