32 research outputs found

    A pathogen-derived metabolite induces microglial activation via odorant receptors

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    Microglia (MG), the principal neuroimmune sentinels in the brain, continuously sense changes in their environment and respond to invading pathogens, toxins, and cellular debris, thereby affecting neuroinflammation. Microbial pathogens produce small metabolites that influence neuroinflammation, but the molecular mechanisms that determine whether pathogen-derived small metabolites affect microglial activation of neuroinflammation remain to be elucidated. We hypothesized that odorant receptors (ORs), the largest subfamily of G protein-coupled receptors, are involved in microglial activation by pathogen-derived small metabolites. We found that MG express high levels of two mouse ORs, Olfr110 and Olfr111, which recognize a pathogenic metabolite, 2-pentylfuran, secreted by Streptococcus pneumoniae. These interactions activate MG to engage in chemotaxis, cytokine production, phagocytosis, and reactive oxygen species generation. These effects were mediated through the G(alpha s)-cyclic adenosine monophosphate-protein kinase A-extracellular signal-regulated kinase and G(beta gamma)-phospholipase C-Ca2+ pathways. Taken together, our results reveal a novel interplay between the pathogen-derived metabolite and ORs, which has major implications for our understanding of microglial activation by pathogen recognition. Database Model data are available in the PMDB database under the accession number PM0082389.N

    Mammalian Ste20-Like Kinase and SAV1 Promote 3T3-L1 Adipocyte Differentiation by Activation of PPARγ

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    The mammalian ste20 kinase (MST) signaling pathway plays an important role in the regulation of apoptosis and cell cycle control. We sought to understand the role of MST2 kinase and Salvador homolog 1 (SAV1), a scaffolding protein that functions in the MST pathway, in adipocyte differentiation. MST2 and MST1 stimulated the binding of SAV1 to peroxisome proliferator-activated receptor γ (PPARγ), a transcription factor that plays a key role in adipogenesis. The interaction of endogenous SAV1 and PPARγ was detected in differentiating 3T3-L1 adipocytes. This binding required the kinase activity of MST2 and was mediated by the WW domains of SAV1 and the PPYY motif of PPARγ. Overexpression of MST2 and SAV1 increased PPARγ levels by stabilizing the protein, and the knockdown of SAV1 resulted in a decrease of endogenous PPARγ protein in 3T3-L1 adipocytes. During the differentiation of 3T3-L1 cells into adipocytes, MST2 and SAV1 expression began to increase at 2 days when PPARγ expression also begins to increase. MST2 and SAV1 significantly increased PPARγ transactivation, and SAV1 was shown to be required for the activation of PPARγ by rosiglitazone. Finally, differentiation of 3T3-L1 cells was augmented by MST2 and SAV1 expression and inhibited by knockdown of MST1/2 or SAV1. These results suggest that PPARγ activation by the MST signaling pathway may be a novel regulatory mechanism of adipogenesis

    Digital Storytelling as an Intervention for Older Adults: A Scoping Review

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    The population of older adults is rapidly increasing worldwide. Owing to fewer interactions between generations, older adults experience ageism and various psychological issues, such as depression and loneliness. Digital storytelling (DST) has the potential to share vivid lived experiences, support the forming of social relationships, and lead to improved well-being. This scoping review examines the potential psychosocial benefits of individual DST interventions for older adults and people with dementia. We adopted the methodological framework for scoping reviews outlined in the Joanna Briggs Institute’s (JBI) manual. A scoping review was performed using the following bibliographic databases: Web of Science, PubMed, Cochrane Library, CINAHL, Research Information Sharing Service, and National Assembly Library. There were 395 references retrieved, of which 19 articles were selected after applying inclusion and exclusion criteria. Our findings revealed that the most common effects of DST on older adults included the promotion of mental health, an increased amount of meaningful community connections, greater digital literacy, the mitigation of negative ageism, and enhanced intellectual ability. We suggest randomized controlled trials are conducted to confirm the efficacy of intergenerational DST intervention and the effects of DST interventions at multilevel outcomes, including the community level

    Sharpness-aware real-time haze removal algorithm for advanced driver assistance systems

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    This paper proposes a new haze removal technique for automotive applications. Unlike to the previous studies, which focus only on the qualitative elements of the recovered images, the proposed haze removal algorithm uses the weighted filter to sharpen the edges of lanes so that the clarity of lanes is remarkably enhanced rather than the general quality of images. In addition, the entire processing time is reduced by eliminating unnecessary steps that are not related to the sharpness quality. As a result, the proposed haze removal algorithm provides the real-time image processing for advanced driver assistance systems, while significantly improving lane sharpness.110Nsciescopuskc

    Sharpness-aware real-time haze removal for advanced driver assistance systems

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    Dye-Cucurbit[n]uril Complexes as Sensor Elements for Reliable Pattern Recognition of Biogenic Polyamines

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    The host-guest complexes between commercially available fluorescence dyes and cucurbit[n] urils (CB[n], n = 6, 7 and 8) were exploited as multiple sensor elements to provide arrays for sensing biogenic amines using principal component analysis (PCA). Since the sensor elements respond differently to each amine, the array generates distinct patterns of fluorescence changes for each amine. We analyzed these results using PCA to allow precise discrimination of individual biogenic amines. This result demonstrated the great potential of these host-guest complexes as useful sensor elements for biogenic molecules, which may be useful to develop a diagnostic tool for diseases including cancers.11Nsciescopu

    Synthesis and Biochemical Evaluation of Baicalein Prodrugs

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    Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a flavonoid analog from Scutellaria baicalensis, possesses several pharmacological activities including antioxidant, antiproliferative, and anti-inflammatory activities. We previously reported that baicalein inhibits the thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) signaling pathways and can be used as an active ingredient in the treatment of asthma and atopic dermatitis. However, baicalein is rapidly metabolized to baicalin and baicalein-6-O-glucuronide in vivo, which limits its preclinical and clinical use. In this study, we designed, synthesized, and evaluated baicalein prodrugs that protect the OH group at the 7-position of the A ring in baicalein with the amino acid carbamate functional group. Comprehensive in vitro and in vivo studies identified compound 2 as a baicalein prodrug candidate that improved the plasma exposure of baicalein in mouse animal studies. Our results demonstrated that this prodrug approach could be further adopted to discover oral baicalein prodrugs
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