Explore the vast range of titles available.

Intraperitoneal administration of hydrogen (H 2 )-containing saline inhibited neuronal cell death in ischemic stroke in a number of animal models, but it is unknown whether H 2 is absorbed from the abdominal cavity into the blood and reaches the brain. In this study, we investigated whether intraperitoneal administration of saline containing H 2 inhibits neuronal cell death caused by cerebral ischemia and measured the concentration of H 2 in the carotid artery and inferior vena cava (IVC). Gerbils were subjected to transient unilateral cerebral ischemia twice, and saline or H 2 -rich saline was administered intraperitoneally three or seven times every 12 hours. We evaluated the number of apoptotic cells in the hippocampus and cerebral cortex on day 3 and the number of viable neurons in the hippocampus and cerebral cortex on day 7. In addition, a single dose of saline or H 2 -rich saline was administered intraperitoneally, and blood H 2 levels in the carotid artery and IVC were measured. On day 3 of ischemia/reperfusion, the number of neurons undergoing apoptosis in the cortex was significantly lower in the H 2 -rich saline group than in the saline group, and on day 7, the number of viable neurons in the hippocampus and cerebral cortex was significantly higher in the H 2 -rich saline group. Intraperitoneal administration of H 2 -rich saline resulted in large increases in H 2 concentration in the IVC ranging from 0.00183 mg/L (0.114%) to 0.00725 mg/L (0.453%). In contrast, carotid H 2 concentrations remained in the range of 0.00008 mg/L (0.0049%) to 0.00023 (0.0146%). On average, H 2 concentrations in carotid artery were 0.04 times lower than in IVC. These results indicate that intraperitoneal administration of H 2 -rich saline significantly suppresses neuronal cell death after cerebral ischemia, even though H 2 hardly reaches the brain.

A recent clinical study demonstrated that haemodialysis with a dialysate containing hydrogen (H 2 ) improves blood pressure control in end-stage kidney disease. Herein, we examined whether H 2 has a salutary effect on hypertension in animal models. We subjected 5/6 nephrectomised rats to inhalation of either H 2 (1.3% H 2  + 21% O 2  + 77.7% N 2 ) or control (21% O 2  + 79% N 2 ) gas mixture for 1 h per day. H 2 significantly suppressed increases in blood pressure after 5/6 nephrectomy. The anti-hypertensive effect of H 2 was also confirmed in rats in a stable hypertensive state 3 weeks after nephrectomy. To examine the detailed effects of H 2 on hypertension, we used an implanted telemetry system to continuously monitor blood pressure. H 2 exerted an anti-hypertensive effect not only during daytime rest, but also during night-time activities. Spectral analysis of blood pressure variability revealed that H 2 improved autonomic imbalance, namely by suppressing the overly active sympathetic nervous system and augmenting parasympathetic nervous system activity; these effects co-occurred with the blood pressure-lowering effect. In conclusion, 1-h daily exposure to H 2 exerts an anti-hypertensive effect in an animal model of hypertension.

We aimed to investigate the reliability and validity of sweat lactate threshold (sLT) measurement based on the real-time monitoring of the transition in sweat lactate levels (sLA) under hypoxic exercise. In this cross-sectional study, 20 healthy participants who underwent exercise tests using respiratory gas analysis under hypoxia (fraction of inspired oxygen [FiO 2 ], 15.4 ± 0.8%) in addition to normoxia (FiO 2 , 20.9%) were included; we simultaneously monitored sLA transition using a wearable lactate sensor. The initial significant elevation in sLA over the baseline was defined as sLT. Under hypoxia, real-time dynamic changes in sLA were successfully visualized, including a rapid, continual rise until volitionary exhaustion and a progressive reduction in the recovery phase. High intra- and inter-evaluator reliability was demonstrated for sLT’s repeat determinations (0.782 [0.607–0.898] and 0.933 [0.841–0.973]) as intraclass correlation coefficients [95% confidence interval]. sLT correlated with ventilatory threshold (VT) (r = 0.70, p < 0.01). A strong agreement was found in the Bland–Altman plot (mean difference/mean average time: − 15.5/550.8 s) under hypoxia. Our wearable device enabled continuous and real-time lactate assessment in sweat under hypoxic conditions in healthy participants with high reliability and validity, providing additional information to detect anaerobic thresholds in hypoxic conditions.

In the evaluation of myocardial infarction, cardiac MRI remains problematic in terms of sensitivity and quantitativeness. Thus, we sought to delineate pathological microstructural alterations across temporal phases subsequent to myocardial ischemia–reperfusion (IR) injury utilizing q-space imaging (QSI), an advanced diffusion imaging methodology proficient in assessing the non-Gaussian diffusion patterns of molecules. Rats were subjected to IR injury, and infarct was evaluated at 2, 7, and 30 days via histopathological staining and MRI using a 9.4‐Tesla system. QSI was performed with gadolinium-enhanced T1-weighted imaging (T1WI) for comparative assessment. Correlation coefficients among images were computed at each level of the left ventricular short-axis cross-section to juxtapose the infarct dimensions and morphology. Axial diffusivity of the kurtosis maps at 2, 7, and 30 days revealed substantial correlations with the hyperintense areas noted on T1WI (R 2  = 0.885, 0.947, and 0.929, respectively). Furthermore, a strong correlation was noted with the transmural extent of infarction. Even in the absence of gadolinium contrast, the high-intensity regions delineated by QSI were concordant with the extent of pathological infarction (R 2  = 0.977). These findings highlight the capability of QSI in identifying pathological changes at the infarct site, independent of gadolinium contrast media and irrespective of the temporal phase subsequent to the IR onset.

A simple, non-invasive algorithm for maximal lactate steady state (MLSS) assessment has not been developed. We examined whether MLSS can be estimated from the sweat lactate threshold (sLT) using a novel sweat lactate sensor for healthy adults, with consideration of their exercise habits. Fifteen adults representing diverse fitness levels were recruited. Participants with/without exercise habits were defined as trained/untrained, respectively. Constant-load testing for 30 min at 110%, 115%, 120%, and 125% of sLT intensity was performed to determine MLSS. The tissue oxygenation index (TOI) of the thigh was also monitored. MLSS was not fully estimated from sLT, with 110%, 115%, 120%, and 125% of sLT in one, four, three, and seven participants, respectively. The MLSS based on sLT was higher in the trained group as compared to the untrained group. A total of 80% of trained participants had an MLSS of 120% or higher, while 75% of untrained participants had an MLSS of 115% or lower based on sLT. Furthermore, compared to untrained participants, trained participants continued constant-load exercise even if their TOI decreased below the resting baseline (P < 0.01). MLSS was successfully estimated using sLT, with 120% or more in trained participants and 115% or less in untrained participants. This suggests that trained individuals can continue exercising despite decreases in oxygen saturation in lower extremity skeletal muscles.

Background/Objectives: Although many healthy foods are used for elderly humans, there are no suitable animal models to test them. We reared microminipigs (MMPs) for over 10 years, establishing aged MMP models. Using this aged preclinical model, we evaluated the effects of a polyphenol-rich diet without sacrificing the animals. Methods: A polyphenol-rich diet containing sweet potato petioles and leaves was administered to the aged MMPs daily for one month. Changes in fecal microbiota and aging-related cells in the peripheral blood before and after administration were assessed. Results: Administration of a diet containing sweet potato petiole and leaf resulted in increased abundance of the genera Muribaculaceae, Oscillibacter, and Desulfovibrio and a decreased abundance of the genus UCG-002 within the family Oscillospiraceae. Prediction of metabolic enzyme activity from microbiota composition identified 77 enzymes significantly altered after administration. KEGG Mapper analysis of these enzymes revealed their involvement in 27 pathways. Flow cytometry analysis of peripheral blood revealed no significant differences in the proportion of ß-galactosidase-positive cells in either group. In contrast, a significant increase in the number of Ki-67-positive cells was observed in some individuals in the treatment group. However, no significant differences in Ki-67 expression were detected after stimulation with anti-CD3/CD28 antibodies. Conclusions: We established an aged MMP model to evaluate the efficacy and safety of drugs and health foods in elderly humans. Using this model, sweet potato petioles and leaves were shown to have potential as candidate materials for future health food research.

Unmethylated cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) induce inflammatory cytokines and type I interferons (IFNs) to activate the immune system. To apply CpG ODNs as vaccine adjuvants, the cellular uptake and stability of phosphodiester-based, non-modified ODNs require further improvement. Previously developed new CpG ODNs forming guanine-quadruplex (G4) structures showed higher nuclease resistance and cellular uptake than linear CpG ODNs; however, the complex formation of G4-CpG ODNs with antigen proteins is necessary for their application as vaccine adjuvants. In this study, we utilized a cationic polymer, ε-poly-L-lysine (ε-PLL), as a carrier for G4-CpG ODNs and antigen. The ε-PLL/G4-CpG ODN complex exhibited enhanced stability against nucleases. Cellular uptake of the ε-PLL/G4-CpG ODN complex positively correlated with the N/P ratio. In comparison to naked G4-CpG ODNs, the ε-PLL/G4-CpG ODN complex induced extremely high levels of interleukin (IL)-6, IL-12, and IFN-β. Relative immune cytokine production was successfully tuned by N/P ratio modification. Mice with the ε-PLL/G4-CpG ODN/ovalbumin (OVA) complex showed increased OVA-specific immunoglobulin (Ig)G, IgG1, and IgG2c levels, whereas total IgE levels did not increase and weight gain rates were not affected. Therefore, ε-PLL can serve as a safe and effective phosphodiester-based, non-modified CpG ODN delivery system, and the ε-PLL/G4-CpG ODN/antigen complex is a highly promising candidate for vaccine adjuvants and can be further used in clinical research.

Unmethylated cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) induce inflammatory cytokines and type I interferons (IFNs) to activate the immune system. To apply CpG ODNs as vaccine adjuvants, the cellular uptake and stability of phosphodiester-based, non-modified ODNs require further improvement. Previously developed new CpG ODNs forming guanine-quadruplex (G4) structures showed higher nuclease resistance and cellular uptake than linear CpG ODNs; however, the complex formation of G4-CpG ODNs with antigen proteins is necessary for their application as vaccine adjuvants. In this study, we utilized a cationic polymer, ε-poly-[sub.L] -lysine (ε-PLL), as a carrier for G4-CpG ODNs and antigen. The ε-PLL/G4-CpG ODN complex exhibited enhanced stability against nucleases. Cellular uptake of the ε-PLL/G4-CpG ODN complex positively correlated with the N/P ratio. In comparison to naked G4-CpG ODNs, the ε-PLL/G4-CpG ODN complex induced extremely high levels of interleukin (IL)-6, IL-12, and IFN-β. Relative immune cytokine production was successfully tuned by N/P ratio modification. Mice with the ε-PLL/G4-CpG ODN/ovalbumin (OVA) complex showed increased OVA-specific immunoglobulin (Ig)G, IgG1, and IgG2c levels, whereas total IgE levels did not increase and weight gain rates were not affected. Therefore, ε-PLL can serve as a safe and effective phosphodiester-based, non-modified CpG ODN delivery system, and the ε-PLL/G4-CpG ODN/antigen complex is a highly promising candidate for vaccine adjuvants and can be further used in clinical research.

Background We investigated the effects of dental infection with Porphyromonas gingivalis ( P.g. ), an important periodontal pathogen, on NASH progression, by feeding mice a high fat diet (HFD)and examining P.g. infection in the liver of NASH patients. Methods C57BL/6J mice were fed either chow-diet (CD) or HFD for 12 weeks, and then half of the mice in each group were infected with P.g. from the pulp chamber (HFD- P.g. (−), HFD- P.g. (+), CD- P.g. (−) and CD- P.g. (+)). Histological and immunohistochemical examinations, measurement of serum lipopolysaccharide (LPS) levels and ELISA for cytokines in the liver were performed. We then studied the effects of LPS from P.g. ( P.g. -LPS) on palmitate-induced steatotic hepatocytes in vitro, and performed immunohistochemical detection of P.g. in liver biopsy specimens of NASH patients. Results Serum levels of LPS are upregulated in P.g. (+) groups. Steatosis of the liver developed in HFD groups, and foci of Mac2-positive macrophages were prominent in HFD- P.g. (+). P.g. was detected in Kupffer cells and hepatocytes. Interestingly, areas of fibrosis with proliferation of hepatic stellate cells and collagen formation were only observed in HFD- P.g. (+). In steatotic hepatocytes, expression of TLR2, one of the P.g. -LPS receptors, was upregulated. P.g. -LPS further increased mRNA levels of palmitate-induced inflammasome and proinflammatory cytokines in steatotic hepatocytes. We demonstrated for the first time that P.g. existed in the liver of NASH patients with advanced fibrosis. Conclusions Dental infection of P.g. may play an important role in NASH progression through upregulation of the P.g. -LPS-TLR2 pathway and activation of inflammasomes. Therefore, preventing and/or eliminating P.g. infection by dental therapy may have a beneficial impact on management of NASH.