• Title/Summary/Keyword: signalling

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Stimulating effect of modified Goa-Gi-Um herbal remedy on melanogenesis in B16F10 melanoma cells (B16F10 멜라노마세포에서 과기음가미방의 멜라닌 생성 촉진 효과)

  • Moon, Na-Rang;Kim, Se Yoon;Lee, Jin Hyuk;Lee, Jung Bok;Park, Sunmin
    • The Korea Journal of Herbology
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    • v.28 no.3
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    • pp.69-74
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    • 2013
  • Objectives : Since hypopigmentation is known to increase the risk of skin cancer, melanogenesis in the skin needs to be regulated. Here, we evaluated the melanogenesis stimulatory effects of a modified Goagium herbal remedy (HR) and HR+ox bile (Bos taurus domesticus) extract (OBE) to address hypopigmentation disorders. Methods : B16F10 melanoma cells were treated with different dosages of HR and HR+OBE for 24 to 48 h after 1 h of 10 nM ${\alpha}$-melanocyte stimulating hormone (${\alpha}$-MSH). After the treatment, cell viability, tyrosinase activity, melanin synthesis and the expression of genes related to melanin synthesis were measured and the regulation of the ${\alpha}$-MSH signalling through cAMP responding element binding protein (CREB) was determined. Results : HR and HR+OBE with the ranges of $15{\sim}100{\mu}g/mL$ did not affect cell viability in melanoma cells. The 1 h treatment of HR+OBE (50 and $100{\mu}g/mL$) potentiated the phosphorylation of CREB by enhancing ${\alpha}$-MSH signaling and its 24 h treatment increased CREB expression. Consistent with CREB potentiation, their treatment for 24 h, the expression of microphthalmia-associated transcription factor (MIFT), tyrosinase, tyrosinase related protein (TRP)-1 and TRP-2 were increased in realtime PCR. Ultimately, the 48 h treatment of HR+OBE (50 and $100{\mu}g/mL$) increased tyrosniase activity and melanin contents in the melanoma cells in comparison to the control. Conclusions : HR+OBE (50 and $100{\mu}g/mL$) increases melanin synthesis in B16F10 melanoma cells via the stimulation of tyrosinase activity and expression of MIFT, tyrosinase, TRP-1 and TRP-2. HR+OBE can be used as the a possible treatment for hypopigmentation of the skin.

Effects of Scutellariae Radix on Gene Expression of Human Cervical Cancer Cells(SNU-703) (황금추출물이 인간 유래 자궁경부암세포의 유전자발현에 미치는 영향)

  • Jo, Hyun-Jung;Gu, Hee-Jun;Cho, Seong-Hee;Park, Kyung-Mi;Yang, Seung-Jeong
    • The Journal of Korean Obstetrics and Gynecology
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    • v.22 no.3
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    • pp.117-134
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    • 2009
  • Purpose: In the theory of traditional medicine, Scutellariae Radix (SR) can clear away heat and remove dampness, purge the sthenic fire and remove toxic materials, cool blood and stop bleeding to prevent miscarriage. Recently, SR is known to have anti-cancer activity. For this reason, the present author designed to investigate the effect of SR on proliferation rates of cervical cancer cell line, then effects on genetic profile by SR. Methods: The genetic profile for the effect of SR on human derived cervical cancer cell line, SNU-703, was measured using microarray technique, and the functional analysis on these genes was conducted. Results: Total 519 genes were up-regulated and 606 genes down-regulated in cells treated with SR. Genes induced or suppressed by SR were all mainly concerned with metabolic process, regulation of biological process and protein binding. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as TNFRSF1A, AKT1, MAPK3, and STAT3 that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of SR as anti-cancer drug and also suggest that related mechanisms are involved in TNFRSF1A, AKT1, MAPK3, and STAT3 related signalling pathways.

Efficacy of the combined supplementation of choline and docosahexaenoic acid during gestation on developmental outcomes of rat pups

  • Rajarethnem Huban Thomas;Kumar Megur Ramakrishna Bhat;Sivakumar Gopalkrishnan;Kiranmai Sesappa Rai
    • Journal of Nutrition and Health
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    • v.56 no.6
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    • pp.655-666
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    • 2023
  • Purpose: Gestational nutrition has an impact on the growth and development of the fetus. Choline (C) and docosahexaenoic acid (DHA) are important and essential nutrients for humans that play a role in the structural integrity of the membranes as well as signalling. C is used in the synthesis of phosphatidylcholine, and cell membranes are highly enriched with DHA. The dietary intake of C or DHA during pregnancy directly influences fetal development. Currently, there is no evidence to prove the effectiveness of the combined dietary supplementation of both C and DHA during gestation on developmental outcomes in the offspring. Methods: The current study was designed to assess the physical, sensory, and motor development of rat pups born to mothers supplemented with C and/or DHA during the entire gestational period. Pregnant rat dams were divided into the following five groups: Normal control (NC), Saline control (SC), Choline (C), DHA, and Choline+DHA (C+DHA). The NC dams did not receive any supplementation during the entire gestation period. The experimental groups were supplemented with Saline, C, and/or DHA, respectively, during the entire gestation (E0 to delivery). Results: Rat pups (n = 6/group) exposed to combined C and DHA showed significant improvement in birth weight, fur development, eye-opening as well as weight gain on the 7th, 14th, and 21st postnatal day and pinnae detachment (assessed from birth to postnatal day 21) when compared with age-matched NC, SC or C or DHA pups. Further, significant reflex responses were observed in visual placing and bar holding of pups exposed to both C and DHA, whereas the differences in surface righting, negative geotaxis, and grasping reflexes were not significant between the groups. Conclusion: Gestational supplementation of both C and DHA rather than either of them alone is better in enhancing developmental outcomes in rat pups.

Antidiabetic Effect of Standardized Chrysanthemum rubellum Hydroethanolic Extract by Targeting α-Glucosidase and the PTP-1B Signaling Pathway for Alleviating Diabetes in Experimental Model

  • Bichitrananda Tripathy;Nityananda Sahoo;Sudhir Kumar Sahoo
    • Journal of Pharmacopuncture
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    • v.26 no.4
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    • pp.319-326
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    • 2023
  • Objectives: The study's goal was to find out whether Chrysanthemum rubellum extract has anti-diabetic properties by concentrating on α-glucosidase and the PTP-1B signaling pathway. C. rubellum flowers were used for extraction using Methanol/water (80/20) as solvent. Methods: LC-MS techniques was used to check the presence of phytoconstituents present in C. rubellum extract. In vitro antidiabetic activity was evaluated using α-glucosidase inhibitory activity and PTP-1B signaling pathway. On Streptozotocin (STZ)-induced rats with diabetes, the in vivo antidiabetic efficacy was assessed using a test for oral glucose tolerance. Results: The phytoconstituents identified in the extract of C. rubellum were apigenin, diosmin, myricetin, luteolin, luteolin-7-glucoside, and Quercitrin as compound 1-6, respectively. Results showed that diosmin exhibited highest α-glucosidase inhibitory activity i.e. 90.39%. The protein level of PTP-1B was lowered and the insulin signalling activity was directly increased by compounds 1-6. The maximum blood glucose levels were seen in all groups' OGTT findings at 30 minutes following glucose delivery, followed by gradual drops. In comparison to the control group, the extract's glucose levels were 141 mg/dL at 30 minutes before falling to 104 mg/dL after 120 minutes. The current study has demonstrated, in summary, that extract with phytoconstituents reduce blood sugar levels in rats. Conclusion: This finding suggests that extract may reduce the chance of insulin resistance and shield against disorders like hyperglycemia.

An In Silico Drug Repositioning Strategy to Identify Specific STAT-3 Inhibitors for Breast Cancer

  • Sruthy Sathish
    • Journal of Integrative Natural Science
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    • v.16 no.4
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    • pp.123-131
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    • 2023
  • Breast cancer continues to pose a substantial worldwide health challenge, thereby requiring the development of innovative strategies to discover new therapeutic interventions. Signal Transducer and Activator of Transcription 3 (STAT-3) has been identified as a significant factor in the development of several types of cancer, including breast cancer. This is primarily attributed to its diverse functions in promoting tumour formation and conferring resistance to therapeutic interventions. This study presents an in silico drug repositioning approach that focuses on identifying specific inhibitors of STAT-3 for the purpose of treating breast cancer. We initially examined the structural and functional attributes of STAT-3, thereby elucidating its crucial involvement in cellular signalling cascades. A comprehensive virtual screening was performed on a diverse collection of drugs that have been approved by the FDA from zinc15 database. Various computational techniques, including molecular docking, cross docking, and cDFT analysis, were utilised in order to prioritise potential candidates. This prioritisation was based on their predicted binding energies and outer molecular orbital reactivity. The findings of our study have unveiled a Dihydroergotamine and Paritaprevir that have been approved by the FDA and exhibit considerable promise as selective inhibitors of STAT-3. In conclusion, the utilisation of our in silico drug repositioning approach presents a prompt and economically efficient method for the identification of potential compounds that warrant subsequent experimental validation as selective STAT-3 inhibitors in the context of breast cancer. The present study highlights the considerable potential of employing computational strategies to expedite the drug discovery process. Moreover, it provides valuable insights into novel avenues for targeted therapeutic interventions in the context of breast cancer treatment.

Regulatory Action of $\beta-adrenergic$ Agonist and 8-bromocyclic AMP on Calcium Currents in the Unfertilized Mouse Eggs

  • Haan, Jae-Hee;Cheong, Seung-Jin;Kim, Yang-Mi;Park, Choon-Ok;Hong, Seong-Geun
    • The Korean Journal of Physiology
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    • v.27 no.2
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    • pp.175-183
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    • 1993
  • There are many report suggesting that influx and intracellular calcium concentration $([Ca^{2+}]_i)$ are related to cell signalling in various cells. However, it has not been reported that calcium channel activation is affected by the substances involved in signal transduction pathways in the mouse eggs. In this study, the effects of isoprenaline (ISP) and cyclic AMP on calcium influx through calcium channels were investigated to show their relationship with the signal transduction process in unfertilized mouse eggs. Using whole cell voltage clamp techniques, calcium currents, elicited by the depolarizing pulses of 300 ms duration (from -50 mV to 50 mV in 10 mV increments) from a holding potential of -80 mV, were recorded. The current-voltage (I-V) relation of calcium currents was shown to be bell-shaped; the current began to activate at -50 mV and reached its maximum $(-1.33{\pm}0.16\;nA:\;mean{\pm}S.E.,\;n=7)$ at -10 mV, then decayed at around 50 mV. Calcium currents were fully activated within $7\;ms{\sim}20\;ms$ and completely inactivated 200 ms after onset of the step pulse. ISP within the concentration ranges of $10^{-8}\;M{\sim}10^{-4}\;M$ dose-dependently increased the amplitude calcium current. The permeable cyclic AMP analogue,8-bromocyclic AMP, also increased its maximal amplitude by 46ft at $10^{-5}\;M$, while protein kinase inhibitor (PKI), which is known to inhibit 0.02 phosphorylating units of cyclic AMP-dependent protein kinase (PKA) per microgram decreased calcium currents. Currents recorded in the presence of PKI were resistant to increase by the application of $10^{-5}\;M$. Also, PKI inhibited the calcium current increase elicited by ISP treatment. These results suggest that $\beta-adrenergic$ regulation of the calcium channel is mediated by the cAMP-dependent protein kinase. This signal transduction pathway might play a role in regulating $[Ca^{2+}]_i$, level due to the increase of calcium influx in mouse eggs.

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Verification of safety integrity for vital data processing device through quantitative safety analysis (정량적 안전성 분석을 통한 Vital 데이터 처리장치의 안전무결성 요구사항 검증)

  • Choi, Jin-Woo;Park, Jae-Young
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.7
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    • pp.4863-4870
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    • 2015
  • Currently, as a priority to secure the safety of the railway signalling system, verification for satisfy of the safety integrity requirements(SIR) is required to the essential elements. Safety Integrity Requirements(SIR) verification is performed based on the system safety analysis. But the probability of securing basic data for system safety analysis significantly dropped because there is no experience yet performed in the country. Therefore we are had to rely on a qualitative analysis. There are methods such as qualitative risk analysis matrix, and risk graphs. The qualitative analysis is wide, the width of the accident. However, the reliability of the result is significantly less has a disadvantage. Therefore, it should be parallel quantitative safety analysis of the system/products in order to compensate for the disadvantages of the qualitative analysis. This paper presents a quantitative safety analysis method to overcome the disadvantages of the qualitative analysis. And through a result, highly reliable Safety Integrity Requirements(SIR) verification measures proposed. Verification results, the dangerous failure incidence for vital data processing device was calculated to be $1.172279{\times}10^{-9}$. The result was verified to exceed the required safety integrity targets more.

Development of Standard Specification of Korea Radio based Train Control System(KRTCS-2) for Conventional & High Speed Railway (일반·고속철도용 무선기반 열차제어시스템(KRTCS-2) 표준사양 개발)

  • Kim, Chan-ho;Park, Jong-won;Lee, Kang-gyoo;Sung, Dong-il;Yun, Hak-sun
    • Journal of the Korean Society for Railway
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    • v.19 no.6
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    • pp.736-743
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    • 2016
  • In accordance with the trend of higher speed and automation, the Train Control System is building on the technology of control methods using radio in the technology of exchanging information by wire, toward a wireless communication method that will be applied using LTE-R radio communication technology with $4^{th}$ generation LTE mobile communication a $2^{nd}$ generation GSM-R. Therefore, a standard specification suitable for the Korea Radio based Train Control System-2(below KRTCS-2) for the 350km/h class using wireless communication is created; a prototype based on the standard specification is installed on a high-speed train and is installed on a test section(Ik san-Jeong eup) on the Honam high speed line to ensure the reliability and safety of the standard specifications, which are verified through various performance tests. In the future, the standard specification that has been established as a national railway standard, and the standard specifications will be commercialized by applying the train control system to conventional and High speed railway lines.

Functional Properties of Human Muscarinic Receptors Hm1, Hm2 and Hm3 Expressed in a Baculovirus/Sf9 Cell System

  • Woo, Hyun-Ae;Woo, Yae-Bong;Bae, Seung-Jin;Kim, Hwa-Jung
    • Biomolecules & Therapeutics
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    • v.7 no.4
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    • pp.307-314
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    • 1999
  • The human muscarinic acetylcholine receptor (mAChR) subtypes Hml, Hm2 and Hm3 have been expressed in insect cells (Spodoptera frugiperda, Sf9) using the baculovirus expression system. Expression of relevant DNA, transcript and receptor proteins was identified by PCR, Northern blotting and [$^{3}H$]QNB binding, respectively. As assessed by [$^{3}H$]QNB binding sites, yields of muscarinic receptors in membrane preparations in this study were as about 5-20 times high as those in mammalian cells reported in previous studies. The [$^{3}H$]QNB competition binding studies with well-known subtype-selective mAChR antagonists showed that the receptors expressed in Sf9 cells retain the pharmacological characteristics expected for the ml , m2 and m3 muscarinic receptors. The ml-selective antagonist, pirenzepine, displayed a considerably higher affinity for Hml by 110-fold and 35-fold than for Hm2 and Hm3, respectively, The m2-selective methoctramine displayed a significantly higher affinity for Hm2 than for Hml and Hm3 (10- and 26-fold, respectively). p-F-HHSiD exhibited high affinity for Hm3 that is not significantly different from those for Hml, but 66-fold higher than its affinity for Hm2. The functional coupling of the recombinant receptors to second messenger systems was also examined. While both Hml and Hm3 stimulated phosphoinositide hydrolysis upon activation by carba-chol, Hm2 produced no response. On the other hand, activation of mAChRs induced the inhibition of forsko-lin-stimulated cyclic AMP formation in Hm2-expressing cells, whereas the significant dose-dependent increase in or poor response on cyclic AMP formation were produced in Hml or Hm3-expressing cells, respectively. These results indicate the differential coupling of recombinant Hml, Hm2 and Hm3 receptors expressed in SF9 cells to intracellular signalling system.

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Apoptotic Pathway Induced by Dominant Negative ATM Gene in CT-26 Colon Cancer Cells (CT-26 대장암 세포에서 Dominant Negative ATM 유전자에 의하여 유도되는 세포자멸사의 경로)

  • Lee, Jung Chang;Yi, Ho Keun;Kim, Sun Young;Lee, Dae Yeol;Hwang, Pyoung Han;Park, Jin Woo
    • Clinical and Experimental Pediatrics
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    • v.46 no.7
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    • pp.679-686
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    • 2003
  • Purpose : Ataxia telangiectasia mutated(ATM) is involved in DNA damage responses at different cell cycle checkpoints, and signalling pathways associated with regulation of apoptosis in response to ionizing radiation(IR). However, the signaling pathway that underlies IR-induced apoptosis in ATM cells has remained unknown. The purpose of this study was, therefore, to investigate the apoptotic pathway that underlies IR-induced apoptosis in a CT-26 cells expressing dominant negative ATM (DN-ATM). Methods : We generated a replication-deficient recombinant adenovirus encoding the DN-ATM(Ad/DN-ATM) or control adenovirus encoding no transgene(Ad/GFP) and infected adenovirus to CT-26 cells. After infection, we examined apoptosis and apoptotic pathway by [$^3H$]-thymidine assay, DNA fragmentation, and Western immunoblot analysis. Results : DN-ATM gene served as the creation of AT phenotype in a CT-26 cells as revealed by decreased cell proliferations following IR. In addition, IR-induced apoptosis was regulated through the reduced levels of the anti-apoptotic protein Bcl-2, the increased levels of the apoptotic protein Bax, and the activation of caspase-9, caspase-3, and PARP. Conclusion : These results indicate that the pathway of IR-induced apoptosis in CT-26 cells expressing DN-ATM is mediated by mitochondrial signaling pathway involving the activation of caspase 9, caspase 3, and PARP.