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Objective We aimed to examine the association between respiratory severity score (RSS; mean airway pressure × fraction of inspired oxygen) and neurodevelopmental outcomes in extremely preterm infants. Study Design This was a single-center, retrospective cohort study. We analyzed data from extremely preterm infants who were admitted to the neonatal intensive care unit at Okayama Medical Center between 2010 and 2019. Infants without invasive respiratory management during the first day of life were excluded. The exposure variable was the highest RSS during the first day of life. RSS was categorized into two groups: low (<3.5) and high (≥3.5) RSS. The primary outcome was death or neurodevelopmental impairment at age 3 years, defined as cognitive impairment (developmental quotient <70) or the presence of cerebral palsy. Secondary outcomes were the components of the primary outcome. We conducted robust Poisson regression analyses to investigate the association between RSS category and primary and secondary outcomes, adjusting for perinatal confounders. Results The cohort included 97 infants with neurodevelopmental data, of whom 34 and 63 infants were in the low- and high-RSS categories, respectively. The median (interquartile range) gestational age and birth weight were 26.0 (24.7–26.9) and 25.7 (24.6–26.7) weeks and 761 (584–866) and 806 (618–898) g for infants in the low- and high-RSS categories, respectively. Compared with infants in the low-RSS category, those in the high-RSS category had a greater risk of death or neurodevelopmental impairment at age 3 years (26.3 vs. 42.3%; adjusted risk ratio [RR], 2.0; 95% confidence interval [CI], 1.1–3.5) and neurodevelopmental impairment at age 3 years (17.6 vs. 28.6%; adjusted RR, 2.7; 95% CI, 1.3–5.9). Conclusion High RSS (≥3.5) during the first day of life was associated with an increased risk of neurodevelopmental impairment at age 3 years in extremely preterm infants. Key Points RSS is a valuable tool for assessing respiratory failure. RSS = Mean airway pressure × fraction of inspired oxygen. RSS at age 1 day was associated with neurodevelopment. [ABSTRACT FROM AUTHOR]

Promising outcomes have been reported in elder patients with acute myeloid leukemia (AML) using combined therapy of venetoclax (VEN) and azacytidine (AZA) in recent years. However, approximately one-third of patients appear to be refractory to this therapy. Vitamin K2 (VK2) shows apoptosis-inducing activity in AML cells, and daily oral VK2 (menaquinone-4, GlakayR) has been approved for patients with osteoporosis in Japan. We observed a high response rate to AZA plus VEN therapy, with no 8-week mortality in the newly diagnosed AML patients consuming daily VK2 in our hospital. The median age of the patients was 75.9 years (range 66–84) with high-risk features. Patients received AZA 75 mg/m2 on D1-7, VEN 400 mg on D1-28, and daily VK2 45 mg. The CR/CRi ratio was 94.7% (18/19), with a CR rate of 79%. Complete cytogenetic CR was achieved in 15 of 19 (79%) patients, and MRD negativity in 2 of 15 (13%) evaluable CR patients. Owing to the extremely high response rate in clinical settings, we further attempted to investigate the underlying mechanisms. The combination of VK2 and VEN synergistically induced apoptosis in all five AML cell lines tested. VK2, but not VEN, induced mitochondrial reactive oxygen species (ROS), leading to the transcriptional upregulation of NOXA, followed by MCL-1 repression. ROS scavengers repressed VK2 induced-NOXA expression and led to the cancellation of pronounced apoptosis and the downregulation of MCL-1 by VK2 plus VEN. Additionally, knockdown and knockout of NOXA resulted in abrogation of the MCL-1 repression as well as enhanced cytotoxicity by the two-drug combination, indicating that VK2 suppresses MCL-1 via ROS-mediated NOXA induction. These data suggest that the dual inhibition of BCL-2 by VEN and MCL-1 by VK2 is responsible for the remarkable clinical outcomes in our patients. Therefore, large-scale clinical trials are required. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the influence of reactive oxygen species (i.e., neutral O atom and O 2 + ion) on deposition rates and film thickness uniformity in tetraethoxysilane (TEOS) plasma, utilizing a combination of plasma-fluid dynamic and quantum chemical (QC) simulations. The plasma simulations employed an improved model based on a previous study [H. Li et al., Jpn. J. Appl. Phys. 58, SEED06 (2019)], specifically tailored for a TEOS/O2/Ar/He gas mixture. In the QC simulations, both flat and step silicon oxide (SiO2) surfaces were employed to investigate the adsorption behavior of SiO molecules, the predominant silicon-containing species in TEOS plasma. These simulations also enabled the examination of the rates of SiO molecule adsorption on SiO2 surfaces, facilitating a direct comparison with the sticking coefficients utilized in the plasma simulation. The results of QC simulations revealed that SiO molecules exhibited a higher energetic preference for adsorption on step surfaces than on flat surfaces, resulting in the formation of new SiOH surface sites. Meanwhile, the plasma simulations demonstrated a strong correlation between the deposition rate and film thickness uniformity and the generation of oxygen species, specifically O atoms and O 2 + ions, as well as their respective fluxes. This relationship takes precedence over the influence of TEOS or its fragments colliding with the surface. Notably, higher plasma source frequencies were found to enhance the production of atomic O, which contributed significantly to achieving higher deposition rates. [ABSTRACT FROM AUTHOR]

The relationship among advanced airway management (AAM), ventilation, and oxygenation in patients with out-of-hospital cardiac arrest (OHCA) who achieve prehospital return of spontaneous circulation (ROSC) has not been validated. This study was designed to evaluate ventilation and oxygenation for each AAM technique (supraglottic devices [SGA] or endotracheal intubation [ETI]) using arterial blood gas (ABG) results immediately after hospital arrival. This observational cohort study, using data from the Japanese Association for Acute Medicine OHCA Registry, included patients with OHCA with prehospital and hospital arrival ROSC between July 1, 2014, and December 31, 2019. The primary outcomes were the partial pressure of carbon dioxide in the arterial blood (PaCO2) and partial pressure of oxygen in the arterial blood (PaO2) in the initial ABG at the hospital for each AAM technique (SGA or ETI) performed by paramedics. The secondary outcome was favorable neurological outcome (cerebral performance category [CPC] 1 or 2) for specific PaCO2 levels, which were defined as good ventilation (PaCO2 ≤45 mmHg) and insufficient ventilation (PaCO2 >45 mmHg). This study included 1,527 patients. Regarding AAM, 1,114 and 413 patients were ventilated using SGA and ETI, respectively. The median PaCO2 and PaO2 levels were 74.50 mmHg and 151.35 mmHg in the SGA group, while 66.30 mmHg and 173.50 mmHg in the ETI group. PaCO2 was significantly lower in the ETI group than in the SGA group (12.55 mmHg; 95% CI 15.27 to 8.20, P-value < 0.001), while no significant difference was found in PaO2 by multivariate linear regression analysis. After stabilizing inverse probability of weighting (IPW), the adjusted odds ratio for favorable neurological outcome at 1 month was significant in the good ventilation group compared to the insufficient ventilation cohort (adjusted odds ratio = 2.12, 95%CI: 1.40 to 3.19, P value < 0.001). The study showed that in OHCA patients with prehospital ROSC, the PaCO2 levels in the initial ABG were lower in the group with AAM by ETI than in the SGA group. Furthermore, patients with prehospital ROSC and PaCO2 ≤45 mmHg on arrival had an increased odds of favorable neurological outcome after stabilized IPW adjustment. [ABSTRACT FROM AUTHOR]

Exercise training integrating physical and cognitive activities is gaining attention because of its potential benefits for brain health. This study focuses on exercise training using a dart game called Wellness Darts. Wellness Darts is a sport involving throwing darts and walking to pull them out of the board, memorizing the score, and subtracting this from the total score, thus requiring the simultaneous performance of two tasks: exercise and calculation. This is expected to maintain and improve cognitive function, and whether this continual darts training affects brain function is of great interest. Before conducting the longitudinal study revealing its effect on brain function, we aimed to cross-sectionally confirm the difference in hemispheric lateralization between expert and non-expert players. Functional near-infrared spectroscopy (fNIRS) was used to measure brain activity for three groups: an expert older group who practiced darts continually, a non-expert older control group, and a non-expert younger control group. Their brain activity patterns were quantified by the lateralization index (LI) and compared between groups. The results showed that the younger and the expert older groups had significantly higher LI values than the non-expert older group, and there was no difference between the expert older and the younger groups. Our results suggest that the Wellness Darts game possibly promotes hemispheric lateralization. [ABSTRACT FROM AUTHOR]

Cepharanthine (CEP), a cyclic alkaloid derived from several Stephania genus species, has been widely utilized in Japan since the 1950s to address a range of ailments. CEP is an optically active compound which belongs to the bisbenzylisoquinoline class of alkaloids and is characterized by its non-phenolic nature and solubility in ether. Renowned for its multifaceted pharmacological properties, CEP exhibits an array of beneficial effects, including antioxidative, anti-inflammatory, immunomodulatory, antitumoral, neuroprotective and antiviral actions. Notably, CEP shows promising potential in combating various cancers such as colorectal, breast, lung, prostate, liver cancer. Additionally, CEP has emerged as a compelling candidate among natural compounds under investigation for its capacity to serve as an effective anti-inflammatory agent, displaying positive outcomes both in vitro and in vivo. Consequently, its therapeutic applications in numerous inflammatory diseases hold great promise. This review provides a comprehensive overview of CEP, including its physicochemical properties, pharmacological effects, mechanisms of action, signalling pathways and therapeutic potential in cancer treatment. The effect of combination therapy of CEP with other anticancer agents has also been summarized emphasizing the potential of CEP to overcome drug resistance and radio resistance. Furthermore, this article provides a summary of novel dosage formulations that have been developed for the efficient, safe and convenient delivery of CEP. [ABSTRACT FROM AUTHOR]

Background: Quercus salicina Blume is an evergreen plant growing southern parts of Korea and Japan, and has been used for the treatment of dysentery, dermatitis, and hemorrhage from possible effects such as anti-inflammatory, anti-endemic and litholytic activities. We investigated the underlying mechanisms of Quercus salicina Blume leaf extracts (QS) protection against cadmium treatment utilizing human kidney origin HK-2 cells. Methods: To ascertain the functional constituents of the hot water-extracted QS, we conducted analyses to determine the total phenolic and flavonoid contents. Subsequently, the antioxidant activity was assessed using DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric ion reducing antioxidant power) methods. After treating HK-2 cells with QS and Cd, we confirmed the production of reactive oxygen species (ROS) and the expression of related proteins through western blotting. This investigation aimed to assess the antioxidant and anti-apoptotic effects of QS against cadmium-induced oxidative stress. Results: QS exhibited strong antioxidative potential, since the samples exhibited significantly high DPPH and FRAP values. Upon exposure of HK-2 cells to cadmium, inducing oxidative stress, the application of QS effectively reinstated cellular antioxidative functions, leading to an augmentation in cell viability. Notably, the presence of QS attenuated the heightened expression of oxidative marker enzymes induced by cadmium treatment, including SOD (superoxide dismutase) 1, catalase, Nrf-2, and Heme-oxygenase. The apparent disappearance of the apoptotic bodies indicates a potential apoptosis controlling effect of QS. Furthermore, the considerable increase in sub-G1 phase with the addition of cadmium was diminished under QS treatment indicating the ability of QS to reduce the degree of apoptosis related cell cycle phase. The apoptotic quenching effects of QS were accompanied by the downregulation of pro-apoptotic protein Bax and up-regulation of pro-apoptotic Bcl-2. The examination of cleaved caspase-9 and caspase-3 has provided evidence that the pronounced anti-apoptotic activities observed in cadmiumchallenged HK-2 cells significantly diminished in the presence of QS. Conclusions: QS is a highly effective antioxidant and reduces cell cytotoxicity caused by cadmium through antioxidant functions and anti-apoptotic capabilities. [ABSTRACT FROM AUTHOR]

Pine wilt disease (PWD) is a devastating disease that threatens pine forests worldwide, and breeding resistant pines is an important management strategy used to reduce its impact. A batch of resistant seeds of P. thunbergii was introduced from Japan. Based on the resistant materials, we obtained somatic plants through somatic embryogenesis. In this study, we performed transcriptome analysis to further understand the defense response of resistant somatic plants of P. thunbergii to PWD. The results showed that, after pine wood nematode (PWN) infection, resistant P. thunbergii stimulated more differential expression genes (DEGs) and involved more regulatory pathways than did susceptible P. thunbergii. For the first time, the alpha-linolenic acid metabolism and linoleic acid metabolism were intensively observed in pines resisting PWN infection. The related genes disease resistance protein RPS2 (SUMM2) and pathogenesis-related genes (PR1), as well as reactive oxygen species (ROS)-related genes were significantly up-expressed in order to contribute to protection against PWN inoculation in P. thunbergii. In addition, the diterpenoid biosynthesis pathway was significantly enriched only in resistant P. thunbergii. These findings provided valuable genetic information for future breeding of resistant conifers, and could contribute to the development of new diagnostic tools for early screening of resistant pine seedlings based on specific PWN-tolerance-related markers. [ABSTRACT FROM AUTHOR]

Introduction: Dotinurad is a newer urate-lowering agent that selectively inhibits urate transporter 1 in the renal proximal tubule and increases urinary urate excretion. Currently, little is known about the clinical efficacies of dotinurad in patients with hyperuricemia and hypertension. The aim of this study was to assess the clinical effects of a selective urate reabsorption inhibitor dotinurad on serum uric acid (SUA) levels and relevant vascular markers in patients with hyperuricemia and treated hypertension. Methods: This investigator-initiated, multicenter, prospective, single-arm, open-label, exploratory clinical trial in Japan enrolled patients with hyperuricemia and treated hypertension who received a 24-week dotinurad therapy (a starting dose at 0.5 mg once daily and up-titrated to 2 mg once daily). The primary endpoint was a percentage change in the SUA level from baseline to week 24. The secondary endpoints were cardiovascular and metabolic measurements, including changes in the cardio-ankle vascular index (CAVI) and derivatives of reactive oxygen metabolites (d-ROMs) concentration at week 24. Results: Fifty patients (mean age 70.5 ± 11.0 years, with 76.0% being men, and mean SUA level 8.5 ± 1.2 mg/dL) were included in the analysis. The percentage change from baseline in the SUA level at week 24 was − 35.8% (95% confidence interval [CI] − 39.7% to − 32.0%, P < 0.001), with approximately three quarters of patients achieving an SUA level of ≤ 6.0 mg/dL at week 24. The proportional changes from baseline in the geometric mean of CAVI and d-ROMs at week 24 were 0.96 (95% CI 0.92 to 1.00, P = 0.044) and 0.96 (95% CI 0.92 to 1.00, P = 0.044), respectively. Conclusion: In addition to meaningful SUA-lowering effects, 24 weeks of dotinurad therapy may favorably affect arterial stiffness and oxidative stress markers, suggesting off-target vascular protection of dotinurad. Further research is expected to verify our findings and elucidate the entire off-target effects of dotinurad. Trial registration jRCTs021210013, registration date June 24, 2021 [ABSTRACT FROM AUTHOR]

Iodine-containing formulations have been widely used to treat iodine deficiency and as antiseptics. Lecithin-bound iodine (LBI) has been approved to treat allergic diseases in Japan; however, its underlying mechanism remains unknown. In this study, we show that LBI ameliorated disease symptoms in an ovalbumin (OVA)-induced allergic rhinitis mouse model. LBI suppressed OVA-specific IgE production by attenuating germinal center (GC) reaction in the draining lymph nodes. The antiallergic effect of LBI is most likely attributed to increased serum iodine levels but not thyroid hormone levels. In vitro treatment of activated B cells with potassium iodide induced ferroptosis by increasing intracellular reactive oxygen species (ROS) and ferrous iron in a concentration-dependent manner. Accordingly, LBI diets increased ROS levels in GC B cells of the draining lymph nodes. This study suggests that iodine directly promotes ferroptosis in activated B cells and attenuates GC reactions, leading to the alleviation of allergic symptoms. [ABSTRACT FROM AUTHOR]

To evaluate the dietary antioxidant content of insects, we analyzed the hydrophilic oxygen radical absorbance capacity (H-ORAC) of silkworms (Bombyx mori Linnaeus), and rice grass hoppers (Oxya yezoensis Shiraki), which have been used as edible insects in Japan for many years, and Japanese buff-tip moths, Phalera flavescens (Bremer et Grey), which feed on cherry blossom tree leaves. Among these three insects, the H-ORAC value was highest (7455 ± 185 µmol Trolox eq./100 g FW) in O. yezoensis adults, followed by B. mori pupae (4417.5 ± 270.1), B. mori larvae (4280 ± 189.1), and P. flavescens larvae (4112.5 ± 409.4). The H-ORAC of all three insect species were more than twice those of most fresh vegetables, suggesting high antioxidant potential. [ABSTRACT FROM AUTHOR]

Background: Advanced glycation end products (AGEs) are end products of protein glycation that bind to the receptor for AGEs (RAGE) and activate nicotinamide adenine dinucleotide phosphate oxidase (NOX), resulting in increased oxidative stress and rotator cuff fragility. Stump classification using the signal intensity ratio of the tendon rupture site to the deltoid muscle in the coronal view of T2-weighted fat-suppressed magnetic resonance imaging (MRI) scans is an indicator of clinical outcomes after rotator cuff repair surgery. Comparing the signal intensities of the deltoid (D) and rotator cuff tears (C), Ishitani et al. classified C/D <0.8 as type 1, 0.8 to 1.3 as type 2, and >1.3 as type 3. Hypothesis/Purpose: It was hypothesized that the oxidative stress and collagen degeneration that occur in the rotator cuff due to accumulation of AGEs can be assessed on MRI scans (stump classification). Therefore, this study aimed to compare AGE-related factors in the rotator cuff tear site tissues based on stump classification. Study Design: Descriptive laboratory study. Methods: The authors included 30 patients (11 with type 1, 9 with type 2, and 10 with type 3; mean age, 62.3 years) who underwent surgery for complete rotator cuff tears at our hospital. Tendon tissue was harvested from the torn rotator cuff site during surgery for tissue and cell evaluation. Results: There was no significant difference in the mean age according to stump classification. The number of patients with diabetes was significantly larger in type 3 than in the other types (P <.05). Tissue evaluation showed significantly higher expression of AGE and RAGE staining in type 3 than in the other types (~6.7-fold; P <.01). Cell evaluation showed that the expression rates of reactive oxygen species and apoptosis were significantly higher in type 3 than in the other types (~4.3-fold; P <.01). Gene expression by real-time polymerase chain reaction showed significantly higher RAGE (~5.1-fold), NOX (~5.3-fold), and IL (~3.0-fold) in type 3 than in the other types (P <.05). Conclusion: Stump classification type 3 exhibited the highest accumulation of AGEs and the highest oxidative stress and apoptosis, suggesting a high degree of degeneration and inflammation. Imaging based on stump classification reflects the degeneration and fragility of the torn rotator cuff site. Clinical Relevance: This study provides evidence of a relationship between stump classification, which reflects rotator cuff fragility on MRI, and pathologies related to advanced glycation end products. [ABSTRACT FROM AUTHOR]

Asbestos fibers have been used as an industrial and construction material worldwide due to their high durability and low production cost. Commercial usage of asbestos is currently prohibited in Japan; however, the risk of asbestos‐induced malignant mesothelioma (MM) remains. According to epidemiological data, the onset of MM is estimated to occur after a latent period of 30–40 years from initial exposure to asbestos fibers; thus, the continuous increase in MM is a concern. To explore the molecular mechanisms of MM using animal models, iron saccharate with iron chelator‐induced sarcomatoid mesothelioma (SM) revealed hallmarks of homozygous deletion of Cdkn2a/2b by aCGH and microRNA‐199/214 by expression microarray. Oral treatment of iron chelation by deferasirox decreased the rate of high‐grade SM. Moreover, phlebotomy delayed MM development in crocidolite‐induced MM in rats. In Divalent metal transporter 1 (Dmt1) transgenic mice, MM development was delayed because of low reactive oxygen species (ROS) production. These results indicate the importance of iron and ROS in mesothelial carcinogenesis. The aims of this review focus on the pathogenesis of elongated mineral particles (EMPs), including asbestos fibers and multiwalled carbon nanotubes (MWCNTs) that share similar rod‐like shapes in addition to the molecular mechanisms of MM development. [ABSTRACT FROM AUTHOR]

Idiopathic leukoderma is a skin disorder characterized by patchy loss of skin pigmentation due to melanocyte dysfunction or deficiency. Rhododendrol (RD) was approved as a cosmetic ingredient in Japan in 2008. However, it was shown to induce leukoderma in approximately 20,000 customers. The prediction of cytotoxicity, especially to melanocytes in vivo, is required to avoid such adverse effects. Since the use of higher vertebrates is prohibited for medicinal and toxicological assays, we used zebrafish, whose melanocytes were regulated by mechanisms similar to mammals. Zebrafish larvae were treated with RD in breeding water for 3 days, which caused body lightening accompanied by a decrease in the number of melanophores. Interestingly, black particles were found at the bottom of culture dishes, suggesting that the melanophores peeled off from the body. In addition, RT‐PCR analysis suggested that the mRNA levels of melanophore‐specific genes were significantly low. An increase in the production of reactive oxygen species was found in larvae treated with RD. The treatments of the fish with other phenol compounds, which have been reported to cause leukoderma, also induced depigmentation and melanophore loss. These results suggest that zebrafish larvae could be used for the evaluation of leukoderma caused by chemicals, including RD. [ABSTRACT FROM AUTHOR]

Background: Assistive use of short-acting ß2 agonists (SABAs) reportedly improves exercise tolerance, activities of daily living, and health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD). However, the effect of SABA on physical activity (PA) is unclear. Objective: This study aimed to determine whether assistive use of SABA increases PA and whether additional pulmonary rehabilitation (PR) can aid further improvement. Methods: Twelve outpatients with COPD and dyspnea during daily activities despite regular use of long-acting bronchodilators were enrolled. This study comprised a 2-week pre-intervention investigation, a 12-week investigation of SABA effects, and an 8-week investigation of the additional effects of PR. Assistive use of SABA was allowed up to 4 times per day after the pre-intervention period. PA was measured for 14 consecutive days using an accelerometer sensor. Dyspnea, exercise tolerance, and HRQOL were evaluated at entry, at 4 and 12 weeks after initiating SABA use, and after completing PR. Results: Assistive use of SABA improved breathlessness during daily activities and increased PA (p < .001). PA and HRQOL were also improved following PR (p < .001 and p = .013, respectively). Conclusions: Combined therapy of SABA and PR can increase PA and HRQOL in COPD patients. [ABSTRACT FROM AUTHOR]

Objectives: The Japanese herbal medicine kyoseihatekigan (KHG) has been used to alleviate the symptoms of croaky voice and globus hystericus, and each of its components has anti-inflammatory and antioxidant effects. However, the mechanisms underlying these beneficial actions of KHG on the vocal folds remain largely unknown. We examined the effects of KHG on rat vocal fold wound healing and assessed its anti-inflammatory and antioxidant properties., Study Design: Animal model., Methods: The vocal folds of Sprague-Dawley rats were unilaterally injured under endoscopy. Rats were divided into three groups based on KHG dosing from pre injury day 4 to post injury day 3: 0 mg/kg/day (sham group), 500 mg/kg/day (1% KHG group) and 1000 mg/kg/day (2% KHG group). Histologic changes were examined to assess the degree of inflammation and oxidative stress at day 3, and fibrosis at day 56. In addition, gene expression related to pro-inflammatory cytokines and transforming growth factor-beta1 (TGF-β1) signaling was examined by quantitative real-time polymerase chain reaction (qPCR)., Results: Histologic analysis showed that the 1% and 2% KHG treatments significantly decreased cell infiltration and the 4-hydroxy-2-nonenalx-immunopositive area, and increased hyaluronic acid at day 3. Both KHG treatments significantly decreased fibrosis at day 56. qPCR revealed that mRNA of interleukin-1β and cyclooxygenase-2 were significantly suppressed at day 1 and TGF-β1 mRNA was significantly downregulated at day 5 in both KHG groups., Conclusions: The current findings suggest that KHG has anti-inflammatory and antioxidant effects in the early phase of vocal fold wound healing, which can lead to better wound healing with less scar formation., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

BACKGROUND: Manual rib cage compression is a chest physiotherapy technique routinely used in clinical practice. However, scientific evidence remains scarce on the effects of manual rib cage compression on airway clearance and oxygenation in mechanically ventilated patients. METHODS: Anesthetized pigs were intubated via the trachea and mechanically ventilated. To create atelectasis, artificial mucus was infused into the airway. Each pig was randomly assigned to 1 of 2 groups: closed suctioning alone (control group, 7 pigs), or manual rib cage compression combined with closed suctioning (manual rib cage compression group, 8 pigs). Hard and brief rib cage compression synchronized with early expiratory phase was tested. Mucus clearance and oxygenation were assessed after the intervention. Sequential changes of hemodynamics were assessed after the intervention. RESULTS: During hard manual rib cage compression, the mean 6 SD peak expiratory flow increased to 44 6 7 L/min compared with 31 6 7 L/min without treatment (P < .001). Manual rib cage compression combined with endotracheal suctioning increased mucus clearance compared with closed suctioning alone (mucus amounts, 5.5 [3.4-9.4] g vs 0.7 [0.5-2.0] g; P 5 .004); however, it did not improve gas exchange and radiologic findings. There were no significant differences in hemodynamic variables between the 2 groups. CONCLUSIONS: Our findings indicated that hard and brief manual rib cage compression combined with closed suctioning was safe and led to improvement of mucus clearance; however, no effectiveness was confirmed with regard to oxygenation and ventilation. [ABSTRACT FROM AUTHOR]

Background: The role of oxygen therapy in end-of-life care for patients with advanced cancer is incompletely understood. We aimed to evaluate the association between oxygen use and survival in patients with advanced cancer and low oxygen saturation in home care. Methods: We conducted a retrospective cohort study at a primary care practice in suburban Tokyo. Adult patients in home care with advanced cancer demonstrating first low oxygen saturation (less than 90%) detected in home visits were consecutively included in the study. Cox proportional hazards regression was used to investigate the effect of oxygen use on overall survival and survival at home, adjusted for systolic blood pressure, decreased level of consciousness, dyspnea, oral intake, performance status, and cardiopulmonary comorbidity. Results: Of 433 identified patients with advanced cancer, we enrolled 137 patients (oxygen use, n = 35; no oxygen use, n = 102) who developed low oxygen saturation. In multivariable analysis, the adjusted hazard ratio (HR) of oxygen use was 0.68 (95% confidence interval 0.39–1.17) for death and 0.70 (0.38–1.27) for death at home. In patients with dyspnea, the HR was 0.35 (0.13–0.89) for death and 0.33 (0.11–0.96) for death at home; without dyspnea, it was 1.03 (0.49–2.17) for death and 0.84 (0.36–1.96) for death at home. Conclusions: Oxygen use was not significantly associated with survival in patients with advanced cancer and low oxygen saturation, after adjusting for potential confounders. It may not be necessary to use oxygen for prolongation of survival in such patients, particularly in those without dyspnea. [ABSTRACT FROM AUTHOR]

When titanium dioxide (TiO2) particles are irradiated with ultrasound, the production of reactive oxygen species (ROS) is enhanced. The application of this phenomenon to infection prevention and cancer treatment has been extensively studied. However, to date, it has not been adequately verified whether the use of TiO2 particles induce the optimal production of ROS. In this study, we compared the enhancement of dihydroxybenzoic acid (DHBA) production as a quantification of ROS production when TiO2 and other particles were irradiated with ultrasound. The results suggested that the production of DHBA was enhanced with the use of TiO2 particles as compared with the use of other particles. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Background: Few studies have assessed associations of non-enzymatic antioxidant capacity (NEAC) in the overall diet with all-cause or specific mortality, and their results have been inconsistent.Objectives: The present study investigated the association between dietary NEAC and all-cause or cause-specific mortality.Methods: The study was a large-scale population-based prospective cohort study in Japan consisting of 42,520 men and 50,207 women aged 44-76 y, who had no history of cancer, stroke, ischemic heart disease, or chronic liver disease. We evaluated FFQ-based dietary NEAC with use of published databases in which the NEACs of individual foods were analyzed by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Dietary NEAC was calculated by multiplying the estimated NEAC with the consumed amount and summing up those values for all foods, and was categorized in quartiles. We identified death and cause of death with use of residential registry and death certificates. HRs and 95% Cls for death from the second survey, which was conducted from April 1995 to December 2014 were estimated with Cox proportional hazards regression analysis.Results: After 1,498,308 person-years of follow-up, 12,978 total deaths occurred. The multivariable-adjusted HRs (95% Cls) for all-cause mortality for the highest compared with the lowest quartile of FRAP and ORAC were 0.85 (0.80, 0.89) and 0.84 (0.79, 0.89), respectively. Dietary NEACs were inversely associated with mortality from cardiovascular disease (CVD), but not from cancer. The multivariable-adjusted HRs (95% Cls) for CVD for the highest compared with the lowest quartile of FRAP and ORAC were 0.83 (0.75, 0.92) and 0.79 (0.70, 0.89), respectively.Conclusions: Higher dietary NEACs from FRAP and ORAC were associated with lower risk of all-cause mortality and mortality from CVD in Japanese adults. [ABSTRACT FROM AUTHOR]

Background: Febrile young infants have a high risk of serious infection. Although measuring vital sign parameters can serve as a rapid and effective assessment in these patients, their predictive value for serious bacterial infection (SBI) has not been fully investigated. Methods: This retrospective observational study enrolled febrile (>38.0°C) infants aged <90 days at the time of presentation. Data from the emergency room triage database at Tokyo Metropolitan Children's Medical Center for the period 1 November 2011–30 November 2013, were reviewed. Variables included patient age, gender, and vital sign data, including body temperature, pulse rate, oxygen saturation, definitive diagnosis, and disposition. Results: Two hundred and sixty‐nine patients were included, with a mean age of 55 days, and 158 (58.7%) were male. Of the total, 43 patients had an SBI. On logistic regression, body temperature ≥38.5°C (OR, 2.80; 95%CI: 1.37–5.74) was a significant predictor of SBI. Conclusion: High‐grade fever was found to be a significant predictor of SBI in febrile young infants. [ABSTRACT FROM AUTHOR]

Background: Bubbly/cystic appearance on chest radiograph is an important factor in severe‐type bronchopulmonary dysplasia (BPD) in Japan. The aim of this study was to determine the perinatal characteristics and neonatal complications of the bubbly/cystic(+) group in extremely preterm infants with BPD, that is, oxygen dependency at day 28 after birth (BPD28). Methods: This was a multicenter retrospective cohort study of population data from infants (birthweight, <1,500 g) enrolled in the Neonatal Research Network of Japan. Of the 15 480 infants born at <28 weeks' gestational age (GA) between 2003 and 2012, 8,979 met the BPD28 criteria. The BPD28 infants were classified according to bubbly/cystic appearance on radiograph (±) at >28 postnatal days. Results: The bubbly/cystic(+) group had lower GA and birthweight and required longer mechanical ventilation and oxygen dependency than the bubbly/cystic(−) group. After adjustment for confounding factors, bubbly/cystic appearance was an independent risk factor for home oxygen therapy at discharge. Conclusion: Bubbly/cystic appearance on chest radiograph was a predictor of short‐term respiratory outcomes in infants with BPD28, which is diagnosed much earlier (≥28 postnatal days), and has a potentially different etiology to BPD36 (oxygen and/or positive pressure respiratory support dependency at 36 weeks' postmenstrual age). [ABSTRACT FROM AUTHOR]

Background: In perinatal medicine, inhaled nitric oxide (iNO) has been an important tool for the treatment of full‐term and late‐preterm infants with persistent pulmonary hypertension of the newborn (PPHN) and hypoxemic respiratory failure (HRF). Its use in more premature infants, however, is controversial. To evaluate the current clinical practices regarding use of acute iNO in extremely preterm infants, a nationwide survey was conducted in Japan. Methods: A questionnaire survey was conducted from May to September, 2015. Questionnaires about PPHN and iNO treatment were sent to the doctor in charge of the neonatal care unit in 213 perinatal medical centers (PMC) that possessed iNO equipment in Japan. Results: A total of 143 of the 213 PMC provided responses (67.1%). A diagnosis of PPHN was made exclusively on echocardiography in all PMC. On definitive PPHN diagnosis, iNO was selected in the majority of the PMC (72%) and started from ≤10 p.p.m. in most PMC (49.7%) for extremely preterm infants. During iNO therapy, cardiac function was checked on echocardiography by a neonatologist every ≤8 h. iNO weaning was started when differential peripheral oxygen saturation (SpO2) disappeared, or when SpO2 reached 100% and so on. After iNO concentration reached 5 p.p.m., it was decreased gradually and carefully in five steps, taking 12–24 h to go from 5 to 0 p.p.m. Conclusions: Inhaled nitric oxide was predominantly used in extremely preterm infants as early rescue therapy for PPHN based on echocardiography performed by a neonatologist. [ABSTRACT FROM AUTHOR]

BACKGROUND: Most heat-and-moisture exchangers (HMEs) for patients with tracheostomy and spontaneously breathing are small and have suction ports that allow some expiratory gas to escape, which loses vapor held in the expired gas. Recently, a heated-and-humidified high-flow system for spontaneously breathing patients with tracheostomy was developed. Little is known, however, about the humidifying performance of HMEs or heated-and-humidified high-flow systems for spontaneous breathing patients with a tracheostomy. OBJECTIVE: To investigate the humidifying performance of the HMEs and heated-and-humidified high-flow systems for spontaneously breathing patients with tracheostomy. METHODS: Adult spontaneously breathing subjects with tracheostomy and were enrolled when their respiratory parameters and ... were stable. We measured absolute humidity, relative humidity, and temperature by using a capacitance-type moisture sensor at the outlet of the tracheostomy tube. Heated-and-humidified high flow was delivered via the a humidifier and tracheostomy interface, and a selected HME. The subjects received heated-and-humidified high flow, after which an HME was used for humidification before switching back to a heated-and-humidified high-flow system. RESULTS: Ten subjects (5 men, 5 women; mean ± SD age, 72 ± 12 y) were enrolled. The admission diagnoses were neurologic (5 subjects), respiratory failure (3), and cardiac arrest (2). The APACHE (Acute Physiology and Chronic Health Evaluation) II score was 24 (interquartile range, 20-27). Tracheostomy was performed on day 7 (interquartile range, 5-11 d) after endotracheal intubation, and the duration of mechanical ventilation was 10 d (interquartile range, 6-11 d). The temperature with the HME was 29.9 ± 1.0°C and, during heated-and-humidified high-flow use was 35.3 ± 0.8°C (P < .001). With both the HME and the heated-and-humidified high-flow system, the relative humidity reached 100%; the absolute humidity with HME was 30.2 ± 1.8 mg/L, and, with the heated-and-humidified high-flow system, was 40.3 ± 1.8 mg/L (P < .001). CONCLUSIONS: In spontaneously breathing subjects with tracheostomy, an heated-and-humidified high-flow system achieved higher absolute humidity than did an HME. [ABSTRACT FROM AUTHOR]

• Reservoir DOM are mixtures of terrestrial (dominance) and microbial DOM. • Ф 1O2 of reservoir surface water ranges from 7.80 × 10−3 to 3.96 × 10−2. • S 350–400 significantly correlate to Ф 1O2 and is effective for Ф 1O2 modeling. • Simple/multiple linear models can estimate Ф 1O2 with low RMSE for reservoirs. • Random forest outperform the linear models in the Ф 1O2 estimation. Man-made reservoirs are important for human daily lives and offer different functions, however they are contaminated due to anthropogenic activities. Dissolved organic matter (DOM) from each reservoir is unique in composition, which further determines its photo-reactivity. Thus, this study aimed to investigate the photo-reactivity of reservoir DOM in terms of the quantum yield for photo-production of singlet oxygen (Ф 1O2). We sampled surface water of 50 reservoirs in Japan and determined their Ф 1O2 using simulated sunlight together with bulk water analysis. Their Ф 1O2 ranged from 1.46 × 10−2 to 6.21 × 10−2 (mean, 2.55 × 10−2), which was identical to those of lakes and rivers reported in the literature, but lower than those of wetland water and wastewater. High-energy triplet-state of DOM accounted for 59.4% of the 1O 2 production in the reservoir water on average. Among the bulk water properties, the spectral slope of wavelength from 350 to 400 nm (S 350–400) was statistically detected as the most important predictor for Ф 1O2. Furthermore, the multiple linear regression model employed S 350–400 and the biological index as predictors with no intercorrelations and reasonable accuracy (r 2 = 0.86), while the random forest model showed a better accuracy (r 2 = 0.90). Overall, these major findings are beneficial for understanding the photo-reactivity of reservoir waters. [Display omitted] [ABSTRACT FROM AUTHOR]

The Japanese Ministry of Health, Labour, and Welfare recently reported an outbreak of bladder cancer among workers who handled aromatic amines in Japan. 2,4-dimethylaniline (2,4-DMA) is one of the chemicals that workers are considered to have the most opportunities to be exposed. Genotoxic events are known to be crucial steps in the initiation of cancer. However, studies on the genotoxicity of 2,4-DMA are limited, particularly studies investigating the mechanism behind the genotoxicity by 2,4-DMA are completely lacking. We examined genotoxic properties of 2,4-DMA using phosphorylated histone H2AX (γ-H2AX), a sensitive and reliable marker of DNA damage, in cultured human urothelial and hepatic cells. Our results clearly showed that 2,4-DMA at a concentration range of 1-10 mM generates γ-H2AX in both cell lines, indicating that 2,4-DMA is genotoxic. During mechanistic investigation, we found that 2,4-DMA boosts intracellular reactive oxygen species, an effect clearly attenuated by disulfiram, a strong inhibitor of cytochrome P450 2E1 (CYP2E1). In addition, CYP2E1 inhibitors and the antioxidant, N-acetylcysteine, also attenuated γ-H2AX generation following exposure to 2,4-DMA. Collectively, these results suggest that γ-H2AX is formed following exposure to 2,4-DMA via reactive oxygen species produced by CYP2E1-mediated metabolism. Continuous exposure to genotoxic aromatic amines such as 2,4-DMA over a long period of time may have contributed to the development of bladder cancer. Our results provide important insights into the carcinogenicity risk of 2,4-DMA in occupational bladder cancer outbreaks at chemical plants in Japan. [ABSTRACT FROM AUTHOR]

Objective: To analyze data from a registry of Japanese neonates with hypoxic respiratory failure associated with pulmonary hypertension (PH) to compare the effectiveness of inhaled nitric oxide (iNO) in neonates born <34 weeks vs. ≥34 weeks gestational age (GA). Materials and methods: iNO was administered according to approved Japanese product labeling. Study data were collected before iNO administration and at predefined intervals until discontinuation. Results: A total of 1,114 neonates were included (n=431, <34 weeks GA; n=675, ≥34 weeks GA; n=8, missing age data). Mean decrease from baseline oxygenation index (OI) was similar in both age groups. OI reduction was more pronounced in the <34 weeks subgroups with baseline OI ≥25. Survival rates were similar in the <34 weeks GA and ≥34 weeks GA groups stratified by baseline OI (OI<15, 89% vs. 93%; 15≤OI<25, 85% vs. 91%; 25≤OI≤40, 73% vs. 79%; OI>40, 64% vs. 66%). Conclusion: iNO improved oxygenation in preterm neonates as effectively as in late preterm and term neonates, without negative impact on survival. If clinically significant PH is present, as measured by pulse oximetry or echocardiography, a therapeutic trial of iNO might be indicated for preterm neonates. [ABSTRACT FROM AUTHOR]

Objective. To identify initial predictors of poor survival in patients with PM/DM-associated interstitial lung disease (ILD). Methods. We established a multicentre retrospective cohort of incident cases of PM/DM-associated ILD from 44 institutions across Japan (Multicentre Retrospective Cohort of Japanese Patients with Myositis-associated ILD, JAMI). Inclusion criteria were an onset age ≽16 years; PM/DM or clinically amyopathic DM according to the published criteria; imaging evidence of ILD; and availability of serum samples for assays of autoantibodies such as anti-melanoma differentiation-associated gene 5 and anti-aminoacyl tRNA synthetase. We collected demographic data and clinical characteristics recorded at the time of diagnosis, as well as follow-up survival data. Predictors of ILD-related mortality were identified by univariate and multivariate analyses. Results. JAMI enrolled a cohort of 497 patients with PM (15%), classic DM (32%) and clinically amyopathic DM (53%). During the observation period (median 20 months), 76 died of respiratory insufficiency directly related to ILD. Univariate analysis revealed several initial parameters associated with ILD mortality, including demographic, clinical, laboratory, imaging and autoantibody variables. We used multivariate analysis with a stepwise selection of parameters to generate an appropriate predictive model, and identified the following independent risk factors for ILD mortality: age at onset ≽60 years [hazard ratio (HR) = 4.3, 95% CI: 2.4, 7.5], CRP ≽1 mg/dl (HR = 2.6, 95% CI: 1.5, 4.8), peripheral capillary oxygen saturation <95% (HR = 2.0, 95% CI: 1.2, 3.4) and anti-melanoma differentiation-associated gene 5 antibody (HR = 7.5, 95% CI: 2.8, 20.2). Conclusion. We established a large cohort of incident cases of PM/DM-associated ILD, and successfully identified independent predictors of short-term ILD mortality. [ABSTRACT FROM AUTHOR]

Two cultivars of Japanese parsley were harvested in different seasons; their antioxidant capacities were evaluated by oxygen radical absorbance capacity (ORAC) methods, and the contents of hydrophilic and lipophilic antioxidants were compared. Japanese parsley possessed potent antioxidant capacities both in hydrophilic and lipophilic extracts when evaluated by ORAC methods. LC/MS/MS analyses revealed that chlorogenic acid and four kinds of quercetin glycosides were major antioxidants in the hydrophilic extract. Lutein was the main contributor to the antioxidant capacity of the lipophilic extract. Antioxidant capacities of the hydrophilic extracts of both cultivars tended to be higher in winter because of the increase in the contents of chlorogenic acid and quercetin glycosides. An obvious trend in the lipophilic antioxidant capacities or lutein contents was not observed irrespective of the cultivar. [ABSTRACT FROM PUBLISHER]

The red blood cell distribution width (RDW) is a quantitative measure of the variability in the size of circulating erythrocytes. We aimed to study whether higher levels of the RDW were associated with heart failure in a Fontan circulation and to analyze its clinical value compared to brain natriuretic peptide. This retrospective study included 38 consecutive pediatric patients with a Fontan circulation who underwent routine cardiac catheterization at the International Medical Center, Saitama Medical University from October 2010 to July 2014. We assessed the relation between the RDW and catheterization data such as the central venous pressure (CVP), mixed venous oxygen saturation (SvO2), and cardiac index (CI). The RDW was positively correlated with the CVP (p = 0.0002). The elevated RDW group had a significantly greater CVP than the normal RDW group (p = 0.0003). Also, the RDW was negatively correlated with the SvO2 (p = 0.0004). The elevated RDW group had a significantly less SvO2 than the normal RDW group (p <0.0001). The CI in the elevated RDW group was lower than that in the normal RDW group (p = 0.0421). In the multivariate regression analysis, the RDW was a significant independent predictor of the CVP and SvO2. The BNP level did not have any significant relation with the CVP, SvO2, or CI. The RDW is a convenient and powerful marker for detecting heart failure in a Fontan circulation. [ABSTRACT FROM AUTHOR]

Aim Antioxidant activities and cytokine levels in human body fluids are considered to be strongly associated with periodontitis. The aim of this study was to elucidate the relationship between salivary antioxidant activities against superoxide or hydroxyl radical, cytokines, and periodontal conditions through a community-based cross-sectional study conducted in Goto city, Japan. Materials and Methods Saliva samples were analysed for superoxide or hydroxyl radical scavenging activities and cytokine levels from 160 participants. We demonstrated that saliva contained superoxide and hydroxyl radical scavenging activities by using electron spin resonance with a spin-trapping agent. The concentrations of eight cytokines were measured using multiplex bead assays. Results There were significant differences in salivary superoxide or hydroxyl radical scavenging activity, and the levels of Interleukin-1 β, Interleukin-6, and Interleukin-8 between periodontitis classifications. Multivariate stepwise logistic regression model showed that salivary superoxide and hydroxyl radical scavenging activities were significantly associated with the classification of periodontitis. In addition, salivary superoxide scavenging activity was found to have significant association with all periodontal parameters using multiple linear regression analysis. Conclusions These findings suggest that the evaluation of salivary antioxidant activities, as assessed by electron spin resonance, are associated with periodontitis and various clinical variables in community-dwelling participants (ClinicalTrials.gov number NCT01742728). [ABSTRACT FROM AUTHOR]

Glycolysis and the pentose phosphate pathway (PPP) are preferentially activated in cancer cells. Accumulating evidence indicated the significance of the altered glucose metabolism in cancer, but the implication for oncotherapy remains unclear. Here we report that the synthesis of glycolytic and PPP enzymes is almost ubiquitously augmented in colorectal carcinoma (CRC) specimens. The mammalian target of rapamycin (mTOR) inhibitor INK128 (300 nM) and phytochemical Avemar (1 mg/ml) inhibited the synthesis of PPP enzymes in CRC cell lines. INK128 (150-600 nM) and resveratrol (75-300 μM) inhibited aerobic glycolysis in the cell lines. INK128 (300 nM) and Avemar (1 mg/ml) decreased the NADPH/NADP+ ratio as well as the GSH/GSSG ratio in the cell lines. Finally, per os administration of INK128 (0.8 mg/kg) or Avemar (1 g/kg) suppressed tumor growth and delayed tumor formation by transplantable CRC specimens derived from patients. Taken together, pharmacological inhibition of the mTOR-PPP axis is a promising therapeutic strategy against CRCs. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective. Bokusoku (BK) is an extract from the Quercus cortex used in folk medicine for treatment of skin disorders and convergence, and is present in jumihaidokuto, a traditional Japanese medicine that is prescribed for purulent skin diseases like acne vulgaris. The excess of sebum production induced by androgen is involved in the development of acne. Our aim is to examine whether BK and its constituents inhibit testosterone metabolism and testosterone-induced sebum synthesis. Methods. Measurements of 5α-reductase activity and lipogenesis were performed using rat liver microsomes and hamster sebocytes, respectively. Results. BK dose-dependently reduced the conversion of testosterone to a more active androgen, dihydrotestosterone in a 5α-reductase enzymatic reaction. Twenty polyphenols in BK categorized as gallotannin, ellagitannin, and flavonoid were identified by LC-MS/MS. Nine polyphenols with gallate group, tetragalloyl glucose, pentagalloyl glucose, eugeniin, 1-desgalloyl eugeniin, casuarinin, castalagin, stenophyllanin C, (-)-epicatechin gallate, and (-)-epigallocatechin gallate, inhibited testosterone metabolism. In particular, pentagalloyl glucose showed the strongest activity. BK and pentagalloyl glucose suppressed testosterone-induced lipogenesis, whereas they weakly inhibited the lipogenic action of insulin. Conclusions. BK inhibited androgen-related pathogenesis of acne, testosterone conversion, and sebum synthesis, partially through 5α-reductase inhibition, and has potential to be a useful agent in the therapeutic strategy of acne. [ABSTRACT FROM AUTHOR]

Elevated postprandial hyperglycaemia and oxidative stress increase the risks of type 2 diabetes and CVD. Green tea catechin possesses antidiabetic properties and antioxidant capacity. In the present study, we examined the acute and continuous effects of ingestion of catechin-rich green tea on postprandial hyperglycaemia and oxidative stress in healthy postmenopausal women. Participants were randomly assigned into the placebo (P, n 11) or green tea (GT, n 11) group. The GT group consumed a catechin-rich green tea (catechins 615 mg/350 ml) beverage per d for 4 weeks. The P group consumed a placebo (catechins 92 mg/350 ml) beverage per d for 4 weeks. At baseline and after 4 weeks, participants of each group consumed their designated beverages with breakfast and consumed lunch 3 h after breakfast. Venous blood samples were collected in the fasted state (0 h) and at 2, 4 and 6 h after breakfast. Postprandial glucose concentrations were 3 % lower in the GT group than in the P group (three-factor ANOVA, group × time interaction, P< 0·05). Serum concentrations of the derivatives of reactive oxygen metabolites increased after meals (P< 0·05), but no effect of catechin-rich green tea intake was observed. Conversely, serum postprandial thioredoxin concentrations were 5 % higher in the GT group than in the P group (three-factor ANOVA, group × time interaction, P< 0·05). These findings indicate that an acute ingestion of catechin-rich green tea has beneficial effects on postprandial glucose and redox homeostasis in postmenopausal women. [ABSTRACT FROM PUBLISHER]

Background Reactive oxygen species may be involved in serious diseases in premature infants. The objective of this study was to assess the relationship between neurodevelopmental outcome and oxidative stress marker level in the urine of very low-birthweight ( VLBW) infants. Methods Spot urine samples were collected from 35 VLBW infants. Urinary excretion of 8-hydroxy-2″-deoxyguanosine (8- OHdG), a marker of oxidative DNA damage, and 8-iso-prostaglandin F2α (8- isoPGF), a marker of lipid peroxidation, was measured at 1, 2, 4, and 6 weeks of age. Neurodevelopmental outcome at 18 months' corrected age was assessed using the Bayley Scales of Infant Development ( BSID)- II. Results Significant correlations were found between urinary 8- OHdG at 2 and 4 weeks and the Mental Development Index of the BSID-II. No significant correlation was found between urinary 8- isoPGF and indices of the BSID-II. Conclusions In VLBW infants, urinary 8- OHdG level correlated with mental development rather than psychomotor development at 18 months' corrected age; urinary 8- OHdG might be a predictive marker of neurodevelopmental outcome in VLBW infants. [ABSTRACT FROM AUTHOR]

The consumption of alkaline reduced water produced by domestic electrolysis devices was approved in Japan in 1965 by the Ministry of Health, Labour and Welfare for the cure of gastro-intestinal disorders. Today, these devices are freely available in several countries and can be easily purchased without reserve. The commercial information included with the device recommends the consumption of 1-1.5 L of water per day, not only for gastro-intestinal disorders but also for numerous other illnesses such as diabetes, cancer, inflammation, etc. Academic research in Japan on this subject has been undergoing since 1990 only but has established that the active ingredient is dissolved dihydrogen that eliminates the free radical HO• in vivo. In addition, it was demonstrated that degradation of the electrodes during functioning of the device releases very reactive nanoparticles of platinum, the toxicity of which has not yet been clearly proven. This report recommends alerting health authorities of the uncontrolled availability of these devices used as health products, but which generate drug substances and should therefore be sold according to regulatory requirements. [ABSTRACT FROM AUTHOR]

Oxidative stress increases with advancing age and is a mediator of several diseases including cancer, cardiovascular disease, and diabetes. Moreover, postmenopausal women have a lower estrogen concentration, which is associated with elevated oxidative stress. However, there is no definitive evidence regarding the relationship between daily physical activity and oxidative stress status in older adults, including postmenopausal women. Twenty- nine adults (age, 70.1 ± 1.0 years, mean ± SE; 12 women and 17 men) were examined in this cross-sectional study. Prior to blood collection, the participants were asked to wear a uniaxial accelerometer for 4 consecutive weeks to determine their level of physical activity. After a 48-h period of physical activity avoidance and a 10-h overnight fast, venous blood samples were obtained from each participant. Fasting plasma derivatives of reactive oxygen metabolites (d-ROMs) and malondialdehyde (MDA) concentrations of oxidative stress markers were negatively correlated with the amount of physical activity in women (d-ROMs; r = -0.708, p = 0.002) (MDA; r = -0.549, p = 0.028), but not in men. Fasting plasma biological antioxidant potential of antioxidant capacity marker was positively correlated with the amount of physical activity in women (BAP; r = 0.657, p = 0.006) (GSH; r = 0.549, p = 0.028), but not in men. Moreover, superoxide dismutase activity of antioxidant capacity marker was positively correlated with the amount of physical activity in men (r = 0.627, p = 0.039), but not in women. There were no associations between physical activity and other oxidative stress markers (reduced and oxidized glutathione, glutathione peroxidise, thioredoxin). These findings suggest that regular physical activity may have a protective effect against oxidative stress by increasing total antioxidant capacity, especially in postmenopausal women. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Rokumi-jio-gan-containing prescriptions, traditional medicine, are widely used to treat renal dysfunction in Japan. Aim of the study: The present study was conducted to examine whether two Rokumi-jio-gan-containing prescriptions (Hachimi-jio-gan and Bakumi-jio-gan) have an ameliorative effect on dyslipidemia in nephrectomized rats. Materials and methods: Each prescription was orally administered to nephrectomized rats at 150mg/kg body weight per day for 10 weeks, and its effect was compared with vehicle-treated nephrectomized rats. Results: Rats given Hachimi-jio-gan and Bakumi-jio-gan showed an improvement of renal functional parameters such as serum urea nitrogen, creatinine, creatinine clearance, and urinary protein. The increased triglyceride, total cholesterol, non-esterified fatty acid, high-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol/low-density lipoprotein cholesterol levels in serum, and triglyceride and total cholesterol contents in the kidney of nephrectomized rats were significantly decreased by Hachimi-jio-gan and Bakumi-jio-gan administration. Furthermore, Hachimi-jio-gan acts as a regulator of peroxisome proliferator-activated receptor α, sterol regulatory element binding protein (SREBP)-1, and SREBP-2. On the contrary, the increased reactive oxygen species and thiobarbituric acid-reactive substance were decreased, while superoxide dismutase and the reduced glutathione/oxidized glutathione ratio were augmented by Hachimi-jio-gan rather than Bakumi-jio-gan. The improvement of nuclear factor-kappa Bp65, cyclooxygenase-2, inducible nitric oxide synthase, NF-E2-related factor 2, and heme oxygenase-1 was marked in the group administered Bakumi-jio-gan. However, oil red O staining showed that the increased lipid deposition in the kidney of nephrectomized rats improved on Hachimi-jio-gan and Bakumi-jio-gan administration. Conclusion: This study provides scientific evidence that two Rokumi-jio-gan-containing prescriptions (Hachimi-jio-gan and Bakumi-jio-gan) improve oxidative stress via dyslipidemia in the remnant kidney of nephrectomized rats. [Copyright &y& Elsevier]

Abstract: The sum of hydrophilic antioxidants of 23 vegetables and 13 fruits commonly consumed in Japan was evaluated by a modified hydrophilic-oxygen radical absorbance capacity (H-ORAC) method. The “typical vegetable” and “typical fruit” in Japan contained hydrophilic antioxidants that are equivalent to 6.95 and 12.23μmol of Trolox per g of the edible portion, respectively, on average. Hence, the daily intake of hydrophilic antioxidants from vegetables and fruits was estimated to be 4423μmol Trolox equivalent (TE)/d based on data of the National Health and Nutrition Survey in Japan. However, the biological significance of these antioxidant values has not yet been clarified. To address this issue, our data will provide a foundation for high-quality epidemiological studies aimed at elucidating the relationship between daily intake of antioxidants and health. In addition, the comparison of the results of the H-ORAC assay with those of polyphenol content and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay was also studied. The H-ORAC values had a strong positive correlation with polyphenol contents (r =0.956), and were 1.0–18.2-times higher than the antioxidant capacities evaluated by the DPPH assay. [Copyright &y& Elsevier]

The optical properties of dissolved organic matter (DOM) from five rivers (Kokubu, Kurose, Ohta, Yamato, and Yodo) in Japan were investigated and contributions of DOM to photoformation of three reactive oxygen species (ROS) (hydroxyl radicals (OH), nitric oxide radicals (NO), and singlet oxygen ( 1 O 2 )) were assessed. The lowest and highest mean dissolved organic carbon concentrations were for the Ohta River (0.95 (mg C) L -1 ) and Yamato River (2.85 (mg C) L -1 ), respectively, and the concentrations correlated with some optical parameters. Absorption ratios (e.g., the E 2 :E 3 and A 280 /A 350 ratios) and the spectral slope S 275-295 indicated that DOM from the Yodo and Kokubu rivers had the lowest and highest molecular weights, respectively. PARAFAC models and DOM excitation-emission matrices were used to assess the sources and fates of DOM in the rivers. The PARAFAC model indicated that the main types of fluorescent DOM in the rivers were terrestrial humic-like (TH-L) and tryptophan-like (TP-L) substances. The Kokubu River contained other compounds such as fluorescent whitening agents, autochthonous humic-like substances, and extracellular polymeric substances. Statistically significant relationships between the dissolved organic carbon and TH-L, TP-L, and extracellular polymeric substance concentrations suggested that TH-L, TP-L, and extracellular polymeric substances are important contributors to total DOM in the rivers. TH-L and TP-L substances strongly contribute to ROS photoformation, but TH-L substances play roles in both ROS generation and scavenging. Comprehensive models for estimating the photoformation rates of different ROS (in M s -1 ) were established by integrating the contributions of the relevant major and minor sources. Examples are R OH (10 -12 ) = 21.0 [NO 2 - ]&#95; μM + 0.460 [TH-L]&#95; QSU + 10.9, R NO (10 -12 ) = 67.9 [NO 2 - ]&#95; μM + 35.2 [a 300 ]&#95; m -1 - 2.51 [TH-L]&#95; QSU - 0.765 [TP-L]&#95; QSU - 8.14, and R 1O 2 (10 -9 ) = 3.81 [a 300 ]&#95; m -1 - 0.101 [TP-L]&#95; QSU + 11.1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aim: Considering the beneficial effects of physical activity on health and disease in older people, the aim of the present study was to investigate the changes in reactive oxygen metabolites and paraoxonase 1 (PON1) activity during an intervention period on increased physical activity among older people. Methods: Serum diacron reactive oxygen metabolites (d-ROMs), PON1 activity and cardiometabolic variables were measured in 43 asymptomatic Japanese volunteers (18 men/25 women, mean age 68.9 years) in the pre- and post-phase of a 6-month intervention program aiming at a mild but sustained increase in physical activity. Results: While the d-ROMs and PON1 activity levels were not significantly altered after the intervention, there was an inverse correlation between percentage changes of d-ROMs and PON1 activity during this intervention period. Multiple regression analysis revealed their significant and inverse correlation as independent of percentage changes of the other cardiometabolic variables (β =−0.3, P < 0.05). Conclusions: The inverse d-ROMs-PON1 relationship may indicate the value of concurrent measurement of these two components of oxidation-antioxidation balance when studying the effects of physical activity in an older population. Further studies are necessary to confirm the observed relationship. [ABSTRACT FROM AUTHOR]

To clarify the relationship between cultivar difference in the sensitivity of net photosynthesis to ozone (O3) and the reactive oxygen species (ROS) scavenging system in wheat ( Triticum aestivum), we investigated the effects of chronic exposure to ambient levels of O3 on gas exchange rates, activity and concentration of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco), activity of ROS scavenging enzymes and concentration of antioxidants of the flag leaf in two Japanese winter wheat cultivars (Norin 61 and Shirogane-komugi). Although the net photosynthetic rate of the flag leaf in Norin 61 was not significantly reduced by exposure to O3, that in Shirogane-komugi was significantly reduced by the exposure to O3 during the anthesis and early grain-filling stages. In the two cultivars, stomatal diffusive conductance to H2O of the flag leaf was not significantly affected by the exposure to O3. The exposure to O3 induced significant reductions in the activity and concentration of Rubisco, activities of catalase (CAT) and monodehydroascorbate reductase (MDAR) and concentrations of reduced form of ascorbate and total glutathione of the flag leaf in Shirogane-komugi. It was concluded that the sensitivity of net photosynthesis of flag leaf to O3 is higher in Shirogane-komugi than in Norin 61, and the difference in the sensitivity to O3 between the two cultivars is mainly due to that in the effects of O3 on the detoxification ability of ROS, mainly determined by the activity of ROS scavenging enzymes, such as CAT and MDAR. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the effects of various concentrations of cysteine (0.0, 0.6, 1.2 and 1.8 mM) added to the maturation medium on nuclear maturation and subsequent embryonic development of bovine oocytes exposed to heat stress (HS: set at 39.5 °C for 5 h, 40.0 °C for 5 h, 40.5 °C for 6 h, and 40.0 °C for 4 h versus 38.5 °C for 20 h as the control group). This regime mimicked the circadian rhythm of the vaginal temperature of lactating dairy cows during the summer season in southwestern Japan. Moreover, we also evaluated the oocyte's reactive oxygen species (ROS) and glutathione (GSH) levels and the apoptosis levels of the oocytes and cumulus cells in the presence or absence of 1.2 mM cysteine. As a result, HS in the without-cysteine group significantly suppressed (p < 0.05) both the nuclear maturation rate up to the metaphase (M)II stage and the blastocyst formation rate compared with that of the control group. In addition, this group showed significantly higher (p < 0.05) ROS levels and significantly lower (p < 0.05) GSH levels than those of the control group. Moreover, the level of TdT-mediated dUTP nick end labelling (TUNEL)-positive cumulus cells in the HS without-cysteine group was significantly higher (p < 0.05) than that of the control group. However, the addition of 1.2 mM cysteine to the maturation medium restored not only the nuclear maturation, blastocyst formation rates and GSH contents, but also increased the ROS and TUNEL-positive levels of the cumulus cells, but not oocytes, to that of the control group. These results indicate that the addition of 1.2 mM cysteine during in vitro maturation (IVM) may alleviate the influence of heat stress for oocyte developmental competence by increasing GSH content and inhibiting the production of oocyte ROS followed by apoptosis of cumulus cells. [ABSTRACT FROM PUBLISHER]

The article presents a study on the effects of apocynin on the integrin-related cell adhesion and proliferation of 3Y1 and HR-3Y1-2 cells. The study involved apocynin purchased from Sigma in Saint Louis, Missouri and HR-3Y1-2 cells purchased from Japanese Collection of Research Bioresources in Osaka, Japan. The results showed that apocynin selectively down-regulates β1-integrin cell surface expression on HR-3Y1-2 cells.

Aim: One of the methods to evaluate oxidative stress in clinical medical settings is the reactive oxygen metabolites (d-ROMs) test. While metabolic syndrome (MetS) is considered an oxidative condition, the oxidative status in MetS has not been fully examined using this test. The aim of the present study was to investigate the possible association between oxidative stress as evaluated by the d-ROMs test and the MetS component number, in a Japanese female population. Methods: The serum oxidant capacity (measured by the d-ROMs test) was cross-sectionally determined in cardiovascular disease-free and non-smoking women who were not taking medications ( n= 180; mean age, 60 ± 10 (standard deviation) years). Their MetS state was determined by the National Cholesterol Education Program Adult Treatment Panel recommendations with minor modifications for a Japanese population. Results: Patients with MetS ( n= 60, 362 ± 53 CARR U) showed a significantly higher oxidant capacity by d-ROMs than those without MetS ( n= 120, 324 ± 55 CARR U, P < 0.01). Moreover, the significant increase in the oxidant capacity by d-ROMs was closely associated with an increase in the MetS component number (trend P < 0.01). Conclusions: These results showed a significantly positive association between the oxidant capacity (by d-ROMs) and the MetS component number in this population. Further studies are required to establish the clinical applications of this test to MetS practice and clarify the biological mechanisms of the observed relationships. [ABSTRACT FROM AUTHOR]

Tsutsumi K, Fujikawa H, Kajikawa T, Takedachi M, Yamamoto T, Murakami S. Effects of L-ascorbic acid 2-phosphate magnesium salt on the properties of human gingival fibroblasts. J Periodont Res 2012; 47: 263-271. © 2011 John Wiley & Sons A/S Background and Objective: l-Ascorbic acid 2-phosphate magnesium salt (APM) is an l-ascorbic acid (AsA) derivative developed to improve AsA stability and display effective biochemical characteristics. This study aimed to investigate the effects of APM on the functions and properties of human gingival fibroblasts with respect to the prevention of periodontal disease in comparison with those of AsA. Material and Methods: Human gingival fibroblasts were incubated in the presence or absence of APM or l-ascorbic acid sodium salt (AsANa). Intracellular AsA was analysed by HPLC. Collagen synthesis was measured by ELISA and real-time RT-PCR. Intracellular reactive oxygen species (ROS) induced by hydrogen peroxide (H2O2) were quantified using a fluorescence reagent, and cell damage was estimated with calcein acetoxymethyl ester. Furthermore, intracellular ROS induced by tumor necrosis factor-α (TNF-α) were quantified, and expression of TNF-α-induced interleukin-8 expression, which increases due to inflammatory reactions, was measured by ELISA and real-time RT-PCR. Results: APM remarkably and continuously enhanced intracellular AsA and promoted type 1 collagen synthesis and mRNA expression. Furthermore, APM decreased cell damage through the suppression of H2O2-induced intracellular ROS and inhibited interleukin-8 production through the suppression of TNF-α-induced intracellular ROS. These effects of APM were superior to those of AsANa. Conclusion: These results suggest that APM is more effective than AsANa in terms of intake, collagen synthesis, decreasing cell damage and inhibiting interleukin-8 expression in human gingival fibroblasts. This suggests that local application of APM can help to prevent periodontal disease. [ABSTRACT FROM AUTHOR]

In Japan, research on functional water, especially on reduced water, is developing at a rapid pace. Reduced water such as electrochemically reduced water and natural reduced water can scavenge reactive oxygen species in cultured cells. Reduced waters are expected to have preventive and positive effects on oxidative stress-related diseases such as diabetes, cancer, arteriosclerosis, neurodegenerative diseases, and side effects of hemodialysis. It has been suggested that the active agents in reduced water are hydrogen (atoms and molecules), mineral nanoparticles, and mineral nanoparticle hydrides. [ABSTRACT FROM AUTHOR]