Activation of silent mating type information regulation 2 homolog 1 by human chorionic gonadotropin exerts a therapeutic effect on hepatic injury and inflammation.

Incidence and prevalence of inflammatory liver diseases has increased over the last years, but therapeutic options are limited. Pregnancy induces a state of immune tolerance, which can result in spontaneous improvement of clinical symptoms of certain autoimmune diseases including autoimmune hepatitis (AIH). We investigated the immune-suppressive mechanisms of the human pregnancy hormone, chorionic gonadotropin (hCG), in the liver. hCG signaling activates silent mating type information regulation 2 homolog 1 (SIRT1), which deacetylates forkhead box o3 (FOXO3a), leading to repression of proapoptotic gene expression, because the immunosuppressive consequence attributed to the absence of caspase-3 activity of hepatocellular interleukin 16 (IL-16) is no longer processed and released. Thus, serum levels of IL-16, a key chemotactic factor for CD4+ lymphocytes, were reduced and migration to injured hepatocytes prevented. Furthermore, elevated IL-16 levels are found in the sera from patients with AIH, hepatitis B virus, hepatitis C virus, and nonalcoholic steatohepatitis. CONCLUSION: Here, we report that hCG regulates the SIRT1/FOXO3a axis in hepatocytes, resulting in immune suppression by attenuating caspase-3-dependent IL-16 processing and release, which concomitantly prevents autoaggressive T-cell infiltration of the liver. Considering the low toxicity profile of hCG in humans, interrupting the inflammatory cycle by hCG opens new perspectives for therapeutic intervention of inflammatory liver diseases. (Hepatology 2017;65:2074-2089).

Molybdenum trioxide nanoparticles with intrinsic sulfite oxidase activity.

Sulfite oxidase is a mitochondria-located molybdenum-containing enzyme catalyzing the oxidation of sulfite to sulfate in the amino acid and lipid metabolism. Therefore, it plays a major role in detoxification processes, where defects in the enzyme cause a severe infant disease leading to early death with no efficient or cost-effective therapy in sight. Here we report that molybdenum trioxide (MoO3) nanoparticles display an intrinsic biomimetic sulfite oxidase activity under physiological conditions, and, functionalized with a customized bifunctional ligand containing dopamine as anchor group and triphenylphosphonium ion as targeting agent, they selectively target the mitochondria while being highly dispersible in aqueous solutions. Chemically induced sulfite oxidase knockdown cells treated with MoO3 nanoparticles recovered their sulfite oxidase activity in vitro, which makes MoO3 nanoparticles a potential therapeutic for sulfite oxidase deficiency and opens new avenues for cost-effective therapies for gene-induced deficiencies.

Piezoelectric actuator design for MR elastography: implementation and vibration issues.

BACKGROUND: MR elastography (MRE) is an emerging technique for tumor diagnosis. MRE actuation devices require precise mechanical design and radiofrequency engineering to achieve the required mechanical vibration performance and MR compatibility. METHOD: A method of designing a general-purpose, compact and inexpensive MRE actuator is presented. It comprises piezoelectric bimorphs arranged in a resonant structure designed to operate at its resonant frequency for maximum vibration amplitude. An analytical model was established to understand the device vibration characteristics. RESULTS: The model-predicted performance was validated in experiments, showing its accuracy in predicting the actuator resonant frequency with an error < 4%. The device MRI compatibility was shown to cause minimal interference to a 1.5 tesla MRI scanner, with maximum signal-to-noise ratio reduction of 7.8% and generated artefact of 7.9 mm in MR images. CONCLUSIONS: A piezoelectric MRE actuator is proposed, and its implementation, vibration issues and future work are discussed.