• Biomolecules & Therapeutics
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• 제27권2호
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• pp.178-184
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• 2019

Parkinson's disease is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta. In the present study, we investigated whether ${\beta}-Lapachone$ (${\beta}-LAP$), a natural naphthoquinone compound isolated from the lapacho tree (Tabebuia avellanedae), elicits neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. ${\beta}-LAP$ reduced the tyrosine hydroxylase (TH)-immunoreactive fiber loss induced by MPTP in the dorsolateral striatum, and alleviated motor dysfunction as determined by the rotarod test. In addition, ${\beta}-LAP$ protected against MPTP-induced loss of TH positive neurons, and upregulated B-cell lymphoma 2 protein (Bcl-2) expression in the substantia nigra. Based on previous reports on the neuroprotective role of nuclear factor-E2-related factor-2 (Nrf2) in neurodegenerative diseases, we investigated whether ${\beta}-LAP$ induces upregulation of the Nrf2-hemeoxygenae-1 (HO-1) signaling pathway molecules in MPTP-injected mouse brains. Western blot and immunohistochemical analyses indicated that ${\beta}-LAP$ increased HO-1 expression in glial fibrillary acidic protein-positive astrocytes. Moreover, ${\beta}-LAP$ increased the nuclear translocation and DNA binding activity of Nrf2, and the phosphorylation of upstream adenosine monophosphate-activated protein kinase (AMPK). ${\beta}-LAP$ also increased the localization of p-AMPK and Nrf2 in astrocytes. Collectively, our data suggest that ${\beta}-LAP$ exerts neuroprotective effect in MPTP-injected mice by upregulating the p-AMPK/Nrf2/HO-1 signaling pathways in astrocytes.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.124.1-124.1
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• 2003

We investigated whether the mushroom extracts can protect neuronal death and ameliorate memory deficits in Alzheimer"s disease induced by $\beta$-amyloid peptide[A$\beta$(25-35)]. Cellular model of Alzheimer"s disease was produced by using SK-N-SH human neuronal cells treated with $A\beta$. Treatment with 40uM $A\beta$ for 48hours caused a 46% loss of cell viability. First, we examined the effects of 22 mushroom extracts on neuronal death using MTT assay. We found that 3 mushroom extracts increased viability of the cells from 46% to 87%. (omitted)

• Membrane and Water Treatment
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• 제7권3호
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• pp.223-240
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• 2016

In this study, poly(vinyl-alcohol) and water insoluble ${\beta}$-cyclodextrin polymer (${\beta}$-CDP) cross-linked with citric acid, have been used as macrocyclic carrier in the preparation of polymer inclusion membranes (PIMs) for aniline (as molecule model) extraction from aqueous media. The obtained membranes were firstly characterized by X-ray diffraction, Fourier transform infrared and water swelling test. The transport of aniline was studied in a two-compartment transport cell under various experimental conditions, such as carrier content in the membranes, stirring rate and initial aniline concentration. The kinetic study was performed and the kinetic parameters were calculated as rate constant (k), permeability coefficient (P) and flux (J). These first results demonstrated the utility of such polymeric membranes for environmental decontamination of toxic organic molecules like aniline. Predictive modeling of transport flux through these materials was then studied using design of experiments; the design chosen was a two level full factorial design $2^k$. An empirical correlation between aniline transport flux and independent variables (Poly ${\beta}$-CD membrane content, agitation speed and initial aniline concentration) was successfully obtained. Statistical analysis showed that initial aniline concentration of the solution was the most important parameter in the study domain. The model revealed the existence of a strong interaction between the Poly ${\beta}$-CD membrane content and the stirring speed of the source solution. The good agreement between the model and the experimental transport data confirms the model's validity.

• Journal of Pharmaceutical Investigation
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• 제39권1호
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• pp.51-54
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• 2009

${\beta}ig$-h3, is a TGF-${\beta}$-induced gene product, extracellular matrix protein with 68 kDa MW(683 amino acids) and has been known for its possible roles in cell adhesion, spreading, migration and proliferation. To minimize a proteolytic degradation of ${\beta}ig$-h3, ${\beta}ig$-h3 incorporated chitosan sponge was prepared and its effects on fibroblast adhesion and migration were investigated. And its wound healing efficacy was evaluated in deep 2nd degree burn rabbit ear wound model. ${\beta}ig$-h3 enhanced fibroblast adhesion and proliferation. In histological observation, a significant over-proliferation of epidermal regeneration was observed in ${\beta}ig$-h3/chitosan dressing applied wound while epidermal regeneration was not proceeded yet in chitosan only treated wound. ${\beta}ig$-h3/sponge dressing could enhance epidermal regeneration.

• Journal of Microbiology and Biotechnology
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• 제23권4호
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• pp.518-526
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• 2013

Gut-derived lipopolysaccharides (LPS) are critical to the development and progression of chronic low-grade inflammation and metabolic diseases. In this study, the effects of probiotics Lactobacillus and Bifidobacterium on gut-derived lipopolysaccharide and inflammatory cytokine concentrations were evaluated using a human colonic microbiota model. Lactobacillus reuteri, L. rhamnosus, L. plantarum, Bifidobacterium animalis, B. bifidum, B. longum, and B. longum subsp. infantis were identified from the literature for their anti-inflammatory potential. Each bacterial culture was administered daily to a human colonic microbiota model during 14 days. Colonic lipopolysaccharides, and Gram-positive and negative bacteria were quantified. RAW 264.7 macrophage cells were stimulated with supernatant from the human colonic microbiota model. Concentrations of TNF-${\alpha}$, IL-$1{\beta}$, and IL-4 cytokines were measured. Lipopolysaccharide concentrations were significantly reduced with the administration of B. bifidum ($-46.45{\pm}5.65%$), L. rhamnosus ($-30.40{\pm}5.08%$), B. longum ($-42.50{\pm}1.28%$), and B. longum subsp. infantis ($-68.85{\pm}5.32%$) (p < 0.05). Cell counts of Gram-negative and positive bacteria were distinctly affected by the probiotic administered. There was a probiotic strain-specific effect on immunomodulatory responses of RAW 264.7 macrophage cells. B. longum subsp. infantis demonstrated higher capacities to reduce TNF-${\alpha}$ concentrations ($-69.41{\pm}2.78%$; p < 0.05) and to increase IL-4 concentrations ($+16.50{\pm}0.59%$; p < 0.05). Colonic lipopolysaccharides were significantly correlated with TNF-${\alpha}$ and IL-$1{\beta}$ concentrations (p < 0.05). These findings suggest that specific probiotic bacteria, such as B. longum subsp. infantis, might decrease colonic lipopolysaccharide concentrations, which might reduce the proinflammatory tone. This study has noteworthy applications in the field of biotherapeutics for the prevention and/or treatment of inflammatory and metabolic diseases.

• 동의생리병리학회지
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• 제20권5호
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• pp.1200-1210
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• 2006

This experiment was designed to investigate the effect of the CMT and MCMT hot water extract & ultra-fine powder on microglia and memory deficit model. The effects of the CMT and MCMT hot water extract on expression of IL-l${\beta}$, IL-6, TNF-${\alpha}$, NOS-II, COX-2, IL-10, TGF-${\beta}$1 mRNA and production of IL-lP, IL-6, TNF-a, NO, ROS in BV2 microglial cell line treated by lipopolysacchaide(LPS) ; serum glucose, uric acid, AChE activity of the memory deficit mice induced by scopolamine , behavior of the memory deficit mice induced by scopolamine and were investigated, respectively. The CMT and MCMT hot water extract suppressed the expression of IL-1${\beta}$, IL-6, TNF-${\alpha}$, NOS-II, COX-2 mRNA, production of IL-l${\beta}$, IL-6, TNF-${\alpha}$, NO, ROS and increased the expression of IL-10, TGF-${\beta}$l mRNA in BV2 microglial cell line treated by LPS. The MCMT hot water extract & ultra-fine powder increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit mice induced by scopolamine. The CMT and MCMT hotwater extract & ultra-fine powder groups showed significantly inhibitory effect on the scopolamine-induced impairment of memory in the experiment of Morris water maze. According to the above result, it is suggested that the CMT and MCMT hot water extract & ultra-fine powder might be usefully applied for prevention and treatment of dementia.

• 동의신경정신과학회지
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• 제19권3호
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• pp.69-84
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• 2008

Objective: This experiment was designed to investigate the effects of the KBHT hot water extract & ultra-fine powder on Alzheimer's Disease Model Induced by $\beta$A. Method: The effects of the KBHT hot water extract on expression of proinflammatory cytokine mRNA in BV2 microglial celll cell line treated by lipopolysacchaide(LPS). The effects of the KBHT hot water extract & ultra-fine powder on (1) the behavior (2) AChE in serum (3) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with $\beta$A were investigated. Results: 1. The KBHT hot water extract suppressed the expression of proinflammatory cytokine mRNA in BV2 microglial cell line treated with LPS. 2. The KBHT hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by $\beta$A in the Morris water maze experiment, which measured stop-through latency and distance movement-through latency 3. The KBHT hot water extract & ultra-fine powder suppressed the over-expression of AChE activity in the serum of the mice with Alzheimer's disease induced by $\alpha$A. 4. The KBHT hot water extract & ultra-fine powder suppressed the expression of TNF-$\alpha$, IL-l$\beta$ protein significantly in the microglial cell of mice with Alzheimer's disease induced by 1$\beta$A. 5. The KBHT ultra-fine powder reduced infarction area of hippocampus significantly in the mice with Alzheimer's disease induced by $\beta$A. Conclusions: These results suggest that the KBHT hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the PMCMT hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.

• Journal of Chest Surgery
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• 제43권6호
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• pp.588-595
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• 2010

배경: 종양의 종류에 따라 발현되는 종양 항원의 종류도 다양하며 그 발현률의 차이는 더욱 다양하다. 이와 같은 이유로 폐암의 치료연구를 위해서는 인체를 대신할 만한 동물 모형이 절대 필요하다. 저자는 편평상피세포암의 세포주를 배양하여 Nude mice의 흉강 내에 주입하는 방법으로 종양형성을 시도하여 종양형성의 성공 유무와 조직학적 변화와 함께 폐암과 관련 있는 EGFR (epidermal growth factor receptor)의 수용기 중 하나인 HER2/neu 종양 유전자와 세포 성장 억제 작용과 악성화 과정에서의 저항성으로 작용하는 TGF-${\beta}_1$을 각각 정량 하도록 하여 인공적인 동소 폐암의 경우 암유전자의 발현에 관하여 조사해보고자 하였다. 대상 및 방법: 면역성이 없는 20마리의 수컷생쥐 (Male BALB/c nude mice)로 5마리를 대조군으로 하였으며, 나머지 15마리는 실험군으로 하고 체중은 20~25 gm (Orient, Japan)의 범위에 있었다. HER2/neu는 채혈하여 보관된 혈액의 혈청을 분리하여 CLIA (chemiluminiscent immunoassay) 법으로 정량적으로 측정하였으며 TGF-${\beta}_1$은 immunosandwitch법을 이용하여 정량 분석하였다. 통계학적 분석을 위하여 SPSS통계(SPSS Version10.0, USA)프로그램을 이용하였으며 Student T test를 하였으며 p값이 0.05 미만인 경우를 유의성이 있는 것으로 간주하였다. 결과: 정상 대조군에서나 인위적으로 주입한 폐암 세포주에 의한 폐암이 만들어진 이후에도 HER2/neu 유전자의 증폭은 전혀 반응을 나타내지 못하였다. 하지만 TGF-${\beta}_1$ 대조군의 정량치는 $28,490{\pm}8,549pg/mL$이었고 폐암 세포 주입군은 $42,362{\pm}14,449pg/mL$로 유의하게 1.48배 높게 나왔다(p<0.483). HER2/neu 유전자와 TGF-${\beta}_1$은 유의한 상관관계가 없는 것으로 나타났다. 결론: TGF-${\beta}_1$유전자는 대조군에 비하여 1.48배 정도의 증폭이 발현되었다. TGF-${\beta}_1$의 증폭은 Nude mice에서 발암에 의한 생체 치유 억제 기전이 확실히 작동하고 있다는 것을 의미하며, 인체의 조기 폐암의 발견에 역할을 가능케 하는 정량 검사법으로 이용할 수도 있을 것이다.

• Molecules and Cells
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• 제39권3호
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• pp.266-279
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• 2016

The mechanism by which 12-O-tetradecanoylphorbol-13-acetate (TPA) bypasses cellular senescence was investigated using human diploid fibroblast (HDF) cell replicative senescence as a model. Upon TPA treatment, protein kinase C (PKC) ${\alpha}$ and $PKC{\beta}1$ exerted differential effects on the nuclear translocation of cytoplasmic pErk1/2, a protein which maintains senescence. $PKC{\alpha}$ accompanied pErk1/2 to the nucleus after freeing it from $PEA-15pS^{104}$ via $PKC{\beta}1$ and then was rapidly ubiquitinated and degraded within the nucleus. Mitogen-activated protein kinase docking motif and kinase activity of $PKC{\alpha}$ were both required for pErk1/2 transport to the nucleus. Repetitive exposure of mouse skin to TPA downregulated $PKC{\alpha}$ expression and increased epidermal and hair follicle cell proliferation. Thus, $PKC{\alpha}$ downregulation is accompanied by in vivo cell proliferation, as evidenced in 7, 12-dimethylbenz(a)anthracene (DMBA)-TPA-mediated carcinogenesis. The ability of TPA to reverse senescence was further demonstrated in old HDF cells using RNA-sequencing analyses in which TPA-induced nuclear $PKC{\alpha}$ degradation freed nuclear pErk1/2 to induce cell proliferation and facilitated the recovery of mitochondrial energy metabolism. Our data indicate that TPA-induced senescence reversal and carcinogenesis promotion share the same molecular pathway. Loss of $PKC{\alpha}$ expression following TPA treatment reduces pErk1/2-activated SP1 biding to the $p21^{WAF1}$ gene promoter, thus preventing senescence onset and overcoming G1/S cell cycle arrest in senescent cells.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.9.1-9.12
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• 2018

Endometriosis is a disease characterized by implants of endometrial tissue outside the uterine cavity and is strongly associated with infertility. Focal adhesion of endometrial tissue to the peritoneum is an indication of incipient endometriosis. In this study, we examined the effect of various cytokines that are known to be involved in the pathology of endometriosis on endometrial cell adhesion. Among the investigated cytokines, transforming growth factor-${\beta}1$ ($TGF-{\beta}1$) increased adhesion of endometrial cells to the mesothelium through induction of ${\alpha}2-6$ sialylation. The expression levels of ${\beta}$-galactoside ${\alpha}2-6$ sialyltransferase (ST6Gal) 1 and ST6Gal2 were increased through activation of $TGF-{\beta}RI/SMAD2/3$ signaling in endometrial cells. In addition, we discovered that terminal sialic acid glycan epitopes of endometrial cells engage with sialic acid-binding immunoglobulin-like lectin-9 expressed on mesothelial cell surfaces. Interestingly, in an in vivo mouse endometriosis model, inhibition of endogenous sialic acid binding by a $NeuAc{\alpha}2-6Gal{\beta}1$-4GlcNAc injection diminished $TGF-{\beta}1$-induced formation of endometriosis lesions. Based on these results, we suggest that increased sialylation of endometrial cells by $TGF-{\beta}1$ promotes the attachment of endometrium to the peritoneum, encouraging endometriosis outbreaks.