• Journal of Korean Medical Science
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• v.33 no.51
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• pp.325.1-325.10
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• 2018

Background: To evaluate survival outcomes and prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who received sunitinib (SU) and pazopanib (PZ) as first-line therapy in real-world Korean clinical practice. Methods: Data of 554 patients with mRCC who received SU or PZ at eight institutions between 2012 and 2016 were retrospectively reviewed. Based on the targeted therapy, the patients were divided into SU (n = 293) or PZ (n = 261) groups, and the clinicopathological variables and survival rates of the two groups were compared. A multivariable Cox proportional hazard model was used to determine the prognostic factors for OS. Results: The median follow-up was 16.4 months (interquartile range, 8.3-31.3). Patients in the PZ group were older, and no significant difference was observed in the performance status (PS) between the two groups. In the SU group, the dose reduction rate was higher and the incidence of grade 3 toxicity was more frequent. The objective response rates were comparable between the two groups (SU, 32.1% vs. PZ, 36.4%). OS did not differ significantly between the two groups (SU, 36.5 months vs. PZ, 40.2 months; log-rank, P = 0.955). Body mass index, Eastern Cooperative Oncology Group PS > 2, synchronous metastasis, poor Heng risk criteria, and liver and bone metastases were associated with a shorter OS. Conclusion: Our real-world data of Korean patients with mRCC suggested that SU and PZ had similar efficacies as first-line therapy for mRCC. However, PZ was better tolerated than SU in Korean patients.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.2
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• pp.155-164
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• 2005

Objective: This study was performed to investigate the effects of pioglitazone, an insulin sensitizing agent, on insulin resistance, ovarian function and intraovarian stromal blood flow in patients with polycystic ovarian syndrome (PCOS). Material and Methods: Thirty patients with PCOS, aged 18~34 years, were recruited. Criteria for diagnosis of PCOS were as defined in 2003 Rotterdam consensus. They were treated for 6 months with pioglitazone at a dose of 30 mg/day orally. The hormonal blood profile, fasting serum glucose levels, a glycemic response to 75 g oral glucose tolerance test (OGTT), and an ovarian stromal artery (OSA) blood flow were assessed at baseline and after 6 months of treatment. Results: Eighteen (60.0%) of 30 patients treated with pioglitazone demonstrated a spontaneous ovulation After pioglitazone treatment, fasting insulin concentrations, serum glucose levels after 75 g OGTT significantly decreased (p=0.001, p=0.04, respectively), and fasting glucose to insulin (G/I) ratio significantly increased (p<0.001). The pioglitazone treatment induced a significant reduction in serum LH, testosterone (T) and free T levels (p<0.001, p=0.02, p=0.002, respectively). The resistance index (RI) values of OSA significantly increased after treatment (p<0.001). In analyzing pioglitazone-treated patients according to their body mass index (BMI), nonobese group as well as obese group showed a significant improvement in fasting G/I ratio (p<0.01). The pioglitazone treatment induced a significant reduction in serum LH and free T levels in nonobese group (p<0.001, p<0.05, respectively) as well as obese group (p=0.001, p<0.05, respectively). The RI values of OSA significantly increased in both nonobese and obese groups after pioglitazone treatment (p<0.001, p=0.003, respectively). Conclusions: Pioglitazone could ameliorate the glycoinsulinemic metabolism, and this beneficial effects of this drug could improve the endocrine-reproductive condition associated with the decrease of ovarian stromal artery blood flow, in both nonobese and obese patients with PCOS.

• Korean Journal of Food Science and Technology
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• v.53 no.5
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• pp.657-668
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• 2021

We prepared the growth and survival models of enterohemorrhagic Escherichia coli (EHEC) and Campylobacter jejuni in milk as a function of temperature and assessed the microbiological risks associated with the consumption of whole milk. EHEC and C. jejuni were not detected in whole milk (n=195) in the retail market. The minimum growth temperature of EHEC in milk was 7℃. The lag time of EHEC in whole milk was longer than that in skim milk. The survival ability of C. jejuni in milk was better at 4℃ than at 10℃. Lower delta values were observed in whole milk than in skim milk, indicating that C. jejuni survived better in skim milk. The probability of foodborne illness from whole milk consumption was 5.70×10^-5 for EHEC and 9.86×10^-9 for C. jejuni. Sensitivity analysis results show that the market temperature of EHEC and the dose-response model of C. jejuni are correlated with the probability of foodborne illness.

• Laboraroty Animal Research
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• v.33 no.2
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• pp.57-67
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• 2017

The inhibitory effects of Asparagus cochinchinensis against inflammatory response induced by lipopolysaccharide (LPS), substance P and phthalic anhydride (PA) treatment were recently reported for some cell lines and animal models. To evaluate the hepatotoxicity and nephrotoxicity of A. cochinchinensis toward the livers and kidneys of ICR mice, alterations in related markers including body weight, organ weight, urine composition, liver pathology and kidney pathology were analyzed in male and female ICR mice after oral administration of 150, 300 and 600 mg/kg body weight/day saponin-enriched extract of A. cochinchinensis (SEAC) for 14 days. The saponin, total flavonoid and total phenol levels were found to be 57.2, 88.5 and 102.1 mg/g in SEAC, respectively, and the scavenging activity of SEAC gradually increased in a dose-dependent manner. Moreover, body and organ weight, clinical phenotypes, urine parameters and mice mortality did not differ between the vehicle and SEAC treated group. Furthermore, no significant alterations were measured in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) and the serum creatinine (Cr) in the SEAC treated group relative to the vehicle treated group. Moreover, the specific pathological features induced by most toxic compounds were not observed upon liver and kidney histological analysis. Overall, the results of the present study suggest that SEAC does not induce any specific toxicity in the livers and kidneys of male and female ICR mice at doses of 600 mg/kg body weight/day.

• Journal of Life Science
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• v.29 no.7
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• pp.785-791
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• 2019

In this study, we investigated the biological antioxidant and antibacterial activity of Chamaecyparis obtusa (C. obtuse) extracts by measuring DPPH radical scavenging and ABTS radical scavenging, and SOD-like activities. The DPPH and ABTS radical scavenging activities were increased in a dose-dependent manner, with maximum activities of 78% and 62% at an extract concentration of $50{\mu}l/ml$. The C. obtusa extracts also showed high SOD-like activity, with a maximum activity of 92.85% at a concentration of $50{\mu}l/ml$. The antibacterial activities of C. obtusa extracts were measured against six types of bacteria known to cause food poisoning and disease. Antibacterial activity was investigated against three gram-positive and three gram-negative bacteria using the paper disc agar diffusion method. The C. obtusa extracts showed antibacterial activities against B. cereus, E. coli, L. monocytogenes, S. aureus, S. typhi and V. parahaemolyticus, among which the activity against B. cereus was greatest. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of C. obtusa extracts were $30-40{\mu}l/ml$ for the 6 strains that showed an antimicrobial response by the paper disc agar diffusion method. These results suggest that C. obtusa extracts could serve as potential antibacterial agents to inhibit the growth of pathogens responsible for food poisoning and disease.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.12
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• pp.1942-1949
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• 2019

Objective: Leukocyte cell-derived chemotaxin 2 (LECT2) is associated with several physiological processes including inflammation, tumorigenesis, and natural killer T cell generation. Chicken LECT2 (chLECT2) gene was originally identified as one of the differentially expressed genes in chicken kidney tissue, where the chickens were fed with different calcium doses. In this study, the molecular characteristics and gene expression of chLECT2 were analyzed under the stimulation of toll-like receptor 3 (TLR3) ligand to understand the involvement of chLECT2 expression in chicken metabolic disorders. Methods: Amino acid sequence of LECT2 proteins from various species including fowl, fish, and mammal were retrieved from the Ensembl database and subjected to Insilco analyses. In addition, the time- and dose-dependent expression of chLECT2 was examined in DF-1 cells which were stimulated with polyinosinic:polycytidylic acid (poly [I:C]), a TLR3 ligand. Further, to explore the transcription factors required for the transcription of chLECT2, DF-1 cells were treated with poly (I:C) in the presence or absence of the nuclear factor ${\kappa}B$ ($NF{\kappa}B$) and activated protein 1 (AP-1) inhibitors. Results: The amino acid sequence prediction of chLECT2 protein revealed that along with duck LECT2 (duLECT2), it has unique signal peptide different from other vertebrate orthologs, and only chLECT2 and duLECT2 have an additional 157 and 161 amino acids on their carboxyl terminus, respectively. Phylogenetic analysis suggested that chLECT2 is evolved from a common ancestor along with the actinopterygii hence, more closely related than to the mammals. Our quantitative polymerase chain reaction results showed that, the expression of chLECT2 was up-regulated significantly in DF-1 cells under the stimulation of poly (I:C) (p<0.05). However, in the presence of $NF{\kappa}B$ or AP-1 inhibitors, the expression of chLECT2 is suppressed suggesting that both $NF{\kappa}B$ and AP-1 transcription factors are required for the induction of chLECT2 expression. Conclusion: The present results suggest that chLECT2 gene might be a target gene of TLR3 signaling. For the future, the expression pattern or molecular mechanism of chLECT2 under stimulation of other innate immune receptors shall be studied. The protein function of chLECT2 will be more clearly understood if further investigation about the mechanism of LECT2 in TLR pathways is conducted.

• Journal of Life Science
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• v.31 no.2
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• pp.192-198
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• 2021

Red yeast rice has been extensively used as food and traditional medicine for thousands of years in East Asian countries. It is produced by the fermentation of a particular yeast (in general, Monascus purpureus) as rice and various cereals (barley, soybean, etc.). Monascus sp. produces many secondary metabolites during its growth, including pigments, monacolins, and γ-aminobutyric acid. Some metabolites―specifically, monacolin K, γ-aminobutyric acid, dimerumic acid, and monascus pigments―have been reported to lower cholesterol and blood pressure while showing anti-obesity effects. In this study, we investigated the anti-obesity effect of ethanol extract from red yeast barley (RYB) fermented with Monascus sp. BHN-MK 2 on 3T3-L1 cells. The anti-obesity effects of RYB extract were examined: its lipid accumulation inhibitory effect was tested by Oil Red O staining, and obesity-related mRNA expression levels were tested by real-time RT-PCR in MDI stimulated 3T3-L1 cells. The intracellular lipid content of MDI-stimulated 3T3-L1 cells decreased significantly to 5.04%, 12.24%, and 23.52% in response to 200, 400, and 800 ㎍/ml RYB, respectively. Moreovers, we evaluated that RYB extract significantly downregulated the expression of C/EBPα, SREBP-1, and PPAR-γ gene in a dose-dependent manner. As a result, red yeast barley ethanol extracts exerted the strongest anti-obesity effects. Also, the results indicate that red yeast barley could be used as a functional anti-obesity food material.

• Molecules and Cells
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• v.44 no.1
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• pp.38-49
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• 2021

Airway mucus secretion is an essential innate immune response for host protection. However, overproduction and hypersecretion of mucus, mainly composed of the gel-forming MUC5AC protein, are significant risk factors for patients with asthma and chronic obstructive pulmonary disease (COPD). The transforming growth factor β (TGFβ) signaling pathway negatively regulates MUC5AC expression; however, the underlying molecular mechanism is not fully understood. Here, we showed that TGFβ significantly reduces the expression of MUC5AC mRNA and its protein in NCI-H292 cells, a human mucoepidermoid carcinoma cell line. This reduced MUC5AC expression was restored by a TGFβ receptor inhibitor (SB431542), but not by the inhibition of NF-κB (BAY11-7082 or Triptolide) or PI3K (LY294002) activities. TGFβ-activated Smad3 dose-dependently bound to MUC5AC promoter. Notably, TGFβ-activated Smad3 recruited HDAC2 and facilitated nuclear translocation of HDAC2, thereby inducing the deacetylation of NF-κB at K310, which is essential for a reduction in NF-κB transcriptional activity. Both TGFβ-induced nuclear translocation of Smad3/HDAC2 and deacetylation of NF-κB at K310 were suppressed by a Smad3 inhibitor (SIS3). These results suggest that the TGFβ-activated Smad3/HDAC2 complex is an essential negative regulator for MUC5AC expression and an epigenetic regulator for NF-κB acetylation. Therefore, these results collectively suggest that modulation of the TGFβ1/Smad3/HDAC2/NF-κB pathway axis can be a promising way to improve lung function as a treatment strategy for asthma and COPD.

• The Korean Journal of Pain
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• v.34 no.1
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• pp.58-65
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• 2021

Background: Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism. Methods: Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague-Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed. Results: Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine. Conclusions: These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.

• BMB Reports
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• v.54 no.5
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• pp.266-271
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• 2021

Estrogen-related receptor γ (ERRγ), a member of the orphan nuclear receptor family, is a key mediator in cellular metabolic processes and energy homeostasis. Therefore, ERRγ has become an attractive target for treating diverse metabolic disorders. We recently reported that ERRγ acts as a negative regulator of osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL). In the present study, we explored the effects of an ERRγ-specific modulator, GSK5182, on ERRγ-regulated osteoclast differentiation and survival. Interestingly, GSK5182 increased ERRγ protein levels much as does GSK4716, which is an ERRγ agonist. GSK5182 inhibited osteoclast generation from bone-marrow-derived macrophages without affecting cytotoxicity. GSK5182 also attenuated RANKL-mediated expression of cFos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), pivotal transcription factors for osteoclastogenesis. Arrested osteoclast differentiation was associated with reduced RANK expression, but not with the M-CSF receptor, c-Fms. GSK5182 strongly blocked the phosphorylation of IκBα, c-Jun N-terminal kinase, and extracellular signal-regulated kinase in response to RANKL. GSK5182 also suppressed NF-κB promoter activity in a dose-dependent manner. In addition to osteoclastogenesis, GSK5182 accelerated osteoclast apoptosis by caspase-3 activation. Together, these results suggest that GSK5182, a synthetic ERRγ modulator, may have potential in treating disorders related to bone resorption.