Optical nanoscale technologies often implement covalent or noncovalent strategies for the modification of nanoparticles, whereby both functionalizations are leveraged for multimodal applications but can affect the intrinsic fluorescence of nanoparticles. Specifically, single-walled carbon nanotubes (SWCNTs) can enable real-time imaging and cellular delivery; however, the introduction of covalent SWCNT sidewall functionalizations often attenuates SWCNT fluorescence. Recent advances in SWCNT covalent functionalization chemistries preserve the SWCNT's pristine graphitic lattice and intrinsic fluorescence, and here, such covalently functionalized SWCNTs maintain intrinsic fluorescencebased molecular recognition of neurotransmitter and protein analytes. The covalently modified SWCNT nanosensor preserves its fluorescence response towards its analyte for certain nanosensors, presumably dependent on the intermolecular interactions between SWCNTs or the steric hindrance introduced by the covalent functionalization that hinders noncovalent interactions with the SWCNT surface. These SWCNT nanosensors are further functionalized via their covalent handles with a targeting ligand, biotin, to self-assemble on passivated microscopy slides, and these dual-functionalized SWCNT materials are explored for future use in multiplexed sensing and imaging applications.
Bruch’s membrane, an extracellular matrix located between the retinal pigment epithelium and the choroid, plays a vital role as structural and functional support to the retinal pigment epithelium. Dysfunction of Bruch’s membrane in both age-related macular degeneration and other ocular diseases is caused mostly by extracellular matrix degeneration, deposit formation, and angiogenesis. Although these factors are dealt in greater detail with respect to the cells that are degenerated such as the retinal pigment epithelium and the endothelial cells, the pathology involving the Bruch’s membrane is often underrated. Since in most of the macular degenerations early degenerative changes are also observed in the Bruch’s membrane, addressing only the cellular component without the underlying membrane will not yield an ideal clinical benefit. This review aims to discuss the factors and the mechanisms affecting the integrity of the Bruch’s membrane, which would aid in developing an effective therapy for these pathologies.
New Findings What is the central question of this study?The aim was to determine the renoprotective effects of serelaxin in the setting of chronic heart failure. What are the main findings and its importance?Our data indicate that serelaxin can reduce renal fibrosis and inflammation in experimental heart failure. Currently, there are no effective treatments to rescue renal function in heart failure patients, and our data suggest that serelaxin might have the potential to reduce renal fibrosis and inflammation in heart failure. Abstract Serelaxin has been demonstrated to attenuate renal fibrosis and inflammation in cardiorenal disease. In the present study, we tested the hypothesis that serelaxin can prevent the decline in renal function in dilated cardiomyopathy (DCM) by targeting renal fibrosis and inflammation. Male transgenic mice with DCM (n = 16) and their wild‐type littermates (WT; n = 20) were administered either vehicle or serelaxin (500 μg kg−1 day−1; subcutaneous minipumps; 8 weeks). Cardiac function was assessed via echocardiography before and during the eighth week of serelaxin treatment. Renal function and inflammation as well as cardiac and renal fibrosis were assessed at the end of the study. Serelaxin had minimal effect on cardiac function (P ≥ 0.99). Tubulointerstitial and glomerular fibrosis were ∼3‐fold greater in vehicle‐treated DCM mice compared with vehicle‐treated WT mice (P ≤ 0.001). Renal mRNA expression of Tnfα and Il1α were ∼4‐ and ∼3‐fold greater, respectively, in vehicle‐treated DCM mice compared with vehicle‐treated WT mice (P ≤ 0.05). Tubulointerstitial and glomerular fibrosis were 46 and 45% less, respectively, in serelaxin‐treated DCM mice than in vehicle‐treated DCM mice (P ≤ 0.01). Renal cortical mRNA expression of Tnfα and Il1α were 56 and 58% less, respectively, in the former group compared with the latter (P ≤ 0.05). The urinary albumin:creatinine ratio was ∼3‐fold greater in vehicle‐treated DCM mice compared with vehicle‐treated WT mice (P = 0.02). The urinary albumin:creatinine ratio was not significantly different between vehicle‐treated DCM mice and serelaxin‐treated DCM mice (P = 0.38). These data suggest that serelaxin can attenuate renal fibrosis and inflammation and has the potential to exert renoprotective effects in DCM.
Autosomal dominant retinitis pigmentosa is a form of retinitis pigmentosa, an inherited retinal degenerative disorder characterized by progressive loss of photoreceptors eventually leading to irreversible loss of vision. Mutations in genes involved in the basic functions of the visual system give rise to this condition. These mutations can either lead to loss of function or toxic gain of function phenotypes. While autosomal dominant retinitis pigmentosa caused by loss of function can be ideally treated by gene supplementation with a single vector to address a different spectrum of mutations in a gene, the same strategy cannot be applied to toxic gain of function phenotypes. In toxic gain of function phenotypes, the mutation in the gene results in the acquisition of a new function that can interrupt the functioning of the wildtype protein by various mechanisms leading to cell toxicity, thus making a single approach impractical. This review focuses on the genes and mechanisms that cause toxic gain of function phenotypes associated with autosomal dominant retinitis pigmentosa and provide a bird’s eye view on current therapeutic strategies and ongoing clinical trials.
Optical nanoscale technologies often implement covalent or noncovalent strategies for the modification of nanoparticles, whereby both functionalizations can affect the intrinsic fluorescence of nanoparticles. Specifically, single-walled carbon nanotubes (SWCNTs) can enable real-time imaging and cellular delivery, however, the introduction of SWCNT sidewall functionalizations attenuates SWCNT fluorescence. Herein, we leverage recent advances in SWCNT covalent functionalization chemistries that preserve the SWCNT's pristine surface lattice and intrinsic fluorescence, and demonstrate that such covalently-functionalized SWCNT can enable fluorescence-based molecular recognition of neurotransmitter and protein analytes.We show that the covalently-modified SWCNT nanosensor fluorescence signal towards its analyte can be preserved only for certain nanosensors, presumably dependent on the steric hindrance of the SWCNT noncovalent coating. We further demonstrate these SWCNT nanosensors can be functionalized via their covalent handles to self-assemble on passivated microscopy slides and discuss future use of these dual-functionalized SWCNT materials for multiplexed applications.
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