Histone acetylation is a well-characterized epigenetic modification controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Imbalanced histone acetylation has been observed in many primary cancers. Therefore, efforts have been made to find drugs or small molecules such as HDAC inhibitors that can revert acetylation levels to normal in cancer cells. We observed dose-dependent reduction in the endogenous and exogenous protein expression levels of KAT8 (also known as human MOF), a member of the MYST family of HATs, and its corresponding histone acetylation at H4K5, H4K8, and H4K16 in chemotherapy drug gemcitabine (GEM)-exposed T24 bladder cancer (BLCA) cells. Interestingly, the reduction in MOF and histone H4 acetylation was inversely proportional to GEM-induced γH2AX, an indicator of chemotherapy drug effectiveness. Furthermore, pGL4-MOF-Luc reporter activities were significantly inhibited by GEM, thereby suggesting that GEM utilizes an MOF-mediated anti-BLCA mechanism of action. In the CCK-8, wound healing assays and Transwell® experiments, the additive effects on cell proliferation and migration were observed in the presence of exogenous MOF and GEM. In addition, the promoted cell sensitivity to GEM by exogenous MOF in BLCA cells was confirmed using an Annexin V-FITC/PI assay. Taken together, our results provide the theoretical basis for elucidating the anti-BLCA mechanism of GEM.
Ruth Ozeki(Japanese-American female novelist)?s recent novel, A Tale for the Time Being (2013) draws our attention because the fiction shows very interesting fictional experiments, especially in terms of post-humanism. Indeed, the novel is not a science fiction at all which has been, and still is, the typical fictional field employed in the discussion for the transhumanism and posthumanism. It also does not include any cybogs, robots, or aliens which provoke the posthumanism-related issues like mind/body, human/nonhuman, nature/culture relations. Indeed, it seems "merely" represent realistic day-to-day lives of ordinary people living in contemporary Japan and Canada, and in very minute and particular details at that. Indeed, the central action of the main characters of the novel seems very traditional, that is on the one hand writing a diary by a teenage girl who is counting the days and weeks before her suicide and on the other hand reading it by a female novelist who happens to find her diary several years later. Nevertheless, I would like to suggest that underneath this traditional narrative surface are simmering post-humanist and post-anthropocentric worldviews beyond liberal Humanism which takes human beings to be exceptional against human or non-human others. Not only in narrative contents and characterizations but also through narrative structure and strategies, the novel enacts post-humanist and post-anthropocentric worldviews which are interestingly drawn from both age-old Buddhist ideas and modern eco-philosophy and quantum physics. I would like to stress that what triggers the author's fictional experiments helping our rethinking and redefining "what human beings are" and "what the relation between humans and nonhumans" is not merely intellectual interests but her keen and passionate response to the heart-breaking pains and sufferings of human and nonhuman beings caused by the contemporary natural-artificial catastrophes and techno-scientific predicaments.
Several types of pain occur following spinal cord injury (SCI); however, neuropathic pain (NP) is one of the most intractable. Invasive and non-invasive brain stimulation techniques have been studied in clinical trials to treat chronic NP following SCI. The evidence for invasive stimulation including motor cortex and deep brain stimulation via the use of implanted electrodes to reduce SCI-related NP remains limited, due to the small scale of existing studies. The lower risk of complications associated with non-invasive stimulation, including transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), provide potentially attractive alternative central neuromodulation techniques. Compared to rTMS, tDCS is technically easier to apply, more affordable, available, and potentially feasible for home use. Accordingly, several new studies have investigated the efficacy of tDCS to treat NP after SCI. In this review, articles relating to the mechanisms, clinical efficacy and safety of tDCS on SCI-related NP were searched from inception to December 2019. Six clinical trials, including five randomized placebo-controlled trials and one prospective controlled trial, were included for evidence specific to the efficacy of tDCS for treating SCI-related NP. The mechanisms of action of tDCS are complex and not fully understood. Several factors including stimulation parameters and individual patient characteristics may affect the efficacy of tDCS intervention. Current evidence to support the efficacy of utilizing tDCS for relieving chronic NP after SCI remains limited. Further strong evidence is needed to confirm the efficacy of tDCS intervention for treating SCI-related NP.
Purpose: This study aimed to develop a situation-specific theory to explain nurses' experiences of the COVID-19 crisis. Methods: The participants were 16 hospital nurses who experienced the COVID-19 crisis. Data were collected through in-depth individual interviews from September 2, 2020 to January 20, 2021. Transcribed interview contents were analyzed using Corbin and Strauss's grounded theory method. Results: A total of 38 concepts and 13 categories were identified through an open coding process. The core category found was becoming a pioneering nurse who turns crises into opportunities. The causal conditions were the chaos of being exposed defenselessly to an unexpected pandemic, fear caused by a nursing care field reminiscent of a battlefield, and moral distress from failing to protect patients' human dignity. The contextual conditions were feeling like the scapegoat of the hospital organization, increasing uncertainty due to the unpredictable state of COVID-19, and relative deprivation due to inappropriate treatment. The central phenomenon was suffering alone while experiencing the dedication of the COVID-19 hero image. The action/interactional strategy were efforts to find a breakthrough and getting the nurse's mind right, and the intervening conditions were gratitude for those who care for broken hearts and getting used to myself with repetitive work. The Consequences were becoming an independent nurse and frustration with the unchanging reality. Conclusion: This study provides the foundation for the nurse's situation-specific theory of the COVID-19 crisis by defining the crisis perceived by nurses who cared for COVID-19 patients and suggesting types of coping with the crisis.
Objectives : Anxiety and depression are stress-related disorders. Their prevalence are increasing rapidly. Ginseng is the root of Panax ginseng C.A. Meyer (Araliaceae) which has been used for many centuries in asian region. Anxiolytic effect is one of the popular effects of ginseng. Several studies reported saponin fraction of ginseng, including ginsenoside, is a major ingredient of anxiolytic effect. In present study, we investigated anxiolytic-like and antidepressant-like effect of non-saponin fraction in mice. Material and Method : Mice were divided into five groups. Experimental groups were administered non-saponin fractions (25 mg/kg; nsp25, 50 mg/kg; nsp50, 100 mg/kg; nsp100) respectively once a day in the morning at 9am for 1 week. Then, we performed elevated plus-maze (EPM) test for investigating the anxiolytic-like effect and forced swimming test (FST) for investigating the antidepressant-like action. Results : Non-saponin fraction 50 mg/kg group increased frequency and time spent (p<0.05) in open arm on EPM test and decreased immobility time (p<0.05) on FST compared with control group. Conclusions : We suggest that non-saponin fraction has anxiolytic-like effect and antidepressant like effect in mice.
Objectives : This study used a network pharmacology approach to elucidate the efficacy and molecular mechanisms of Daehwangmokdanpitang (DHMDPT) on Psoriasis. Methods : Using OASIS databases and PubChem database, compounds of DHMDPT and their target genes were collected. The putative target genes of DHMDPT and known target genes of psoriasis were compared and found the correlation. Then, the network was constructed using Cytoscape 3.10.1. The key target genes were screened by Analyzer network and their functional enrichment analysis was conducted based on the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways to predict the mechanisms. Results : The result showed that total 30 compounds and 439 related genes were gathered from DHMDPT. 264 genes were interacted with psoriasis gene set, suggesting that the effects of DHMDPT are closely related to psoriasis. Based on GO enrichment analysis and KEGG pathways, 'Binding', 'Cytokine Activity', 'Receptor Ligand Activity' 'HIF-1 signaling pathway', 'IL-17 signaling pathway', 'Toll-like receptor signaling pathway', and 'TNF signaling pathway' were predicted as functional pathways of 16 key target genes of DHMDPT on psoriasis. Among the target genes, IL6, IL1B, TNF, AKT1 showed high correlation with the results of KEGG pathways. Additionally, Emodin, Acetovanillone, Gallic acid, and Ferulic acid showed a high relevance with key genes and their mechanisms. Conclusion : Through a network pharmacological method, DHMDPT was predicted to have high relevance with psoriasis. This study could be used as a basis for studying therapeutic effects of DHMDPT on psoriasis.
1) In whole anesthetized rabbits and spinal rabbits, the potentiating effect of syrosingopine and reserpine on pressor action of norepinephrine (NE) was compared. 2) The doses of syrosingopine and reserpine were 8, 40, $200\;{\mu}g$ and 1 mg per kg of body weight. The pressor responses to NE(0.1, 0.5, 0.25, 1.2, 6.0, 30.0, $150.0\;{\mu}g/kg$) were examine at 4, 10 and 24 hours after administration of the drugs. 3) In whole rabbits, potentiation by syrosingopine of pressor effect of NE was observed after administration of above the dose of $40\;{\mu}g/kg$, potentiation by reserpine was above $8\;{\mu}g/kg$. The maximal potentiation was achieved 10 hours after administration of $200\;{\mu}g/kg$ of each agent. 4) In spinal rabbits, syrosingopine $(200\;{\mu}g/kg)$ produced slight potentiation of pressor effect of NE. The same dose of reserpine produced more pronounced potentiation. 5) In the whole rabbits carbachol inhibited the potentiation observed 4 hours after administration of $40\;{\mu}g/kg$ of reserpine and syrosingopine. 6) In spinal rabbits, the potentiation observed 10 hours after $200\;{\mu}g/kg$ of reserpine and syrosingopine was inhibited by administration of carbachol. 7) The onset of potentiation of the pressor effect of NE was within 15 min after administration of syrosingopine and reserpine (1 mg/kg, each). 8) The above data suggest that the development of NE supersensitivity by syrosingopine and reserpine in rabbits has more intimate relationship with the decrease of central catecholamine contents than with that of peripheral ones. The depression of central sympathetic tone produced by these agents seems to play an important role in development of supersensitivity.
In view of the facts that dopamine (DA) when given directly into a lateral ventricle (i.c.v.) of the rabbit brain induces antidiuresis and that haloperidol, a non-specific antagonist of DA receptors, produces anti-diuresis in smaller doses and diuresis and natriuresis in larger doses, the present study was undertaken to delineate the roles of various DA receptors involved in the center-mediated regulation of renal function. Bromocriptine (BRC), a relatively specific agonist of D-2 receptors and at the same time a D-,1 antagonist, elicited natriuresis and diuresis when given i.c.v. in doses ranging from 20 to 600 {\mu}g/kg$, roughly in dose-related fashion, while the renal perfusion and glomerular filtration progressively decreased with doses, indicating that the diuretic, natriuretic action resides in the tubules, not related to the hemodynamic effects. These diuresis and natriuresis were most marked with 200 ${\mu}g/kg$, with the fractional sodium excretion reaching about 10%. With 600 ${\mu}g/kg$, however, the diuretic, natriuretic action was preceded by a transient oliguria resulting from severe reduction of renal perfusion, concomitant with marked but transient hypertension. When given intravenously, however, BRC produced antidiuresis and antinatriuresis along with decreases in renal hemodynamics associated with systemic hypotension, thus indicating that the renal effects produced by i.c.v. BRC is not caused by a direct renal effects of the agent which might have reached the systemic circulation. In experiments in which DA was given i.c.v. prior to BRC, 150 ${\mu}g/kg$ DA did not affect the effects of BRC (200 ${\mu}g/kg$), while 500 ${\mu}g/kg$ DA abolished the BRC effect. In rabbits treated with reserpine, 1 mg/kg i.v.,24 h prior to the experiment, i.c.v. BRC could unfold its renal effects not only undiminished but rather exaggerated and more promptly. In preparations in which one kidney is deprived of nervous connection, the denervated kidney responded with marked diuresis and natriuresis, whereas the innervated, control kidney exhibited antidiuresis. These observations suggest that i.c.v. BRC influences the renal function through release of some humoral natriuretic factor as well as by increasing sympathetic tone, and that various DA receptors might be involved with differential roles in the center-mediated regulation of the renal function.
Journal of Korean Home Economics Education Association
/
v.30
no.2
/
pp.77-102
/
2018
The purpose of this study was to contribute to Home Economics(HE) teachers' culture by figuring out acknowledging characteristics of cultures of HE teachers and impeding factors on development of HE education. For this intensive interview were used. Intensive interviews were made with 14 HE teachers who completed coursework for master's or doctor's program of graduate school and belong to HE Teachers' Study Associations of each region or Korean Home Economics Education Association and analyzed by subject analysis method. The results of the study are as follows. First, HE teachers establish the philosophy of HE education, and practice education to provide profit to adolescents, their families, as well as society through HE class with their belief that HE is a practical and critical subject to benefit individual adolescents, families, and society. Second, HE teachers form culture to make an effort to continue to improve their expertises by attending graduate school, joining HE teachers' associations to enhance teaching methods, evaluation methods, and work ability or disclosing their own class. Third, HE teachers settle culture to conduct classes focusing on practical issues by converting the paradigm of HE education to that of practical critique. They also see that the system of three actions(technical action, communicative action, and emancipative action) should be applied in circulating ways to improve quality and value of life. Forth, for impeding factors of development of HE education, there are educational system and social recognition. However, with HE teachers' efforts, HE education settles well, as it reflects demands from students and society, finds students' talents, and actualizes its own goals. HE teachers believe that student will recognize that HE education is necessary for happiness of individuals and families. As a way to develop Home Economics teacher culture, Home Economics teachers should have the opportunity to develop more Home Economics teachers by participating in and working in research sessions in each area. It also called for a control tower to enable and lead collaborative networks between local Home Economics curriculum research committees. The Korean Home Economics Education Association should play a central role in the academic research community of each region and be able to help Home Economics teachers by moving more quickly and systematically to cope with the upcoming changes in education. Finally, participants said that in order to prepare a basic framework for the change in Home Economics education, practical critical Home Economics teacher training are needed. To this end, students can understand the essence of Home Economics education and establish their identity by taking a deeper Home Economics education curriculum philosophy for Home Economics teacher training.
In vitro inhibitory activity of 34 insecticides and 31 fungicides to glutathione-S-transferase and esterases extracted from rats was determined. Of tested pesticides, the pesticides with high activity on both detoxifying enzymes were mixed with pesticides that are known to be detoxified by detoxifying enzymes. Glutathione-S-transferase was inhibited by thiodicarb $(I_{50}:1.87\times10^{-4}M)$, thiocyclam $(7.40\times10^{-4}M)$, dithianon $(7.55\times10^{-5}M)$, and tolylfluanide $(8.66\times10^{-5}M)$, while esterases by dichlorvos $(8.95\times10^{-8}M)$, pirimicarb $(2.74\times10^{-6}M)$, pyrazophos $(3.31\times10^{-5}M)$, and benomyl $(4.96\times10^{-5}M)$. After acephate known to be detoxified by glutathione-S-transferase was mixed with glutathione-S-transferase-inhibiting pesticides and phenthoate known to be detoxified by esterases was mixed with esterases-inhibiting pesticides, insecticidal activities of such mixtures were determined against diamondback moth (PlutelLa xylostella L.). Synergistic action was observed in all pesticide combinations. The highest synergistic action was obtained when phenthoate was combined with dichlorvos, showing that co-toxicity coefficients were 1512 and 1877 after 24 and 48 hours of treatment, respectively. Several other combinations of pesticides, such as phenthoate with benomyl, and acephate with dithianon, also showed synergism, showing that their co-toxicity coefficients were about 1,000 and 500, after 24 hours of treatment, respectively. Our results showed that combinations of pesticides inhibited by detoxifying enzymes and ones detoxified by detoxifying enzymes resulted in increased toxicities of pesticides, suggesting that such combinations could be used to develop pesticide mixtures with more broad spectrum and high effectiveness.
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