Journal of Holistic Integrative Pharmacy,
Год журнала:
2023,
Номер
4(3), С. 241 - 247
Опубликована: Ноя. 1, 2023
The
proliferation
of
vascular
smooth
muscle
cells
(VSMCs)
is
a
key
pathogenic
characteristic
remodeling
diseases.
signal
transducers
and
activators
transcription-3
(STAT3)
signaling
pathway
crucial
for
VSMCs
growth,
its
role
in
cytokine-induced
proliferation,
calcification,
phenotypic
switching
essential
developing
new
treatment
targets.
can
transform
from
contractile
to
synthetic
phenotypes
response
stimuli,
such
as
mechanical
forces,
growth
factors,
pro-inflammatory
cytokines,
injury.
Understanding
the
mechanism
triggered
by
STAT3
important
identifying
potential
therapeutic
targets
Redox Biology,
Год журнала:
2023,
Номер
67, С. 102894 - 102894
Опубликована: Окт. 6, 2023
The
present
review
summarizes
the
beneficial
and
detrimental
roles
of
reactive
oxygen
species
in
myocardial
ischemia/reperfusion
injury
cardioprotection.
In
first
part,
continued
need
for
cardioprotection
beyond
that
by
rapid
reperfusion
acute
infarction
is
emphasized.
Then,
pathomechanisms
to
myocardium
coronary
circulation
different
modes
cell
death
are
characterized.
Different
mechanical
pharmacological
interventions
protect
ischemic/reperfused
elective
percutaneous
artery
bypass
grafting,
cardiotoxicity
from
cancer
therapy
detailed.
second
part
keeps
focus
on
ROS
providing
a
comprehensive
overview
molecular
cellular
mechanisms
involved
injury.
Starting
mitochondria
as
main
sources
targets
myocardium,
complex
network
extracellular
processes
discussed,
including
relationships
with
Ca2+
homeostasis,
thiol
group
redox
balance,
hydrogen
sulfide
modulation,
cross-talk
NAPDH
oxidases,
exosomes,
cytokines
growth
factors.
While
mechanistic
insights
needed
improve
our
current
therapeutic
approaches,
advancements
knowledge
ROS-mediated
indicate
facets
oxidative
stress
opposed
requirement
physiological
protective
reactions.
This
inevitable
contrast
likely
underlie
unsuccessful
clinical
trials
limits
development
novel
cardioprotective
simply
based
upon
removal.
Basic Research in Cardiology,
Год журнала:
2024,
Номер
119(4), С. 691 - 697
Опубликована: Июнь 12, 2024
Abstract
The
mitochondrial
metabolite
succinate
is
a
key
driver
of
ischemia/reperfusion
injury
(IRI).
Targeting
metabolism
by
inhibiting
dehydrogenase
(SDH)
upon
reperfusion
using
malonate
an
effective
therapeutic
strategy
to
achieve
cardioprotection
in
the
short
term
(<
24
h
reperfusion)
mouse
and
pig
vivo
myocardial
infarction
(MI)
models.
We
aimed
assess
whether
IRI
with
given
could
prevent
post-MI
heart
failure
(HF)
assessed
after
28
days.
Male
C57BL/6
J
mice
were
subjected
30
min
left
anterior
coronary
artery
(LAD)
occlusion,
before
for
Malonate
or
without-malonate
control
was
infused
as
single
dose
reperfusion.
Cardiac
function
echocardiography
fibrosis
Masson’s
trichrome
staining.
Reperfusion
without
significantly
reduced
ejection
fraction
(~
47%),
fractional
shortening
23%)
elevated
collagen
deposition
days
post-MI.
Malonate,
administered
infusion
(16
mg/kg/min
10
min)
reperfusion,
gave
significant
cardioprotective
effect,
60%)
30%)
preserved
less
deposition.
Using
acidified
formulation,
enhance
its
uptake
into
cardiomyocytes
via
monocarboxylate
transporter
1,
both
1.6
16
led
robust
long-term
(>
30%),
well
than
hearts.
administration
prevents
HF.
Acidification
enables
lower
doses
also
Therefore,
promising
Mitochondrial Communications,
Год журнала:
2024,
Номер
2, С. 1 - 13
Опубликована: Янв. 1, 2024
Signal
transducer
and
activator
of
transcription
(STAT)
3
has
been
found
within
mitochondria
in
addition
to
its
canonical
role
shuttling
between
cytoplasm
nucleus
during
cytokine
signaling.
Mitochondrial
STAT3
implicated
modulation
cellular
metabolism,
largely
through
effects
on
the
respiratory
electron
transport
chain.
However,
structural
requirements
underlying
mitochondrial
targeting
function
have
remained
unclear.
Here,
we
show
that
partitions
compartments
defined
by
differential
detergent
solubility,
suggesting
is
membrane
associated.
The
majority
was
an
SDS
soluble
fraction
copurifying
with
chain
proteins,
including
numerous
components
complex
I
NADH
dehydrogenase,
while
a
minor
component
proteins
translation
machinery.
required
amino-terminal
domain,
internal
linker
domain
motif
also
directed
translocation.
neither
phosphorylation
serine
727
nor
presence
DNA
for
localization
STAT3.
Two
cysteine
residues
SH2
which
previously
suggested
be
targets
protein
palmitoylation,
were
not
translocation,
but
as
enhancer
activity.
These
determinants
provide
potential
therapeutic
disrupting
activity
diseases
such
cancer.
Basic Research in Cardiology,
Год журнала:
2024,
Номер
119(4), С. 509 - 544
Опубликована: Июнь 15, 2024
Despite
recent
progress,
ischemic
heart
disease
poses
a
persistent
global
challenge,
driving
significant
morbidity
and
mortality.
The
pursuit
of
therapeutic
solutions
has
led
to
the
emergence
strategies
such
as
preconditioning,
postconditioning,
remote
conditioning
shield
from
myocardial
ischemia/reperfusion
injury
(MIRI).
These
approaches,
applied
before,
after,
or
at
distance
affected
organ,
inspire
future
strategies,
including
pharmacological
conditioning.
Gasotransmitters,
comprising
nitric
oxide,
hydrogen
sulfide,
sulfur
dioxide,
carbon
monoxide,
play
pivotal
roles
in
physiological
pathological
processes,
exhibiting
shared
features
smooth
muscle
relaxation,
antiapoptotic
effects,
anti-inflammatory
properties.
potential
risks
high
concentrations,
levels
gasotransmitters
induce
vasorelaxation
promote
cardioprotective
effects.
Noble
gases,
notably
argon,
helium,
xenon,
exhibit
organ-protective
properties
by
reducing
cell
death,
minimizing
infarct
size,
enhancing
functional
recovery
post-ischemic
organs.
protective
role
noble
gases
appears
hinge
on
their
modulation
molecular
pathways
governing
survival,
leading
both
pro-
Among
helium
xenon
emerge
particularly
promising
field
cardioprotection.
This
overview
synthesizes
our
current
understanding
played
context
MIRI
In
addition,
we
underscore
developments
involving
utilization
gasotransmitter
donor
molecules
advancing
strategies.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(8), С. 4491 - 4491
Опубликована: Апрель 19, 2024
Myocardial
ischemia/reperfusion
injury
is
reduced
by
cardioprotective
adaptations
such
as
local
or
remote
ischemic
conditioning.
The
stimuli
activate
signaling
cascades,
which
converge
on
mitochondria
and
maintain
the
function
of
organelles,
critical
for
cell
survival.
cascades
include
not
only
extracellular
molecules
that
sarcolemmal
receptor-dependent
-independent
protein
kinases
signal
at
plasma
membrane
in
cytosol,
but
also
involve
kinases,
are
located
to
within
mitochondria,
phosphorylate
mitochondrial
target
proteins,
thereby
modify,
e.g.,
respiration,
generation
reactive
oxygen
species,
calcium
handling,
dynamics,
mitophagy,
apoptosis.
In
present
review,
we
give
a
personal
opinionated
overview
selected
localized
to/within
myocardial
summarize
available
data
their
role
protection
from
it.
We
highlight
regulation
these
kinases.
Pharmaceuticals,
Год журнала:
2025,
Номер
18(2), С. 146 - 146
Опубликована: Янв. 23, 2025
Background:
Our
research
team
analyzed
the
microRNA
(miRNA)-197-3p
involved
in
cardioprotection,
and
we
demonstrated
that
overexpression
of
miRNA-197-3p
could
be
linked
to
a
higher
risk
cardiac
damage.
Recent
indicated
inhibits
effector
proteins
anaesthetic
preconditioning
mechanism
halogenated
drugs.
In
this
scenario,
proposed
determine
role
injury
its
effects
on
myocardial
conditioning
under
exposure.
Hypothesis:
Patients
having
revascularization
surgery
have
increased
heart
damage
due
postoperative
upregulation.
Methods:
Human
myocytes
(HCMs)
were
used
an
vitro
hypoxia/reperfusion
(H/R)
model.
The
miRNA-197-3p-MIMIC
was
transfected
into
HCMs.
Three
H/R-induced
HCM
groups
performed:
negative
MIMIC-control
transfected,
MIMIC
non-transfected.
Each
H/R
cell
group
exposed
Propofol
(P),
Sevoflurane
(S),
or
non-exposed.
Healthy
cultures
control
group.
ELISA
assays
assess
Akt1
p53
secretion
capacity,
Next
Generation
Sequencing
assay
measure
differential
expression
miRNA
targets.
Results:
capacity
HCMs
with
sevoflurane
exposure
regarding
Akt-1
cytokine
(I/R
+
S:
0.80
±
0.06
ng/mL;
I/R
P:
0.45
0.28
p
>
0.05),
lower
38.62
6.93
43.34
15.20
0.05)
compared
propofol.
addition,
significant
gene
five
miRNAs,
group,
cardioprotection:
miRNA-29-3p,
24-3p,
21-3p,
532,
miRNA-335-5p.
Conclusions:
cardioprotection
induced
by
can
considered
biomarker
Additional
is
required
validate
our
findings
other
clinical
settings.
Cellular and Molecular Life Sciences,
Год журнала:
2025,
Номер
82(1)
Опубликована: Фев. 22, 2025
Abstract
Chronic
inflammatory
diseases
are
a
significant
global
burden
and
associated
with
dysregulated
resolution
of
inflammation.
Therefore,
promoting
the
process
is
promising
therapeutic
approach.
This
study
presents
potent
anti-inflammatory
pro-resolving
effects
natural
product-derived
compound
called
C81.
Administration
C81
in
window
resolved
inflammation
murine
imiquimod-induced
psoriasis
model,
reduced
microglial
infiltration
laser-induced
choroidal
neovascularisation
model.
Investigations
into
underlying
mechanisms
identified
DYRK1B/STAT3
axis
as
new
regulator
processes
leukocytes.
The
inhibition
DYRK1B
by
resulted
attenuated
STAT3
phosphorylation.
depletion
STAT3-regulated
gene
expression
led
to
leukocyte
adhesion
migration
due
integrin
activation,
addition
release
pro-inflammatory
mediators
such
cytokines
eicosanoids.
Importantly,
included
cell
type-specific
induction
apoptosis
neutrophils
subsequent
increase
efferocytosis.
In
conclusion,
we
report
novel
target
for
activating
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