• Journal of Microbiology and Biotechnology
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• 제18권7호
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• pp.1298-1307
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• 2008

In this study, we investigated the inhibition effects of single and mixed heavy metal ions ($Zn^{2+},\;Ni^{2+},\;Cu^{2+},\;and\;Cd^{2+}$) on iron oxidation by Acidithiobacillus ferrooxidans. Effects of metals on the iron oxidation activity of A. ferrooxidans are categorized into four types of patterns according to its oxidation behavior. The results indicated that the inhibition effects of the metals on the iron oxidation activity were noncompetitive inhibitions. We proposed a reduced inhibition model, along with the reduced inhibition constant ($\alpha_i$), which was derived from the inhibition constant ($K_I$) of individual metals and represented the tolerance of a given inhibitor relative to that of a reference inhibitor. This model was used to evaluate the toxicity effect (inhibition effect) of metals on the iron oxidation activity of A. ferrooxidans. The model revealed that the iron oxidation behavior of the metals, regardless of metal systems (single, binary, ternary, or quaternary), is closely matched to that of any reference inhibitor at the same reduced inhibition concentration, $[I]_{reduced}$, which defines the ratio of the inhibitor concentration to the reduced inhibition constant. The model demonstrated that single metal systems and mixed metal systems with the same reduced inhibitor concentrations have similar toxic effects on microbial activity.

• Archives of Pharmacal Research
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• 제28권7호
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• pp.848-853
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• 2005

Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong analgesic activity in vivo. In this study, new anti-inflammatory formulation containing S. deltoides extract as a major ingredient was prepared and in vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part of S. deltoides extract, 0.9 part of Angelica gigas extract and 0.9 part of glucosamine sulfate (w/w). SAG inhibited dose-dependently edematic response of arachidonic acid (AA)- and 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema in mice, which is an animal model of acute inflammation. SAG showed 44.1 % inhibition of AA-induced ear edema at an oral dose of 50 mg/kg. In an animal model of chronic inflammation, SAG clearly reduced the edematic response of 7 -day model of multiple treatment of TPA (38.1 % inhibition at 200 mg/kg/day). Furthermore, SAG (50-800 mg/kg/day) as well as S. deltoides extract (285 mg/kg/day) significantly inhibited prostaglandin $E_2$ production from the skin lesion of the animals of 7-day model. These results were well correlated with in vitro finding that SAG as well as S. deltoides extract reduced cyclooxygenase (COX)-1- and COX-2-induced prostanoid production, measured in mouse bone marrow-derived mast cells. Therefore, these results suggest that SAG possesses anti-inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX-1/COX-2 inhibition. And COX inhibition of SAG is possibly contributed by S. deltoides extract among the ingredients. Although the anti-inflammatory potencies of SAG were less than those of currently used anti-inflammatory drugs, this formulation may have beneficial effect on inflammatory disorders as a neutraceutical.

• BMB Reports
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• 제51권1호
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• pp.3-4
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• 2018

Parkinson's disease (PD) is a debilitating disorder resulting from loss of dopamine neurons. In dopamine deficient state, the basal ganglia increases inhibitory synaptic outputs to the thalamus. This increased inhibition by the basal ganglia output is known to reduce firing rate of thalamic neurons that relay motor signals to the motor cortex. This 'rate model' suggests that the reduced excitability of thalamic neurons is the key for inducing motor abnormalities in PD patients. We reveal that in response to inhibition, thalamic neurons generate rebound firing at the end of inhibition. This rebound firing increases motor cortical activity and induces muscular responses that triggers Parkinsonian motor dysfunction. Genetic and optogenetic intervention of the rebound firing prevent motor dysfunction in a mouse model of PD. Our results suggest that inhibitory synaptic mechanism mediates motor dysfunction by generating rebound excitability in the thalamocortical pathway.

• Journal of Microbiology and Biotechnology
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• 제30권3호
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• pp.448-458
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• 2020

We investigated the therapeutic effects of microRNA-139-5p in relation to osteoporosis of bone marrow-derived mesenchymal stem cell (BMSCs) and its underlying mechanisms. In this study we used a dexamethasone-induced in vivo model of osteoporosis and BMSCs were used for the in vitro model. Real-time quantitative polymerase chain reaction (RT-PCR) and gene chip were used to analyze the expression of microRNA-139-5p. In an osteoporosis rat model, the expression of microRNA-139-5p was increased, compared with normal group. Down-regulation of microRNA-139-5p promotes cell proliferation and osteogenic differentiation in BMSCs. Especially, up-regulation of microRNA-139-5p reduced cell proliferation and osteogenic differentiation in BMSCs. Overexpression of miR-139-5p induced Wnt/β-catenin and down-regulated NOTCH1 signaling in BMSCs. Down-regulation of miR-139-5p suppressed Wnt/β-catenin and induced NOTCH1 signaling in BMSCs. The inhibition of NOTCH1 reduced the effects of anti-miR-139-5p on cell proliferation and osteogenic differentiation in BMSCs. Activation of Wnt/β-catenin also inhibited the effects of anti-miR-139-5p on cell proliferation and osteogenic differentiation in BMSCs. Taken together, our results suggested that the inhibition of microRNA-139-5p promotes osteogenic differentiation of BMSCs via targeting Wnt/β-catenin signaling pathway by NOTCH1.

• Annals of Clinical Neurophysiology
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• 제8권2호
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• pp.107-124
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• 2006

The basal ganglia are a group of nuclei located in the deep portion of the brain. Along with the cerebellum, the basal ganglia have a major role in controlling human voluntary movements, and their dysfunction is apparently responsible for various involuntary movements. Although the exact mechanism of how the basal ganglia control movements has yet to be clarified, the model of focused selection (through the direct pathway) and tonic inhibition (via the indirect pathway) is proposed to be a principal functional model of the basal ganglia. Parkinson's disease (PD) is classically characterized by bradykinesia, rigidity and tremor-at-rest. All features seem to be associated with dopamine depletion resulting from the degeneration of the nigrostriatal pathway, which produces reduced activity of the direct pathway and a concurrent enhancement of excitatory output from STN. This change may result in increased tonic background inhibition and reduced focused selection via the direct pathway, causing difficulties in performing voluntary movements selectively. However, it has not been possible to define a single underlying pathophysiologic mechanism that explains all parkinsonian symptoms. Here the data that give separate understanding to each of the three classic features are discussed.

• Childhood Kidney Diseases
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• 제21권1호
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• pp.1-7
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• 2017

Mitogen-activated protein kinases (MAPKs) play important roles in various cellular functions including proliferation, differentiation, and apoptosis. We showed that MAPKs are developmentally regulated in the rat kidney. p38 MAPK (p38) and extracellular signal-regulated kinase (ERK) were strongly expressed in the fetal kidney, whereas c-Jun N-terminal kinase (JNK) was detected predominantly in the adult kidney. The inhibition of p38 or ERK in organ culture resulted in reduced nephron formation with or without reduced kidney size. On the other hand, persistent fetal expression pattern of MAPKs, i.e., upregulation of p38 and ERK and downregulation of JNK, was observed in the cyst epithelium of human renal dysplasia, ovine fetal obstructive uropathy, and pcy mice, a model of polycystic kidney disease. Furthermore, activated p38 and ERK induced by cyclic stretch mediated proliferation and $TGF-{\beta}1$ expression in ureteric bud cells, probably leading to cyst formation and dysplastic changes. Inhibition of ERK slowed the disease progression in pcy mice. Finally, ERK and p38 were inactivated in the early embryonic kidney subjected to maternal nutrient restriction, characterized by reduced ureteric branching and nephron number. Thus, MAPKs mediate the development of normal and diseased kidney. Their modulation may result in novel therapeutic strategies against developmental abnormalities of the kidney.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2020년도 춘계학술대회
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• pp.87-87
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• 2020

In this study, we investigated the immune-enhancing activity of water extracts from Hydrangea macrophylla subsp. serrata (WE-HML). WE-HML increased cell viability and production of immunomodulators, which contributed to activating phagocytic activity in RAW264.7 cells. Inhibition of JNK and NF-κB reduced the production of immunomodulators by WE-HML. ROS inhibition suppressed the production of immunomodulators, and the activation of JNK and NF-κB signaling by WE-HML. TLR4 inhibition attenuated the production of immunomodulators, and activation of JNK and NF-κB signaling by WE-HML. In the immunosuppressed mouse model, WE-HML increased the spleen index, the levels of the cytokines, the numbers of white blood cells, lymphocytes, and neutrophils. However, WE-HML inhibited LPS-mediated overproduction of pro-inflammatory mediators in RAW264.7 cells, which indicated that WE-HML may have anti-inflammatory activity under excessive inflammatory conditions. Taken together, WE-HML may be considered to have immune-enhancing activity and expected to be used as a potential immune-enhancing agent.

• IMMUNE NETWORK
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• 제21권3호
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• pp.22.1-22.17
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• 2021

Chitinase-3-like-1 (CHI3L1) is known to induce inflammation in the progression of allergic diseases. Previous our studies revealed that 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the CHI3L1 inhibiting compound, has the anti-inflammatory effect on neuroinflammation. In this study, we investigated that K284 treatment could inhibit the development of atopic dermatitis (AD). To identify the effect of K284, we used phthalic anhydride (5% PA)-induced AD animal model and in vitro reconstructed human skin model. We analyzed the expression of AD-related cytokine mediators and NF-κB signaling by Western blotting, ELISA and quantitative real-time PCR. Histological analysis showed that K284 treatment suppressed PA-induced epidermal thickening and infiltration of mast cells. K284 treatment also reduced PA-induced release of inflammatory cytokines. In addition, K284 treatment inhibited the expression of NF-κB activity in PA-treated skin tissues and TNF-α and IFN-γ-treated HaCaT cells. Protein-association network analysis indicated that CHI3L1 is associated with lactoferrin (LTF). LTF was elevated in PA-treated skin tissues and TNF-α and IFN-γ-induced HaCaT cells. However, this expression was reduced by K284 treatment. Knockdown of LTF decreased the expression of inflammatory cytokines in TNF-α and IFN-γ-induced HaCaT cells. Moreover, anti-LTF antibody treatment alleviated AD development in PA-induced AD model. Our data demonstrate that CHI3L1 targeting K284 reduces AD-like skin inflammation and K284 could be a promising therapeutic agent for AD by inhibition of LTF expression.

• Bulletin of the Korean Chemical Society
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• 제21권12호
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• pp.1217-1221
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• 2000

L-alanine dehydrogenase from Bacillus subtilis exhibits allosteric kinetic properties in the presence of $ZN^{2+}$. $ZN^{2+}$ induces the binding of substrate (L-alanine) to be cooperative at pH 8.0. The effect of pH variation between pH 7.0 and pH 10.0 on the inhibition by $ZN^{2+}$ correlates with the pH effect on the $K_m$ values for L-alanine within these pH range indicating that $ZN^{2+}$ and substrate compete for the same site. No such cooperativity is induced by $ZN^{2+}$ when the reaction is carried out at pH 10. At this higher pH, $ZN^{2+}$ binds with the enzyme with lower affinity and noncompetitive with respect to L-alanine. Inhibition of L-alanine dehydrogenase by $ZN^{2+}$ depends on the ionic strength. Increase in KCI concentration reduced the inhibition, but allosteric property in $ZN^{2+}$ binding is conserved. A model for the regulatory mechanism of L-alanine dehydrogenase as a noncooperative substrate-cooperative cofactor allosteric enzyme, which is compatible in both concerted and the sequential allosteric mechanism, is proposed.

• The Korean Journal of Physiology and Pharmacology
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• 제19권6호
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• pp.491-497
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• 2015

Traumatic brain injury (TBI) is a major cause of mortality and long-term disability, which can decrease quality of life. In spite of numerous studies suggesting that Epigallocatechin-3- gallate (EGCG) has been used as a therapeutic agent for a broad range of disorders, the effect of EGCG on TBI remains unknown. In this study, a weight drop model was established to evaluate the therapeutic potential of EGCG on TBI. Rats were administered with 100 mg/kg EGCG or PBS intraperitoneally. At different times following trauma, rats were sacrificed for analysis. It was found that EGCG (100 mg/kg, i.p.) treatment significantly reduced brain water content and vascular permeability at 12, 24, 48, 72 hour after TBI. Real-time PCR results revealed that EGCG inhibited TBI-induced IL-$1{\beta}$ and TNF-${\alpha}$ mRNA expression. Importantly, CD68 mRNA expression decreasing in the brain suggested that EGCG inhibited microglia activation. Western blotting and immunohistochemistry results showed that administering of EGCG significantly inhibited the levels of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression. TBI-induced oxidative stress was remarkably impaired by EGCG treatment, which elevated the activities of SOD and GSH-PX. Conversely, EGCG significantly reduced the contents of MDA after TBI. In addition, EGCG decreased TBI-induced NADPH oxidase activation through inhibition of $p47^{phox}$ translocation from cytoplasm to plasma membrane. These data demonstrate that EGCG treatment may be an effective therapeutic strategy for TBI and the underlying mechanism involves inhibition of oxidative stress.