Dual-Acting Nitric Oxide Donor and Phosphodiesterase Inhibitor TOP-N53 Increases Lifespan and Health Span of .

The quest for extending lifespan and promoting a healthy aging has been a longstanding pursuit in the field of aging research. The control of aging and age-related diseases by nitric oxide (NO) and cGMP signaling is a broadly conserved process from worms to human. Here we show that TOP-N53, a dual-acting NO donor and PDE5 inhibitor, can increase both lifespan and health span in .

A Dual-Acting Nitric Oxide Donor and Phosphodiesterase 5 Inhibitor Activates Autophagy in Primary Skin Fibroblasts.

Wound healing pathologies are an increasing problem in ageing societies. Chronic, non-healing wounds, which cause high morbidity and severely reduce the quality of life of affected individuals, are frequently observed in aged individuals and people suffering from diseases affected by the Western lifestyle, such as diabetes. Causal treatments that support proper wound healing are still scarce.

Orphan receptor IL-17RD regulates Toll-like receptor signalling via SEFIR/TIR interactions.

Receptor families of the innate immune response engage in 'cross-talk' to tailor optimal immune responses against invading pathogens. However, these responses are subject to multiple levels of regulation to keep in check aberrant inflammatory signals. Here, we describe a role for the orphan receptor interleukin-17 receptor D (IL-17RD) in negatively regulating Toll-like receptor (TLR)-induced responses.

Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia.

Interleukin-17A, the prototypical member of the interleukin-17 cytokine family, coordinates local tissue inflammation by recruiting neutrophils to sites of infection. Dysregulation of interleukin-17 signalling has been linked to the pathogenesis of inflammatory diseases and autoimmunity. The interleukin-17 receptor family members (A-E) have a broad range of functional effects in immune signalling yet no known role has been described for the remaining orphan receptor, interleukin-17 receptor D, in regulating interleukin-17A-induced signalling pathways.

Mal mediates TLR-induced activation of CREB and expression of IL-10.

TLRs initiate immune responses by direct detection of molecular motifs that distinguish invading microbes from host cells. Five intracellular adaptor proteins, each containing a Toll/IL-1R (TIR) domain, are used by TLRs and play key roles in dictating gene expression patterns that are tailored to the invader. Such gene expression is mediated by transcription factors, and although TIR adaptor-induced activation of NF-κB and the IFN regulatory factors have been intensively studied, there is a dearth of information on the role of TIR adaptors in regulating CREB.