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Simple Summary: Living bodies comprise approximately 55–75% water to maintain homeostasis. However, little is known about the differences in in vivo water molecule dynamics (water structure dynamics; WSD) under physiological and pathophysiological statuses. Here, we examined the WSD of ex vivo samples in tumor-bearing mice versus healthy mice by dielectric spectroscopy using time domain reflectometry. Tumor tissues, from early after engrafting, exhibited remarkable features of WSD close to pure water, different from the other organs of tumor-bearing and healthy mice. Further, certain organs in tumor-bearing mice temporally revealed different WSD features compared to those in healthy mice. Conclusively, tumor-bearing mice revealed aberrant WSD, unlike healthy mice. Thus, dielectric spectroscopy in terms of WSD may provide novel pathophysiological perspectives in living organisms. Living bodies comprise approximately 55–75% water to maintain homeostasis. However, little is known about the comprehensive differences in in vivo water molecule dynamics (water structure dynamics; WSD) between physiological and pathophysiological statuses. Here, we examined the WSD of ex vivo tumor tissues and organs from tumor-bearing mice with engrafted mouse malignant melanoma cells (B16-F10) in the right flanks to compare with those in healthy mice, using time domain reflectometry of dielectric spectroscopy at days 9, 11, and 14 after engrafting. The relaxation parameters of relaxation time (τ), relaxation time distribution parameter (β), and relaxation strength (∆ε) were measured on tumor tissues and lung, liver, kidney, and skin tissues. Immediately afterward, the water contents (%) in the tumor and the other organs were calculated by measuring their weights before and after freeze-drying. Each parameter of the tumor was compared to that of pooled values of other organs in tumor-bearing (TO) and healthy mice (HO). The tumor water content temporarily increased compared to that of HO at day 11; the tumor volume was also prone to increase. In contrast, tumor tissues exhibited significantly higher values of β close to 1 of ultrapure water and ∆ε compared to TO and HO at all times. Moreover, β in the viscera of TO was prone to increase compared to that of HO with significantly higher levels at day 11. Conclusively, tumor-bearing mice exhibited systemically aberrant WSD, unlike healthy mice. Thus, dielectric spectroscopy in terms of WSD may provide novel pathophysiological perspectives in tumor-bearing living bodies. [ABSTRACT FROM AUTHOR]

Simple Summary: Fulminant myocarditis (FM) is a serious inflammatory lesion of the myocardium accompanied by cardiac dysfunction, transitioning to end-stage heart failure. Due to such a difficult pathology, a therapeutic strategy that exerts a steadfast effect has yet to be developed. Blood mononuclear cells (MNCs) have been previously shown to enhance the quality and quantity of cellular fractions (QQMNCs) with anti-inflammatory and vasculogenic potential using the one culture system. The aim of this study was to investigate whether transplantation therapy with hybrid cell sheets of fibroblasts and QQMNCs improves cardiac function in a rat model with experimental autoimmune myocarditis (EAM) induced by purified porcine cardiac myosin. The transplanted hybrid cell sheet exerts cardioprotective effects against EAM, resulting in limited left ventricular remodeling and partially improved cardiac functions due to revascularization, anti-inflammation, and anti-fibrosis. Thus, tissue engineering using hybrid cell sheets of fibroblasts constructed with QQMNCs is expected to provide an effective therapeutic option for patients with severe FM. Fulminant myocarditis causes impaired cardiac function, leading to poor prognosis and heart failure. Cell sheet engineering is an effective therapeutic option for improving cardiac function. Naïve blood mononuclear cells (MNCs) have been previously shown to enhance the quality and quantity of cellular fractions (QQMNCs) with anti-inflammatory and vasculogenic potential using the one culture system. Herein, we investigated whether autologous cell sheet transplant with QQMNCs improves cardiac function in a rat model with experimental autoimmune myocarditis (EAM). Fibroblast sheets (F-sheet), prepared from EAM rats, were co-cultured with or without QQMNCs (QQ+F sheet) on temperature-responsive dishes. QQ+F sheet induced higher expression of anti-inflammatory and vasculogenic genes (Vegf-b, Hgf, Il-10, and Mrc1/Cd206) than the F sheet. EAM rats were transplanted with either QQ+F sheet or F-sheet, and the left ventricular (LV) hemodynamic analysis was performed using cardiac catheterization. Among the three groups (QQ+F sheet, F-sheet, operation control), the QQ+F sheet transplant group showed alleviation of end-diastolic pressure–volume relationship on a volume load to the same level as that in the healthy group. Histological analysis revealed that QQ+F sheet transplantation promoted revascularization and mitigated fibrosis by limiting LV remodeling. Therefore, autologous QQMNC-modified F-sheets may be a beneficial therapeutic option for EAM. [ABSTRACT FROM AUTHOR]

Simple Summary: Molecular hydrogen (MH) reportedly exerts therapeutic effects against inflammatory diseases by alleviating oxidative stress. We investigated the cardiovascular protective effects of molecular hydrogen water (MHW) intake using high-fat diet-induced obesity (DIO) mice. We observed that MHW intake for 2 weeks did not improve the blood sugar level or body weight but decreased heart weight in DIO mice. Notably, MHW intake alleviated oxidative stress in both the heart and the adipose tissue. Moreover, it improved cardiac hypertrophy and restored left ventricular function in DIO mice, and promoted the histological conversion of energy storage to expenditure in adipose tissues with the upregulation of thermogenic and cardiovascular protective genes. Furthermore, MHW restored endothelial progenitor cell (EPC) bioactivity to maintain vascular homeostasis. Taken together, MHW intake exerts cardiovascular protective effects in DIO mice. Hence, MHW intake is a potential prophylactic strategy against cardiovascular disorders in metabolic syndrome. Molecular hydrogen (MH) reportedly exerts therapeutic effects against inflammatory diseases as a suppressor of free radical chain reactions. Here, the cardiovascular protective effects of the intake of molecular hydrogen water (MHW) were investigated using high-fat diet-induced obesity (DIO) mice. MHW was prepared using supplier sticks and degassed water as control. MHW intake for 2 weeks did not improve blood sugar or body weight but decreased heart weight in DIO mice. Moreover, MHW intake improved cardiac hypertrophy, shortened the width of cardiomyocytes, dilated the capillaries and arterioles, activated myocardial eNOS-Ser-1177 phosphorylation, and restored left ventricular function in DIO mice. MHW intake promoted the histological conversion of hypertrophy to hyperplasia in white and brown adipose tissues (WAT and BAT) with the upregulation of thermogenic and cardiovascular protective genes in BAT (i.e., Ucp-1, Vegf-a, and eNos). Furthermore, the results of a colony formation assay of bone-marrow-derived endothelial progenitor cells (EPCs) indicated that MHW activated the expansion, differentiation, and mobilization of EPCs to maintain vascular homeostasis. These findings indicate that the intake of MHW exerts cardiovascular protective effects in DIO mice. Hence, drinking MHW is a potential prophylactic strategy against cardiovascular disorders in metabolic syndrome. [ABSTRACT FROM AUTHOR]

The dynamics of a hydrogen bonding network (HBN) relating to macroscopic properties of hydrogen bonding liquids were observed as a significant relaxation process by dielectric spectroscopy measurements. In the cases of water and water rich mixtures including biological systems, a GHz frequency relaxation process appearing at around 20 GHz with the relaxation time of 8.2 ps is generally observed at 25 °C. The GHz frequency process can be explained as a rate process of exchanges in hydrogen bond (HB) and the rate becomes higher with increasing HB density. In the present work, this study analyzed the GHz frequency process observed by suitable open-ended coaxial electrodes, and physical meanings of the fractal nature of water structures were clarified in various aqueous systems. Dynamic behaviors of HBN were characterized by a combination of the average relaxation time and the distribution of the relaxation time. This fractal analysis offered an available approach to both solution and dispersion systems with characterization of the aggregation or dispersion state of water molecules. In the case of polymer-water mixtures, the HBN and polymer networks penetrate each other, however, the HBN were segmented and isolated more by dispersed and aggregated particles in the case of dispersion systems. These HBN fragments were characterized by smaller values of the fractal dimension obtained from the fractal analysis. Some examples of actual usages suggest that the fractal analysis is now one of the most effective tools to understand the molecular mechanism of HBN in aqueous complex materials including biological systems. [ABSTRACT FROM AUTHOR]