Effect of Orally Ingested Water Containing H2-Filled Ultrafine Bubbles (UFBs) on Ethanol-Induced Oxidative Stress in Rats.

Ultrafine bubbles (UFBs), which are bubbles with diameters of less than 1 µm, are widely recognized for their ability to exist stably in liquid as a result of the effects of Brownian motion. In this study, we focused on hydrogen, known for its antioxidant potential, and explored the function of H2-filled UFBs, which encapsulate hydrogen, to determine their potential use as oral carriers for the delivery bioactive gases to living organisms. To this end, rats were orally administered ethanol to induce hepatic oxidative stress, and the effects of drinking H2-filled UFBs (H2 NanoGAS®) water for two weeks were evaluated to assess the reduction of oxidative stress. Continuous alcohol consumption was found to significantly increase the blood lipid peroxidation levels in the control group, confirming the induction of oxidative stress. An increase in blood lipid peroxidation was significantly inhibited by the consumption of concentrated H2 NanoGAS® (C-HN) water. Furthermore, the measurement of mitochondrial activity in the liver revealed that drinking H2 NanoGAS® water helped to maintain at a normal level and/or boosted the functional activity of the electron transport system in mitochondria affected by ethanol intake. To our knowledge, this study is the first to provide evidence for the use of orally ingested UFBs as carriers for the delivery gases to tissues, thereby exerting their physiological activity in the body. Our findings highlight the potential for the application of UFBs to various physiologically active gases and their utilization in the medical field in the future.

In Vivo Proof of Biological Safety and Physiological Effects of Orally Ingested Water Containing H2-Filled Ultrafine Bubbles (UFBs).

Owing to their unique physicochemical properties and diverse biological effects, ultrafine bubbles (UFBs) have recently been expected to be utilized for industrial and biological purposes. Thus, this study investigated the biological safety of UFBs in water for living beings in drinking the water with a view to future use in health sciences. In this study, we used H2-filled UFBs (NanoGAS®) that can hold hydrogen in the aqueous phase for a long time. Mice were randomly assigned to one of three groups: those receiving NanoGAS® water, reverse osmosis water, or natural mineral water, and they ingested it ad libitum for one month or three months. As a result, subchronic drinking of NanoGAS® water does not affect either the common blood biochemical parameters or the health of the organs and mucosal membranes. Our results, for the first time, scientifically demonstrated the biological safety of H2-filled UFBs water for subchronic oral consumption.

Ultrafine bubble water mitigates plant growth in damaged soil.

Water containing ultrafine/nano bubbles (UFBs) promoted the growth of tomato (Solanum lycopersicum) in soil damaged by cultivation of tomato in the previous year or bacterial wilt-like disease and also promoted the growth of lettuce (Lactuca sativa) when lettuce was grown in the soil damaged by repeated cultivation of lettuce. On the other hand, UFB supply did not affect plant growth in rock wool or healthy soil. Furthermore, the growth of lettuce was not affected by UFB water treatment in the soil damaged by the cultivation of tomato. UFB water partly suppressed the growth of the pathogen of bacteria wilt disease, Ralstonia solanacearum in vitro. These data suggest that UFB water is effective to recover the plant growth from soil damage.

Ozone ultrafine bubble water induces the cellular signaling involved in oxidative stress responses in human periodontal ligament fibroblasts.

Periodontitis is a chronic inflammatory disease caused by oral microorganisms in the subgingival biofilm. Stable aqueous ozone ultrafine bubble water (OUFBW) has recently begun to be used as an antiseptic in the treatment of periodontitis. The effectiveness of OUFBW is thought to depend on the bactericidal actions of dissolved ozone exerted via its oxidizing effect. On the other hand, the effects of ozone on the periodontal tissues are largely unknown. In this paper we examined the cellular responses after OUFBW treatment. Human primary periodontal ligament fibroblasts (hPDLFs) or Ca9-22 human gingival epithelial cells were treated with OUFBW or UV-inactivated OUFBW. The production of reactive oxygen species (ROS), the activation of mitogen-activated protein kinase (MAPK) and the nuclear factor-kappa B (NF-κB) activation were analyzed. The transcript profiles of hPDLFs after OUFBW treatment were also analyzed by RNA sequencing (RNA-seq). Our results showed that OUFBW induces oxidative stress by generating ROS, which, in turn, activated the MAPK pathway. OUFBW triggered activation of c-Fos, a major component of the transcription factor activator protein 1 (AP-1), and also nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), which possessed a high sensitivity to oxidative stress. The results of RNA-seq analysis revealed that the numerous genes involved in oxidative stress responses or MAPK signaling pathway were up-regulated after OUFBW treatment. Investigation of the signaling pathways activated by OUFBW highlights another aspect of the biological roles of OUFBW, in addition to its bactericidal activity, in the treatment of periodontitis.

Plaque-removal effect of ultrafine bubble water: Oral application in patients undergoing orthodontic treatment.

During orthodontic treatment, plaque tends to form around fixed orthodontic appliances, which increases the risk of dental caries. It has been reported that ultarafine bubble with a diameter <1 µm water (UFBW) effectively removes organic matter. In addition, UFBW is harmless and stable for at least one month with refrigeration. The aim of this study was to examine the plaque-removal effect of ultrafine bubble water (UFBW) to establish a new method to prevent dental caries in patients during orthodontic treatment procedures. The in vitro study examined different concentrations of UFBW and compared the cleaning effect to that of existing mouthwashes. High-concentration UFBW (HUFBW) was most effective in cleaning. In the subsequent clinical study, HUFBW showed a significantly higher plaque-removal effect compared to distilled water (p<0.01). Thus, supplementary use of HUFBW could decrease the incidence of dental caries during orthodontic treatment.

Destabilization of ultrafine bubbles in water using indirect ultrasonic irradiation.

Ultrafine bubble (UFB) is a bubble with a diameter of less than 1 µm. Little attention has been paid to the defoaming and removal of UFBs. This study proposes a method to destabilize UFBs by using indirect ultrasonic irradiation. Besides, the destabilization mechanism of UFB was investigated. The ultrasonic frequency was 1.6 MHz and the dissipated power was 30 W. UFB dispersions were prepared using two different types of bubble generators: pressurized dissolution method and swirling liquid flow method. The effects of ultrasonic irradiation on the stability of UFBs were evaluated by particle tracking analysis (PTA) and electrophoretic zeta potential measurement. Results showed that the indirect ultrasonic irradiation for 30 min reduced the number concentration of UFBs by 90% regardless of the generation method. This destabilization was attributed to a decrease in the magnitude of zeta potential of UFBs due to the changes in pH and electrical conductivity. These changes in the electrochemical properties were caused by the formation of nitric acid. To study the destabilization mechanism, the pH of the UFB dispersions were modified by titration; the chemical and mechanical effects of ultrasound were separately examined. It was found that not only the chemical effect caused by the formation of nitric acid but also the mechanical effect contributed to the destabilization of UFB. Feasibility studies were also performed for UFBs in an aqueous surfactant solution and UFBs in a solid particle dispersion. The proposed method selectively destabilized UFBs in the solutions.

Nutrition and Cancer Risk from the Viewpoint of the Intestinal Microbiome.

There are various important factors in reducing the risk of cancer development and progression; these factors may correct an unbalanced intake of nutrients to maintain the living body's homeostasis, detoxify toxic materials, acting as an external factor, and maintain and strengthen the body's immune function. In a normal cell environment, nutrients, such as carbohydrates, lipids, proteins, vitamins, and minerals, are properly digested and absorbed into the body, and, as a result, an environment in which cancer can develop and progress is prevented. It is necessary to prevent toxic materials from entering the body and to detoxify poisons in the body. If these processes occur correctly, cells work normally, and genes cannot be damaged. The most important factor in the fight against cancer and prevention of the development and progression of cancer is the immune system. This requires a nutritional state in which the immune system works well, allowing the intestinal microbiome to carry out all of its roles. In order to grow intestinal microbiota, the consumption of prebiotics, such as organic vegetables, fruits, and dietary fiber, and probiotics of effective intestinal microbiota, such as fermented foods and supplements, is required. Symbiosis, in which these organisms work together, is an effective means of reducing the risk of cancer. In addition, fecal microbiota transplantation (FMT) using ultrafine bubble water, produced specially by the Association for Clinical Research of Fecal Microbiota Transplantation Japan, is also useful for improving the nutritional condition and reducing the risk of cancer.

Oxidation of flooded paddy soil through irrigation with water containing bulk oxygen nanobubbles.

Nanobubbles (NBs) with a diameter of <1 µm have unique properties, including a long lifetime in water. Our previous study showed that irrigation with water containing bulk oxygen NBs (oxygen NB water) reduced seasonal methane (CH4) emissions from flooded rice cultivation by 21%. We therefore hypothesize that the CH4 emission reduction attributed to soil oxidation. To test this hypothesis, we carried out three sequential soil-column experiments under flooded and rice-unplanted conditions. They shared the same experimental settings, except for the lengths of soil storage before experiment (2-3 years) and of aerobic soil preincubation (7-13 days). The columns were manually irrigated with aerated tap water (control) or oxygen NB water. A tubing pump was operated to constantly drain leaching water from the column bottom. During the 57-day experimental periods, we regularly measured dissolved greenhouse gases in the drainage and leached heavy metals. The greater amount of leached manganese than of leached iron indicates that the reductive soil conditions were relatively weak in the three experiments. Oxygen NB water reduced the total dissolved CH4 emissions by 20-28% compared to control water. However, a significant difference (p < 0.05) was found only when the CH4 emission was greatest in the experiment with the shortest length of soil storage due to a high availability of soil labile carbon. Soil oxygen profiling using a microelectrode revealed that oxygen depletion at shallow depths (4-15 mm from the soil surface) was ameliorated by oxygen NB water on day 35 of experiment when the CH4 emission was smaller due to a limited soil labile carbon. The results confirm that irrigation with oxygen NB water reduces CH4 production in a flooded paddy soil through the oxidation of shallow soil.

Unraveling the mystery of ultrafine bubbles: Establishment of thermodynamic equilibrium for sub-micron bubbles and its implications.

HYPOTHESIS: We test the validity of the Young-Laplace equation and Henry's law for sub-micron bubble suspensions, which has long been a questionable issue. Application of the two theories allows characterization of bubble diameter and gas molecule partitioning between gaseous and dissolved phases using two easily measurable variables: total gas content (CT) and bubble volume concentration (BVC). EXPERIMENTS: We measure CT and BVC for sub-micron bubble suspensions generated from three pure gases, which allows calculation of bubble diameter for each suspension using the Young-Laplace equation and Henry's law. Uncertainties involved in the experimental measurements are assessed. Bubble size for each suspension is also directly measured using a dynamic light scattering (DLS) technique for comparison. FINDINGS: Applying the two theories we calculate that the bubble diameters are in the range of 304-518 nm, which correspond very well with the DLS-measured diameters. Sensitivity analyses demonstrate that the correspondence of the calculated and DLS-measured bubble diameters should take place only if the two theories are valid. The gas molecule partitioning analysis shows that >96% of gas molecules in the suspension exist as dissolved phase, which suggests the significance of the dissolved phase for applications of the bubble suspensions.