Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
167, С. 115493 - 115493
Опубликована: Сен. 19, 2023
Sepsis,
a
life-threatening
dysregulated
status
of
the
host
response
to
infection,
can
cause
multiorgan
dysfunction
and
mortality.
Sepsis
places
heavy
burden
on
cardiovascular
system
due
pathological
imbalance
hyperinflammation
immune
suppression.
Myocardial
injury
cardiac
caused
by
aberrant
responses
pathogens
lead
cardiomyopathy,
one
most
critical
complications
sepsis.
However,
many
questions
about
specific
mechanisms
characteristics
this
complication
remain
be
answered.
The
causes
sepsis-induced
include
abnormal
perfusion,
myocardial
inhibitory
substances,
autonomic
dysfunction,
mitochondrial
calcium
homeostasis
dysregulation.
fight
between
acts
as
trigger
for
cardiomyopathy.
Pyroptosis,
form
programmed
cell
death,
plays
role
in
progress
Toll-like
receptors
(TLRs)
act
pattern
recognition
participate
innate
pathways
that
recognize
damage-associated
molecular
patterns
well
pathogen-associated
mediate
pyroptosis.
Notably,
pyroptosis
is
tightly
associated
with
sepsis
septic
shock.
In
line
these
observations,
induction
TLR-mediated
may
promising
therapeutic
approach
treat
This
review
focuses
potential
roles
shed
light
approach,
thus
helping
prevent
control
shock
disorders
improve
prognosis
patients.
Journal of Advanced Research,
Год журнала:
2023,
Номер
62, С. 175 - 186
Опубликована: Сен. 3, 2023
Osteoporosis
is
recognized
as
a
skeletal
disorder
characterized
by
diminished
bone
tissue
quality
and
density.
Regular
physical
exercise
widely
acknowledged
to
preserve
enhance
health,
but
the
detailed
molecular
mechanisms
involved
remain
unclear.
Irisin,
factor
derived
from
muscle
during
exercise,
influences
muscle.
Since
its
discovery
in
2012,
irisin
has
been
found
promote
growth
reduce
resorption,
establishing
tangible
link
between
exertion
health.
Consequently,
mechanism
which
prevents
osteoporosis
have
attracted
significant
scientific
interest.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(9), С. 4710 - 4710
Опубликована: Апрель 26, 2024
Sepsis-induced
cardiomyopathy
(SICM)
is
one
of
the
leading
indicators
for
poor
prognosis
associated
with
sepsis.
Despite
its
reversibility,
varies
widely
among
patients.
Mitochondria
play
a
key
role
in
cellular
energy
production
by
generating
adenosine
triphosphate
(ATP),
which
vital
myocardial
metabolism.
Over
recent
years,
mounting
evidence
suggests
that
severe
sepsis
not
only
triggers
mitochondrial
structural
abnormalities
such
as
apoptosis,
incomplete
autophagy,
and
mitophagy
cardiomyocytes
but
also
compromises
their
function,
to
ATP
depletion.
This
metabolic
disruption
recognized
significant
contributor
SICM,
yet
effective
treatment
options
remain
elusive.
Sepsis
cannot
be
effectively
treated
inotropic
drugs
failing
myocardium
due
excessive
inflammatory
factors
blunt
β-adrenergic
receptors.
review
will
share
knowledge
on
cell
death
molecular
mechanisms,
focusing
mitochondria
an
important
regulator
discuss
potential
developing
therapies
sepsis-induced
injury.
Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Фев. 20, 2024
Abstract
Pyroptosis
plays
a
crucial
role
in
sepsis,
and
the
abnormal
handling
of
myocyte
calcium
(Ca
2+
)
has
been
associated
with
cardiomyocyte
pyroptosis.
Specifically,
inositol
1,4,5-trisphosphate
receptor
type
2
(IP3R2)
is
Ca
release
channel
endoplasmic
reticulum
(ER).
However,
specific
IP3R2
sepsis-induced
cardiomyopathy
(SIC)
not
yet
determined.
Thus,
this
study
aimed
to
investigate
underlying
mechanism
by
which
channel-mediated
signaling
contributes
lipopolysaccharide
(LPS)—induced
cardiac
The
SIC
model
was
established
rats
intraperitoneal
injection
LPS
(10
mg/kg).
Cardiac
dysfunction
assessed
using
echocardiography,
protein
expression
relevant
pathways
analyzed
ELISA,
RT-qPCR,
western
blot.
Small
interfering
RNAs
(siRNA)
an
inhibitor
were
used
explore
neonatal
rat
cardiomyocytes
(NRCMs)
stimulated
vitro.
LPS-induced
NLRP3
overexpression
GSDMD-mediated
pyroptosis
rats’
heart.
Treatment
MCC950
alleviated
Furthermore,
increased
ATP-induced
intracellular
NRCMs.
Inhibiting
IP3R
activity
xestospongin
C
(XeC)
or
knocking
down
reversed
release.
Additionally,
inhibiting
suppressing
NLRP3/Caspase-1/GSDMD
pathway.
We
also
found
that
ER
stress
IP3R2-mediated
mutually
regulated
each
other,
contributing
promotes
NLRP3-mediated
regulating
release,
mutual
regulation
further
cardiomyocytes.
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
171, С. 116007 - 116007
Опубликована: Янв. 3, 2024
Diabetic
cardiomyopathy
(DCM)
is
a
common
complication
of
diabetes
mellitus
(DM).
However,
the
mechanisms
underlying
DCM-induced
cardiac
injury
remain
unclear.
Recently,
role
cyclic
GMP-AMP
synthase/stimulator
interferon
gene
(cGAS/STING)
signaling
and
pyroptosis
in
DCM
has
been
investigated.
Based
on
our
previous
results,
this
study
was
designed
to
examine
impact
irisin,
mitochondrial
ubiquitin
ligase
(MITOL/MARCH5),
cGAS/STING
dysfunction
effect
gasdermin
D
(GSDMD)-dependent
pyroptosis.
High-fat
diet-induced
mice
H9c2
cells
were
used
for
geometry
function
or
pyroptosis-related
biomarker
assessment
at
end
experiments.
Here,
we
show
that
impairs
by
increasing
fibrosis
GSDMD-dependent
pyroptosis,
including
activation
MITOL
signaling.
Our
results
confirmed
protective
irisin
partially
offset
We
also
demonstrated
plays
pivotal
pathological
process
pathogenesis.
indicate
treatment
protects
against
injury,
homeostasis,
through
upregulation.
Redox Biology,
Год журнала:
2024,
Номер
76, С. 103321 - 103321
Опубликована: Авг. 19, 2024
Cell
death
constitutes
a
critical
component
of
the
pathophysiology
cardiovascular
diseases.
A
growing
array
non-apoptotic
forms
regulated
cell
(RCD)-such
as
necroptosis,
ferroptosis,
pyroptosis,
and
cuproptosis-has
been
identified
is
intimately
linked
to
various
conditions.
These
RCD
are
governed
by
genetically
programmed
mechanisms
within
cell,
with
epigenetic
modifications
being
common
crucial
regulatory
method.
Such
include
DNA
methylation,
RNA
histone
acetylation,
non-coding
RNAs.
This
review
recaps
roles
modifications,
RNAs
in
diseases,
well
which
regulate
key
proteins
involved
death.
Furthermore,
we
systematically
catalog
existing
pharmacological
agents
targeting
novel
their
action
article
aims
underscore
pivotal
role
precisely
regulating
specific
pathways
thus
offering
potential
new
therapeutic
avenues
that
may
prove
more
effective
safer
than
traditional
treatments.
Frontiers in Pharmacology,
Год журнала:
2023,
Номер
14
Опубликована: Март 13, 2023
Cell
survival
or
death
is
critical
for
cardiac
function.
Myocardial
pyroptosis,
as
a
newly
recognized
programmed
cell
death,
remains
poorly
understood
in
sepsis.
In
this
study,
we
evaluated
the
effect
of
aldehyde
dehydrogenase
(ALDH2)
on
myocardial
pyroptosis
and
revealed
underlying
mechanisms
We
established
septic
shock
mice
model
by
intraperitoneal
injection
Lipopolysaccharide
(LPS,
15
mg/kg)
12
h
before
sacrifice.
It
was
found
that
significantly
inhibited
NOD-like
receptor
protein
3
(NLRP3)
inflammasome
activation
Caspase-1/GSDMD-dependent
which
remarkably
improved
rate
shock-induced
dysfunction,
relative
to
control
group.
While
knockout
knockdown
aggravated
these
phenomena.
Intriguingly,
LPS-induced
deacetylation
Hydroxyacyl-CoA
trifunctional
multienzyme
complex
α
subunit
(HADHA)
suppressing
translocation
Histone
deacetylase
(HDAC3)
from
nuclei
mitochondria.
Acetylated
HADHA
essential
mitochondrial
fatty
acid
β-oxidation,
its
interruption
can
result
accumulation
toxic
lipids,
induce
mROS
cause
mtDNA
ox-mtDNA
release.
Our
results
confirmed
role
activation.
Hdac3
remarkedly
suppressed
but
Hadha
eliminated
effect.
3,
protected
ac-HADHA
deacetylation,
reduced
aldehyde,
ox-mtDNA,
thereby
avoided
pyroptosis.
This
study
provided
novel
mechanism
through
3/HADHA-
pathway
demonstrated
significant
therapeutic
target
