Fibroblast Growth Factor 21 Protects Against Cerebral Ischemia/Reperfusion Injury by Inhibiting Oxidative Stress and Ferroptosis
Neuropsychiatric Disease and Treatment,
Год журнала:
2025,
Номер
Volume 21, С. 355 - 371
Опубликована: Фев. 1, 2025
Cerebral
ischemia/reperfusion
injury
(CIRI)
severely
impacts
patient
outcomes
and
quality
of
life,
with
limited
treatment
options.
Although
fibroblast
growth
factor21
(FGF21)
is
known
for
its
metabolic
anti-inflammatory
effects,
role
mechanisms
in
CIRI
are
not
well
explored.
After
developing
an
MCAO/R
model,
mice
received
intraperitoneal
injections
FGF21
(1.5
mg/kg)
15
min
pre-reperfusion,
as
8
16
h
post-reperfusion.
The
TTC,
TUNEL,
H&E,
Nissl
stainings
were
used
24
post-reperfusion
to
determine
the
infarct
volume,
apoptotic
cells,
brain
pathological
damage,
nerve
cell
survival,
respectively.
ELISA
Western
blotting
employed
detect
oxidative
stress
(OxS)
products
ferroptosis-related
markers.
RNA-seq
ischemic
penumbra
tissues
was
conducted,
followed
by
bioinformatics
analysis
screen
identify
differentially
expressed
genes
(DEGs).
Then,
we
qPCR
validate
relevant
molecule
mRNA
expression
while
using
immunofluorescence
staining
assess
CYBB
protein
localization
expression.
reduced
volume
MCAO/R-injured
mice,
diminished
numbers,
alleviated
damage
tissue.
Furthermore,
inhibited
OxS
ferroptosis
post-CIRI.
revealed
a
significant
differential
numerous
genes,
extensively
involving
diverse
biological
processes
post-
(IRI).
Bioinformatics
validation
results
indicated
that
most
significantly
molecule,
it
may
be
novel
key
regulatory
mediating
anti-IRI
FGF21.
protects
inhibiting
ferroptosis.
CYBB,
new
regulator,
mediate
anti-ferroptotic
offering
insights
into
therapies.
Язык: Английский
Neuroprotective effects of hirudin against cerebral ischemia-reperfusion injury via inhibition of CCL2-mediated ferroptosis and inflammatory pathways
Brain Research Bulletin,
Год журнала:
2025,
Номер
unknown, С. 111293 - 111293
Опубликована: Март 1, 2025
Cerebral
ischemia-reperfusion
injury
(CIRI)
is
a
leading
cause
of
neurological
impairment
in
stroke,
primarily
correlated
to
oxidative
stress,
inflammation,
and
ferroptosis.
This
study
investigates
the
neuroprotective
effects
hirudin
on
CIRI,
focusing
its
role
modulating
neuronal
survival,
ferroptosis
markers
through
inhibition
CCL2.
A
middle
cerebral
artery
occlusion
(MCAO)
model
mice
an
oxygen-glucose
deprivation/reoxygenation
(OGD/R)
HT22
cells
were
used
simulate
ischemic
conditions.
Hirudin
significantly
improved
function
reduced
edema
infarct
size
MCAO
model.
In
vitro,
enhanced
viability
apoptosis
OGD/R-stimulated
cells.
Integrative
network
pharmacology
transcriptomic
analysis
identified
CCL2
as
potential
target
hirudin.
treatment
suppressed
expression,
which
turn
TLR4/NF-κB
signaling
activation,
thereby
mitigating
inflammatory
responses
neurons.
Overexpression
partially
reversed
these
protective
effects,
underscoring
injury.
These
findings
suggest
that
alleviates
CIRI
by
preventing
ferroptosis,
offering
insights
into
therapeutic
agent
for
Язык: Английский
Natural flavonoids from herbs and nutraceuticals as ferroptosis inhibitors in central nervous system diseases: current preclinical evidence and future perspectives
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Март 24, 2025
Flavonoids
are
a
class
of
important
polyphenolic
compounds,
renowned
for
their
antioxidant
properties.
However,
recent
studies
have
uncovered
an
additional
function
these
natural
flavonoids:
ability
to
inhibit
ferroptosis.
Ferroptosis
is
key
mechanism
driving
cell
death
in
central
nervous
system
(CNS)
diseases,
including
both
acute
injuries
and
chronic
neurodegenerative
disorders,
characterized
by
iron
overload-induced
lipid
peroxidation
dysfunction
the
defense
system.
This
review
discusses
therapeutic
potential
flavonoids
from
herbs
nutraceuticals
as
ferroptosis
inhibitors
CNS
focusing
on
molecular
mechanisms,
summarizing
findings
preclinical
animal
models,
providing
insights
clinical
translation.
We
specifically
highlight
such
Baicalin,
Baicalein,
Chrysin,
Vitexin,
Galangin,
Quercetin,
Isoquercetin,
Eriodictyol,
Proanthocyanidin,
(−)-epigallocatechin-3-gallate,
Dihydromyricetin,
Soybean
Isoflavones,
Calycosin,
Icariside
II,
Safflower
Yellow,
which
shown
promising
results
models
injuries,
ischemic
stroke,
cerebral
ischemia-reperfusion
injury,
intracerebral
hemorrhage,
subarachnoid
traumatic
brain
spinal
cord
injury.
Among
these,
Baicalin
its
precursor
Baicalein
stand
out
due
extensive
research
favorable
outcomes
injury
models.
Mechanistically,
not
only
regulate
Nrf2/ARE
pathway
activate
GPX4/GSH-related
pathways
but
also
modulate
metabolism
proteins,
thereby
alleviating
overload
inhibiting
While
show
promise
especially
settings,
further
needed
evaluate
efficacy,
safety,
pharmacokinetics,
blood-brain
barrier
penetration
application.
Язык: Английский
Neuroprotective effects of arctigenin on cerebral ischemia-reperfusion injury in rats via the EPO/EPOR-JAK2-STAT5 signaling pathway
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Март 26, 2025
Introduction
Cerebral
ischemia-reperfusion
injury
(CIRI)
is
a
complex
pathophysiological
process
with
significant
morbidity
and
mortality,
there
no
specific
agent.
Previous
studies
have
found
that
arctigenin
can
play
an
anti-CIRI
role
through
anti-inflammatory
antioxidant
effects.
This
study
further
explored
the
mechanism
of
via
EPO/EPOR-JAK2-STAT5
signaling
pathway.
Methods
TTC
H&E
staining
were
used
to
observe
infarct
volume
morphological
changes
in
brain,
RT-PCR
was
detect
EPO,
EPOR,
HIF,
JAK2,
STAT5,
NF-κB
mRNA
expression,
EPO/EPOR
ratio
detected
by
immunofluorescence,
HIF
observed
immunohistochemical
staining.
The
protein
expression
levels
JAK2
STAT5
detected,
western
blot.
Results
Our
results
indicate
significantly
reduced
improved
histopathological
brain
tissues
from
CIRI
rats
at
24
h,
48
72
h
after
reperfusion
analysis
showed
could
upregulate
expressions
downregulate
reperfusion.
Immunofluorescence
assay
post-reperfusion
elevated
arctigenin.
Arctigenin
while
NFκB
regulation
also
confirmed
Western
blot
reperfusion,
consistent
above
results.
Discussion
In
conclusion,
demonstrated
neuroprotective
properties
against
potentially
These
findings
provide
scientific
rationale
for
exploration
as
therapeutic
agent
stroke.
Язык: Английский
Investigation of Ferroptosis Mechanisms in Ischemic Stroke Treated with Electroacupuncture: Focusing on the NCOA4-FTH1 Signaling Pathway
Neurochemical Research,
Год журнала:
2025,
Номер
50(2)
Опубликована: Апрель 1, 2025
Язык: Английский
MT1G promotes iron autophagy and inhibits the function of gastric cancer cell lines by intervening in GPX4/SQSTM1
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Ноя. 18, 2024
Gastric
cancer
(GC)
is
the
fifth
most
common
and
third
cause
of
death
globally,
with
high
invasiveness,
recurrence
rate,
poor
prognosis.
Multiple
studies
have
shown
that
Metallothionein-1G
(MT1G)
closely
associated
oxidative
stress,
ferroptosis,
autophagy.
However,
role
potential
mechanisms
MT1G
in
GC
not
been
fully
elucidated.
This
study
aims
to
explore
biological
functions
regulatory
GC.
Perform
bioinformatics
analysis
using
TCGA
database
investigate
expression
RT-qPCR
Western
blot
were
used
detect
MT1G,
ferroptosis
related
proteins,
autophagy
proteins
ARNTL
clock
Hgc27,
MKN45
AGS
cell
lines.
Exploring
overexpressing
lines
through
wound
healing
transwell
experiments.
Use
specific
fluorescence
probes
examine
mitochondrial
membrane
Fe2+
intensity.
Using
immunoprecipitation
(CO-IP)
elucidate
association
between
GPX4,
SQSTM
ARNTL.
flow
cytometry
ROS
expression.
Observation
morphological
changes
cells
transmission
electron
microscopy.
Compared
gastric
mucosal
lines,
decreased
three
(Hgc27,
AGS).
Overexpression
inhibits
proliferation,
migration,
invasion
cells,
reduces
SOD
GSH
content,
increases
MDA
weaken
promote
transformation
JC-1
aggregates
monomer,
Fe2+,
affects
ROS,
GPX4
SLC7A11
protein
expression,
promoting
ferroptosis.
promotes
LC3B
I
II,
SQSTM1
leads
appearance
more
autophagosomes
autolysosomes
at
low
magnification.
At
magnification,
autophagy,
endoplasmic
reticulum
lipid
droplet
wrinkled
cristae
are
observed,
thereby
affecting
as
a
vector
EGLN2,
GPX4/SQSTM1
axis.
Our
research
findings
overexpression
iron
centered
around
via
axis,
inhibiting
function
providing
new
molecular
mechanism
therapeutic
target
for
development
Язык: Английский
The cGAS-STING pathway in ischemia-reperfusion injury in acute cerebral infarction: a new therapeutic opportunities?
Frontiers in Neurology,
Год журнала:
2024,
Номер
15
Опубликована: Дек. 17, 2024
The
innate
immune
response
is
the
body's
first
line
of
defense
against
external
pathogens
and
endogenous
damage
signals.
cGAS-STING
pathway
a
crucial
component
response,
playing
key
role
in
initiating
antiviral
anti-infective
responses
by
recognizing
cytosolic
DNA.
Acute
cerebral
infarction
one
leading
causes
death
disability
worldwide,
with
primary
treatment
approach
being
restoration
blood
flow
to
ischemic
brain
tissue.
However,
reperfusion
injury
remains
significant
challenge
during
treatment.
overactivation
its
association
ischemia-reperfusion
have
been
confirmed
numerous
studies.
This
article
will
systematically
elucidate
mechanisms
pathway,
acute
infarction,
current
research
status
inhibitors,
application
nanomaterials
this
context,
evaluating
therapeutic
potential
pathway.
Язык: Английский
Therapeutic Effect of Thymoquinone on Melatonin, Ferritin, and Renal Function in Renal Ischemia/Reperfusion Injury in Rats
European Journal of Therapeutics,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 12, 2024
Objective:
Ischemia/reperfusion
(I/R)
injury
is
the
period
of
tissue
or
organ
damage
that
develops
after
tissue's
blood
flow
restored.
The
extent
varies
according
to
severity
and
cell
damage.
Thymoquinone
(TQ)
has
a
wide
therapeutic
spectrum.
effect
thymoquinone
on
melatonin
ferritin
in
I/R
can
regulate
renal
function
by
combining
these
two
mechanisms
improve
Therefore,
levels
as
well
its
regulatory
role
functions
have
been
investigated.
Methods:
Thirty-six
male
Sprague
Dawley
rats
were
included
study
(250-300
g,
8-10
weeks).
randomly
assigned
6
groups
with
animals
each
group.
Groups;
1-
Control,
2-
Sham,
3-
Solvent,
4-
Renal
ischemia/reperfusion
(I/R),
5-
I/R+
(5
mg/kg/day),
6-
TQ
mg/kg/day).
dorsal
region
was
surgically
opened,
left
artery
clamped
for
30
minutes
then
reperfused
24
hours.
(i.p)
applied
treatment
15
days.
At
end
experiment,
samples
taken
from
all
groups,
kidney
tests
(Na+,
K+,
Creatinine,
urea,
BUN)
performed.
Melatonin
analyzed
ELISA
method
samples.
Results:
Data
showed
short-term
effective
serum
K+
(P
=
0.010)
tissue.
iron
activity,
which
normal
healthy
decreased
increased
significantly
positively
regulated
dysregulation
molecules
I/R.
Conclusion:
may
contribute
healing
improving
levels,
indicates
insufficiency
ferritin,
interacting
I/R,
are
TQ,
indicating
they
management
Язык: Английский
PKCδ modulates SP1 mediated mitochondrial autophagy to exacerbate diacetylmorphine-induced ferroptosis in neurons
Mengjie Zhuang,
Sensen Zhu,
Liping Su
и другие.
International Immunopharmacology,
Год журнала:
2024,
Номер
143, С. 113468 - 113468
Опубликована: Окт. 28, 2024
Diacetylmorphine
(DA)
is
widely
implicated
in
neuronal
injury;
however,
the
underlying
mechanisms
remain
unclear.
We
investigated
role
of
iron
metamorphosis
DA-induced
neurotoxicity
using
Sprague-Dawley
rats
and
PC12
SH-SY5Y
cells.
Tandem
mass
tag
proteomics
analysis
showed
that
upregulation
protein
kinase
C
delta
(PKCδ)
metabolism-related
transferrin
receptor
(TFRC)
significantly
enriched
metabolism
pathway.
Subsequent
experiments
DA
exposure
upregulated
PKCδ
cells,
which
increased
nuclear
translocation
specificity
1
(SP1),
intracellular
free
lipid
peroxide
levels.
In
addition,
silencing
improved
behaviour
restored
expression
level
glutathione
peroxidase
4
(GPX4).
activated
mitochondrial
autophagy
leading
to
a
decrease
membrane
potential,
accumulation
reactive
oxygen
species
(ROS),
elevation
LC3
(which
plays
key
autophagy),
p62
expression.
Following
inhibition
autophagy,
potential
ROS
were
restored,
as
was
voltage-dependent
anion
channel
(VDAC1)
GPX4.
conclusion,
present
study
suggests
regulates
SP1,
further
exacerbating
ferroptosis.
Therefore,
or
ferroptosis
may
be
therapeutic
target
ameliorate
following
exposure.
Язык: Английский
AEBP1 Silencing Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating Neuron Ferroptosis and Microglia M2 Polarization Through PRKCA‐PI3K‐Akt Axis
Drug Development Research,
Год журнала:
2024,
Номер
85(8)
Опубликована: Дек. 1, 2024
ABSTRACT
Cerebral
ischemia/reperfusion
injury
is
one
of
the
main
causes
neuronal
damage.
Neuron
ferroptosis
and
microglia
polarization
are
considered
as
critical
processes
during
cerebral
ischemia/reperfusion.
Adipocyte
enhancer‐binding
protein
1
(AEBP1)
usually
acts
a
transcriptional
repressor
which
involved
in
various
diseases.
However,
it
still
remains
unknown
whether
AEBP1
could
have
important
roles
regulating
neuron
injury.
The
oxygen‐glucose
deprivation
reperfusion
(OGD/R)‐treated
cells
middle
artery
occlusion
(MCAO)‐treated
mice
were
used
vitro
vivo
models.
differentially
expressed
factors
analyzed
according
to
GEO
datasets.
Relative
mRNA
expression
levels
detected
by
qRT‐PCR
western
blot
analysis.
Cell
viability
was
measured
CCK‐8
assay.
ROS,
GSH
iron
contents
using
specifical
assay
kits.
CD26
CD206
immunofluorescence
Inflammatory
cytokines
ELISA.
association
between
PRKCA
assessed
luciferase
reporter
ChIP
analyses.
damage
TTC
staining
neurological
deficit
score.
Transcription
factor
increased
OGD/R‐treated
HT22
BV2
cells.
silencing
attenuated
OGD/R‐induced
cell
through
increasing
viability,
GPX4
levels,
decreasing
ACSL4
levels.
knockdown
promoted
M2
CD206‐positive
Arg‐1
level,
reducing
iNOS,
TNF‐α,
IL‐1β
IL‐6
transcriptionally
repressed
expression,
further
regulated
PI3K/Akt
signaling
activation.
Inhibition
or
reversed
effects
on
polarization.
downregulation
infarct
size
scores
MCAO‐treated
mice.
mitigated
activating
signaling,
indicating
potentially
protective
action
Язык: Английский