Resveratrol has been reported to exert anticancer activity via modulation of multiple pathways and genes. In this study, we examined the effect of resveratrol on YD-10B human oral squamous cell carcinoma cells and its molecular mechanisms of action. We found that resveratrol inhibited the proliferation of YD-10B cells in a dose- and timedependent manner. The suppressive effect of resveratrol was accompanied by a reduction in Bmi-1 gene expression.We observed that silencing the Bmi-1 gene by small interfering RNA effectively downregulated the levels of GLUT1 mRNA and protein, which were also repressed by resveratrol. Bmi-1 silencing increased the number of YD-10B cells in S-phase arrest by approximately 2.3-fold compared with the control. In conclusion, the results of the present study demonstrate, for the first time, that resveratrol suppresses Bmi-1-mediated GLUT1 expression in human oral squamous cell carcinoma cells and suggest that the specific molecular targeting of Bmi-1 and/or GLUT1 expression can be combined with a chemotherapeutic strategy to improve the response of oral cancer cells to resveratrol.

PURPOSE: To study the effect of recombinant human epidermal growth factor (rhEGF) on oral mucositis induced by cisplatin and radiotherapy in a mouse model. MATERIALS AND METHODS: Twenty-four ICR mice were divided into three groups? the normal control group, the no rhEGF group (treatment with cisplatin and radiation) and the rhEGF group (treatment with cisplatin, radiation and rhEGF). A model of mucositis induced by cisplatin and radiotherapy was established by injecting mice with cisplatin (10 mg/kg) on day 1 and with radiation exposure (5 Gy/day) to the head and neck on days 1~5. rhEGF was administered subcutaneously on days -1 to 0 (1 mg/kg/day) and on days 3 to 5 (1 mg/kg/day). Evaluation included body weight, oral intake, and histology. RESULTS: For the comparison of the change of body weight between the rhEGF group and the no rhEGF group, a statistically significant difference was observed in the rhEGF group for the 5 days after day 3 of the experiment. The rhEGF group and no rhEGF group had reduced food intake until day 5 of the experiment, and then the mice demonstrated increased food intake after day 13 of the of experiment. When the histological examination was conducted on day 7 after treatment with cisplatin and radiation, the rhEGF group showed a focal cellular reaction in the epidermal layer of the mucosa, while the no rhEGF group did not show inflammation of the oral mucosa. CONCLUSION: These findings suggest that rhEGF has a potential to reduce the oral mucositis burden in mice after treatment with cisplatin and radiation. The optimal dose, number and timing of the administration of rhEGF require further investigation.
Animals ; Body Weight ; Cisplatin* ; Eating ; Epidermal Growth Factor* ; Head ; Humans* ; Inflammation ; Mice* ; Mice, Inbred ICR ; Mouth Mucosa ; Mucositis ; Mucous Membrane ; Neck ; Radiotherapy* ; Stomatitis*

BACKGROUND: Many patients with "cold hands/feet syndrome" have been taking herbal medicine or medicine to improve blood circulation without proven evidence. Raynaud's disease had been neglected in primary care. This study was conducted to investigate the recognition for Raynaud's disease and "cold hands/feet syndrome" by family doctors. METHODS: A questionnaire was posted to 905 family doctors who were in practice from January to July 2003. RESULTS: Among the 274 respondents, 58 (21%) reported that they have seen patients with "sensitive to cold" frequently and 208 (76%) doctors have seen such patients sometimes. Only 8 (3%) doctors answered that they have never seen patients with such symptoms. When such patients see a doctor and complain of "cold hands/feet syndrome", most doctors (60%) prescribed medicine that improved blood circulation (83%) or calcium channel blockers (9%). In case of questions like 'Do you suspect "cold hands/feet syndrome" or "sensitive to cold" contain Raynaud's disease?', 132 (48%) doctors answered 'yes'. And among the 132 doctors, only 15 (11.2%) doctors thought that those patients with "cold hands/feet syndrome" had Raynaud's disease. In addition when the doctors diagnosed the condition as Raynaud's disease, 54% prescribed medicine that improved blood circulation (52%) or calcium channel blockers (40%). CONCLUSION: Most doctors prescribe medicine that improves blood circulation for cold hands/feet syndrome. Many doctors also prescribe medicine to improve blood circulation for Raynaud's disease frequently. The result of our study suggests that there is a need to train doctors so that recognized and diagnosed Raynaud's disease can be correctly.
Blood Circulation ; Calcium Channel Blockers ; Surveys and Questionnaires ; Herbal Medicine ; Humans ; Primary Health Care ; Raynaud Disease*

BACKGROUND: Many patients with "cold hands/feet syndrome" have been taking herbal medicine or medicine to improve blood circulation without proven evidence. Raynaud's disease had been neglected in primary care. This study was conducted to investigate the recognition for Raynaud's disease and "cold hands/feet syndrome" by family doctors. METHODS: A questionnaire was posted to 905 family doctors who were in practice from January to July 2003. RESULTS: Among the 274 respondents, 58 (21%) reported that they have seen patients with "sensitive to cold" frequently and 208 (76%) doctors have seen such patients sometimes. Only 8 (3%) doctors answered that they have never seen patients with such symptoms. When such patients see a doctor and complain of "cold hands/feet syndrome", most doctors (60%) prescribed medicine that improved blood circulation (83%) or calcium channel blockers (9%). In case of questions like 'Do you suspect "cold hands/feet syndrome" or "sensitive to cold" contain Raynaud's disease?', 132 (48%) doctors answered 'yes'. And among the 132 doctors, only 15 (11.2%) doctors thought that those patients with "cold hands/feet syndrome" had Raynaud's disease. In addition when the doctors diagnosed the condition as Raynaud's disease, 54% prescribed medicine that improved blood circulation (52%) or calcium channel blockers (40%). CONCLUSION: Most doctors prescribe medicine that improves blood circulation for cold hands/feet syndrome. Many doctors also prescribe medicine to improve blood circulation for Raynaud's disease frequently. The result of our study suggests that there is a need to train doctors so that recognized and diagnosed Raynaud's disease can be correctly.
Blood Circulation ; Calcium Channel Blockers ; Surveys and Questionnaires ; Herbal Medicine ; Humans ; Primary Health Care ; Raynaud Disease*

Although anti-aging activities of melatonin, a hormone secreted by the pineal gland, have been reported in senescence-accelerated mouse models and several types of cells, its impact and mechanism on the senescence of human dental pulp cells (HDPCs) remains unknown. In this study, we examined the impact of melatonin on cellular premature senescence of HDPCs. Here, we found that melatonin markedly inhibited senescent characteristics of HDPCs after exposure to hydrogen peroxide (H₂O₂), including the increase in senescence-associated β-galactosidase (SA-β-gal)-positive HDPCs and the upregulation of p21 protein, an indicator for senescence. In addition, as melatonin attenuated H₂O₂-stimulated phosphorylation of c-Jun N-terminal kinase (JNK), while selective inhibition of JNK activity with SP600125 significantly attenuated H₂O₂-induced increase in SA-beta-gal activity. Results reveal that melatonin antagonizes premature senescence of HDPCs via JNK pathway. Thus, melatonin may have therapeutic potential to prevent stress-induced premature senescence, possibly correlated with development of dental pulp diseases, and to maintain oral health across the life span.
Aging* ; Animals ; Dental Pulp Diseases ; Dental Pulp* ; Humans* ; Hydrogen Peroxide ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Signaling System ; Melatonin* ; Mice ; Oral Health ; Phosphorylation ; Pineal Gland ; Up-Regulation

Fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to evaluate the effects of dopamine cntdot HCl on the range of the rotatioanl mobility of bulk bilayer structure of the synaptosomal plasma membrane vesicles (SPMV) isolated from whole bovine brain. In a dose-dependent manner, dopamine decreased the anisotropy (gamma), limiting anisotropy (gammainfin) and order parameter (S) of DPH in the membranes. These indicate that dopamine increased the rotational mobility of the probe in the neuronal membranes. Cationic 1-(4-(trimethylammonio)-phenyl)-6-phenylhexa-1,3,5-hexatriene (TMA-DPH) and anionic 3-(p-(6-phenyl)-1,3,5-hexatrienyl)-phenylpropionic acid (PRO-DPH) were utilized to examine the range of transbilayer asymmetric rotational mobility of the neuronal membranes. Dopamine had a greater increasing effect on the mobility of the inner monolayer as compared to the outer monolayer of the neuronal membranes. It has been proven that dopamine exhibits a selective rather than nonselective fluidizing effect within the transbilayer domains of the SPMV.
Anisotropy ; Brain* ; Cell Membrane* ; Diphenylhexatriene ; Dopamine* ; Fluorescence Polarization ; Membranes ; Neurons ; Plasma*

Using fluorescence polarization of 12-(9-anthroyloxy)stearic acid (12-AS) and 2-(9-anthroyloxy)stearic acid (2-AS), we evaluated the differential effects of local anesthetics on differential rotational rate between the surface (in carbon number 2 and its surroundings including the head group) and the hydrocarbon interior (in carbon number 12 and its surroundings) of the outer monolayer of the total lipid fraction liposome extracted from synaptosomal plasma membrane vesicles. The anisotropy (r) values for the hydrocarbon interior and the surface region of the liposome outer monolayer were 0.078+/-0.001 and 0.114+/-0.001, respectively. This means that the rate of rotational mobility in the hydrocarbon interior is faster than that of the surface region. In a dose-dependent manner, the local anesthetics decreased the anisotropy of 12-AS in the hydrocarbon interior of the liposome outer monolayer but increased the anisotropy of 2-AS in the surface region of the monolayer. These results indicate that local anesthetics have significant disordering effects on the hydrocarbon interior but have significant ordering effects on the surface region of the liposome outer monolayer.
Anesthetics, Local* ; Anisotropy ; Carbon ; Cell Membrane ; Fluorescence Polarization ; Head ; Liposomes ; Membranes*

To elucidate the molecular mechanism of pharmacological action of local anesthetics, we studied membrane actions of tetracaine, bupivacaine, lidocaine, prilocaine and procaine. Fluorescence polarization of n- (9-anthroyloxy) stearic acid (n-AS) was used to examine the effects of these local anesthetics on differential rotational mobility of different positions of the number of synaptosomal plasma membrane vesicle (SPMV) phospholipid carbon atoms. The four membrane components differed with respect to 3, 6, 9 and 16- (9-anthroyloxy) stearic acid (3-AS, 6-AS, 9-AS and 16-AP) probes, indicating that differences in the membrane fluidity might be present. Degrees of the rotational mobility of 3-AS, 6-AS, 9-AS and 16-AP were different depending on depth of hydrocarbon interior. In a dose-dependent manner, tetracaine, bupivacaine, lidocaine, prilocaine and procaine decreased anisotropy of 3-AS, 6-AS, 9-AS and 16-AP in the hydrocarbon interior of the SPMV. These results indicate that local anesthetics have significant disordering effects on hydrocarbon interior of the SPMV, thus affecting the transport of Na+ and K+ in nerve membranes and leading to anesthetic action.
Anesthetics, Local* ; Anisotropy ; Bupivacaine ; Carbon ; Cell Membrane ; Fluorescence Polarization ; Lidocaine ; Membrane Fluidity ; Membranes* ; Neurons* ; Prilocaine ; Procaine ; Tetracaine

In order to provide a basis for studying the molecular mechanism of pharmacological action of local anesthetics and to develop a fluorescence spectroscopic method which can detect the microviscosity of native and model membranes using intramolecular excimerization of 1,3-di(l-pyrenyl)propane (Py-3-Py), we examined the effect of lidocaine cntdot HCl on the microviscosity of model membranes of phosphatidylcholine fraction extracted from synaptosomal plasma membrane vesicles (SPMVPC). The excimer to monomer fluorescence intensity ratio (I'/I) of Py-3-Py in liquid paraffin was a simple linear function of T/eta. Based on this calibration curve, the microviscosity values of the direct probe environment in SPMVPC model membranes ranged from 234.97 +/- 48.85 cP at 4degreeC to 19.21 +/- 1.11 cP at 45degreeC. At 37degreeC, a value of 27.25 +/- 0.44 cP was obtained. The lidocaine cntdot HCl decreased the microviscosity of SPMVPC model membranes in a concentration-dependent manner, with a significant decrease in microviscosity value by injecting the local anesthetic even at the concentration of 0.5 mM. These results indicate that the direct environment by Py-3-Py in the SPMVPC model membranes is significantly fluidized by the lidocaine cntdot HCl. Also, the present study explicitly shows that an interaction between local anesthetics and membrane lipids is of importance in the molecular mechanism of pharmacological action of lidocaine cntdot HCl.
Anesthetics, Local ; Calibration ; Cell Membrane ; Fluorescence ; Lidocaine* ; Membrane Lipids ; Membranes* ; Mineral Oil ; Phosphatidylcholines*

Very little research has been carried out on safflower seed for the prevention and treatment of the bone deficiency diseases, including osteoporosis, which are supported by scientific evidences. In the present study, 3microliter of 0.1% dried crude extract or 2microliter of 0.1% dried aqueous fraction were shown to significantly accelerate the rate of differentiation of osteoblast. Also, the crude extract and aqueous fraction increased the [Ca2+]i of the cultured osteoblast cells: 3microliter of 0.1% dried crude extract and 2microliter of 0.1% dried aqueous fraction significantly increased the [Ca2+]i of the cultured osteoblast cells (8x104) to the extent that it deserves a considerable attention. Furthermore, the crude extract and aqueous fraction increased the [Ca2+]i of the cultured osteoblast cells, and 300microM Cd2+, specific calcium channel blocker, completely blocked the increase. Therefore, the increased [Ca2+]i of the cultured osteoblast cells by safflower seed component continued to activate calcium channel.
Calcium Channels ; Calcium* ; Carthamus tinctorius* ; Deficiency Diseases ; Osteoblasts* ; Osteoporosis