Estrogen can promote or inhibit cellular proliferation depending on tissue cell types and physiological condition and acts through the signal transduction pathways mediated primarily by estrogen receptors. This study examined the effects of fulvestrant (Ful), a well-known antagonist for the estrogen receptor, on the action of $17{\beta}$-estradiol (E2) with respect to the proliferation and apoptosis of Chinese hamster ovarian (CHO) cells. We used different concentrations of E2, Ful, and E2 plus Ful during different treatment durations. Treatment with 15-40 ${\mu}M$ E2 significantly inhibited proliferation in a time-dependent manner, although it had no influence in concentrations up to 1 ${\mu}M$. Interestingly, Ful at 10-40 ${\mu}M$ also inhibited cellular proliferation in both a concentration- and time-dependent manner. In addition, Ful enhanced rather than decreased the inhibitory effect on cellular proliferation by E2 in combined treatment for 10 days. Thus, Ful does not appear to have an antagonistic effect on estrogen's anti-proliferative action in CHO cells. In TUNEL assays to confirm DNA fragmentation by E2 and/or Ful, CHO cells treated with 20 ${\mu}M$ E2 showed a TUNEL-positive reaction in most DAPI-stained nuclei, and cells treated with either 40 ${\mu}M$ Ful or 40 ${\mu}M$ Ful plus 20 ${\mu}M$ E2 also exhibited a TUNEL-positive reaction but at a lower rate compared to the E2-treated cells. These results indicate that Ful does not have an antagonistic effect on estrogen's anti-proliferative action in CHO cells, suggesting that the anti-proliferative and apoptosis-related mechanism(s) through DNA fragmentation by E2 and Ful may be mediated by different signal transduction pathways.
Lee, Hyun Ah;Kim, Ji Eun;Song, Sung Hwa;Sung, Ji Eun;Jung, Min Gi;Kim, Dong Seob;Son, Hong Joo;Lee, Chung Yeoul;Lee, Hee Seob;Hwang, Dae Youn
Journal of Life Science
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v.26
no.5
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pp.509-518
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2016
Asparagus cochinchinensis is a medical plant that has long been used to treat fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease in northeast Asian countries. Although several studies have been conducted on the anti-neuroinflammatory effects of A. cochinchinensis, the correlation between these effects and nerve growth factor (NGF) has not yet been examined. In this study, we investigated the effects of an aqueous extract of A. cochinchinensis (AEAC) on the secretion and action mechanism of NGF in neuronal cells. The concentration of the NGF protein in the supernatant collected from cultured cells increased significantly in B35 cells treated with AEAC in comparison with the vehicle-treated group without any specific cytotoxicity. Furthermore, the mRNA expression of NGF showed a very similar pattern to its protein concentration. To examine the bioactivity of NGF secreted from B35 cells, undifferentiated PC12 cells were cultured in an AEAC-conditioned medium and neuritic outgrowth was observed. The dendrite length of PC12 cells in the AEAC-treated group was significantly higher than that in the vehicle-treated group. Moreover, the level of the downstream effectors p-TrkA and p-ERK of the high-affinity NGF receptor was significantly higher in the AEAC-treated group, while the expression of the downstream effectors of the low-affinity NGF receptor was significantly lower in the same group. These results suggest that AEAC may contribute to the regulation of NGF expression and secretion in neuronal cells; it is therefore an excellent candidate for further investigation as a therapeutic drug for neurodegenerative diseases.
Although MR imaging is generally applicable to depict knee joint deterioration it, is sometimes occurred to mis-read and mis-diagnose the common knee joint diseases. In this study, we employed magnetization transfer ratio (MTR) method to improve the diagnosis of the various knee joint diseases. Spin-echo (SE) T2-weighted images (TR/TE 3,400-3,500/90-100 ms) were obtained in seven cases of knee joint deterioration, FSE T2-weighted images (TR/TE 4,500-5,000/100-108 ms) were obtained in seven cases of knee joint deterioration, gradient-echo (GRE) T2-weighted images (TR/TE 9/4.56/$50^{\circ}$ flip angle, NEX 1) were obtained in 3 cases of knee joint deterioration, In six cases of knee joint deterioration, fat suppression was performed using a T2-weighted short T1/tau inverse recovery (STIR) sequence (TR/TE =2,894-3,215 ms/70 ms, NEX 3, ETL 9). Calculation of MTR for individual pixels was performed on registration of unsaturated and saturated images. After processing to make MTR images, the images were displayed in gray color. For improving diagnosis, three-dimensional isotropic volume images, the MR tristimulus color mapping and the MTR map was employed. MTR images showed diagnostic images quality to assess the patients' pathologies. The intensity difference between MTR images and conventional MRI was seen on the color bar. The profile graph on MTR imaging effect showed a quantitative measure of the relative decrease in signal intensity due to the MT pulse. To diagnose the pathologies of the knee joint, the profile graph data was shown on the image as a small cross. The present study indicated that MTR images in the knee joint were feasible. Investigation of physical change on MTR imaging enables to provide us more insight in the physical and technical basis of MTR imaging. MTR images could be useful for rapid assessment of diseases that we examine unambiguous contrast in MT images of knee disorder patients.
Lee, Chea Yeon;Park, Hyo Sung;Kong, Deok-Hoon;Kim, Young Kwan;Cho, Whajung
Journal of Nutrition and Health
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v.53
no.5
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pp.452-463
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2020
Purpose: Aster tataricus (AT) is one of the Asteraceae perennial herbs used in traditional Chinese medicine. The herb contains various bioactive substances, such as flavonoids, isoflavonoids, and phenolic compounds in the roots, and exhibits a range of effects including anti-bacterial, anti-oxidant, and anti-inflammatory activities. This study compared the immunomodulatory effects of ethanol and water extracts of whole AT, except the roots, and analyzed the molecular mechanisms for the regulatory effects on cytokine secretion from THP-1 cells. Methods: The effects of AT extract on the cell viability and proliferation of THP-1 cells were analyzed using the Cell Counting Kit-8 method. The concentrations of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the cell culture supernatant of the AT-treated THP-1 cells were measured using an enzyme-linked immunosorbent assay. The protein levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), inhibitor of nuclear factor kappa B (IκBα), and mitogen-activated protein kinase (MAPK) phosphorylation in the cell lysates were determined by western blotting. Results: The water extract and the ethanol extract of AT did not affect the cell viability, and increased the proliferation of THP-1 cells significantly compared to the vehicle. The water extract increased the secretion of IL-1β from THP-1 cells in a dose-dependent manner, but the ethanol extract had no effect. The expression of COX-2 and iNOS protein and the phosphorylation of MAPK and Akt were induced in AT-treated cells. In addition, IκBα was degraded by AT in a concentration-dependent manner. IL-1β secretion by AT was reduced by extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitors, while TNF-α secretion was decreased by inhibitors of ERK, p38 MAPK, and JNK. Interestingly, the p38 MAPK inhibitor increased the production of IL-1β by AT further. Conclusion: The water extract of the above-ground parts of AT contains immunomodulatory bioactive substances that stimulate immune cells through the MAPK signaling pathway.
Interfacial and microfailure properties of the modified steel, carbon and glass fibers/cement composites were investigated using electro-pullout test under tensile and compressive tests with acoustic emission (AE). The hand-sanded steel composite exhibited higher interfacial shear strength (IFSS) than the untreated and even neoalkoxy zirconate (Zr) treated steel fiber composites. This might be due to the enhanced mechanical interlocking, compared to possible hydrogen or covalent bonds. During curing process, the contact resistivity decreased rapidly at the initial stage and then showed a level-off. Comparing to the untreated case, the contact resistivity of either Zr-treated or hand-sanded steel fiber composites increased to the infinity at latter stage. The number of AE signals of hand-sanded steel fiber composite was much more than those of the untreated and Zr-treated cases due to many interlayer failure signals. AE waveforms for pullout and frictional signals of the hand-sanded composite are larger than those of the untreated case. For dual matrix composite (DMC), AE energy and waveform under compressive loading were much higher and larger than those under tensile loading, due to brittle but well-enduring ceramic nature against compressive stress. Vertical multicrack exhibits fur glass fiber composite under tensile test, whereas buckling failure appeared under compressive loading. Electro-micromechanical technique with AE can be used as an efficient nondestructive (NDT) method to evaluate the interfacial and microfailure mechanisms for conductive fibers/brittle and nontransparent cement composites.
The activity of CAR can be regulated not only by ligand binding but also by phosphorylation of regulatory factors involved in extracellular signaling pathways, cross-talk interactions with transcription factors, and the recruitment, degradation, and expression of coactivators and corepressors. This regulation of CAR activity can in turn have effects on the control of diverse physiological homeostasis, including xenobiotic and energy metabolism, cellular proliferation, and apoptosis. CAR is phosphorylated by the ERK1/2 signaling pathway, which causes formation of a complex with Hsp-90 and CCRP, leading to its cytoplasmic retention, whereas phenobarbital inhibits ERK1/2, which causes dephosphorylation of the downstream signaling molecules, leading to the recruitment to CAR of the activated RACK-1/PP2A components for the dephosphorylation, nuclear translocation, and the transcriptional activation of CAR. Activated CAR cross-talks with FoxO1 to induce inhibition of its transcriptional activity and with PGC-1α to induce protein degradation by ubiquitination, resulting in the transcriptional suppression of PEPCK and G6Pase involved in gluconeogenesis. Regulation by CAR of lipid synthesis and oxidation is achieved by its functional cross-talks, respectively, with PPARγ through the degradation of PGC-1α to inhibit expression of the lipogenic genes and with PPARα through either the suppression of CPT-1 expression or the interaction with PGC-1α each to induce tissue-specific inhibition or stimulation of β-oxidation. Whereas CAR stimulates cellular proliferation by suppressing p21 expression through the inhibition of FoxO1 transcriptional activity and inducing cyclin D1 expression, it suppresses apoptosis by inhibiting the activities of MKK7 and JNK-1 through the expression of GADD45B. In conclusion, CAR is involved in the maintenance of homeostasis by regulating not only xenobiotic metabolism but also energy metabolism, cellular proliferation, and apoptosis through diverse cross-talk interactions with extracellular signaling pathways and intracellular regulatory factors.
Kim, Nambeom;Lee, Jae Jun;Cho, Seo-Eun;Kang, Seung-Gul
Sleep Medicine and Psychophysiology
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v.27
no.1
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pp.24-31
/
2020
Objectives: Subjective-objective discrepancy of sleep (SODS) is a common symptom and one of the major phenotypes of insomnia. A distorted perception of sleep deficit might be related to abnormal brain reactivity to insomnia-related stimuli. We aimed to investigate differences in brain activation to insomnia-related stimuli vs. general anxiety-inducing stimuli among insomnia patients with SODS, insomnia patients without SODS, and healthy controls (HCs). Methods: All participants were evaluated for subjective sleep status using a sleep diary and questionnaires; occult sleep disorders and objective sleep status were assessed using polysomnography and actigraphy. Task functional magnetic resonance imaging was performed during insomnia-related stimuli (Ins) and general anxiety-inducing stimuli (Gen). Brain reactivity to Ins versus Gen was compared among insomnia with SODS, insomnia without SODS, and HC groups, and a combined insomnia disorder group (ID, insomnia with and without SODS) was also compared with HCs. Results: In the insomnia with SODS group compared to the insomnia without SODS group, the right precuneus and right supplementary motor areas showed significantly increased BOLD signals in response to Ins versus Gen. In the ID group compared to the HC group, the left anterior cingulate cortex showed significantly increased BOLD signals in response to Ins versus Gen. Conclusion: The insomnia with SODS and ID groups showed higher brain activity in response to Ins versus Gen, while this was not observed in the insomnia without SODS and HC groups, respectively. These results suggest that insomnia patients with sleep misperception are more sensitive to sleep-related threats than general anxiety-inducing threats.
Seo, Man-Kil;Han, Woo-Sang;Lee, Kyung-Kyu;Yu, Bum-Hee;Lee, Yu-Ri;Kim, E-Yong;Kim, Hyun-Woo
Sleep Medicine and Psychophysiology
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v.6
no.1
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pp.38-45
/
1999
Objectives: We explored the characteristics of physiological variables such as electrodermal response(EDR) and electromyography(EMG) in patients with insomnia, panic disorder, and other anxiety disorders. we aimed to decide the minimum sessions in biofeedback treatment to make the treatment effective and examine the effects of long-term biofeedback treatment by measuring the physiological variables. Methods: Thirty seven outpatients who received biofeedback treatment were divided into 3 groups according to the number of biofeedback sessions(patients who received 4-5 sessions, who received 6-9 sessions, and who received more than 10 sessions). We measured mean and delta values of EDR and EMG levels, and the Hamilton Anxiety Rating Scale(HARS), and Slef-Relaxation Inventory(SRI) in all patients. Data were analyzed by t-test and repeated measures analysis of variance. Results: The mean and delta values of EDR and EMG levels were not different among the 3 groups during the first 4 biofeedback sessions. However, patients who received more than 10 biofeedback sessions had higher baseline mean EDR value(F=2.233, p=0.036) in the first session, compared with other patients. In patients who received more than 10 biofeedback sessions, mean EDR was significantly reduced after $5^{th}$ session(F=10.41, p<0.01). They showed significant improvement in SRI scores at 12th biofeedback session(t=2.726, p<0.05) and in HARS scores at $6^{th}$(t=3.10, p<0.05) and $12^{th}$ biofeedback session(t=10.93, p<0.001). Conclusions: Wesuggest that patients should receive more than 5 biofeedback sessions to experience internal cues and get a good clinical response to biofeedback treatment.
This study investigated the anti-inflammatory activity of barley leaf extract in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and hairless mice. Pre-treatment with barley leaf extract significantly inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-II (COX-II) in a dose-dependent manner in LPS-stimulated RAW264.7 cells. Barley leaf extract also significantly inhibited the secretion of inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and interleukin-6 (IL-6). Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) were strongly suppressed by barley leaf extract in LPS-stimulated cells. In hairless mice, barley extract significantly decreased the pathological phenotypes of contact dermatitis, such as erythema, edema, and scabs. These results indicate that barley leaf extract has an anti-inflammatory effect and therefore a possible role in the treatment of inflammatory diseases or in functional cosmetics.
Jin, Kyong-Suk;Park, Jung Ae;Lee, Ji Young;Kang, Ji Sook;Kwon, Hyun Ju;Kim, Byung Woo
Microbiology and Biotechnology Letters
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v.42
no.2
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pp.170-176
/
2014
In this study, the anti-oxidative and anti-inflammatory activities of Euptelea pleiosperma ethanol extract (EPEE) were evaluated using in vitro assays and cell culture model systems. EPEE possessed a more potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl than the ascorbic acid used as a positive control. EPEE effectively suppressed lipopolysaccharide (LPS), in addition to hydrogen peroxide induced reactive oxygen species on RAW 264.7 cells. Furthermore, EPEE induced the expression of the anti-oxidative enzyme heme oxygenase 1 (HO-1) and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2), dose and time dependently. The modulation of HO-1 and Nrf2 expression might be regulated by mitogen-activated protein kinases and phosphatidyl inositol 3 kinase/Akt as their upstream signaling pathways. On the other hand, EPEE inhibited LPS induced nitric oxide (NO) formation without cytotoxicity. Suppression of NO formation was the result of the down regulation of inducible NO synthase (iNOS) by EPEE. Suppression of NO and iNOS by EPEE may be modulated by their upstream transcription factor, nuclear factor ${\kappa}B$, and AP-1 pathways. Taken together, these results provide important new insights into E. pleiosperma, namely that it possesses anti-oxidative and anti-inflammatory activities, indicating that it could be utilized as a promising material in the field of nutraceuticals.
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