Theranostics,
Год журнала:
2023,
Номер
13(15), С. 5435 - 5451
Опубликована: Янв. 1, 2023
Doxorubicin
(Dox)
is
an
effective
anticancer
molecule,
but
its
clinical
efficacy
limited
by
strong
cardiotoxic
side
effects.
Lysosomal
dysfunction
has
recently
been
proposed
as
a
new
mechanism
of
Dox-induced
cardiomyopathy.
However,
to
date,
there
paucity
therapeutic
approaches
capable
restoring
lysosomal
acidification
and
function
in
the
heart.
Methods:
We
designed
novel
poly(lactic-co-glycolic
acid)
(PLGA)-grafted
silica
nanoparticles
(NPs)
investigated
their
potential
primary
prevention
Dox
cardiotoxicity
cardiomyocytes
mice.
Results:
showed
that
NPs-PLGA
internalized
rapidly
accumulated
inside
lysosomes.
Mechanistically,
restored
presence
doxorubicin
or
bafilomycin
A1,
thereby
improving
autophagic
flux.
Importantly,
mitigated
Dox-related
mitochondrial
oxidative
stress,
two
main
mechanisms
cardiotoxicity.
In
vivo,
inhalation
led
rapid
targeting
myocardium,
which
prevented
adverse
remodeling
cardiac
Conclusion:
Our
findings
demonstrate
pivotal
role
for
cardiomyopathy
highlight
first
time
pulmonary-driven
administration
promising
strategy
against
anthracycline
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
166, С. 115268 - 115268
Опубликована: Авг. 8, 2023
Apelin
and
Elabela
(Ela)
are
peptides
encoded
by
APLN
APELA,
respectively,
which
act
on
their
receptor
APJ
play
crucial
roles
in
the
body.
Recent
research
has
shown
that
they
not
only
have
important
effects
endocrine
system,
but
also
promote
vascular
development
maintain
homeostasis
of
myocardial
cells.
From
a
molecular
biology
perspective,
we
explored
Ela
apelin
cardiovascular
system
summarized
mechanisms
apelin-APJ
signaling
progression
infarction,
ischemia-reperfusion
injury,
atherosclerosis,
pulmonary
arterial
hypertension,
preeclampsia,
congenital
heart
disease.
Evidences
indicated
diseases,
there
many
studies
focused
developing
apelin,
Ela,
analogues
for
clinical
treatments.
However,
literature
therapeutic
potential
other
agonists
is
still
limited.
This
review
regulatory
pathways
apelin/ELA-APJ
axis
function
cardiovascular-related
diseases
were
included.
Journal of Nanobiotechnology,
Год журнала:
2024,
Номер
22(1)
Опубликована: Авг. 2, 2024
Abstract
Background
Doxorubicin
(DOX)
is
a
first-line
chemotherapeutic
drug
for
various
malignancies
that
causes
cardiotoxicity.
Plant-derived
exosome-like
nanovesicles
(P-ELNs)
are
growing
as
novel
therapeutic
agents.
Here,
we
investigated
the
protective
effects
in
DOX
cardiotoxicity
of
ELNs
from
Momordica
charantia
L.
(MC-ELNs),
medicinal
plant
with
antioxidant
activity.
Results
We
isolated
MC-ELNs
using
ultracentrifugation
and
characterized
them
canonical
mammalian
extracellular
vesicles
features.
In
vivo
studies
proved
ameliorated
enhanced
cardiac
function
myocardial
structure.
vitro
assays
revealed
promoted
cell
survival,
diminished
reactive
oxygen
species,
protected
mitochondrial
integrity
DOX-treated
H9c2
cells.
found
treatment
decreased
protein
level
p62
through
ubiquitin-dependent
degradation
pathway
NRVM
However,
suppressed
DOX-induced
ubiquitination
degradation,
recovered
bound
Keap1
promoting
Nrf2
nuclear
translocation
expressions
downstream
gene
HO-1.
Furthermore,
both
knockdown
inhibition
p62-Keap1
interaction
abrogated
cardioprotective
effect
MC-ELNs.
Conclusions
Our
findings
demonstrated
beneficials
via
increasing
stability,
shedding
light
on
preventive
approaches
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
179, С. 117312 - 117312
Опубликована: Авг. 20, 2024
Anthracyclines
are
broad-spectrum
anticancer
drugs,
but
their
clinical
use
is
limited
due
to
severe
cardiotoxicity.
Anthracycline-induced
cardiotoxicity
(AIC)
remains
a
significant
cause
of
heart
disease-related
mortality
in
many
cancer
survivors.
The
underlying
mechanisms
AIC
have
been
explored
over
the
past
few
decades.
Reactive
oxygen
species
and
drug-induced
inhibition
topoisomerase
II
beta
well-studied
mechanisms,
with
mitochondria
being
prominently
investigated
organelle.
Emerging
such
as
ferroptosis,
Ca
Inflammation,
Год журнала:
2023,
Номер
46(6), С. 2343 - 2358
Опубликована: Авг. 4, 2023
ELABELA
(ELA),
a
recently
discovered
peptide,
is
highly
expressed
in
adult
kidneys
and
the
endothelium
system.
It
has
been
identified
as
novel
endogenous
ligand
for
apelin
receptor
(APJ).
This
study
aims
to
investigate
role
of
ELA
diabetic
glomerular
endothelial
pyroptosis
its
underlying
mechanism.
Initially,
significant
decrease
mRNA
levels
was
observed
renal
cortex
db/db
mice
high
glucose-treated
cells
(GECs).
also
found
that
deficiency
ELA+/-
significantly
accelerated
injury,
shown
by
exacerbated
morphological
damage,
increased
serum
creatine
blood
urea
nitrogen,
elevated
24-h
urinary
albumin
excretion.
In
addition,
vivo
overexpression
prevented
reduced
von
Willebrand
factor
expression,
restored
marker
CD31
attenuated
production
adhesive
molecules
such
intercellular
adhesion
molecule-1
vascular
cell
molecule-1.
Furthermore,
vitro
studies
confirmed
treatment
with
inhibited
GEC
injury
regulating
NOD-like
protein
3
(NLRP3)
inflammasome,
indicated
blocking
NLRP3
inflammasome
formation,
decreasing
cleaved
Caspase-1
production,
inhibiting
interleukin-1β
interleukin-18
production.
Moreover,
experiments
demonstrated
protective
effects
GECs
during
hyperglycemia
were
diminished
adenosine
monophosphate-activated
kinase
(AMPK)
using
Compound
C
or
APJ
deficiency.
Taken
together,
this
provides
first
evidence
could
prevent
which
partly
mediated
regulation
AMPK/NLRP3
signaling
pathway.
Therefore,
pharmacologically
targeting
may
serve
therapeutic
strategy
kidney
disease.
Medicinal Research Reviews,
Год журнала:
2024,
Номер
44(6), С. 2472 - 2509
Опубликована: Май 6, 2024
Previously,
lysosomes
were
primarily
referred
to
as
the
digestive
organelles
and
recycling
centers
within
cells.
Recent
discoveries
have
expanded
lysosomal
functional
scope
revealed
their
critical
roles
in
nutrient
sensing,
epigenetic
regulation,
plasma
membrane
repair,
lipid
transport,
ion
homeostasis,
cellular
stress
response.
Lysosomal
dysfunction
is
also
found
be
associated
with
aging
several
diseases.
Therefore,
function
of
macroautophagy,
a
lysosome-dependent
intracellular
degradation
system,
has
been
identified
one
updated
twelve
hallmarks
aging.
In
this
review,
we
begin
by
introducing
concept
quality
control
(LQC),
which
machinery
that
maintains
number,
morphology,
through
different
processes
such
biogenesis,
reformation,
fission,
fusion,
turnover,
lysophagy,
exocytosis,
permeabilization
repair.
Next,
summarize
results
from
studies
reporting
association
between
LQC
dysregulation
aging/various
disorders.
Subsequently,
explore
emerging
therapeutic
strategies
target
distinct
aspects
for
treating
diseases
combatting
Lastly,
underscore
existing
knowledge
gap
propose
potential
avenues
future
research.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(11), С. 5833 - 5833
Опубликована: Май 27, 2024
Doxorubicin
is
an
effective
drug
for
cancer
treatment;
however,
cardiotoxicity
limits
its
use.
Cardiotoxicity
pathophysiology
multifactorial.
GLP-1
analogues
have
been
shown
to
reduce
oxidative
stress
and
inflammation.
In
this
study,
we
evaluated
the
effect
of
pretreatment
with
liraglutide
on
doxorubicin-induced
acute
cardiotoxicity.
A
total
60
male
Wistar
rats
were
allocated
into
four
groups:
Control
(C),
(D),
Liraglutide
(L),
+
(DL).
L
DL
received
subcutaneous
injection
0.6
mg/kg
daily,
while
C
D
saline
2
weeks.
Afterwards,
a
single
intraperitoneal
doxorubicin
20
mg/kg;
saline.
Forty-eight
hours
after
administration,
subjected
echocardiogram,
isolated
heart
functional
euthanasia.
Liraglutide-treated
ingested
significantly
less
food
gained
body
weight
than
animals
that
did
not
receive
drug.
Rats
lost
injection.
At
echocardiogram
doxorubicin-treated
had
systolic
diastolic
function
impairment.
Myocardial
catalase
activity
was
statistically
higher
in
rats.
protein
expression
tumor
necrosis
factor
alpha
(TNF-α),
phosphorylated
nuclear
factor-κB
(p-NFκB),
troponin
T,
B-cell
lymphoma
(Bcl-2)
lower,
NFκB/p-NFκB
ratio
TLR-4
OPA-1,
MFN-2,
DRP-1,
topoisomerase
2β
differ
between
groups
(p
>
0.05).
conclusion,
accompanied
by
decreased
Bcl-2
NFκB
increased
expression.
failed
improve
Antioxidants and Redox Signaling,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 9, 2025
Aims:
Autophagy
is
a
protective
mechanism
of
cardiomyocytes.
Hyperhomocysteinemia
(HHcy)
elevates
oxidative
and
nitrosative
stress
levels,
leading
to
an
abnormal
increase
in
nitration
protein,
possibly
autophagy
regulation
However,
the
regulatory
effect
HHcy
on
at
post-translational
modification
level
still
unclear.
Here,
we
aimed
explore
transcription
factor
EB
(TFEB)
CCAAT/enhancer-binding
protein
beta
(C/EBPβ),
transcriptional
repressor
Tfeb,
British Journal of Pharmacology,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 11, 2025
Abstract
Background
and
Purpose
Doxorubicin
(DOX),
an
anthracycline
chemotherapeutic
agent,
whose
use
is
limited
owing
to
its
dose‐dependent
cardiotoxicity.
Mitochondrial
oxidative
stress
plays
a
crucial
role
in
the
pathogenesis
of
DOX‐induced
cardiotoxicity
(DIC).
Trilobatin
(TLB),
naturally
occurring
food
additive,
exhibits
strong
antioxidant
properties,
but
cardioprotective
effects
DIC
unclear.
This
study
investigates
effect
TLB
on
DIC.
Experimental
Approach
DOX
was
used
generate
vivo
vitro
model
Echocardiography,
enzyme‐linked
immunosorbent
assay
(ELISA)
haematoxylin
eosin
(H&E)
staining
were
evaluate
cardiac
function
these
models.
To
identify
targets
TLB,
RNA‐sequence
analysis,
molecular
dynamics
simulations,
surface
plasmon
resonance
binding
assays
protein
immunoblotting
techniques
used.
Transmission
electron
microscopy,
along
with
dihydroethidium
Mito‐SOX
staining,
conducted
examine
impact
trilobatin
mitochondrial
stress.
SiRNA
transfection
performed
confirm
ferredoxin
1
(FDX1)
development.
Key
Results
In
mice,
improved
manner
inhibited
myocardial
fibrosis
mice.
also
attenuated
dysfunction
reduced
found
directly
bind
FDX1
suppresses
cuproptosis
after
treatment,
causing
significant
inhibition
cuproptosis‐related
proteins.
Conclusions
Implications
first
show
that
strongly
inhibits
by
reducing
controlling
DOX‐mediated
targeting
FDX1.
Therefore,
as
potential
phytochemical
candidate
for
ameliorating
