Search bioRxiv⌕ Search

Biology subjects

Liu, S. S.

Publications and source records attributed to Liu, S. S..

2 recordsLinked to original sources

Harnessing Neutrophils to Deliver Antibiotics Non-Invasively across the Tympanic Membrane for Otitis Media Treatment

Acute otitis media (AOM) is a leading cause of pediatric antibiotic prescriptions. Systemic antibiotics cause side effects and antibiotic resistance, whereas local delivery of antibiotics (directly to the middle ear) is hindered by an impermeable biological barrier, the tympanic membrane (TM). Here, we report on a liposome that hitchhikes on neutrophils to deliver antibiotics to the site of infection. Distinct from previous immune-cell-based therapies, we enable neutrophil hitchhiking via a topical application of hydroxylated liposomes, thus bypassing the invasive neutrophil harvesting procedures. The hydroxylated liposomes are opsonized by the complement protein fragments and subsequently internalized by native neutrophils. A simple topical application completely cures AOM in an established chinchilla model. It points to a low-cost and non-invasive treatment for this prevalent disease, poised to reduce pediatric antibiotic usage.

bioengineering↗

Aging is associated with a systemic length-driven transcriptome imbalance

Aging manifests itself through a decline in organismal homeostasis and a multitude of cellular and physiological functions1. Efforts to identify a common basis for vertebrate aging face many challenges; for example, while there have been documented changes in the expression of many hundreds of mRNAs, the results across tissues and species have been inconsistent2. We therefore analyzed age-resolved transcriptomic data from 17 mouse organs and 51 human organs using unsupervised machine learning3-5 to identify the architectural and regulatory characteristics most informative on the differential expression of genes with age. We report a hitherto unknown phenomenon, a systemic age-dependent length-driven transcriptome imbalance that for older organisms disrupts the homeostatic balance between short and long transcript molecules for mice, rats, killifishes, and humans. We also demonstrate that in a mouse model of healthy aging, length-driven transcriptome imbalance correlates with changes in expression of splicing factor proline and glutamine rich (Sfpq), which regulates transcriptional elongation according to gene length6. Furthermore, we demonstrate that length-driven transcriptome imbalance can be triggered by environmental hazards and pathogens. Our findings reinforce the picture of aging as a systemic homeostasis breakdown and suggest a promising explanation for why diverse insults affect multiple age-dependent phenotypes in a similar manner.

systems biology↗