Exploring the Anti-PANoptosis Mechanism of Dachaihu Decoction Against Sepsis-Induced Acute Lung Injury: Network Pharmacology, Bioinformatics, and Experimental Validation
Drug Design Development and Therapy,
Год журнала:
2025,
Номер
Volume 19, С. 349 - 368
Опубликована: Янв. 1, 2025
Dachaihu
decoction
(DCHD)
is
a
common
Chinese
medicine
formula
against
sepsis-induced
acute
lung
injury
(SALI).
PANoptosis
novel
type
of
programmed
cell
death.
Nevertheless,
The
mechanisms
DCHD
SALI
via
anti-PANoptosis
remains
unknown.
First,
we
identified
the
intersecting
targets
among
DCHD,
SALI,
and
using
relevant
databases
published
literature.
Then,
protein-protein
interaction
(PPI)
network,
molecular
docking,
functional
enrichment
analysis
were
conducted.
In
vivo,
cecal
ligation
puncture
(CLP)
was
used
to
construct
sepsis
mouse
model,
therapeutic
effects
on
evaluated
hematoxylin
eosin
(H&E)
staining,
quantitative
real-time
PCR
(qRT-PCR),
ELISA.
Finally,
qRT-PCR,
immunofluorescence
Western
blotting
verify
effect
DCHD-containing
serum
(DCHD-DS)
LPS-induced
RAW
264.7
macrophages
in
vitro.
82
by
mapping
PANoptosis.
Enrichment
showed
that
modulating
tumor
necrosis
factor
(TNF),
AGE-RAGE,
phosphoinositide
3-kinase
(PI3K)-AKT,
Toll-like
receptor
signaling
pathways
targeting
Casp3,
cellular
antigen
p53
(TP53),
B-cell
lymphoma
2
(Bcl2),
toll-like
receptor-4
(TLR4),
STAT3,
STAT1,
RELA,
NF-κB1,
myeloid
leukemia-1
(MCL1),
JUN,
IL-1β,
HSP90AA1,
Casp9,
Casp8,
Bcl2l1.
Molecular
docking
revealed
key
components
have
high
binding
affinity
core
targets.
improved
histopathological
injury,
reduced
inflammatory
expression,
alleviated
oxidative
stress
tissues.
vitro,
DCHD-DS
morphology
changes,
release
pro-inflammatory
factors,
p65
nucleus
aggregation.
Furthermore,
verified
inhibited
downregulating
PI3K/AKT/NF-κB
signalling
pathway.
attenuates
inhibiting
control
Our
study
provides
solid
foundation
for
investigating
its
clinical
application
treatment
SALI.
Язык: Английский
Recent Advances in Pathogenesis and Anticoagulation Treatment of Sepsis-Induced Coagulopathy
Cheng Man,
Yuan An,
Guoxin Wang
и другие.
Journal of Inflammation Research,
Год журнала:
2025,
Номер
Volume 18, С. 737 - 750
Опубликована: Янв. 1, 2025
Coagulopathy
in
sepsis
is
common
and
associated
with
high
mortality.
Although
immunothrombosis
necessary
for
infection
control,
excessive
thrombus
formation
can
trigger
a
systemic
thrombo-inflammatory
response.
Immunothrombosis
plays
core
role
sepsis-induced
coagulopathy,
research
has
revealed
complex
interplay
between
inflammation
coagulation.
Different
mechanisms
underlying
sepsis-related
coagulopathy
are
discussed,
including
factors
contributing
to
the
imbalance
of
pro-
anticoagulation
relevant
endothelial
cells.
The
potential
therapeutic
implications
anticoagulants
on
these
discussed.
This
review
contributes
our
understanding
pathogenesis
patients
sepsis.
Recent
studies
suggest
that
cells
play
an
important
immunoregulation
hemostasis.
Meanwhile,
non-anticoagulation
effects
anticoagulants,
especially
heparin,
which
act
septic
patients,
have
been
partially
revealed.
We
believe
further
insights
into
will
help
physicians
evaluate
patient
conditions
effectively,
leading
advanced
early
recognition
better
decision-making
treatment
Язык: Английский
Emodin protects against severe acute pancreatitis-associated acute lung injury by activating Nrf2/HO-1/GPX4 signal and inhibiting ferroptosis in vivo and in vitro
BMC Gastroenterology,
Год журнала:
2025,
Номер
25(1)
Опубликована: Фев. 5, 2025
Severe
acute
pancreatitis
(SAP)
has
high
morbidity,
a
complicated
and
dangerous
course,
many
complications,
including
severe
pulmonary
complications.
SAP-associated
lung
injury
(SAP-ALI)
is
still
significant
challenge
for
surgeons
because
of
its
mortality.
Therefore,
more
effective
treatment
methods
are
urgently
needed.
Emodin
(EMO)
shown
tremendous
potential
in
treating
refractory
diseases.
However,
protection
mechanism
SAP-ALI
needs
to
be
further
clarified.
This
study
was
undertaken
investigate
the
protective
effects
EMO
against
SAP
rats
alveolar
epithelial
cells,
with
particular
focus
on
classical
ferroptosis
pathway.
In
an
vivo
study,
forty
SD
were
evenly
split
into
five
groups:
sham
operation
(SO)
group,
biliopancreatic
duct
retrogradely
injected
5%
sodium
taurocholate
(STC)
create
+
group
administered
via
gavage
following
modeling,
ML385
(a
given
inhibitor
nuclear
factor
erythroid
2-related
2
(Nrf2)),
group.
vitro
A549
cell
lines
exposed
lipopolysaccharide
(LPS)
treated
EMO.
also
used
inhibit
expression
Nrf2.
Pancreatic
tissue
damage
evaluated
using
histological
examination
molecular
experiments.
Enzyme-linked
immunosorbent
assays
(ELISA)
assess
levels
pro-inflammatory
cytokines,
Fe2+,
associated
oxidative
stress
indicators
serum
supernatant.
Real-time
polymerase
chain
reaction
(PCR),
Western
blot
(WB),
immunofluorescence
find
expressions
related
mRNAs
proteins
or
cells.
The
findings
demonstrated
that
suppressing
Nrf2
exacerbated
inflammatory
response
brought
by
pathological
alterations
SAP-ALI.
reversed
this
change
activating
Nrf2/Heme
Oxygenase-1
(HO-1)/glutathione
peroxidase
4
(GPX4)
signal
path.
Moreover,
these
results
showed
EMO,
contrary
ML385,
suppressed
response,
which
manifested
as
up-regulated
glutathione
(GSH)
GPX4
down-regulated
malondialdehyde
(MDA),
superoxide
dismutase
(SOD),
reactive
oxygen
species
(ROS)
levels.
Our
effectively
inhibited
both
vitro,
while
modulating
Nrf2/HO-1/GPX4
signaling
pathway
provide
Язык: Английский
Focus on the role of calcium signaling in ferroptosis: a potential therapeutic strategy for sepsis-induced acute lung injury
Frontiers in Medicine,
Год журнала:
2024,
Номер
11
Опубликована: Сен. 17, 2024
By
engaging
in
redox
processes,
ferroptosis
plays
a
crucial
role
sepsis-induced
acute
lung
injury
(ALI).
Although
iron
stimulates
calcium
signaling
through
the
stimulation
of
redox-sensitive
pathways,
function
signals
physiological
process
septic
ALI
remains
unidentified.
Iron
homeostasis
disequilibrium
is
frequently
accompanied
by
aberrant
signaling.
Intracellular
overflow
can
be
symptom
dysregulation
cellular
state,
which
characterized
overload
during
early
phase
ferroptosis.
This
lead
to
disruptions
and
The
mechanisms
controlling
are
reviewed
here,
along
with
their
significance
injury,
potential
these
processes
clarified.
We
propose
that
development
combined
involving
bidirectional
interaction
between
Our
goal
raise
awareness
about
pathophysiology
investigate
relationship
also
aimed
develop
calcium-antagonistic
therapies
target
improve
quality
survival
for
patients
suffering
from
injury.
Язык: Английский
Targeting ferroptosis offers therapy choice in sepsis-associated acute lung injury
European Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
283, С. 117152 - 117152
Опубликована: Дек. 8, 2024
Язык: Английский
Toosendanin Alleviates Acute Lung Injury by Reducing Pulmonary Vascular Barrier Dysfunction Mediated by Endoplasmic Reticulum Stress Through mTOR
Phytomedicine,
Год журнала:
2024,
Номер
136, С. 156277 - 156277
Опубликована: Ноя. 24, 2024
Язык: Английский
Sepsis-Induced Endothelial Dysfunction: Permeability and Regulated Cell Death
Journal of Inflammation Research,
Год журнала:
2024,
Номер
Volume 17, С. 9953 - 9973
Опубликована: Ноя. 1, 2024
Sepsis
is
a
life-threatening
organ
dysfunction
caused
by
dysregulated
host
response
to
infection.
Endothelial
cells
(ECs)
are
an
important
cell
type
typically
affected
in
sepsis,
resulting
compromised
barrier
function
and
various
forms
of
regulated
death
(RCD).
However,
the
precise
mechanisms
underlying
sepsis-induced
EC
damage
remain
unclear.
This
review
summarizes
recent
research
progress
on
factors
that
may
affect
permeability
RCD
ECs
under
septic
conditions,
including
glycocalyx,
damage-associated
molecular
patterns,
ECs,
such
as
apoptosis,
pyroptosis,
ferroptosis,
autophagy.
offers
insights
into
endothelial
aiming
contribute
developing
small-molecule
targeted
clinical
therapies.
Язык: Английский