Background:
Severe
heat
stroke
is
often
complicated
by
multiple
organ
failure,
including
liver
injury.
Recent
evidence
indicates
that
the
underlying
mechanism
constitutes
sterile
inflammation
triggered
cell
damage,
in
which
hepatocyte
NOD-like
receptor
family
pyrin
domain-containing
3
inflammasome
activation
and
pyroptosis
play
key
roles.
As
extracellular
histones
act
as
damage-associated
molecular
patterns
mediate
tissue
toxicity
inflammation,
we
aimed
to
investigate
whether
contribute
inducing
following
stroke,
promoting
development
of
injury,
elucidate
potential
mechanisms.
Methods:
Exogenous
were
administered
AML-12
murine
hepatocytes
or
male
aged
8~12
week
mice
hyperthermic
treatment
(at
39°C
a
chamber
with
60%
relative
humidity).
Prior
exposure,
endogenous
neutralized
using
neutralizing
antibodies,
inflammasomes
inhibited
RNA
silencing,
Toll-like
9
was
modulated
pharmacological
agonist
antagonist.
Inflammasome
assembly,
caspase-1
activation,
histological
changes,
enzyme
levels
measured.
Statistical
comparison
more
than
two
groups
performed
one-way
ANOVA
Tukey’s
post-hoc
testing.
The
correlations
analyzed
Pearson’s
correlation
test.
All
experiments
repeated
thrice.
A
p-value
<
0.05
considered
significant.
Results:
Heat
induced
histone
release
into
space
at
correlating
Moreover,
augmented
stroke-induced
injury
both
vitro
vivo
dose-
time-dependent
manner,
whereas
conferred
protection
stroke.
Histones
mediated
through
signaling
pathway,
resulted
inflammation.
Conclusions:
Our
findings
show
are
critical
mediators
aggravate
setting.
Therefore,
suggest
therapeutic
targets
limit
death
Biomedicine & Pharmacotherapy,
Journal Year:
2023,
Volume and Issue:
159, P. 114173 - 114173
Published: Jan. 20, 2023
The
study
aimed
to
investigate
the
effect
of
isoliquiritigenin
(ISL)
on
model
alcoholic
liver
fibrosis
(ALF).
C57BL/6
mice
were
used
establish
animal
ALF,
HSC-T6
cells
alcohol-activated
cell
model,
and
tandem
mass
tag
(TMT)
assays
analyze
proteome.
results
showed
that
ISL
obviously
alleviated
hepatic
in
mice.
visually
improved
area
pathological
stasis
deposition
fibrillar
collagen
(Sirius
Red
staining,
Masson
staining),
inhibited
mRNA
expression
levels
interleukin
6
(IL-6),
tumor
necrosis
factor
α
(TNF-α)
1β
(IL-1β)
tissues.
down-regulated
IL-6
transforming
growth
factor-β1(TGF-β1)
activated
stellate
(HSCs).
And
significantly
reduced
annexin
A2
(ANXA2)
vitro
detected
by
TMT
proteomics
technology.
Interestingly,
it
was
found
for
first
time
could
inhibit
ANXA2
both
vivo
vitro,
block
sphingosine
kinases
(SPHKs)/sphingosine-1-phosphate
(S1P)/interleukin
17
(IL-17)
signaling
pathway
regulate
α-smooth
muscle
actin
(α-SMA)
inhibiting
phosphorylation
signal
transducer
activator
transcription
3
(STAT3)
at
downstream
finally
reverse
HSCs
activation
fibrosis.
Thus,
we
demonstrated
is
a
drug
monomer
with
notable
anti-hepatic
activity.
Heliyon,
Journal Year:
2024,
Volume and Issue:
10(20), P. e39139 - e39139
Published: Oct. 1, 2024
Globally,
plastic
pollution
threatens
human
health,
particularly
affecting
the
hearts
of
offspring
exposed
to
maternal
environmental
factors
early
in
development.
Few
studies
have
specifically
addressed
sex-specific
cardiac
injury
resulting
from
exposure
polystyrene
nanoplastics
(PS-NPs).
This
study
investigates
potential
following
1
mg/L
PS-NPs.
Pregnant
C57BL/6J
mice
were
PS-NPs
until
3
weeks
postpartum
establish
a
model.
Heart
tissues
collected
and
weighed,
transcriptomes
sequenced
analyzed
using
high-throughput
RNA
sequencing.
Immunohistochemical
staining
was
performed
assess
effects
on
immune
infiltration,
fibrosis,
apoptosis
offspring.
caused
significant
reduction
heart
body
weight
female
compared
males.
Additionally,
induced
transcriptional
reprogramming
metabolic
disruptions
also
apoptosis,
increased
CD68
Frontiers in Pharmacology,
Journal Year:
2025,
Volume and Issue:
15
Published: Jan. 8, 2025
In
patients
with
acute
respiratory
distress
syndrome,
mechanical
ventilation
often
leads
to
ventilation-induced
lung
injury
(VILI),
which
is
attributed
unphysiological
strain
(UPLS)
in
dynamics.
Platelet
endothelial
cell
adhesion
molecule-1
(PECAM-1),
a
transmembrane
receptor,
senses
signals.
The
Src/STAT3
pathway
plays
crucial
role
the
mechanotransduction
network,
concurrently
triggering
pyroptosis
related
inflammatory
responses.
We
hypothesized
that
stretch
caused
by
UPLS
can
be
sensed
PECAM-1
lungs,
leading
VILI
via
and
pathway.
A
model
was
established
rats
through
UPLS.
link
between
as
well
change
activation
of
PECAM-1,
Src/STAT3,
firstly
being
explored.
Then,
inhibitors
Src,
STAT3
were
adopted
respectively,
effect
on
VILI,
inflammation,
pathway,
evaluated.
vitro,
human
umbilical
vein
cells
(HUVECs)
used
validate
findings
vivo.
activated
signaling
rats,
whereas
inhibition
or
decreased
injury,
responses,
pyroptosis.
Inhibition
also
reduced
mechanism
validated
HUVECs
exposed
overload
cyclic
stretch.
This
study
suggests
contributes
activating
PECAM-1/Src/STAT3
inducing
responses
aspyroptosis.
Molecular & Cellular Proteomics,
Journal Year:
2025,
Volume and Issue:
unknown, P. 100921 - 100921
Published: Jan. 1, 2025
Nonalcoholic
fatty
liver
disease
(NAFLD)
is
a
hepatic
condition
characterized
excessive
fat
accumulation
in
the
with
advanced
stage
nonalcoholic
steatohepatitis
(NASH),
potentially
leading
to
fibrosis,
cirrhosis,
and
cancer.
Currently,
identification
classification
of
NASH
require
invasive
biopsy,
which
has
certain
limitations.
Mass
spectrometry-based
proteomics
can
detect
crucial
proteins
pathways
implicated
development
progression.
We
collected
serum
samples
from
choline-deficient,
L-amino
acid-defined
high-fat
diet
fed
C57BL/6J
mice
human
examine
proteomic
alterations
identify
early
biomarkers
for
diagnosis.
In-depth
targeted
multiple
reaction
monitoring
(MRM)
scanning
immunoblotting
assays
were
used
verify
biomarker
candidates
mouse
samples,
enzyme-linked
immunosorbent
assay
(ELISA)
was
employed
analyze
samples.
The
MRM
analysis
revealed
50
altered
expression
(18
up-
32
downregulated)
that
are
involved
biological
processes
such
as
detoxification,
inflammation,
acid
metabolism.
Ingenuity
pathway
identified
impaired
protein
synthesis,
cellular
stress
defense,
communication,
metabolism
liver.
Immunoblotting
confirmed
associated
(Aldo
B
Fasn)
urea
cycle
(Arg1,
Cps1,
Otc)
serum.
Further
on
using
ELISA
increased
proteins,
including
Aldo
B,
Asl,
Lgals3,
demonstrating
values
0.917,
0.979,
0.965
area
under
curve
These
findings
offer
valuable
insights
into
molecular
mechanisms
possible
diagnostic
detection.
Biomedicines,
Journal Year:
2025,
Volume and Issue:
13(2), P. 393 - 393
Published: Feb. 6, 2025
Non-alcoholic
fatty
liver
disease
(NAFLD)
and
its
advanced
form,
non-alcoholic
steatohepatitis
(NASH),
are
the
leading
causes
of
chronic
globally.
They
driven
by
complex
mechanisms
where
inflammation
plays
a
pivotal
role
in
progression.
Current
therapies,
including
lifestyle
changes
pharmacological
agents,
limited
efficacy,
particularly
addressing
stages
disease.
Emerging
approaches
targeting
inflammation,
metabolic
dysfunction,
fibrosis
offer
promising
new
directions,
though
challenges
such
as
treatment
complexity
heterogeneity
persist.
This
review
concludes
main
therapeutic
targets
to
manage
currently
emphasizes
critical
need
for
future
drug
development
combination
therapy
NAFLD/NASH
management.
