International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(7), С. 3581 - 3581
Опубликована: Март 22, 2024
Cardiovascular
diseases
are
a
leading
cause
of
morbidity
and
mortality
world-wide.
While
many
factors
like
smoking,
hypertension,
diabetes,
dyslipidaemia,
sedentary
lifestyle,
genetic
can
predispose
to
cardiovascular
diseases,
the
natural
process
aging
is
by
itself
major
determinant
risk.
Cardiac
marked
conglomerate
cellular
molecular
changes,
exacerbated
age-driven
decline
in
cardiac
regeneration
capacity.
Although
phenotypes
well
characterised,
underlying
mechanisms
far
less
explored.
Recent
advances
unequivocally
link
dysregulation
critical
signalling
pathways
fibroblasts,
which
compromises
role
these
cells
maintaining
structural
functional
integrity
myocardium.
Clearly,
identification
fibroblast-specific
that
regulate
fibroblast
function
senescent
myocardium
immense
importance.
In
this
regard,
recent
studies
show
Discoidin
domain
receptor
2
(DDR2),
collagen-activated
tyrosine
kinase
predominantly
located
has
an
obligate
fibrosis.
Incisive
on
basis
dysregulated
heart
would
pave
way
for
effective
strategies
mitigate
rapidly
growing
elderly
population.
Biomedicines,
Год журнала:
2024,
Номер
12(6), С. 1331 - 1331
Опубликована: Июнь 14, 2024
In
systemic
sclerosis
(SSc,
or
scleroderma),
defective
angiogenesis,
clinically
manifesting
with
abnormal
capillary
architecture
and
severe
reduction,
represents
a
hallmark
of
early-stage
disease,
usually
preceding
the
onset
tissue
fibrosis,
is
caused
by
several
cellular
molecular
mechanisms
affecting
microvascular
endothelial
cells
different
outcomes.
Indeed,
once
damaged,
can
be
dysfunctionally
activated,
thus
becoming
unable
to
undergo
angiogenesis
promoting
perivascular
inflammation.
They
also
apoptosis,
transdifferentiate
into
profibrotic
myofibroblasts,
acquire
senescence-associated
secretory
phenotype
characterized
release
exosomes
proinflammatory
mediators.
this
narrative
review,
we
aimed
give
comprehensive
overview
recent
studies
dealing
underlying
SSc
related
cell
dysfunctions,
mainly
endothelial-to-mesenchymal
transition
process.
We
discussed
potential
novel
vascular
treatment
strategies
able
restore
angiogenic
process
reduce
in
complex
disease.
Antioxidants,
Год журнала:
2025,
Номер
14(2), С. 199 - 199
Опубликована: Фев. 10, 2025
Aging
is
a
general
biological
process
inherent
in
all
living
organisms.
It
characterized
by
progressive
cellular
dysfunction.
For
many
years,
aging
has
been
widely
recognized
as
highly
effective
mechanism
for
suppressing
the
progression
of
malignant
neoplasms.
However,
recent
increasing
evidence
suggests
“double-edged”
role
cancer
development.
According
to
these
data,
not
only
tumor
suppressor
that
leads
cell
cycle
arrest
neoplastic
cells,
but
also
promoter
ensures
chronic
proinflammatory
and
immunosuppressive
microenvironment.
In
this
regard,
our
review,
we
discuss
data
on
destructive
senescent
cells
pathogenesis
cancer.
We
identify
first
time
correlations
between
modulation
senescence-associated
secretory
phenotype
antitumor
effects
naturally
occurring
molecules.
Journal of Hypertension,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 10, 2025
Background
and
purpose:
Ponatinib,
a
tyrosine
kinase
inhibitor
(TKI)
leads
to
hypertension;
however,
the
mechanisms
remain
elusive.
We
aimed
investigate
whether
lysine
acetyltransferase
7
(KAT7),
key
regulator
of
cellular
senescence
that
is
closely
associated
with
cardiovascular
diseases,
involves
in
ponatinib-induced
hypertension.
Methods
results:
After
administering
ponatinib
Sprague–Dawley
(SD)
rats
for
8
days,
we
measured
blood
pressure,
vasodilation,
endothelial
function
using
tail-cuff
plethysmography,
isometric
myography,
Total
NO
Assay
kit,
respectively.
The
results
indicated
increased
impaired
endothelium-dependent
relaxation
(EDR),
caused
injury
cells
SD
rats.
Furthermore,
PCR
Western
blot
experiments
demonstrated
an
upregulation
KAT7
expression
rat
mesenteric
artery
(MAECs)
following
treatment.
To
further
study
role
hypertension,
divided
into
four
groups:
control,
ponatinib,
WM-3835
(a
inhibitor),
plus
WM-3835.
Notably,
administration
significantly
improved
hypertension
EDR
dysfunction
Mechanistically,
over-expression
(OE-KAT7)
MAECs
led
inflammation,
phenomena
were
also
observed
arteries
ponatinib-treated
exposed
ponatinib.
However,
mitigated
these
detrimental
effects
both
vivo
vitro
experiments.
Additionally,
OE-KAT7
treatment
induced
H3K14
acetylation
(H3K14ac),
elevating
recruitment
H3K14ac
p21
promoter.
Moreover,
BAY
11-7085,
nuclear
factor
(NF)-κB
inhibitor,
potently
alleviated
accumulation
IL-6
IL-8,
as
well
cell
by
overexpression.
Conclusion:
Our
data
indicate
elevation
inflammatory
responses
through
NF-κB
signaling
pathway,
subsequently
vasotoxicity
Journal of Translational Internal Medicine,
Год журнала:
2025,
Номер
13(1), С. 33 - 47
Опубликована: Фев. 1, 2025
Aging
and
age-related
diseases
are
major
drivers
of
multimorbidity
mortality
worldwide.
Cellular
senescence
is
a
hallmark
aging.
The
accumulation
senescent
cells
causally
associated
with
pathogenesis
various
age-associated
disorders.
Due
to
their
promise
for
alleviating
disorders
extending
healthspan,
therapeutic
strategies
targeting
(senotherapies)
as
means
combat
aging
have
received
much
attention
over
the
past
decade.
Among
conventionally
used
approaches,
one
usage
small-molecule
compounds
specifically
exhibit
cytotoxicity
toward
or
inhibit
deleterious
effects
senescence-associated
secretory
phenotype
(SASP).
Alternatively,
there
immunotherapies
directed
at
surface
antigens
upregulated
in
(seno-antigens),
including
chimeric
antigen
receptor
(CAR)
therapies
senolytic
vaccines.
This
review
gives
an
update
current
status
discovery
development
therapies,
translational
progress
from
preclinical
clinical
trials.
We
highlight
challenges
faced
by
senotherapeutic
context
heterogeneity,
aim
offering
novel
perspectives
future
anti-aging
interventions
aimed
enhancing
healthy
longevity.
