Frontiers in Pharmacology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 7, 2025
Mitochondria,
as
the
energy
factories
of
cells,
are
involved
in
a
wide
range
vital
activities,
including
cell
differentiation,
signal
transduction,
cycle,
and
apoptosis,
while
also
regulating
growth.
However,
current
pharmacological
treatments
for
stroke
challenged
by
issues
such
drug
resistance
side
effects,
necessitating
exploration
new
therapeutic
strategies.
This
review
aims
to
summarize
regulatory
effects
natural
compounds
targeting
mitochondria
on
neuronal
mitochondrial
function
metabolism,
providing
perspectives
treatment.
Numerous
vitro
vivo
studies
have
shown
that
products
berberine,
ginsenosides,
baicalein
protect
reduce
stroke-induced
damage
through
multiple
mechanisms.
These
apoptosis
modulating
expression
mitochondrial-associated
apoptotic
proteins.
They
inhibit
activation
permeability
transition
pore
(mPTP),
thereby
decreasing
ROS
production
cytochrome
C
release,
which
helps
preserve
function.
Additionally,
they
regulate
ferroptosis,
fission,
promote
autophagy
trafficking,
further
enhancing
protection.
As
multi-target
chemical
agents,
offer
high
efficacy
with
fewer
present
promising
potential
innovative
therapies.
Future
research
should
investigate
effectiveness
safety
these
clinical
applications,
advancing
their
development
strategy
stroke.
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.
Journal of Hematology & Oncology,
Год журнала:
2024,
Номер
17(1)
Опубликована: Июнь 6, 2024
Abstract
Ferroptosis,
an
iron-dependent
form
of
cell
death
characterized
by
uncontrolled
lipid
peroxidation,
is
governed
molecular
networks
involving
diverse
molecules
and
organelles.
Since
its
recognition
as
a
non-apoptotic
pathway
in
2012,
ferroptosis
has
emerged
crucial
mechanism
numerous
physiological
pathological
contexts,
leading
to
significant
therapeutic
advancements
across
wide
range
diseases.
This
review
summarizes
the
fundamental
mechanisms
regulatory
pathways
underlying
ferroptosis,
including
both
GPX4-dependent
-independent
antioxidant
mechanisms.
Additionally,
we
examine
involvement
various
conditions,
cancer,
neurodegenerative
diseases,
sepsis,
ischemia–reperfusion
injury,
autoimmune
disorders,
metabolic
disorders.
Specifically,
explore
role
response
chemotherapy,
radiotherapy,
immunotherapy,
nanotherapy,
targeted
therapy.
Furthermore,
discuss
pharmacological
strategies
for
modulating
potential
biomarkers
monitoring
this
process.
Lastly,
elucidate
interplay
between
other
forms
regulated
death.
Such
insights
hold
promise
advancing
our
understanding
context
human
health
disease.
Liver
cancer
is
the
third
leading
cause
of
cancer-related
deaths
and
ranks
as
sixth
most
prevalent
type
globally.
NAFLD
or
metabolic
dysfunction-associated
steatotic
liver
disease,
its
more
severe
manifestation,
NASH
steatohepatitis
(MASH),
pose
a
significant
global
health
concern,
affecting
approximately
20%-25%
population.
The
increased
prevalence
disease
MASH
parallel
to
increasing
rates
obesity-associated
diseases,
including
2
diabetes,
insulin
resistance,
fatty
diseases.
can
progress
MASH-related
HCC
(MASH-HCC)
in
about
2%
cases
each
year,
influenced
by
various
factors
such
genetic
mutations,
carcinogen
exposure,
immune
microenvironment,
microbiome.
MASH-HCC
exhibits
distinct
molecular
characteristics
compared
other
causes
affects
both
men
women
equally.
management
early
intermediate-stage
typically
involves
surgery
locoregional
therapies,
while
advanced
treated
with
systemic
anti-angiogenic
therapies
checkpoint
inhibitors.
In
this
comprehensive
review,
we
consolidate
previous
research
findings
also
providing
current
insights
into
intricate
processes
underlying
development.
We
delve
MASH-HCC-associated
variations
somatic
progression
models,
multiomics
analysis,
immunological
microenvironmental
impacts,
discuss
targeted/combined
overcome
evasion
biomarkers
recognize
treatment
responders.
By
furthering
our
comprehension
mechanisms
MASH-HCC,
goal
catalyze
advancement
potent
strategies,
ultimately
enhanced
patient
outcomes.
Journal of Hematology & Oncology,
Год журнала:
2024,
Номер
17(1)
Опубликована: Апрель 23, 2024
Abstract
Tumor
is
a
local
tissue
hyperplasia
resulted
from
cancerous
transformation
of
normal
cells
under
the
action
various
physical,
chemical
and
biological
factors.
The
exploration
tumorigenesis
mechanism
crucial
for
early
prevention
treatment
tumors.
Epigenetic
modification
common
important
in
cells,
including
DNA
methylation,
histone
modification,
non-coding
RNA
m6A
modification.
mode
cell
death
programmed
by
death-related
genes;
however,
recent
researches
have
revealed
some
new
modes
death,
pyroptosis,
ferroptosis,
cuproptosis
disulfidptosis.
regulation
deaths
mainly
involved
key
proteins
affects
up-regulating
or
down-regulating
expression
levels
proteins.
This
study
aims
to
investigate
epigenetic
modifications
regulating
disulfidptosis
tumor
explore
possible
triggering
factors
development
microscopic
point
view,
provide
potential
targets
therapy
perspective
antitumor
drugs
combination
therapies.
Abstract
Ferroptosis
is
a
type
of
regulated
cell
death
characterized
by
iron
accumulation
and
uncontrolled
lipid
peroxidation,
leading
to
plasma
membrane
rupture
intracellular
content
release.
Originally
investigated
as
targeted
therapy
for
cancer
cells
carrying
oncogenic
RAS
mutations,
ferroptosis
induction
now
exhibits
potential
complement
chemotherapy,
immunotherapy,
radiotherapy
in
various
types.
However,
it
can
lead
side
effects,
including
immune
death,
bone
marrow
impairment,
liver
kidney
damage,
cachexia
(severe
weight
loss
muscle
wasting),
secondary
tumorigenesis.
In
this
review,
we
discuss
the
advantages
offer
an
overview
diverse
range
documented
effects.
Furthermore,
examine
underlying
mechanisms
explore
strategies
effect
mitigation.
Redox Biology,
Год журнала:
2024,
Номер
69, С. 103029 - 103029
Опубликована: Янв. 4, 2024
Hepatocyte
ferroptosis
promotes
the
pathogenesis
and
progression
of
liver
fibrosis.
Salvianolic
acid
B
(Sal
B)
exerts
antifibrotic
effects.
However,
pharmacological
mechanism
target
has
not
yet
been
fully
elucidated.
In
this
study,
fibrosis
was
induced
by
CCl4
in
wild-type
mice
hepatocyte-specific
extracellular
matrix
protein
1
(Ecm1)-deficient
mice,
which
were
separately
treated
with
Sal
B,
ferrostatin-1,
sorafenib
or
cilengitide.
Erastin-
CCl4-induced
hepatocyte
models
without
Ecm1
gene
knockdown
evaluated
vitro.
Subsequently,
interaction
between
xCT
binding
kinetics
determined.
We
found
that
significantly
attenuated
mice.
deletion
hepatocytes
abolished
effect
B.
Mechanistically,
protected
against
upregulating
Ecm1.
Further
research
revealed
as
a
direct
for
treating
Interestingly,
interacted
to
regulate
ferroptosis.
vitro
treatment,
abrogated
after
LO2
cells.
Therefore,
alleviates
targeting
up-regulation
inhibiting
The
regulates
EBioMedicine,
Год журнала:
2024,
Номер
102, С. 105088 - 105088
Опубликована: Март 26, 2024
Metabolic
dysfunction-associated
steatohepatitis
(MASH)
is
characterised
by
cell
death
of
parenchymal
liver
cells
which
interact
with
their
microenvironment
to
drive
disease
activity
and
fibrosis.
The
identification
the
major
type
could
pave
way
towards
pharmacotherapy
for
MASH.
To
date,
increasing
evidence
suggest
a
regulated
death,
named
ferroptosis,
occurs
through
iron-catalysed
peroxidation
polyunsaturated
fatty
acids
(PUFA)
in
membrane
phospholipids.
Lipid
enjoys
renewed
interest
light
as
druggable
target
This
review
recapitulates
molecular
mechanisms
ferroptosis
physiology,
human
MASH
critically
appraises
results
targeting
preclinical
models.
Rewiring
redox,
iron
PUFA
metabolism
creates
proferroptotic
environment
involved
MASH-related
hepatocellular
carcinoma
(HCC)
development.
Ferroptosis
induction
might
be
promising
novel
approach
eradicate
HCC,
while
its
inhibition
ameliorate
progression.
