Immunomodulatory Effects of Radon Inhalation on Lipopolysaccharide-Induced Inflammation in Mice

Typical indications for radon therapy include autoimmune diseases such as rheumatoid arthritis (RA). We had previously reported that radon inhalation inhibits Th17 immune responses in RA mice by activating Th1 and Th2 immune responses. However, there are no reports on how radon inhalation affects the activated Th1 and Th17 immune responses, and these findings may be useful for identifying new indications for radon therapy. Therefore, in this study, we investigated the effect of radon inhalation on the lipopolysaccharide (LPS)-induced inflammatory response, focusing on the expression of related cytokines and antioxidant function. Male BALB/c mice were exposed to 2000 Bq/m(3) radon for one day. Immediately after radon inhalation, LPS was administered intraperitoneally at 1.0 mg/kg body weight for 4 h. LPS administration increased the levels of Th1- and Th17-prone cytokines, such as interleukin-2, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor, compared to no treatment control (sham). However, these effects were suppressed by radon inhalation. IL-10 levels were significantly increased by LPS administration, with or without radon inhalation, compared to sham. However, radon inhalation did not inhibit oxidative stress induced by LPS administration. These findings suggest that radon inhalation has immunomodulatory but not antioxidative functions in LPS-induced injury

Effects of low-dose/high-dose-rate X-irradiation on oxidative stress in organs following forced swim test and its combined effects on alcohol-induced liver damage in mice

The liver's susceptibility to oxidative stress after a combination of forced swim test (FST) and low-dose-rate gamma-irradiation has been observed. Therefore, this study aims to clarify the effects of low-dose (0.1 and 0.5 Gy)/high-dose-rate (1.2 Gy/min) irradiation on combined oxidative stressors-liver damage associated with FST and alcohol administration. In addition, the effects of similar irradiation on FST-induced immobility, which induces psychomotor retardation, and antioxidative effects on the brain, lungs, liver and kidneys were investigated, and the results were compared with those of a similar previous study that utilized low-dose-rate irradiation. Low-dose/high-dose-rate (especially 0.5 Gy) irradiation temporarily worsened liver antioxidant function and hepatic function with FST- and alcohol administration-related oxidative damage; however, the damages improved soon after. In addition, the increase in total glutathione content in the liver contributed to the early improvement of hepatic functions. However, pre-irradiation did not suppress immobility during the FST. The results also suggested that the effects of low-dose/high-dose-rate irradiation on the antioxidant functions of each organ after the FST were different from those of low-dose/low-dose-rate irradiation. Overall, this study provides further insights into the effects of low-dose irradiation on exposure to a combination of different oxidative stressors. It will also contribute to the elucidation of dose rate effects on oxidative stress in the low-dose irradiation range

Structure of corrosion product formed on carbon steel covered with NiSO4-Added resin coating under sulfuric acid mist environment containing chloride

Corrosion resistance of carbon steel covered with resin coating containing nickel sulfate has been evaluated under chloride and sulfuric acid mist environment. The structure of corrosion products formed on steel surface was investigated by XRD and XAFS analyses using synchrotron radiation. Nickel sulfate promoted the formation of goethite and akaganeite. It was considered that this akaganeite was not tetragonal β-FeOOH but monoclinic akaganeite containing nickel.Shota Hayashida, Masamitsu Takahashi, Hiroshi Deguchi, Hiroaki Tsuchiya, Koushu Hanaki, Masato Yamashita, Shinji Fujimoto, Structure of Corrosion Product Formed on Carbon Steel Covered with NiSO4-Added Resin Coating under Sulfuric Acid Mist Environment Containing Chloride, Materials Transactions, 2021, Volume 62, Issue 6, Pages 781-787, Released on J-STAGE May 25, 2021, Advance online publication May 14, 2021, Online ISSN 1347-5320, Print ISSN 1345-9678, https://doi.org/10.2320/matertrans.C-M2021819

Development of in-house fully residual deep convolutional neural network-based segmentation software for the male pelvic CT

[Background] This study aimed to (1) develop a fully residual deep convolutional neural network (CNN)-based segmentation software for computed tomography image segmentation of the male pelvic region and (2) demonstrate its efficiency in the male pelvic region. [Methods] A total of 470 prostate cancer patients who had undergone intensity-modulated radiotherapy or volumetric-modulated arc therapy were enrolled. Our model was based on FusionNet, a fully residual deep CNN developed to semantically segment biological images. To develop the CNN-based segmentation software, 450 patients were randomly selected and separated into the training, validation and testing groups (270, 90, and 90 patients, respectively). In Experiment 1, to determine the optimal model, we first assessed the segmentation accuracy according to the size of the training dataset (90, 180, and 270 patients). In Experiment 2, the effect of varying the number of training labels on segmentation accuracy was evaluated. After determining the optimal model, in Experiment 3, the developed software was used on the remaining 20 datasets to assess the segmentation accuracy. The volumetric dice similarity coefficient (DSC) and the 95th-percentile Hausdorff distance (95%HD) were calculated to evaluate the segmentation accuracy for each organ in Experiment 3. [Results] In Experiment 1, the median DSC for the prostate were 0.61 for dataset 1 (90 patients), 0.86 for dataset 2 (180 patients), and 0.86 for dataset 3 (270 patients), respectively. The median DSCs for all the organs increased significantly when the number of training cases increased from 90 to 180 but did not improve upon further increase from 180 to 270. The number of labels applied during training had a little effect on the DSCs in Experiment 2. The optimal model was built by 270 patients and four organs. In Experiment 3, the median of the DSC and the 95%HD values were 0.82 and 3.23 mm for prostate; 0.71 and 3.82 mm for seminal vesicles; 0.89 and 2.65 mm for the rectum; 0.95 and 4.18 mm for the bladder, respectively. [Conclusions] We have developed a CNN-based segmentation software for the male pelvic region and demonstrated that the CNN-based segmentation software is efficient for the male pelvic region

Resveratrol inhibits development of colorectal adenoma via suppression of LEF1; comprehensive analysis with connectivity map

Although many chemopreventive studies on colorectal tumors have been reported, no effective and safe preventive agent is currently available. We searched for candidate preventive compounds against colorectal tumor comprehensively from United States Food and Drug Administration (FDA)-approved compounds by using connectivity map (CMAP) analysis coupled with in vitro screening with colorectal adenoma (CRA) patient-derived organoids (PDOs). We generated CRA-specific gene signatures based on the DNA microarray analysis of CRA and normal epithelial specimens, applied them to CMAP analysis with 1309 FDA-approved compounds, and identified 121 candidate compounds that should cancel the gene signatures. We narrowed them down to 15 compounds, and evaluated their inhibitory effects on the growth of CRA-PDOs in vitro. We finally identified resveratrol, one of the polyphenolic phytochemicals, as a compound showing the strongest inhibitory effect on the growth of CRA-PDOs compared with normal epithelial PDOs. When resveratrol was administered to ApcMin/+ mice at 15 or 30 mg/kg, the number of polyps (adenomas) was significantly reduced in both groups compared with control mice. Similarly, the number of polyps (adenomas) was significantly reduced in azoxymethane-injected rats treated with 10 or 100 mg/resveratrol compared with control rats. Microarray analysis of adenomas from resveratrol-treated rats revealed the highest change (downregulation) in expression of LEF1, a key molecule in the Wnt signaling pathway. Treatment with resveratrol significantly downregulated the Wnt-target gene (MYC) in CRA-PDOs. Our data demonstrated that resveratrol can be the most effective compound for chemoprevention of colorectal tumors, the efficacy of which is mediated through suppression of LEF1 expression in the Wnt signaling pathway

上皮成長因子受容体を標的とした結腸直腸腫瘍の分子イメージング : 動物モデルにおける腫瘍の検出と治療評価

To overcome the problem of overlooking colorectal tumors, a new and highly sensitive modality of colonoscopy is needed. Moreover, it is also important to establish a new modality to evaluate viable tumor volume in primary lesions of colorectal cancer (CRC) during chemotherapy. Therefore, we carried out molecular imaging of colorectal tumors targeting epidermal growth factor receptor (EGFR), which is highly expressed on tumor cells, for evaluating chemotherapeutic efficacy and for endoscopic detection of colorectal adenomas. We first attempted to image five CRC cell lines with various levels of EGFR expression using an Alexa Fluor‐labeled anti‐EGFR monoclonal antibody (AF‐EGFR‐Ab). A strong fluorescence signal was observed in the cells depending on the level of EGFR expression. When nude mice xenografted with LIM1215 CRC cells, which highly express EGFR, were i.v. injected with AF‐EGFR‐Ab, a strong fluorescence signal appeared in the tumor with a high signal to noise ratio, peaking at 48 hours after injection and then gradually decreasing, as shown using an IVIS Spectrum system. When the xenografted mice were treated with 5‐fluorouracil, fluorescence intensity in the tumor decreased in proportion to the viable tumor cell volume. Moreover, when the colorectum of azoxymethane‐treated rats was observed using a thin fluorescent endoscope with AF‐EGFR‐Ab, all 10 small colorectal adenomas (≤3 mm) were detected with a clear fluorescence signal. These preliminary results of animal experiments suggest that EGFR‐targeted fluorescent molecular imaging may be useful for quantitatively evaluating cell viability in CRC during chemotherapy, and also for detecting small adenomas using a fluorescent endoscope

Decorrelation Signal of Diabetic Hyperreflective Foci on Optical Coherence Tomography Angiography

Diabetic hyperreflective foci in the outer retinal layers are a clinically relevant finding on optical coherence tomography (OCT) images, although their characteristics remain to be elucidated. Here we investigated the decorrelation signal around hyperreflective foci on OCT angiography (OCTA) images in diabetic retinopathy (DR). We retrospectively reviewed sufficient quality OCTA images from 102 eyes of 66 patients that were obtained using split-spectrum amplitude-decorrelation angiography algorithm. Most confluent hyperreflective foci were randomly deposited or appeared in a radiating array on the en-face structural OCT images in the inner nuclear layer (INL) or Henle’s fiber layer (HFL), respectively. Within the INL, hyperreflective foci were not accompanied by decorrelation signals and attached to capillaries on OCTA images. Decorrelation signals were sometimes delineated in hyperreflective foci in the HFL and other times appeared to be pseudopod-like or wrapping around hyperreflective foci, referred to as reflectance-decorrelated foci. The decorrelation signal intensity of hyperreflective foci in the HFL was associated with logMAR VA (R = 0.553, P < 0.001) and central subfield thickness (R = 0.408, P < 0.001) but not with DR severity. These data suggest that reflectance-decorrelated foci on OCTA images are clinically relevant as well as shed lights on the properties in diabetic hyperreflective foci