• International Journal of Stem Cells
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• v.15 no.2
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• pp.203-216
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• 2022

Background and Objectives: Epidemiological investigations have shown positive correlations between increased diesel exhaust particles (DEP) in ambient air and adverse health outcomes. DEP are the major constituent of particulate atmospheric pollution and have been shown to induce proinflammatory responses both in the lung and systemically. Here, we report the effects of DEP exposure on the properties of human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs), including stemness, regeneration, and immunomodulation. Methods and Results: Non-apoptotic concentrations of DEP (10 ㎍/ml) inhibited the migration and osteogenic differentiation capacity of WJ-MSCs. Gene expression profiling showed that DEP increased intracellular reactive oxygen species (ROS) and expression of pro-inflammatory and metabolic-process-related genes including cFos. Furthermore, WJ-MSCs cultured with DEP showed impaired suppression of T cell proliferation that was reversed by inhibition of ROS or knockdown of cFos. ERK inhibition assay revealed that DEP-induced ROS regulated cFos through activation of ERK but not NF-κB signaling. Overall, low concentrations of DEP (10 ㎍/ml) significantly suppressed the stemness and immunomodulatory properties of WJ-MSCs through ROS/ERK/cFos signaling pathways. Furthermore, WJ-MSCs cultured with DEP impaired the therapeutic effect of WJ-MSCs in experimental colitis mice, but was partly reversed by inhibition of ROS. Conclusions: Taken together, these results indicate that exposure to DEP enhances the expression of pro-inflammatory cytokines and immune responses through a mechanism involving the ROS/ERK/cFos pathway in WJ-MSCs, and that DEP-induced ROS damage impairs the therapeutic effect of WJ-MSCs in colitis. Our results suggest that modulation of ROS/ERK/cFos signaling pathways in WJ-MSCs might be a novel therapeutic strategy for DEP-induced diseases.

• Molecules and Cells
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• v.27 no.4
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• pp.417-422
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• 2009

Lipoxygenase (LO) metabolites are generated in inflamed tissues. However, it is unclear whether the inhibition of the LO activity regulates the expression of c-Fos protein, a pain marker in the spinal cord. Here we used a carrageenan-induced inflammation model to examine the role of LO in the development of c-Fos expression. Intradermally injected carrageenan caused elevated number of cells exhibiting Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn, and decreased the thermal and mechanical threshold in Hargreaves and von Frey tests. Pretreatment with an inhibitor of phospholipase A2, that generates the LO substrate, prior to the carrageenan injection significantly reduced the number of Fos-(+) cells. A general LO inhibitor NDGA, a 5-LO inhibitor AA-861 and a 12-LO inhibitor baicalein also exhibited the similar effects. Moreover, the LO inhibitors suppressed carrageenan-induced thermal and mechanical hyperalgesic behaviors, which inidcates that the changes in Fos expression correlates with those in the nociceptive behaviors in the inflamed rats. LO products are endogenous TRPV1 activators and pretreatment with BCTC, a TRPV1 antagonist inhibited the thermal but not the mechanical hypersensitivity. Overall, our results from the Fos-LI and behavior tests suggest that LO products released from inflamed tissues contribute to nociception during carrageenan-induced inflammation, indicating that the LO pathway is a possible target for modulating inflammatory pain.

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.375-380
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• 2002

Cytochrome P4501A2 (CYP1A2) is a member of the cytochrome P450 family of isozymes involved in the phase I drug metabolism of vertebrates. CYP1A2 is responsible for the activation of a number of aromatic amines to mutagenic and carcinogenic forms. Thus, the level of CYP1A2, which varies among different populations, may determine an individual's susceptibility to these chemicals. We have previously reported on the importance of a cis element named PRB (protected region B) in the regulation of human Cytochrome P4501A2 (CYP1A2) gene, which appeared to act as a positive regulatory element. Closer examination of the PRB sequence (-2218 to -2187 bp) revealed a putative AP-1 binding site, TGACTAA, at -2212 bp (Chung and Bresnick, 1997). To elucidate the role of AP-1 in CYP1A2 regulation, we transiently overexpressed c-Jun and c-Fos transcription factors in human hepatoma HepG2 cells, and examined their influence on the CYP1A2 promoter activity by reporter gene assays. Cotransfection of the c-Jun and the c-Fos expression vectors increased the induced transactivation by five to six fold from the CYP1A2 promoter constructs. However, deletion of the PRB element did not affect the degree of activation by the c-Jun and the c-Fos. Therefore, it is unlikely that the c-Jun and the c-Fos activate the CYP1A2 promoter through this AP-1 consensus-like sequence in the PRB region.

• The Journal of Korean Medicine
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• v.24 no.2
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• pp.66-80
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• 2003

Objectives : Recently, herbal acupuncture has been developed in the Korea since the earlier 1960' applied to various diseases including the cerebrovascular accident. The main characteristics of herbal acupuncture are a combination the merit of acupuncture and herbal medicine. It was not well known the therapeutic effect and the mechanism of herbal acupuncture on transient forebrain ischemic injury, although it has been used frequently in clinics. Ramulus Uncariae Cum Uncis (釣鉤藤) has been claimed to possess sedative, anti-spasmodic actions, and treat childhood epilepsy in oriental medical preparation. Also, it has been stated that Ramulus Uncariae Cum Uncis was antioxidatvie effect and neuroprotection against glutamateinduced neuronal death. Methods : In this study, effects of Ramulus Uncariae Cum Uncis' herbal acupuncture on the $GV_{20}{\;}or{\;}LR_3$, named Baek-hue or Tae-chung, on neuroprotection after the transient forebrain ischemia were investigated in Sprague-Dawely rats. Expressions of cFos, FosB and BDNF protein in the hippocampus and cortex were observed at 2 hrs and 48 hrs after transient forebrain ischemia by immunohistochemistry and ELISA technique. Results : Expression of cFos protein was increased slightly in the hippocampus and cortex at 2 hrs after transient forebrain ischemia, but FosB protein was increased highly comparing to cFos protein. However, pretreatment with Ramulus Uncariae Cum Uncis' herbal acupuncture on $GV_{20}{\;}or{\;}LR_3$ significantly increased expression of cFos protein and significantly decreased expression of FosB protein compared to control group, respectively. These features were observed in the motor cortex and retrosplenial granular cortex as well as the hippocampus. Especially, cFos expression was more increased at the herbal acupuncture on $GV_{20}{\;}than{\;}LR_3$, but FosB expression was more decreased in $LR_3$ group than $GV_{20}$ group. Also, pretreatment with Ramulus Uncariae Cum Uncis' herbal acupuncture on $GV_{20}{\;}or{\;}LR_3$ significantly increased the expression of BDNF protein in the hippocampus ($254.88{\pm}12{\;}pg/ml{\;}in{\;}GV_{20}$ group, $245.93{\pm}44.4{\;}pg/ml{\;}in{\;}LR_3$ group) and the cortex ($85.81{\pm}3.45{\;}pg/ml{\;}in{\;}GV_{20}$ group, $111.51{\pm}15.79{\;}pg/ml{\;}in{\;}LR_3$, group) compared to the hippocampus ($134.07{\pm}2.96{\;}pg/ml$) and the cortex ($61.16{\pm}4.11{\;}pg/ml$) in control group at 48 hrs after transient forebrain ischemia. Conclusion : These results suggest that pretreatment with Ramulus Uncariae Cum Uncis' herbal acupuncture on $GV_{20}{\;}or{\;}LR_3$ has neuroprotective effect on transient forebrain ischemia and the herbal acupunture on $GV_{20}{\;}or{\;}LR_3$ may be related to antioxidative effect and calcium channel block of Ramulus Uncariae Cum Uncis. Also, it could be mentioned there is specificity of acupoints treating ischemic injury through the difference between the herbal acupuncture of $GV_{20}{\;}and{\;}LR_3$.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.29 no.3
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• pp.150-158
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• 2016

Objectives : We want to know the effect of Gyejakjimo-tang in mice model of acute pain.Methods : We investigated writhing reflex in mice with acetic acid-induced abdominal pain using mice, we observed c-Fos protien expression by immunohistochemistry dyeing method in the paraventricular nucleus(PVN) and supraoptic nucleus(SON) of the hypothalamus.Results : All of Gyejakjimo-tang treated group suppressed acetic acid-induced writhing response as acetic acid injuction group, but in 100㎎/㎏ Gyejakjimo-tang treated group and 200㎎/㎏ Gyejakjimo-tang treated groups represernted significance. All of Gyejakjimo-tang treated groups(50, 100 and 200㎎/㎏ Gyejakjimo-tang-treated group), Fos-positive cells in PNV significantly decreased as acetic acid injuction group, and All of Gyejakjimo-tang-treated groups Fos-positive cells in SON significantly decreased as acetic acid injuction group.Conclusions : The present results showed that the mice pre-treated with the aqueous extract of Gyejakjimo-tang showed analgesic effect on acetic acid-induced abdominal pain.

• Korean Journal of Acupuncture
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• v.19 no.1
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• pp.47-56
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• 2002

The frequency of the hypertension is increasing as the life level is improved and an average span of the life is extended since we approached modern stage. The hypertension is also dangerous disease which raises fatal complication for example with the bleeding aproplexy and the ischemic attack. The medicinal treatment about the hypertension is required patients to take continually. The acupuncture have been introduced because a medicine-chemical treatment hasn't good influence on the human body. It recently has been processed that studies acupuncture effect for blood pressure and have been found out that blood pressure go down. The object of this study observe the effect of LR3 acupuncture on hypertension in Renal Hypertension RAT induced by 2K1C. The 2K1C model was based on renin-angiotensin system. We put the silver clip in renal artery to induce renal hypertension. We try to observe that LR3 acupuncture influence on the blood pressure and c-fos expression in CVLM, NTS, RVLM. In results, the blood pressure was decreased during acupuncture than before acupuncture, after acupuncture. The heart rate was also decreased during acupuncture than before acupuncture, after acupuncture. The LR3 acupuncture significantly effects on blood pressure and heart rate (P<0.05). The increased expression of c-fos was shown in CVLM, NTS, but not in RVLM. In conclusion, LR3 was relived the action of control upon the hypertension and related with medulla, particularly CVLM, NTS. It needs to be closely examined pharmacological mechanism and studied combination with other acupoints.

• Molecules and Cells
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• v.23 no.1
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• pp.88-93
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• 2007

Neuropeptide Y (NPY) is an orexigenic and hypothermic peptide. To understand its role in hypothermic conditions, male rats were placed in a $24^{\circ}C$ or $4^{\circ}C$ air chamber for 1.5 h. The expression of c-Fos protein, and NPY mRNA and protein, was analyzed in the hypothalamus 1 h-2 h later. The cold treatment increased the number of c-Fos-immunoreactive cells in the paraventricular hypothalamic nucleus (PVN) and arcuate nucleus (ARC). At the same time it decreased the density of NPY-immunoreactive components in the PVN, dorsomedial hypothalamic nucleus and ARC, as well as of NPY transcripts in the PVN and ARC. No colocalization of c-Fos with NPY was detected. These results suggest that short-term cold exposure should reduce indirectly NPY production in some hypothalamic nuclei to facilitate thermogenesis without inducing feeding behavior.

• The Korea Journal of Herbology
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• v.26 no.2
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• pp.59-66
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• 2011

Objectives : The goal of this study was to investigate the antidepressant effects of Mixture of Lycii Radicis Cortex and Moutan Cortex on the change of HPA-Axis and Catecholamic system. Methods : We were performed the Forced Swimming Test. The expressions of Corticotropin-Releasing Factor (CRF) and c-Fos at paraventricular nucleus (PVN), and tyrosine hydroxylase (TH) at ventral tegmental area (VTA) and locus coeruleus (LC) were evaluated by immunohistochemical method. Results : The duration of immobility in the Forced Swimming Test was significantly decreased in A100, A400(p<0.05~p<0.01). CRF expressions at PVN was significantly decreased in A400(p<0.05).No other group showed significant difference in expression of c-Fos at PVN comparing with control group. TH expressions at VTA was significantly decreased in A100 and A400, respectively(p<0.001). TH expressions at LC was significantly decreased in A100(p<0.01). Conclusions : According to the above results, Mixture of Lycii Radicis Cortex and Moutan Cortex has antidepressant effects via the reduction of CRF expression and the Catecholamine System activity.

• Herbal Formula Science
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• v.17 no.1
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• pp.163-173
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• 2009

Objectives : The goal of this study was to investigative the effect of Gardeniae Fructus (GF)as antidepressant in the forced swimming test(FST) model rats. Methods : The expressions of corticotropin-releasing factor(CRF), tyrosine hydroxylase (TH) and c-fos were measured by immunohistochemical method at paraventricular nucleus(PVN), locus coeruleus (LC) and ventral tegmental area(VTA). Results : The duration of immobility in FST was significantly decreased in the GF 100mg/kg groups (p<0.05). CRF expression was significantly decreased at PVN in the GF 100 mg/kg and 400mg/kg treated group in comparison with the control group, respectively (p<0.01). c-fos expression was decreased at PVN in the GF 100 mg/kg treated group with no significance. TH expression was significantly decreased in the GF 100 mg/kg and 400mg/kg treated group in comparison with the control group, at LC and VTA respectively (p<0.001). Conclusion : According to the results, it can be considered that Gardeniae Fructus has antidepressant effect by showing the reduction of immobility in FST through the reduction of CRF, TH expression.

• Journal of Animal Science and Technology
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• v.44 no.6
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• pp.727-738
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• 2002

This study was conducted to investigate the effect of essential amino acid(EAA) deficient diets on short-term feeding response and the Fos expression in brain area when methionine deficiency diet fed, and thereby to know the mechanism of feed intake regulation. In all trials, experimental diets were formulated with pure amino acid mixture to level of 15% nitrogen. Rats were adapted to a 6-hr single-meal feeding per day(17:00${\sim}$21:00). Feed intake and body weight were monitored every hour after 7-day of feeding of individual EAA deficient diets in Exp. Ⅰ. In Exp. Ⅱ, Fos immuno- histochemistry was determined in various regions of brain to identify the regions that is related to suppressed feed intake following feeding methionine-deficient diet. Fos expression was examined to know the initial sensitive region in the brains of rats at 3h after feeding of the control and methionine deficient diet(-Met). Initial response to EAA deficiency diets was severely depressed in methionine deficiency diet, but the depression was low in threonine deficiency diet. However, the feed intake at 3rd day in rats was depressed in the order of His(71%), Leu(68%), Ile(66%), Thr(63%), Trp(61%), Val(55%), Phe(52%), Met(51%), Lys(44%) and Arg(24%). Fos immunoreaction in neural regions(PPC, amygdala and EPC) of pyrifrom cortex was increased in the -Met group more than in the control diet group, but those in LH, VMH and PVM were similar. Thus, based on these data, the PPC was identified as the initial response area in the -EAA diet.