• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.134-144
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• 2019

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and $3{\beta}$, $7{\alpha}$-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and ${\alpha}/{\gamma}$-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.326-334
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• 2019

Background: The objective of our study was to analyze the neuroprotective effects of ginsenoside derivatives Rb1, Rb2, Rc, Rd, Rg1, and Rg3 against glutamate-mediated neurotoxicity in HT22 hippocampal mouse neuron cells. Methods: The neuroprotective effect of ginsenosides were evaluated by measuring cell viability. Protein expressions of mitogen-activated protein kinase (MAPK), Bcl2, Bax, and apoptosis-inducing factor (AIF) were determined by Western blot analysis. The occurrence of apoptotic and death cells was determined by flow cytometry. Cellular level of $Ca^{2+}$ and reactive oxygen species (ROS) levels were evaluated by image analysis using the fluorescent probes Fluor-3 and 2',7'-dichlorodihydrofluorescein diacetate, respectively. In vivo efficacy of neuroprotection was evaluated using the Mongolian gerbil of ischemic brain injury model. Result: Reduction of cell viability by glutamate (5 mM) was significantly suppressed by treatment with ginsenoside Rb2. Phosphorylation of MAPKs, Bax, and nuclear AIF was gradually increased by treatment with 5 mM of glutamate and decreased by co-treatment with Rb2. The occurrence of apoptotic cells was decreased by treatment with Rb2 ($25.7{\mu}M$). Cellular $Ca^{2+}$ and ROS levels were decreased in the presence of Rb2, and in vivo data indicated that Rb2 treatment (10 mg/kg) significantly diminished the number of degenerated neurons. Conclusion: Our results suggest that Rb2 possesses neuroprotective properties that suppress glutamate-induced neurotoxicity. The molecular mechanism of Rb2 is by suppressing the MAPKs activity and AIF translocation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.1
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• pp.56-62
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• 2019

To investigate the effect of Bombycis Corpus on male osteoporosis, we performed Dual Energy X-Ray Absorptiometry(DEXA) and histochemical methods. The animals were used ICR-based male mice of 8 weeks and 50 weeks, respectively. ICR male mice at 8 weeks were used in the control group, and ICR male mice at 50 weeks were used in aging group and Bombycis Corpus group(BC group). In the aging group, 0.5 ml of distilled water was administered once a day for 6 months. In BC group, Bombycis Corpus(0.78g/kg) was dissolved in distilled water for 6 months once a day. As a result, Bombycis Corpus decreased bone loss, increased bone density by reducing the loss of bone matrix in the femur due to aging, and increased osteoblast - induced osteopontin(OPN) and osteocalcin(OPC) positivite reaction. In addition, administration of Bombycis Corpus decreased Reaction of activation of nuclear factor kappa B ligand(RANKL) positive reaction, increased osteoprotegerin(OPG) positive reaction, and decreased matrix metalloproteinase-3(MMP-3) and 8-hydroxy-2'-deoxyguanosine(8-OHdG) positivite reaction. Taken together, Bombycis Corpus increases the activity of osteoblasts, inhibits osteoclast function, promotes osteoblast function, inhibits bone tissue degradation, and inhibits bone loss due to oxidative stress. It was observed that Bombycis Corpus reduced bone loss and increased bone density caused by aging to improve male osteoporosis. Therefore, Bombycis Corpus may be used as a preventive and therapeutic agent for male osteoporosis.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.593-601
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• 2021

Primary cilia on kidney tubular cells play crucial roles in maintaining structure and physiological function. Emerging evidence indicates that the absence of primary cilia, and their length, are associated with kidney diseases. The length of primary cilia in kidney tubular epithelial cells depends, at least in part, on oxidative stress and extracellular signal-regulated kinase 1/2 (ERK) activation. Hydrogen sulfide (H₂S) is involved in antioxidant systems and the ERK signaling pathway. Therefore, in this study, we investigated the role of H₂S in primary cilia elongation and the downstream pathway. In cultured Madin-Darby Canine Kidney cells, the length of primary cilia gradually increased up to 4 days after the cells were grown to confluent monolayers. In addition, the expression of H₂S-producing enzyme increased concomitantly with primary cilia length. Treatment with NaHS, an exogenous H₂S donor, accelerated the elongation of primary cilia whereas DL-propargylglycine (a cystathionine γ-lyase inhibitor) and hydroxylamine (a cystathionine-β-synthase inhibitor) delayed their elongation. NaHS treatment increased ERK activation and Sec10 and Arl13b protein expression, both of which are involved in cilia formation and elongation. Treatment with U0126, an ERK inhibitor, delayed elongation of primary cilia and blocked the effect of NaHS-mediated primary cilia elongation and Sec10 and Arl13b upregulation. Finally, we also found that H₂S accelerated primary cilia elongation after ischemic kidney injury. These results indicate that H₂S lengthens primary cilia through ERK activation and a consequent increase in Sec10 and Arl13b expression, suggesting that H₂S and its downstream targets could be novel molecular targets for regulating primary cilia.

• Korean Journal of Food Science and Technology
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• v.53 no.2
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• pp.111-114
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• 2021

Phytochemicals in fruits, vegetables, cereals, and nuts, advertised as "antioxidants", combat undesirable effects of reactive oxygen species (ROS) in the body. These undesirable effects include cancer, cardiovascular diseases, and neurodegenerative disorders. Although ROS were initially considered to be primarily damaging agents, ROS have been discovered to play a role in signaling immune and other physiological responses in recent years. Several studies have demonstrated that ROS act as essential signaling molecules to promote metabolic health. Therefore, the overall advantage of the interference of ROS signals by antioxidants could be questionable. Future research is required to understand the implications of the application of phytochemicals in functional foods and supplements for health benefits on ROS levels in the body. This study describes the new roles of ROS and hormesis of various phytochemicals to provide a possible research guideline to food and nutrition scientists.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.449-457
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• 2021

The sleep-wake cycle is regulated by the alternating activity of sleep- and wake-promoting neurons. The dorsal raphe nucleus (DRN) secretes 5-hydroxytryptamine (5-HT, serotonin), promoting wakefulness. Melatonin secreted from the pineal gland also promotes wakefulness in rats. Our laboratory recently demonstrated that daily changes in nitric oxide (NO) production regulates a signaling pathway involving with-no-lysine kinase (WNK), Ste20-related proline alanine rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1), and cation-chloride co-transporters (CCC) in rat DRN serotonergic neurons. This study was designed to investigate the effect of melatonin on NO-regulated WNK-SPAK/OSR1-CCC signaling in wake-inducing DRN neurons to elucidate the mechanism underlying melatonin's wake-promoting actions in rats. Ex vivo treatment of DRN slices with melatonin suppressed neuronal nitric oxide synthase (nNOS) expression and increased WNK4 expression without altering WNK1, 2, or 3. Melatonin increased phosphorylation of OSR1 and the expression of sodium-potassium-chloride co-transporter 1 (NKCC1), while potassium-chloride co-transporter 2 (KCC2) remained unchanged. Melatonin increased the expression of tryptophan hydroxylase 2 (TPH2, serotonin-synthesizing enzyme). The present study suggests that melatonin may promote its wakefulness by modulating NO-regulated WNK-SPAK/OSR1-KNCC1 signaling in rat DRN serotonergic neurons.

• Journal of the Korean Applied Science and Technology
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• v.38 no.5
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• pp.1249-1254
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• 2021

UV induce oxidative stress and increase matrix metalloproteinase (MMP) expression, resulting in skin aging. Thus, preventing skin damage from ultraviolet B (UVB)-induced skin damage can attenuate skin aging. Spirulina is comprised of prokaryotes a powerful antioxidant. This study aimed to investigate the photoprotective effects of spirulina-derived phycocyanin (PC) against UVB radiation using human skin fibroblast. As a results, PC showed no toxicity at concentrations of 5-40 ㎍/mL in terms of fibroblast viability. Survival rate of UVB-irradiated fibroblast incresased to 73.5% from 50.5% with PC treatment. UVB treatment increased MMP-1 and MMP-9 expression whereas PC treatment decreased it. The results indicate that PC might reduce or prevent skin aging by reducing UVB irradiation-induced skin wrinkles and free radicals.

• Korean Journal of Agricultural Science
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• v.48 no.1
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• pp.163-170
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• 2021

Bacterial infections in the female reproductive tract negatively affect ovarian function, follicular development, and embryo development, leading to the eventual failure of fertilization. Moreover, bacterial lipopolysaccharides (LPS) can interfere with the immune system and reproductive system of the host animal. Therefore, this study examined the effect of LPS on the in vitro maturation (IVM) of pig oocytes. Oocytes were matured in TCM199 medium in the presence of varying concentrations of LPS (0 - 50 ㎍·mL^-1). The maturation rate, cortical granules (CGs) migration, and chromosome alignment were subsequently evaluated during the meiotic development of the oocytes. We observed a dose-dependent and significant decrease in the metaphase II (MII) rate with increasing concentrations of LPS (97.6% control [0 ㎍·mL^-1 LPS] vs. 10.4-74.9% LPS [1 - 50 ㎍·mL^-1], p < 0.05). In addition, compared to the control oocytes without LPS, higher levels of abnormal CGs distribution (18.1 - 50.0% LPS vs. 0% control), chromosome/spindle alignment (20.3 - 56.7% LPS vs. 0% control), and intracellular ROS generation were observed in oocytes matured with LPS (p < 0.05). Nitrite levels were also increased in the maturation medium derived from the oocytes matured with LPS (p < 0.05). These results indicate that LPS induces oxidative stress during IVM and affects oocyte maturation, including CGs migration and chromosome alignment of pig oocytes.

• Biomedical Science Letters
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• v.27 no.3
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• pp.142-153
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• 2021

Liver fibrosis is a wound-healing response to chronic liver injury, which is caused by the continuous and excess deposition of extracellular matrix (ECM). The aim of this study is to investigate whether Uncaria rhynchophylla water extract (UR) can ameliorate thioacetamide (TAA)-induced liver fibrosis. The liver fibrosis model was induced on C57BL/6 mice by intraperitoneal injection with TAA three times a week for 8 weeks. UR (200 mg/kg) or silymarin (50 mg/kg) was administered orally daily for 8 weeks. Biochemical analyses including AST, ALT, MPO, and Ammonia levels were measured in serum. In the mice liver tissues, western blot and histological staining were analyzed. As a result, UR dramatically reduced the levels in serum AST, ALT, MPO, and Ammonia levels. UR treatment regulated NADPH oxidase factors expression, and antioxidant enzymes except for GPx-1/2 were significantly increased via Nrf2 activation. Furthermore, pro-inflammatory mediators, such as COX-2 and iNOS were markedly suppressed through the inhibition of NF-κB activation. Expressions of ECM-related protein including α-SMA and Collagen I were noticeably decreased. The additional histological evaluation confirmed that hepatocyte damage and collagenous fiber accumulation were attenuated. Taken together, these data suggest that UR possessed hepatoprotective effects in TAA-induced liver fibrosis via the NF-κB inactivation and Nrf2 activation. Therefore, UR may act as a potential therapeutic drug against liver fibrosis.

• Fisheries and Aquatic Sciences
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• v.24 no.5
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• pp.197-206
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• 2021

Marine brown seaweeds are a source of functional ingredients with various biological properties. They have been used in the food and functional food industries. Brown seaweeds are divided into three parts of blades, stipe, and root. Normally seaweed blades were used as raw materials for biological research. However, there are limited uses on stipes of Ecklonia maxima (E. maxima) depending on the physicochemical, nutritional, and biological properties. Besides, the comparative studies of two structures of E. maxima, blades and stipe didn't discover previously. This study aimed to compare the potent antioxidant and anti-inflammatory activities of the two structures of E. maxima, blades and stipe in vitro studies to increase the utilization of the two structures of E. maxima. The enzyme-assisted hydrolysate from E. maxima showed significant antioxidant and anti-inflammatory activities. Among them, celluclast-assisted hydrolysate from E. maxima blades (EMBC) and viscozyme-assisted hydrolysate from E. maxima stipe (EMSV) expressed significant protection on hydrogen peroxide-induced oxidative stress. Moreover, EMBC and EMSV treatment remarkably reduced nitric oxide production by downregulation of pro-inflammatory cytokine expressions in lipopolysaccharide-stimulated Raw 264.7 cells. Especially EMBC showed strong inhibition on pro-inflammatory cytokine production compared to EMSV. Taken together research findings suggest that EMBC and EMSV possessed potent antioxidant and anti-inflammatory properties and may be utilized as functional ingredients in the food and functional food sectors.