Molecular Medicine,
Journal Year:
2025,
Volume and Issue:
31(1)
Published: Feb. 14, 2025
Abstract
Cell
death
can
terminate
in
plasma
membrane
rupture
to
release
potent
pro-inflammatory
intracellular
contents
thereby
contributing
inflammatory
diseases.
is
an
active
process,
mediated
by
the
protein
ninjurin-1
(NINJ1)
pyroptosis,
post-apoptosis
lysis,
ferroptosis,
and
forms
of
necrosis.
Once
activated,
NINJ1
clusters
into
large
oligomers
within
initiate
cellular
lysis.
Recent
preclinical
studies
have
demonstrated
that
inhibiting
a
new
strategy
for
treating
immune-mediated
Indeed,
both
small
molecule
inhibitors
neutralizing
antibodies
target
clustering
preserve
integrity
mitigate
disease
pathogenesis.
In
this
Perspective
,
we
provide
summary
current
state
knowledge
recent
developments
targeting
during
cell
through
inhibition
treat
disease,
with
focus
on
liver
injury.
As
these
NINJ1-mediated
pathways
are
pivotal
maintaining
health
contribute
pathogenesis
when
dysregulated,
discussed
broad
implications
across
immunologic
basis
molecular
medicine.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: March 7, 2024
Abstract
Despite
the
successful
application
of
immune
checkpoint
therapy,
no
response
or
recurrence
is
typical
in
lung
cancer.
Cancer
stem
cells
(CSCs)
have
been
identified
as
a
crucial
player
immunotherapy-related
resistance.
Ferroptosis,
form
cell
death
driven
by
iron-dependent
lipid
peroxidation,
highly
regulated
cellular
metabolism
remolding
and
has
shown
to
synergistic
effects
when
combined
with
immunotherapy.
Metabolic
adaption
CSCs
drives
tumor
resistance,
yet
mechanisms
their
ferroptosis
defense
evasion
remain
elusive.
Here,
through
metabolomics,
transcriptomics,
epithelial-specific
Cpt1a
-knockout
mouse
model,
clinical
analysis,
we
demonstrate
that
CPT1A,
key
rate-limiting
enzyme
fatty
acid
oxidation,
acts
L-carnitine,
derived
from
tumor-associated
macrophages
drive
ferroptosis-resistance
CD8
+
T
inactivation
Mechanistically,
CPT1A
restrains
ubiquitination
degradation
c-Myc,
while
c-Myc
transcriptionally
activates
expression.
The
CPT1A/c-Myc
positive
feedback
loop
further
enhances
antioxidant
capacity
activating
NRF2/GPX4
system
reduces
amount
phospholipid
polyunsaturated
acids
ACSL4
downregulating,
thereby
suppressing
CSCs.
Significantly,
targeting
blockade-induced
anti-tumor
immunity
tumoral
tumor-bearing
mice.
results
illustrate
potential
mechanism-guided
therapeutic
strategy
metabolic
vulnerability
improve
efficacy
cancer
Journal of Hematology & Oncology,
Journal Year:
2024,
Volume and Issue:
17(1)
Published: April 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.
Cell,
Journal Year:
2024,
Volume and Issue:
187(9), P. 2079 - 2094
Published: April 1, 2024
Several
conceptual
pillars
form
the
foundation
of
modern
immunology,
including
clonal
selection
theory,
antigen
receptor
diversity,
immune
memory,
and
innate
control
adaptive
immunity.
However,
some
immunological
phenomena
cannot
be
explained
by
current
framework.
Thus,
we
still
do
not
know
how
to
design
vaccines
that
would
provide
long-lasting
protective
immunity
against
certain
pathogens,
why
autoimmune
responses
target
antigens
others,
or
response
infection
sometimes
does
more
harm
than
good.
Understanding
these
mysteries
may
require
question
existing
assumptions
develop
test
alternative
explanations.
Immunology
is
increasingly
at
a
point
when,
once
again,
exploring
new
perspectives
becomes
necessity.
Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
15
Published: Jan. 7, 2025
The
intestinal
epithelium,
beyond
its
role
in
absorption
and
digestion,
serves
as
a
critical
protective
mechanical
barrier
that
delineates
the
luminal
contents
gut
microbiota
from
lamina
propria
within
resident
mucosal
immune
cells
to
maintain
homeostasis.
is
manifested
contiguous
monolayer
of
specialized
epithelial
(IEC),
interconnected
through
tight
junctions
(TJs).
integrity
this
paramount.
Consequently,
excessive
IEC
death
advances
permeability
consequence
thereof
translocation
bacteria
into
propria,
subsequently
triggering
an
inflammatory
response,
which
underpins
clinical
disease
trajectory
bowel
(IBD).
A
burgeoning
body
evidence
illustrates
landscape
where
undergoes
several
model
programmed
cell
(PCD)
pathophysiology
pathogenesis
IBD.
Apoptosis,
necroptosis,
pyroptosis
represent
principal
modalities
PCD
with
intricate
specific
pathways
molecules.
Ample
has
revealed
substantial
mechanistic
convergence
crosstalk
among
these
three
aforementioned
forms
death,
expanding
conceptualization
PANoptosis
orchestrated
by
PNAoptosome
complex.
This
review
provides
concise
overview
molecular
mechanisms
apoptosis,
pyroptosis.
Furthermore,
based
on
between
deaths
IEC,
details
current
knowledge
regarding
regulation
natural
products.
Our
objective
broaden
comprehension
innovative
underlying
IBD
furnish
foundation
for
developing
more
drugs
treatment
IBD,
benefiting
both
practitioners
research
workers.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(3), P. 1193 - 1193
Published: Jan. 30, 2025
The
structural
and
functional
integrity
of
the
retinal
pigment
epithelium
(RPE)
plays
a
key
role
in
normal
functioning
visual
system.
RPE
cells
are
characterized
by
an
efficient
system
photoreceptor
outer
segment
phagocytosis,
high
metabolic
activity,
risk
oxidative
damage.
dysfunction
is
common
pathological
feature
various
diseases.
Dysregulation
cell
proteostasis
redox
homeostasis
accompanied
increased
reactive
oxygen
species
generation
during
impairment
lysosomal
mitochondrial
failure,
accumulation
waste
lipidic
protein
aggregates.
They
inducers
can
trigger
specific
pathways
death.
Autophagy
serves
as
important
mechanism
endogenous
defense
system,
controlling
survival
under
conditions
cellular
responses
stress
through
degradation
intracellular
components.
Impairment
autophagy
process
itself
result
In
this
review,
we
summarize
classical
types
stress-induced
with
emphasis
on
mediated
molecular
chaperones.
Heat
shock
proteins,
which
represent
hubs
connecting
life
supporting
cells,
play
special
these
mechanisms.
Regulation
stress-counteracting
essential
strategy
for
protecting
against
damage
when
preventing
degenerative
disease
progression.
Cell Death and Disease,
Journal Year:
2024,
Volume and Issue:
15(11)
Published: Nov. 26, 2024
Abstract
Regulated
cell
death
(RCD)
refers
to
the
form
of
that
can
be
regulated
by
various
biomacromolecules.
Each
modalities
have
their
distinct
morphological
changes
and
molecular
mechanisms.
However,
intense
evidences
suggest
lipid
peroxidation
common
feature
initiates
propagates
death.
Excessive
alters
property
membrane
further
damage
proteins
nucleic
acids,
which
is
implicated
in
human
pathologies.
Here,
we
firstly
review
classical
chain
process
peroxidation,
clarify
current
understanding
myriad
roles
mechanisms
RCD
types.
We
also
discuss
how
involves
diseases
such
intimate
association
between
peroxidation-driven
leveraged
develop
rational
therapeutic
strategies.
