The lower urinary tract symptoms (LUTS) show in benign prostatic hyperplasia (BPH). The three major micturition centers in brain are pontine micturition center (PMC), ventrolateral periaqueductal gray (vlPAG), and medial preopticnucleus (MPA) regions. Previous study showed that c-Fos expression change was associated with LUTS. In present study, the effect of P. ginseng on c-Fos expression in PMC, vlPAG, and MPA regions in rat brain was tested. P. ginseng is the four year-old Korean ginseng. It was collected at the department of medicinal crop research (Eumsunggun, Chungbuk, Korea) in September 2010. The four groups (n = 6) are control group, BPH-induced group, BPHinduced and P. ginseng-treated group, and BPH-induced and finasteride-treated group. BPH in rats was induced by testosterone. After 4 weeks, all animals were sacrificed to evaluate c-Fos expression in PMC, vlPAG, and MPA regions in rat brain. The c-Fos expression was evaluated in the regions of rat brain by immunohistochemistry (IHC). Present results showed that c-Fos expressions in PMC, vl-PAG, and MPA regions in brain of rats in the BPH-induced group were higher compared to c-fos expression of the control group. The increased c-Fos expression in three regions (PMC, vlPAG, and MPA) were decreased by treatment with P. ginseng (200 mg/kg). These results suggest that P. ginseng has an inhibitory effect on the symptoms of BPH and is associated with regulation of c-Fos expression in the brain in a testosterone induced BPH rat model.

c-Fos is known to related to synaptic plasticity and apoptosis in damage from ischemia or external injury. The purpose of this study was to investigate whether needle electrode electrical stimulation(NEES) is effective in increasing the number of c-Fos response cells and c-Fos expression in striatum after global ischemia in rats. There were no treatment and occlusion in the control group, global ischemia(GI) group were no treatment after carotid artery occlusion, and needle electrode electrical stimulation(NEES) group were treated with NEES after GI induced. The number of striatum c-Fos response cells and c-Fos protein expression significantly decreased in the NEES group compared to the GI group after 12, 24, 48 hours. The results of the present study suggest that NEES is ineffective in improving global ischemia in rats and may also be ineffective in the globally ischemic human brain.

Osteoclasts originated from hematopoietic stem cells are multi-nucleated cells that can resorb the bone matrix. Receptor activator of nuclear factor kappa-B (RANK)/RANK ligand (RANKL) signaling pathway is crucial for the differentiation and activation of osteoclasts. In this study, we investigated for the first time whether or not RANKL induced mitogen- and stress-activated kinase 1 (MSK1) phosphorylation at Ser 376. Activation of MSK1 was detected as soon as 5 min after RANKL stimulation and sparsely detected at 30 min after stimulation. RANKL-induced MSK1 phosphorylation occurred in a dose-dependent manner. MSK1 is known as a downstream signaling molecule of cAMP-dependent protein kinase (PKA). Treatment with the PKA inhibitor H89 significantly suppressed c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) induction upon RANKL stimulation. In addition, cAMP response element-binding protein (CREB) phosphorylation was extremely inhibited by H89 treatment. Mitogen-activated protein kinases (MAPKs) have been investigated for induction of MSK1 phosphorylation. Specific signaling pathway inhibitors for p38 and extracellular signal-regulated kinases (ERKs) significantly blocked RANKL-induced MSK1 activation. Finally, as a downstream effector of the p38-MSK1 pathway, c-Fos transcriptional activity was determined. RANKL-mediated elevation of c-Fos transcriptional activity was significantly suppressed by p38 inhibitor. Moreover, a dominant negative form of CREB suppressed activation of NFATc1. In conclusion, RANKL-stimulated MSK1 phosphorylation could play a role in induction of NFATc1 through CREB and c-Fos activation as a downstream molecule of p38, ERK MAPKs, and PKA. Our results support basic information for the development of osteoclast specific inhibitors.

Sucrose and alcohol are rewarding and appetitive. They are occasionally over-consumed and cause addiction. The parabrachial nuclei (PbN) are the second taste relay in the central taste pathway. The nucleus accumbens (NAcc) is an important neural substrate in the reward system. Intake of sucrose or alcohol induces dopamine release in the NAcc. Although alcohol is not classified as a taste stimulus, a substantial number of sucrose-responsive neurons in the PbN respond to stimulation by alcohol on the tongue. In the present study, we investigated whether or not application of 0.5 M sucrose, 10% ethanol (EtOH), mixture of sucrose and EtOH, and double-distilled water (DDW) to the tongue induces c-Fos-like immunoreactivity (cFLI) in the PbN and NAcc. We also examined whether or not the number of cFLI following sucrose/EtOH is comparable to the number of cFLIs following sucrose and EtOH, respectively. Male Sprague-Dwaley rat was anesthetized with a mixture of Zoletil and Rompun while stimulation solution was applied to the anterior tongue. The rat was sacrificed by perfusion, and the fixed brain was sectioned and immunostained. Data from a total of 18 animals were analyzed. The number of cFLI following stimulation with sucrose and/or EtOH was greater than that of DDW in the PbN. Numbers of cFLI following sucrose, EtOH, and sucrose/EtOH were not significantly different from each other in the PbN. The number of cFLI in response to stimulation solution was not different from that of DDW in the NAcc. The result of the present study suggests that not only sucrose but also EtOH activates some neurons in the PbN, and that some pontine neurons possibly respond to both sucrose and EtOH.

Taste receptors of the anterior tongue are innervated by the chorda tympani (CT) branch of the facial (VIIth) nerve. The CT nerve transmits information on taste to the ipsilateral nucleus of the solitary tract (NST), which is the first taste central nucleus in the medulla. Taste information is known to be transferred ipsilaterally along the taste pathway in the central nervous system. Some patients with unilateral CT damage often retain their ability to sense taste. This phenomenon is not explained by the unilateral taste pathway. We examined whether neurons in the NST receive information on taste from the contralateral side of the tongue by measuring c-Fos-like Immunoreactivity (cFLI) following taste stimulation of the contralateral side of the tongue in the anesthetized rats. We used four basic taste stimuli, 1.0 M sucrose, 0.3 M NaCl, 0.01 M citric acid, 0.03 M QHCl, and distilled water. Stimulation of one side of the tongue with taste stimuli induced cFLI in the NST bilaterally. The mean number of cFLI ranged from 23.28 ± 2.46 by contralateral QHCl to 30.28 ± 2.26 by ipsilateral NaCl stimulation. The difference between the number of cFLI in the ipsilaterl and contralateral NST was not significant. The result of the current study suggests that neurons in the NST receive information on taste not only from the ipsilateral but also the contralateral side of the tongue.

Ischemia that causes stroke induces inflammation of brain cells and apoptosis and as a result, it influences much on the functional part of a man. The needle electrode electrical stimulation (NEES) that combines acupuncture of oriental medicine with electric therapy of western medicine relieves inflammation of cells and has effect on regrowth of nerve tissues. This study was conducted to verify the influence of NEES on the occurrence of c-Fos of cerebrum after applying NEES to the meridian point, Zusanli (ST 36) of a rats with induced ischemia. Global ischemia was induced by using ligation method on common carotid artery of male Sprague Dawley (SD) rats. The ligation was maintained for 5 minutes and then suture was removed for blood reperfusion. After inducing global ischemia, NEES was done to the left and right meridian points of Joksamri of a rat for 30 minutes after 12 hours, 24 hours, and 48 hours. The findings were as follows. 1. In the result of immunohistochemical method, the number of c-Fos immune response cells significantly decreased (P<.05) in NEES group than the control group (GI) that did not get NEES. 2. In the result of western blotting, the occurrence of c-Fos after 24 hours from the inducement of ischemia significantly decreased (P<.05) in NEES group than the control group (GI) that did not get NEES. Therefore, as the effect of NEES was shown highest after 24 hours from the ischemia, it is suspected that NEES would take important role in early treatment after cerebral stroke.

The purpose of this study was to evaluate the role of c-fos and c-jun expression in the odontogenic cysts. For this study, 20 subjects of odontoenic dysts: 8 subjects of keratocysts and 12 subjects of periodontal cysts referred to the Dept. of Oral Pathology, School of Dentistry, Kyung Hee University, were used as experimental group, and 5 subjects of normal oral mucosa without any inflammatory changes. were used as control groups respectively. All the tissues of experimental and control group were fixed in neutral formalin solution and embedded in paraffin, serial tissue section were made 5㎛ in thickness and processed in the standard way for immunohistochemical method, using primary antibodies, for c-fos, c-jun was diluted at 1:100 each, followed by the super sensitive non-biotin horse radish peroxidase system with DAB as chromogen application, counter stained with Gill's hematoxylin stainmethod, mounted. And examined under the biologic microscope with the criteria of -(no epithelial stain), +(weak or focal epithelial stain), ++(moderate or focal intensive epithelial stain), +++(intense generalized epithelial staining) for the epithelial, and stromal tissues on each. Attained results as follows. In normal oral mucosa, it is noted that moderate positive responses in cytoplasm and nuclei to c-fos and c-jun protein on each.. In the responses to c-fos, c-jun protein, moderate positive responses in nuclei and cytoplasms of the epithelial lining in keratocysts and periodontal cysts, but more intense reaction is noted on the periodontal cyst compare to that on the keratocysts. In the responses to c-fos, c-jun, it is noted that more intense responses in odontogenic cyst compare to that in the oral mucosa. In the responses to c-fos and c-jun on submucoas of oral normal mucosa, focal epithelial stain was noted. and more intensive reaction was noted on the odontogenic cysts, most in periodontal cysts. This results suggests that c-fos and c-jun protein effected on the induction of development and growth of the cysts

1'he purpose 0 1' this study was to evaluate the ro1e of c• fos and c-jun expression in the salivary gland tumol‘ s , For this study‘ 11 s ubj ects of sali vary gland tumors ; 4 su이 ects of p1eomorphic adenomas, 3 s ubj ects of adenoid cystic car cinomas , 2 s ubjects of adenocar cinomas, 2 subjects of mucoepidermoid tumors, referred to the Dept, of Ora l Path College of Dentis t l'Y, Kyung Hee Univer sity, were used as experimental group, and 2 subj ect s of normal minor salivary gla nds without a ny infla mmator y changes, were used as control group respectively, All the tissues experimenta l and control group were fixed in 10% neutral formalin solution and embedded in paraffin , serial ti ssue section were made 5 I1I1l in thickness a nd processed in the s t andard way for immunohistochemical method, using primary and secondar y a ntibodi es, for c-fos, c-jun, foll owed by the Streptavidin-Horse Radish Peroxidase, all BioGenex U,S,A, made, appli cat ion counter s t ained with Mayer's hematoxylin stain method, mounted And examined under the biologic mi croscope, with the criteria : -(no epitheli al s ta in), +(weak or focal epithelial stain), ++(moder a te or focal intensive epithelial sta in)‘ +++(intense generali zed epithelial staining) for the epithelial, and stromal ti ssues on each Attained results as follows : 1 1n nonna l minor saliva ry gla nds , it is noted that negative responses on the acini minimal res ponses in nucl ei and cytoplams of se rous demilun e, myoepi theli al cells, and intensive r esponses in nuclei and cytoplam of ducta l cells to c-fos and c-jun, 2 1n the res ponses to c-fos, positive responses in nuclei and cytoplasms of the lining cells o[ the ad e nαd tissues, e pidermoid, and mucous cells in mucoepidermoid tumors are noted and in other tumor tissuses, negative nuclei wi th pos itive cyto plasms are revealed 3 1n the responses to c- jun, it is noted that positive r es ponse in nuclei and cytolasm i n the cells of adenoid tissues in pl eomorphic adenoma, epidermoid cell s, mucous cell in mucoe pi dermoid tumor but in other tumor s, only positive responses in cytoplasm are noted, Intensive r esponses on c-fos‘ c-jun were noted on the high a typical cells 1'his results suggest that c-fos and c-jun may be affected t o the reactivation on growt h and development of the salivary gland tumors

The purpose of this study was to evaluate the role of c-fos and c-jun expression in the oral squamous cell carcinoma and ameloblastomas. For this study, 12 subjects diagnosed as squamous cell carcinoma and 7 subjects of ameloblastomas referred to the Dept. of Oral Path. School of Dentistry, Kyung Hee University, 2 subjects of normal oral mucosa without any inflammatory changes were used as experimental, control groups respectively. All the tissues ; experimental and control group were fixed in neutral formalin solution and embedded in paraffin, serial tissue section were made 5㎛ in thickness and processed in the standard way for immunohistochemical method, using primary and secondary antibodies, for c-fos (Anti-c-fos protein, rabbit polyclonal kit at 1:100 dilution), c-jun( anti-c-jun protein, rabbit polyclonal at 1:100 dilution), all BioGenex U.S.A. made, followed by the Streptavidin - Horse Radish Peroxidase(InnoGenex, Human-Avidin kit) application, counter stained with Mayer's hematoxylin stain method, mounted. And examined under the biologic microscope, with the criteria-(no epithelial stain), +(weak or focal epithelial stain), ++(moderate or focal intensive epithelial stain), +++(intense generalized epithelial staining) for the epithelial, and connective tissue component in squamous cell carcinomas, ameloblastomas and normal mucosal epithelium on each. Attained results as follows ; 1. In oral mucosa, c-fos and c-jun intensely expressed on the all cell layers except on the basal layer. Intense reaction is noted in the c-jun than in the c-fos. and a few cells with positive cytoplasm, negative nuclear are scattered in all layer. 2. The response to c-fos in ameloblastomas, is various according to the histological type, but intense resposes are nodted in nuclear and cytoplasm on the tall columnar cells at the periphery of the follicles compare to that on the stellate cells. 3. The respone to c-fos in squamous cell carcinoma, intense reaction is noted in cytoplasm and nuclei of the tumor cells in well differentiated, poorly differentiated type. 4. The response to c-jun in ameloblastoma, it is noted that moderate respone in nuclear and cytoplasm, at the tall columnar cells at the periphery of follicular or plexiform type but intense respone was notes on the columnar cells, and stellate cell in cytoplasm and nuclear of acanthomatous type. 5. The respon to c-jun in squamous cell carcinoma, it is noted that intensive responses only in cytoplasm in well differentiated type, but intensive responses in nuclei and cytoplasm in the poorly differentiated type are revealed. Intensive responses on c-fos, c-jun were noted on the high atypical cells. This results suggest that c-fos and c-jun may be affected to the reactivation on growth and development of the squamous cell carcinoma.

Background : This study aimed to determine the anti-osteoclastogenic effects of extracts from CK berry’s and identify the underlying mechanisms in vitro. Methods and Results : Reactive oxygen species (ROS) are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW264.7 cells in a dose-dependent manner and exhibited strong radical scavenging activity. The extracts also attenuated the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. To attain molecular insights, the effect of the extracts on the signaling pathways induced by receptor activator of nuclear factor kappa B ligand (RANKL) were also investigated. RANKL triggers many transcription factors through the activation of mitogen-activated protein kinase (MAPK) and ROS, leading to the induction of osteoclast-specific genes. The extracts significantly suppressed RANKL-induced activation of MAPKs, such as extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK), and p38, and consequently led to the downregulation of c-Fos and nuclear factor of activated T cells 1 (NFATc1) protein expression which ultimately suppress the activation of the osteoclast-specific genes, cathepsin K, TRAP, calcitonin receptor, and integrin β3. Conclusion : In conclusion, our findings suggest that AM extracts inhibited RANKL-induced osteoclast differentiation by downregulating ROS generation and inactivating JNK/ERK/p38, nuclear factor kappa B (NF-κB)-mediated c-Fos and NFATc1 signaling pathway.

The immediate early gene c-fos has long been known as a molecular marker of neural activity. The neuron's activity is transformed into intracellular calcium influx through NMDA receptors and L-type voltage sensitive calcium channels. For the transcription of c-fos, neural activity should be strong enough to activate mitogen-activated protein kinase (MAPK) signaling pathway which shows low calcium sensitivity. Upon translation, the auto-inhibition by Fos protein regulates basal Fos expression. The pattern of external stimuli and the valence of the stimulus to the animal change Fos signal, thus the signal reflects learning and memory aspects. Understanding the features of multiple components regulating Fos signaling is necessary for the optimal generation and interpretation of Fos signal.