• Food Science and Biotechnology
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• 제17권6호
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• pp.1146-1150
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• 2008

Peroxisome proliferator-activated receptor-gamma ($PPAR_{\gamma}$), a member of the nuclear receptor of ligand-activated transcription factors, plays a key role in lipid and glucose metabolism or adipocytes differentiation. A lignan compound was isolated from mace (the aril of Myristica fragrans Houtt.) as a $PPAR_{\gamma}$ ligand, which was identified as fragrin A or 2-(4-allyl-2,6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)-propane. To ascertain whether fragrin A has $PPAR_{\gamma}$ ligand-binding activity, it was performed that GAL-4/$PPAR_{\gamma}$ transactivation assay. $PPAR_{\gamma}$ ligand-binding activity of fragrin A increased 4.7, 6.6, and 7.3-fold at 3, 5, and $10{\mu}M$, respectively, when compared with a vehicle control. Fragrin A also enhanced adipocytes differentiation and increased the expression of $PPAR_{\gamma}$ target genes such as adipocytes fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and phosphoenol pyruvate carboxykinase (PEPCK). Furthermore, it significantly increased the expression level of glucose transporter 4 (GLUT4). These results indicate that fragrin A can be developed as a $PPAR_{\gamma}$ agonist for the improvement of insulin resistance associated with type 2 diabetes.

• 한국발생생물학회지:발생과생식
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• 제23권3호
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• pp.263-275
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• 2019

Based on our preliminary results, we examined the possible role of low-dose and chronic-exposing of the chemicals those are known as endocrine disrupting chemical (EDC), on the proliferation of uterine endometrium and the localization of steroid receptors. Immunohistochemical or immunofluorochemical methodology were employed to evaluate the localization of antigen identified by monoclonal antibody Ki 67 protein (MKI67), estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), and progesterone receptor (PGR). In $133{\mu}g/L$ and $1,330{\mu}g/L$ di(2-ethylhexyl) phthalate (DEHP) and $50{\mu}g/L$ nonylphenol (NP) groups, the ratio of MKI67 positive stromal cells was significantly increased but not in $500{\mu}g/L$ NP group. The ratios of MKI67 positive glandular and luminal epithelial cells were also changed by the chronic administration of NP and DEHP in tissue with dose specific manner. ESR1 signals were localized in nucleus in glandular and luminal epithelia of control group but its localization was mainly in cytoplasm in DEHP and NP administered groups. On the other hand, it was decreased at nucleus of stromal cells in $1,330{\mu}g/L$ DEHP group. The colocalization patterns of these nuclear receptors were also modified by the administration of these chemicals. Such a tissue specific and dose specific localization of ESR2 and PGR were detected as ESR1 in all the uterine endometrial tissues. These results show that the chronic lows-dose exposing of NP or DEHP modify the localization and colocalization of ESRs and PGR, and of the proliferation patterns of the endometrial tissues.

• BMB Reports
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• 제54권9호
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• pp.476-481
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• 2021

Liver receptor homolog-1 (LRH-1) has emerged as a regulator of hepatic glucose, bile acid, and mitochondrial metabolism. However, the functional mechanism underlying the effect of LRH-1 on lipid mobilization has not been addressed. This study investigated the regulatory function of LRH-1 in lipid metabolism in maintaining a normal liver physiological state during fasting. The Lrh-1^f/f and LRH-1 liver-specific knockout (Lrh-1^LKO) mice were either fed or fasted for 24 h, and the liver and serum were isolated. The livers were used for qPCR, western blot, and histological analysis. Primary hepatocytes were isolated for immunocytochemistry assessments of lipids. During fasting, the Lrh-1^LKO mice showed increased accumulation of triglycerides in the liver compared to that in Lrh-1^f/f mice. Interestingly, in the Lrh-1^LKO liver, decreases in perilipin 5 (PLIN5) expression and genes involved in β-oxidation were observed. In addition, the LRH-1 agonist dialauroylphosphatidylcholine also enhanced PLIN5 expression in human cultured HepG2 cells. To identify new target genes of LRH-1, these findings directed us to analyze the Plin5 promoter sequence, which revealed -1620/-1614 to be a putative binding site for LRH-1. This was confirmed by promoter activity and chromatin immunoprecipitation assays. Additionally, fasted Lrh-1^f/f primary hepatocytes showed increased co-localization of PLIN5 in lipid droplets (LDs) compared to that in fasted Lrh-1^LKO primary hepatocytes. Overall, these findings suggest that PLIN5 might be a novel target of LRH-1 to mobilize LDs, protect the liver from lipid overload, and manage the cellular needs during fasting.

• Journal of Periodontal and Implant Science
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• 제51권4호
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• pp.254-263
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• 2021

Purpose: Periodontitis is associated with a dysbiosis of periodontopathic bacteria, which stimulate the interleukin (IL)-23/IL-17 axis that plays an essential role in the immunopathogenesis of this disease, leading to alveolar bone destruction through receptor activator of nuclear factor κB ligand (RANKL). IL-23 receptor mRNA (IL-23R) has been identified in periodontitis, and IL-17 receptor A mRNA (IL-17RA) and its protein have not yet been evaluated in patients with periodontitis. In this study was measure IL-23R and IL-17RA in gingival tissue (GT) from patients with generalized chronic periodontitis (GCP) and generalized aggressive periodontitis (GAP) and to explore correlations with clinical parameters. Methods: We included 16 healthy subjects (HS), 18 patients with GCP, and 14 with GAP. GT samples were collected during periodontal surgery. Both IL-23R and IL-17RA were detected by enzyme-linked immunosorbent assay. Results: The results were analyzed with Mann-Whitney U test and Spearman' rank correlation coefficients using SPSS version 25.0. We found lower IL-23R levels in patients with GCP and GAP than in HS. Contrarily, we observed higher IL-17RA levels in GCP and GAP patients than in HS. Moreover, we found negative correlations between IL-23R in GT and probing depth and clinical attachment loss (CAL). Likewise, a positive correlation of IL-17RA in GT with CAL was found. Conclusions: The results of these findings suggest that the reverse behavior between IL-23R and IL-17RA in periodontitis patients may also be involved with the activation of RANKL, which promotes alveolar bone loss.

• BMB Reports
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• 제55권11호
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• pp.547-552
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• 2022

Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, induces ferroptosis in hepatocellular carcinoma (HCC) cells. Several pathways that mitigate sorafenib-induced ferroptosis confer drug resistance; thus strategies that enhance ferroptosis increase sorafenib efficacy. Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is upregulated in human HCC tissues and plays a role in cancer cell proliferation. The aim of this study was to determine whether inhibition of ERRγ with DN200434, an orally available inverse agonist, can overcome resistance to sorafenib through induction of ferroptosis. Sorafenib-resistant HCC cells were less sensitive to sorafenibinduced ferroptosis and showed significantly higher ERRγ levels than sorafenib-sensitive HCC cells. DN200434 induced lipid peroxidation and ferroptosis in sorafenib-resistant HCC cells. Mechanistically, DN200434 increased mitochondrial ROS generation by reducing glutathione/glutathione disulfide levels, which subsequently reduced mTOR activity and GPX4 levels. DN200434 induced amplification of the antitumor effects of sorafenib was confirmed in a tumor xenograft model. The present results indicate that DN200434 may be a novel therapeutic strategy to re-sensitize HCC cells to sorafenib.

• Nutrition Research and Practice
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• 제17권1호
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• pp.32-47
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• 2023

BACKGROUND/OBJECTIVES: Benign prostatic hyperplasia (BPH) characterized by an enlarged prostate gland is common in elderly men. Corni Fructus (CF) and Schisandrae Fructus (SF) are known to have various pharmacological effects, including antioxidant and anti-inflammatory activities. In this study, we evaluated the inhibitory efficacy of CF, SF, and their mixture (MIX) on the development of BPH using an in vivo model of testosterone-induced BPH. MATERIALS/METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into seven groups. To induce BPH, testosterone propionate (TP) was injected to rats except for those in the control group. Finasteride, saw palmetto (SP), CF, SF, and MIX were orally administered along with TP injection. At the end of treatment, histological changes in the prostate and the level of various biomarkers related to BPH were evaluated. RESULTS: Our results showed that BPH induced by TP led to prostate weight and histological changes. Treatment with MIX effectively improved TP-induced BPH by reducing prostate index, lumen area, epithelial thickness, and expression of BPH biomarkers such as 5α-reductase type 2, prostate-specific antigen, androgen receptor, and proliferating cell nuclear antigen compared to treatment with CF or SF alone. Moreover, MIX further reduced levels of elevated serum testosterone, dihydrotestosterone, and prostate-specific antigen in BPH compared to the SP, a positive control. BPH was also improved more by MIX than by CF or SF alone. CONCLUSIONS: Based on the results, MIX is a potential natural therapeutic candidate for BPH by regulating 5α-reductase and AR signaling pathway.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2003년도 학술발표대회 발표논문초록집
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• pp.69-69
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• 2003

Although effect of TGF$\beta$$_1$ on preimplantation embryo development was reported at mice, little information relevant to this subject is known in bovine. The objectives of this study were to investigate TGF$\beta$$_1$, and TGF$\beta$$_1$ receptors type I and II expression, known as important factors in the embryo development, at unfertilized oocytes and fertilized embryos that will be used as basic data to be compared to NT embryos. We postulated that TGF$\beta$$_1$ may have a beneficial effect on the preimplantation embryo and show different expression patterns as embryo stages change. We have used immunocytochemistry to investigate the presence in unfertilized oocytes and preimplantation embryos of TGF$\beta$$_1$ and the essential components of the TGF$\beta$$_1$ signalling pathway, TGF$\beta$$_1$ receptors type I and II. We found that both receptors, as well as TGF$\beta$$_1$, were present in the unfertilized oocytes. This indicates that TGF$\beta$$_1$, is a maternally expressed protein. At the morulae and blastocyst stages the TGF$\beta$$_1$ receptor type II was not present, but the TGF$\beta$$_1$ receptor type I was present at both stages and we can confirm the TGF$\beta$$_1$ expression of high level at 8-cell stage. These findings support our hypothesis that the TGF$\beta$$_1$, and TGF$\beta$$_1$ receptors may interact with the oocyte and preimplantation embryo, and that TGF$\beta$$_1$ signalling may be important for the development of the oocyte and the preimplahtation embryo.

• Annals of Occupational and Environmental Medicine
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• 제34권
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• pp.5.1-5.10
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• 2022

Background: Some epidemiological studies have estimated exposure among flight attendants with and without breast cancer. However, it is difficult to find a quantitative evaluation of occupational exposure factors related to cancer development individually in the case of breast cancer in flight attendants. That is, most, if not all, epidemiological studies of breast cancer in flight attendants with quantitative exposure estimates have estimated exposure in the absence of individual flight history data. Case presentation: A 41-year-old woman visited the hospital due to a left breast mass after a regular check-up. Breast cancer was suspected on ultrasonography. Following core biopsy, she underwent various imaging modalities. She was diagnosed invasive ductal carcinoma of no special type (estrogen receptor positive in 90%, progesterone receptor positive in 3%, human epidermal growth factor receptor 2/neu equivocal) with histologic grade 3 and nuclear grade 3 in the left breast. Neoadjuvant chemotherapy was administered to reduce the tumor size before surgery. However, due to serious chemotherapy side effects, the patient opted for alternative and integrative therapies. She joined the airline in January, 1996. Out of all flights, international flights and night flights accounted for 94.9% and 26.2, respectively. Night flights were conducted at least four times per month. Moreover, based on the virtual computer program CARI-6M, the estimated dose of cosmic radiation exposure was 78.81 mSv. There were no other personal triggers or family history of breast cancer. Conclusions: This case report shows that the potentially causal relationship between occupational harmful factors and the incidence of breast cancer may become more pronounced when night shift workers who work continuously are exposed to cosmic ionizing radiation. Therefore, close attention and efforts are needed to adjust night shift work schedules and regulate cosmic ionizing radiation exposure.

• International Journal of Oncology
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• 제55권1호
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• pp.320-330
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• 2019

The aim of this study was to investigate the underlying mechanisms responsible for the anticancer effects of lupeol on human non-small cell lung cancer (NSCLC). MTT assay and Trypan blue exclusion assay were used to evaluate the cell viability. DAPI staining and flow cytometric analysis were used to detect apoptosis. Molecular docking and western blot analysis were performed to determine the target of lupeol. We found that lupeol suppressed the proliferation and colony formation of NSCLC cells in a dose-dependent manner. In addition, lupeol increased chromatin condensation, poly(ADP-ribose) polymerase (PARP) cleavage, sub-G1 cell populations, and the proportion of Annexin V-positive cells, indicating that lupeol triggered the apoptosis of NSCLC cells. Notably, lupeol inhibited the phosphorylation of epithelial growth factor receptor (EGFR). A docking experiment revealed that lupeol directly bound to the tyrosine kinase domain of EGFR. We observed that the signal transducer and activator of transcription 3 (STAT3), a downstream molecule of EGFR, was also dephosphorylated by lupeol. Lupeol suppressed the nuclear translocation and transcriptional activity of STAT3 and downregulated the expression of STAT3 target genes. The constitutive activation of STAT3 by STAT3 Y705D overexpression suppressed lupeol-induced apoptosis, demonstrating that the inhibition of STAT3 activity contributed to the induction of apoptosis. The anticancer effects of lupeol were consistently observed in EGFR tyrosine kinase inhibitor (TKI)-resistant H1975 cells (EGFR L858R/T790M). Taken together, the findings of this study suggest that lupeol may be used, not only for EGFR TKI-naïve NSCLC, but also for advanced NSCLC with acquired resistance to EGFR TKIs.

• The Korean Journal of Physiology and Pharmacology
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• 제10권3호
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• pp.131-135
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• 2006

Coeruleo-vestibular pathway which connects locus coeruleus and vestibular nuclei is noradrenergic. This study was designed to elucidate the effects of phenylephrine on the spontaneous activity of acutely isolated medial vestibular nuclear neurons of rat by whole-cell patch-clamp technique. Sprague-Dawley rats, aged 14 to 16 days, were used. After enzymatic digestion, dissociated medial vestibular neurons were transferred to a recording chamber mounted on an inverted microscope, and spontaneous action potentials were recorded by standard patch-clamp techniques. In current-clamp mode, the frequency of spontaneous action potential of medial vestibular nuclear neurons was decreased by phenylephrine (n=15). Phenylephrine increased the amplitude of afterhyperpolarization without changes in the resting membrane potential and spike width. In voltage-clamp mode, the whole potassium currents of the medial vestibular nuclear neurons were increased by phenylephrine (n=12). These experimental results suggest that ${\alpha}-receptor$ mediates the inhibitory effects on the neuronal activity of the medial vestibular nuclear neuron.