Combination of cGMP analogue and drug delivery system provides functional protection in hereditary retinal degeneration.

Inherited retinal degeneration (RD) is a devastating and currently untreatable neurodegenerative condition that leads to loss of photoreceptor cells and blindness. The vast genetic heterogeneity of RD, the lack of "druggable" targets, and the access-limiting blood-retinal barrier (BRB) present major hurdles toward effective therapy development. Here, we address these challenges () by targeting cGMP (cyclic guanosine- 3',5'-monophosphate) signaling, a disease driver common to different types of RD, and () by combining inhibitory cGMP analogs with a nanosized liposomal drug delivery system designed to facilitate transport across the BRB.

New cGMP analogues restrain proliferation and migration of melanoma cells.

Melanoma is one of the most aggressive cancers and displays high resistance to conventional chemotherapy underlining the need for new therapeutic strategies. The cGMP/PKG signaling pathway was detected in melanoma cells and shown to reduce migration, proliferation and to increase apoptosis in different cancer types. In this study, we evaluated the effects on cell viability, cell death, proliferation and migration of novel dimeric cGMP analogues in two melanoma cell lines (MNT1 and SkMel28).

New dimeric cGMP analogues reduce proliferation in three colon cancer cell lines.

Activation of the cGMP-dependent protein kinase G (PKG) can inhibit growth and/or induce apoptosis in colon cancer. In this study we evaluated the effects on cell viability, cell death and proliferation of novel dimeric cGMP analogues, compared to a monomeric compound. Three colon cancer cell lines, which only express isoform 2 of PKG, were treated with these novel cGMP analogues and responded with increased PKG activity.

The spleen and skin wound healing in Xenopus adults.

In most vertebrates, the regenerative capacity to restore lost/damage tissues to original structure and functionality decreases at some time during ontogenesis. To evaluate the role of the acquired immunity in the decline of regenerative potential, we examined the cellular responses elicited in the spleen during skin repair in Xenopus adults. Modifications in the architecture were found to be induced and were remarkable 14 days postinjury when the spleen increased significantly in size.

The thymus and skin wound healing in Xenopus laevis adults.

The capacity to heal wounds without scars is generally lost during the development in vertebrates. To explore the involvement of cells of the adaptive immune system in a scar-like tissue based repair, we studied the thymus in 15-month-old Xenopus after skin incisional wounding. After injury, the organ size significantly increased and marked changes in structure and TNF-α immunoreactivity were detected in the medullary microenvironment when the granulation tissue was present in the repair area.

Skin wound healing in different aged Xenopus laevis.

Xenopus froglets can perfectly heal skin wounds without scarring. To explore whether this capacity is maintained as development proceeds, we examined the cellular responses during the repair of skin injury in 8- and 15-month-old Xenopus laevis. The morphology and sequence of healing phases (i.

The thymus and tail regenerative capacity in Xenopus laevis tadpoles.

A morphofunctional analysis of the thymus from differently aged Xenopus laevis tadpoles during regeneration of the tail is reported. In stage 50 larvae, competent to regenerate, the appendage cut provoked thymic structural modifications that affected the medullary microenvironment cells and changes in TNF-α immunoreactivity. Mucocyte-like cells, multicellular epithelial cysts, myoid cells and cells immunoreactive to TNF-α increased in number.

Tail regenerative capacity and iNOS immunolocalization in Xenopus laevis tadpoles.

The morphology and the immuno-distribution of the inducible isoform of nitric oxide synthase (iNOS) have been examined in regenerating tails from differently aged Xenopus laevis larvae. By comparing stage-50 and stage-55/56 tadpoles, various morphological aspects and immunoreactivity to anti-iNOS antibody in terms of the number and duration of positive cells have been demonstrated in the regenerating buds. Unlike in stage-50 larvae, the extent of responses to tail amputation in older larvae is more dependent on the individual tadpole and a high percentage (70%-80%) of malformed tails has been seen.