• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3667-3671
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• 2015

Invasion and metastasis is the major cause of tumor recurrence, difficulty for cure and low survival rate. Excavating key transcription factors, which can regulate tumor invasion and metastasis, are crucial to the development of therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription factor and a vital regulator in life. Here, we report that, compared to adjacent non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular carcinoma (HCC), but not primary HCC, was significantly down-regulated. In addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of PU.1 suppressed the invasion of these cells. However, knockdown and overexpression of PU.1 did not influence proliferation. Finally, we tried to explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP-qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre- and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene IGF2. These data indicate that PU.1 inhibits invasion of human HCC through promoting miR-615-5p and suppressing IGF2. These findings improve our understanding of PU.1 regulatory roles and provided a potential target for metastatic HCC diagnosis and therapy.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.39-47
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• 2010

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor involved in neuronal differentiation, plasticity, survival and regeneration. BDNF draws massive attention mainly due to the potential as a therapeutic target in neurological diseases such as depression and Alzheimer's disease. In a primary screening for the natural compounds enhancing BDNF release from cultured rat primary cortical neuron, we found that compounds such as baicalein, tanshinone IIa, cinnamic acid, epiberberine, genistein and wogonin among many others increased BDNF release. All the compounds at $0.1{\mu}M$ of concentration barely showed stimulatory effect on BDNF induction, however, their combination (mixture 1; baicalein, tanshinone IIa and cinnamic acid, mixture 2; epiberberine, genistein and wogonin) showed synergistic increase in BDNF release as well as mRNA and protein expression. The level of BDNF expression was comparable to the maximum BDNF stimulation attainable by a positive control oroxylin A ($20{\mu}M$) without cell toxicity as determined by MTT analysis. Both mixtures synergistically increased the phosphorylation of extracellular signal-regulated kinase (ERK) as well as cAMP response element binding protein (CREB), an immediate and essential regulator of BDNF expression. Similar to these results, mixture of these compounds synergistically inhibited the up-regulation of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide treatments in rat primary astrocytes. These results suggest that the combinatorial treatment of natural compounds in lower concentration might be a useful strategy to obtain sufficient BDNF stimulation in neurological disease condition such as depression, while minimizing potential side effects and toxicity of higher concentration of a single compound.

• The Korea Journal of Herbology
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• v.30 no.1
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• pp.67-75
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• 2015

Objectives : The aim of this study is to examine the neuroprotective effect of wheat bran extract (WBE) against ${\beta}$-amyloid ($A{\beta}$)-induced apoptotic cell death in SH-SY5Y human neuroblastoma cells and memory impairment in triple transgenic animal model's of Alzheimer's disease (3xTg AD mice). Methods : In SH-SY5Y cells, MTT assay and TUNEL staining were conducted to evaluate the protective effect of WBE against $A{\beta}_{25-35}$-induced neurotoxicity and apoptosis. Alterations in mitochondrial transmembrane potential (MMP), expression of proapoptotic Bax and antiapoptotic Bcl-2 proteins, cleavage of PARP, and brain-derived neurotrophic factor (BDNF) levels were analyzed to elucidate the neuroprotective mechanism of WBE. To further investigate the memory enhancing effect of WBE, Morris water maze test was performed in 3xTg AD mice. Results : In SH-SY5Y cells, WBE protected against $A{\beta}_{25-35}$-caused cytotoxicity and apoptosis as shown by the restoration of cell viability in MTT assay and inhibition of DNA fragmentation in TUNEL staining. $A{\beta}_{25-35}$-induced apoptotic signals such as dissipation of MMP, decreased Bcl-2/Bax ratio, and cleavage of PARP were suppressed by WBE. Moreover, WBE up-regulated the protein levels of BDNF, which seemed to be mediated by activation of cAMP response element-binding protein (CREB). In 3xTg AD mice, oral administration of WBE attenuated learning and memory deficit as verified by reduced mean escape latency in water maze test. Conclusions : WBE protects neuronal cells from $A{\beta}_{25-35}$-induced apoptotic cell death and restores learning and memory impairments in 3xTg AD mice. These findings suggest that WBE exhibit neuroprotective potential for the management of AD.

• Journal of Korean society of Dental Hygiene
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• v.9 no.2
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• pp.73-88
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• 2009

The purpose of the study was to provide the basic for the prevention of infection control by analyzing the level of recognition and practice of dental hygiene students. It is important for dental clinic staffs to know and practice infection control measures in favor of effective infection control. Thus, this study conducted an one-month questionnaire survey (during October 2008) for dental hygiene students who ever experienced in 16-week clinical practice, and analyzed total 206 questionnaire forms as collected from them, so that it could determine potential associations between their recognition and practice of infection control and thereby suggest an efficient solution for infection control in dental hygiene. 1. It was found that our students' recognition about infection control averaged $4.49{\pm}.58$ points on the whole, and they were best aware of instrumental disinfection and sterilization among other measures, which was followed by hand washing, extirpation control, post-sterilization management, personal protective outfit and instrumental surface maintenance respectively. 2. It was found that our students' practice of infection control averaged $3.85{\pm}.57$ points on the whole, and they practiced hand washing most actively among other measures, which was followed by extirpation control, post-sterilization management, instrumental disinfection and sterilization, personal protective outfit and instrumental surface maintenance respectively. 3. It was found that our students scored higher mean points in recognition about every measure of infection control than those in practice (t=15.676, p=0.000). Particularly, it was notable that there were significant differences between their mean points in recognition and practice of some infection control measures, such as instrumental surface maintenance (t=15.361, p=0.000), personal protective outfit (t=15.245, p=0.000) and instrumental disinfection and sterilization (t=11.169, p=0.000). But there was least significant difference between mean points in recognition and practice of hand washing (t=5.460, p=0.000). 4. For potential associations between recognition and practice of infection control, it was found that higher recognition was in significantly positive associations with higher practice in every measure of infection control (r=.478, p=.000), such as extirpation control (r=.630, p=.000), instrumental disinfection and sterilization (r=.477, p=.000) and post-sterilization management (r=.433, p=.000). 5. It was found that there were differences in our students' recognition depending upon availability of infection control guideline (t=4.587, p=.011), and there were significant differences in practice depending on necessity of infection control education on a statistical basis (t=2.229, p=.027). Overall, it is found that our dental hygiene students are very likely to practice hand washing and extirpation control, because both of these measures are relatively easy to practice or are considered legally binding.

• Journal of Marine Bioscience and Biotechnology
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• v.2 no.2
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• pp.102-107
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• 2007

Environmental contamination becomes a great public concern as our society gets industrialized rapidly. The present study examine the role of chitosan in a effort to intervene the environmental pollutant-induced toxicity. PCB-induced neurotoxicity with respect to the PKC signaling was examined. Since the developing neuron is particularly sensitive to PCB-induced neurotoxicity, we isolated cerebellar granule cells derived from 7-day old SD rats and grew cells in culture for additional 7 days to mimic PND-14 conditions. PCB showed the alteration of PKC signaling pathway. The alteration was structure-dependent. Mono-ortho-substituted congeners at a high dose showed a significant increase of total PKC activity at [$^3H$]PDBu binding assay, indicating that mono-ortho-substituted congeners are more neuroactive than non-ortho-substituted congeners in neuronal cells. PKC isoforms were immunoblotted with respective monoclonal antibodies. PKC-beta II and -epsilon were activated with mono-ortho-substituted congeners exposure. The result suggests that the position with ortho has a higher potential of altering the signaling pathway. Alteration of PKC was blocked with treatment of high molecular weight of chitosan. The study demonstrated that the ortho position in PCBs are important in assessing the structure-activity relationship. The results suggest a potential use of marine bioactive materials as a means of nutritional intervention to prevent the harmful effects of pollutant-derived toxicity.

• Journal of Life Science
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• v.29 no.6
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• pp.645-652
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• 2019

Non-small cell lung cancer (NSCLC) has the infamous distinction of being the leading cause of global cancer-related death over the past decade, and novel molecular targets are urgently required to change this status. We previously conducted a microarray analysis to investigate the association of transcription factor activating enhancer-binding protein 2C (TFAP2C) with NSCLC and revealed its oncogenic roles in NSCLC development. In this study, to identify new biomarkers for NSCLC, we focused on several oncogenes from the microarray analysis that are transcriptionally regulated by TFAP2C. Here, the cell division cycle 20 (CDC20) and tribbles pseudokinase 3 (TRIB3) were subsequently found as potential potent oncogenes as they are positively regulated by TFAP2C. The results showed that the mRNA and protein levels of CDC20 and TRIB3 were down-regulated in two NSCLC cell lines (NCI-H292 and NCI-H838), which were treated with TFAP2C siRNA, and that the overexpression of either CDC20 or TRIB3 was responsible for promoting cell viability in both NSCLC cell lines. In addition, apoptotic levels of NCI-H292 and NCI-H838 cells treated with TFAP2C siRNA were found to be suppressed by the overexpression of either CDC20 or TRIB3. Together, these results suggest that CDC20 and TRIB3 are positively related to NSCLC tumorigenesis and that they should be considered as potential prognostic markers for developing an NSCLC therapy.

• Journal of Microbiology and Biotechnology
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• v.29 no.4
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• pp.651-657
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• 2019

Although smallpox was eradicated in 1980, it is still considered a potential agent of biowarfare and bioterrorism. Smallpox has the potential for high mortality rates along with a major public health impact, eventually causing public panic and social disruption. Passive administration of neutralizing monoclonal antibodies (mAbs) is an effective intervention for various adverse reactions caused by vaccination and the unpredictable nature of emerging and bioterrorist-related infections. Currently, vaccinia immune globulin (VIG) is manufactured from vaccinia vaccine-boosted plasma; however, this production method is not ideal because of its limited availability, low specific activity, and risk of contamination with blood-borne infectious agents. To overcome the limitations of VIG production from human plasma, we isolated two human single-chain variable fragments (scFvs), (SC34 and SC212), bound to vaccinia virus (VACV), from a scFv phage library constructed from the B cells of VACV vaccine-boosted volunteers. The scFvs were converted to human IgG1 (VC34 and VC212). These two anti-VACV mAbs were produced in Chinese Hamster Ovary (CHO) DG44 cells. The binding affinities of VC34 and VC212 were estimated by competition ELISA to $IC_{50}$ values of $2{\mu}g/ml$ (13.33 nM) and $22{\mu}g/ml$ (146.67 nM), respectively. Only the VC212 mAb was proven to neutralize the VACV, as evidenced by the plaque reduction neutralization test (PRNT) result with a $PRNT_{50}$ of ~0.16 mg/ml (${\sim}1.07{\mu}M$). This VC212 could serve as a valuable starting material for further development of VACV-neutralizing human immunoglobulin for a prophylactic measure against post-vaccination complications and for post-exposure treatment against smallpox.

• Clean Technology
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• v.27 no.1
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• pp.55-60
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• 2021

Antibiotics are compounds broadly used to treat patients with infectious diseases and to enhance productivity in agriculture, fisheries, and livestock industries. However, due to the overuse of antibiotics and their low biodegradability, a substantial amount of antibiotics is leaking into the sewer, subsequently resulting in pollution and the emergence of antibiotic-resistant bacteria. This study explores biodegradable serum albumin's potential as an adsorbent to remove antibiotics from water. Serum albumin is a natural blood protein that transports various metabolites and hormones to all tissues' extravascular spaces. While serum albumin is highly water-soluble, it has intrinsic binding sites which readily accommodate ionic, hydrophilic, or hydrophobic molecules, rendering it a good building block for a nano-adsorbent. To induce coacervation, a desolvating agent, ethanol, was added dropwise into the aqueous albumin solution, resulting in dehydration and liquid-liquid phase separation of albumins into albumin nanoparticles within a size range of 150 ~ 170 nm. The addition of glutaraldehyde as a cross-linker improved the size stability and homogeneity of albumin nanoparticles. Adsorption of amoxicillin antibiotics on albumin nanoparticles was dependent upon glutaraldehyde concentration used in desolvation and pH during adsorption. The maximum adsorption capacity measured by spectrophotometry was found to be 12.4 micrograms of amoxicillin per milligram of albumin nanoparticle. These results demonstrate serum albumin's potential as a building block for fabricating a natural nano-adsorbent to remove antibiotics from water.

• Journal of Life Science
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• v.32 no.5
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• pp.331-339
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• 2022

Melanin is a pigment produced by melanocytes to protect the skin from external stimuli, mainly ultraviolet (UV) rays. However, abnormal and excessive production of melanin causes hyperpigmentation disorders, such as freckles, age spots, and discoloration. Natural cosmeceuticals are a new trend for treating or preventing hyperpigmentation due to fewer side effects and biocompatibility. In this context, the current study focused on Cnidium japonicum, a halophyte with several uses in folk medicine, to evaluate its potential as a skin-whitening agent. The effect of C. japonicum extract (CJE) on melanin production was analyzed in melanogenesis-stimulated B16F10 melanoma cells. The results showed that CJE successfully inhibited the oxidation of tyrosine and L-DOPA by tyrosinase and subsequently decreased the production of the key enzymes responsible for melanin production: tyrosinase, tyrosinase-related protein-1, and protein-2. This effect was confirmed by decreased intracellular and extracellular melanin levels in B16F10 melanoma cells after CJE treatment. Further experiments to elucidate the action mechanism revealed that CJE treatment suppressed melanin production by inhibiting the activation of glycogen synthase kinase 3 β (GSKβ)/β-catenin and protein kinase A (PKA)/cAMP-response element binding protein (CREB) pathways, which are the upstream activators of melanogenesis. In conclusion, the present study suggests that C. japonicum is a potential natural source of bioactive substances for the development of novel cosmeceuticals that can act against hyperpigmentation.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.36 no.4
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• pp.30-50
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• 2023

Objectives : To investigate the active compounds and therapeutic mechanisms of Atractylodes Lancea(Thunb.) D.C. and Magnolia Officinalis Rehder et Wilson in the treatment of dermatitis accompanied by pruritus, as well as their potential to complement or replace standard drugs. Methods : We conducted the network pharmacological analysis. We selected effective ingredients among the active compounds of research target herbs. Then we explore pathway/terms of the common target proteins among research target herbs, fexofenadine and disease. Results : We selected 9 active compounds are selected from Atractylodes lancea and identified 231 target proteins. Among them, 74 proteins are associated with inflammatory skin diseases that cause pruritus. These proteins are involved in various pathways including, 'Nitric-oxide synthase regulator activity', 'Hydroperoxy icosatetraenoate dehydratase activity, Aromatase activity', 'RNA-directed DNA polymerase activity', 'Arachidonic acid metabolism', 'Peptide hormone processing', 'Chemokine binding' and 'Sterol biosynthetic process'. Additionally, coregenes are involved in 'IL-17 signaling pathway'. Similarly, we selected 2 active compounds from Magnolia officinalis and identified 133 target proteins. Among them, 33 proteins are related to inflammatory skin diseases that cause pruritus. These proteins are primarily involved in 'Vascular associated smooth muscle cell proliferation' and 'Arachidonic acid metabolism'. There is no significant difference between the pathways in which coregenes are involved. Conclusions : It is expected that Atractylodes Lancea will be able to show direct or indirect anti-pruritus and anti-inflammatory effects on skin inflammation accompanied pruritus through suppressing inflammation and protecting skin barrier. Meanwhile, it is expected that Magnolia Officinalis will only be able to show indirect anti-inflammation effects. Therefore, Atractylodes Lancea and fexofenadine are believed to complement each other, whereas Magnolia Officialinalis is expected to provide supplementary support on skin disease.