European Journal of Neuroscience,
Journal Year:
2024,
Volume and Issue:
60(1), P. 3629 - 3642
Published: May 2, 2024
Abstract
Microglia
are
endogenous
immune
cells
in
the
brain,
and
their
pyroptosis
phenotype
dichotomy
proved
to
play
roles
neurodegenerative
diseases.
We
investigated
whether
how
hypoxia
affected
polarization
mouse
microglia.
Primary
microglia
BV2
were
exposed
hypoxia.
Pyroptosis
M1/M2
assessed
by
measuring
gasdermin
D
truncation
surface
marker
expression.
Mechanisms
including
purinergic
ionotropic
receptor
(P2XR),
peroxisome
proliferator‐activated
coactivator‐1α
(PGC‐1α)
NOD‐like
protein
3
(NLRP3)
inflammasome
investigated.
reported
(90%
N
2
,
5%
O
CO
)
induced
promoted
M1
primary
microglia,
effect
appeared
after
6
h
exposure.
Although
h)
had
no
on
P2X1R
P2X7R
expression,
it
increased
P2X4R
expression
decreased
PGC‐1α
Interestingly,
blockade
of
or
abolished
hypoxia‐modulated
polarization.
overexpression
overactivation
alleviated
hypoxia‐induced
polarization,
while
knockdown
deactivation
under
normoxic
situation.
Further,
NLRP3
activated
caspase‐1
phosphorylation
NF‐κB
reduced
STAT3/6.
inhibitor
pyroptosis,
STAT
inducer
ameliorated
In
addition,
activator
STAT3/6
caused
concluded
cultured
may
induce
via
P2XR/PGC‐1α/NLRP3/caspase‐1
pathway
trigger
through
P2XR/PGC‐1α/NF‐κB/STAT3/6
pathway.
Inflammation,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 26, 2025
There
is
increasing
interest
in
developing
therapeutic
interventions
aimed
at
preventing
neuroinflammation
Parkinson's
disease
(PD).
However,
the
specific
characteristics
of
inflammation
across
different
cell
types
and
underlying
mechanisms
PD-related
remain
inadequately
understood.
In
this
study,
we
conducted
an
analysis
single-cell
RNA
sequencing
(scRNA-seq)
microarray
data
derived
from
human
PD
midbrain
tissue,
specifically
focusing
on
substantia
nigra
compacta
(SNc).
These
datasets
were
sourced
(GEO)
database.
We
utilized
GSVA,
GSEA,
as
well
KEGG
GO
analyses
to
explore
transcriptional
variations
associated
with
PD.
Furthermore,
trajectory
SCENIC
uncover
progression.
Subsequent
animal
cellular
experiments
validated
role
regulon
regulating
neuroinflammation.
Results:
Our
revealed
that
microglia
displayed
highest
levels
inflammatory
activity,
characterized
by
increased
abundance
proinflammatory
activated
state
within
SNc
patients.
This
finding
was
further
a
mouse
model
induced
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP).
The
transcription
factor
STAT3
demonstrated
significant
upregulation
implicated
promoting
response
activating
context.
1-methyl-4-phenylpyridine
(MPP
+)-induced
BV2
model,
inhibition
led
reduced
inflammation,
hindered
phosphorylation,
decreased
production
factors.
downregulation
P-STAT3
alleviated
harmful
effects
SH-SY5Y
cells
cocultured
conditioned
medium.
Conclusions:
study
underscored
pivotal
central
regulator
activation
findings
offer
fresh
insights
into
pathogenesis
suggest
potential
avenues
for
development
novel
strategies.
The FASEB Journal,
Journal Year:
2024,
Volume and Issue:
38(2)
Published: Jan. 24, 2024
Abstract
Immune‐mediated
acute
hepatic
injury
is
characterized
by
the
destruction
of
a
large
number
hepatocytes
and
severe
liver
function
damage.
Interleukin‐28A
(IL‐28A),
member
IL‐10
family,
notable
for
its
antiviral
properties.
However,
despite
advances
in
our
understanding
IL‐28A,
role
immune‐mediated
remains
unclear.
The
present
study
investigated
IL‐28A
concanavalin
A
(Con
A)‐induced
immune
injury.
After
Con
injection
mice,
level
significantly
increased.
deficiency
was
found
to
protect
mice
from
injury,
prolong
survival
time,
reduce
serum
aspartate
aminotransferase
alanine
levels.
In
contrast,
recombinant
aggravated
mice.
proportion
activated
M1
macrophages
lower
IL‐28A‐deficiency
group
than
wild‐type
mouse
group.
adoptive
transfer
experiments,
WT
could
exacerbate
symptoms
Furthermore,
expression
proinflammatory
cytokines,
including
tumor
necrosis
factor‐α
(TNF‐α),
IL‐12,
IL‐6,
IL‐1β,
decreased
Western
blotting
demonstrated
that
limit
macrophage
polarization
modulating
nuclear
factor
(NF)‐κB,
mitogen‐activated
protein
kinase
(MAPK),
interferon
regulatory
(IRF)
signaling
pathways.
summary,
deletion
plays
an
important
protective
A‐induced
model
inhibits
activation
inhibiting
NF‐κB,
MAPK,
IRF
These
results
provide
potential
new
target
treatment
immune‐related
Molecules,
Journal Year:
2024,
Volume and Issue:
29(7), P. 1497 - 1497
Published: March 27, 2024
Iridoid
components
have
been
reported
to
significant
neuroprotective
effects.
However,
it
is
not
yet
clear
whether
the
efficacy
and
mechanisms
of
iridoid
with
similar
structures
are
also
similar.
This
study
aimed
compare
effects
eight
(catalpol
(CAT),
genipin
(GE),
geniposide
(GEN),
geniposidic
acid
(GPA),
aucubin
(AU),
ajugol
(AJU),
rehmannioside
C
(RC),
D
(RD))
based
on
corticosterone
(CORT)-induced
injury
in
PC12
cells.
cells
were
randomly
divided
into
a
normal
control
group
(NC),
model
(M),
positive
drug
(FLX),
administration
groups.
Firstly,
induced
CORT
simulate
neuronal
injury.
Then,
MTT
method
flow
cytometry
applied
evaluate
protective
cell
damage.
Thirdly,
metabolomics
ultra-performance
liquid
chromatography–quadrupole–time-of-flight
mass
spectrometry
(UPLC-Q/TOF-MS)
was
performed
explore
changes
relevant
biomarkers
metabolic
pathways
following
intervention
administration.
The
assay
analysis
showed
that
can
improve
viability,
inhibit
apoptosis,
reduce
intracellular
ROS
levels,
elevate
MMP
levels.
In
PCA
score
plots,
sample
points
treatment
groups
trend
towards
approaching
NC
group.
Among
them,
AU,
AJU,
RC
had
weaker
effect.
There
38
metabolites
(19
each
negative
ion
modes,
respectively)
identified
as
potential
during
experiment,
among
which
23
common
Pathway
enrichment
revealed
regulated
metabolism
mainly
relation
D-glutamine
D-glutamate
metabolism,
arginine
biosynthesis,
TCA
cycle,
purine
glutathione
metabolism.
conclusion,
could
reverse
an
imbalanced
state
by
regulating
amino
neurotransmitters,
interfering
energy
harmonizing
level
oxidized
substances
exhibit
