ABSTRACT
BACKGROUND@#Autophagy plays important roles in odontogenic differentiation of dental pulp cells (DPCs) in the developmental stage of tooth bud. Few studies have reported the role of autophagy during reparative dentin formation process. The objective of this study was to discover gene expression pattern correlated to autophagy and their role during odontogenic differentiation process in DPCs. @*METHODS@#After tooth cavities were prepared on the mesial surface of lower first molar crown of rats. Odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining. @*RESULTS@#After tooth cavities were prepared on the mesial surface of lower first molar crown of rats, odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining and dentin sialophosphoprotein (DSPP), whereas autophagy inhibitor 3-methyladenine (3MA) reversed. @*Results@#of quantitative polymerized chain reaction array of autophagosome formation related genes revealed that GABARAPL2 was prominently upregulated while expression of other ATG8 family members were moderately increased after tooth cavity preparation. In addition, human DPCs incubated in differentiation medium predominantly upregulated MAP1LC3C, which selectively decreased by 3MA but not by autophagy enhancer trehalose. Knock-down of MAP1LC3C using shRNA resulted in strong downregulation of dentin matrix protein 1 and DSPP as well-known odontogenic marker compared to knock-down of MAP1LC3B during odontogenic differentiation process of human DPCs. @*CONCLUSION@#Our results suggest that MAP1LC3C plays a crucial role in odontogenic differentiation of human DPCs via regulating autophagic flux.
ABSTRACT
Associations between periodontal infection and cardiovascular disease have been documented. Porphyromonas gingivalis is a well-established periodontal pathogen, and tissue factor (TF) is a key initiator of the coagulation cascade. In this context, P. gingivalis has been reported to enhance TF expression in human endothelial cells. The present study investigated the underlying mechanisms of TF induction by P. gingivalis in human umbilical vein endothelial cells. P. gingivalis increased TF expression in a dose- and time-dependent manner. Not only live bacteria but also glutaraldehyde-fixed bacteria increased TF expression to the same extent. However, sonicates of P. gingivalis did not induce TF expression. Cytochalasin D and SMIFH2, which are inhibitors of actin polymerization and actin nucleation, respectively, inhibited the TF expression induced by P. gingivalis. Finally, TF production was decreased or increased in the presence of various signaling inhibitors, including mitogen-activated protein kinases. These results suggest that P. gingivalis induces endothelial TF expression by a bacterial internalization-dependent mechanism and through diverse signal transduction mechanisms.
ABSTRACT
Associations between periodontal infection and cardiovascular disease have been documented. Porphyromonas gingivalis is a well-established periodontal pathogen, and tissue factor (TF) is a key initiator of the coagulation cascade. In this context, P. gingivalis has been reported to enhance TF expression in human endothelial cells. The present study investigated the underlying mechanisms of TF induction by P. gingivalis in human umbilical vein endothelial cells. P. gingivalis increased TF expression in a dose- and time-dependent manner. Not only live bacteria but also glutaraldehyde-fixed bacteria increased TF expression to the same extent. However, sonicates of P. gingivalis did not induce TF expression. Cytochalasin D and SMIFH2, which are inhibitors of actin polymerization and actin nucleation, respectively, inhibited the TF expression induced by P. gingivalis. Finally, TF production was decreased or increased in the presence of various signaling inhibitors, including mitogen-activated protein kinases. These results suggest that P. gingivalis induces endothelial TF expression by a bacterial internalization-dependent mechanism and through diverse signal transduction mechanisms.
ABSTRACT
BACKGROUND@#Autophagy plays important roles in odontogenic differentiation of dental pulp cells (DPCs) in the developmental stage of tooth bud. Few studies have reported the role of autophagy during reparative dentin formation process. The objective of this study was to discover gene expression pattern correlated to autophagy and their role during odontogenic differentiation process in DPCs. @*METHODS@#After tooth cavities were prepared on the mesial surface of lower first molar crown of rats. Odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining. @*RESULTS@#After tooth cavities were prepared on the mesial surface of lower first molar crown of rats, odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining and dentin sialophosphoprotein (DSPP), whereas autophagy inhibitor 3-methyladenine (3MA) reversed. @*Results@#of quantitative polymerized chain reaction array of autophagosome formation related genes revealed that GABARAPL2 was prominently upregulated while expression of other ATG8 family members were moderately increased after tooth cavity preparation. In addition, human DPCs incubated in differentiation medium predominantly upregulated MAP1LC3C, which selectively decreased by 3MA but not by autophagy enhancer trehalose. Knock-down of MAP1LC3C using shRNA resulted in strong downregulation of dentin matrix protein 1 and DSPP as well-known odontogenic marker compared to knock-down of MAP1LC3B during odontogenic differentiation process of human DPCs. @*CONCLUSION@#Our results suggest that MAP1LC3C plays a crucial role in odontogenic differentiation of human DPCs via regulating autophagic flux.
ABSTRACT
L-ascorbic acid (L-AA; vitamin C) induces apoptosis in cancer cells. This study aimed to elucidate the molecular mechanisms of L-AA-induced apoptosis in human laryngeal epidermoid carcinoma Hep-2 cells. L-AA suppressed the viability of Hep-2 cells and induced apoptosis, as shown by the cleavage and condensation of nuclear chromatin and increased number of Annexin V-positive cells. L-AA decreased Bcl-2 protein expression but upregulated Bax protein levels. In addition, cytochrome c release from the mitochondria into the cytosol and activation of caspase-9, -8, and -3 were enhanced by L-AA treatment. Furthermore, apoptosis-inducing factor (AIF) and endonuclease G (EndoG) were translocated into the nucleus during apoptosis of L-AA-treated Hep-2 cells. L-AA effectively inhibited the constitutive nuclear factor-κB (NF-κB) activation and attenuated the nuclear expression of the p65 subunit of NF-κB. Interestingly, L-AA treatment of Hep-2 cells markedly activated Akt and mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase [JNK]) and and LY294002 (Akt inhibitor), SB203580 (p38 inhibitor) or SP600125 (a JNK inhibitor) decreased the levels of Annexin V-positive cells. These results suggested that L-AA induces the apoptosis of Hep-2 cells via the nuclear translocation of AIF and EndoG by modulating the Bcl- 2 family and MAPK/Akt signaling pathways.
ABSTRACT
Green tea polyphenol (–)-epigallocatechin-3-gallate (EGCG) is a potent antioxidant with protective effects against neurotoxicity. However, it is currently unclear whether EGCG protects neuronal cells against radiation-induced damage. Therefore, the objective of this study was to investigate the effects of EGCG on ultraviolet (UV)-induced oxidative stress and apoptosis in PC12 cells. The effects of UV irradiation included apoptotic cell death, which was associated with DNA fragmentation, reactive oxygen species (ROS) production, enhanced caspase-3 and caspase-9 activity, and poly (ADP-ribose) polymerase cleavage. UV irradiation also increased the Bax/Bcl-2 ratio and mitochondrial pathway-associated cytochrome c expression. However, pretreatment with EGCG before UV exposure markedly decreased UV-induced DNA fragmentation and ROS production. Furthermore, the UV irradiationinduced increase in Bax/Bcl-2 ratio, cytochrome c upregulation, and caspase-3 and caspase-9 activation were each ameliorated by EGCG pretreatment. Additionally, EGCG suppressed UV-induced phosphorylation of p38 and rescued UV-downregulated phosphorylation of ERK. Taken together, these results suggest that EGCG prevents UV irradiationinduced apoptosis in PC12 cells by scavenging ROS and inhibiting the mitochondrial pathways known to play a crucial role in apoptosis. In addition, EGCG inhibits UV-induced apoptosis via JNK inactivation and ERK activation in PC12 cells. Thus, EGCG represents a potential neuroprotective agent that could be applied to prevent neuronal cell death induced by UV irradiation.
ABSTRACT
L-ascorbic acid (L-AA; vitamin C) induces apoptosis in cancer cells. This study aimed to elucidate the molecular mechanisms of L-AA-induced apoptosis in human laryngeal epidermoid carcinoma Hep-2 cells. L-AA suppressed the viability of Hep-2 cells and induced apoptosis, as shown by the cleavage and condensation of nuclear chromatin and increased number of Annexin V-positive cells. L-AA decreased Bcl-2 protein expression but upregulated Bax protein levels. In addition, cytochrome c release from the mitochondria into the cytosol and activation of caspase-9, -8, and -3 were enhanced by L-AA treatment. Furthermore, apoptosis-inducing factor (AIF) and endonuclease G (EndoG) were translocated into the nucleus during apoptosis of L-AA-treated Hep-2 cells. L-AA effectively inhibited the constitutive nuclear factor-κB (NF-κB) activation and attenuated the nuclear expression of the p65 subunit of NF-κB. Interestingly, L-AA treatment of Hep-2 cells markedly activated Akt and mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase [JNK]) and and LY294002 (Akt inhibitor), SB203580 (p38 inhibitor) or SP600125 (a JNK inhibitor) decreased the levels of Annexin V-positive cells. These results suggested that L-AA induces the apoptosis of Hep-2 cells via the nuclear translocation of AIF and EndoG by modulating the Bcl- 2 family and MAPK/Akt signaling pathways.
ABSTRACT
Green tea polyphenol (–)-epigallocatechin-3-gallate (EGCG) is a potent antioxidant with protective effects against neurotoxicity. However, it is currently unclear whether EGCG protects neuronal cells against radiation-induced damage. Therefore, the objective of this study was to investigate the effects of EGCG on ultraviolet (UV)-induced oxidative stress and apoptosis in PC12 cells. The effects of UV irradiation included apoptotic cell death, which was associated with DNA fragmentation, reactive oxygen species (ROS) production, enhanced caspase-3 and caspase-9 activity, and poly (ADP-ribose) polymerase cleavage. UV irradiation also increased the Bax/Bcl-2 ratio and mitochondrial pathway-associated cytochrome c expression. However, pretreatment with EGCG before UV exposure markedly decreased UV-induced DNA fragmentation and ROS production. Furthermore, the UV irradiationinduced increase in Bax/Bcl-2 ratio, cytochrome c upregulation, and caspase-3 and caspase-9 activation were each ameliorated by EGCG pretreatment. Additionally, EGCG suppressed UV-induced phosphorylation of p38 and rescued UV-downregulated phosphorylation of ERK. Taken together, these results suggest that EGCG prevents UV irradiationinduced apoptosis in PC12 cells by scavenging ROS and inhibiting the mitochondrial pathways known to play a crucial role in apoptosis. In addition, EGCG inhibits UV-induced apoptosis via JNK inactivation and ERK activation in PC12 cells. Thus, EGCG represents a potential neuroprotective agent that could be applied to prevent neuronal cell death induced by UV irradiation.
ABSTRACT
The subgranular zone (SGZ) of hippocampal dentate gyrus (HDG) is a primary site of adult neurogenesis. Toll-like receptors (TLRs), are involved in neural system development of Drosophila and innate immune response of mammals. TLR2 is expressed abundantly in neurogenic niches such as adult mammalian hippocampus. It regulates adult hippocampal neurogenesis. However, the role of TLR2 in adult neurogenesis is not well studied in global or focal cerebral ischemia. Therefore, this study aimed to investigate the role of TLR2 in adult neurogenesis after photochemically induced cerebral ischemia. At 7 days after photothrombotic ischemic injury, the number of bromodeoxyuridine (BrdU)-positive cells was increased in both TLR2 knock-out (KO) mice and wild-type (WT) mice. However, the increment rate of BrdU-positive cells was lower in TLR2 KO mice compared to that in WT mice. The number of doublecortin (DCX) and neuronal nuclei (NeuN)-positive cells in HDG was decreased after photothrombotic ischemia in TLR2 KO mice compared to that in WT mice. The survival rate of cells in HDG was decreased in TLR2 KO mice compared to that in WT mice. In contrast, the number of cleaved-caspase 3 (apoptotic marker) and the number of GFAP (glia marker)/BrdU double-positive cells in TLR2 KO mice were higher than that in WT mice. These results suggest that TLR2 can promote adult neurogenesis from neural stem cell of hippocampal dentate gyrus through increasing proliferation, differentiation, and survival from neural stem cells after ischemic injury of the brain.
Subject(s)
Adult , Animals , Humans , Mice , Brain , Brain Ischemia , Bromodeoxyuridine , Dentate Gyrus , Drosophila , Hippocampus , Immunity, Innate , Ischemia , Mammals , Neural Stem Cells , Neurogenesis , Neurons , Survival Rate , Toll-Like Receptor 2 , Toll-Like ReceptorsABSTRACT
Adult hippocampal dentate granule neurons are generated from neural stem cells (NSCs) in the mammalian brain, and the fate specification of adult NSCs is precisely controlled by the local niches and environment, such as the subventricular zone (SVZ), dentate gyrus (DG), and Toll-like receptors (TLRs). Epigallocatechin-3-gallate (EGCG) is the main polyphenolic flavonoid in green tea that has neuroprotective activities, but there is no clear understanding of the role of EGCG in adult neurogenesis in the DG after neuroinflammation. Here, we investigate the effect and the mechanism of EGCG on adult neurogenesis impaired by lipopolysaccharides (LPS). LPS-induced neuroinflammation inhibited adult neurogenesis by suppressing the proliferation and differentiation of neural stem cells in the DG, which was indicated by the decreased number of Bromodeoxyuridine (BrdU)-, Doublecortin (DCX)- and Neuronal Nuclei (NeuN)-positive cells. In addition, microglia were recruited with activatingTLR4-NF-kappaB signaling in the adult hippocampus by LPS injection. Treating LPS-injured mice with EGCG restored the proliferation and differentiation of NSCs in the DG, which were decreased by LPS, and EGCG treatment also ameliorated the apoptosis of NSCs. Moreover, pro-inflammatory cytokine production induced by LPS was attenuated by EGCG treatment through modulating the TLR4-NF-kappaB pathway. These results illustrate that EGCG has a beneficial effect on impaired adult neurogenesis caused by LPSinduced neuroinflammation, and it may be applicable as a therapeutic agent against neurodegenerative disorders caused by inflammation.
Subject(s)
Adult , Animals , Humans , Mice , Apoptosis , Brain , Bromodeoxyuridine , Dentate Gyrus , Hippocampus , Inflammation , Lipopolysaccharides , Microglia , Neural Stem Cells , Neurodegenerative Diseases , Neurogenesis , Neurons , Tea , Toll-Like ReceptorsABSTRACT
Nitric oxide (NO) is important in the regulation of bone remodeling, whereas high concentration of NO promotes cell death of osteoblast. However, it is not clear yet whether NO-induced autophagy is implicated in cell death or survival of osteoblast. The present study is aimed to examine the role of NO-induced autophagy in the MC3T3-E1 cells and their underlying molecular mechanism. The effect of sodium nitroprusside (SNP), an NO donor, on the cytotoxicity of the MC3T3-E1 cells was determined by MTT assay and expression of apoptosis or autophagy associated molecules was evaluated by western blot analysis. The morphological observation of autophagy and apoptosis by acridine orange stain and TUNEL assay were performed, respectively. Treatment of SNP decreased the cell viability of the MC3T3-E1 cells in dose- and time-dependent manner. SNP increased expression levels of p62, ATG7, Beclin-1 and LC3-II, as typical autophagic markers and augmented acidic autophagolysosomal vacuoles, detected by acridine orange staining. However, pretreatment with 3-methyladenine (3MA), the specific inhibitor for autophagy, decreased cell viability, whereas increased the cleavage of PARP and caspase-3 in the SNP-treated MC3T3-E1 cells. AMP-activated protein kinase (AMPK), a major autophagy regulatory kinase, was activated in SNP-treated MC3T3-E1 cells. In addition, pretreatment with compound C, an inhibitor of AMPK, decreased cell viability, whereas increased the number of apoptotic cells, cleaved PARP and caspase-3 levels compared to those of SNP-treated MC3T3-E1 cells. Taken together, it is speculated that NO-induced autophagy functions as a survival mechanism via AMPK activation against apoptosis in the MC3T3-E1 cells.
Subject(s)
Humans , Acridine Orange , AMP-Activated Protein Kinases , Apoptosis , Autophagy , Blotting, Western , Bone Remodeling , Caspase 3 , Cell Death , Cell Survival , Cytoprotection , In Situ Nick-End Labeling , Nitric Oxide , Nitroprusside , Osteoblasts , Phosphotransferases , Tissue Donors , VacuolesABSTRACT
Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory responses. NO is produced by nitric oxide synthase (NOS), and NOS is abundantly expressed in the human dental pulp cells (HDPCs). NO produced by NOS can be cytotoxic at higher concentrations to HDPCs. However, the mechanism by which this cytotoxic pathway is activated in cells exposed to NO is not known. The purpose of this study was to elucidate the NO-induced cytotoxic mechanism in HDPCs. Sodium nitroprusside (SNP), a NO donor, reduced the viability of HDPCs in a dose- and time-dependent manner. We investigated the in vitro effects of nitric oxide on apoptosis of cultured HDPCs. Cells showed typical apoptotic morphology after exposure to SNP. Besides, the number of Annexin V positive cells was increased among the SNP-treated HDPCs. SNP enhanced the production of reactive oxygen species (ROS), and N-acetylcysteine (NAC) ameliorated the decrement of cell viability induced by SNP. However, a soluble guanylate cyclase inhibitor (ODQ) did not inhibited the decrement of cell viability induced by SNP. SNP increased cytochrome c release from the mitochondria to the cytosol and the ratio of Bax/Bcl-2 expression levels. Moreover, SNP-treated HDPCs elevated activities of caspase-3 and caspase-9. While pretreatment with inhibitors of caspase (z-VAD-fmk, z-DEVD-fmk) reversed the NO-induced apoptosis of HDPCs. From these results, it can be suggested that NO induces apoptosis of HDPCs through the mitochondria-dependent pathway mediated by ROS and Bcl-2 family, but not by the cyclic GMP pathway.
Subject(s)
Humans , Acetylcysteine , Annexin A5 , Apoptosis , Caspase 3 , Caspase 9 , Cell Survival , Cyclic GMP , Cytochromes c , Cytosol , Dental Pulp , Guanylate Cyclase , Mitochondria , Nitric Oxide , Nitric Oxide Synthase , Nitroprusside , Reactive Oxygen Species , Tissue DonorsABSTRACT
The purpose of this study is to evaluate salivary flow rate, salivary pH, and cariogenic activity using unstimulated saliva of the head and neck cancer patients. Twenty three cancer patients (19 males, 4 females) who had undergone chemotherapy and radiation therapy and twenty four healthy volunteers (14 males, 10 females) as a control were included. Salivary flow rate, salivary pH, and cariogenic activity using unstimulated saliva were examined. Compared to saliva of the control group, salivary flow rate (p<0.001) and salivary pH (p<0.001) were significantly lower in head and neck cancer patients. The colony counts of Lactobacilli was higher in head and neck cancer patients (p<0.05) than in control group. These salivary factors and cariogenic activity can increase the prevalence of dental caries in head and neck cancer patients.
Subject(s)
Humans , Male , Dental Caries , Drug Therapy , Head and Neck Neoplasms , Healthy Volunteers , Hydrogen-Ion Concentration , Prevalence , SalivaABSTRACT
Common variable immunodeficiency (CVID) is the most common symptomatic primary antibody deficiency syndrome and has a high prevalence of gastrointestinal complications. We report the case of a 36-year-old male with CVID who presented with chronic intractable diarrhea and malabsorption. A comprehensive evaluation revealed no secondary causes of his symptoms. He was treated symptomatically without improvement. After receiving systemic steroid treatment, his symptoms improved, but returned soon after tapering the steroid. When he was subsequently administered oral budesonide, his symptoms and quality of life improved; this effect lasted for 20 months without unacceptable side effects.
Subject(s)
Adult , Humans , Male , Budesonide , Common Variable Immunodeficiency , Diarrhea , Immunologic Deficiency Syndromes , Prevalence , Quality of LifeABSTRACT
BACKGROUND: Arterial stiffness is an important factor in atherosclerosis. Thus we examined whether aerobic exercise could reduce arterial stiffness in obese women with type 2 diabetes without diabetic complication. METHODS: A total of 35 women with type 2 diabetes (body mass index, 26.6+/-2.8 kg/m2; age, 56.4+/-1.9 years; duration of diabetes, 4.7+/-4.8 years) were assigned to aerobic exercise group (AEG) or control group (CG). AEG completed a 12-week exercise program (3.6 to 5.2 metabolic equivalents, 3 day/week, 60 min/day), with their exercise activities monitored by accelerometers. We measured abdominal total fat area (TFA), visceral fat area (VFA), and subcutaneous fat area (SFA) by computed tomography, insulin sensitivity by insulin tolerance test (K(ITT)), and augmentation index (AIx) by SphygmoCor at baseline and at the end of the 12-week program. RESULTS: The AIx was improved in the AEG compared with the CG (P<0.001). The percent change of AIx had significant correlation with the improvement of physical activity energy expenditure (PAEE), aerobic capacity, TFA, and SFA (r=-0.416, P=0.013; r=0.560, P<0.001; r=0.489, P=0.003; r=0.531, P=0.001, respectively), but not with insulin sensitivity, energy intake, or VFA. CONCLUSION: Improvement in aortic stiffness by aerobic exercise is related with the improvement of aerobic capacity, PAEE, and total fat but not with insulin sensitivity or energy intake in obese women with type 2 diabetes.
Subject(s)
Female , Humans , Abdominal Fat , Atherosclerosis , Diabetes Complications , Diabetes Mellitus, Type 2 , Energy Intake , Energy Metabolism , Exercise , Insulin , Insulin Resistance , Intra-Abdominal Fat , Metabolic Equivalent , Motor Activity , Subcutaneous Fat , Vascular StiffnessABSTRACT
Various voltage-gated K+ currents were recently described in dorsal root ganglion (DRG) neurons. However, the characterization and diversity of voltage-gated K+ currents have not been well studied in trigeminal root ganglion (TRG) neurons, which are similar to the DRG neurons in terms of physiological roles and anatomy. This study was aimed to investigate the characteristics and diversity of voltage-gated K+ currents in acutely isolated TRG neurons of rat using whole cell patch clamp techniques. The first type (type I) had a rapid, transient outward current (I(A)) with the largest current size having a slow inactivation rate and a sustained delayed rectifier outward current (I(K)) that was small in size having a fast inactivation rate. The I(A) currents of this type were mostly blocked by TEA and 4-AP, K channel blockers whereas the I(K) current was inhibited by TEA but not by 4-AP. The second type had a large I(A) current with a slow inactivation rate and a medium size-sustained delayed IK current with a slow inactivation rate. In this second type (type II), the sensitivities of the I(A) or I(K) current by TEA and 4-AP were similar to those of the type I. The third type (type III) had a medium sized I(A) current with a fast inactivation rate and a large sustained I(K) current with the slow inactivation rate. In type III current, TEA decreased both I(A) and I(K) but 4-AP only blocked I(A) current. The fourth type (type IV) had a smallest I(A) with a fast inactivation rate and a large IK current with a slow inactivation rate. TEA or 4-AP similarly decreased the I(A) but the I(K) was only blocked by 4-AP. These findings suggest that at least four different voltage-gated K+ currents in biophysical and pharmacological properties exist in the TRG neurons of rats.
Subject(s)
Animals , Rats , Diagnosis-Related Groups , Ganglia, Spinal , Ganglion Cysts , Neurons , Patch-Clamp Techniques , Potassium , TeaABSTRACT
The purpose of this study is to investigate the antinociceptive effects of ginsenosides on toothache. c-Fos immunoreactive (IR) neurons were examined after noxious intrapulpal stimulation (NS) by intrapulpal injection of 2 M KCl into upper and lower incisor pulps exposed by bone cutter in Sprague Dawley rats. The number of Fos-IR neurons was increased in the trigeminal subnucleus caudalis (Vc) and the transitional region between Vc and subnucleus interpolaris (Vi) by NS to tooth. The intradental NS raised arterial blood pressure (BP) and heart rate (HR). The number of Fos-IR neurons was also enhanced in thalamic ventral posteromedial nucleus (VPMN) and centrolateral nucleus (CLN) by NS to tooth. The intradental NS increased the number of Fos-IR neurons in the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM), hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN), central cardiovascular regulation centers. Ginsenosides reduced the number of c-Fos-IR increased by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Naloxone, an opioid antagonist, did not block the effect of ginsenoside on the number of Fos-IR neurons enhanced by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Ginsenosides ameliorated arterial BP and HR raised by NS to tooth and reduced the number of Fos-IR neurons increased by NS to tooth in the NTS, RVLM, hypothalamic SON, and PVN. These results suggest that ginsenosides have an antinociceptive effect on toothache through non-opioid system and attenuates BP and HR increased by NS to tooth.
Subject(s)
Animals , Rats , Arterial Pressure , Brain , Ginsenosides , Heart Rate , Incisor , Naloxone , Neurons , Paraventricular Hypothalamic Nucleus , Rats, Sprague-Dawley , Solitary Nucleus , Supraoptic Nucleus , Tooth , Toothache , Ventral Thalamic NucleiABSTRACT
BACKGROUND: We investigated the effects of exercise intensity on abdominal and mid-thigh adipose tissue, attenuation of skeletal muscle, and insulin sensitivity in overweight women with type 2 diabetes mellitus (T2DM). METHODS: Twenty-eight patients were randomly assigned to control (CG, n=12), moderate intensity exercise (MEG, n=8), or vigorous intensity exercise (VEG, n=8) group. Subjects in both exercise groups completed a 12-week exercise program (MEG, 3.6 to 5.2 METs; VEG, > or =5.2 METs) that was monitored by accelerometers. We assessed body mass index (BMI), total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), mid-thigh intramuscular adipose tissue (TIMAT), total skeletal muscle (TTM), low density skeletal muscle (TLDM), and normal density skeletal muscle (TNDM) using computed tomography, and measured insulin sensitivity with an insulin tolerance test (KITT), before and after the intervention. RESULTS: At baseline, the mean age was 53.8+/-7.9 years, duration of diabetes was 3.8+/-2.3 years, and BMI was 26.6+/-2.6 kg/m2. After 12 weeks, the percent change (%C) in BMI, TIMAT, and TLDM were not different among three groups. However, %C in TFA and VFA were significantly reduced in MEG compared to CG (P=0.026 and P=0.008, respectively). %C SFA was significantly reduced in VEG compared to CG (P=0.038) and %C TTM, TNDM, and KITT were significantly increased in VEG compared to the CG (P=0.044, P=0.007, and P=0.016, respectively). CONCLUSION: Although there was no difference in the change in BMI among groups, TFA and VFA were more reduced in MEG, and only VEG increased TTM, TNDM, and insulin sensitivity compared to CG.
Subject(s)
Female , Humans , Abdominal Fat , Adipose Tissue , Body Mass Index , Diabetes Mellitus, Type 2 , Exercise , Insulin , Insulin Resistance , Intra-Abdominal Fat , Muscle, Skeletal , Overweight , Subcutaneous Fat , ThighABSTRACT
BACKGROUND: The purpose of this study was to evaluate the usefulness of an accelerometer in predicting body weight (BW) change during a lifestyle intervention and to find out whether exercise or overall physical activity is associated with change in insulin sensitivity and body composition. METHODS: A total of 49 overweight (body mass index [BMI] > or = 23 kg/m2) women with diabetes were enrolled and performed lifestyle intervention while monitoring BW, total energy expenditure (TEE) and physical activity energy expenditure (PAEE) using an accelerometer, and energy intake (EI) using a three-day dietary record at baseline and every 2 weeks for 12 weeks. We assessed body composition using bioimpedance analysis and compared the actual BW change to the predicted BW change, which was calculated from the energy deficit (ED) between EI and TEE (ED = EI-TEE). RESULTS: Mean age was 57.2 years, duration of diabetes was 8.0 years, and BMI was 27.8 kg/m2. There was no significant difference between EI and TEE at baseline. For 12 weeks, the ED was 474.0 kcal.day-1, which was significantly correlated with BW change (-3.1 kg) (r = 0.725, P < 0.001). However, the actual BW change was 50% lower than the predicted BW change. Both TEE and PAEE correlated with change in KITT (r = 0.334, P = 0.019; r = 0.358, P = 0.012, respectively), BMI (r = -0.395, P = 0.005; r = -0.347, P = 0.015, respectively), and fat mass (r = -0.383, P = 0.007; r = -0.395, P = 0.005, respectively), but only TEE correlated with fat free mass change (r = -0.314, P = 0.030). CONCLUSION: The accelerometer appears to be a useful tool for measuring TEE under free-living conditions for both short- and long-term periods.
Subject(s)
Female , Humans , Body Composition , Body Weight , Body Weight Changes , Diet Records , Energy Intake , Energy Metabolism , Insulin Resistance , Life Style , Motor Activity , OverweightABSTRACT
Understanding the genetic control of tooth eruption is one of the major issues in tooth development. Thus far, it is known that eruption-related molecules are secreted from follicular cells surrounding the germs and are related mainly to osteoclast formation. This study examined the involvement of CD147 and its downstream molecules in the eruption of rat developing molars using immunohistochemistry, RT-PCR and histomorphometry. CD147 was expressed differentially in the cap (3rd molar germs) and root formation (2nd molar germs) stages in tooth development. CD147 was localized immunohistochemically in the follicular cells and osteoclasts as well as in the ameloblasts and odontoblasts. The expression pattern of CD147 and mmps was investigated because CD147 is an mmp inducer. The expression of both mmp-2 and -9 increased at the root formation stage compared to that at the cap stage and increased in a stage dependent manner. However, the level of mmp-13 was not changed notably. The histomorphometrical study suggested that the number of osteoclasts that appeared occlusal to the molar germs for the resorption of alveolar bone increased significantly during development. These results suggest that CD147 may play an important role in the formation of the eruption pathway along with the mmps.