• Journal of Nutrition and Health
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• v.55 no.6
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• pp.617-629
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• 2022

Purpose: Osteoporosis is characterized by structural deterioration of the bone tissue because of the loss of osteoblastic activity or the increase in osteoclastic activity, resulting in bone fragility and an increased risk of fractures. Hederagenin (Hed) is a pentacyclic triterpenoid saponin isolated from Dipsaci Radix, the dried root of Dipsacus asper Wall. Dipsaci Radix has been used in Korean herbal medicine to treat bone fractures. In this study, we attempted to demonstrate the potential anti-osteoporotic effect of Hed by examining its effect on osteoblast differentiation in MC3T3-E1 cells. Methods: Osteoblastic MC3T3-E1 cells were cultured in 0, 1, and 10 ㎍/mL Hed for 3 and 7 days. The activity of alkaline phosphatase (ALP), bone nodule formation and level of expression of bone-related genes and proteins were measured in MC3T3-E1 cells exposed to Hed. The western blot test was used to detect the activation of the bone morphogenetic protein-2 (BMP2)/ Suppressor of Mothers against Decapentaplegic (SMAD)1 pathway. Results: Hed significantly increased the proliferation of MC3T3-E1 cells. Intracellular ALP activity was significantly increased in the 1 ㎍/mL Hed-treated group. Hed significantly increased the concentration of calcified nodules. Furthermore, Hed significantly upregulated the expression of genes and proteins associated with osteoblast proliferation and differentiation, such as Runt-related transcription factor 2 (Runx2), ALP, osteopontin (OPN), and type I procollagen (ProCOL1). Induction of osteoblast differentiation by Hed was associated with increased BMP2. In addition, Hed induced osteoblast differentiation by increasing the activity of SMAD1/5/8. These results suggest that Hed has the potential to prevent osteoporosis by promoting osteoblastogenesis in osteoblastic MC3T3-E1 cells via the modulation of the BMP2/SMAD1 pathway. Conclusion: The results presented in this study indicate that Hed isolated from Dipsaci Radix has the potential to be developed as a healthcare food and functional material possessing anti-osteoporosis effects.

• Microbiology and Biotechnology Letters
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• v.50 no.4
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• pp.533-547
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• 2022

This study investigated the hair growth effect of Schisandra chinensis extract (TS-SC) and TS-SC fermented by Lactobacillus plantarum (TS-SCLF) on human dermal papilla cells (hDPCs). The production of vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), keratinocyte growth factor/fibroblast growth factor 7 (KGF/FGF-7) and hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGF-β1) were examined. The secretion rates of VEGF and KGF/FGF-7 were high in TS-SC, and the secretion rates of IGF-1 and HGF were high in TS-SCLF. TGF-β1 was inhibited in a concentration-dependent manner in all samples. Gene expression of VEGF, IGF-1, KGF, HGF and alkaline phosphatase, relevant to hair growth, were examined. The data revealed that TS-SC and TS-SCLF successfully promoted hair growth in hDPCs. The IGF-1 gene was expressed in a dose-dependent manner in TS-SCLF. These results indicate that TS-SC and TS-SCLF fermented extract effectively promoted hair growth and gene expression relevant to hair growth in hDPCs. Used in clinical trials the test substance 'CMK-LPF01' showed a statistically significant increase in the number of hairs at 8 weeks, 16 weeks, and 24 weeks compared to before product use, and a change in hair growth, a secondary efficacy evaluation variable. Through additional research in the future, it is expected that "CMK-LPF01" can be developed as a functional material that can help alleviate symptoms of hair loss.

• Journal of Veterinary Clinics
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• v.40 no.2
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• pp.130-134
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• 2023

A 12-year-old Standard Poodle presented with intermittent weakness and occasional dyspnea at the Veterinary Medicine Teaching Hospital of Kangwon National University. A grade of 4 out of 6 systolic murmur with an irregular tachycardic rhythm was auscultated on both sides of the chest. Systolic blood pressure was 140 mmHg. Panting was noticed in the hospital, but there was no crackle sound. Blood analysis revealed mild increases in liver panel levels (alanine aminotransferase 149 [reference interval, 19-70] U/L; and alkaline phosphatase, 185 [reference interval, 15-127] U/L) and severe increases in cardiac biomarker levels (n-terminal pro-brain natriuretic peptide, 4169 [reference interval, 50-900] pmol/L; and cardiac troponin I, 0.22 [reference interval, 0.03-0.12] ng/mL). On electrocardiography, irregularly irregular supraventricular tachycardic rhythm with an f-wave and no distinct p-wave was observed. Generalized cardiomegaly with an enlarged right atrium and left ventricle was confirmed on thoracic radiography. Moreover, hepatomegaly and an enlarged caudal vena cava were observed. Echocardiographic evaluation revealed a fibromuscular diaphragm in the right ventricle. Because of the obstructive lesion in the right ventricle, the right atrium and ventricle were enlarged (right atrial area index, 38.82 cm²/m² [reference interval, 4.2-10.2 cm²/m²]; right ventricle end-diastolic area index, 14.152 cm²/m² [reference interval, 4.9-10.92 cm²/m²]). Accordingly, the patient was diagnosed with double-chambered right ventricle (DCRV). Pimobendan, furosemide, enalapril, diltiazem, and S-adenosylmethionine (SAMe) were prescribed, and all symptoms were relieved. DCRV is a right-sided congenital heart defect resembling pulmonic valve stenosis. If symptoms are not severe, medical therapy can be facilitated without surgery or the balloon dilation.

• The Journal of Internal Korean Medicine
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• v.44 no.3
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• pp.354-365
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• 2023

Objective: This study aimed to assess the safety and effect on glucose level of Bojungikgi-tang in patients with type 2 diabetes mellitus. Methods: To review patients' clinical characteristics and laboratory tests retrospectively, we investigated 15 hospitalized patients with type 2 diabetes mellitus who took Bojungikgi-tang at Kyung Hee University Korean Medical Hospital for at least one day between January 2012 and December 2022. The blood glucose levels, including fasting blood sugar (FBS), 2-hour postprandial glucose (PP2) levels, and glycated hemoglobin level, were collected to determine the effect of the Bojungikgi-tang on blood sugar changes. Furthermore, to evaluate the safety of Bojungikgi-tang, hepatic function and renal function tests were implemented, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyltransferase, blood urea nitrogen, creatinine, and Modification of Diet in Renal Disease estimated glomerular filtration rate. Results: When Bojungikgi-tang and a standard treatment for diabetes were administered for patients with type 2 diabetes, it was confirmed that there were no statistically significant changes in FBS and PP2 levels in the analysis of each medication taken. There was no significant difference in the safety profile after taking Bojungikgi-tang. Conclusions: The combined administration of Bojungikgi-tang with standard hypoglycemic medication for patients with type 2 diabetes may not affect blood glucose levels and safety.

• Journal of Life Science
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• v.33 no.11
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• pp.859-867
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• 2023

Lupeol is a type of pentacyclic triterpene that has been reported to have therapeutic effects for treating many diseases; however, its effect on insulin resistance is unclear clear. This study examined the inhibitory effect of lupeol on the serine phosphorylation of insulin receptor substrate-1 in insulin resistance-induced 3T3-L1 adipocytes. 3T3-L1 cells were cultured and treated with tumor necrosis factor-α (TNF-α) for 24 hours to induce insulin resistance. Cells treated with different concentrations of lupeol (15 μM or 30 μM) or 100 nM of rosiglitazone were incubated. Then, lysed cells underwent western blotting. Lupeol exhibited a positive effect on the negative regulator of insulin signaling and inflammation-activated protein kinase caused by TNF-α in adipocytes. Lupeol inhibited the activation of protein tyrosine phosphatase-1B (PTP-1B)-a negative regulator of insulin signaling-and c-Jun N-terminal kinase (JNK); it was also an inhibitor of nuclear factor kappa-B kinase (IKK) and inflammation-activated protein kinases. In addition, Lupeol downregulated serine phosphorylation and upregulated tyrosine phosphorylation in insulin receptor substrate-1. Then, the downregulated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway was activated, the translocation of glucose transporter type 4 was stimulated to the cell membrane, and intracellular glucose uptake increased in the insulin resistance-induced 3T3-L1 adipocytes. Lupeol may improve TNF-α-induced insulin resistance by downregulating the serine phosphorylation of insulin receptor substrate 1 by inhibiting negative regulators of insulin signaling and inflammation-activated protein kinases in 3T3-L1 adipocytes.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.4
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• pp.284-290
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• 2023

Adefovir dipivoxil (ADV) is used for the treatment of hepatitis and acquired immunodeficiency syndrome, but long-term use can cause osteoporosis. In this study, the effect of ADV on the osteocyte maturation process was evaluated at the level of undifferentiated cells using mesenchymal stem cells (MSCs) and osteoblasts (MG63). First, MSCs and MG63 cells were treated with ADV at different concentrations, and then a Cell Counting Kit-8 analysis was performed to determine the effect on the proliferation of each cell. Additionally, crystal violet and Hoechst staining were performed for the morphological analysis of each cell and nucleus. To determine the cause of cell hypertrophy, the transforming growth factor-beta (TGF-β) expression was investigated, and alkaline phosphatase (ALP) staining and activity were measured to determine the degree of differentiation of the MSCs and MG63 cells into mature osteocytes. The results confirmed that the ADV increases the expression of TGF-β in MSCs and MG63 cells, causing cellular and nuclear hypertrophy, and can cause osteoporosis by inhibiting cell proliferation and affecting the differentiation of mature osteocytes. Therefore, it is believed that these results can be used as a basis for understanding the adverse effects of ADV at a cytological level in basic medicine and clinical research.

• IMMUNE NETWORK
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• v.21 no.6
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• pp.43.1-43.14
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• 2021

Group 3 innate lymphoid cells (ILC3), which express IL-22 and IL-17A, has been introduced as one of pathologic cells in axial spondyloarthritis (axSpA). Dyslipidaemia should be managed in axSpA patients to reduce cardiovascular disease, and dyslipidaemia promotes inflammation. This study aimed to reveal the role of circulating ILC3 in axSpA and the impact of dyslipidaemia on axSpA pathogenesis. AxSpA patients with or without dyslipidaemia and healthy control were recruited. Peripheral blood samples were collected, and flow cytometry analysis of circulating ILC3 and CD4⁺ T cells was performed. The correlation between Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) and circulating immune cells was evaluated. The effect of oxidized low-density lipoprotein cholesterol (oxLDL-C) on immune cell differentiation was confirmed. AxSpA human monocytes were cultured with with oxLDL-C, IL-22, or oxLDL-C plus IL-22 to evaluate osteoclastogenesis using tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative PCR of osteoclast-related gene expression. Total of 34 axSpA patients (13 with dyslipidaemia and 21 without) were included in the analysis. Circulating IL-22⁺ ILC3 and Th17 were significantly elevated in axSpA patients with dyslipidaemia (p=0.001 and p=0.034, respectively), and circulating IL-22⁺ ILC3 significantly correlated with ASDAS-CRP (Rho=0.4198 and p=0.0367). Stimulation with oxLDL-C significantly increased IL-22⁺ ILC3, NKp44^- ILC3, and Th17 cells, and these were reversed by CD36 blocking agent. IL-22 and oxLDL-C increased TRAP⁺ cells and osteoclast-related gene expression. This study suggested potential role of circulating IL-22⁺ ILC3 as biomarker in axSpA. Furthermore, dyslipidaemia augmented IL-22⁺ ILC3 differentiation, and oxLDL-C and IL-22 markedly increased osteoclastogenesis of axSpA.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.1
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• pp.76-83
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• 2022

Backgrounds/Aims: The aim of this study was to evaluate longitudinal changes of post-liver transplantation (LT) biliary anatomy and to assess the association of increased laboratory values after LT with the development of post-LT anastomotic biliary stricture (ABS). Methods: Adult deceased donor LT recipients from 2008 and 2019 were evaluated. ABS was defined after blinded review of endoscopic cholangiograms. Controls were patients who underwent LT for hepatocellular carcinoma who did not have any clinical or biochemical concerns for ABS. Results: Of 534 patients who underwent LT, 57 patients had ABS and 57 patients served as controls. On MRI, ABS patients had a narrower anastomosis (2.47 ± 1.32 mm vs. 3.38 ± 1.05 mm; p < 0.01) and wider bile duct at 1-cm proximal to the anastomosis (6.73 ± 2.45 mm vs. 5.66 ± 1.95 mm; p = 0.01) than controls. Association between labs at day 7 and ABS formation was as follows: aspartate aminotransferase hazard ratio (HR): 1.014; 95% confidence interval (CI): 1.008-1.020, p = 0.001; total bilirubin HR: 1.292, 95% CI: 1.100-1.517, p = 0.002; and conjugated bilirubin HR: 1.467, 95% CI: 1.216-1.768, p = 0.001. Corresponding analysis results for day 28 were alanine aminotransferase HR: 1.004, 95% CI: 1.002-1.006, p = 0.001; alkaline phosphatase HR: 1.005, 95% CI: 1.003-1.007, p = 0.001; total bilirubin HR: 1.233, 95% CI: 1.110-1.369, p = 0.001; and conjugated bilirubin HR: 1.272, 95% CI: 1.126-1.437, p = 0.001. Conclusions: Elevation of laboratory values early after LT is associated with ABS formation.

• Korean Journal of Agricultural Science
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• v.49 no.4
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• pp.1015-1023
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• 2022

Production of high-quality horses is important to make the horse industry grow. Grazing during the growing period can be an important factor affecting the production of high-quality horses. The objective of this study was to determine the effects of grazing on growing horses by analyzing their blood components and intestinal microbiota. Twelve growing horses for evaluating blood components and ten growing horses for evaluating intestinal microbiota were raised for about seven months and separated by two treatments: grazing vs. stable. Complete blood count, blood chemistry, and creatine kinase levels were analyzed as blood components and a 16s rRNA gene sequence analysis was performed to analyze intestinal microbiota. Calcium ions tended to be lower in the group with grazing treatment. Alkaline phosphatase and creatine kinase tended to be higher in the group with grazing treatment. These results indicate that grazing can provide horses with more exercise than staying in stables. At the phylum level, Firmicutes/Bacteroidetes ratios in grazing and stable groups were 4.2 and 6.5, respectively. Because various studies have reported that a. high Firmicutes/Bacteroidetes ratio indicates obesity, the method of raising horses might affect their physical ability. At the species level, rates of Clostridium butyricum in grazing and stable groups were 3.2% and 13.1%, respectively. Some strains of C. butyricum can cause several diseases such as botulism. These results indicate that grazing can positively affect growing horses in terms of blood components and intestinal microbiota. Moreover, grazing can be helpful to make growing horses healthy through proper exercise.

• International Journal of Stem Cells
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• v.15 no.3
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• pp.324-333
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• 2022

Background and Objectives: This study was to investigate the role of microRNA-29a-3p (miR-29a-3p) in human bone marrow mesenchymal stem cells (hBMSCs), and its relationship with steroid-associated osteonecrosis. Methods and Results: The online tool GEO2R was used to screen out the differentially expressed genes (DEGs) in GSE123568 dataset. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-29a-3p, forkhead box O3 (FOXO3), alkaline phosphatase (ALP), bone gamma-carboxyglutamate protein (OCN) and RUNX family transcription factor 2 (Runx2) in the hBMSCs isolated from the patients with steroid-associated osteonecrosis. CCK-8 assay was executed to measure cell viability; western blot assay was utilized to detect FOXO3, ALP, Runx2, OCN and β-catenin expression. Cell apoptosis and cell cycle were detected by flow cytometry. Immunofluorescence assay was used to detect the sub-cellular localization of β-catenin. Bioinformatics analysis and luciferase reporter gene assay were performed to confirm whether miR-29a-3p can combine with FOXO3 3'UTR. MiR-29a-3p was markedly up-regulated in the hBMSCs of patients with steroid-associated osteonecrosis, while FOXO3 mRNA was significantly down-regulated. Transfection of miR-29a-3p mimics significantly inhibited the hBMSCs' proliferation, osteogenic differentiation markers' expressions, including ALP, Runx2, OCN, and repressed the ALP activity, as well as promoted cell apoptosis and cell-cycle arrest. FOXO3 was identified as a target gene of miR-29a-3p, and miR-29a-3p can inhibit the expression of FOXO3 and β-catenin, and inhibition of miR-29a-3p promoted translocation of β-catenin to the nucleus. Conclusions: MiR-29a-3p can modulate FOXO3 expression and Wnt/β-catenin signaling to inhibit viability and osteogenic differentiation of hBMSCs, thereby promoting the development of steroid-associated osteonecrosis.