Capric Acid Inhibits NO Production and STAT3 Activation during LPS-Induced Osteoclastogenesis

Capric acid is a second medium-chain fatty acid, and recent studies have shown that fatty acids are associated with bone density and reduce bone turnover. In this study, we investigated the effects of capric acid on lipopolysaccharide (LPS)-induced osteoclastogenesis in RAW264.7 cells. After treatment with capric acid (1 mM), the number of tartrate resistant acid phosphatase (TRAP)-positive cells decreased significantly. Capric acid reduced LPS-induced TRAP expression, an osteoclast differentiation marker, without inhibiting cell viability. LPS strongly upregulated inducible nitric oxide synthase (iNOS) mRNA levels and nitric oxide (NO) production, whereas capric acid inhibited them. Furthermore, capric acid also inhibited monocyte chemoattractant protein-1 (MCP-1) mRNA expression. Subsequently, we investigated various intracellular signaling proteins, including nuclear factor-κB (NF-κB), c-Jun-N-terminal kinase (JNK), extracellular signal regulated kinase 1/2 (ERK1/2), and signal transducer and activator of transcription 1 (STAT1) and STAT3 associated with osteoclastogenesis. Capric acid had no effects on LPS-induced activation of the NF-κB, JNK, ERK1/2, and STAT1 pathways. However, capric acid inhibited LPS-induced phosphorylation of Ser727 in STAT3. Additionally, stattic (a STAT3 inhibitor) inhibited LPS-induced iNOS and MCP-1 gene expression. In conclusion, we demonstrated that capric acid inhibited LPS-induced osteoclastogenesis by suppressing NO production via the STAT3 pathway. These results suggest that capric acid has important therapeutic implications for treating bone diseases associated with excessive osteoclastogenesis

Combined Treatment of an Intratumoral Injection of Dendritic Cells and Systemic Chemotherapy (Paclitaxel) for Murine Fibrosarcoma

A novel combined treatment of conventional chemotherapy with an intratumoral injection of syngeneic dendritic cells (DCs) has emerged as a potent cancer treatment strategy. In this study, we evaluated the synergistic effect of an intraperitoneal (i.p.) injection of a chemotherapeutic drug, paclitaxel, and an intratumoral (i.t.) injection of syngeneic bone marrow-derived DCs for the treatment of pre-existing fibrosarcoma. Subcutaneous tumors were established using MCA102 fibrosarcoma cells in syngeneic C57BL/6 mice. The results demonstrated that the combined treatment of paclitaxel chemotherapy and the injection of DCs led to complete tumor regression, in contrast to only partial eradication of the tumors with chemotherapy or DCs alone. Furthermore, the tumor-free mice were able to resist a repeat challenge with the same type of tumor. These findings suggest that a combination therapy of systemic chemotherapy along with the intratumoral administration of DCs is a potent treatment strategy for fibrosarcoma

Diode Laser—Can It Replace the Electrical Current Used in Endoscopic Submucosal Dissection?

Background/Aims A new medical fiber-guided diode laser system (FDLS) is expected to offer high-precision cutting with simultaneous hemostasis. Thus, this study aimed to evaluate the feasibility of using the 1,940-nm FDLS to perform endoscopic submucosal dissection (ESD) in the gastrointestinal tract of an animal model. Methods In this prospective animal pilot study, gastric and colorectal ESD using the FDLS was performed in ex vivo and in vivo porcine models. The completeness of en bloc resection, the procedure time, intraprocedural bleeding, histological injuries to the muscularis propria (MP) layer, and perforation were assessed. Results The en bloc resection and perforation rates in the ex vivo study were 100% (10/10) and 10% (1/10), respectively; those in the in vivo study were 100% (4/4) and 0% for gastric ESD and 100% (4/4) and 25% (1/4) for rectal ESD, respectively. Deep MP layer injuries tended to occur more frequently in the rectal than in the gastric ESD cases, and no intraprocedural bleeding occurred in either group. Conclusions The 1,940-nm FDLS was capable of yielding high en bloc resection rates without intraprocedural bleeding during gastric and colorectal ESD in animal models

Study on changes in electrical and switching characteristics of NPT-IGBT devices by fast neutron irradiation

We studied the irradiation effects of fast neutron generated by a 30 MeV cyclotron on the electrical and switching characteristics of NPT-IGBT devices. Fast neutron fluence ranges from 2.7 × 109 to 1.82 × 1013 n/cm2. Electrical characteristics of the IGBT device such as I–V, forward voltage drop and additionally switching characteristics of turn-on and -off were measured. As the neutron fluence increased, the device's threshold voltage decreased, the forward voltage drop increased significantly, and the turn-on and turn-off time became faster. In particular, the delay time of turn-on switching was improved by about 35% to a maximum of about 39.68 ns, and that of turn-off switching was also reduced by about 40%–84.89 ns, showing a faster switching

Effects of gamma irradiation on the electrical characteristics of trench-gate non-punch-through insulated gate bipolar transistor

We studied the effects of gamma-ray irradiation on the static and dynamic electrical characteristics of a trench-gate non-punch-through insulated gate bipolar transistor (IGBT) device. The threshold voltage and breakdown voltage decreased after irradiation, whereas the collector leakage current increased. Turn-on and turn-off switching times decreased and increased, respectively, with the irradiation dose. The irradiation-induced changes in the electrical characteristics can be attributed to the buildup of the positive oxide-trapped charges in the gate oxide by gamma irradiation. The evaluated characteristics data were compared with the data for gamma-irradiated planar-gate IGBTs reported in the literature. It was found that a significant degradation occurred in the shift of the threshold voltage and switching times for trench-gate IGBTs

Performance evaluation of a beta-spectrometer comprising a plastic scintillator and multi-wire chamber using a coincidence method

This paper describes an experimental setup developed to measure the beta-ray energy spectrum as well as a Geant4 simulation study conducted to characterize the properties of a beta-spectrometer. The beta-spectrometer comprises a multi-wire chamber to generate signals to indicate the incidence of beta rays and a plastic scintillation detector to measure its energy. The coincidence method of the detector signals was used to remove high gamma-ray interference. To evaluate the performance of the developed spectrometer, the energy spectra were measured with the radionuclide sources (Cs-137 and Bi-207) emitting internal conversion electrons and gamma rays. The gamma-ray interference removal rate of the spectrometer using the coincidence method was 99.12 +/- 0.09%. To reconstruct the beta spectrum from the measured spectrum, Monte Carlo simulations using the Geant4 toolkit were performed to calculate the coefficient related to the effect of gamma rays. The obtained spectrum confirmed that the energy resolution and intrinsic internal conversion peak detection efficiency of the beta-spectrometer were 10.2% at 1 MeV and 91.6%, respectively

On-the-fly Estimation Strategy for Uncertainty Propagation in Two-Step Monte Carlo Calculation for Residual Radiation Analysis

AbstractIn analyzing residual radiation, researchers generally use a two-step Monte Carlo (MC) simulation. The first step (MC1) simulates neutron transport, and the second step (MC2) transports the decay photons emitted from the activated materials. In this process, the stochastic uncertainty estimated by the MC2 appears only as a final result, but it is underestimated because the stochastic error generated in MC1 cannot be directly included in MC2. Hence, estimating the true stochastic uncertainty requires quantifying the propagation degree of the stochastic error in MC1. The brute force technique is a straightforward method to estimate the true uncertainty. However, it is a costly method to obtain reliable results. Another method, called the adjoint-based method, can reduce the computational time needed to evaluate the true uncertainty; however, there are limitations. To address those limitations, we propose a new strategy to estimate uncertainty propagation without any additional calculations in two-step MC simulations. To verify the proposed method, we applied it to activation benchmark problems and compared the results with those of previous methods. The results show that the proposed method increases the applicability and user-friendliness preserving accuracy in quantifying uncertainty propagation. We expect that the proposed strategy will contribute to efficient and accurate two-step MC calculations