DOC-1R (deleted in oral cancer-1 related) is a novel putative tumor suppressor. This study investigated DOC-1R antitumor activity and the underlying molecular mechanisms. Cell phenotypes were assessed using flow cytometry, BrdU incorporation and CDK2 kinase assays in DOC-1R overexpressing HeLa cells. In addition, RT-PCR and Western blot assays were used to detect underlying molecular changes in these cells. The interaction between DOC-1R and CDK2 proteins was assayed by GST pull-down and immunoprecipitation-Western blot assays. The data showed that DOC-1R overexpression inhibited G1/S phase transition, DNA replication and suppressed CDK2 activity. Molecularly, DOC-1R inhibited CDK2 expression at the mRNA and protein levels, and there were decreased levels of G1-phase cyclins (cyclin D1 and E) and elevated levels of p21, p27, and p53 proteins. Meanwhile, DOC-1R associated with CDK2 and inhibited CDK2 activation by obstructing its association with cyclin E and A. In conclusion, the antitumor effects of DOC-1R may be mediated by negatively regulating G1 phase progression and G1/S transition through inhibiting CDK2 expression and activation.
BACKGROUND: Ginsenoside Rb1 is one of the major bioactive components of Panax ginseng C.A. Meyer (Araliaceae), a medicinal plant that has been used for therapeutic purposes for thousands of years in Asian countries. The pharmaceutical activity of ginsenoside Rb1 highly depends on molecular structure and its deglycosylated metabolites are known to be more potent bioactive compounds. However, these deglycosylated ginsenosides do not exist naturally so they are usually obtained by poorly selective methods, like chemical hydrolysis.RESULTS: In this study, the development and characterization of an alginate-based immobilized enzyme microreactor for the catalytic conversion of ginsenoside Rb1 to more bioactive metabolites have been reported. Enzyme kinetic parameters were calculated and characterization tests (such as determination of surface area of alginate matrix, long-term use, and effect of residence time on conversion yield) were conducted. The system was operated under continuous-flow conditions and compared with acidic and batch enzymatic hydrolysis experiments, as conventional approaches. The enzymatic microreactor showed an enhanced activity by producing 13-fold higher amount of ginsenoside F2 than batch enzymatic hydrolysis. CONCLUSION: Obtained results indicated that the newly developed enzymatic microreactor could successfully convert ginsenoside Rb1 to more active metabolites and have a potential for the biocatalysis of multiple ginsenosides, as well as pharmaceutically active compounds.
Smart
materials possess a high potential for application in process
engineering. Among these smart materials, stimuli-responsive hydrogels
exhibit the chemically inherent characteristic to significantly change
their macroscopic properties through shifts in environmental conditions.
This enables response-triggered actuation caused by a reaction or
process deviation. Thereby, smart process concepts are facilitated,
which are capable of self-contained process control without external
input. Through additive manufacturing of responsive hydrogels, intricate
geometries can be generated, with which the response-triggered actuation
can perform sophisticated control tasks. Periodic open-cell structures
are such geometries, which improve the mass transport in multiphase
flows through the distribution of the disperse phase. Responsive hydrogels
fabricated as periodic open-cell structures enable the actuation of
multiphase flows through an environmental switch allowing for adjustment
of flow conditions. Herein, we demonstrate the application of switchable
smart structures that facilitate the adaptation of fluid-dynamic properties
and mass transfer in cocurrent gas–liquid flows depending on
environmental conditions. Smart structures, which are additively manufactured
from acrylate photoresist formulations, are applied for in
situ and in operandi adjustment of phase
distribution through expansion and collapse of these structures in
flow channels. Further, diverse photoresist formulations with different
associated response triggers are shown, which demonstrate the versatility
for application as an in situ and in operandi switch for mass transfer in process units operating with multiphase
flows.
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