Oxaliplatin is a platinum (Pt)-based chemotherapeutic
drug that is widely used to treat gastrointestinal and pancreatic cancers. The
authors hypothesized that the DNA-binding capacity
is one of the properties of reactive Pt species and aimed to evaluate the
contribution of the kidney to the plasma levels of DNA-reactive Pt in an animal
model and a hemodialysis patient. The results of this
study showed that severe renal dysfunction has a limited effect on the plasma
levels of DNA-reactive Pt after oxaliplatin administration.
Vascular damage is often seen in patients
with diabetes and is thought to be caused by oxidative stress. Xanthine
oxidoreductase exists both intracellularly and extracellularly and causes
vascular injury by producing reactive oxygen species. The authors investigated
the effects of topiroxostat, a xanthine oxidase inhibitor, and its mechanism of
action in a rodent model of diabetes. They found that topiroxostat inhibited
anchored xanthine oxidase bound to the surface of vascular endothelial cells in
the thoracic aorta and suppressed damage to these cells, suggesting that
topiroxostat could potentially have a vasoprotective effect in patients with
diabetes-induced macrovascular disease.
mRNA has
many challenges including insufficient delivery owing to the high molecular
weight and high negative charge. Authors chemically synthesized a minimal mRNA
vaccine encoding human gp10025-33 peptide (KVPRNQDWL), as a
potential treatment for melanoma and iontophoresis (IP) was used for its
delivery into the skin. After combining IP with the newly synthetized minimal
mRNA vaccine, successful intradermal and intracellular delivery of the minimal mRNA
was achieved. Results showed stimulation of the immune system which led to tumor
inhibition and infiltration of cytotoxic CD8+ T cells in the
tumor tissue. This is the first report combining IP and chemically synthesized minimal
mRNA vaccine.
Cholinergic
neurons in the basal forebrain are known to degenerate early stage of
Alzheimer's disease (AD), and amyloid-β (Aβ) oligomers are suggested to be deeply
involved in AD pathogenesis. Authors
here established an Aβ oligomer-induced neurodegeneration model using human
induced pluripotent stem cell-derived cholinergic neurons and demonstrated the
neuroprotective effect of plantainoside B identified from herbal extracts as an
Aβ-binding small molecule. Radioisotope-labeled plantainoside B showed
affinities to Aβ oligomers and brain sections from a mouse model of AD. Results
suggest the potential of developing “theranostics” in AD that simultaneously performs
diagnoses (Aβ detection) and therapy (neuroprotection).