The Role of Mast Cells in the Remodeling Effects of Molecular Hydrogen on the Lung Local Tissue Microenvironment under Simulated Pulmonary Hypertension.

Molecular hydrogen (H) has antioxidant, anti-inflammatory, and anti-fibrotic effects. In a rat model simulating pulmonary fibrotic changes induced by monocrotaline-induced pulmonary hypertension (MPH), we had previously explored the impact of inhaled H on lung inflammation and blood pressure. In this study, we further focused the biological effects of H on mast cells (MCs) and the parameters of the fibrotic phenotype of the local tissue microenvironment.

Synaptic effects of xenon on NMDA receptor-mediated response in rat spinal neuron.

To investigate the precise mechanism of xenon (Xe), pharmacologically isolated AMPA/KA and NMDA receptor-mediated spontaneous (s) and evoked (e) excitatory postsynaptic currents (s/eEPSC and s/eEPSC) were recorded from mechanically isolated single spinal sacral dorsal commissural nucleus (SDCN) neurons attached with glutamatergic nerve endings (boutons) using conventional whole-cell patch-clamp technique. We analysed kinetic properties of both s/eEPSC and s/eEPSC by focal single- and/or paired-pulse electrical stimulation to compare them. The s/eEPSC showed smaller amplitude, slower rise time, and slower 1/e decay time constant (τ) than those of s/eEPSC.

Protein Kinase A Is Responsible for the Presynaptic Inhibition of Glycinergic and Glutamatergic Transmissions by Xenon in Rat Spinal Cord and Hippocampal CA3 Neurons.

The effects of a general anesthetic xenon (Xe) on spontaneous, miniature, electrically evoked synaptic transmissions were examined using the "synapse bouton preparation," with which we can clearly evaluate pure synaptic responses and accurately quantify pre- and postsynaptic transmissions. Glycinergic and glutamatergic transmissions were investigated in rat spinal sacral dorsal commissural nucleus and hippocampal CA3 neurons, respectively. Xe presynaptically inhibited spontaneous glycinergic transmission, the effect of which was resistant to tetrodotoxin, Cd, extracellular Ca, thapsigargin (a selective sarcoplasmic/endoplasmic reticulum Ca-ATPase inhibitor), SQ22536 (an adenylate cyclase inhibitor), 8-Br-cAMP (membrane-permeable cAMP analog), ZD7288 (an hyperpolarization-activated cyclic nucleotide-gated channel blocker), chelerythrine (a PKC inhibitor), and KN-93 (a CaMKII inhibitor) while being sensitive to PKA inhibitors (H-89, KT5720, and Rp-cAMPS).

Mast Cells as a Potential Target of Molecular Hydrogen in Regulating the Local Tissue Microenvironment.

Knowledge of the biological effects of molecular hydrogen (H), hydrogen gas, is constantly advancing, giving a reason for the optimism in several healthcare practitioners regarding the management of multiple diseases, including socially significant ones (malignant neoplasms, diabetes mellitus, viral hepatitis, mental and behavioral disorders). However, mechanisms underlying the biological effects of H are still being actively debated. In this review, we focus on mast cells as a potential target for H at the specific tissue microenvironment level.

Hydrogen-Rich Water Ameliorates Metabolic Disorder via Modifying Gut Microbiota in Impaired Fasting Glucose Patients: A Randomized Controlled Study.

Objective: Molecular hydrogen (H) exhibits antioxidant, anti-inflammatory and anti-apoptotic effects, and has shown benefits in glucose and lipid metabolism in certain animal metabolic disorder models. However, the potential benefits of H treatment in individuals with impaired fasting glucose (IFG) has seldom been studied. This randomized controlled study (RCT) aims to investigate the effects of hydrogen-rich water (HRW) on IFG subjects and explore the underlying mechanism involved.

Microglia states and nomenclature: A field at its crossroads.

Microglial research has advanced considerably in recent decades yet has been constrained by a rolling series of dichotomies such as "resting versus activated" and "M1 versus M2." This dualistic classification of good or bad microglia is inconsistent with the wide repertoire of microglial states and functions in development, plasticity, aging, and diseases that were elucidated in recent years. New designations continuously arising in an attempt to describe the different microglial states, notably defined using transcriptomics and proteomics, may easily lead to a misleading, although unintentional, coupling of categories and functions.

Daphnetin ameliorates Aβ pathogenesis via STAT3/GFAP signaling in an APP/PS1 double-transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) has become a major public health problem that affects the elderly population. Therapeutic compounds with curative effects are not available due to the complex pathogenesis of AD. Daphnetin, a natural coumarin derivative and inhibitor of various kinases, has anti-inflammatory and antioxidant activities.

Safflower leaf ameliorates cognitive impairment through moderating excessive astrocyte activation in APP/PS1 mice.

In addition to beta-amyloid (Aβ) plaques and neurofibrillary tangles, Alzheimer's disease (AD) is typically triggered or accompanied by abnormal inflammation, oxidative stress and astrocyte activation. Safflower ( L.) leaf, featuring functional ingredients, is a commonly consumed leafy vegetable.

Homeostatic and endocrine responses as the basis for systemic therapy with medical gases: ozone, xenon and molecular hydrogen.

Among medical gases, including gases used therapeutically, this review discusses the comparative physiological activity of three gases - ozone (O), xenon (Xe) and molecular hydrogen (H), which together form representatives of three types of substances - typical oxidizing, inert, and typical reducing agents. Upon analysis of published and proprietary data, we concluded that these three medical gases can manipulate the neuroendocrine system, by modulating the production or release of hormones via the hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-gonadal axes, or the gastrointestinal pathway. With repeated administration of the gases over time, these modulations become a predictable consequence of conditioned homeostatic reflexes, resulting in regulation of physiological activity.

A novel strategy for treating cancer: understanding the role of Ca signaling from nociceptive TRP channels in regulating cancer progression.

Cancer is an aging-associated disease and caused by genomic instability that is driven by the accumulation of mutations and epimutations in the aging process. Although Ca signaling, reactive oxygen species (ROS) accumulation, DNA damage response (DDR) and senescence inflammation response (SIR) are processed during genomic instability, the underlying mechanism for the cause of genomic instability and cancer development is still poorly understood and needs to be investigated. Nociceptive transient receptor potential (TRP) channels, which firstly respond to environmental stimuli, such as microbes, chemicals or physical injuries, potentiate regulation of the aging process by Ca signaling.

Sex Differences in Dendritic Spine Formation in the Hippocampus and Animal Behaviors in a Mouse Model of Hyperthyroidism.

Thyroid hormones are critical for the regulation of development and differentiation of neurons and glial cells in the central nervous system (CNS). We have previously reported the sex-dependent changes of glial morphology in the brain under the state of hyperthyroidism. Here, we examined sex-dependent changes in spine structure of granule neurons in the dentate gyrus of hippocampus in male and female mice with hyperthyroidism.

Neuroprotective and Preventative Effects of Molecular Hydrogen.

One of the beneficial effects of molecular hydrogen (H, hydrogen gas) is neuroprotection and prevention of neurological disorders. It is important and useful if taking H every day can prevent or ameliorate the progression of neurodegenerative disorders, such as Parkinson's disease or Alzheimer's disease, both lacking specific therapeutic drugs. There are several mechanisms of how H protects neuronal damage.

Activation of Toll-like receptor 5 in microglia modulates their function and triggers neuronal injury.

Microglia are the primary immune-competent cells of the central nervous system (CNS) and sense both pathogen- and host-derived factors through several receptor systems including the Toll-like receptor (TLR) family. Although TLR5 has previously been implicated in different CNS disorders including neurodegenerative diseases, its mode of action in the brain remained largely unexplored. We sought to determine the expression and functional consequences of TLR5 activation in the CNS.

Extracellular pH modulation of excitatory synaptic transmission in hippocampal CA3 neurons.

In this study, the effect of extracellular pH on glutamatergic synaptic transmission was examined in mechanically dissociated rat hippocampal CA3 pyramidal neurons using a whole-cell patch-clamp technique under voltage-clamp conditions. Native synaptic boutons were isolated without using any enzymes, using a so-called "synapse bouton preparation," and preserved for the electrical stimulation of single boutons. Both the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) were found to decrease and increase in response to modest acidic (~pH 6.

The Effects of 24-Week, High-Concentration Hydrogen-Rich Water on Body Composition, Blood Lipid Profiles and Inflammation Biomarkers in Men and Women with Metabolic Syndrome: A Randomized Controlled Trial.

Purpose: Metabolic syndrome is associated with several medical risk factors including dyslipidemia, hyperglycemia, and obesity, which has become a worldwide pandemic. The sequelae of this condition increase the risk of cardiovascular and neurological disease and increased mortality. Its pathophysiology is associated with redox dysregulation, excessive inflammation, and perturbation of cellular homeostasis.

Facilitation of microglial motility by thyroid hormones requires the presence of neurons in cell culture: A distinctive feature of the brainstem versus the cortex.

Microglia are critical for the refinement of neural networks that takes place during the perinatal period. Their phenotype and actions are guided by the signals produced by neighbouring cells and hormones present in their surrounding milieu. Cell populations and the signals they produce differ between regions.

Downregulation of the DNA 5-hydroxymethylcytosine is involved in mitochondrial dysfunction and neuronal impairment in high fat diet-induced diabetic mice.

DNA 5-hydroxymethylcytosine (5hmC), converted from 5-methylcytosine (5mC), is highly enriched in the central nervous system and is dynamically regulated during neural development and metabolic disorders. However, whether and how neural 5hmC is involved in metabolic disorders shows little evidence. In this study, significant downregulation of the DNA 5hmC were observed in the cerebral cortex of HFD-induced diabetic mice, while phosphated AMP-activated protein kinase (p-AMPK) and ten-eleven translocation 2 (TET2) reduced, and mitochondrial dysfunction.

Circulating messenger for neuroprotection induced by molecular hydrogen.

Molecular hydrogen (H) showed protection against various kinds of oxidative-stress-related diseases. First, it was reported that the mechanism of therapeutic effects of H was antioxidative effect due to inhibition of the most cytotoxic reactive oxygen species, hydroxy radical (•OH). However, after chronic administration of H in drinking water, oxidative-stress-induced nerve injury is significantly attenuated even in the absence of H.

Metabolic Plasticity of Astrocytes and Aging of the Brain.

As part of the blood-brain-barrier, astrocytes are ideally positioned between cerebral vasculature and neuronal synapses to mediate nutrient uptake from the systemic circulation. In addition, astrocytes have a robust enzymatic capacity of glycolysis, glycogenesis and lipid metabolism, managing nutrient support in the brain parenchyma for neuronal consumption. Here, we review the plasticity of astrocyte energy metabolism under physiologic and pathologic conditions, highlighting age-dependent brain dysfunctions.

Glial Activation and Expression of the Serotonin Transporter in Chronic Fatigue Syndrome.

Fatigue is commonly reported in a variety of illnesses and has major impact on quality of life. Chronic fatigue syndrome (CFS) is a debilitating syndrome of unknown etiology. The clinical symptoms include problems in neuroendocrine, autonomic, and immune systems.

Effects of Derinat on ischemia-reperfusion-induced pressure ulcer mouse model.

Sodium salt of deoxyribonucleic acid (DNA), Derinat, isolated from the soft roes of Russian sturgeon, has been utilized as an immunomodulator for the treatment of reactive oxygen species (ROS)-associated diseases in clinics. Here we show that treatment with Derinat has an anti-inflammatory and anti-oxidative effects on cutaneous ischemia-reperfusion (IR) injury in pressure ulcer (PU) model mice. Dorsal skin damage and dermal edema in mild PU model mice were attenuated by treatment with Derinat.

Correction to: Nicotine inhibits activation of microglial proton currents via interactions with α7 acetylcholine receptors.

The article Nicotine inhibits activation of microglial proton currents via interactions with α7 acetylcholine receptors, written by Mami Noda and AI Kobayashi, was originally published Online First without open access. After publication in volume 67, issue 1, pages 235-245.

Thyroid Hormone in the CNS: Contribution of Neuron-Glia Interaction.

The endocrine system and the central nervous system (CNS) are intimately linked. Among hormones closely related to the nervous system, thyroid hormones (THs) are critical for the regulation of development and differentiation of neurons and neuroglia and hence for development and function of the CNS. T3 (3,3',5-triiodothyronine), an active form of TH, is important not only for neuronal development but also for differentiation of astrocytes and oligodendrocytes, and for microglial development.