Targeting regulated cell death: Apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis in anticancer immunity
Journal of Translational Internal Medicine,
Год журнала:
2025,
Номер
13(1), С. 10 - 32
Опубликована: Фев. 1, 2025
In
the
evolving
landscape
of
cancer
treatment,
strategic
manipulation
regulated
cell
death
(RCD)
pathways
has
emerged
as
a
crucial
component
effective
anti-tumor
immunity.
Evidence
suggests
that
tumor
cells
undergoing
RCD
can
modify
immunogenicity
microenvironment
(TME),
potentially
enhancing
its
ability
to
suppress
progression
and
metastasis.
this
review,
we
first
explore
mechanisms
apoptosis,
necroptosis,
pyroptosis,
ferroptosis,
cuproptosis,
along
with
crosstalk
between
these
modalities.
We
then
discuss
how
processes
activate
antigen-presenting
cells,
facilitate
cross-priming
CD8+
T
trigger
immune
responses,
highlighting
complex
effects
novel
forms
on
TME
biology.
Furthermore,
summarize
potential
drugs
nanoparticles
induce
or
inhibit
emerging
their
therapeutic
roles
in
treatment.
Finally,
put
forward
existing
challenges
future
prospects
for
targeting
anti-cancer
Overall,
review
enhances
our
understanding
molecular
biological
impacts
RCD-based
therapies,
providing
new
perspectives
strategies
Язык: Английский
Ferroptosis: A Targetable Vulnerability for Melanoma Treatment
Journal of Investigative Dermatology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
Melanoma
is
a
devastating
form
of
skin
cancer
characterized
by
high
mutational
burden,
limited
treatment
success,
and
dismal
prognosis.
Although
immunotherapy
targeted
therapies
have
significantly
revolutionized
melanoma
treatment,
the
majority
patients
fail
to
achieve
durable
responses,
highlighting
urgent
need
for
novel
therapeutic
strategies.
Ferroptosis,
an
iron-dependent
regulated
cell
death
driven
overwhelming
accumulation
lipid
peroxides,
has
emerged
as
promising
approach
in
preclinical
models.
A
deeper
understanding
ferroptosis
landscape
based
on
its
biology
characteristics,
including
phenotypic
plasticity,
metabolic
state,
genomic
alterations,
epigenetic
changes,
well
complex
role
mechanisms
immune
cells
could
provide
foundation
developing
effective
treatments.
In
this
review,
we
outline
molecular
ferroptosis,
decipher
regulation,
reveal
potential
melanoma,
discuss
pressing
questions
that
should
guide
future
investigations
into
melanoma.
Язык: Английский
Single-cell multi-omics analysis identifies SPP1+ macrophages as key drivers of ferroptosis-mediated fibrosis in ligamentum flavum hypertrophy
Biomarker Research,
Год журнала:
2025,
Номер
13(1)
Опубликована: Фев. 25, 2025
Abstract
Background
Ligamentum
flavum
hypertrophy
(LFH)
is
a
primary
contributor
to
lumbar
spinal
stenosis.
However,
thorough
understanding
of
the
cellular
and
molecular
mechanisms
driving
LFH
fibrotic
progression
remains
incomplete.
Methods
Single-cell
RNA
sequencing
(scRNA-seq)
was
performed
construct
single-cell
map
human
ligamentum
(LF)
samples.
An
integrated
multi-omics
approach,
encompassing
scRNA-seq,
bulk
(bulk
RNA-seq),
Mendelian
randomization
(MR),
applied
conduct
comprehensive
functional
analysis.
Clinical
tissue
specimens
animal
models
were
employed
further
confirm
findings.
Results
ScRNA-seq
provided
level
view
microenvironment
in
LF,
revealing
significantly
increased
proportions
fibroblasts,
myofibroblasts,
macrophages
LFH.
Using
transmission
electron
microscopy,
gene
set
scoring,
MR
analysis,
ferroptosis
identified
as
critical
risk
factor
pathway
within
Subcluster
analysis
fibroblasts
revealed
heterogeneity
among
distinct
subpopulations,
highlighting
characteristics
metabolic
dynamics
fibroblast
with
high
score
(High
Ferro-score
FB).
The
quantification
expression
at
that
along
fibrosis
specimens,
finding
validated
both
mice
sections.
Consistently,
RNA-seq
confirmed
underscoring
strong
correlation
between
these
cell
types
through
Spearman
Notably,
subcluster
mononuclear
phagocytes
specific
subset
SPP1
+
(SPP1
Mac)
enriched
LFH,
which
exhibited
activation
ferroptosis-related
pathways.
Cell-cell
communication
highlighted
Mac
strongest
outgoing
incoming
interactions
microenvironment.
Ligand-receptor
SPP1-CD44
axis
could
serve
key
mediator
regulating
activity
High
FB.
Multiplex
immunofluorescence
substantial
Collagen
I
deposition
reduced
Ferritin
Light
Chain
regions
co-localization
specimens.
Conclusions
Our
findings
indicated
may
contribute
by
FB
axis.
This
study
enhances
our
underlying
progression,
potentially
improving
early
diagnostic
strategies
identifying
new
therapeutic
targets.
Язык: Английский
Dysregulated metabolic pathways of pulmonary fibrosis and the lipids associated with the effects of nintedanib therapy
Respiratory Research,
Год журнала:
2025,
Номер
26(1)
Опубликована: Апрель 28, 2025
Pulmonary
fibrosis
(PF)
is
a
disease
with
poor
prognosis,
and
its
pathogenesis
not
fully
understood.
Identifying
dysregulation
of
lipid
metabolism
in
PF
may
provide
insight
promote
the
development
novel
therapies.
The
present
study
was
designed
to
clarify
dysregulated
pathways
identify
lipids
correlated
treatment
response.
This
research
comprised
two
prospective
cohort
studies.
Study
1
aimed
metabolic
peripheral
blood
patients,
compared
healthy
control
(HC)
subjects.
2
associated
decline
%
forced
vital
capacity
(%FVC)
survival
patients
treated
anti-fibrotic
drug,
nintedanib.
As
preliminary
ancillary
experiment,
we
attempted
endothelial
cells
fibroblasts.
In
1,
38
were
identified
that
differed
between
(n
=
66)
HC
63)
groups.
Compared
subjects,
phosphatidylcholine
(PC)
36:5
most
up-regulated
lysophosphatidylcholine
(LPC)
18:0
down-regulated
patients.
Glycerophospholipid
enriched
pathway.
Plasmenyl
phosphatidylethanolamine
(pPE)
plasmanyl
(pPC)
determined
be
endothelial-related
lipids,
(PE)
fibroblast-related
PF.
2,
10
absolute
%FVC
<
2.5%
group
(6
M
responders,
n
14)
>
non-responders,
6)
after
6
nintedanib
therapy,
5%
(12
15)
5)
12
therapy.
Four
consistently
detected
at
M,
among
them,
higher
levels
pPE
18:0p/22:6
showed
poorer
prognosis
for
24
(p
0.05,
HR
6.547,
95%
CI
1.471-29.13).
Under
species
progressive
fibrosis,
considered
an
lipid.
Lipidomic
profiling
revealed
distinct
strongly
responses
Targeting
or
catabolic
enzymes
involved
has
potential
ameliorate
Registry
UMIN,
analysis
on
plasma
idiopathic
pulmonary
Trial
registry
number,
UMIN000020872.
Registered
3
February
2016,
https://center6.umin.ac.jp/cgiopenbin/ctr/index.cgi
.
Язык: Английский
Mechanistic role of environmental toxicants in inducing cellular ferroptosis and its associated diseases
Ecotoxicology and Environmental Safety,
Год журнала:
2025,
Номер
298, С. 118269 - 118269
Опубликована: Май 10, 2025
Язык: Английский
Asiaticoside enhances the effect of propofol on the invasion, ferroptosis and immune escape of bladder cancer
Drug Development Research,
Год журнала:
2024,
Номер
85(6)
Опубликована: Авг. 19, 2024
Bladder
cancer
is
a
highly
prevalent
malignancy.
Asiaticoside
(AC),
triterpenoid
derivative,
exhibits
antitumor
effect
on
different
tumors.
This
study
aimed
to
explore
the
role
and
mechanism
of
AC
bladder
cancer.
J82
T24
cells
were
treated
with
and/or
propofol,
nude
mice
subcutaneously
administrated
cells.
The
propofol
explored
by
cell
counting
kit-8,
transwell,
flow
cytometry,
enzyme-linked
immunosorbent
assay,
immunohistochemistry
western
blot
assays
both
in
vitro
vivo.
Cell
viability
was
inhibited
IC50
value
2.43
μM
2.16
μM,
42.51
48.37
respectively.
or
alone
decreased
proliferation,
invasion,
immune
escape
increased
ferroptosis,
as
well
downregulating
level
PI3K/AKT
pathway
animal
experiments.
above-mentioned
indicators
further
enhanced
co-treatment
Taken
together,
promoted
ameliorative
involved
pathway.
Язык: Английский
Peritoneal fibrosis: from pathophysiological mechanism to medicine
Frontiers in Physiology,
Год журнала:
2024,
Номер
15
Опубликована: Сен. 4, 2024
Peritoneal
dialysis
(PD)
is
currently
one
of
the
effective
methods
for
treating
end-stage
renal
disease
(ESRD).
However,
long-term
exposure
to
high
concentration
glucose
in
peritoneal
environment
could
lead
fibrosis
(PF),
impaired
filtration
function,
decreased
efficiency,
and
even
withdrawal
from
patients.
Considerable
evidence
suggests
that
after
related
crucial
factors
such
as
mesothelial-to-mesenchymal
transition
(MMT),
inflammatory
response,
angiogenesis,
etc.
In
our
review,
we
summarize
pathophysiological
mechanisms
further
illustrate
future
strategies
against
PF.
Язык: Английский
Exploring Endogenous Tryptamines: Overlooked Agents Against Fibrosis in Chronic Disease? A Narrative Review
Livers,
Год журнала:
2024,
Номер
4(4), С. 615 - 637
Опубликована: Ноя. 28, 2024
Long
regarded
as
illicit
substances
with
no
clinical
value,
N-dimethylated
tryptamines—such
N,N-dimethyltryptamine,
5-methoxy-N,N-dimethyltryptamine,
and
bufotenine—have
been
found
to
produce
naturally
in
a
wide
variety
of
species,
including
humans.
Known
for
their
psychoactive
effects
through
serotonin
receptors
(5-HTRs),
tryptamines
are
currently
being
reinvestigated
clinically
long-term
benefits
mental
disorders.
Endogenous
tryptamine
is
methylated
by
indolethylamine-N-methyltransferase
(INMT),
which
can
then
serve
an
agonist
pro-survival
pathways,
such
sigma
non-opioid
intracellular
receptor
1
(SIGMAR1)
signaling.
Fibrogenic
diseases,
like
metabolic-associated
fatty
liver
disease
(MAFLD),
steatohepatitis
(MASH),
chronic
kidney
(CKD)
have
shown
changes
INMT
SIGMAR1
activity
the
progression
pathogenesis.
At
cellular
level,
endothelial
cells
fibroblasts
express
various
tissues;
however,
little
known
about
injury
fibrosis.
In
this
review,
I
will
give
overview
biochemistry,
molecular
biology,
current
evidence
INMT’s
role
hepatic
fibrogenesis.
also
discuss
pre-clinical
findings
N-methylated
highlight
new
upcoming
therapeutic
strategies
that
may
be
adapted
mitigating
fibrogenic
diseases.
Finally,
mention
recent
mutualistic
gut
bacteria
influencing
endogenous
signaling
metabolism.
Язык: Английский