• Title/Summary/Keyword: response suppression function

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New Players in the BRCA1-mediated DNA Damage Responsive Pathway

  • Kim, Hongtae;Chen Junjie
    • Molecules and Cells
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    • v.25 no.4
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    • pp.457-461
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    • 2008
  • DNA damage checkpoint is an important self-defense mechanism for the maintenance of genome stability. Defects in DNA damage signaling and repair lead to various disorders and increase tumor incidence in humans. In the past 10 years, we have identified many components involved in the DNA damage-signaling pathway, including the product of breast cancer susceptibility gene 1 (BRCA1). Mutations in BRCA1 are associated with increased risk of breast and ovarian cancers, highlighting the importance of this DNA damage-signaling pathway in tumor suppression. While it becomes clear that BRCA1 plays a crucial role in the DNA damage responsive pathway, exactly how BRCA1 receives DNA damage signals and exerts its checkpoint function has not been fully addressed. A series of recent studies reported the discovery of many novel components involved in DNA damage-signaling pathway. These newly identified checkpoint proteins, including RNF8, RAP80 and CCDC98, work in concern in recruiting BRCA1 to DNA damage sites and thus regulate BRCA1 function in G2/M checkpoint control. This review will summarize these recent findings and provide an updated view of the regulation of BRCA1 in response to DNA damage.

Ginsan Improved Th1 Immune Response Inhibited by Gamma Radiation

  • Han Seon Kyu;Song Jie Young;Yun Yeon Sook;Yi Seh Yoon
    • Archives of Pharmacal Research
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    • v.28 no.3
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    • pp.343-350
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    • 2005
  • Gamma radiation causes suppression of the immune function, and immune properties are related to cytokine production. In the present study, the polysaccharide, Ginsan, purified from an ethanol-insoluble fraction of Ginseng (Panax ginseng C.A. Meyer, Araliaceae) water extract was studied to assess its effects on the immunosuppressive activities of gamma radiation. Gin­san was found to stimulate murine normal splenocytes by inducing the mRNA expressions of Th1 and Th2 type cytokines, and also restore the mRNA expression of IFN-$/gamma$, Th1 cytokine, after its inhibition by whole-body gamma irradiation. Therefore, Ginsan was found to restore the T lymphocytes function that had been suppressed by gamma irradiation in allogenic MLR (mixed lymphocyte reactions). However, Ginsan exhibited no excessive stimulatory effects on the control group. The above results indicated that Ginsan may constitute a new noble agent for the improvement of gamma radiation-induced immunosuppression.

The Effect of EH-HA(Ephedrae Herba Herbal Acupuncture) at ST36 on OVA-induced Asthma in Mice (마황(麻黃) 약침(藥鍼)의 천식억제(喘息抑制) 및 면역조절효과(免疫調節效果)에 대(對)한 실험적(實驗的) 연구(硏究))

  • Song, Hyong-Gun;Lee, Hyeon
    • Journal of Acupuncture Research
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    • v.23 no.1
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    • pp.1-14
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    • 2006
  • Background : Recently, so many people are suffered from the allergic or auto-immune disease, and the representative disease is just Allergic Asthma. It is because human immune function has been decreased. Many treatments were done to treat this disease, and many methods were studied to increase immune function and to suppress the asthma. But, the effect of asthma-suppression and improvement of immune response of EH-HA(Ephedrae Herba Herbal Acupuncture) has not been studied in detail. To study the effects of EH-HA, we injected EH-HA at Joksamni(ST36) of C57BL/6 mice. Objectives : The purpose of this study is to investigate the effect of asthma-suppression and improvement of immune response of EH-HA(Ephedrae Herba Herbal Acupuncture). EH-HA was done at Joksamni(ST36) of the mice with ovalbumin-induced asthma. Methods : C57BL/6 mice were sensitized and challenged with OVA(ovalbumin) for 12 weeks. Two experimental groups were treated with different concentrations(1%, 0.1%) of EH-HA at Joksamni(ST36) for the later 8 weeks(3times/week). Results : 1. The lung weight of the group treated with EH-HA decreased significantly compared with that of control group. 2. The total cells in lung, total leukocytes and eosinophils in BALF of the group treated with EH-HA decreased significantly compared with those of control group. 3. Eosinophils in BALF of the group treated with EH-HA in photomicrographs decreased significantly compared with those of control group. 4. The concentrations of IL-13, IgE, IL-4 in serum and IL-4 in BALF of the group treated with EH-HA decreased significantly compared with those of control group. 5. The numbers of $Gr-1^+/CD11b^+\;cells,\;CD3e^-/CCR3^+\;cells,\;CD4^+\;cells,\;CD8^+\;cells,\;CD3e^+/CD69^+\;cells\;and\;IgE^+/B220^+\;cells$ in lung of the group treated with EH-HA decreased significantly compared with those of control group. 6. In RT-PCR, the mRNA expression of IL-4, IL-5 and IL-13 in the group treated with EH-HA decreased compared with those of control group. Conclusion : These results suggested that EH-HA at Joksamni(ST36) in C57BL/6mice may be effective to OVA-induced asthma of C57BL/6 mice.

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Imrnunodepression during experimental Naegzeria meningoencephalitis in mice (Naegleria 수막뇌염에 있어 세포매개성 면역에 관한 실험적 연구)

  • Im, Gyeong-Il;Yu, Jae-Suk;Lee, Geun-Tae
    • Parasites, Hosts and Diseases
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    • v.25 no.2
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    • pp.195-198
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    • 1987
  • In order to test the function of Iymphocytes in Naegleria fowleri-nniected mice, the in nitro blastogenic response of splenocyte cultures to non-specific mitogens was studied. Concanavalin A and lipopolysaccharide stimulation were used as tests of T cell and B cell function. For the first 14 days following N. fowleri infection, Iymphoblastic transformation induced by T-cell mitogen was markedly reduced in comparison to the uninfected control mice. The blastogenic response to B-cell mitogen remained depressed in the infected mice up to 14 days after infection. The fluorescent antibody titers of sera of N. fowleri infected mice were between 1 : 4 and 1 : 32. The results suggest that there is a suppression of cell mediated immunity during the acute course of experimental Naegleria meningoencephalitis in mice.

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The Meaning of P50 Suppression : Interaction of Gamma and Alpha Waves

  • Lee, Kyungjun;Kang, Ung Gu
    • Korean Journal of Biological Psychiatry
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    • v.21 no.4
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    • pp.168-174
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    • 2014
  • Objectives Sensory gating dysfunctions in patients with schizophrenia and bipolar disorder have been investigated through two similar methods ; P50 suppression and prepulse inhibition paradigms. However, recent studies have demonstrated that the two measures are not correlated but rather constitute as distinct neural processes. Recent studies adopting spectral frequency analysis suggest that P50 suppression reflects the interaction between gamma and other frequency bands. The aim of the present study is to investigate which frequency component shows more significant interaction with gamma band. Methods A total of 108 mood disorder patients and 36 normal subjects were included in the study. The P50 responses to conditioning and test stimuli with an intra-pair interval of 500 msec were measured in the study population. According to P50 ratio (amplitude to the test stimulus/amplitude to the conditioning stimulus), the subjects with P50 ratio less than 0.2 were defined as suppressed group (SG) ; non-suppressed group (NSG) consisted of P50 ratio more than 0.8. Thirty-five and 25 subjects were included in SG and NSG, respectively. Point-to-point correlation coefficients (PPCCs) of both groups were calculated between two time-windows : the first window (S1) was defined as the time-window of one hundred millisecond after the conditioning auditory stimulus and the second window (S2) was defined as the time-window of 100 msec after the test auditory stimulus. Spectral frequency analysis was performed to investigate which frequency band results in the difference of PPCC between SG and NSG. Results Significant reduction of PPCC between S1 and S2 was observed in the SG (Pearson's r = 0.24), compared to PPCC of the NSG (r = 0.58, p < 0.05). In spectral frequency analysis, gamma band showed "phase-reset" and similar responses after the two auditory stimuli in suppressed and non-suppressed group. However in the case of alpha band, comparison showed significantly low PPCC in SG (r = -0.14) compared to NSG (r = 0.36, p < 0.05). This may be reflecting "phase-out" of alpha band against gamma band at approximately 50 msecs after the test stimulus in the SG. Conclusions Our study suggests that normal P50 suppression is caused by phase-out of alpha band against gamma band after the second auditory stimulus. Thus it is demonstrated that normal sensory gating process is constituted with attenuated alpha power, superimposed on consistent gamma response. Implications of preserved gamma and decreased alpha band in sensory gating function are discussed.

A Study on the Stability Fatigue according to the Accommodation Change due to the Use of Smartphone (스마트폰의 사용으로 인한 조절 변화에 따른 안정피로도에 대한 연구)

  • Kim, Bong-Hwan;Han, Sun-Hee;Park, Seon-Mi;Bae, Sang-Bin;Woo, Yong-Jun;Song, Gyeong-Jun;Bang, Eun-Min;Seo, Da-Eun
    • Journal of Korean Clinical Health Science
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    • v.8 no.1
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    • pp.1362-1368
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    • 2020
  • Purpose. In this study, The change of the accommodation function due to the use of a smartphone was objectively evaluated using an Auto Refractokeratometer and was to investigate the effect of accommodation response and microfluctuations of accommodation on stable fatigue. Methods. Twenty subjects (20 males, 20 females) who had no abnormalities in ophthalmic disease and strabismus, diplopia, suppression, convergence and ocular movement, and corrected visual acuity and unaided visual acuity of 0.8 or more were performed. The average age of the participants is (21.78 ± 1.78) years old. The refractive power of the eye was measured using an Auto Refractokeratometer (Speedy-i K-model, Righton Mfg Co. Tokyo Japan), and the equivalent spherical power was automatically calculated from the measured refractive power. The accommodation response amount was calculated for the accommodation stimulation amount in 8 steps in 0.5D increments from + 0.50D to -3.00D in the calculated equivalent spherical power. The microfluctuations of accommodation in the high frequency region was calculated according to the change in the amount of the accommodation stimulus. At this time, the spectral power of the microfluctuations of accommodation was analyzed by Fast Fourier Transformation (FFT). Results. After using the smartphone, it was found that the accommodation response to accommodation stimulation decreased and the microfluctuations of accommodation increased. Conclusions. It can be said that the use of a smartphone affects the accommodation response and the microfluctuations of accommodation, thereby causing a accommodative stable fatigue. Therefore, it is thought that the use of a smartphone for a long time may bring about a change in the accommodation function.

Design and Implementation of Low Power Touch Screen Controller for Mobile Devices (모바일용 저전력 터치 스크린 제어 회로 설계 및 구현)

  • Park, Sang-Bong
    • The Journal of the Institute of Internet, Broadcasting and Communication
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    • v.12 no.6
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    • pp.279-283
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    • 2012
  • In is paper, we design and implement the low power, high speed touch screen controller that calculates and outputs the coordinate of touch point on the touch screen of mobile devices. The system clock is 10HMz, the number of input channels is 21, standby current is $20{\mu}A$, dynamic range of input is 140pF~400pF and the response time is 0.1ms/frame. It contains the power management unit for low power, automatic impedance calibration unit in order to adapt to humidity, temperature and evaluation board, adjacent key and pattern interference suppression unit, serial interface unit of I2C and SPI. The function and performance is verified by using FPGA and $0.18{\mu}m$ CMOS standard process. The implemented touch screen is designed for using in the double layer ITO(Indium Thin Oxide) module with diamond pattern and single layer ITO module for cost-effective which are applied to mobile phone or smart remote controller.

A Medium-Chain Fatty Acid, Capric Acid, Inhibits RANKL-Induced Osteoclast Differentiation via the Suppression of NF-κB Signaling and Blocks Cytoskeletal Organization and Survival in Mature Osteoclasts

  • Kim, Hyun-Ju;Yoon, Hye-Jin;Kim, Shin-Yoon;Yoon, Young-Ran
    • Molecules and Cells
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    • v.37 no.8
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    • pp.598-604
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    • 2014
  • Fatty acids, important components of a normal diet, have been reported to play a role in bone metabolism. Osteoclasts are bone-resorbing cells that are responsible for many bone-destructive diseases such as osteoporosis. In this study, we investigated the impact of a medium-chain fatty acid, capric acid, on the osteoclast differentiation, function, and survival induced by receptor activator of NF-${\kappa}B$ ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Capric acid inhibited RANKL-mediated osteoclastogenesis in bone marrow-derived macrophages and suppressed RANKL-induced $I{\kappa}B{\alpha}$ phosphorylation, p65 nuclear translocation, and NF-${\kappa}B$ transcriptional activity. Capric acid further blocked the RANKL-stimulated activation of ERK without affecting JNK or p38. The induction of NFATc1 in response to RANKL was also attenuated by capric acid. In addition, capric acid abrogated M-CSF and RANKL-mediated cytoskeleton reorganization, which is crucial for the efficient bone resorption of osteoclasts. Capric acid also increased apoptosis in mature osteoclasts through the induction of Bim expression and the suppression of ERK activation by M-CSF. Together, our results reveal that capric acid has inhibitory effects on osteoclast development. We therefore suggest that capric acid may have potential therapeutic implications for the treatment of bone resorption-associated disorders.

ST5 Positively Regulates Osteoclastogenesis via Src/Syk/Calcium Signaling Pathways

  • Kim, Min Kyung;Kim, Bongjun;Kwon, Jun-Oh;Song, Min-Kyoung;Jung, Suhan;Lee, Zang Hee;Kim, Hong-Hee
    • Molecules and Cells
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    • v.42 no.11
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    • pp.810-819
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    • 2019
  • For physiological or pathological understanding of bone disease caused by abnormal behavior of osteoclasts (OCs), functional studies of molecules that regulate the generation and action of OCs are required. In a microarray approach, we found the suppression of tumorigenicity 5 (ST5) gene is upregulated by receptor activator of nuclear $factor-{\kappa}B$ ligand (RANKL), the OC differentiation factor. Although the roles of ST5 in cancer and ${\beta}-cells$ have been reported, the function of ST5 in bone cells has not yet been investigated. Knockdown of ST5 by siRNA reduced OC differentiation from primary precursors. Moreover, ST5 downregulation decreased expression of NFATc1, a key transcription factor for osteoclastogenesis. In contrast, overexpression of ST5 resulted in the opposite phenotype of ST5 knockdown. In immunocytochemistry experiments, the ST5 protein is colocalized with Src in RANKL-committed cells. In addition, ST5 enhanced activation of Src and Syk, a Src substrate, in response to RANKL. ST5 reduction caused a decrease in RANKL-evoked calcium oscillation and inhibited translocation of NFATc1 into the nucleus. Taken together, these findings provide the first evidence of ST5 involvement in positive regulation of osteoclastogenesis via Src/Syk/calcium signaling.

A formulated red ginseng extract inhibits autophagic flux and sensitizes to doxorubicin-induced cell death

  • Park, Han-Hee;Choi, Seung-Won;Lee, Gwang Jin;Kim, Young-Dae;Noh, Hyun-Jin;Oh, Seung-Jae;Yoo, Iseul;Ha, Yu-Jin;Koo, Gi-Bang;Hong, Soon-Sun;Kwon, Sung Won;Kim, You-Sun
    • Journal of Ginseng Research
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    • v.43 no.1
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    • pp.86-94
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    • 2019
  • Background: Ginseng is believed to have antitumor activity. Autophagy is largely a prosurvival cellular process that is activated in response to cellular stressors, including cytotoxic chemotherapy; therefore, agents that inhibit autophagy can be used as chemosensitizers in cancer treatment. We examined the ability of Korean Red Ginseng extract (RGE) to prevent autophagic flux and to make hepatocellular carcinoma (HCC) cells become more sensitive to doxorubicin. Methods: The cytotoxic effects of total RGE or its saponin fraction (RGS) on HCC cells were examined by the lactate dehydrogenase assay in a dose- or time-dependent manner. The effect of RGE or RGS on autophagy was measured by analyzing microtubule-associated protein 1A/1B-light chain (LC)3-II expression and LC3 puncta formation in HCC cells. Late-stage autophagy suppression was tested using tandem-labeled green fluorescent protein (GFP)-monomeric red fluorescent protein (mRFP)-LC3. Results: RGE markedly increased the amount of LC3-II, but green and red puncta in tandem-labeled GFP-mRFP-LC3 remained colocalized over time, indicating that RGE inhibited autophagy at a late stage. Suppression of autophagy through knockdown of key ATG genes increased doxorubicin-induced cell death, suggesting that autophagy induced by doxorubicin has a protective function in HCC. Finally, RGE and RGS markedly sensitized HCC cells, (but not normal liver cells), to doxorubicin-induced cell death. Conclusion: Our data suggest that inhibition of late-stage autophagic flux by RGE is important for its potentiation of doxorubicin-induced cancer cell death. Therapy combining RGE with doxorubicin could serve as an effective strategy in the treatment of HCC.