Explore the vast range of titles available.

We investigated the radiation-quality-dependent bystander cellular effects using heavy-ion microbeams with different ion species. The heavy-ion microbeams were produced in Takasaki Ion Accelerators for Advanced Radiation Application, National Institutes for Quantum Science and Technology. Carbon (12C5+, 220 MeV), neon (20Ne7+, 260 MeV) and argon (40Ar13+, 460 MeV) ions were used as the microbeams, collimating the beam size with a diameter of 20 μm. After 0.5 and 3 h of irradiation, the surviving fractions (SFs) are significantly lower in cells irradiated with carbon ions without a gap-junction inhibitor than those irradiated with the inhibitor. However, the same SFs with no cell killing were found with and without the inhibitor at 24 h. Conversely, no cell-killing effect was observed in argon-ion-irradiated cells at 0.5 and 3 h; however, significantly low SFs were found at 24 h with and without the inhibitor, and the effect was suppressed using vitamin C and not dimethyl sulfoxide. The mutation frequency (MF) in cells irradiated with carbon ions was 8- to 6-fold higher than that in the unirradiated control at 0.5 and 3 h; however, no mutation was observed in cells treated with the gap-junction inhibitor. At 24 h, the MFs induced by each ion source were 3- to 5-fold higher and the same with and without the inhibitor. These findings suggest that the bystander cellular effects depend on the biological endpoints, ion species and time after microbeam irradiations with different pathways.

Drug-induced pseudoaldosteronism is a typical adverse effect of Kampo formulas. Previous research described the potential risks of Kampo formula-linked pseudoaldosteronism. However, few studies assessed the risk factors using a real-world database and a data-mining approach. Using the Japanese Adverse Drug Event Report database, we extracted pseudoaldosteronism reports for 148 Kampo formulas covered by Japanese national health insurance. Adverse events were decided according to the preferred terminology of the Medical Dictionary for Regulatory Activities/Japanese version 25.1. We calculated reporting odds ratio (RORs) and identified Kampo formulas as suspected causes of pseudoaldosteronism. Moreover, we evaluated clinical factors associated with Kampo formula-induced pseudoaldosteronism via logistic regression. From April 2004 to November 2022, 6334 adverse events related to the Kampo formulas were reported. We selected 2471 reports containing complete clinical data, including 210 reports on pseudoaldosteronism. In the pseudoaldosteronism group, 69.0% of patients were female, and 85.2% were ≥70 years old. The formulas most commonly associated with pseudoaldosteronism were Shakuyakukanzoto, Yokukansan, and Ryokeijutsukanto (ROR [95% confidence interval CI] = 18.3 [13.0–25.9], 8.1 [5.4–12.0], and 5.5 [1.4–21.9], respectively). Logistic analysis identified female sex (odds ratio [OR] [95% CI] = 1.7 [1.2–2.6]; P = 0.006), older age (≥70, 5.0 [3.2–7.8]; P < 0.001), low body weight (<50 kg, 2.2 [1.5–3.2]; P < 0.001), diuretics usage (2.1 [1.3–4.8]; P = 0.004), hypertension (1.6 [1.1–2.4]; P = 0.014), and dementia (7.0 [4.2–11.6]; P < 0.001) as pseudoaldosteronism-related factors. Additionally, the daily Glycyrrhiza dose (OR = 2.1 [1.9–2.3]; P < 0.001) and duration of administration (>14 days, OR = 2.8 [1.7–4.5]; P < 0.001) were associated with adverse events. We did not observe an interaction between aging and hypertension. Careful follow-up is warranted during long-term Glycyrrhiza-containing Kampo formula use in patients with multiple clinical factors for pseudoaldosteronism.

There are few studies on the relationship between the frequency of acupuncture use and subjective health status. Therefore, we investigated this relationship using data of a previously performed cross-sectional survey of patients visiting Japanese acupuncture clinics. This study used data from a cross-sectional survey conducted in 2011 on patients visiting 180 acupuncture clinics nationwide that were run by members of the alumni association of Meiji University of Integrative Medicine Faculty of Acupuncture and Moxibustion, and did not provide treatment other than acupuncture. We calculated the frequency of visits to acupuncture clinics (< 24 times, 24-47 times, 48-95 times, or ≥ 96 times per year) and the Short Form-36 (SF-36) summary scores (physical, mental, role/social) based on the response of the questionnaire conducted at the time of the survey. Multiple linear regression analysis with multiple imputation was performed with three SF-36 summary scores as the dependent variables, and the frequency of visits to acupuncture clinics as the independent variable. The questionnaire was distributed to 2,379 outpatients of acupuncture clinics, 1,409 of whom met the criteria and were included in the analysis. More frequent visits to acupuncture clinics were associated with lower scores on all three SF-36 summary scores. Compared to those who visited < 24 times a year, those who visited ≥ 96 times a year had unstandardized regression coefficients (95% confidence interval) of -5.6 (-7.8 to -3.3) for the physical, -2.0 (-3.9 to -0.1) for the mental, and -2.9 (-5.4 to -0.4) for the role/social SF-36. Frequent visits to acupuncture clinics were associated with poor subjective health status, especially physical health.

Background DNA damage is generated by various intrinsic and extrinsic sources such as reactive oxygen species (ROS) and environmental mutagens, and causes genomic alterations. DNA damage response (DDR) is activated to induce cell cycle arrest and DNA repair. Oxidation resistance 1 (OXR1) is a protein that defends cells against oxidative stress. We previously reported that OXR1 protein functions in the regulation of G2-phase cell cycle arrest in cells irradiated with gamma-rays, suggesting that OXR1 directly responds to DNA damage. Purpose To clarify the functions of OXR1 against ROS-independent DNA damage, HeLa and OXR1-depleted HeLa cells were treated with heavy-ion beams and the ROS-independent DNA-damaging agent methyl methanesulfonate (MMS). Results First, OXR1-depleted cells exhibited higher sensitivity to MMS and heavy-ion beams than control cells. Next, OXR1 depletion increased micronucleus formation and shortened the duration of G2-phase arrest after treatment with MMS or heavy-ion beams. These results suggest that OXR1 functions in the maintenance of cell survival and genome stability in response to DNA damage. Furthermore, the OXR1 protein level was increased by MMS and heavy-ion beams in HeLa cells. Conclusions Together with our previous study, the present study suggests that OXR1 plays an important role in the response to DNA damage, not only when DNA damage is generated by ROS.

Track-structure Monte Carlo simulations are useful tools to evaluate initial DNA damage induced by irradiation. In the previous study, we have developed a Gean4-DNA-based application to estimate the cell surviving fraction of V79 cells after irradiation, bridging the gap between the initial DNA damage and the DNA rejoining kinetics by means of the two-lesion kinetics (TLK) model. However, since the DNA repair performance depends on cell line, the same model parameters cannot be used for different cell lines. Thus, we extended the Geant4-DNA application with a TLK model for the evaluation of DNA damage repair performance in HSGc-C5 carcinoma cells which are typically used for evaluating proton/carbon radiation treatment effects. For this evaluation, we also performed experimental measurements for cell surviving fractions and DNA rejoining kinetics of the HSGc-C5 cells irradiated by 70 MeV protons at the cyclotron facility at the National Institutes for Quantum and Radiological Science and Technology (QST). Concerning fast- and slow-DNA rejoining, the TLK model parameters were adequately optimized with the simulated initial DNA damage. The optimized DNA rejoining speeds were reasonably agreed with the experimental DNA rejoining speeds. Using the optimized TLK model, the Geant4-DNA simulation is now able to predict cell survival and DNA-rejoining kinetics for HSGc-C5 cells.

Masquelet’s induced membrane technique (MIMT) is widely applied two-step surgery of large bone defects. MIMT involves the fibrous encapsulation of a polymethyl methacrylate cement spacer inserted into the bone defect in the primary surgery. Although the biological characteristics of the fibrous membrane have been studied, the postoperative environment of the bone defect encapsulated with the induced membrane has not been investigated. In this study, critical-sized bone defects encapsulated with the induced membrane were filled with porous calcium-deficient bioresorbable hydroxyapatite granules in the secondary surgery. Single-step non-Masquelet conventional surgery (NMCS) was also performed, and the biological characteristics of the stromal tissues induced around the ceramic granules were compared between the two procedures. Compared with NMCS, the stromal tissue induced in MIMT expressed significantly higher levels of CXCL3, RANKL, BMP-2, and BMP-7. Coculture of the primary osteoblast-like cells with the stromal tissue derived from MIMT significantly stimulated the differentiation of primary osteoblast-like cells compared with that derived from NMCS. When hydroxyapatite granules mixed with bone isografts (50% v/v) were implanted, the amount of newly formed bone was significantly larger in MIMT than in NMCS. These results suggest that MIMT induces mesenchymal stromal cells that support bone metabolism and promote bone regeneration.

Previously reported studies have revealed that the application of a magnetic field longitudinal to a carbon-ion beam enhances its biological effectiveness. Here we investigated how timing of the magnetic field application with respect to beam irradiation influenced this effect. Human cancer cells were exposed to carbon-ion beams with linear energy transfer (LET) of 12 and 50 keV/µm. The longitudinal magnetic field of 0.3 T was applied to the cells just before, during or immediately after the beam irradiation. The effects of the timing on the biological effectiveness were evaluated by cell survival. The biological effectiveness increased only if the magnetic field was applied during beam irradiation for both LETs.

The aim of this study was to investigate whether carbon-ion beam irradiation in combination with 5-fluorouracil (5-FU) is superior to carbon-ion beam irradiation alone in targeting colorectal cancer stem-like cells (CSCs). Human colorectal cancer (CRC) cells, HCT116 and HT29, were treated with carbon-ion beam irradiation alone or in combination with 5-FU. Cell viability assay, colony and spheroid formation assay, apoptotic assay, and quantitative real-time PCR analysis of apoptosis- and autophagy-related gene expression were performed. Carbon-ion beam irradiation dose-dependently decreased CRC cell viability and showed significantly enhanced cell killing effect when combined with 5-FU. Carbon-ion beam irradiation in combination with 5-FU significantly increased the percentage of apoptotic cells. The expression of some apoptotic and autophagy-related genes such as , , and was significantly induced by carbon-ion beam irradiation alone and was further enhanced when the beam was combined with 5-FU. The spheroid forming capacity of CD133+ cell subpopulations was significantly inhibited by carbon-ion beam in combination with 5-FU. Histopathologically, the combination of carbon-ion beam irradiation and 5-FU destroyed more xenograft tumor cells, and resulted in increased necrosis, cavitation, and fibrosis, compared to carbon-ion beam irradiation alone. In conclusion, carbon-ion beam treatment combined with 5-FU has the potential to kill CRC cells including CSCs by inducing increased apoptosis and autophagy.

The study investigated the molecular mechanisms that killed pancreatic cancer cells, including cancer stem cells (CSCs), by carbon ion beam irradiation alone or in combination with miRNA-200c under in vitro and in vivo conditions. Human pancreatic cancer (PC) cells, PANC1 and PK45, were treated with carbon-ion beam irradiation alone or in combination with microRNA-200c (miR-200c) mimic. Cell viability assay, colony and spheroid formation assay, quantitative real-time PCR analysis of apoptosis-, autophagy-, and angiogenesis-related gene expression, xenograft tumor control and histopathological analyses were performed. The cell viability assay showed that transfection of the miRNA-200c (10 nM) mimic into pancreatic CSC (CD44+/ESA+) and non-CSC (CD44-/ESA-) significantly suppressed proliferation of both types of cell populations described above. Combining carbon-ion beam irradiation with the miRNA-200c mimic significantly reduced the colony as well as spheroid formation abilities compared to that observed with the treatment of carbon-ion beam alone or X-ray irradiation combined with the miRNA-200c mimic. Moreover, the combination of carbon ion beam irradiation and miRNA-200c mimic increased the expression of apoptosis-related gene BAX, autophagy-related genes and , addition of gemcitabine (GEM) further enhanced the expression of these genes. In vivo data showed that carbon-ion beam irradiation in combination with the miRNA-200c mimic effectively suppressed xenograft tumor growth and significantly induced tumor necrosis and cavitation. The combination of miRNA-200c mimic and carbon ion beam irradiation may be powerful radiotherapy that significantly kills pancreatic cancer cells containing CSCs and enhances the effect of carbon-ion beam irradiation compared to carbon-ion beam irradiation alone.

Background Acupuncture is known to improve exercise capacity in patients with chronic obstructive pulmonary disease (COPD), but its mechanism remains unknown. Whether acupuncture improves exercise capacity in patients with COPD through alleviation of leg fatigue and dyspnea is examined by applying causal mediation analysis to previous trial data. Methods Sixty-two patients with COPD completed treatments with either real or placebo acupuncture once a week for 12 weeks. Walk distance measured using the 6-minute walk test and intensities of leg fatigue and dyspnea in the modified Borg scale were evaluated at baseline and after treatment. The intervention effect of acupuncture against the placebo acupuncture on two mediators, changes in leg fatigue and dyspnea, and whether they mediated improvements in walk distance, were analyzed. Results Linear regression analysis showed that the unstandardized regression coefficients [95% confidence interval (CI)] for the intervention effect by acupuncture were -4.9 (-5.8–-4.0) in leg fatigue and -3.6 (-4.3–-2.9) in dyspnea. Mediation analysis showed that when changes in leg fatigue were considered as a mediator, direct effect, indirect effect and proportion mediated were 47.1 m (95% CI, 4.6–85.1), 34.3 m (-2.1–82.1), and 42.1%, respectively, and when changes in dyspnea were considered as a mediator, they were 9.8 m (-32.9–49.9), 72.5 m (31.3–121.0), and 88.1%, respectively, and the effects of joint mediator were -5.8 m (-55.4–43.9), 88.9 m (32.7–148.5), and 107.0%, respectively. Conclusion The improvement in exercise capacity by acupuncture is explained by changes in both leg fatigue and dyspnea.