• Microbiology and Biotechnology Letters
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• v.48 no.4
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• pp.569-573
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• 2020

Brucellosis is a zoonotic disease caused by Brucella infections and humans usually contract this disease from close contact with infected animals or their products, usually via the ingestion of cheese or crude milk. Macrophage migration inhibitory factor (MIF) and Pro- and anti-inflammatory cytokines play an important role in susceptibility/resistance and the immunopathogenesis of Brucella infection. These cytokines are crucial factors in the initiation and progression of protective immunity against Brucella infection but the role of MIF has not been well studied in the human response to intracellular microbes. This study was designed to investigate the effect of MIF expression on Brucella susceptibility. A total of 85 positive rose Bengal tests and 24 samples from healthy individuals were collected for this study and subjected to polymerase chain reaction assays (PCR) of the bcsp31 diagnostic gene. MIF concentrations were evaluated using Enzyme-Linked immunosorbent assay (ELISA) and the results showed that 46 (54%) of the rose Bengal test samples were positive and 39 (46%) were negative for bcsp31 (p ≤ 0.05) and used as the gold standard for all of the comparisons in this study. The ELISA results indicate that the mean concentration of MIF was significantly higher in patients with positive rose Bengal tests when compared to the control groups and that its concentration increases with increasing age in both the patient and control groups (p ≤ 0.05).

• Journal of Trauma and Injury
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• v.31 no.3
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• pp.166-173
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• 2018

Purpose: Many traumatic patients die from sepsis and multiple organ failure. Early recognition of post-traumatic sepsis in traumatic patients will help improve the prognosis. Recently, procalcitonin (PCT), macrophage migration inhibitory factor (MIF), and lactic acid have emerged as predictive factors. Our study aims to explore the significance of PCT, MIF and lactic acid as a predictor of posttraumatic-sepsis in trauma patients. Methods: This study was conducted on prospective observational study patients who visited an emergency medical center in a university hospital from March 2014 to February 2016. We measured the white blood cells, c-reactive protein (CRP), lactic acid, PCT, and MIF with serum taken from the patient's blood within 1 hour of the occurrence of the trauma. The definition of post-traumatic sepsis was defined as being part of systemic inflammation response syndrome criteria with infections within a week. Results: A total of 132 patients were analyzed, wherein 74 patients were included in the low injury severity score (ISS) group (ISS <15) and 58 patients were included in the high ISS group (ISS ${\geq}15$). The mean PCT, MIF, and lactic acid levels were higher in the high ISS group (p<0.05). Meanwhile, 38 patients were included in the early sepsis group and 94 patients were included in the non-sepsis group. The mean MIF levels were higher in the sepsis group than the non-sepsis group (p<0.05) and there were no significant differences in the initial CRP, lactic acid, and PCT levels in these two groups. Conclusions: MIF may be considered as a predictive factor for sepsis in trauma patients.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.3
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• pp.337-344
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• 2018

Hepatocellular carcinoma (HCC), a major type of hepatoma, is associated with high recurrence and mortality because of its uncontrolled metastatic feature. Silymarin is a polyphenolic flavonoid from Silybum marianun (milk thistle) and exhibits anti-carcinogenic activity through modulation of the epithelial-mesenchymal transition (EMT) in several cancer cells. In this study, the inhibitory mechanism of silymarin against migration and invasion was investigated in the Huh7 HCC cell line. Wound healing and in vitro invasion assays were conducted to examine the effects of silymarin on migration and invasion. Western blot analysis was also applied to evaluate the inhibitory effects of silymarin on the EMT-related genes and their upstream signaling molecules. Silymarin inhibited the migratory and invasive activities of Huh7 cells. In addition, silymarin attenuated the protein expression levels of vimentin and matrix metalloproteinase (MMP)-9 as well as their transcription factors, Snail, and nuclear factor $(NF)-{\kappa}B$, while the expression of E-cadherin was increased by the silymarin treatment. Among the upstream signaling molecules, the phosphorylation of Akt was inhibited by the silymarin treatment, which was confirmed by the selective inhibitor, LY294002. Consequently, silymarin inhibited the invasive and migratory activities in Huh7 cells through the modulation of EMT-related gene expression by the PI3K/Akt signaling pathway, which may have potential as a chemopreventive agent against HCC metastasis.

• The Korean Journal of Pain
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• v.36 no.1
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• pp.60-71
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• 2023

Background: The purpose of this research was to assess the role of heparanase (HPSE)/syndecan1 (SDC1)/nerve growth factor (NGF) on cancer pain from melanoma. Methods: The influence of HPSE on the biological function of melanoma cells and cancer pain in a mouse model was evaluated. Immunohistochemical staining was used to analyze HPSE and SDC1. HPSE, NGF, and SDC1 were detected using western blot. Inflammatory factors were detected using ELISA assay. Results: HPSE promoted melanoma cell viability, proliferation, migration, invasion, and tumor growth, as well as cancer pain, while SST0001 treatment reversed the promoting effect of HPSE. HPSE up-regulated NGF, and NGF feedback promoted HPSE. High expression of NGF reversed the inhibitory effect of HPSE down-regulation on melanoma cell phenotype deterioration, including cell viability, proliferation, migration, and invasion. SST0001 down-regulated SDC1 expression. SDC1 reversed the inhibitory effect of SST0001 on cancer pain. Conclusions: The results showed that HPSE promoted melanoma development and cancer pain by interacting with NGF/SDC1. It provides new insights to better understand the role of HPSE in melanoma and also provides a new direction for cancer pain treatment.

• Oncology Reports
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• v.43 no.6
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• pp.2045-2052
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• 2020

Although the effects of stem cells expressing anticancer genes on tumor growth have been demonstrated by many researchers in various types of cancer, relatively few studies have investigated their inhibitory effects on cancer metastasis. In the present study, we examined the inhibitory effects of cytosine deaminase (CD)/5-fluorocytosine (5-FC) and interferon-β (IFN-β) using genetically engineered neural stem cells (hNSCs) in a cellular and metastasis model of renal cell carcinoma (RCC). The CD/5-FC method has the advantage of minimizing damage to normal tissues since it selectively targets cancer cells by the CD gene, which converts prodrug 5-FC to the drug 5-fluorouracil. Moreover, we used hNSCs as a tool to effectively deliver the anticancer genes to the tumor site. These stem cells are known to possess tumor-tropism because of chemoattractant factors expressed in cancer cells. Therefore, we ascertained the expression of these factors in A498 cells, a cell line of RCC, and identified the A498-specific migration ability of hNSCs. We also confirmed that the proliferation of A498 cells was significantly reduced by therapeutic hNSCs in the presence of 5-FC. Furthermore, we established an A498 metastasis model. In the animal experiment, the weight of the lungs increased in response to cancer metastasis, but was normalized by hNSCs expressing CD and/or IFN-β genes, while the incidence of liver metastasis was suppressed by the hNSCs. Overall, the results of this study demonstrate that stem cells expressing anticancer genes have the potential for use as an alternative to conventional therapy for metastatic cancer.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.137-143
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• 1994

Enhancement or diminution of leukocyte migration to the specific site might be important factors for the development of inflammatory diseases. To investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on chemotaxis of neutrophil, we obtained neutrophils by Hypaque-Ficoll step gradient centrifugation and tested the effects of seven drugs on the n-formyl-leucyl-phenylalanine (FMLP)-induced migration of neutrophil using a 48-well micro chemotaxis assembly. Oxyphenbutazone, phenylbutazone, sulindac, zomepirac, and ibuprofen suppressed the migration of neutrophil at the therapeutic concentrations, however, indomethacin showed stimulation effect. IC50s for inhibition of neutrophil migration by these drugs are less than 100uM. When drugs were preincubated with FMLP, no inhibition on migration of neutrophil was observed. These results indicated that inhibitory effects of these drugs on migration of neutrophil might be related to the receptor sites of neutrophil rather than molecular inactivation of chemoattractant (FMLP). In conclusion, we suggested that the property of inhibition effects on neutrophil migration of several NSAIDs might be another mode of pharmacological action for anti-iflammatory effect, which showed significant effects at concentrations below therapeutic levels, in addition to cyclooxygenase inhibition.

• KSBB Journal
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• v.18 no.1
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• pp.25-29
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• 2003

In this study, we examined the effects of the methanolic extract(CL-ex) of Codonopsis lanceolata on the angiogenesis stimulated with basic fibroblast growth factor(bFGF) in vitro, using porcine pulmonary arterial endothelial cells(PPAECs). In addition, we investigated the endothelial functions involved in angiogenesis, such as proliferation, migration and secretion of matrix metalloproteinases(MMPs), using human umbilical vein endothelial cells(HUVECS). CL-ex inhibited FGF-induced sprout formation in vitro at concentrations of 0.1-100 ug/ml. Although CL-ex did not affect the proliferation of endothelial cells, CL-ex strongly inhibited the FGF-induced migration of HUVECS at concentrations of 0.1-1 ug/ml; the degree of inhibition of endothelial cells by C-ex was 49.4% at 0.1 ug/ml and 71.9 % at 1.0 ug/ml. Moreover, CL-ex inhibited the secretion of MMPs from HUVECS stimulated with FGF. Therefore, the inhibitory effect of CL-ex on angiogenesis in vitro could be explained by the inhibition of endothelial cell migration. From these results, we suggest that Codonopsis lanceolata is a useful herb for the development of therapeutics or preventive food factors for angiogenesis related diseases, such as tumors.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.337.2-337.2
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• 2002

Conjugated linoleic acid (CLA) is a potent inhibitor of mammary carcinogenesis. Cancer cells produce various angiogenic factors which stimulate host vascular endothelial cell mitogenesis and chemotaxis for their growth and metastasis. Basic fibroblast growth factor (bFGF) is a potent angiogenic factor that is expressed in many tumors. In this study. we found that CLA decreased bFGF-induced endothelial cell proliferation and DNA synthesis in a dose-dependent manner. However, CLA did not inhibit endothelial cell migration. Furthermore CLA showed a potent inhibitory effect on embryonic vasculogenesis and bF GF-induced angiogenesis in vivo. Collectively. these results suggest that CLA selectively inhibis the active proliferating endothelial edll induced by bFGF. which may explain its anti-carcinogenix properties in vivo.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.5
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• pp.175-180
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• 2022

The seeds of Trichosanthes kirilowii (STK) used in traditional Oriental medicine for the treatment of dry cough and constipation have diverse pharmacological activities, including hypolipidemic, antioxidant, immunosuppressive, and anticancer effects. However, the effect of STK on angiogenesis has not been studied yet. In this study, we investigated whether the ethanolic extract of STK (ESTK) can regulate the migration and tube formation of human umbilical vein endothelial cells (HUVECs) and explored the underlying mechanism. Results of transwell assay showed that ESTK treatment dose-dependently suppressed the migration of HUVECs. The conditioned medium collected from H1299 human lung cancer cells was used as a chemoattractant. Our observation suggests that ESTK would inhibit the recruitment of endothelial cells into tumors. In addition, ESTK treatment significantly reduced the tube formation of HUVECs. As a molecular mechanism, we found that vascular endothelial growth factor (VEGF)-induced phosphorylation of VEGF receptor 2 (VEGFR2) was completely blocked by ESTK treatment. The expression of angiogenic factors, including VEGFA, fibroblast growth factor 2 (FGF2), angiopoietin, placental growth factor (PGF), platelet derived growth factor (PDGF), angiogenin, and tumor necrosis factor (TNF)-α, was commonly decreased by ESTK treatment in H1299 cells, indicating that ESTK would reduce the production of angiogenic factors from cancer cells. Taken together, our results clearly demonstrated that ESTK exhibited anti-angiogenic effects in HUVECs, which provides another possible mechanism underlying the anticancer activities of STK.

• Korean Journal of Food Science and Technology
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• v.50 no.1
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• pp.105-110
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• 2018

Melittin is the main component of apitoxin (bee venom) that has been reported to have anti-inflammatory and anti-cancer effects. Herein, we demonstrated that inhibition of epithelial-mesenchymal transition (EMT) by melittin causes suppression of cancer cell migration and invasion. Melittin significantly suppressed the epidermal growth factor (EGF)-induced cell migration and invasion in lung cancer cells. Moreover, melittin up-regulated the expression of epithelial marker protein, E-cadherin, and down-regulated the expression of EMT related proteins, vimentin and fibronectin. Mechanistic studies revealed that melittin markedly suppressed the expression of EMT mediated transcription factors, ZEB2, Slug, and Snail. The EGF-induced phosphorylation of AKT, mTOR, P70S6K, and 4EBP1 was also inhibited by melittin, but not that of ERK and JNK. Therefore, the inhibitory effect of melittin on migration and invasion of lung cancer cells may be associated with the inhibition of EMT via blocking of the AKT-mTOR-P70S6K-4EBP1 pathway.