• International Journal of Oral Biology
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• v.34 no.1
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• pp.29-36
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• 2009

Cyclosporin A (CsA) has been used clinically as an immunosuppressive drug to prevent organ transplant rejection and in basic research as a mitochondrial permeability blocker. It has been reported that CsA has a protective role in severed neurons and a neurotrophic effect in neuronal cells. However, the molecular mechanisms underlying the stimulation of neuronal cell proliferation by CsA have not yet been elucidated. In our current study, we investigated CsA responsive proteins in PC12 cells using a systematic proteomic approach. The viability of these cells following CsA treatment increased in a dose- and time-dependent manner. Proteins in the CsA-treated PC12 cells were profiled by two-dimensional gel electrophoresis (2-DE) and identified by matrix-assisted laser desorption ionization time-of flight (MALDI-TOF) and electrospray ionization quadupole time-of-flight mass spectrometries (EIQ-TOFMS). This differential expression analysis showed significant changes for 10 proteins (6 up-regulated and 4 down-regulated) upon CsA treatment that were related to cell proliferation, metabolism and the stress response. These proteomics data further our understanding of the proliferation mechanisms of PC12 cells exposed to CsA and demonstrate that our methodology has potential to further elucidate the mechanisms and pathways involved.

• Archives of Pharmacal Research
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• v.29 no.7
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• pp.566-569
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• 2006

This study examined whether or not acute stress is linked to increases in the neurosteroid levels, which is a well-known neurotransmitters associated with stress stimuli. The ginsenoside, Rb1, was tested in order to better understand its potential effects on altering the neurosteroid levels and ultimately attenuating stress. The optimal stressed condition was checked by measuring the 5a-dihydroprogesterone (DHP) and allopregnanolone (THP) levels in the brain after immobilization stress at various times. Based on this result, an acute stress model was set up to give 30 min of immobilization stress. The DHP and THP brain levels of the stressed mice were then investigated after administering Rb1 orally (10 mg/kg). These results were compared with the neurosteroid level in the stressed mice not given Rb1. Saline was administered orally to the nonstressed mice to check the placebo effect. Acute immobilization stress induced an increase in the THP and DHP concentration in the frontal cortex and cerebellum. When Rb1 was administered orally prior to immobilization stress, the THP level in the frontal cortex and cerebellum was significantly lower than that in the stressed animals not given Rb1. On the other hand, the DHP level was lower in the cerebellum only. This suggests that the metabolism of the brain neurosteroids is linked to psychological stress, and Rb1 attenuates the stressinduced increase in neurosteroids.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.309-318
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• 2015

Alcohol consumption increases the risk of type 2 diabetes. However, its effects on prediabetes or early diabetes have not been studied. We investigated endoplasmic reticulum (ER) stress in the pancreas and liver resulting from chronic alcohol consumption in the prediabetes and early stages of diabetes. We separated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type-2 diabetic animal model, into two groups based on diabetic stage: prediabetes and early diabetes were defined as occurrence between the ages of 11 to 16 weeks and 17 to 22 weeks, respectively. The experimental group received an ethanol-containing liquid diet for 6 weeks. An intraperitoneal glucose tolerance test was conducted after 16 and 22 weeks for the prediabetic and early diabetes groups, respectively. There were no significant differences in body weight between the control and ethanol groups. Fasting and 120-min glucose levels were lower and higher, respectively, in the ethanol group than in the control group. In prediabetes rats, alcohol induced significant expression of ER stress markers in the pancreas; however, alcohol did not affect the liver. In early diabetes rats, alcohol significantly increased most ER stress-marker levels in both the pancreas and liver. These results indicate that chronic alcohol consumption increased the risk of diabetes in prediabetic and early diabetic OLETF rats; the pancreas was more susceptible to damage than was the liver in the early diabetic stages, and the adaptive and proapoptotic pathway of ER stress may play key roles in the development and progression of diabetes affected by chronic alcohol ingestion.

• Journal of Nutrition and Health
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• v.4 no.1
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• pp.21-28
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• 1971

1. The effects of chloroform to the tissue lactic dehydrogenase (LDH) activities and its isozymes and to the tissue glutamic dehydrogenase (GDH) activities and its isoaymes are studied using the experimental albino male adult rats in this paper. The tissues studies are liver, kidney, heart, and brain. Besides the control group, two experimental groups are studied providing succeedingly 4 days interpariental administrations of chloroform, 0.0025ml and 0.025ml per day respectively. The changes of body weights, weights of organs, activities of GDH and LDH and their isozymes of each tissues, are analysed. 2. The body weights of rats are decreased due to the chloroform administration. 3. There are no significant differences of weights of organs due to the chloroform administration. 4. The significant decreases of tissue GDH activities and the significant changes in percent distribution of the GDH isozymes are found due to the chloroform administration. This weight be interpretated that chloroform effects to the protein and amino acid metabolism of rats. 5. Due to the chloroform administration, the significant changes in tissue LDH activities and in percent distribution of tissue LDH isozymes indicating the decreases of $LDH_1$ which is the aerobic heart type and the increase of $LDH_5$ which is the anaerobic muscle type, are observed. This could be estimated that chloroform effects to the carbohydrate metabolism, particularly to the anaerobic glycolysis of rats.

• Korean Journal of Biological Psychiatry
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• v.15 no.3
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• pp.175-185
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• 2008

Accumulating evidence has suggested the existence of reciprocal communication between immune, endocrine, and neurotransmitter system. Cytokine hypothesis of depression implies that increased pro-inflammatory cytokine such as -1, IL-6, IL-12, TNF-${\alpha}$, and IFN-${\gamma}$ in major depression, acting neuromodulators, play a key role in the mediation of behavioral, neuroendocrine, and neurochemical disturbances in depression. Concerning the relation between cytokines and serotonin metabolism, pro-inflammatory cytokines have profound effects on the metabolism of brain serotonin through the enzyme indoleamine-2,3-dioxygenase(IDO) that metabolizes tryptophan, the precursor of 5-HT to neurodegenerative quinolinate and neuroprotective kynurenate. The neurodegeneration process is reinforced by the neurotoxic effect of the hypercortisolemia during depression. From this perspective, it is possible that efficacy of antidepressants in the treatment of depression may, at least in part, rely on downregulation of pro-inflammatory cytokine synthesis. So, the use of cytokine synthesis inhibitors or cytokine antagonists may be a new treatment approach in depression. However, at present the question whether cytokines play a causal role in the onset of depression or are mere epiphenomena sustaining depressive symptoms remains to be elucidated. Nevertheless, cytokine hypothesis has created new perspectives in the study of psychological and pathophysiological mechanism that are associated with major depression, as well as the prospect for developing a new generation antidepressants.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.439-444
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• 2000

Tricyclic antidepressant clomipramine or selective serotonin reuptake inhibitors (SSRIs) have been commonly used for the treatment of premature ejaculation. In the present study, we analyzed the concentrations of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) in the medial preoptic area (MPOA) of the hypothalamus by awakening animal microdialysis following administration of clomipramine and various SSRIs. We then compared the serotonin metabolism and clinical effects of clomipramine and SSRIs on premature ejaculation. Basal extracellular serotonin level in the MPOA was higher than other brain regions and it was significantly increased by clomipramine and the SSRIs. The rank order of the concentration of serotonin at the MPOA was clomipramine, sertraline, paroxetine and fluoxetine and the concentrations of 5-HIAA was vice versa. The changes in serotonin concentration at the MPOA appeared closely associated with the clinical effects of these drugs on premature ejaculation. These results suggest that the serotonergic neuronal activity in the MPOA may have an selective inhibitory influence on ejaculation, and the effects of clomipramine and SSRIs on erectile function are mainly mediated by MPOA of the hypothalamus.

• Journal of Ginseng Research
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• v.15 no.2
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• pp.112-116
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• 1991

The metabolic fate of ginsenosides including gastrointestinat absorption, organ distribution, excretion and metabolism in liver was investigated by tracer studies using the radio-labeled ginsenosides. 3H-ginsenosides were shown to be absorbed from the mouse digestive tract and then to be excreted rapidly into urine and/or bile. Bile juice was concluded to play a significant role in absorption of ginsenosides. The total concentration of radioactivity persisted in tissues 24 hrs after oral administration was less than 1.3% of the administered dose and Rbl showed the highest value. The concentrations of radioactivity were relatively high in the liver and kidney. After administration of Rbl radioactivity was detected in the brain. After oral administration of 8H-ginsenosides, major component excreted into urine was found to be the intact ginsenosides and decomposed and/or metabolized products were found in GIT in the case of Rbl. 3H-ginsenoside Rbl was shown to be metabolized in the liver and the metabolite was suggested to be an acylated compound of Rbl by a certain organic acid.

• Natural Product Sciences
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• v.25 no.2
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• pp.165-171
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• 2019

Although the functions of a standardized extract of Gingko biloba leaves (EGb $761^{(R)}$) has been reported with regard to neurobiological properties, no attention has been paid to the impact of EGb $761^{(R)}$ on the neuronal regulation of energy homeostasis. To evaluate the hypothesis that EGb $761^{(R)}$ affect the secretion of peptide tyrosine tyrosine (PYY) and the activation of free fatty acid receptor 4 (FFA4), which are involved in the neuronal circuitries that control energy homeostasis by inducing the transfer of information about the influx of energy to the brain, we examined whether EGb $761^{(R)}$ can stimulate PYY secretion in the enteroendocrine NCI-H716 cells and if EGb $761^{(R)}$ can activate FFA4 in FFA4-expressing cells. In NCI-H716 cells, EGb $761^{(R)}$ stimulated PYY secretion and the EGb $761^{(R)}$-induced PYY secretion was involved in the increase in intracellular $Ca^{2+}$ concentration and the activation of FFA4. Furthermore, in FFA4-expressing cells, EGb $761^{(R)}$ activated FFA4. These results suggest that EGb $761^{(R)}$ may affect the control of energy homeostasis via the regulation of PYY secretion and FFA4 activation.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1431-1434
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• 2015

Background: Breast cancer is one of the most common cancers among women worldwide and the HER2 receptor plays an important role in its development and progression. This systematic review aimed to summarize the role of HER2 in brain metastasis in patients with breast cancer. Materials and Methods: We conducted a literature search by advanced search in title field using the Scopus, Pubmed, and Google scholar databases until the end of June 2014. With metastasis, metastatic, HER2, brain, and breast cancer, as terms of search we selected 31 articles, which were reviewed by two independent and blinded expert reviewers. The studies were first selected according to their titles and abstracts. Quality of the studies were then assessed using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) protocol for observational studies and CONSORT(Consolidation of Standards for Reporting Trials) protocol for clinical trials. For statistical analyses, we used STATA, version 11.0 software. Forest and funnel diagrams were drawn and for heterogeneity, index was also considered. Also we used meta regression analysis. Results: Finally, we reviewed 10 studies. The prevalence of brain metastasis in HER2-positive breast cancer patients was 24.9%. There was publication bias in the reviewed studies. Meta regression analysis showed that follow up time had no significant effect (p=0.396) on the prevalence of brain metastasis. Conclusions: The results showed a high prevalence of brain metastasis in HER2 positive breast cancer patients.

• Journal of Nutrition and Health
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• v.28 no.5
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• pp.375-386
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• 1995

This study was designed to investigate the changes in energy substrates, glucose and non-esterified fatty acid(NEFA), and fatty acid compositions in serum, following physiolgical stress in rats fed diets containing various fatty acids. Forty two Sprague-Dawley strain male rats, weighing 108$\pm$2.1g, were fed 3 different experimental diets for 4 weeks. The diets were composed of 105 fat(w/w) of either corn oil(CO;18:2 n6:57%), plant perilla oil(PO;18:3 n3:59%), or tuna fish oil(FO;20:5 n3:17%%, 22:6 n3:19%). After 4 weeks of feeding, each group wa subdiveided into (a) control, (b) 2 min swim in ice-cold water. Animals wer decapitated 20min after commencing the swim; trunk blood, brain, liver and epididymal fat pad were obtained. The levels of serum corticosterone, glucose, NEFA, triglyceride, fatty acid compositions, brain serotonin and 5-hydroxyindoleacetic acid were determined. Basal levels of corticosterone na NEFA of serum were significantly lower in fish oil fed animals than those of any other oil fed animals. Compared to either perilla oil-fed or corn oil-fed rats, cold swim stress in fish oil fed rats produced significantly smaller NEFA and larger corticosterone responses. However, there was no significant difference in basal levels of serum glucose. Stress increased serum glucose levels slightly, and the amount of increment was larger in fish oil rats than those of any other oil fed rats than those of any other oil fed rats, although all the values were normal level. Dietary fats and stress did not affect serotonin metabolism. In additions, the composition of fatty acids in serum was significantly affected by the dietary compostion of fatty acids and stress. Stress induced decreases in monounsaturated fatty acid and non-polyunsaturated fatty acid concentration in either perilla oil fed or fish group, but did not in corn oil fed group. Stress resulted in changes in fatty acid metabolism similar to that associated with essential fatty acid(EFA) dificiency, when feeding animals n-3 fatty acids in diet. In conclusion, feeding fish oil was more effective to decrease NEFA in serum than feeding perilla oil or corn oil and improved lipid metabolism, when the rats were maintained in normal or exposed to stressful environment. However, the fact that feeding diet containing n-3 fatty acids decreased EFA status under stress suggests that the requirement of n-6 PUFA should be increased in these groups.