Extensive studies in recent years have revealed important functions of
the Hippo intracellular signaling pathway in the control of organ development,
stem cell biology, regeneration, and cancer. While a number of novel drugs are
currently under development to modulate the Hippo pathway for cancer treatment
and regenerative medicine, the molecular networks involving in the regulation
of the Hippo pathway are just beginning to be elucidated. The review article by
Shimoda and Moroishi summarizes the emerging understanding of the interplay
between the Hippo pathway and non-coding RNAs, discussing a new approach to target this pathway for future
drug discovery.
Yoshioka and Miura et
al. have focused on the relationship between the injection timings and the
severity of toxicity, which they advocated as “chronotoxicology”. The aim of this
study was to investigate the “chronotoxicity” of streptomycin (SM) in relation
to its circadian periodicity. Both the mortality and the nephrotoxicity levels
were severe by the SM injection during the “dark phase” than during the “light
phase”, representing that SM showed evident chronotoxicity. The results
indicated that chronotoxicology may provide valuable information on the
importance of injection timings for evaluations of toxicity, and considering
when determining any undesirable side effects.
Allergic contact
dermatitis (ACD) is one of the most common
skin diseases caused by hapten-modified
proteins. The article demonstrated that metformin inhibited inflammatory responses in macrophages. Furthermore, metformin also enhanced autophagic flux,
inhibited the phosphorylation of AKT/mTOR, MAPKs related protein levels and the
level of miR-221 in macrophages. Besides, metformin attenuated 2,4-dinitrofluorobenzene
(DNFB) -induced ACD partly through the inhibition of macrophage activation and
the induction of autophagic flux. Taken together, the results indicated that
metformin ameliorates ACD through enhanced autophagic flux to inhibit
macrophage activation and provides a potential contribution to ACD treatment.
Thrombin is a serine protease as a blood
coagulation factor, but also has been implicated in the pathology of brain
ischemia, stroke or neurogenerative diseases. In this study, Akaishi et al. have
demonstrated that the
synthetic curcumin derivative CNB-001 suppresses thrombin-induced NO production
through the inhibition of ERK and p38 MAPK pathways in microglia. In contrast, the
authors have previously reported that CNB-001 suppressed LPS-induced NO
production through the inhibition of p38 MAPK, but not ERK. Therefore, additional
studies on differences in signaling
cascades by which thrombin and LPS promote ERK phosphorylation will help to identify
the direct molecular target of CNB-001.
Hypersensitive
reaction to pathogenic attacks in plants triggers the expression of numerous
plant genes encoding defense proteins. Pathogenesis-related (PR) proteins play
an important role in inducing strong self-defense systems by getting
accumulated in intercellular parts and vacuoles. Joo et al. cloned a PR protein
gene from Oenanthe javanica (OJPR),
which included PR-10 allergen without putative IgE binding residues, comprising
154-amino acids with a molecular mass of 16 kDa. The results of this study
suggested that the newly identified and expressed OJPR may possess the
biological activity and play a role in modulating host defense responses via
Toll-like receptor signal cascades together with anti-viral activities in immune
cells.