The article by Nomura et al. suggested a
novel mechanism of radiation-induced DNA damage repair contributing to
radioresistance in melanoma. Authors have shown that the transient receptor
potential melastatin 8 (TRPM8) channel is involved in radiation-induced DNA
damage response, cell death, and cell cycle regulation. Furthermore, TRPM8
channel inhibitor enhanced tumor growth-inhibitory effect by gamma-ray in
vivo. These findings proposed that the TRPM8 channel contributes to the resistance
of the growth-inhibitory effect of radiation in melanoma and could be a novel
molecular target to improve the efficiency of radiation therapy for melanoma.
proliferator-activated receptor ɤ (PPARɤ) agonists, such as pioglitazone, are
anti-diabetic drugs, but they cause PPARɤ-related adverse effects such as body weight
gain, cardiac hypertrophy, and bone loss. The authors found that
a novel PPARɤ modulator,
KY-903, has similar anti-diabetic
effects without PPARɤ-related adverse effects in diabetic mice, possibly due
to increases in adiponectin without adipogenesis. KY-903 also has anti-obesity
effects with slight bone loss in obese rats, possibly by PPARɤ antagonism against endogenous or diet-derived
ligands. These findings are useful for research on PPARɤ, and KY-903 is a potential candidate of
anti-diabetic and/or anti-obesity drugs.
The authors investigated the effects of
rivaroxaban on right ventricular (RV) remodeling in a rat model of pulmonary
arterial hypertension (PAH), created with Sugen5416 and chronic hypoxia (SuHx).
The Fulton index, RV systolic pressure, and RV Tei index increased by SuHx were
significantly decreased when treated with rivaroxaban. Rivaroxaban has the
potential of improving RV remodeling in PAH model rats through the suppression
of multiple signaling pathways, including ERK, JNK, and NF-kB,
associated with protease-activated receptor-2. These findings suggest the
additive effects that rivaroxaban may have on the RV remodeling in PAH.
The authors indicated
that the protonation of the histidine residue at the extracellular site in human
oligopeptide transporter (hPEPT1) results in a decrease in the efflux activity,
which is distinct from the sites of proton coupling for transport operation and
substrate binding. Furthermore, they found that the decrease in extracellular
pH reduced the turnover rate of transporters; in other words, the number of
available transporters in the cycle was reduced. The protonation/deprotonation state
of histidine determines the transport activity; the deprotonated histidine
residue can participate in the transport cycle, whereas the protonated histidine
residue can cease the transport.
fibrillation (AF) is one of the most frequent arrhythmias in patients with hypertension.
The authors found that an L/N-type calcium channel blocker cilnidipine exerts anti-AF
effects in the remodeled atria of Dahl salt-sensitive rats more potently than
amlodipine. Since plasma catecholamine levels is lower in the cilnidipine-treated
animals than those in amlodipine-treated ones, blockade of N-type calcium
channels presumably contributes to the superior cardioprotective effect of
cilnidipine. These findings provide important information for considering
treatment of hypertension complicating AF.