The Molecular Mechanisms of Bergapten Against Abdominal Aortic Aneurysm: Evidence From Network Pharmacology, Molecular Docking/Dynamics, and Experimental Validation
Journal of Cellular Biochemistry,
Год журнала:
2025,
Номер
126(4)
Опубликована: Март 30, 2025
ABSTRACT
This
study
endeavors
to
assess
the
potential
protective
role
of
bergapten
(BP)
in
mitigating
abdominal
aortic
aneurysm
(AAA)
and
decipher
underlying
mechanisms
molecular
targets.
Network
pharmacology
was
utilized
search
for
targets
BP
against
AAA.
Molecular
docking
dynamics
simulations
were
validate
interaction
with
core
targets,
then
therapeutic
effect
mechanism
on
AAA
verified
by
using
an
elastase‐induced
model.
analysis
identified
five
pharmacological
BP,
including
EGFR,
SRC,
PIK3CA,
PIK3CB,
JAK2.
further
prioritized
JAK2
as
most
promising
candidate
treatment
The
results
animal
experiments
demonstrated
that
significantly
reduced
expression
inflammatory
cytokines
IL‐6,
TNF‐α,
IL‐1β
tissue
mouse
model,
inhibited
phosphorylation
STAT3.
plays
important
AAA,
it
may
become
a
drug
combat
progression.
inhibitory
vascular
progression
attenuation
cell
infiltration
be
related
regulation
JAK2/STAT3
signaling
pathway.
Язык: Английский
Molecular Basis of Oncogenic PI3K Proteins
Cancers,
Год журнала:
2024,
Номер
17(1), С. 77 - 77
Опубликована: Дек. 30, 2024
The
dysregulation
of
phosphatidylinositol
3-kinase
(PI3K)
signaling
plays
a
pivotal
role
in
driving
neoplastic
transformation
by
promoting
uncontrolled
cell
survival
and
proliferation.
This
oncogenic
activity
is
primarily
caused
mutations
that
are
frequently
found
PI3K
genes
constitutively
activate
the
pathway.
However,
tumorigenesis
can
also
arise
from
nonmutated
proteins
adopting
unique
active
conformations,
further
complicating
understanding
PI3K-driven
cancers.
Recent
structural
studies
have
illuminated
functional
divergence
among
highly
homologous
proteins,
revealing
how
subtle
alterations
significantly
impact
their
contribute
to
tumorigenesis.
In
this
review,
we
summarize
current
knowledge
Class
I
aim
unravel
complex
mechanism
underlying
traits.
These
insights
will
not
only
enhance
our
PI3K-mediated
oncogenesis
but
pave
way
for
design
novel
PI3K-based
therapies
combat
cancers
driven
Язык: Английский