• Reproductive and Developmental Biology
• /
• v.37 no.4
• /
• pp.175-183
• /
• 2013

Cathepsin B is abundantly expressed peptidase of the papain family in the lysosomes, and closely related to the cell degradation system such as apoptosis, necrosis and autophagy. Abnormal degradation of organelles often occurs due to release of cathepsin B into the cytoplasm. Many studies have been reported that relationship between cathepsin B and intracellular mechanisms in various cell types, but porcine embryos has not yet been reported. Therefore, this study evaluated the effect of cathepsin B inhibitor (E-64) on preimplantation developmental competence and quality of porcine embryos focusing on apoptosis and oxidative stress. The expression of cathepsin B mRNA in porcine embryos was gradually decreased in inverse proportion to E-64 concentration by using real-time RT-PCR. When putative zygotes were cultured with E-64 for 24 h, the rates of early cleavage and blastocyst development were decreased by increasing E-64 concentration. However, the rate of blastocyst development in $5{\mu}M$ treated group was similar to the control. On the other hand, both the index of apoptotic and reactive oxygen species (ROS) of blastocysts were significantly decreased in the $5{\mu}M$ E-64 treated group compared with control. We also examined the mRNA expression levels of apoptosis related genes in the blastocysts derived from $5{\mu}M$ E-64 treated and non-treated groups. Expression of the pro-apoptotic Bax gene was shown to be decreased in the E-64 treated blastocyst group, whereas expression of the anti-apoptotic Bcl-xL gene was increased. Taken together, these results suggest that proper inhibition of cathepsin B at early development stage embryos improves the quality of blastocysts, which may be related to not only the apoptosis reduction but also the oxidative stress reduction in porcine embryos.

• The Korean Journal of Physiology and Pharmacology
• /
• v.10 no.2
• /
• pp.85-94
• /
• 2006

A splanchic artery occlusion for 90 min followed by reperfusion of the mesenteric circulation resulted in a severe form of circulatory shock, characterized by endothelial dysfunction, severe hypotension, marked intestinal tissue injury, and a high mortality rate. The effect of defibrotide, a complex of single-stranded polydeoxyribonucleotides having antithrombotic effect, was investigated in a model of splanchnic artery occlusion (SAO) shock in urethane anesthetized rats. Occlusion of the superior mesenteric artery for 90 min produced a severe shock state, resulting in a fatal outcome within 120 min of reperfusion in many rats. Defibrotide (10 mg/kg body weight) 10 min prior to reperfusion significantly improved mean arterial blood pressure in comparison to vehicle treated rats (p＜0.05). Defibrotide treatment also significantly attenuated in the increase of plasma amino nitrogen concentration, intestinal myeloperoxidase activity, intestinal lipid peroxidation, infiltration of neutrophils in intestine and thrombin induced adherence of neutrophils to superior mesentric artery segments. Superoxide anion and hydrogen peroxide production in $1{\mu}M$ formylmethionylleucylphenylalanine (fMLP)-activated PMNs was inhibited by defibrotide in a dose-dependent fashion. Defibrotide effectively scavenged hydrogen peroxide, but not hydroxyl radical. Treatment of SAO rats with defibrotide inhibited tumor necrosis factor-${\alpha}$, and interleukin-1${\beta}$ productions in blood in comparison with untreated rats. These results suggest that defibrotide partly provides beneficial effects by preserving endothelial function, attenuating neutrophil accumulation, and antioxidant in the ischemic reperfused splanchnic circulation

• The Journal of Korean Obstetrics and Gynecology
• /
• v.18 no.1
• /
• pp.181-191
• /
• 2005

Purpose : ${\beta}$-sitosterol is kind of phytosterols or plant which are structurally similar to cholesterol. This study was aimed to investigate the inhibitory effect of the ${\beta}$-sitosterol on the proliferation of human uterine leiomyoma cells and the expression of gene related the mechanism of cell apoptosis. Methods : We counted the number of death cells treated with indicated time of the ${\beta}$-sitosterol and investigated cell death rate by cell count assay. Furthermore, flow cytometry analysis and DNA fragmentation assay were used to dissect between necrosis and apoptosis. and then we observed the differential gene expression by western blot analysis. Results : 1) The inhibitory effect on the growth of uterine leiomyoma cell treated with the ${\beta}$-sitosterol $16{\mu}M$ was increased in a time dependent. 2) The result of flow cytometry analysis, subG1 phase arrest related cell apoptosis was investigated 16.97% in uterine leiomyoma cell treated with the ${\beta}$-sitosterol $16{\mu}M$ and showed the fashion of proportional time dependent. 3) The gene expression of p27, p21 related cell cycle was increased according to increasing time interval but cyclin E-CDK2 complex was decreased expression. 4) The character of apoptosis, DNA fragmentation was significantly observed on the time dependent. 5) The expression of pro-caspase 3 and PARP were decreased dependent on treatment with time dependent. Conclusion : This study showed that the ${\beta}$-sitosterol have the inhibitory effect on the proliferation of human uterine leiomyoma cell and the effect was related with apoptosis.

• Archives of Plastic Surgery
• /
• v.37 no.6
• /
• pp.726-731
• /
• 2010

Purpose: Autologous fat grafting is a popular procedure for the correction of the soft tissue depression and deformity. But there are several issues required to be carefully considered in relation to this procedure, mainly about the unpredictability and the low survival rate of the grafted fat due to absorption and partial necrosis. Sphingosine-1-phosphate (S1P) is a lysophospholipid mediator that has been proposed to promote angiogenesis and to regulate the differentiation of adipose derived stromal cells (ASCs). In this study, we analyzed the viability of the grafted fat tissue mixed with S1P into each 12 nude mice (cann.cg-fox1nu/crlori) compared to the group of mice grafted fat tissue only. Methods: Human aspirated fat was grafted subcutaneously into the backs of 8-week-old nude mice with or without S1P. Eight weeks later, the grafted fat was harvested and the weight and volume were checked. The fat was stained with hematoxylin-eosin and 4',6-diamidino-2-phenylindole. Results: S1P group weighed significantly more than the control group (p=0.009), and the volume from the S1P group was considerably larger than that of the control group (p=0.004) either. In histological features, the surviving layer of the S1P group was thicker than the control group and microvasculature appeared to be prominent in the S1P group, especially in the outer layers. Conclusion: These findings suggest that S1P plays a vital role in the soft tissue augmentation, potentially providing a novel point of the control in adipose tissue for microfat graft.

• Journal of Korean Neurosurgical Society
• /
• v.60 no.1
• /
• pp.114-117
• /
• 2017

A 42-year-old man was admitted to our hospital with complaints of low back pain and intermittent right thigh pain. Twelve weeks before admission, the patient received intradiscal electrothermal therapy (IDET) at a local hospital. The patient still reported low back pain after the procedure that was managed with narcotic analgesics. Follow-up magnetic resonance imaging (MRI) was performed, and his referring physician thought the likely diagnosis was spondylodiscitis at the L4-5 spinal segment with a small epidural abscess. At admission to our department, the patient reported aggravated low back pain. Blood test results, including the erythrocyte sedimentation rate and C-reactive protein levels, were slightly elevated. Biopsy samples of the L4, L5 vertebral bodies and disk were obtained. The material underwent aerobic, anaerobic, fungal, mycobacterial cultures and histologic examination. Results of all cultures were negative. Histologically, necrosis of the bone was evident from the number of empty osteocyte lacunae. In addition, there was no evidence of infection based on biopsy results. No antibiotic treatment was administered on discharge. Repeat computed tomography and MRI performed 12 months after IDET showed a bony defect in the L4 and L5 vertebral bodies, and a decrease in the size of the L4-5 intervertebral disc lesion. We report a case of lumbar vertebral osteonecrosis induced by IDET and discuss etiology and radiologic features.

• Nutrition Research and Practice
• /
• v.11 no.4
• /
• pp.290-299
• /
• 2017

BACKGROUND/OBJECTIVES: Spirulina is a known a functional food related to lipid profiles, immune functions, and antioxidant capacity. Circulating monocyte chemoattractant protein-1 (MCP-1) level is associated with inflammation markers. Single nucleotide polymorphism in the MCP-1 promoter region -2518 have been identified and shown to affect gene transcription. Gene variation may also impact functional food supplementary effects. The current study investigated the interaction of MCP-1 -2518 polymorphism with spirulina supplements on anti-inflammatory capacity in Korean elderly. SUBJECTS/METHODS: After genotyping, healthy elderly subjects (n = 78) were included in a randomized, double blind, and placebo controlled study. Baseline characteristic, body composition, and dietary intake were measured twice (baseline vs. week 16). For 16 weeks, subjects consumed 8 g either spirulina or placebo daily. Plasma MCP-1, interleukin (IL) -2, IL-6, tumor necrosis factor (TNF)-${\alpha}$, complement (C) 3, immunoglobulin (Ig) G, and Ig A concentrations and lymphocyte proliferation rate (LPR) were analyzed as inflammatory markers. RESULTS: In the placebo group with A/A genotype, MCP-1 level was significantly increased, but the spirulina group with A/A genotype was unchanged. IL-2 was significantly increased only in subjects with spirulina supplementation. TNF-${\alpha}$ was significantly reduced in subjects with the G carrier. C3 was significantly increased in the placebo group, particularly when A/A increased more than G, but not when spirulina was ingested. LPR was significantly different only in subjects with A/A genotype; there was a significant increase in phytohemagglutinin and lipopolysaccharide induced LPR in the spirulina group. CONCLUSION: In healthy Korean elderly, spirulina supplementation may influence different inflammatory markers by the MCP-1 genotype. These results may be useful for customized dietary guidelines to improve immune function in Koreans.

• Clinical and Experimental Pediatrics
• /
• v.64 no.2
• /
• pp.68-75
• /
• 2021

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading worldwide since December 2019. Hundreds of cases of children and adolescents with Kawasaki disease (KD)-like hyperinflammatory illness have been reported in Europe and the United States during the peak of the COVID-19 pandemic with or without shock and cardiac dysfunction. These patients tested positive for the polymerase chain reaction or antibody test for SARS-CoV-2 or had a history of recent exposure to COVID-19. Clinicians managing such patients coined new terms for this new illness, such as COVID-19-associated hyperinflammatory response syndrome, pediatric inflammatory multisystem syndrome temporally associated with COVID-19, or COVID-19-associated multisystem inflammatory syndrome in children (MIS-C). The pathogenesis of MIS-C is unclear; however, it appears similar to that of cytokine storm syndrome. MIS-C shows clinical features similar to KD, but differences between them exist with respect to age, sex, and racial distributions and proportions of patients with shock or cardiac dysfunction. Recommended treatments for MIS-C include intravenous immunoglobulin, corticosteroids, and inotropic or vasopressor support. For refractory patients, monoclonal antibody to interleukin-6 receptor (tocilizumab), interleukin-1 receptor antagonist (anakinra), or monoclonal antibody to tumor necrosis factor (infliximab) may be recommended. Patients with coronary aneurysms require aspirin or anticoagulant therapy. The prognosis of MIS-C seemed favorable without sequelae in most patients despite a reported mortality rate of approximately 1.5%.

• The Journal of Korean Medicine
• /
• v.39 no.4
• /
• pp.86-113
• /
• 2018

Objectives: We examined the effects of a mixed formula consisting of dried pomegranate concentrate powder (PCP) and the aqueous extracts of Eucommiae cortex (EC) and Achyranthis radix (AR) in rats with surgically induced osteoarthritis (OA). Methods: Two weeks after OA-inducing surgery, a PCP:EC:AR 5:4:1 (g/g) combination or single formula was orally administered. Changes in body weight, knee thickness, maximum knee extension angle, bone mineral density of the knee joints, femoral and tibial articular surfaces, and compressive strength of the femoral and tibial articular cartilage (AC) were assessed, along with the prostaglandin E2 level, 5-lipoxygenase, matrix metalloproteinase (MMP)-2 and MMP-9 activity, and chondrogenic gene mRNA expression in the femoral and tibial AC with the synovial membrane (SM). In addition, the number of cleaved poly(ADP-ribose) polymerase, cyclooxygenase and tumor necrosis factor-${\alpha}$-immunoreactive cells in the femoral and tibial AC with SM were monitored, and the rate of cell proliferation was determined with a 5-bromo-2'-deoxyuridine uptake assay. Results : The signs of surgically induced OA in rats were significantly inhibited by both PCP, EC and AR combined and single formulas. In particular, the combination formula-treated OA model rats showed dose-dependent, significantly increased inhibitory activity against all tested criteria compared with single formula-treated rats. Conclusions: Taken together, our results suggest that the combination formula synergistically increased the anti-OA effects of its components through anti-inflammatory and chondrogenic activity in rats with surgically induced OA. In addition, 200, 100 and 50 mg/kg combination formula treatments showed dose-dependent inhibitory activity against all of the tested criteria.

• Journal of Periodontal and Implant Science
• /
• v.48 no.6
• /
• pp.337-346
• /
• 2018

Purpose: Peripheral artery disease (PAD) is a form of arteriosclerosis that occurs in the extremities and involves ischemia. Previous studies have reported that patients with periodontitis are at high risk for PAD. However, the relationship between these 2 diseases has not yet been fully elucidated. In this cross-sectional study, we investigated this relationship by comparing patients with PAD to those with arrhythmia (ARR) as a control group. Methods: A large-scale survey was conducted of patients with cardiovascular disease who visited Tokyo Medical and Dental University Hospital. We investigated their oral condition and dental clinical measurements, including probing pocket depth, bleeding on probing, clinical attachment level, and number of missing teeth; we also collected salivary and subgingival plaque samples and peripheral blood samples. All patients with PAD were extracted from the whole population (n=25), and a matching number of patients with ARR were extracted (n=25). Simultaneously, ARR patients were matched to PAD patients in terms of age, gender, prevalence of diabetes, hypertension, dyslipidemia, obesity, and the smoking rate (n=25 in both groups). Real-time polymerase chain reaction was performed to measure the bacterial counts, while the enzyme-linked immunosorbent assay method was used to measure anti-bacterial antibody titers and proinflammatory cytokine levels in serum. Results: PAD patients had more missing teeth ($18.4{\pm}2.0$) and higher serum levels of C-reactive protein ($1.57{\pm}0.85mg/dL$) and tumor necrosis factor-alpha ($70.3{\pm}5.7pg/mL$) than ARR patients ($12.0{\pm}1.7$, $0.38{\pm}0.21mg/dL$, and $39.3{\pm}4.5pg/mL$, respectively). Meanwhile, no statistically significant differences were found in other dental clinical measurements, bacterial antibody titers, or bacterial counts between the 2 groups. Conclusions: Our findings suggested that PAD patients had poorer oral and periodontal state with enhanced systemic inflammation.

• Journal of Microbiology and Biotechnology
• /
• v.29 no.1
• /
• pp.151-159
• /
• 2019

Lipoteichoic acid isolated from Lactobacillus plantarum K8 (pLTA) alleviates lipopolysaccharide (LPS)-induced excessive inflammation through inhibition of $TNF-{\alpha}$ and interleukin (IL)-6. In addition, pLTA increases the survival rate of mice in a septic shock model. In the current study, we have found that pLTA contributes to homeostasis through regulation of pro- and anti-inflammatory cytokine production. In detail, pLTA decreased the production of IL-10 by phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells stimulated with prostaglandin E2 (PGE-2) and LPS. However, $TNF-{\alpha}$ production which was inhibited by PGE-2+LPS increased by pLTA treatment. The regulatory effects of IL-10 and $TNF-{\alpha}$ induced by PGE-2 and LPS in PMA-differentiated THP-1 cells were mediated by pLTA, but not by other LTAs isolated from either Staphylococcus aureus (aLTA) or L. sakei (sLTA). Further studies revealed that pLTA-mediated IL-10 inhibition and $TNF-{\alpha}$ induction in PGE-2+LPS-stimulated PMA-differentiated THP-1 cells were mediated by dephosphorylation of p38 and phosphorylation of c-Jun N-terminal kinase (JNK), respectively. Reduction of pLTA-mediated IL-10 inhibited the metastasis of breast cancer cells (MDA-MB-231), which was induced by IL-10 or conditioned media prepared from PGE-2+LPS-stimulated PMA-differentiated THP-1 cells. Taken together, our data suggest that pLTA contributes to inflammatory homeostasis through induction of repressed pro-inflammatory cytokines as well as inhibition of excessive anti-inflammatory cytokines.