• Nutrition Research and Practice
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• v.11 no.6
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• pp.461-469
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• 2017

BACKGROUND/OBSECTIVE: Airway inflammation by eosinophils, neutrophils and alveolar macrophages is a characteristic feature of asthma that leads to pathological subepithelial thickening and remodeling. Our previous study showed that oxidative stress in airways resulted in eosinophilia and epithelial apoptosis. The current study investigated whether glutathione-containing dry yeast extract (dry-YE) ameliorated eosinophilia, goblet cell hyperplasia and mucus overproduction. MATERIALS/METHOD: This study employed $2{\mu}g$/mL lipopolysaccharide (LPS)- or 20 ng/mL eotaxin-1-exposed human bronchial epithelial cells and ovalbumin (OVA)-challenged mice. Dry-YE employed in this study contained a significant amount of glutathione (140 mg in 100 g dry yeast). RESULTS: Human bronchial epithelial cell eotaxin-1 and mucin 5AC (MUC5AC) were markedly induced by the endotoxin LPS, which was dose-dependently attenuated by nontoxic dry-YE at 10-50 ${\mu}g$/mL. Moreover, dry-YE inhibited the MUC5AC induction enhanced by eotaxin-1, indicating that eotaxin-1-mediated eosinophilia may prompt the MUC5AC induction. Oral supplementation with 10-100 mg/kg dry-YE inhibited inflammatory cell accumulation in airway subepithelial regions with a reduction of lung tissue level of intracellular adhesion molecule-1. In addition, ${\geq}50$ mg/kg dry-YE diminished the lung tissue levels of eotaxin-1, eosinophil major basic protein and MUC5AC in OVA-exposed mice. Alcian blue/periodic acid schiff staining revealed that the dry-YE supplementation inhibited goblet cell hyperplasia and mucus overproduction in the trachea and bronchiolar airways of OVA-challenged mice. CONCLUSIONS: Oxidative stress may be involved in the induction of eotaxin-1 and MUC5AC by endotoxin episode and OVA challenge. Dry-YE effectively ameliorated oxidative stress-responsive epithelial eosinophilia and mucus-secreting goblet cell hyperplasia in cellular and murine models of asthma.

• Journal of Yeungnam Medical Science
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• v.25 no.1
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• pp.19-30
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• 2008

Osteoporosis, a disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and fracture risk, is a major public health problem. The diagnostic methods for osteoporosis include simple radiography, bone scan, DXA (Dual energy X-ray Absortiometry) and biochemical markers of bone turnover. Optimal treatment and prevention of osteoporosis require modification of risk factors, particularly smoking cessation, adequate physical activity, and attention to diet, in addition to pharmacologic intervention. The estrogens and raloxifene both prevent bone loss in postmenopausal women, and the estrogens probably also decrease the risk of first fracture. There is good evidence that raloxifene prevents further fractures in postmenopausal women who already have had fractures and some evidence that estrogen does as well. Bisphosphonate prevents bone loss and reduces fractures in healthy and osteoporotic postmenopausal women and in osteoporotic men as well. Risedronate is more potent and has fewer side effects than alendronate and reduces the incidence of fractures in osteoporotic women. Calcitonin increases bone mineral density in early postmenopausal women and men with idiopathic osteoporosis, and also reduces the risk of new fractures in osteoporotic women. All of the agents discussed above prevent bone resorption, whereas teriparatide and strontium increase bone formation and are effective in the treatment of osteoporotic women and men. New avenues for targeting osteoporosis will emerge as our knowledge of the regulatory mechanisms of bone remodeling increases, although issues of tissue specificity may remain to be addressed.

• Journal of Life Science
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• v.30 no.7
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• pp.651-659
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• 2020

Cardiovascular disease is one of the leading causes of death across the world, and gold-standard treatments such as percutaneous coronary intervention and artery bypass grafting have various limitations including myocardial damage and subsequent maladaptive cardiac remodeling. To overcome this, stem-cell therapies are emerging as a promising strategy for cardiovascular regeneration. Endothelial progenitor cells (EPCs) have high potential to proliferate and differentiate into endothelial cells for vascularization and tissue regeneration, and several clinical trials have explored EPC function in tissue repair in relation to clinical safety and improving cardiac function. Consequently, EPC has been suggested as a feasible stem-cell therapy. However, autologous EPC transplantation in cardiovascular disease patients is restricted by risk factors such as age, smoking status, and hypertension that lead to reduced bioactivity in the EPCs. New approaches for improving EPC function and stem-cell efficacy have therefore been suggested, including cell priming, organoid culture systems, and enhancing transplantation efficiency through 3D bioprinting methods. In this review, we provide a comprehensive understanding of EPC characteristics, therapeutic approaches, and the current state of clinical research into EPCs as stem-cell therapy for cardiovascular disease.

• Clinical and Experimental Reproductive Medicine
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• v.25 no.2
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• pp.161-170
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• 1998

Protein expression patterns of matrix metalloproteinases (MMPs) were examined in mouse reproductive organs during estrous cycle. Estrous cycle was classified into diestrus, proestrus, estrus or metestus and MMP expression was analyzed by zymography using gelatin as a substrate. Uterine fluid (UF) obtained both at diestrus and proestrus exhibited 4 major MMPs including 106kDa, 64kDa, 62kDa and 59kDa gelatinases. However, in UF at estrus, the gelatinolytic activity of 64kDa MMP disappeared and that of 106kDa and 62kDa MMPs dramatically decreased. At metestrus, 64kDa MMP activity reappeared and 106kDa and 62kDa MMP exhibited increased activities such that the band intensity of 106kDa was comparable to that in UF at diestrus. Gelatinolytic activity of 59kDa MMP was not changed throughout the cycle. Both ovarian and oviductal tissue homogenate revealed 4 MMPs which corresponded to the 4 MMPs of UF. However, unlike UF MMPs, gelatinolytic activity of these MMPs did not show distinct changes throughout the cycle. Either an inhibitor of MMP, 1,10-phenanthroline, or a metal chelator, EDTA, abolished the appearance of the above MMP activities in gelatinated gel whereas a serine proteinase inhibitor, phcnylmethylsulfonyl fluoride, failed to inhibit the appearance of MMP activities, proving that gelatinolytic activity of the above reproductive tissues were due to the enzymatic activity of MMP. When gclatinolytic activity of mouse serum was examined, it revealed 5 MMPs (131kDa, 106kDa, 89kDa, 64kDa and 62kDa bands) and one gelatinase (84kDa) band. From these results, it is concluded that the protein expression of MMPs of mouse reproductive organs, particularly uterus, is temporally regulated during estrous cycle and uterine 106kDa, 64kDa and 62kDa MMPs are suggested to play an important role in cyclic tissue remodeling of mouse uterus.

• Tuberculosis and Respiratory Diseases
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• v.77 no.2
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• pp.73-80
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• 2014

Background: Low levels of serum vitamin D is associated with several lung diseases. The production and activation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of emphysema. The aim of the current study therefore is to investigate if vitamin D modulates the expression and activation of MMP-2 and MMP-9 in human lung fibroblasts (HFL-1) cells. Methods: HFL-1 cells were cast into three-dimensional collagen gels and stimulated with or without interleukin-$1{\beta}$ (IL-$1{\beta}$) in the presence or absence of 100 nM 25-hydroxyvitamin D (25(OH)D) or 1,25-dihydroxyvitamin D ($1,25(OH)_2D$) for 48 hours. Trypsin was then added into the culture medium in order to activate MMPs. To investigate the activity of MMP-2 and MMP-9, gelatin zymography was performed. The expression of the tissue inhibitor of metalloproteinase (TIMP-1, TIMP-2) was measured by enzyme-linked immunosorbent assay. Expression of MMP-9 mRNA and TIMP-1, TIMP-2 mRNA was quantified by real time reverse transcription polymerase chain reaction. Results: IL-$1{\beta}$ significantly stimulated MMP-9 production and mRNA expression. Trypsin converted latent MMP-2 and MMP-9 into their active forms of MMP-2 (66 kDa) and MMP-9 (82 kDa) within 24 hours. This conversion was significantly inhibited by 25(OH)D (100 nM) and $1,25(OH)_2D$ (100 nM). The expression of MMP-9 mRNA was also significantly inhibited by 25(OH)D and $1,25(OH)_2D$. Conclusion: Vitamin D, 25(OH)D, and $1,25(OH)_2D$ play a role in regulating human lung fibroblast functions in wound repair and tissue remodeling through not only inhibiting IL-$1{\beta}$ stimulated MMP-9 production and conversion to its active form but also inhibiting IL-$1{\beta}$ inhibition on TIMP-1 and TIMP-2 production.

• The korean journal of orthodontics
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• v.26 no.4
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• pp.455-467
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• 1996

This study was designed to evaluate the expression of type I collagen in periodontal tissue during the experimental movement of rat incisors. Twenty-one Sprague-Dawley rats were divided into a control group(3 rats), and experimental groups(18 rats) where a force(75g) from helical springs across the maxillary incisors was applied. Experimental groups were sacrificed at 12 hours, 1, 4, 7, 14 and 28 days after force application, respectively. And tissue slides of control and experimental groups were studied histologically and immunohistochemically by LSAB(Labelled streptavidine Biotin) immunohistochemical staining for type I collagen. The results were as follows: 1. Until 28-day after force application, periodontal fibers were strectched on the tension side, and compressed in pressure side, and the arrangement of periodontal fibers was not recovered by that time. 2. The degree of type I collagen expression in control group was rare in the oral epithelium, predentin, pulp and periodontal ligament, but was mildly positive in osteoblasts, acellular cementum, cementoblasts, intermaxillary suture. 3. At acellular cementum of experimental group, the expression of type I collagen was moderate in 1-day and severe in 7-day, which was maintained until 28-day. 4. Type I collagen was observed in the newly formed fibrous connective tissue and osteoblasts at intermaxillary suture, moderately in 1-day, and severely in 14-day. 5. The tension side of periodontal ligament showed a more positive expression of type I collagen than the pressure side in 4-day. The degree was highest in 7-day and was not differentiated between sides in 14-day. 6. In the side wall of bone matrix on which osteoblasts were attached, type I collagen was expressed severely, especially in 7-day. From the above findings, we could suggest that bone remodeling in tooth movement be intimately related to the cell differentiation and the resulting formation of type I collagen.

• Journal of Chest Surgery
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• v.35 no.6
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• pp.407-419
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• 2002

Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by progressive accumulation of lipids, cells, and extracellular matrix. Matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinases(TIMPS) contribute to vascular matrix remodeling in atherosclerosis, and some cytokines may play role in the synthesis or activation of MMPs or TIMPs. Material and Method： We produced experimental atherosclerotic plaques in 9 rabbits by atherogenic hypercholesterol diet for 12 weeks, and 10 other rabbits were used as control group with standard laboratory chow, At that time, 19 rabbits were sacrificed and aorta, coronary arteries and blood specimens were prepared. The expressions of MMP-9, TIMP-2 and interleukin(IL)-18, and the bioactivity of IL-6 were investigated with H&E stain, immunohistochemical stain, immunoblotting(Western blot analysis), and bioassay. Result： Serum cholesterol in the experimental group increased up to 1258$\pm$262 mg/dL(control group： 41$\pm$7 mg/dL). All experimental group showed well-developed atherosclerotic plaques in aorta and coronary artery. The expression of MMP-9 in aorta and coronary artery of the experimental group showed significant increase than that of the control group by immunohistochemistry. Among the experimental group, complicated lesions with intimal rupture or complete luminal occlusion, demonstrated stronger expression of MMP-9. Interestingly, there was no difference in expression of TIMP-2 between the experimental and the control group. These findings were confirmed by Western blot analysis. The bioassay revealed significant up-regulation of serum bioactivity of IL-6 in the experimental group(4819.60$\pm$2021.25 IU/$m\ell$) compared to that of IL-6 in the control group(27.20 $\pm$ 12.19 IU/$m\ell$). IL-18 was expressed in all atherosclerotic plaques, whereas little or no expression was detected in the control group. Conclusion： The increased MMP-9 expression along with the unchanged TIMP-2 expression seem to be contributory factors in extracellular matrix degradation in atherosclerosis. Focal overexpression of MMP-9 may promote plaque destabilization and cause complications of atherosclerotic plaques such as thrombosis with/without acute coronary syndrome. Elevation of IL-6 and IL-18 may be more than just markers of atherosclerosis but actual participants in lesion development. Identification of critical regulatory pathway is important to improve the understanding of the cellular and molecular basis of atherosclerosis and may open the way for novel therapeutic strategies.

• The korean journal of orthodontics
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• v.36 no.2 s.115
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• pp.103-113
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• 2006

Most elderly women experience a decrease in their bone density due to a deficiency of calcium intake, ovariectomy, or menopause. This study evaluated the usability of the microscrew as a skeletal anchorage system in these orthodontic treatment cases, using rats as a research group. The 4 month old sprague-dawley species rats were divided into two groups, the OS (Ovariectomy Screw), and the SS (Sham operation Screw) group. In both the OS and SS groups, microscrews were implanted into the palatal bone between the upper molar teeth and two upper incisors were retracted using NETE coil spring with 75 g of force. After 3days, the again after 7 days, 7 rats in each group were sacrificed. Three days before they were sacrificed, Alizarin red S was intraperitoneally injected, and their maxillary bone, tibia and blood from their hearts were taken. The components of the extracted blood were biochemically analyzed and non-decalcified grinding resin sections for maxillary bone and tibia were made. The sections were examined with a polarization microscope, and fluorescent microscope. Smaller concentrations of Ca and P, the inorganic substances closely related to bone density, were found in the extracted blood of the OS group. Both OS and SS groups showed a possibility of bone remodeling with a high concentration of ALP after 7 days. An increase in bone density on the tension and compression sides of the microscrew and the tension side of the tooth for both OS and SS groups was confirmed with a polarization microscope. However, the bone density of the pressure side of the tooth and apical side was decreased. More deposits of Alizarin red S in the bone after 7 days rather than 3 days seen with a fluorescent microscope suggested the existence of new bone formation.

• The korean journal of orthodontics
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• v.30 no.3 s.80
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• pp.317-333
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• 2000

The purpose of this study was to determine the proliferative activity of the osteoblasts and fibroblasts in the midpalatal area and to investigate the adjacent periodontal tissues of individual tooth following rapid expansion of the palate. Ten young adult dogs, aged approximately ten months, were used in the experiment. The experimental design was consisted of 1 week expansion group(Group E1, 3 dogs), 2 week expansion group(Group E2, 3 dogs), 2 week expansion and 2 week retention group(Group E3, 3 dogs), and control group(Group C, 1 dog). For each group, expansion screw was activated one time per day(1/4 turn;$90^{\circ}$) following Hyrax-screw application. The experimental animals in each group were sacrificed at 1, 2 and 4 weeks following palatal expansion. Maxillary tissue blocks were obtained and prepared ior the histomorphologic and immunohistochemical studies. Light mcroscope, polarizing microscope, and soft X-ray apparatus were used in this study, and following results were obtained. 1. In polarizing microscopic study, the expansion groups(E1 & E2) showed blue color representing bone resorption and new bone formation in midpalatal suture area. E3 groups skewed less blue color compared to the E1 and E2 group. But yellow color increased by calcification in the E3 groups. 2. Immunohistochemical study revealed that positive responses of the osteoblasts to PCNA and undifferentiated fibroblasts to EGF in E1 group were somewhat increased. Positive response to PCNA and EGF were increased in fibroblasts and the osteoblasts forming new bone in E2 group. In E3 group, the positive response cell concentrated the periphery of edge of palatal process in both PCNA and EGF. 3. Throughout the expansion period(E1 & E2), light microscopic study showed the edges of the extensive resorption and new palatal processes, indicating bone remodeling within the suture. E3 group exhibited less remodeling of midpalatal suture area. E2 group and E3 group showed cementum formation and resorption at the apex of 3rd premolar and 1st molar E3 group exhibited extensive hyalinized zone on the cervical portion of buccal side of 1st molar. 4. Soft X-ray analysis of E1 group showed hypomineralized defect and microfractures in various parts of the suture areas when compared with control animals. There was no significant difference in the degree of mineralization in the midpalatal suture region between the C and E3 groups. Tooth axis showed tipping of 3rd premolar and 1st molar in the E2 group and E3 group. Based upon these experimental results, it is concluded that the undifferentiated mesenchymal cells always presented in midpalatal suture area following RPE. Differentiated osteoblasts and fibroblasts possess proliferating cellular activity until the 2 week retention period. The posterior teeth are tend to tip buccally as RPE force applied. Retention group exhibited irreversible response with severe hyalinized zone on the buccal surface of the first molar.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.297-303
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• 2006

Background : Pulmonary tuberculosis is frequently accompanied with complications such as bronchiectasis, cavities, fibrosis and a deterioration of the lung function. However, there is little information available on the pathogenesis of these complications in pulmonary tuberculosis. Among the many factors involving in tissue remodeling, transforming growth factor-${\beta}1$ ($TGF-{\beta}1$) is a potent stimulus of the extracellular matrix fomation and a mediator of potential relevance for airway wall remodeling. Therefore, this study examined the relationship between the radiological changes and the $TGF-{\beta}1$ level in patients with pulmonary tuberculosis. Methods : Serum and bronchoalveolar lavage fluid (BALF) were collected from total of 35 patients before treating them for active pulmonary tuberculosis, and the $TGF-{\beta}1$ levels were measured using an enzyme-linked immunosorbent assay (ELISA). The BALF levels were recalculated as the epithelial lining fluid (ELF) levels using the albumin method. pulmonary function test (PFT) and high resolution computed tomography (HRCT) were performed before and after treatment. Results : There was a strong correlation between the serum $TGF-{\beta}1$ level and the presence of cavities (r=0.404, p=0.006), even though the BAL $TGF-{\beta}1$ level showed a weak correlation with complications. In addition, there was no correlation between the $TGF-{\beta}1$ levels before treatment and the changes in the PFT and HRCT during treatment. Conclusion : There is a correlation between the serum $TGF-{\beta}1$ level and cavity formation in pulmonary tuberculosis before treatment. However, further study will be needed to confirm this.