• Title/Summary/Keyword: Brain activation

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Oncolytic Viruses - A New Era for Cancer Therapy (종양 용해성 바이러스-암 치료에서의 새 시대)

  • Ngabire, Daniel;Niyonizigiye, Irvine;Kang, Min-jae;Kim, Gun-Do
    • Journal of Life Science
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    • v.29 no.7
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    • pp.824-835
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    • 2019
  • In recent decades, oncolytic viruses (OVs) have extensively been investigated as a potential cancer drug. Oncolytic viruses have primarily the unique advantage in the fact that they can only infect and destroy cancer cells. Secondary, oncolytic viruses induce the activation of specific adaptive immunity which targets tumor-associated antigens that were hidden during the initial cancer progression. In 2015, one genetically modified oncolytic virus, talimogene laherparepvec (T-VEC), was approved by the American Food and Drug Administration (FDA) for the treatment of melanoma. Currently, various oncolytic viruses are being investigated in clinical trials as monotherapy or in combination with preexistent cancer therapies like immunotherapy, radiotherapy or chemotherapy. The efficacy of oncolytic virotherapy relies on the balance between the induced anti-tumor immunity and the anti-viral response. Despite the revolutionary outcome, the development of oncolytic viruses for the treatment of cancer faces a number of obstacles such as delivery method, neutralizing antibodies and induction of antiviral immunity due to the complexity, variability and reactivity of tumors. Intratumoral administration has been successful reducing considerably solid tumors with no notable side effects unfortunately some tumors are not accessible (brain) and require a systemic administration of the oncolytic viruses. In order to overcome these hurdles, various strategies to enhance the efficacy of oncolytic viruses have been developed which include the insertion of transgenes or combination with immune-modulatory substances.

A Systematic Review of the Application Nonpharmacological Cognitive Interventions in Patients With Dementia (치매 환자에게 적용된 비약물적 인지중재방법에 대한 체계적 고찰)

  • Kwak, Ho-Soung;Park, Ji-Hyuk
    • Korean Journal of Occupational Therapy
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    • v.26 no.4
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    • pp.13-26
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    • 2018
  • Objective : The aim of the study was to investigate the application of nonpharmacological cognitive interventions in patients with dementia. Methods : We searched published studies in KISS, PubMed, and Sciencedirect databases from January 2013 to December 2017. The main keywords used were "Dementia" AND "Cognitive stimulation OR Cognitive rehabilitation OR Cognitive training" and a total of ten studies were selected for analysis from 753 searched articles. Results : Seven of the ten selected studies showed significant improvements in cognitive function after intervention, whereas three studies showed no improvement in cognitive function; however, activation of brain waves, improvement in the relationship between care givers and patients, improvement in the quality of life of care givers, and improvements in visual motor skills were shown. Mini-Mental State Examination(MMSE) was used as the assessment tool for identifying the effects of the cognitive function improvement, and in four studies the quality of life of dementia patients was measured as an intervention effect. The main subject of the cognitive intervention is patients with mild to moderate dementia. Conclusion : The results of this study can be used as a basis for the selection of intervention methods, as well as their duration and assessment, according to the characteristics of dementia patients.

Role of Sirtuin 1 in Depression and Associated Mechanisms (우울증에 관한 Sirtuin 1의 역할과 관련된 기전)

  • Seog, Dae-Hyun;Park, Sung Woo
    • Journal of Life Science
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    • v.31 no.12
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    • pp.1120-1127
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    • 2021
  • Depression has a negative impact on social functioning due to its high prevalence and increased suicide rate, and is a disease with a high economic burden. Depression is related to diverse brain-related phenomena, such as neuroinflammation, synaptic dysfunction, and cognitive deficit. As antidepressant drugs used in clinical trials have shown poor therapeutic effects, antidepressant drugs that show rapid efficacy urgently need to be developed. Although studies on various genes, proteins, and signaling pathways related to depression have been conducted, the pathogenesis of depression has not been clearly elucidated. Sirtuin 1 is a nicotinamide-adenine dinucleotide- (NAD+-) dependent histone deacetylase and is involved in cell differentiation, apoptosis, autophagy, and cancer metabolism. Recent genetic studies found that sirtuin 1 is a potential target gene for depression. In addition, preclinical studies reported that sirtuin 1 signaling affects depression-like behavior. In this review, we attempt to present up-to-date knowledge of depression and sirtuin 1. We describe the various roles of sirtuin 1 in the regulation of glial activation, circadian rhythm, neurogenesis, and cognitive function and the effects of its expression on depression. Further, we discuss the effect of sirtuin 1 on the impairment of neural plasticity, one of the key mechanisms of depression, and the associated mechanisms of sirtuin 1.

Effect of Fritillariae Thunbergii Bulbus for Allergic Inflammation on HaCaT and RBL2H3 Cells (HaCaT 세포와 RBL2H3 세포에서 패모 추출물의 알레르기 염증 완화 효과)

  • Kim, Eun-Young;Lee, Bina;Kim, Jae-Hyun;Hong, SooYeon;Kim, Minsun;Park, Jae Ho;Kim, Jwa-Jin;Sohn, Youngjoo;Jung, Hyuk-Sang
    • The Korea Journal of Herbology
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    • v.34 no.1
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    • pp.23-31
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    • 2019
  • Objectives : The aim of this study was to investigate the effect for allergic-inflammation of Fritillariae Thunbergii Bulbus (FTB) on HaCaT cells and RBL2H3 cells. Methods : To investigate the effects of FTB for anti-inflammation in HaCaT cells, the cells were pretreated with FTB for 1h and then stimulated with $TNF-{\alpha}/IFN-{\beta}$ for 24h. Then thymus and activation-regulated chemokine (TARC) and Macrophage-derived chemokine (MDC) levels were analyzed with ELISA kit. Also to investigate the effect of skin barrier protein, the cells were treated with FTB of various concentrations, and then cells were harvested, expressions of skin barrier protein were measured with RT-PCR. To investigate the effects of FTB for anti-allergy in RBL2H3 cells, the cells were pre-treated with FTB for 1h, and then stimulated with A23187 for 30 min. ${\beta}$-hexosaminidase, IL-4 and $TNF-{\alpha}$ were measured using cultured media. The cells were harvested to analyze the mechanism of the effect for FTB via Western blot. Results : FTB did not show cytotoxicity in HaCaT and RBL2H3. In HaCaT cells, FTB significantly suppressed the expression of TARC, MDC at a dose-dependent manner and markedly increased formation of the skin barrier proteins. In RBL2H3 cells, FTB decreased release of the ${\beta}$-hexosaminidase, IL-4 and $TNF-{\alpha}$ in RBL2H3 through inhibition of the phosphorylation of JNK and p38, which are include in the signaling mechanism of MAPK Conclusion : These results indicate that FTB has an anti-inflammatory effect on the allergic response through blocking MAPK pathway. This suggest that FTB could be a therapeutic agent for allergic response.

Mountain-cultivated ginseng protects against cognitive impairments in aged GPx-1 knockout mice via activation of Nrf2/ChAT/ERK signaling pathway

  • Bao Trong Nguyen;Eun-Joo Shin;Ji Hoon Jeong;Naveen Sharma;Ngoc Kim Cuong Tran;Yen Nhi Doan Nguyen;Dae-Joong Kim;Myung Bok Wie;Yi Lee;Jae Kyung Byun;Sung Kwon Ko;Seung-Yeol Nah;Hyoung-Chun Kim
    • Journal of Ginseng Research
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    • v.47 no.4
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    • pp.561-571
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    • 2023
  • Background: Escalating evidence shows that ginseng possesses an antiaging potential with cognitive enhancing activity. As mountain cultivated ginseng (MCG) is cultivated without agricultural chemicals, MCG has emerged as a popular herb medicine. However, little is known about the MCG-mediated pharmacological mechanism on brain aging. Methods: As we demonstrated that glutathione peroxidase (GPx) is important for enhancing memory function in the animal model of aging, we investigated the role of MCG as a GPx inducer using GPx-1 (a major type of GPx) knockout (KO) mice. We assessed whether MCG modulates redox and cholinergic parameters, and memory function in aged GPx-1 knockout KOmice. Results: Redox burden of aged GPx-1 KO mice was more evident than that of aged wild-type (WT) mice. Alteration of Nrf2 DNA binding activity appeared to be more evident than that of NFκB DNA binding activity in aged GPx-1 KO mice. Alteration in choline acetyltransferase (ChAT) activity was more evident than that in acetylcholine esterase activity. MCG significantly attenuated reductions in Nrf2 system and ChAT level. MCG significantly enhanced the co-localization of Nrf2-immunoreactivity and ChAT-immunoreactivity in the same cell population. Nrf2 inhibitor brusatol significantly counteracted MCG-mediated up-regulation in ChAT level and ChAT inhibition (by k252a) significantly reduced ERK phosphorylation by MCG, suggesting that MCG might require signal cascade of Nrf2/ChAT/ERK to enhance cognition. Conclusion: GPx-1 depletion might be a prerequisite for cognitive impairment in aged animals. MCG-mediated cognition enhancement might be associated with the activations of Nrf2, ChAT, and ERK signaling cascade.

Effect of the Suicide Prevention Program to the Impulsive Psychology of the Elementary School Student (자살예방 프로그램이 초등학교 충동심리에 미치는 영향)

  • Kang, Soo Jin;Kang, Ho Jung;Cho, Won Cheol;Lee, Tae Shik
    • Journal of Korean Society of Disaster and Security
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    • v.6 no.1
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    • pp.65-72
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    • 2013
  • In this study, the early suicide prevention program was applied to the elementary school students and compared the prior & post effect of the program, and verified the status of psychology change like emotional status, or temptation to take a suicide, and presented the possibility as a suicide prevention program. The period of adolescence is the very unstable period in the process of growth being cognitively immature, emotionally impulsive period. It is the period emotionally unstable and unpredictable possible to select the method of suicide as an extreme method to escape the reality, or impulsive problem solving against small conflict or dispute situation. Many stress of the student such as recent nuclear family, expectation of parents to their children, education problem, socio-environmental elements, individual psychological factor lead students to the extreme activity of suicide in recent days. In this study, the scope of stress experienced in the elementary school as well as idea and degree of temptation regarding suicide by the suicide prevention program were identified, and through prevention program such as meditation training, breath training and through experience of anger control, emotion-expression, self overcome and establish positive self-identity and make understanding Self-control, Self-esteem & preciousness of life based on which the effect to suicide prevention was analyzed. The study was made targeting 51 students of 2 classes of 6th grade of elementary school of Goyang-si and processed 30 minutes every morning focused on through experience & activity of the principle & method of brain science. The data was collected for 20 times before starting morning class by using Suicide Probability Scale(herein SPS-A) designed to predict effectively suicide Probability, suicide risk prediction scale, surveyed by 7 areas such as Positive outlook, Within the family closeness, Impulsivity, Interpersonal hostility, Hopelessness, Hopelessness syndrome, suicide accident. Analytical methods and validation was used the Wilcoxon's signed rank test using SPSS Program. Though the process of program in short period, but there was a effective and positive results in the 7 areas in the average comparison. But in the t-test result, there was a different outcome. It indicated changes in the 3 questionnaires (No.7, No.14, No.19) out of 31 SPS-A questionnaires, and there was a no change to the rest item. It also indicated more changes of the students in the class A than class B. And in case of the class A students, psychological changes were verified in the areas of Hopelessness syndrome, suicide accident among 7 areas after the program was processed. Through this study, it could be verified that different results could be derived depending on the Student tendency, program professional(teacher in charge, processing lecturer). The suicide prevention program presented in this article can be a help in learning and suicide prevention with consistent systematization, activation through emotion and impulse control based on emotional stress relief and positive self-identity recovery, stabilization of brain waves, and let the short period program not to be died out but to be continued connecting from childhood to adolescence capable to make surrounding environment for spiritual, physical healthy growth for which this could be an effective program for suicide prevention of the social problem.

Neuroprotective Effects of Cirsium setidens, Pleurospermum kamtschaticumin, and Allium victorials Based on Antioxidant and p38 Phosphorylation Inhibitory Activities in SK-N-SH Neuronal Cells (SK-N-SH 신경세포내 항산화 효과와 p38 인산화 억제에 의한 곤드레, 누룩치 그리고 산마늘의 신경 보호 효과)

  • Chung, Mi Ja;Park, Yong Il;Kwon, Ki Han
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.3
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    • pp.347-355
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    • 2015
  • Oxidative stress is one of the key mechanisms involved in neuronal damage. Neuroprotective effects and underlying mechanisms of action of several wild vegetables, Cirsium setidens (CS), Pleurospermum kamtschaticumin (PK), and Allium victorials (AV), against oxidative stress induced by hydrogen peroxide in SK-N-SH cells were investigated. CS and AV up to $400{\mu}g/mL$ showed no detectable effects on cell viability of human SK-N-SH neuro-blastoma cells compared with control. Incubation of SK-N-SH cells with hydrogen peroxide resulted in significant induction of cell death and reaction oxygen species (ROS) production, whereas treatment of cells with CS and AV significantly reduced cell death and ROS production, respectively. Among the wild vegetables tested, CS and PK showed more effective DPPH radical scavenging activity than AV, whereas PK showed strong cytotoxicity in SK-N-SH cells compared with the control. CS showed much higher inhibitory effects on cell death and ROS generation against oxidative stress than AV. Thus, CS was selected for subsequent experiments. Ethyl acetate (EA), hexane, butanol, aqueous, and chloroform extracts from CS significantly inhibited cell death and ROS generation in SK-N-SH cells induced by oxidative stress. EA extract from CS (CS-EA) showed the highest DPPH radical-scavenging activity, intra-cellular ROS-scavenging activity, and neuroprotective effects. CS-EA attenuated apoptosis signal-regulating p38 activation by inhibiting phosphorylation. The findings suggest that CS-EA protects neuronal cells through antioxidant activity and inhibition of phosphorylation of p38 in brain neural cells.

Neural Bases of Empathy in Competitive vs. non-Competitive situation (경쟁과 비경쟁 상황에서 공감의 신경학적 기제)

  • Hwang, Su-Young;Yoon, Mi-Sun
    • Korean Journal of Cognitive Science
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    • v.27 no.3
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    • pp.441-467
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    • 2016
  • This fMRI study is aim to investigate effects of competitive environment in cognitive empathic process in human brain. Empathy is known as a crucial factor for human's adaptive behavior in aspects of social cognition and it is almost automatic process, on the other hand competitive situation is psychologically devastated environment to win someone for getting rewards. We hypnotized that reading and understanding of other person's mind are a specific characteristic related to survival evolutionarily, however competition would have an effect on the empathic cognitive process because of mechanisms of competition. To manipulate the competitive atmosphere, one researcher took a role of competitor against participants and they were instructed to get monetary rewards when their performance was better than a competitor. 21 participants(9 males and 12 females) performed to judge the emotional valence of the empathic task consisted of illustrated images with various situation could be experienced in real world as on $1^{st}$ person perspective in both competitive and non-competitive condition, and did same performance with objects stimulus in control condition. In order to examine the competition effects on empathic process,, hemodynamic response were obtained during fMRI session and the imaging data were analyzed to identify brain regions where responses to each condition across the two consecutive runs. Participants' reaction time in competitive condition was faster statistically significant than non-competitive one. Activation for competitive condition increased in the following areas: ACC, mPFC, SMG, thalamus extended caudate and Nacc, parahippocampal gyrus, and for non-competitive condition increased paracingulate gyrus, temporal pole, vmPFC, superior occipital gyrus. As a result of regression analysis using empathic scores as covariance, the rSMG, IFG, fusiform gyrus, thalamus, putamen were correlated with higher empathic levels, and TPJ were correlated with lower empathic scores. We suggest that these observations could mean competitive environment have an effect on neural base of cognitive empathic process.

The Effect of Exercise Training on Aβ-42, BDNF, GLUT-1 and HSP-70 Proteins in a NSE/ APPsw-transgenic Model for Alzheimer's Disease. (지구성 운동이 NSE/APPsw 알츠하이머 질환 생쥐의 인지능력, Aβ-42, BDNF, GLUT-1과 HSP-70 단백질 발현에 미치는 영향)

  • Eum, Hyun-Sub;Kang, Eun-Bum;Lim, Yea-Hyun;Lee, Jong-Rok;Cho, In-Ho;Kim, Young-Soo;Chae, Kab-Ryoung;Hwang, Dae-Yean;Kwak, Yi-Sub;Oh, Yoo-Sung;Cho, Joon-Yong
    • Journal of Life Science
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    • v.18 no.6
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    • pp.796-803
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    • 2008
  • Mutations in the APP gene lead to enhanced cleavage by ${\beta}-$ and ${\gamma}-secretase$, and increased $A{\beta}$ formation, which are closely associated with Alzheimer's disease (AD)-like neuropathological changes. Recent studies have shown that exercise training can ameliorate pathogenic phenotypes ($A{\beta}-42$, BDNF, GLUT-1 and HSP70) in experimental models of Alzheimer's disease. Here, we have used NSE/APPsw transgenic mice to investigate directly whether exercise training ameliorates pathogenic phenotypes within Alzheimer's brains. Sixteen weeks of exercise training resulted in a reduction of $A{\beta}-42$ peptides and also facilitated improvement of cognitive function. Furthermore, GLUT -1 and BDNF proteins produced by exercise training may protect brain neurons by inducing the concomitant expression of genes that encode proteins (HSP-70) which suppress stress induced neuron cell damages from APPsw transgenic mice. Thus, the improved cognitive function by exercise training may be mechanistically linked to a reduction of $A{\beta}-42$ peptides, possibly via activation of BDNF, GLUT-1, and HSP-70 proteins. On the basis of the evidences presented in this study, exercise training may represent a practical therapeutic management strategy for human subjects suffering from Alzheimer's disease.

Histone Methylation Regulates Retinoic Acid-induced Hoxc Gene Expression in F9 EC Cells (F9 EC 세포에서 레티노산에 의해 유도되는 Hoxc 유전자의 발현에 히스톤 메틸화가 미치는 영향)

  • Min, Hyehyun;Kim, Myoung Hee
    • Journal of Life Science
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    • v.25 no.6
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    • pp.703-708
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    • 2015
  • Hox genes encode a highly conserved family of homeodomain-containing transcription factors controlling vertebrate pattern formation along the anteroposterior body axis during embryogenesis. Retinoic acid (RA) is a key morphogen in embryogenesis and a critical regulator of both adult and embryonic cellular activity. Specifically, RA regulates Hox gene expression in mouse- or human-derived embryonic carcinoma (EC) cells. Histone modification has been reported to play a pivotal role in the process of RA-induced gene expression and cell differentiation. As histone modification is thought to play an essential role in RA-induced Hox gene expression, we examined RA-induced initiation of collinear expression of Hox genes and the corresponding histone modifications in F9 murine embryonic teratocarcinoma (EC) cells. Hox expression patterns and histone modifications were analyzed by semiquantitative RT-PCR, RNA-sequencing, and chromatin immuno-precipitation (ChIP)-PCR analyses. The Hoxc4 gene (D0) was initiated earlier than the Hoxc5 to –c10 genes (D3) upon RA treatment (day 0 [D0], day 1 [D1], and day 3 [D3]). The Hox nonexpressing D0 sample had a strong repressive marker, H3K27me3, than the D1 and D3 samples. In the D1 and D3 samples, reduced enrichment of the H3K27me3 marker was observed in the whole cluster. The active H3K4me3 marker was closely associated with the collinear expression of Hoxc genes. Thus, the Hoxc4 gene (D1) and all Hoxc genes (D3) expressed H3K4me3 upon transcription activation. In conclusion, these data indicated that removing H3K27me3 and acquiring H3K4me3 regulated RA-induced Hoxc gene collinearity in F9 cells.