Induction of an IFN-Mediated Antiviral Response by a Self-Amplifying RNA Vaccine: Implications for Vaccine Design.

RNA-based vaccines have recently emerged as a promising alternative to the use of DNA-based and viral vector vaccines, in part because of the potential to simplify how vaccines are made and facilitate a rapid response to newly emerging infections. SAM vaccines are based on engineered self-amplifying mRNA (SAM) replicons encoding an Ag, and formulated with a synthetic delivery system, and they induce broad-based immune responses in preclinical animal models. In our study, in vivo imaging shows that after the immunization, SAM Ag expression has an initial gradual increase.

Identification of transforming growth factor beta1-driven genetic programs of acute lung fibrosis.

Lung fibrosis is characterized by excessive accumulation of extracellular matrix components leading to progressive airflow limitation. Distinct profibrotic pathways converge on the activation of transforming growth factor-beta (TGF-beta), a central growth factor implicated in most fibroproliferative diseases. Recently, enforced expression of bioactive human TGF-beta1 (hTGF-beta1) in lungs of transgenic mice was shown to recapitulate several key pathophysiologies observed in fibrotic disorders of the lung, including cellular inflammation, tissue fibrosis, and myofibroblast hyperplasia.

Prostacyclin antagonism reduces pain and inflammation in rodent models of hyperalgesia and chronic arthritis.

The inhibition of prostaglandin (PG) synthesis is at the center of current anti-inflammatory therapies. Because cyclooxygenase-2 (COX-2) inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the formation of multiple PGs, there is currently a strong focus on characterizing the role of the different PGs in the inflammation process and development of arthritis. Evidence to date suggests that both PGE(2) and PGI(2) act as mediators of pain and inflammation.