Background: The primary aims of periodontal disease treatment is to remove dental plaque and calculus, the main causes of tooth loss, and restore periodontal tissue destroyed by inflammation. Periodontal disease treatment should also help maintain the alveolar bone, alleviate inflammation, and promote periodontal ligament cell proliferation, which is essential for tissue regeneration. Conventional antibiotics and anti-inflammatories have adverse side effects, especially during long-term use, so there is a need for adjunct treatment agents derived from natural products. The purpose of this study was to investigate whether the herbal flavone baicalein has the osteogenic activity under inflammatory conditions, and assess the involvement of osteoblast immediate early response 3 (IER3) expression. Methods: Human osteoblastic MG-63 cells were cultured with the pro-inflammatory cytokines tumor necrosis factor α and interleukin 1β in the presence and absence of baicalein. Proliferation was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and expression of IER3 mRNA was assessed using real-time polymerase chain reaction. The expression of IER3 protein levels and activation of associated signal transduction pathways were assessed using western blotting. Results: Baicalein increased IER3 mRNA and protein expression synergistically. In addition, baicalein reversed the suppression of cell proliferation, and the downregulation of osteogenic transcription factor runt-related transcription factor 2 and osterix induced by pro-inflammatory cytokines. Baicalein also upregulated the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK 1/2). The upregulation of IER3 by pro-inflammatory cytokines was blocked by pretreatment with inhibitors of AKT, p38, JNK, and ERK 1/2. Conclusion: Baicalein mitigates the deleterious responses of osteoblasts to pro-inflammatory cytokines. Further, IER3 enhanced the effect of baicalein via activation of AKT, p38, JNK, and ERK pathways.
Objectives : In this study, the roles of Interleukin (IL)-4 and Signal transducer and activator of transcription 6 (STAT6), which have been reported to play a role in the pathogenesis of inflammation and cancer, were evaluated in snake venom toxin (SVT)-induced apoptosis. Methods : Inflammation was induced in human HaCaT kerationocytes, by lipopolysaccharide (LPS; $1{\mu}g/mL$) or tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), followed by treatment with SVT (0, 1, or $2{\mu}g/mL$). Cell viability was assessed by MTT assays after 24 h, and the expression of levels of IL-4, STAT6, and the apoptosis-related proteins p53, Bax, and Bcl-2 were evaluated by western blotting. Electro mobility shift assays (EMSAs) were performed to evaluate the DNA binding capacity of STAT6. Results : MTT assays showed that inflammation-induced growth of HaCaT cells following LPS or TNF-${\alpha}$ stimulation was inhibited by SVT. Western blot analysis showed that p53 and Bax, which promote apoptosis, were increased, whereas that of Bcl-2, an anti-apoptotic protein, was decreased in a concentration-dependent manner in LPS- or TNF-${\alpha}$-induced HaCaT cells following treatment with SVT. Moreover, following treatment of HaCaT cells with LPS, IL-4 concentrations were increased, and treatment with SVT further increased IL-4 expression in a concentration-dependent manner. Western blotting and EMSAs showed that the phosphorylated form of STAT6 was increased in HaCaT cells in the context of LPS- or TNF-${\alpha}$-induced inflammation in a concentration-dependent manner, concomitant with an increase in the DNA binding activity of STAT6. Conclusion : SVT can effectively promote apoptosis in HaCaT cells in the presence of inflammation through a pathway involving IL-4 and STAT6.
Cha, Seung Keun;Kim, Se Hyun;Ha, Kyooseob;Shin, Soon Young;Kang, Ung Gu
Korean Journal of Biological Psychiatry
/
v.20
no.4
/
pp.159-165
/
2013
Objectives Mechanisms of clinical synergistic effects, induced by co-treatments of lithium and valproate, are unclear. Extracellular signal-regulated kinase (ERK) has been suggested to play important roles in mechanisms of the action of mood stabilizers. In this study, effects of co-treatments of lithium and valproate on the ERK1/2 signal pathway and its down-stream transcription factors, ELK1 and C-FOS, were investigated in vitro. Methods PC12 cells, human pheochromocytoma cells, were treated with lithium chloride (30 mM), valproate (1 mM) or lithium chloride + valproate. The phosphorylation of ERK1/2 was analyzed with immunoblot analysis. Transcriptional activities of ELK1 and C-FOS were analyzed with reporter gene assay. Results Single treatment of lithium and valproate increased the phosphorylation of ERK and transcriptional activities of ELK1 and C-FOS, respectively. Combined treatments of lithium and valproate induced more robust increase in the phosphorylation of ERK1/2 and transcriptional activities of ELK1 and C-FOS, compared to those in response to single treatment of lithium or valproate. Conclusions Co-treatments of lithium and valproate induced synergistic increase in the phosphorylation of ERK1/2 and transcriptional activities of its down-stream transcription factors, ELK1 and C-FOS, compared to effects of single treatment. The findings might suggest potentiating effects of lithium and valproate augmentation treatment strategy.
Objective: This study was performed to investigate the effect of acupuncture at HT8 on brain activity in perimenopausal women using fMRI. Methods: 15 healthy perimenopausal women volunteered in the study. No stimulation, sham stimulation, duration of acupuncture treatment on HT8, and rotation of acupuncture treatment on HT8 were randomly given for 6 minutes, with 20 seconds' intervals. Results: 1. In comparison with sham stimulation(Sham-B) and duration of acupucture (S1-B, S1-Sham, S2-S1), the areas of fMRI signal activation areas were just like cases including no stimulation. But the areas of vision were activated in S1-Sham. 2. In comparison with duration of acupuncture(S1-B, S1-Sham, S2-S1) and rotation of acupuncture(S2-B, S2-Sham, S2-S1), the areas of vision were activated in duration of acupuncture, and Supplementary motor area(SMA) were especially activated in rotation of acupuncture. Conclusions: After using fMRI and analysing effect of acupuncture treatment at HT8, we could confirm that fMRI signal activation areas by acupuncture treatment at HT8 were different from areas by sham stimulation. And according to acupuncture stimulation methods with duration and rotation, etc, we could confirm the specific reactions of series, and could get useful basic data for research of acupuncture from now on.
Although statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have been shown to increase melanin synthesis, the exact mechanism of this action is not fully understood. In this study we investigated the possible involvement of intracellular $Ca^{2+}$ signal in the mechanism of stimulation of melanin synthesis induced by lovastatin in B16 cells. Lovastatin stimulated the production of melanin in a dose-dependent manner in the cells. Treatment with mevalonate, FPP and GGPP, precursors of cholesterol, did not significantly suppress the lovastatin-induced melanin production, suggesting that inhibition of cholesterol synthesis may not be involved in the mechanism of the action of lovastatin. In addition, lovastatin did not significantly alter the cAMP concentration and the stimulated production of melanin by lovastatin was not significantly changed by treatment with H89, a potent inhibitor of protein kinase A, which demonstrates that cAMP pathway may not be involved. However, lovastatin increased intracellular $Ca^{2+}$ concentration in a dose-related fashion. Treatment with EGTA, an extracellular $Ca^{2+}$ chelator did not significantly alter the lovastatin-induced intracellular $Ca^{2+}$ increase and melanin synthesis, whereas intracellular $Ca^{2+}$ reduction with BAPTA/AM and intracellular $Ca^{2+}$ release blockers (dantrolene and TMB-8) completely blunted these actions of lovastatin. Taken together, these results suggest that the intracellular $Ca^{2+}$ release may play an important role in the lovastatin-induced stimulation of melanin synthesis in B16 cells. These results further suggest that lovastatin may be useful for the treatment of hypopigmentation disorders, such as vitiligo.
Signalized intersections are operated without a signal preemption control strategy in Korea, thus there is no priority treatment for an emergency vehicle passing through the intersections. In this paper, a signal preemption control strategy is introduced to improve the safety and operational efficiency of an emergency vehicle. Using the micro simulation tool, the effects on delay and travel speed of the signal preemption control strategy are analyzed for various traffic conditions to identify the general performance trends. Then, another simulation analysis is performed to verify the feasibility of the control strategy using real network data collected from field study. Results show that the preemption control strategy provides the positive impact on emergency vehicles' operation, but the positive impact is reduced as the v/c ratios increase. As expected, the average delays of the normal vehicles are slightly increased, but the magnitude is not significant. Therefore, it is expected that the introduction of the preemption control strategy in Korea would produce the positive social benefits.
Journal of the Institute of Convergence Signal Processing
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v.22
no.2
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pp.45-50
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2021
With the recent development of IT technology, research and interest in various bio-signal measuring devices are increasing. But studies related to ECG(electrocardiogram), which is one of the most representative bio-signals, particularly arrhythmic signal detection, are incomplete. Since arrhythmia has various causes and has a poor prognosis after onset, preventive treatment through early diagnosis is best. However, the 24-hour Holter electrocardiogram, a tool for diagnosing arrhythmia, has disadvantages in the limitation of use time, difficulty in analyzing motion artifact due to daily life, and the user's real-time alarm function in danger. In this study, an ECG and pulse monitoring device capable of continuous measurement for a long time, a real-time monitoring app, and software for analysis were developed, and the trend of the measured values was confirmed. In future studies, research on derivation of quantitative results of ECG signal measurement analysis is required, and further research on the development of an arrhythmic signal detection algorithm based on this is required.
Background: The purpose of this study was to evaluate the usefulness of diffusion-weighted magnetic resonance imaging for monitoring the response to radiation therapy in metastatic bone marrow of the spines. Materials and Methods: Twenty-one patients with metastatic bone marrow of the spines were examined with MRI. Diffusion-weighted and spin-echo MRI were performed in 10 patients before and after radiation therapy with or without systemic chemotherapy, and performed in 11 patients after radiation therapy alone. Follow up spin-echo and diffusion-weighted MRI were obtained at 1 to 6 months after radiation therapy according to patients' condition. The diffusion-weighted imaging sequence was based on reversed fast imaging with steady-state precession (PSIF). Signal intensity changes of the metastatic bone marrows before and after radiation therapy on conventional spin-echo sequence MRI and diffusion-weighted MRI were evaluated. Bone marrow contrast ratios and signal-to-noise ratios before and after radiation therapy of diffusion- weighted MRI were analyzed. Results: All metastatic bone marrow of the spinal bodies were hyperintense to normal bone marrow of the spinal bodies on pretreatment diffusion-weighted MRI and positive bone marrow contrast ratios(p<0.001), and hypointense to normal spinal bodies on posttreatment diffusion-weighted MRI and negative bone marrow contrast ratios(p<0.001). The signal to noise ratios after treatment decreased comparing with those of pretreatment. Decreased signal intensity of the metastatic bone marrows on diffusion-weighted MRI began to be observed at average more than one month after the initiation of the radiation therapy. Conclusion: These results suggest that diffusion-weighted MRI would be an excellent method for monitoring the response to therapy of metastatic bone marrow of the spinal bodies, however, must be investigated in a larger series of patients with longer follow up period.
Kim Jong-Hoon;Lee Byung-Hwan;Jeong Sang Min;Nah Seung-Yeol
Journal of Ginseng Research
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v.29
no.1
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pp.37-43
/
2005
We performed in vitro and in vivo studies to know whether the inhibitory effects of ginsenosides on $5-HT_{3A}$ receptor channel acctivity are coupled to anti-nausea and anti-vomiting action. In vitro study, we investigated the effect of compound K (CK) and M4, which are ginsenoside metabolites, on human $5-HT_{3A}$ receptor channel activity expressed in Xenopus oocytes using two-electrode voltage clamp technique. Treatment of CK or M4 themselves had no effect in both oocytes injected with $H_2O\;and\;5-HT_{3A}$ receptor cRNA. In oocytes injected with $5- HT_{3A}$ receptor cRNA, M4 treatment inhibited more potently 5-HT-induced inward peak current $(I_{5-HT})$ than CK with dose-dependent and reversible manner. The half-inhibitory concentrations $(IC_{50})$ of CK and M4 were $36.9\;\pm\;10.1\;and\;7.3\;\pm\;2.2\;{\mu}M$, respectively. The inhibition of $I_{5-HT}$ by M4 was non-competitive and voltage-independent. These results indicate that M4 might regulate $5-HT_{3A}$ receptors. In vivo experiments, injection of cisplatin (7.5 mg/kg, i.v.) induced both nausea and vomiting with 1 h latency. These episodes reached to peak after 2 h and persisted for 4 h. Pre-treatment of GTS (500 mg/kg, p.o.) significantly reduced cisplatin-induced nausea and vomiting by $51\;\pm\;8.4\;and\;48.8\;\pm\;6.4\%$ during 4 h compared to GISuntreated group, respectively. These results show the possibility that in vitro inhibition of $5-HT_{3A}$ receptor channel activity by ginsenosides might be coupled to in vivo anti-emetic activity.
Perioperative treatment with conventional cytotoxic chemotherapy for resectable non-small cell lung cancer (NSCLC) has proven clinical benefits in terms of achieving a higher overall survival (OS) rate. With its success in the palliative treatment of NSCLC, immune checkpoint blockade (ICB) has now become an essential component of treatment, even as neoadjuvant or adjuvant therapy in patients with operable NSCLC. Both pre- and post-surgery ICB applications have proven clinical efficacy in preventing disease recurrence. In addition, neoadjuvant ICB combined with cytotoxic chemotherapy has shown a significantly higher rate of pathologic regression of viable tumors compared with cytotoxic chemotherapy alone. To confirm this, an early signal of OS benefit has been shown in a selected population, with programmed death ligand 1 expression ≥50%. Furthermore, applying ICB both pre- and post-surgery enhances its clinical benefits, as is currently under evaluation in ongoing phase III trials. Simultaneously, as the number of available perioperative treatment options increases, the variables to be considered for making treatment decisions become more complex. Thus, the role of a multidisciplinary team-based treatment approach has not been fully emphasized. This review presents up-to-date pivotal data that lead to practical changes in managing resectable NSCLC. From the medical oncologist's perspective, it is time to dance with surgeons to decide on the sequence of systemic treatment, particularly the ICB-based approach, accompanying surgery for operable NSCLC.
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