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Endogenous neural stem/progenitor cells (NPCs) can migrate toward sites of injury, but the migration activity of NPCs is insufficient to regenerate damaged brain tissue. In this study, we showed that p38 MAP kinase (p38) is expressed in doublecortin-positive adult NPCs. Experiments using the p38 inhibitor SB203580 revealed that endogenous p38 participates in NPC migration. To enhance NPC migration, we generated a cell-permeable wild-type p38 protein (PTD-p38WT) in which the HIV protein transduction domain (PTD) was fused to the N-terminus of p38. Treatment with PTD-p38WT significantly promoted the random migration of adult NPCs without affecting cell survival or differentiation; this effect depended on the cell permeability and kinase activity of the fusion protein. These findings indicate that PTD-p38WT is a novel and useful tool for unraveling the roles of p38, and that this protein provides a reasonable approach for regenerating the injured brain by enhancing NPC migration.

Molecular hydrogen (H2) is an antioxidant and anti-inflammatory agent; however, the molecular mechanisms underlying its biological effects are largely unknown. Similar to other gaseous molecules such as inhalation anesthetics, H2 is more soluble in lipids than in water. A recent study demonstrated that H2 reduces radical polymerization-induced cellular damage by suppressing fatty acid peroxidation and membrane permeability. Thus, we sought to examine the effects of short exposure to H2 on lipid composition and associated physiological changes in SH-SY5Y neuroblastoma cells. We analyzed cells by liquid chromatography-high-resolution mass spectrometry to define changes in lipid components. Lipid class analysis of cells exposed to H2 for 1 hour revealed transient increases in glycerophospholipids including phosphatidylethanolamine, phosphatidylinositol, and cardiolipin. Metabolomic analysis also showed that H2 exposure for 1 hour transiently suppressed overall energy metabolism accompanied by a decrease in glutathione. We further observed alterations to endosomal morphology by staining with specific antibodies. Endosomal transport of cholera toxin B to recycling endosomes localized around the Golgi body was delayed in H2-exposed cells. We speculate that H2-induced modification of lipid composition depresses energy production and endosomal transport concomitant with enhancement of oxidative stress, which transiently stimulates stress response pathways to protect cells. [ABSTRACT FROM AUTHOR]

To date, 10 types of human papillomavirus have been identified that cause flat warts, including human papillomavirus type 3, which belongs to species group 2 of the genus alpha papillomavirus. Among these 10 types, human papillomavirus type 94 is most closely related to human papillomavirus type 10, sharing 86% homology. In this study, we conducted polymerase chain reaction analysis with sequencing on samples obtained from cutaneous lesions located on the face and lower legs of an individual, revealing the presence of human papillomavirus type 94. Dermatoscopic findings revealed numerous dotted vessels within one group of macular brown lesions located on the lower leg, which contributed to the diagnosis of flat warts. An online search revealed that human papillomavirus type 94 has previously been detected in various skin diseases, and we provide a review of prior reports. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA)‐associated interstitial lung disease (ILD), a primary cause of mortality in patients with RA, has limited treatment options. A previously established RA model in D1CC transgenic mice aberrantly expressed major histocompatibility complex class II genes in joints, developing collagen II‐induced polyarthritis and anti‐cyclic citrullinated peptide antibodies and interstitial pneumonitis, similar to those in humans. Molecular hydrogen (H2) is an efficient antioxidant that permeates cell membranes and alleviates the reactive oxygen species‐induced injury implicated in RA pathogenesis. We used D1CC mice to analyse chronic lung fibrosis development and evaluate H2 treatment effects. We injected D1CC mice with type II collagen and supplied them with H2‐rich or control water until analysis. Increased serum surfactant protein D values and lung densities images were observed 10 months after injection. Inflammation was patchy within the perilymphatic stromal area, with increased 8‐hydroxy‐2ʹ‐deoxyguanosine‐positive cell numbers and tumour necrosis factor‐α, BAX, transforming growth factor‐β, interleukin‐6 and soluble collagen levels in the lungs. Inflammatory and fibrotic changes developed diffusely within the perilymphatic stromal area, as observed in humans. H2 treatment decreased these effects in the lungs. Thus, this model is valuable for studying the effects of H2 treatment and chronic interstitial pneumonia pathophysiology in humans. H2 appears to protect against RA‐ILD by alleviating oxidative stress. [ABSTRACT FROM AUTHOR]

Vertebrate animals detect odors through olfactory receptors (ORs), members of the G protein-coupled receptor (GPCR) family. Due to the difficulty in the heterologous expression of ORs, studies of their odor molecule recognition mechanisms have progressed poorly. Functional expression of most ORs in heterologous cells requires the co-expression of their chaperone proteins, receptor transporting proteins (RTPs). Yet, some ORs were found to be functionally expressed without the support of RTP (RTP-independent ORs). In this study, we investigated whether amino acid residues highly conserved among RTP-independent ORs improve the functional expression of ORs in heterologous cells. We found that a single amino acid substitution at one of two sites (NBW3.39 and 3.43) in their conserved residues (E and L, respectively) significantly improved the functional expression of ORs in heterologous cells. E3.39 and L3.43 also enhanced the membrane expression of RTP-dependent ORs in the absence of RTP. These changes did not alter the odorant responsiveness of the tested ORs. Our results showed that specific sites within transmembrane domains regulate the membrane expression of some ORs. [ABSTRACT FROM AUTHOR]

Molecular hydrogen (H 2 ) is an antioxidant and anti-inflammatory agent; however, the molecular mechanisms underlying its biological effects are largely unknown. Similar to other gaseous molecules such as inhalation anesthetics, H 2 is more soluble in lipids than in water. A recent study demonstrated that H 2 reduces radical polymerization-induced cellular damage by suppressing fatty acid peroxidation and membrane permeability. Thus, we sought to examine the effects of short exposure to H 2 on lipid composition and associated physiological changes in SH-SY5Y neuroblastoma cells. We analyzed cells by liquid chromatography-high-resolution mass spectrometry to define changes in lipid components. Lipid class analysis of cells exposed to H 2 for 1 hour revealed transient increases in glycerophospholipids including phosphatidylethanolamine, phosphatidylinositol, and cardiolipin. Metabolomic analysis also showed that H 2 exposure for 1 hour transiently suppressed overall energy metabolism accompanied by a decrease in glutathione. We further observed alterations to endosomal morphology by staining with specific antibodies. Endosomal transport of cholera toxin B to recycling endosomes localized around the Golgi body was delayed in H 2 -exposed cells. We speculate that H 2 -induced modification of lipid composition depresses energy production and endosomal transport concomitant with enhancement of oxidative stress, which transiently stimulates stress response pathways to protect cells., Competing Interests: None

Aim: To investigate the effects of hydrogen (H 2 ) on Cu, Zn superoxide dismutase (SOD1) activation in a rat model of corneal alkali burn., Methods: In each rat, one cornea was subjected to alkali exposure. Physiological saline (saline group) or H 2 -dissolved saline (H 2 group) was instilled continuously on the cornea for 5min before and after alkali exposure. Inflammatory cells, neovascularization, and cytoplasmic SOD1 levels were evaluated immunohistochemically in enucleated eyes from both groups. Three-dimensional ultrastructural tissue changes in the eyes were analyzed using low-vacuum scanning electron microscopy., Results: The numbers of both inflammatory and vascular endothelial cells were significantly reduced in the corneas of the H 2 group ( P <0.01). Furthermore, H 2 treatment increased both cytoplasmic SOD1 levels ( P <0.01) and activity in corneal epithelial cells ( P <0.01). Notably, the SOD1 activity level in the H 2 group was approximately 2.5-fold greater than that in the saline group., Conclusion: H 2 treatment suppresses inflammation and neovascularization in the injured cornea and indirectly suppresses oxidative insult to the cornea by upregulating the SOD1 enzyme protein level and activity., (International Journal of Ophthalmology Press.)

Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD), a primary cause of mortality in patients with RA, has limited treatment options. A previously established RA model in D1CC transgenic mice aberrantly expressed major histocompatibility complex class II genes in joints, developing collagen II-induced polyarthritis and anti-cyclic citrullinated peptide antibodies and interstitial pneumonitis, similar to those in humans. Molecular hydrogen (H 2 ) is an efficient antioxidant that permeates cell membranes and alleviates the reactive oxygen species-induced injury implicated in RA pathogenesis. We used D1CC mice to analyse chronic lung fibrosis development and evaluate H 2 treatment effects. We injected D1CC mice with type II collagen and supplied them with H 2 -rich or control water until analysis. Increased serum surfactant protein D values and lung densities images were observed 10 months after injection. Inflammation was patchy within the perilymphatic stromal area, with increased 8-hydroxy-2'-deoxyguanosine-positive cell numbers and tumour necrosis factor-α, BAX, transforming growth factor-β, interleukin-6 and soluble collagen levels in the lungs. Inflammatory and fibrotic changes developed diffusely within the perilymphatic stromal area, as observed in humans. H 2 treatment decreased these effects in the lungs. Thus, this model is valuable for studying the effects of H 2 treatment and chronic interstitial pneumonia pathophysiology in humans. H 2 appears to protect against RA-ILD by alleviating oxidative stress., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)