Mirogabalin inhibits scratching behavior of spontaneous model mouse of atopic dermatitis.

Atopic dermatitis (AD) is one of the most prevalent intractable chronic itch diseases worldwide. In recent years, new molecular-targeted drugs have emerged, but side effects and economic challenges remain. Therefore, since it is important for AD patients to have a wider range of treatment options, it is important to explore new therapeutic agents.

Photobiomodulation transiently increases the spontaneous firing in the superficial layer of the rat spinal dorsal horn.

The therapeutic benefits of photobiomodulation (PBM) in pain management, although well documented, are accompanied by concerns about potential risks, including pain, particularly at higher laser intensities. This study investigated the effects of laser intensity on pain perception using behavioral and electrophysiological evaluations in rats. Our results show that direct laser irradiation of 1000 mW/cm to the sciatic nerve transiently increases the frequency of spontaneous firing in the superficial layer without affecting the deep layer of the spinal dorsal horn, and this effect reverses to pre-irradiation levels after irradiation.

Quantitative analysis of liver standardized uptake value repeatability in SPECT/CT implications for clinical practice.

. The aim of this study was to assess the repeatability of the SUV normalized by liver volume (SUVL) between two liver receptor SPECT/CT studies performed on different days in patients with ICG-R15 values within normal range..

Combined Experiments with in Vivo Fiber Photometry and Behavior Tests Can Facilitate the Measurement of Neuronal Activity in the Primary Somatosensory Cortex and Hyperalgesia in an Inflammatory Pain Mice Model.

The pain matrix, which includes several brain regions that respond to pain sensation, contribute to the development of chronic pain. Thus, it is essential to understand the mechanism of causing chronic pain in the pain matrix such as anterior cingulate (ACC), or primary somatosensory (S1) cortex. Recently, combined experiment with the behavior tests and in vivo calcium imaging using fiber photometry revealed the interaction between the neuronal function in deep brain regions of the pain matrix including ACC and the phenotype of chronic pain.

Isolation and Purification of Harpagogenin as an Nrf2-ARE Activator from the Tubers of Chinese Artichoke (Stachys sieboldii).

Chinese artichoke tuber (Stachys sieboldii Miq.) is used as an herbal medicine as well as edible food. This study examined the effect of the Chinese artichoke extracts on the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway that induces the expression of antioxidant enzymes to explore its novel characteristics.

Detection of Dietary Chalcone and Flavonoid Metabolites in Mice Using UPLC-MS/MS and Their Modulatory Effects on Amyloid β Aggregation.

Amyloid β-protein (Aβ42) aggregates have been demonstrated to induce cognitive decline and neurodegeneration in Alzheimer's disease (AD). Thus, functional food ingredients that inhibit Aβ42 aggregation are valuable for AD prevention. Although several food ingredients have been studied for their anti-aggregation activity, information on their bioavailability in the brain, incorporated forms, and relevance to AD etiology is limited.

Relationship between Laser Intensity at the Peripheral Nerve and Inhibitory Effect of Percutaneous Photobiomodulation on Neuronal Firing in a Rat Spinal Dorsal Horn.

Photobiomodulation is an effective treatment for pain. We previously reported that the direct laser irradiation of the exposed sciatic nerve inhibited firing in the rat spinal dorsal horn evoked by mechanical stimulation, corresponding to the noxious stimulus. However, percutaneous laser irradiation is used in clinical practice, and it is unclear whether it can inhibit the firing of the dorsal horn.

Combining 99mTc-GSA single-photon emission-computed tomography and Gd-EOB-DTPA-enhanced magnetic resonance imaging for staging liver fibrosis.

Preoperative assessment of the degree of liver fibrosis is important to determine treatment strategies. In this study, galactosyl human serum albumin single-photon emission-computed tomography and ethoxybenzyl (EOB) contrast-enhanced magnetic resonance imaging (MRI) were used to assess the changes in hepatocyte function after liver fibrosis, and the standardized uptake value (SUV) was combined with gadolinium EOB-diethylenetriaminepentaacetic acid to evaluate its added value for liver fibrosis staging. A total of 484 patients diagnosed with hepatocellular carcinoma who underwent liver resection between January 2010 and August 2018 were included.

Near-Infrared Photobiomodulation of the Peripheral Nerve Inhibits the Neuronal Firing in a Rat Spinal Dorsal Horn Evoked by Mechanical Stimulation.

Photobiomodulation has analgesic effects via inhibition of nerve activity, but few reports have examined the effects on the spinal dorsal horn, the entry point for nociceptive information in the central nervous system. In this study, we evaluated the effects of laser irradiation of peripheral nerve axons, which are conduction pathways for nociceptive stimuli, on the neuronal firing in lamina II of the spinal dorsal horn of a rat evoked by mechanical stimulation with von Frey filaments (vFF). In order to record neuronal firing, electrodes were inserted into lamina II of the exposed rat spinal dorsal horn.

Chronic Treatment with Aβ42 with a Toxic Conformer and LPS Induces Inflammatory Responses in BV-2 Microglia with Dysregulation of Hypoxia-Inducible Factor Expression.

Amyloid β (Aβ) plays a key role in the pathology of Alzheimer's disease (AD) and is toxic owing to its ability to aggregate into oligomers and fibrils. Aβ has high aggregative ability and potent toxicity due to the "toxic turn" at positions 22 and 23. Furthermore, APP knock-in mice producing E22P-Aβ with the toxic turn exhibited AD-related phenotypes such as cognitive impairment, Aβ plaque accumulation, and tau hyperphosphorylation.

APP Knock-In Mice Produce E22P-Aβ Exhibiting an Alzheimer's Disease-like Phenotype with Dysregulation of Hypoxia-Inducible Factor Expression.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that requires further pathological elucidation to establish effective treatment strategies. We previously showed that amyloid β (Aβ) toxic conformer with a turn at positions 22-23 is essential for forming highly toxic oligomers. In the present study, we evaluated phenotypic changes with aging in AD model (NL-P-F) mice with Swedish mutation (NL), Iberian mutation (F), and mutation (P) overproducing E22P-Aβ, a mimic of toxic conformer utilizing the knock-in technique.

Light-Touch-Induced Afterdischarge Firing in the Superficial Spinal Dorsal Horn Neurons in Hairless Mice with Irritant Contact Dermatitis.

The skin is an important barrier that protects against invasion by foreign substances, including irritants and harmful microorganisms, and holds water in the body. Washing the skin with cleansers and shampoos containing anionic surfactants, for example sodium dodecyl sulfate (SDS), is important for maintaining skin homeostasis. However, surfactants can cause dermatitis, cutaneous hypersensitivity (e.

Optimization of the Linker Length in the Dimer Model of E22P-Aβ40 Tethered at Position 38.

Since amyloid β (Aβ) oligomers are more cytotoxic than fibrils, various dimer models have been synthesized. We focused on the C-terminal region that could form a hydrophobic core in the aggregation process and identified a toxic conformer-restricted dimer model (E22P,G38DAP-Aβ40 dimer) with an l,l-2,6-diaminopimelic acid linker ( = 3) at position 38, which exhibited moderate cytotoxicity. We synthesized four additional linkers ( = 2, 4, 5, 7) to determine the most appropriate distance between the two Aβ40 monomers for a toxic dimer model.

TPNA10168, an Nrf-2 activator, attenuates inflammatory responses independently of Nrf2 in microglial BV-2 cells: Involvement of the extracellular-signal-regulated kinase pathway.

Some chemical Nrf2 inducers possess antioxidant and anti-inflammatory properties. TPNA10168, which was identified from a chemical library as a potential activator of the Keap1-Nrf2-ARE pathway, exhibits a neuroprotective effect against oxidative stress-induced injury. However, it has not been investigated as an anti-inflammatory agent.

Histamine enhances ATP-induced itching and responsiveness to ATP in keratinocytes.

Mechanical stimulation of cultured keratinocytes and a living epidermis increases intracellular calcium ion concentrations ([Ca]) in stimulated cells. This action propagates a Ca wave to neighboring keratinocytes via ATP/P2Y receptors. Recent behavioral, pharmacological studies revealed that exogenous ATP induces itching via P2X receptors in mice.

Establishing a high throughput drug screening system for cerebral ischemia using zebrafish larvae.

We previously generated an ischemic stroke in a zebrafish model using N gas perfusion; however, this model was an unsuitable drug screening system due to low throughput. In this study, we examined a zebrafish ischemic stroke model using an oxygen absorber to assess drug effects. Hypoxic exposure more than 2 h using the oxygen absorber significantly induced cell death in the brain and damage to the neuronal cells.

Panaxytriol Inhibits Lipopolysaccharide-Induced Microglia Activation in Brain Inflammation in Vivo.

Brain inflammation is a pathological characteristic of neurodegenerative diseases. In this condition, excessively activated microglia elevate proinflammatory mediator levels. We previously reported that panaxytriol inhibited lipopolysaccharide (LPS)-induced microglia activation in vitro.

In vivo brain ischemia-reperfusion model induced by hypoxia-reoxygenation using zebrafish larvae.

Cerebral infarct is caused by cerebrovascular occlusion and results in brain damage. Although many rodent models of cerebral infarct exist, there is none based on zebrafish. In this study, we developed a novel ischemia-reperfusion model induced by hypoxic treatment using zebrafish.

Inhibitory effect of panaxytriol on BV-2 microglial cell activation.

Activated microglia induce brain inflammation and neuronal death. Panaxytriol, ((3R,9R,10R)-Heptadec-1-en-4,6-diyne-3,9,10-triol), is a component of Panax ginseng C. A.

Synthetic and Biophysical Studies on the Toxic Conformer in Amyloid β with the E22Δ Mutation in Alzheimer Pathology.

The toxic conformer of the 40- or 42-mer-amyloid β-proteins (Aβ) (Aβ40, Aβ42) with a turn at positions 22 and 23 plays a role in oligomer formation, leading to neurotoxicity as part of the pathogenesis of Alzheimer's disease (AD). A deletion mutant at Glu22 (E22Δ) of Aβ, known as an Osaka mutation, accelerates oligomerization. Although E22Δ-Aβ has not been found to be toxic to cultured neuronal cells and is instead synaptotoxic in long-term potentiation, there is no information on the toxic conformer of E22Δ-Aβ in AD.

Protective effects of Nrf2-ARE activator on dopaminergic neuronal loss in Parkinson disease model mice: Possible involvement of heme oxygenase-1.

Parkinson disease (PD) is a neurodegenerative disorder characterized by a selective loss of dopaminergic neurons in the substantia nigra, and oxidative stress is thought to contribute to this pathogenesis. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which induces the production of antioxidant enzymes, is thereby a potential target for therapeutics to reduce neurodegeneration in PD. Previously, we identified TPNA10168 from a chemical library as an activator of the Nrf2-ARE pathway, and the present study examined the effects of TPNA10168 on an in vivo PD model.