Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Апрель 8, 2024
The
death
of
cells
can
occur
through
various
pathways,
including
apoptosis,
necroptosis,
mitophagy,
pyroptosis,
endoplasmic
reticulum
stress,
oxidative
ferroptosis,
cuproptosis,
and
disulfide-driven
necrosis.
Increasing
evidence
suggests
that
mitophagy
ferroptosis
play
crucial
regulatory
roles
in
the
development
stroke.
In
recent
years,
incidence
stroke
has
been
gradually
increasing,
posing
a
significant
threat
to
human
health.
Hemorrhagic
accounts
for
only
15%
all
strokes,
while
ischemic
is
predominant
type,
representing
85%
cases.
Ischemic
refers
clinical
syndrome
characterized
by
local
ischemic-hypoxic
necrosis
brain
tissue
due
cerebrovascular
disorders,
leading
rapid
onset
corresponding
neurological
deficits.
Currently,
specific
therapeutic
approaches
targeting
pathophysiological
mechanisms
injury
mainly
include
intravenous
thrombolysis
endovascular
intervention.
Despite
some
efficacy,
these
inevitably
lead
ischemia-reperfusion
injury.
Therefore,
exploration
treatment
options
remains
challenging
task.
light
this
background,
advancements
targeted
therapy
diseases
offer
new
direction
such
diseases.
review,
we
summarize
progress
regulating
emphasize
their
potential
molecular
pathogenesis.
Importantly,
systematically
elucidate
role
medicinal
plants
active
metabolites
stroke,
providing
insights
perspectives
drugs
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Март 18, 2025
Ferulic
acid
(FA)
has
shown
potential
in
treating
atherosclerosis
(AS)
by
improving
lipid
metabolism
and
exerting
anti-hypoxic
effects.
This
study
aimed
to
validate
the
mechanism
of
FA
AS
through
vitro
experiments.
Network
analysis
was
employed
predict
mechanisms
underlying
therapeutic
effects
on
AS.
An
foam
cell
model
established
using
RAW
264.7
cells
treated
with
ox-LDL.
Cellular
accumulation
detected
Oil
Red
O
staining;
viability
assessed
counting
kit-8;
mitochondrial
morphology
function
were
evaluated
transmission
electron
microscopy
JC-1
apoptosis
levels
TUNEL
DAPI
Fe2+
content
measured
Mito-FerroGreen;
Western
blot
performed
determine
protein
expression
HIF-1α,
Bax,
Bcl2,
GPX4,
EGFR.
suggested
that
may
exert
its
HIF-1
signaling
pathway
is
closely
associated
regulation
ferroptosis
apoptosis.
upregulated
ALOX5,
BCL2,
ERN1,
NOS3,
SLC2A1
mRNA
downregulated
BAX,
CYCS,
EGFR,
FLT1,
HIF1A,
NFKB1,
NOS2,
PARP1,
STAT3
mRNA.
In
experiments
demonstrated
reduces
accumulation,
increases
viability,
improves
function,
decreases
reactive
oxygen
species
content.
Additionally,
inhibited
suppressing
pathway,
up-regulating
GPX4
down-regulating
HIF-1α
Bax
protein.
agonists
reversed
these
activating
pathway.
suppresses
inhibiting
thereby
Heliyon,
Год журнала:
2024,
Номер
10(2), С. e24573 - e24573
Опубликована: Янв. 1, 2024
Ischemia-reperfusion
injury
(IRI)
is
a
significant
contributor
to
acute
kidney
(AKI)
and
associated
with
substantial
morbidity
mortality
rates.
In
this
study,
we
aimed
investigate
the
role
of
NAT10
its
ac4C
RNA
modification
in
IRI-induced
renal
injury.
Our
findings
revealed
that
both
expression
level
kidneys
were
elevated
IRI
group
compared
sham
group.
Functionally,
observed
inhibition
activity
Remodelin
or
specific
knockout
led
attenuation
Furthermore,
vitro
experiments
demonstrated
markedly
suppressed
global
modification,
providing
protection
against
hypoxia/reoxygenation-induced
tubular
epithelial
cell
ferroptosis.
Mechanistically,
our
study
uncovered
promoted
NCOA4
mRNA,
thereby
enhancing
stability
contributing
ferroptosis
cells
(TECs).
These
underscore
potential
as
promising
therapeutic
targets
for
treatment
AKI.
Overall,
sheds
light
on
critical
involvement
pathogenesis
injury,
offering
valuable
insights
development
novel
AKI
strategies.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Фев. 3, 2025
Radioresistance
is
thought
to
be
a
major
consequence
of
tumor
milieu
acidification
resulting
from
the
Warburg
effect.
Previously,
using
ogremorphin
(OGM),
small
molecule
inhibitor
GPR68,
an
extracellular
proton
sensing
receptor,
we
demonstrated
that
GPR68
key
pro-survival
pathway
in
glioblastoma
cells.
Here,
demonstrate
inhibition
also
induces
ferroptosis
lung
cell
carcinoma
(A549)
and
pancreatic
ductal
adenocarcinoma
(Panc02)
Moreover,
OGM
synergized
with
ionizing
radiation
induce
lipid
peroxidation,
hallmark
ferroptosis,
as
well
reduce
colony
size
2D
3D
culture.
not
acutely
detrimental
but
increases
intracellular
free
ferrous
iron,
which
known
trigger
reactive
oxygen
species
(ROS)
generation.
In
summary,
peroxidation
cancer
cells
sensitizes
them
part
through
mobilization
iron.
Our
results
suggest
mediator
radioresistance
activated
by
acidic
microenvironment.
