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.

Emergence of Novel Type C Botulism Strain in Household Outbreak, Japan.

In 2021, an outbreak of food poisoning caused by Clostridium botulinum type C occurred in Kumamoto, Japan. Analysis of the isolated strain revealed that it possessed the bont/C gene and was slightly different from the reference bont/C gene. The risk for human infection with this new toxin type may be low.

Alteration of hemoglobin ß gene expression in mucosal tissues of Japanese flounder, Paralichthys olivaceus, in response to heat stress, Edwardsiella piscicida infection, and immunostimulants administration.

Hemoglobin beta (Hbß) is a heme-binding protein capable of oxygen delivery. The oligopeptides derived from Hbß in fish mucus are active against a variety of gram-negative bacteria and protozoa. To gain information on the physiological and immunological roles of Hbß in the mucosal tissues of fish, we analyzed changes in Hbß gene expression levels in the epidermis, gills, and intestine of Japanese flounder, Paralichthys olivaceus, in response to heat stress, Edwardsiella piscicida infection, and trial feeding of immunostimulants, high-concentration ascorbic acid (AsA) or lactoferrin (LF). The results of quantitative real-time PCR showed that expression of the Hbß gene in the gills decreased markedly when exposed to heat stress, whereas that in the epidermis exhibited an increase 3h after infection with E. piscicida. Seven days after starting to feed either immunostimulant, epidermal Hbß gene expression in all AsA or LF dose groups was significantly higher than in the control group. The results of in situ hybridization showed that the abundance and intensity of the stained cells in the epidermis and in the gills were consistent with the expression levels of Hbß gene obtained from the infection and immunosuppressant experiments and the heat stress experiment, respectively. Our results suggest that mucosal Hbß gene expression is closely related to physiological and immunological status and could be a useful indicator for monitoring condition of fish health.

Enhancement of immune proteins expression in skin mucus of Japanese flounder Paralicthys olivaceus upon feeding a diet supplemented with high concentration of ascorbic acid.

To search immune defense proteins in skin mucus of Japanese flounder fed with a diet containing high concentration of ascorbic acid, we carried out 2D-PAGE and compared the resolved pattern of proteins between control group that fed commercial diet and ascorbic acid supplemented group (AsA group) fed a diet supplemented with high concentration of ascorbic acid (2,000 mg/kg) for 7 days. The results revealed that there were many proteins exhibited distinct increase in AsA group. Among them, 6 regions that showed a dramatic elevation were chosen for protein identification using LC-MS/MS analysis and Mascot database search. Six proteins were identified, i.e. serotransferrin (Sero), transferrin (Trans), warm temperature acclimation-related 65 kDa protein (Wap65), complement component c3 (C3), hemoglobin beta-A chain (Hbß) and apolipoprotein A-1 (Apo). Quantitative RT-PCR analysis showed that the mRNA level of Hbß in epidermis of AsA group gave much higher increase (11.6 folds) than control group; the levels of Sero/Trans, Wap65, C3 and Apo showed no apparent difference between the two groups. The mRNA levels of wap65 and c3 in the liver and Apo in the kidney of AsA group exhibited significant increase in comparison to control group. In the case of secreted immunoglobulin M (IgM) and lysozyme (lyz), no difference of the mRNA levels of IgM in epidermis, gill, kidney, spleen and intestine, and lyz in epidermis, gill, spleen and intestine, was observed. The results of in situ hybridization confirmed the elevation of Hbß mRNA level in the epidermis tissue of AsA group. Our present study provided additional evidence showing the effectiveness of AsA in activating innate immune defense system in skin mucosal tissue of fish.

Birch-Type Reduction of Arenes in 2-Propanol Catalyzed by Zero-Valent Iron and Platinum on Carbon.

Catalytic arene reduction was effectively realized by heating in 2-propanol/water in the presence of Pt on carbon (Pt/C) and metallic Fe. 2-Propanol acted as a hydrogen source, obviating the need for flammable (and hence, dangerous and hard-to-handle) hydrogen gas, while metallic Fe acted as an essential co-catalyst to promote reduction. The chemical states of Pt and Fe in the reaction mixture were determined by X-ray absorption near-edge structure analysis, and the obtained results were used to suggest a plausible reaction mechanism, implying that catalytic reduction involved Pt- and Fe-mediated single-electron transfer and the dehydrogenation of 2-propanol.

Histone deacetylase inhibitors sensitize 5-fluorouracil-resistant MDA-MB-468 breast cancer cells to 5-fluorouracil.

Resistance to 5-fluorouracil (5-FU) is a serious problem in cancer therapy and overcoming it is required in order to improve the efficacy of cancer chemotherapy. Histone deacetylase (HDAC) inhibitors are used in cancer treatments and, recently, it has been reported that HDAC inhibitors can overcome resistance to various anti-cancer drugs in vitro. In the present study, a 5-FU-resistant breast cancer cell line was established, and the effects of HDAC inhibitors in these cells were examined. The 5-FU-resistant cell line MDA-MB-468 (MDA468/FU) was established by continuous exposure of the parental cells to 5-FU. This subline was characterized by high resistance to 5-FU, higher mRNA expression levels of thymidylate synthetase and dihydropyrimidine dehydrogenase (DPD), and lower mRNA expression levels of uridine monophosphate synthetase (UMPS) than the parental cells. Gimeracil, a DPD inhibitor, did not affect the sensitivity of MDA468/FU cells to 5-FU. Oteracil, a UMPS inhibitor, decreased the cytotoxicity of 5-FU in MDA468 cells, but not in MDA468/FU cells. The HDAC inhibitors, valproic acid and suberanilohydroxamic acid sensitized the two cell lines to 5-FU in a concentration-dependent manner. In conclusion, the results of the present study revealed that HDAC inhibitors increase the sensitivity to 5-FU in 5-FU-sensitive and -resistant cells.

Augmentation of the cytotoxic effects of nitrogen-containing bisphosphonates in hypoxia.

OBJECTIVES: Tumour hypoxia is a major obstacle in cancer therapy that leads to poor prognosis. Therefore, the development of cancer treatments that are effective in hypoxia is necessary. Nitrogen-containing bisphosphonates (N-BPs), which are used to treat bone disease, are cytotoxic to several cancer cells in normoxia. Therefore, we investigated the cytotoxicity of N-BPs in cancer cells in hypoxia. METHODS: We studied the cytotoxicities of N-BPs, statins and anticancer drugs in human cancer cells under hypoxic conditions (1% O2 ). The expression levels of enzymes in the mevalonate pathway in hypoxia were measured by real-time reverse transcription polymerase chain reaction and Western blotting. KEY FINDINGS: In hypoxia, cell growth inhibition by 5-fluorouracil and cisplatin was not changed as compared to that in normoxia; however, cell growth inhibition by N-BPs and via zoledronate-induced apoptosis was higher in hypoxia than that in normoxia. Furthermore, geranylgeraniol completely inhibited the growth inhibitory effects of zoledronate. Additionally, the mRNA and protein levels of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase significantly decreased in hypoxia. Moreover, simvastatin potentiated the growth inhibitory effect of zoledronate. CONCLUSIONS: The cytotoxicity of N-BPs, but not 5-fluorouracil and cisplatin, is potentiated in hypoxia, through the loss of HMG-CoA reductase function. N-BPs may be effective against cancer in normoxia and hypoxia.

Why nurses make medication errors: a simulation study.

The purpose of this study was to investigate about the communication problems in the team nursing systems, if the requests for medication between nurses happen. For this study, we developed a simulation involving a nurse giving a medication prepared by another nurse. Baseline data was collected from 100 third-year nursing students and 163 nurses of two municipal hospitals further subdivided into three groups by their service years. The responders attributing to the errors in the simulation were compared. As a result, the more service years the fewer nurses there were who attributed medication errors to no explanation and no confirmation between nurses. The nurses whose service years were less than five years had a low level of awareness regarding no explanation of a nurse leader requesting the medications as well as the students. These findings suggested that there is the possibility that some medication errors occur due to preoccupation that nurses feel it is less necessary to explain and confirm everything related to medication administrations as their length of service increase. Nurses have a communication problem that is influenced by the relationship in the workplace in the team nursing system. Therefore, the requests for medication should no be permitted.