Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
165, С. 115252 - 115252
Опубликована: Авг. 2, 2023
Intervertebral
disc
degeneration
(IVDD)
leads
to
a
series
of
degenerative
spine
diseases.
Clinical
treatment
IVDD
is
mainly
surgery,
lacking
effective
drugs
alleviate
intervertebral
degeneration.
In
this
study,
we
analysed
the
mRNA
sequencing
dataset
human
tissues
and
revealed
participation
ferroptosis
in
IVDD.
Furthermore,
confirmed
that
TNF-α,
an
important
cytokine
IVDD,
induces
nucleus
pulposus
cells.
Subsequently,
inhibitors
screening
strategy
using
multiple
indicators
was
developed.
Through
screen
various
natural
compounds,
cynarin,
product
enriched
Artichoke,
discovered
inhibit
Cynarin
can
dose-dependently
catabolism
cells,
increase
expression
key
ferroptosis-inhibiting
genes
(GPX4
NRF2),
increment
cellular
Fe2+,
lipid
peroxides,
reactive
oxygen
species.
It
also
prevent
mitochondria
shrinkage,
reduce
cristae
density
ferroptosis,
rat
model.
conclusion,
cynarin
potential
candidate
for
drug
development
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Март 8, 2024
Ferroptosis
is
a
non-apoptotic
form
of
regulated
cell
death
characterized
by
the
lethal
accumulation
iron-dependent
membrane-localized
lipid
peroxides.
It
acts
as
an
innate
tumor
suppressor
mechanism
and
participates
in
biological
processes
tumors.
Intriguingly,
mesenchymal
dedifferentiated
cancer
cells,
which
are
usually
resistant
to
apoptosis
traditional
therapies,
exquisitely
vulnerable
ferroptosis,
further
underscoring
its
potential
treatment
approach
for
cancers,
especially
refractory
cancers.
However,
impact
ferroptosis
on
extends
beyond
direct
cytotoxic
effect
cells.
induction
not
only
inhibits
but
also
promotes
development
due
negative
anticancer
immunity.
Thus,
comprehensive
understanding
role
crucial
successful
translation
therapy
from
laboratory
clinical
applications.
In
this
review,
we
provide
overview
recent
advancements
cancer,
covering
molecular
mechanisms,
functions,
regulatory
pathways,
interactions
with
microenvironment.
We
summarize
applications
immunotherapy,
radiotherapy,
systemic
therapy,
well
inhibition
various
conditions.
finally
discuss
markers,
current
challenges
future
directions
cancer.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Дек. 10, 2023
Abstract
Ferroptosis,
a
unique
modality
of
cell
death
with
mechanistic
and
morphological
differences
from
other
modes,
plays
pivotal
role
in
regulating
tumorigenesis
offers
new
opportunity
for
modulating
anticancer
drug
resistance.
Aberrant
epigenetic
modifications
posttranslational
(PTMs)
promote
resistance,
cancer
progression,
metastasis.
Accumulating
studies
indicate
that
can
transcriptionally
translationally
determine
vulnerability
to
ferroptosis
functions
as
driver
nervous
system
diseases
(NSDs),
cardiovascular
(CVDs),
liver
diseases,
lung
kidney
diseases.
In
this
review,
we
first
summarize
the
core
molecular
mechanisms
ferroptosis.
Then,
roles
processes,
including
histone
PTMs,
DNA
methylation,
noncoding
RNA
regulation
such
phosphorylation,
ubiquitination,
SUMOylation,
acetylation,
ADP-ribosylation,
are
concisely
discussed.
The
PTMs
genesis
cancers,
NSD,
CVDs,
well
application
PTM
modulators
therapy
these
then
discussed
detail.
Elucidating
mediated
by
will
facilitate
development
promising
combination
therapeutic
regimens
containing
or
PTM-targeting
agents
inducers
be
used
overcome
chemotherapeutic
resistance
could
prevent
addition,
highlight
potential
approaches
chemoresistance
halt
Nature,
Год журнала:
2024,
Номер
631(8021), С. 654 - 662
Опубликована: Июль 10, 2024
Abstract
Large-scale
cell
death
is
commonly
observed
during
organismal
development
and
in
human
pathologies
1–5
.
These
events
extend
over
great
distances
to
eliminate
large
populations
of
cells,
raising
the
question
how
can
be
coordinated
space
time.
One
mechanism
that
enables
long-range
signal
transmission
trigger
waves
6
,
but
this
might
used
for
remains
unclear.
Here
we
demonstrate
ferroptosis,
an
iron-
lipid-peroxidation-dependent
form
death,
propagate
across
cells
long
(≥5
mm)
at
constant
speeds
(around
5.5
μm
min
−1
)
through
reactive
oxygen
species
(ROS).
Chemical
genetic
perturbations
indicate
a
primary
role
ROS
feedback
loops
(Fenton
reaction,
NADPH
oxidase
signalling
glutathione
synthesis)
controlling
progression
ferroptotic
waves.
We
show
introducing
stress
suppression
cystine
uptake
activates
these
loops,
converting
cellular
redox
systems
from
being
monostable
bistable
thereby
priming
become
media
which
propagate.
Furthermore,
ferroptosis
its
propagation
accompany
massive,
yet
spatially
restricted,
muscle
remodelling
embryonic
avian
limb,
substantiating
use
as
tissue-sculpting
strategy
embryogenesis.
Our
findings
highlight
coordinating
global
events,
providing
paradigm
investigating
large-scale
pathologies.
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
171, С. 116112 - 116112
Опубликована: Янв. 2, 2024
Ferroptosis
is
a
newly
identified
form
of
non-apoptotic
programmed
cell
death,
characterized
by
the
iron-dependent
accumulation
lethal
lipid
reactive
oxygen
species
(ROS)
and
peroxidation
membrane
polyunsaturated
fatty
acid
phospholipids
(PUFA-PLs).
unique
among
other
death
modalities
in
many
aspects.
It
initiated
excessive
oxidative
damage
due
to
iron
overload
compromised
antioxidant
defense
systems,
including
system
Xc-/
glutathione
(GSH)/glutathione
peroxidase
4
(GPX4)
pathway
GPX4-independent
pathways.
In
past
ten
years,
ferroptosis
was
reported
play
critical
role
pathogenesis
various
cardiovascular
diseases,
e.g.,
atherosclerosis
(AS),
arrhythmia,
heart
failure,
diabetic
cardiomyopathy,
myocardial
ischemia-reperfusion
injury.
Studies
have
dysfunctional
metabolism
abnormal
expression
profiles
ferroptosis-related
factors,
iron,
GSH,
GPX4,
ferroportin
(FPN),
SLC7A11
(xCT),
as
indicators
for
atherogenesis.
Moreover,
plaque
cells,
i.e.,
vascular
endothelial
(VEC),
macrophage,
smooth
muscle
(VSMC),
positively
correlate
with
atherosclerotic
development.
Many
macromolecules,
drugs,
Chinese
herbs,
food
extracts
can
inhibit
atherogenic
process
suppressing
cells.
contrast,
some
inducers
significant
pro-atherogenic
effects.
However,
mechanisms
through
which
affects
progression
AS
still
need
be
well-known.
This
review
summarizes
molecular
their
emerging
AS,
aimed
at
providing
novel,
promising
druggable
targets
anti-AS
therapy.
Redox Biology,
Год журнала:
2024,
Номер
70, С. 103024 - 103024
Опубликована: Янв. 10, 2024
Due
to
the
cardiotoxicity
of
doxorubicin
(DOX),
its
clinical
application
is
limited.
Lipid
peroxidation
caused
by
excessive
ferrous
iron
believed
be
a
key
molecular
mechanism
DOX-induced
cardiomyopathy
(DIC).
Dexrazoxane
(DXZ),
an
chelator,
only
drug
approved
FDA
for
reducing
DIC,
but
it
has
many
side
effects
and
cannot
used
as
preventive
in
practice.
Single-nucleus
RNA
sequencing
(snRNA-seq)
analysis
identified
myocardial
epithelial
cells
that
are
susceptible
ferroptosis.
The
glutathione
peroxidase
4
(GPX4)
activator
selenomethione
(SeMet)
significantly
reduced
polyunsaturated
fatty
acids
(PUFAs)
oxidized
lipid
levels
vitro.
Consistently,
SeMet
decreased
H9C2
mortality
C57BL/6
mice
compared
DXZ,
ferrostatin-1,
normal
saline.
can
effectively
reduce
serum
markers
cardiac
injury
breast
cancer
patients.
Depletion
GPX4
gene
resulted
increase
acid
(PUFA)
eliminated
protective
effect
against
DIC.
Notably,
exerted
antitumor
on
models
with
DOX
while
providing
protection
same
animal
without
detectable
toxicities.
These
findings
suggest
pharmacological
activation
valuable
promising
strategy
preventing
doxorubicin.
