Inspired by the well-known phenomenon of stretch-induced airway dilation
in normal lung and the emerging stretch-responsive Piezo1 channels, the authors
in this study demonstrated that chemical activation of Piezo1 channels by
agonist YODA1 dramatically reduced the contractility of cultured ASMCs in terms
of cells stiffness, traction force, migration, and expression of molecules
associated with cell mechanics. These findings indicate that chemical
activation of Piezo1 can indeed modulate biomechanical behaviors of ASMCs
towards relaxation. And this novel regulatory mechanism as alternative to the
conventional b2-adrenergic receptor for relaxation of ASMCs
may provide a potentially new target for bronchodilation in asthma therapy.
Various factors affect the prognosis of
dialysis patients. Analysis of the drugs used and clinical and demographic
characteristics of the patient at the time of dialysis initiation is a useful
means of estimating prognosis. The authors investigated the drugs used by
dialysis patients during the induction phase of dialysis and performed a
detailed analysis of variables predictive of prognosis. As a result,
antihypertensives, hemoglobin, and age at start of dialysis were found to have
significant effects on dialysis duration. It was posited that antihypertensives
prolong dialysis duration, thereby improving life expectancy. These findings
may be used to improve drug adherence in dialysis patients and guide physicians
in their treatment.
Tropomyosin
receptor kinase B (TrkB) may be a key modulator of the pharmacological effects of barbiturates. Suzuki, et al., used a TrkB
agonist 7,8-dihydroxyflavone (DHF) in the animal study for phenobarbital-induced
general anesthesia, demonstrating that rats receiving the DHF pretreatment readily
fell into anesthesia in a shorter time than those without the pretreatment. They
then showed that DHF promotes the TrkB to be phosphorylated and that the
protein expression of the potassium chloride transporter KCC2 was consequently suppressed.
It was thus revealed that DHF potentiates the pharmacological effects of phenobarbital
as it causes the functional activation of the TrkB.
Bortezomib is widely used in treating
multiple myeloma, but causes serious adverse effects, such as peripheral
neuropathy, leading to discontinuation of Bortezomib treatment. To explore the
mechanism, the authors, unlike previous reports, applied relatively low
concentrations of bortezomib at clinical concentration, to primary cultured
Schwann cells, satellite glial cells, macrophages, and dorsal root ganglion
neurons. The results showed that bortezomib caused Schwann cell dedifferentiation,
increased GFAP levels in satellite glial cells without inducing inflammatory
responses, and decreased ion channel expression in dorsal root ganglion
neurons. This may explain the mechanism of bortezomib-induced peripheral
neuropathy.
Ependymal cilia on the ventricular surface play pivotal roles in cerebrospinal fluid flow.
Authors newly constructed the polarized primary culture system of ependymal
multiciliated cells (MCCs) from undifferentiated glial cells using a permeable
filter in which they retained ciliary movement. Fetal bovine serum (FBS) on the
ventricular side of culture inhibited the differentiation with ciliary
movement. Transforming growth factor-b1 (TGF-b1) and
Bone morphogenetic protein (BMP)-2 mimic the inhibitory action of FBS. The
inhibition on the differentiation by FBS was recovered by the TGF-b1
and BMP-2 inhibitors in combination. Taken together,
TGF-b1 and BMP-2
are found to be major inhibitors in the differentiation of ependymal MCCs.