Synthetic polymers have the potential to
work as protein affinity reagents by mimicking protein–protein interactions. The authors report the recent research in the design of
synthetic polymer nanoparticles (NPs) that capture and neutralize target
molecules for intractable disease therapy. The authors found that lightly crosslinked (2%) N-isopropylacrylamide (pNIPAm)-based NPs bind
to target small molecules, peptides, and proteins in vivo by the inclusion of
several functional monomers, such as charged and hydrophobic monomers. In
addition, modification of linear polymer onto lipid nanoparticles improved
polymer circulation time in vivo and binding affinity for the target. These
results will provide information for the in vivo application of synthetic
polymers.
Acetylcholine (ACh) dilates retinal blood vessels through nitric oxide
(NO)-dependent and NO-independent mechanisms. In the rat retinal arteriole, NO
stimulates the cyclooxygenase-1 (COX-1)/prostaglandin I2 (PGI2)/prostanoid
IP receptor/cAMP signaling pathway and activates 4-aminopyridine-sensitive KV
channels (KV). The article by Mori et al. provides evidence
suggesting that cytochrome P450 (CYP)
epoxygenase-derived epoxyeicosatrienoic acids (EETs) activate large-conductance Ca2+-activated
K+ channels (BKCa)
in rat retinal arterioles. The NO-independent component of ACh-induced retinal vasodilator
response is mediated partly by an
endothelium-dependent hyperpolarization mechanism, through CYP epoxygenase-derived EETs. EETs may function as an endothelium-derived hyperpolarizing factor in rat retinal arterioles.
Snail-induced epithelial-mesenchymal transition (EMT) enhanced
P-glycoprotein (P-gp) function and drug resistance to P-gp substrate anticancer
drug in a human NSCLC cell line, HCC827. This study indicates that multidrug
resistance-associated proteins (MRPs) and breast cancer resistance protein
(BCRP) are regulated differently in HCC827 cells with Snail-induced EMT.
Specifically, the function of MRP5 appears to be enhanced via an increase in
membrane localization, whereas the function of BCRP is reduced via a decrease
in the expression level. Therefore, it was suggested that MRPs and BCRP are
regulated differently in HCC827 cells with Snail-induced EMT.
Advanced glycation
end-products (AGEs) are produced by the non-enzymatic reaction of sugars with
proteins. It has been revealed that glyceraldehyde-derived toxic AGEs (TAGE)
are elevated with the non-alcoholic steatohepatitis (NASH) that causes such as liver
fibrosis. Liver fibrosis is caused by activation of hepatic stellate cells
(HSCs). Herein, it was found that the suppression of apoptosis in activated
LX-2 cells which are HSCs by TGF-β1 and TAGE co-treatment is
related to an increase in the production of the extracellular matrix such as
collagen Ⅰ. This result suggests that TAGE might aggravate the
liver fibrosis of chronic hepatitis, such as NASH.
This retrospective
observational cohort study evaluated the chronological order of acute kidney
injury (AKI) and hypokalemia with Yokukansan preparation in 258 patients. Among the patients with AKI and hypokalemia, 92% developed hypokalemia associated
with Yokukansan preparation after AKI. Excluding one patient with hypokalemia
before AKI, the incidence of hypokalemia was higher in patients with AKI than in those without
AKI (32% vs. 12%; p = 0.005). Furthermore, the prevalence of hypokalemia
differed according to AKI recovery (AKI with recovery, 36%; AKI without
recovery, 22%; and no AKI, 12%; p = 0.014).