Tumors of the Respiratory Tract.

Thoracic neoplasia often presents with generalized and nonspecific clinical signs and should be considered as a differential especially when patients are nonresponsive to therapeutic intervention for more common differential diagnoses of respiratory disease (such as equine asthma) and where there is evidence thoracic and/or abdominal effusion upon examination. Antemortem diagnosis can be challenging and working closely with a pathologist to differentiate the respective neoplasia is helpful. Early recognition and appropriate management of thoracic neoplasia are vital for patient welfare as rapid disease progression can be relatively quick, and/or the relatively advanced stage of disease in which these patients frequently present.

GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates.

Growth differentiation factor 15 (GDF15), a distant member of the transforming growth factor (TGF)-β family, is a secreted protein that circulates as a 25-kDa dimer. In humans, elevated GDF15 correlates with weight loss, and the administration of GDF15 to mice with obesity reduces body weight, at least in part, by decreasing food intake. The mechanisms through which GDF15 reduces body weight remain poorly understood, because the cognate receptor for GDF15 is unknown.

Systematic chemical modifications of single stranded siRNAs significantly improved CTNNB1 mRNA silencing.

Single-stranded silencing RNAs (ss siRNA), while not as potent as duplex RNAs, have the potential to become a novel platform technology in RNA interference based gene silencing by virtue of their simplicity and plausibly favorable characteristics in pharmacokinetics and biodistribution. Like other therapeutic pharmaceutical agents, ss siRNA can be optimized to achieve higher potency through a structure-activity based approach. Systematic chemical modification at each position of a 21-mer oligonucleotide identified 2',5'-linked 3'-deoxythymidine (3dT) at position 1 and locked nucleic acids (LNAs) at the seed region as key components to afford significant enhancement in knockdown activity both in vitro and in vivo.

Noninvasive imaging of lipid nanoparticle-mediated systemic delivery of small-interfering RNA to the liver.

Mouse models with liver-specific expression of firefly luciferase were developed that enable a noninvasive and longitudinal assessment of small-interfering RNA (siRNA)-mediated gene silencing in hepatocytes of live animals via bioluminescence imaging. Using these models, a set of lipid nanoparticles (LNPs) with different compositions of cationic lipids, polyethylene glycol (PEG), and cholesterol, were tested for their abilities in delivering a luciferase siRNA to the liver via systemic administration. A dose-dependent luciferase knockdown by LNP/siRNA assemblies was measured by in vivo bioluminescence imaging, which correlated well with the results from parallel ex vivo analyses of luciferase mRNA and protein levels in the liver.