• Journal of Life Science
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• v.22 no.1
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• pp.41-48
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• 2012

Bee venom (BV) has been used in medicine to treat a variety of diseases including arthritis, rheumatism, and various cancers. Recent reports indicate that BV has anti-angiogenic effects, but the precise molecular mechanism underlying the effects of BV against colorectal cancer remains to be elucidated. We examined the effects of BV and its major components (melittin and apamin) on tumor angiogenesis and found that BV significantly decreased protein levels of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), an important factor involved in angiogenesis and tumor progression, in human colorectal carcinoma HCT116 cells. BV also suppressed the transcription of HIF-$1{\alpha}$ under hypoxia, leading to a decrease in the expression of vascular endothelial growth factor (VEGF), a major target gene of HIF-$1{\alpha}$. We also found that these effects were mainly elicited by apamin, but not melittin. BV specifically inhibited the phosphorylation of ERK1/2 without changing the total levels of this protein, but had no effect on kinases of p38/JNK and AKT. Our results suggest that BV may inhibit human colorectal cancer progression and angiogenesis by inhibiting HIF-$1{\alpha}$ and VEGF expression, thereby providing a novel potential mechanism for the anticancer action of BV.

• Journal of Chest Surgery
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• v.43 no.5
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• pp.499-505
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• 2010

Background: There have been several reports using animal experiments that CD1-restricted T-cells have a key role in tumor immunity. To address this issue, we studied the expression of markers for CD1c+ myeloid dendritic cells (DCs) isolated from peripheral blood in the clinical setting. Material and Method: A total of 24 patients with radiologically suspected or histologically confirmed lung cancer who underwent pulmonary resection were enrolled in this study. The patients were divided according to histology findings into three groups: primary adenocarcinoma of lung (PACL), primary squamous cell carcinoma of lung (PSqCL) and benign lung disease (BLD). We obtained 20 mL of peripheral venous blood from patients using heparin-coated syringes. Using flow-cytometry after labeling with monoclonal antibodies, data acquisition and analysis were done. Result: The ratio of CD1c+CD19- dendritic cells to CD1c+ dendritic cells were not significantly different between the three groups. CD40 (p=0.171), CD86 (p=0.037) and HLA-DR (p=0.036) were less expressed in the PACL than the BLD group. Expression of CD40 (p=0.319), CD86 (p=0.036) and HLA-DR (p=0.085) were less expressed in the PACL than the PSqCL group, but the differences were only significant for CD86. Expression of co-stimulatory markers was not different between the PSqCL and BLD groups. Expression of markers for activated DCs were dramatically lower in the PACL group than in groups with other histology (CD40 (p=0.005), CD86 (p=0.013) HLA-DR (p=0.004). Conclusion: These results suggest the possibility that CD1c+ myeloid DCs participate in control of the tumor immunity system and that low expression of markers results in lack of an immune response triggered by dendritic cells in adenocarcinoma of the lung.

• Tuberculosis and Respiratory Diseases
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• v.56 no.2
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• pp.178-186
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• 2004

Background : Photodynamic therapy (PDT) is a new therapeutic method aimed at the selective destruction of cancer cells. The outcome is death of cancer cells through apoptosis or necrosis. The aim of this study was to investigate the characterization of PDT induced cell death in A549 lung cancer cells. Materials and methods : A549 cells were used as the lung cancer cell. 5 aminolevulinic acid (ALA) was used as the photosensitizer and a 632nm diode laser (Biolitec, Germany) as the light source. Cells were incubated with various concentrations of ALA. The 632nm diode laser was then administered for various laser irradiation times. The treated cells were incubated with 24, 48 and 72 hours. The cell viabilities were measured using the crystal violet assay and light microscopy. To observe the cell death mechanism after PDT, cells were observed under fluorescence microscopy after double staining with Hoechst 33342 and propium iodide after PDT. Results : In the crystal violet assay at 24 hours after PDT with a $3.2J/cm^2$ laser irradiation power, the cell viabilities were $89.56{\pm}4.11$, $87.67{\pm}5.48$, and $69.37{\pm}8.84$ with ALA concentrations of 10, 100, and $1mg/m{\ell}$, respectively. In crystal violet assay at 24 hours after PDT with $1mg/m{\ell}$ of ALA, the cell viabilities were $74{\pm}19.85$, $55{\pm}6.1$, and $49.06{\pm}16.64%$ with 1.6, 3.2 and $6.4J/cm^2$ laser irradiation powers, respectively. However, increasing the interval time after PDT did not change the cell viabilities. In the apoptosis assay, photodynamic therapy was inducing the apoptotic cell death. Conclusions : This study shows the apoptotic anticancer effect of photodynamic therapy in A549 lung cancer cells. However, further evaluations with other cancer cells and photosensitizers are necessary.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.6
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• pp.708-713
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• 2008

The effects of administration alone or mixed of Angelica keiskei and turmeric extract on blood lipids were evaluated in hypercholesterolemic diet or P-407-induced hyperlipidemic rats. In the study 1, female Sprague-Dawley rats weighing 160-180 g were divided into each groups and fed high cholesterol diets for 8 weeks. Experimental groups were administered with following diets: basal diet (Normal), high cholesterol diets (1% cholesterol). We did the oral administration for evaluation in experimental groups: C (vehicle), A (angelica extract), T (turmeric extract), AT (angelica extract, turmeric extract/ 1:1 complex). The concentrations of serum total cholesterol, and LDL-cholesterol were decreased by 6.8%, 9.8% in A group, by 22.1%, 28.8% in C group and by 28.2%, 35.6% in AT group, compared to the C group, respectively. HDL-cholesterol levels were not different among the experimental groups. In the study 2, we induced the hypertriglyceridemia in rats by intraperitoneal injection of P-407 (0.5 g/kg) once per three days. From the next day after P-407 injection beginning, we did the oral administration as the study 1. Angelica keiskei extract, turmeric extract and complex extract decreased serum triglyceride by 17.2%, 19.7% and 48.3%, respectively. These results suggested that Angelica keiskei and turmeric extract complex might have synergistic effect in lowering total cholesterol, LDL-cholesterol and triglyceride in hyperlipidemic rats.

• Journal of Yeungnam Medical Science
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• v.18 no.2
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• pp.215-225
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• 2001

Background: There are many evidences that inflammation is an important determinant of the development of atherosclerosis and one of the systemic markers of inflammation, C-reactive protein(CRP), is associated with extent of coronary artery disease and risk of coronary events. We assessed the time response of CRP response after coronary angioplasty and it's influence on the clinical restenosis in angina patients. Materials and Methods: Patients included 36 angina patients undergoing single vessel angioplasty. Levels of CRP were measured before and 12, 24, 48, and 72 hours after angioplasty. Clinical restenosis was assessed at 6 months after procedure. Results: Baseline CRP level was $0.30{\pm}0.01$ mg/dL in stable and $0.46{\pm}0.28$ mg/dL in unstable angina patients(p<0.05). After angioplasty, CRP level was increased with peak at 24 hour and persisted to 72 hours after angioplasty. At 24 hour after angioplasty, the magnitude of CRP change was $0.32{\pm}0.31$ mg/dL in stable and $0.79{\pm}0.73$ mg/dL in unstable angina patient(p<0.05). The change of CRP level was not associated with troponin-T after angioplasty. In unstable angina patients, clinical restenosis was developed in 8% of patients with low baseline CRP levels and in 50% of those with high baseline CRP levels more than 0.6 mg/dL(p<0.05). Conclusion: In unstable angina patients, inflammatory response is more increased than stable angina patients, and increased inflammatory response effects on the restenosis after coronary angioplasty.

• Journal of Oral Medicine and Pain
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• v.30 no.1
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• pp.87-106
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• 2005

In order to evaluate the mechanism of transmission as well as processing of sensory information originating from low-threshold mechanoreceptor in oral and maxillofacial region at primary synaptic region of trigeminal nervous system, vibrissa afferent fibers of adult cat were labeled with intra-axonal HRP injection. Serial sections containing labeled boutons were obtained from the piece of trigeminal interpolar nucleus. Under electron microscope, total 30 labeled boutons were observed, and ultrastructural characteristics, frequency of occurence, synaptic organizations of vibrissa afferent terminals were analysed. The results were as follows: 1. Labeled boutons contained clear, spherical synaptic vesicles with diameter of 45$\sim$55nm. They formed asymmetrical synapse with dendrites showing definite postsynaptic density, larger synaptic cleft, multiple synaptic structures at various regions. With unlabeled axon terminals(p-ending) containing polymorphic synaptic vesicles, they formed symmetrical synapse showing indefinite postsynaptic density and narrower synaptic area. 2. Each labeled bouton formed 1 to 15 synapses, the average of 4.77$\pm$3.37 contacts per labeled bouton, with adjacent neuronal profiles. Relatively complex synaptic organization, which formed synapses with more than 5 neuronal profiles, was observed in a large number(46.7%, n=14) of labeled boutons. 3. Axo-somatic synapse was not observed. The number of axo-dendritic synapse was 1.83$\pm$1.37 per labeled bouton. Majority(85.0%) of axo-dendritic synapses were formed with dendritic shafts, nonprimary dendrites(n=47, 1.57$\pm$1.38/1 bouton), however, synapses formed with primary dendrites(n=6, 0.20$\pm$0.41/1 bouton) or dendritic spines(n=2, 0.07$\pm$0.25/1 bouton) were rare. 4. 76.7%(n=23) of labeled boutons formed axo-axonic synapse (2.93$\pm$2.36/1 bouton) with p-endings containing pleomorphic vesicles. Synaptic triad, in which p-endings formed synapses with labeled boutons and dendrites adjacent to the labeled boutons simultaneoulsy, were also observed in 60.0%(n=18) of labeled boutons. From the above results, vibrissa afferent terminals of adult cat showed distinctive synaptic organization in the trigeminal interpolar nucleus, thus, suggests their correlation with the function of the trigeminal interpolaris nucleus, which participates in processing of complex sensory information such as two-point discrimination and motivational-affective action. Further studies on physiologic functions such as quantitative analysis on ultrastructures of afferent terminals and nerve transmitters participating in presynaptic inhibition are required.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.1047-1057
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• 1998

Background : Sarcoidosis is a systemic granulomatous disorder of unknown origin and characterized by accumulation of T cells and macrophages. Various cytokines may play crucial roles in the activation of T cells and macrophages, and thereby in the formation of granulomas. However, little is known about the balance between proinflammatory cytokines and antiinflammatory cytokines in the development of sarcoid granulomas and disease activities. In the present study, we measured IL-6, IL-8 and IL-10 in the bronchoalveolar lavage fluid(BALF) from patients with pulmonary sarcoidosis to find out whether there is an imbalance between proinflammatory cytokines and antiinflammatory cytokines in the lung. Methods: Fourteen subjects with the diagnosis of sarcoidosis and six healthy volunteers were included. BALF was concentrated ten-fold by pressure ultrafiltration and each cytokine levels were measured by EUSA method. Active sarcoidosis was defined by major organ involvement or clinically progressive diseases. Results: The mean IL-6 levels in the BALF of the active sarcoidosis group were significantly increased than in controls or inactive sarcoidosis group(p<0.05). Meanwhile, the IL-8 levels were increased and IL-10 levels were decreased in the active sarcoidosis group than in controls or inactive sarcoidosis group without significance(p>0.05). In active pulmonary sarcoidosis patients, the IL-6 levels in BALF correlated with the BALF CD4/CD8 ratio(r=0.768, p<0.05) and IL-8 levels(r=0.564, p<0.05). Conclusions : The data presented showed that pro-inflammatory cytokine IL-6 is important in the pathogenesis of sarcoidosis and decreased tendency of anti-inflammatory cytokine IL-10 might also be involved in the development of granulomatous inflammation in sarcoidosis.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.3
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• pp.207-216
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• 2010

Objective: This study was performed to clarify the role of HomeoboxA (HOXA) and its related signaling molecules in the decidualization of primary cultured endometrial cells. Methods: Human endometrial tissues were obtained by curettage of hysterectomy specimens from patients with conditions other than endometrial diseases. Tissues were minced and digested with Trypsin-EDTA for 20 min, $37^{\circ}C$. Cells were cultured with DMEM/F12 medium in $37^{\circ}C$, 5% $CO_2$ incubator for 24 hrs. Cells were treated with HOXA10 siRNA and added transforming growth factor (TGF)-${\beta}1$ (10 ng/mL) for 48 hrs to induces decidualization in vitro. Reverse transcription polymerase chain reaction analysis was accomplished to observe the expression of HOXA10, prolactin, cyclooxygenase (COX)-2, peroxisome proliferatoractivated receptor (PPAR)-$\gamma$, and wingless-type MMTV integration site family (Wnt). Results: HOXA10 expression was increased (1.8 fold vs. non-treated control) in TGF-${\beta}1$ treated cells. Decidualization marker, prolactin, was significantly increased in TGF-${\beta}1$ treated cells compared with HOXA10 siRNA treated cells. Endometrial cell differentiation marker, COX-2 was down-regulated by HOXA10 siRNA even if cells were treated with TGF-${\beta}1$. Wnt4 was down-regulated by treated with HOXA10 siRNA, this expression patters was not changed by TGF-${\beta}1$. Expression of PPAR-$\gamma$ was down regulated by TGF-${\beta}1$ in regardless of HOXA10 siRNA treatment. Conclusion: TGF-${\beta}1$ which is induced by progesterone in endometrial epithelial cells may induces stromal cell decidualization via HOXA10 and Wnt signaling cascade.

• The Korean Journal of Medicine
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• v.99 no.3
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• pp.149-157
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• 2024

Background/Aims: Carbapenems are recommended for treating bacteremia caused by extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae (ESBL-E). However, this has resulted in a significant rise in the utilization of carbapenems in cases of ESBL-E infection. We evaluated the clinical outcomes of patients with ESBL-E bacteremia treated with non-carbapenem antimicrobials. Methods: We conducted a retrospective case-control study of a cohort of patients with documented ESBL-E bacteremia from January 2021 to December 2021. The patients were divided into two groups according to whether they received non-carbapenem or carbapenem therapy. The rates of treatment failure, 30-day mortality and microbiologic failure, and the durations of hospitalization and of antimicrobial therapy were compared between the two groups. Antimicrobial susceptibility testing and phenotypic identification of ESBL-E were performed using the Vitek 2 system. Results: Of 118 patients with ESBL-E bacteremia, 54 received non-carbapenem drugs (non-carbapenem group [NCG]) and 64 received carbapenems (carbapenem group [CG]). Treatment failure at 30 days occurred in 16.7% of the patients in the NCG and in 18.8% in the CG (p = 0.65). The 30-day mortality rate was 14.8% in the NCG and 17.2% in the CG (p = 0.63). Extra-urinary tract infection and prior antimicrobial therapy within 30 days were risk factors for treatment failure in patients with ESBL-E bacteremia. The clinical outcomes did not differ significantly between the two groups, challenging the prevailing preference for carbapenems in the treatment of ESBL-E bacteremia. Conclusions: Non-carbapenem antimicrobials such as piperacillin/tazobactam are recommended for patients with mild ESBL-E bacteremia in South Korea.

• 한국유가공학회:학술대회논문집
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• 2007.09a
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• pp.49-58
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• 2007

Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.