MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on th...MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on the use of ultra- small super-paramagnetic iron oxide (USPIO) nanoparticles and related susceptibility weighted imaging methods. Al-though immunohistochemistry can robustly differentiate the expression of protein variants, there is currently no direct gene assay technique that is capable of differentiating established to differentiate the induction profiles of c-Fos mRNA in vivo. To visualize the differential FosB gene expression profile in vivo after burn trauma, we developed MR probes that link the T2* contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with an oligodeoxynucleotide (ODN) sequence complementary to FosB mRNA to visualize endogenous mRNA targets via in vivo hybridization. The presence of this SPION-ODN probe in cells results in localized signal reduction in T2*-weighted MR images, in which the rate of signal reduction (R2*) reflects the regional iron concentration at different stages of amphetamine (AMPH) exposure in living mouse tissue. Our aim was to produce a superior contrast agent that can be administered using sys- temic as opposed to local administration and which will target and accumulate at sites of burn injury. Specifically, we developed and evaluated a PEGylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparti- cles (USPION, a T2 susceptibility agent) coated with cationic fusogenic lipids, used for cell transfection and gene de- livery and covalently linked to a phosphorothioate modified oligodeoxynucleotide (sODN) complementary to c-Fos mRNA (SPION-cFos) and used the agent to image mice with leg burns. Our study demonstrated the feasibility of monitoring burn injury using MR imaging of c-Fos transcription in vivo, in a clinically relevant mouse model of burn injury for the first time.展开更多
Bitter(T2R)and sweet(T1R)taste receptors have been implicated in sinonasal innate immunity and in the pathophysiology of chronic rhinosinusitis(CRS).Taste receptors are expressed on several sinonasal cell types includ...Bitter(T2R)and sweet(T1R)taste receptors have been implicated in sinonasal innate immunity and in the pathophysiology of chronic rhinosinusitis(CRS).Taste receptors are expressed on several sinonasal cell types including ciliated epithelial cells and solitary chemosensory cells.Bitter agonists released by pathogenic microbes elicit a T2R dependent signaling cascade which induces the release of bactericidal nitric oxide,increases mucociliary clearance,and promotes secretion of antimicrobial peptides.Genetic variation conferred by polymorphisms in T2R related genes is associated with differential CRS susceptibility,symptomatology and post-treatment outcomes.More recently,based on our understanding of T1R and T2R function,investigators have discovered novel potential therapeutics in T2R agonists and T1R antagonists.This review will discuss bitter and sweet taste receptor function in sinonasal immunity,explore the emerging diagnostic and therapeutic implications stemming from the most recent findings,and suggest directions for future research.展开更多
文摘MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on the use of ultra- small super-paramagnetic iron oxide (USPIO) nanoparticles and related susceptibility weighted imaging methods. Al-though immunohistochemistry can robustly differentiate the expression of protein variants, there is currently no direct gene assay technique that is capable of differentiating established to differentiate the induction profiles of c-Fos mRNA in vivo. To visualize the differential FosB gene expression profile in vivo after burn trauma, we developed MR probes that link the T2* contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with an oligodeoxynucleotide (ODN) sequence complementary to FosB mRNA to visualize endogenous mRNA targets via in vivo hybridization. The presence of this SPION-ODN probe in cells results in localized signal reduction in T2*-weighted MR images, in which the rate of signal reduction (R2*) reflects the regional iron concentration at different stages of amphetamine (AMPH) exposure in living mouse tissue. Our aim was to produce a superior contrast agent that can be administered using sys- temic as opposed to local administration and which will target and accumulate at sites of burn injury. Specifically, we developed and evaluated a PEGylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparti- cles (USPION, a T2 susceptibility agent) coated with cationic fusogenic lipids, used for cell transfection and gene de- livery and covalently linked to a phosphorothioate modified oligodeoxynucleotide (sODN) complementary to c-Fos mRNA (SPION-cFos) and used the agent to image mice with leg burns. Our study demonstrated the feasibility of monitoring burn injury using MR imaging of c-Fos transcription in vivo, in a clinically relevant mouse model of burn injury for the first time.
基金This work was supported by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health under award number R01DC013588-04S2(to IWM).
文摘Bitter(T2R)and sweet(T1R)taste receptors have been implicated in sinonasal innate immunity and in the pathophysiology of chronic rhinosinusitis(CRS).Taste receptors are expressed on several sinonasal cell types including ciliated epithelial cells and solitary chemosensory cells.Bitter agonists released by pathogenic microbes elicit a T2R dependent signaling cascade which induces the release of bactericidal nitric oxide,increases mucociliary clearance,and promotes secretion of antimicrobial peptides.Genetic variation conferred by polymorphisms in T2R related genes is associated with differential CRS susceptibility,symptomatology and post-treatment outcomes.More recently,based on our understanding of T1R and T2R function,investigators have discovered novel potential therapeutics in T2R agonists and T1R antagonists.This review will discuss bitter and sweet taste receptor function in sinonasal immunity,explore the emerging diagnostic and therapeutic implications stemming from the most recent findings,and suggest directions for future research.
