Novel carbon film induces precocious calcium oscillation to promote neuronal cell maturation.

Different types of carbon materials are biocompatible with neural cells and can promote maturation. The mechanism of this effect is not clear. Here we have tested the capacity of a carbon material composed of amorphous sp3 carbon backbone, embedded with a percolating network of sp2 carbon domains to sustain neuronal cultures. We found that cortical neurons survive and develop faster on this novel carbon material. After 3 days in culture, there is a precocious increase in the frequency of neuronal activity and in the expression of maturation marker KCC2 on carbon films as compared to a commonly used glass surface. Accelerated development is accompanied by a dramatic increase in neuronal dendrite arborization. The mechanism for the precocious maturation involves the activation of intracellular calcium oscillations by the carbon material already after 1 day in culture. Carbon-induced oscillations are independent of network activity and reflect intrinsic spontaneous activation of developing neurons. Thus, these results reveal a novel mechanism for carbon material-induced neuronal survival and maturation.

Effect of topical glaucoma medication on tear lipid layer thickness in patients with unilateral glaucoma.

Purpose: To compare the lipid layer thickness (LLT) using the LipiView® ocular surface interferometer (TearScience® Inc, Morrisville, NC) between the eye treated with glaucoma medication and untreated normal eye in the unilateral glaucoma patients, and evaluate the effect of topical glaucoma medication on the LLT parameters in glaucoma eyes. Methods: The participants in this cross-sectional comparative study were unilateral glaucoma patients treated with topical glaucoma medications for more than 12 months. Three LLT parameters (average, minimum, and maximum) obtained by the LipiView® were compared between the glaucomatous eye and normal eye. The factors associated with LLT parameters in the eyes treated with glaucoma medication were investigated with multiple regression analysis. Results: Thirty patients with unilateral normal tension glaucoma were enrolled in the present study. Lipid layer average, minimum, and maximum were 64.83 ± 16.50, 51.63 ± 16.73, and 82.53 ± 20.62 in glaucomatous eyes, 77.26 ± 17.81, 62.83 ± 20.99, and 86.13 ± 15.42 in normal eyes. Lipid layer average and minimum were significantly thinner than those in normal eyes (P < 0.001, P < 0.001, respectively). Longer duration of glaucoma eye drops and a greater number of glaucoma medications were associated with the lower LLT average (ß = -0.456, P < 0.001, ß = -8.517, P = 0.003, respectively), and increasing glaucoma medications have a significant correlation with lower LLT minimum in glaucoma eyes (ß = -8.814, P = 0.026). Conclusion: The present study highlights that patients with long-term glaucoma medications need to be assessed for LLT parameters objectively evaluate their ocular surface health.

Therapeutic targets for treating fibrotic kidney diseases.

Renal fibrosis is the hallmark of virtually all progressive kidney diseases and strongly correlates with the deterioration of kidney function. The renin-angiotensin-aldosterone system blockade is central to the current treatment of patients with chronic kidney disease (CKD) for the renoprotective effects aimed to prevent or slow progression to end-stage renal disease (ESRD). However, the incidence of CKD is still increasing, and there is a critical need for new therapeutics. Here, we review novel strategies targeting various components implicated in the fibrogenic pathway to inhibit or retard the loss of kidney function. We focus, in particular, on antifibrotic approaches that target transforming growth factor (TGF)-ß1, a key mediator of kidney fibrosis, and exciting new data on the role of autophagy. Bone morphogenetic protein (BMP)-7 and connective tissue growth factor (CTGF) are highlighted as modulators of profibrotic TGF-ß activity. BMP-7 has a protective role against TGF-ß1 in kidney fibrosis, whereas CTGF enhances TGF-ß-mediated fibrosis. We also discuss recent advances in the development of additional strategies for antifibrotic therapy. These include strategies targeting chemokine pathways via CC chemokine receptors 1 and 2 to modulate the inflammatory response, inhibition of phosphodiesterase to restore nitric oxide-cyclic 3',5'-guanosine monophosphate function, inhibition of nicotinamide adenine dinucleotide phosphate oxidase 1 and 4 to suppress reactive oxygen species production, and inhibition of endothelin 1 or tumor necrosis factor α to ameliorate progressive renal fibrosis. Furthermore, a brief overview of some of the biomarkers of kidney fibrosis is currently being explored that may improve the ability to monitor antifibrotic therapies. It is hoped that evidence based on the preclinical and clinical data discussed in this review leads to novel antifibrotic therapies effective in patients with CKD to prevent or delay progression to ESRD.