Project description:In order to perform transcriptional analyses of two stromal subsets carrying the gain-of-function mutation of CXCR4, bulk RNA Sequencing (RNA-Seq) was conducted on SSC and OPC sorted from WT (Cxcr4+/+) , heterozygous (Cxcr4+/1013) and homozygous (Cxcr41013/1013) mutant mice for Cxcr4.
Project description:An Affimetrix GeneChip Human Genome U133 Plus 2.0 Array was used to study the effect of oleoylethnolamide on gene expression. The addition of 0.01 mM oleoylethanolamide (OEA) to human subcutaneous adipocytes significantly affected the expression of 1013 genes, with 556 being up-regulated and 457 being down-regulated.
Project description:An Affimetrix GeneChip Human Genome U133 Plus 2.0 Array was used to study the effect of oleoylethnolamide on gene expression. The addition of 0.01 mM oleoylethanolamide (OEA) to human subcutaneous adipocytes significantly affected the expression of 1013 genes, with 556 being up-regulated and 457 being down-regulated. Human subcutaneous adipocytes were incubated with oleoylethanolamide (0.01 mM). After 24 hr, the gene expression in human subcutanous adipocytes was analyzed using Affymetrix microarrays.
Project description:The management of antibiotic-resistant, bacterial biofilm infections in chronic skin wounds is a significant clinical challenge. Despite advances in diagnosis, many patients do not derive benefit from current anti-infective/antibiotic therapies. Here we report a novel class of epoxy-tiglianes and demonstrate their antimicrobial activity (modifying bacterial growth and inducing biofilm disruption), with structure/activity relationships established against important human pathogens. In vitro, the lead candidate, EBC-1013 stimulated PKC-dependent neutrophil ROS induction and NETosis, and increased expression of wound healing associated cytokines, chemokines and antimicrobial peptides in keratinocytes and fibroblasts. In vivo, topical EBC-1013 induced rapid resolution of infection with increased matrix remodelling in acute thermal injuries. In chronically-infected, diabetic wounds, treatment induced cytokine/chemokine production, inflammatory cell recruitment and complete healing (in 6/7 wounds) with ordered keratinocyte differentiation. These results highlight a non-antibiotic approach involving contrasting, orthogonal mechanisms of action: targeted biofilm disruption and innate immune induction in the treatment of chronic wounds.
Project description:The management of antibiotic-resistant, bacterial biofilm infections in chronic skin wounds is a significant clinical challenge. Despite advances in diagnosis, many patients do not derive benefit from current anti-infective/antibiotic therapies. Here we report a novel class of epoxy-tiglianes and demonstrate their antimicrobial activity (modifying bacterial growth and inducing biofilm disruption), with structure/activity relationships established against important human pathogens. In vitro, the lead candidate, EBC-1013 stimulated PKC-dependent neutrophil ROS induction and NETosis, and increased expression of wound healing associated cytokines, chemokines and antimicrobial peptides in keratinocytes and fibroblasts. In vivo, topical EBC-1013 induced rapid resolution of infection with increased matrix remodelling in acute thermal injuries. In chronically-infected, diabetic wounds, treatment induced cytokine/chemokine production, inflammatory cell recruitment and complete healing (in 6/7 wounds) with ordered keratinocyte differentiation. These results highlight a non-antibiotic approach involving contrasting, orthogonal mechanisms of action: targeted biofilm disruption and innate immune induction in the treatment of chronic wounds.
