Transient receptor potential melastatin 3 (TRPM3)
is Ca2+-permeable channel that is highly expressed in the brain and activated
by the neurosteroid pregnenolone sulfate (PS) and body temperature. Here, it is
shown that TRPM3 was expressed in cultured rat oligodendrocyte precursor cells
(OPCs) and activated by PS, resulting in extracellular Ca2+ influx. Moreover, TRPM3 expression was increased by treatment with tumor
necrosis factor a. In demyelinated lesions
of endothelin-1-induced ischemic rat model (lacunar infarction model), TRPM3
was upregulated in OPCs, a type of glial cells that differentiate into myelinating
oligodendrocytes. These imply that TRPM3 is involved in the regulation of
specific behaviors of OPCs in inflammatory pathological conditions. Scale bar
shows 200 mm.
The
article by Kitabatake et al. suggested a novel mechanism of radiation resistance
and radiation-induced acquisition of malignant profile in glioblastoma. Authors
have shown that CD73, an enzyme that metabolizes extracellular ATP to adenosine,
and activation of adenosine A2B receptor (CD73-A2B receptor pathway) are
involved in radiation-induced DNA damage response, cell death, and enhancement of
cell migration in A172 cells. These findings proposed that the CD73-A2B
receptor pathway contributes to the resistance of the antitumor effect of
radiation in glioblastoma and could be a novel molecular target to improve the
efficiency of radiation therapy for glioblastoma.
Most of therapeutic peptides like insulin are administered parenteral
because of rapid hydrolysis and enzymatic degradation after oral
administration. Many techniques have been investigated for overcoming the
problems and meeting the shortage of current conventional dosage forms such as
iontophoresis.In this study, authors investigated if iontophoresis can be used to
enhance permeation of insulin nanoparticles across the intestinal membrane and
thus enhance the oral delivery of insulin.Gut iontophoresis is a promising technology that can substantially
improve the transport of insulin nanoparticles across the intestinal membrane
barrier.
Acidified extracellular
pH (pHe) characterized of tumor microenvironment (TME) impairs the responses of
tumors to anti-cancer chemotherapies. In this study, the authors showed that
daily oral dosing of sodium potassium citrate (K/Na citrate) increased blood bicarbonate
concentrations and then neutralized the tumor pHe. In addition, this tumor neutralization
potentiated the therapeutic effect of anticancer agent TS-1 on Panc-1
pancreatic cancer-xenograft murine model. The authors strongly propose that the
neutralization of acidic TME by oral dosing of K/Na citrate must be a smart
approach for enhancing the therapeutic effects of anticancer agents for
pancreatic cancer in the end stage.
α-Defensin
5 has a particularly broad antibacterial spectrum, eliminates pathogenic
microorganisms and regulates intestinal flora. There are few reports of
measuring the secretory capacity of α-defensin 5 in vitro. In this
study, author found Caco-2 cells, which are gastrointestinal model cells, secreted
α-defensin 5 and examined the relationship between α-defensin 5 secretion and
cytokines mRNA levels such as TNF-α. These results suggest that Caco-2 cells
may be a simple model for screening health food components and drugs that
affect α-defensin 5 secretion.