• Molecules and Cells
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• v.43 no.1
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• pp.66-75
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• 2020

Saturated fatty acids contribute to β-cell dysfunction in the onset of type 2 diabetes mellitus. Cellular responses to lipotoxicity include oxidative stress, endoplasmic reticulum (ER) stress, and blockage of autophagy. Palmitate induces ER Ca²⁺ depletion followed by notable store-operated Ca²⁺ entry. Subsequent elevation of cytosolic Ca²⁺ can activate undesirable signaling pathways culminating in cell death. Mitochondrial Ca²⁺ uniporter (MCU) is the major route for Ca²⁺ uptake into the matrix and couples metabolism with insulin secretion. However, it has been unclear whether mitochondrial Ca²⁺ uptake plays a protective role or contributes to lipotoxicity. Here, we observed palmitate upregulated MCU protein expression in a mouse clonal β-cell, MIN6, under normal glucose, but not high glucose medium. Palmitate elevated baseline cytosolic Ca²⁺ concentration ([Ca²⁺]_i) and reduced depolarization-triggered Ca²⁺ influx likely due to the inactivation of voltage-gated Ca²⁺ channels (VGCCs). Targeted reduction of MCU expression using RNA interference abolished mitochondrial superoxide production but exacerbated palmitate-induced [Ca²⁺]_i overload. Consequently, MCU knockdown aggravated blockage of autophagic degradation. In contrast, co-treatment with verapamil, a VGCC inhibitor, prevented palmitate-induced basal [Ca²⁺]_i elevation and defective [Ca²⁺]_i transients. Extracellular Ca²⁺ chelation as well as VGCC inhibitors effectively rescued autophagy defects and cytotoxicity. These observations suggest enhanced mitochondrial Ca²⁺ uptake via MCU upregulation is a mechanism by which pancreatic β-cells are able to alleviate cytosolic Ca²⁺ overload and its detrimental consequences.

• Korean Journal of Environmental Agriculture
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• v.40 no.3
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• pp.211-218
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• 2021

BACKGROUND: Fine particulate matter (PM_2.5) is produced by chemical reactions between various precursors. PM_2.5 has been found to create greater human risk than particulate matter (PM₁₀), with diameters that are generally 10 micrometers and smaller. Ammonia (NH₃) and nitrogen oxides (NOx) are the sources of secondary generation of PM_2.5. These substances generate PM_2.5 through some chemical reactions in the atmosphere. Through chemical reactions in the atmosphere, NH₃ generates PM_2.5. It is the causative agent of PM_2.5. In 2017 the annual ammonia emission recorded from the agricultural sector was 244,335 tons, which accounted for about 79.3% of the total ammonia emission in Korea in that year. To address this issue, the agricultural sector announced the inclusion of reducing fine particulate matter and ammonia emissions by 30% in its targets for the year 2022. This may be achieved through analyses of its emission characteristics by monitoring the PM_2.5 and NH₃. METHODS AND RESULTS: In this study, the PM_2.5 concentration was measured real-time (every 1 hour) by using beta radiation from the particle dust measuring device (Spirant BAM). NH₃ concentration was analyzed real-time by Cavity Ring-Down Spectroscopy (CRDS). The concentrations of ozone (O₃) and nitrogen dioxide (NO₂) were continuously measured and analyzed for the masses collected on filter papers by ultraviolet photometry and chemiluminescence. CONCLUSION: This study established air pollutant monitoring system in agricultural areas to analyze the NH₃ emission characteristics. The amount of PM_2.5 and NH₃ emission in agriculture was measured. Scientific evidence in agricultural areas was obtained by identifying the emission concentration and characteristics per season (monthly) and per hour.

• Journal of Microbiology and Biotechnology
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• v.31 no.4
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• pp.540-549
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• 2021

The Wnt/β-catenin signaling pathway is involved in breast cancer and Myxococcus fulvus KYC4048 is a myxobacterial strain that can produce a variety of bioactive secondary metabolites. Although a previous study revealed that KYC4048 metabolites exhibit anti-proliferative effects on breast cancer, the biochemical mechanism involved in their effects remains unclear. In the present study, KYC4048 metabolites were separated into polar and non-polar (ethyl acetate and n-hexane) fractions via liquid-liquid extraction. The effects of these polar and non-polar KYC4048 metabolites on the viability of breast cancer cells were then determined by MTT assay. Expression levels of Wnt/β-catenin pathway proteins were determined by Western blot analysis. Cell cycle and apoptosis were measured via fluorescence-activated cell sorting (FACS). The results revealed that non-polar KYC4048 metabolites induced cell death of breast cancer cells and decreased expression levels of WNT2B, β-catenin, and Wnt target genes (c-Myc and cyclin D1). Moreover, the n-hexane fraction of non-polar KYC4048 metabolites was found most effective in inducing apoptosis, necrosis, and cell cycle arrest, leading us to conclude that it can induce apoptosis of breast cancer cells through the Wnt/β-catenin pathway. These findings provide evidence that the n-hexane fraction of non-polar KYC4048 metabolites can be developed as a potential therapeutic agent for breast cancer via inhibition of the Wnt/β-catenin pathway.

• Journal of the Korean Applied Science and Technology
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• v.35 no.4
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• pp.1250-1259
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• 2018

In this study, Momordica charantia (MC) fermented with Leuconostoc mesenteroides (MC-LM) were assessed for the antioxidant and the antidiabetic activities. Antioxidant activities of MC and MC-LM were evaluated using 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) radical. Although MC-treated groups showed little activity, 47% of activity was observed at $500{\mu}g/mL$ concentration for MC-LM and increased significantly(p<0.05) as MC-LM concentration increased. MC-LM more effectively inhibited the oxidative damage of DNA by peroxyl radical than MC and the inhibition of the strand breakage increased significantly as MC-LM concentration increased(p<0.05). Measuring the inhibition of ${\alpha}-glucosidase$ activity, which is closely related to the regulation of blood sugar, resulted in MC reduced the activity of ${\alpha}-glucosidase$ by 30% at 8 mg/mL and MC-LM at the same concentration by 60%. In addition, the effect of MC-LM on the cell viability of alloxan-treated RIN-m5F resulted in a significant increase in cell survival(p<0.05) in the group treated with MC-LM and a 20% increase in the concentration of $1000{\mu}g/mL$. As a result of insulin secretion by alloxan-treated RIN-m5F cell, the level of insulin secretion tended to increase in all group treated with MC-LM. At the concentration of $1000{\mu}g/mL$, the insulin secretion was increased by 15% in MC-LM group than in MC group. In conclusion, the results of this study suggest that fermented bitter gourd has antioxidant and antidiabetic effects.

• Journal of IKEEE
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• v.23 no.2
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• pp.727-734
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• 2019

This paper confirms whether the movement or specific operation of the muscles in the process of transferring a person from the brain can find a signal showing an essential feature of a certain part of the brain. As a rule, the occurrence of EEG(Electroencephalogram) changes when a signal is received from a specific action or from an induced action. These signals are very vague and difficult to distinguish from the naked eye. Therefore, it is necessary to define a signal for analysis before classification. The EEG form can be divided into the alpha, beta, delta, theta and gamma regions in the frequency ranges. The specific size of these signals does not reflect the exact behavior or intention, since the band or energy difference of the activated frequencies varies depending on the EEG measurement domain. However, if different actions are performed in a specific method, it is possible to classify the movement based on EEG activity and to determine the EEG tendency affecting the movement. Therefore, in this article, we first study the EEG expression pattern based on the activation of the left and right biceps EMG, and then we determine whether there is a significant difference between the EEG due to the activation of the left and right muscles through EEG. If we can find the EEG classification criteria in accordance with the EMG activation, it can help to understand the form of the transmitted signal in the process of transmitting signals from the brain to each muscle. In addition, we can use a lot of unknown EEG information through more complex types of brain signal generation in the future.

• Biomolecules & Therapeutics
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• v.27 no.5
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• pp.474-483
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• 2019

Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, ${\beta}$-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.

• Korean Journal of Food Science and Technology
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• v.51 no.4
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• pp.361-368
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• 2019

The present study aimed to evaluate the effect of Dendropanax morbifera (DM) extract on postmenopausal syndrome and to develop DM extract as an alternative for hormonal therapy. The following seven groups of rats; normal control (sham), ovariectomized (OVX) control, Punica granatum (PG)-treated group (770 mg/kg), estradiol treated group (0.5 mg/kg), and three DM-treated groups (200, 500, 1000 mg/kg) were compared. Indicated compounds were administrated once a day for eight weeks. To evaluate the estrogenic effect of DM extract, western blot analysis was performed on the liver tissue to confirm the expression of estrogen receptor ($ER-{\alpha}$, $ER-{\beta}$). Our analysis showed that after DM administration, collagen cross-linked C-telopeptide (CTX) value decreased while $ER-{\alpha}$ protein expression increased in a dose-dependent manner through the MAPK/ERK pathway in OVX rats. These results suggest that Dendropanax morbifera exerts estrogenic effect by inducing estrogen receptor expression and activating MAPK/ERK pathway.

• The Journal of the Convergence on Culture Technology
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• v.5 no.3
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• pp.229-239
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• 2019

Rapid economic development has changed the dietary habits and patterns. Especially, western style diet has increased the risk of type 2 diabetes (T2DM) in Korea. To provide more specific and appropriate diet guideline for the prevention and for the treatment of T2DM, the investigation on the characteristics of diebetic patients related to the diet needs to be done. In this study, we therefore analyzed eating behaviors, dietary attitudes, and intake of food and nutrients of normal subjects (control, n=26) and diabetic patients (case, n=18) diagnosed T2DM within one year in Daegu Gyeongbuk area. Body mass index of the patients were significantly higher than the control (p<0.05). Overeating, high fried food and low whole grain intake were revealed as risk factors for T2DM. From the food frequency questionnaire analysis, salty foods such as fermented soybean paste (Doenjang) and watery Kimch intake were associated with T2DM. Intake of vegetable lipid, ${\beta}$-carotene, calcium, copper, and vitamin K were also shown to be associated with T2DM. Taken together, these findings suggest that maintaining ideal body weight and intake the foods with low salt, fat, and refined grain in appropriate amount may help to prevent and to manage T2DM.

• Journal of Life Science
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• v.29 no.8
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• pp.922-940
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• 2019

Obesity, represented by abnormal fat accumulation due to an imbalance between energy intake and expenditure, is a major public health issue worldwide, leading to multiple noncommunicable diseases, including atherosclerosis, hypertension, type 2 diabetes, and cancer. Diverse solutions have been proposed to combat obesity. Attention has focused on two types of adipose tissues as a promising therapeutic target in obesity: traditional brown and beige or brite. Unlike energy-storing white adipose (endocrine) tissue, traditional brown adipose tissue and beige adipose tissue have energy-dissipating thermogenic properties. Both types of tissue are present in adult humans and inducible through external stimuli, such as cold exposure, ${\beta}3$-adrenergic receptor agonists, and phytochemicals. Among these stimuli, microbiota present in the human intestinal tract participate in multiple metabolic activities. Modulation of gut microbiota may offer a potent and possibly curative strategy against various metabolic diseases. Numerous studies have focused on the effects of established antiobesity treatments on the gut microenvironment or brown-adipose-tissue activation. In this review, we focus mainly on stimuli known to alleviate obesity, weight gain, and metabolic diseases, in addition to known and possible inter-relations between gut microbiota modulation and similar interventions and adipose tissue browning. The findings may pave the way toward new strategies against obesity.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.414-422
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• 2019

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-$1{\beta}$ and tumor-necrosis factor-${\alpha}$ in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and $NF-{\kappa}B$ in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.