Activity

In mice, only treatments with holo-BLG prevented allergic sensitization and anaphylaxis, while sustaining regulatory T cells. BLG facilitated quercetin-dependent AhR-activation and, downstream AhR, lung Cyp1A1 expression. Holo-BLG shuttled iron into monocytic cells and impaired their antigen-presentation. Conclusion The cargo of holo-BLG is decisive in preventing allergy in vivo. BLG without cargo acted as allergen in vivo and further primed human mast cells for degranulation in an antigen-independent fashion. Our data provide mechanistic explanation why the same proteins can either act as tolerogen or allergen.Background IgG4-related disease (IgG4-RD) is an immune-mediated fibrotic disorder that has been linked to CD4+ cytotoxic T lymphocytes (CD4+CTLs). The effector phenotype of CD4+CTLs, the relevance of both CD8+ cytotoxic T lymphocytes (CD8+CTLs) and of apoptotic cell death remain undefined in IgG4-RD. Objective The goals of this study were to define CD4+CTL heterogeneity, characterize the CD8+CTL response in the blood and in lesions, and determine whether enhanced apoptosis may contribute to the pathogenesis of IgG4-RD. Methods Blood analyses were undertaken using flow cytometry, cell sorting, transcriptomic analyses at the population and single cell levels and next generation sequencing for the TCR repertoire. Tissues were interrogated using multi-color immunofluorescence. Results were correlated with clinical data. Results We establish that among circulating CD4+CTLs in IgG4-RD, CD27loCD28loCD57hi cells are the dominant effector subset, exhibit marked clonal-expansion and differentially express genes relevant to cytotoxicity, activation and enhanced metabolism. We also observed prominent infiltration of granzyme A-expressing CD8+CTLs in disease tissues and clonal-expansion in the blood of effector/memory CD8+ T cells with an activated and cytotoxic phenotype. Tissue studies revealed an abundance of cells undergoing apoptotic cell death disproportionately involving non-immune, non-endothelial cells of mesenchymal origin. Apoptotic cells showed significant upregulation of HLA-DR. Conclusion CD4+CTLs and CD8+CTLs may induce apoptotic cell death in tissues of patients with IgG4-RD with preferential targeting of non-endothelial, non-immune cells of mesenchymal origin. Clinical implication T cell mediated apoptosis in disease lesions may contribute to the induction of fibrosis in IgG4-RD. Effector CD4+CTLs and CD8+CTLs correlate with disease severity in IgG4-RD.Objective The aim of this study was to investigate the effects of two radiopaque agents, barium sulfate (BaSO4) or zirconium oxide (ZrO2) in double antibiotic paste (DAP), on the proliferation and mineral deposition of human dental pulp stem cells (DPSC). Materials and methods Radiopaque antimicrobial medicaments composed of methylcellulose (MC) thickening polymer with BaSO4 or ZrO2 and either 1 or 5 mg/mL DAP (equal portions of metronidazole and ciprofloxacin) were used to investigate DPSC proliferation after 3 days, and alkaline phosphatase (ALP) activity and mineral deposition after 7 and 14 days. Radiopaque agents without DAP and Ca(OH)2 were used as controls. Results MC-BaSO4 DAP and MC-ZrO2 DAP at 1 or 5 mg/mL had no adverse effect on DPSC proliferation, compared to the media and MC controls. MC-ZrO2 (DAP-free) greatly increased ALP activity after 7 days. DPSC mineral deposition was modestly reduced at 7 days by MC-BaSO4 DAP and MC-ZrO2 DAP, but not by DAP-free radiopaque agents, and was most reduced by 5 mg/mL DAP in the 14-day cultures. Conclusions MC-BaSO4 or MC-ZrO2 medicaments containing up to 5 mg/mL of DAP supported the proliferation and early osteogenic differentiation of DPSC. Low DAP concentrations and short culture times led to more favorable effects on ALP activity and mineral deposition by DPSC. The findings suggest that radiopaque agents added for the purpose of detecting whether medicaments occupy the full extent of the root canal may have clinical applications. Radiopaque antibiotic medicaments containing low DAP concentrations may be an alternative to Ca(OH)2 for regenerative endodontic procedures.This study presents the first complete mitochondrial genome (mitogenome) of Caecobarbus geertsii, the Congo blind barb, a cave-dwelling, CITES-protected, cyprinid fish endemic to the Lower Congo basin (DRC). The length of the circular mitogenome is 16,565 base pairs. The 13 protein coding genes, 2 ribosomal RNA genes and 22 transfer RNA genes are similar in position and direction to those of other members of the family Cyprinidae. Phylogenetic analyses including 28 complete mitogenomes from representatives of the subfamily Smiliogastrinae (Cyprinidae), showed that Caecobarbus was nested within a clade including representatives of the genus Enteromius. The data presented in this study provide information on the molecular identification and classification of this threatened species. The results further suggest the need for a taxonomic revision of the genus Enteromius.Sago pith cellulose nanofibril (SPCNF) aerogel derived from sago pith waste (SPW) was successfully produced through three consecutive steps, namely dewaxing and delignification, ultra-sonication and homogenization and freeze drying. The aerogel was characterized using field emission scanning electron microscopy (FE-SEM), Fourier-transform infra-red spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Results of the analyses collectively showed that lignin & hemicellulose were absent in the SPCNF aerogel product which has a high crystallinity index of 88%. The diameters of individual nanofibril constituents of the SPCNF were between 15 and 30 nm and aspect ratios >1000 were observed. SCH727965 The SPCNF aerogel, with a density measured at 2.1 mg/cm3, was efficient in methylene blue (MB) removal with a maximum MB adsorption of 222.2 mg/g at 20 °C. The adsorption of MB onto the SPCNF aerogel was rapid and found to follow a pseudo-second-order kinetic model with the adsorption isotherm being in congruence with the Langmuir model. The SPCNF aerogel exhibited outstanding MB removal efficacies with 5 mg and 20 mg of SPCNF capable of removing over 90% and almost 99% MB, respectively. The optimized pH value and temperature for MB adsorption were determined as pH 7 and 20 °C.