Reportedly, a large number of microRNAs (miRNAs) play an important role in inflammatory lung diseases such as asthma, idiopathic pulmonary fibrosis (IPF), acute respiratory distress syndrome (ARDS), and pulmonary arterial hypertension (PAH). Sevoflurane is routinely used to various patients, and its safety has been confirmed by clinical outcomes; however, its effects to lungs at the miRNA level have not been elucidated. In our previous genomic studies, we showed that sevoflurane anesthesia affected the expression of many genes and mRNAs in rat lungs. In this study, we comprehensively investigated changes in miRNA expression caused by sevoflurane anesthesia (2.0% and 4.0%). Sevoflurane anesthesia resulted in apparent changes in miRNA expression in rat lungs, and the pattern of 2.0% sevoflurane-induced changes in miRNA expression was similar to that of 4.0% sevoflurane. Some of the differentially expressed miRNAs are known to be involved in asthma, IPF, and PAH. Especially, miR-146a, the most up-regulated miRNA, is known to attenuate the toxic effects associated with LPS stimulation. We showed, for the first time, dynamic changes in miRNA expression caused by sevoflurane anesthesia, and moreover, our results were important to understand the influence of sevoflurane anesthesia on any patients suffered from various lung diseases.

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Gangliosides (sialic acid-containing glycosphingolipids) play important roles in many physiological functions, including synaptic plasticity in the hippocampus, which has been suggested as the basal cellular process of learning and memory in the brain. In the present study, long-term potentiation (LTP) and long-term depression (LTD) in CA1 hippocampal neurons and learning behavior were examined in mice treated with _D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (_D-PDMP), an inhibitor of ganglioside biosynthesis. Mice treated with _D-PDMP, but not those treated with _L-PDMP, showed impairment of LTP induction in hippocampal CA1 neurons without any significant change in LTD formation and also showed a failure of learning in the 4-pellet taking test. These results indicate that de novo synthesis of gangliosides in the brain is involved in synaptic plasticity of LTP in mouse hippocampal CA1 neurons and plays important roles in learning and memory.

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The present study examined the effects of enzymatically hydrolyzed collagen peptides on the level of hippocampal neurogenesis and emotional behavior in adult mice. For this purpose, two kinds of enzymatically hydrolyzed collagen peptides, the lower or higher molecular weight peptides (LP: below 2,000, HP: about 30,000) were administered orally to C57BL/6 mice for 4 weeks. As a result, the density of proliferating cells in subgranular zone of hippocampus showed a 1.2-fold increase in LP mice as compared with HP mice. Additionally, LP mice spent less time in closed arms than HP mice in elevated plus maze test to examine anxiety-related behavior. These results suggest that oral administration of the lower molecular weight peptides derived from collagen enhanced the hippocampal neurogenesis and exerted emotional behavior in adult mice.

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Cell culture medium, which must be discarded during medium change, may contain many cells that do not attach to culture plates. In the present study, we focused on these floating cells and attempted to determine their usefulness for cartilage regeneration. We counted the number of floating cells discarded during medium change and compared the proliferation and differentiation between floating cells and their adherent counterparts. Chondrocyte monolayer culture at a density of 5 × 103 cells/cm₂ produced viable floating cells at a rate of 2.7-3.2 × 10₃ cells/cm₂ per primary culture. When only the floating cells from one dish were harvested and replated in another dish, the number of cells was 2.8 × 10₄ cells/cm₂ (approximately half confluency) on culture day 7. The number of cells was half of that obtained by culturing only adherent cells (5 × 10₄ cells/cm₂). The floating and adherent cells showed similar proliferation and differentiation properties. The recovery of floating cells from the culture medium could provide an approximately 1.5-fold increase in cell number over conventional monolayer culture. Thus, the collection of floating cells may be regarded as a simple, easy, and reliable method to increase the cell harvest for chondrocytes.

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Am80, a synthetic retinoid, has been used in differentiation therapy for acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) as one of natural retinoid has been also used to treat APL. ATRA treatment causes neuronal differentiation by inducing tropomyosin-related kinase B (TrkB) expression and increasing the sensitivity to brain-derived neurotrophic factor (BDNF), a TrkB ligand. In the present study, we investigated the effects of Am80 on neuronal differentiation, BDNF sensitivity and TrkB expression in human neuroblastoma SH-SY5Y cells. Treatment with Am80 induced morphological differentiation of neurite outgrowth and increased the expression of GAP43 mRNA, a neuronal differentiation marker. Additionally, TrkB protein was also increased, and exogenous BDNF stimulation after treatment with Am80 induced greater neurite outgrowth than without BDNF treatment. These results suggest that Am80 induced neuronal differentiation by increasing TrkB expression and BDNF sensitivity.

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The perennial grass Vetiveria zizanioides (vetiver) is mainly cultivated for its fragrant essential oil. Although the components of the oil and their biological activities have been studied extensively, the effect of the volatiles emitted from the roots of V. zizanioides on humans has so far remained unexplored. We investigated the effects of volatile compounds emitted from the cut roots of V. zizanioides (1.0 g, low-dose conditions; 30 g, high-dose conditions) on individuals during a visual display terminal task. Participants who breathed the volatile compounds emitted under low-dose conditions showed faster reaction times and stimulation of sympathetic nerve activity as measured by electrocardiography. These effects were not observed under high-dose conditions. The total amounnt of volatiles emitted during the experiment was 0.25 μg under low-dose conditions and 1.35 &me;g under high-dose conditions. These findings indicate that volatile compounds emitted from the roots of V. zizanioides under low-dose conditions may have helped subjects to maintain performance in visual discrimination tasks while maintaining high sympathetic nerve system activity.

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Our previous study showed that tumor budding is a significant indicator of a poor prognosis in lung squamous cell carcinoma patients. Tumor budding-positive (Bud(+)) cases of lung squamous cell carcinoma (SqCC) showed locally aggressive growth, and the positivity was a useful indicator of the lymph node status and prognosis. The present study focused on the clinicopathologic significance of laminin-5γ2 chain expression for local aggressiveness in lung SqCC. Laminin-5γ2 chain immunohistochemical stains in tissue samples were divided into three distinct types: basement membrane (B type; laminin-5γ2 present in basement membrane), cytoplasmic (C type; laminin- 5γ2 present in intracellular matrix), and invasive front (F type; laminin-5γ2 present in cytoplasm, and strongly in part of peripheral nest). The F type was more common in Bud(+) cases than tumor budding-negative (Bud(-)) cases; B and C types were less common in Bud(+) cases (P ⟨ 0.001). The F type was more closely associated with decreased overall survival than the B and C types (P ⟨ 0.001 for both). Univariate analysis showed that the F type could be used to predict tumor size, lymph node metastasis, lymphatic invasion, tumor infiltrative patterns, tumor budding, and laminin-5γ2 chain staining. Multivariate analysis showed that laminin-5γ2 chain staining and tumor budding could be used to predict patient mortality (P ⟨ 0.001 and P = 0.005, respectively). The overall survival rate after curative resection was lower in patients with the F/Bud(+) type than in those with B+C/Bud(-) and B+C/Bud(+) types (P < 0.001 for both, log-rank test), and also lower with the F/Bud(-) type than the B+C/Bud(-) type. On the other hand, there was no significant difference between the F/Bud(+) and F/Bud(-) types. In conclusion, both laminin- 5γ2 chain staining and tumor budding are associated with tumor cell invasiveness and are independent predictors of mortality in lung SqCC patients.

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Peroxiredoxins (Prxs) are a family of multifunctional antioxidant thioredoxin-dependent peroxidases. We used Drosophila melanogaster to examine the function of Prx3, the Drosophila homolog of human PRDX3. The oxidative stress response in adult Drosophila is age-dependent. RNAiinduced Prx3 knockdown in adult flies did not change their phenotype in normal conditions, but they had a shorter survival than the Prx3⁺ controls in the presence of H₂O₂. The expression levels of the Prx3 were reduced by aging. These results suggest that Prx3 plays an important role in the oxidative stress response and is involved in the age-dependent competence of the oxidative stress response.

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