Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Апрель 30, 2024
Oncolytic
viruses
(OVs)
show
promise
as
a
cancer
treatment
by
selectively
replicating
in
tumor
cells
and
promoting
antitumor
immunity.
However,
the
current
immunogenicity
induced
OVs
for
is
relatively
weak,
necessitating
thorough
investigation
of
mechanisms
underlying
its
induction
Here,
we
that
HSV-1-based
(oHSVs)
trigger
ZBP1-mediated
PANoptosis
(a
unique
innate
immune
inflammatory
cell
death
modality),
resulting
augmented
effects.
Mechanistically,
oHSV
enhances
expression
interferon-stimulated
genes,
leading
to
accumulation
endogenous
Z-RNA
subsequent
activation
ZBP1.
To
further
enhance
potential
oHSV,
conduct
screening
identify
Fusobacterium
nucleatum
outer
membrane
vesicle
(Fn-OMV)
can
increase
execution
proteins.
The
combination
Fn-OMV
demonstrates
potent
immunogenicity.
Taken
together,
our
study
provides
deeper
understanding
oHSV-induced
immunity,
promising
strategy
combines
with
Fn-OMV.
Computational and Structural Biotechnology Journal,
Год журнала:
2021,
Номер
19, С. 4641 - 4657
Опубликована: Янв. 1, 2021
Pyroptosis,
apoptosis
and
necroptosis
are
the
most
genetically
well-defined
programmed
cell
death
(PCD)
pathways,
they
intricately
involved
in
both
homeostasis
disease.
Although
identification
of
key
initiators,
effectors
executioners
each
these
three
PCD
pathways
has
historically
delineated
them
as
distinct,
growing
evidence
highlighted
extensive
crosstalk
among
them.
These
observations
have
led
to
establishment
concept
PANoptosis,
defined
an
inflammatory
pathway
regulated
by
PANoptosome
complex
with
features
pyroptosis,
and/or
that
cannot
be
accounted
for
any
alone.
In
this
review,
we
provide
a
brief
overview
research
history
necroptosis.
We
then
examine
intricate
discuss
current
PANoptosis.
also
detail
molecular
assembly
complex,
scaffold
contemporaneous
engagement
molecules
from
apoptosis,
PANoptosis
is
now
known
critically
many
diseases,
including
infection,
sterile
inflammation
cancer,
future
discovery
novel
PANoptotic
components
will
continue
broaden
our
understanding
fundamental
processes
inform
development
new
therapeutics.
Cell Reports,
Год журнала:
2021,
Номер
37(3), С. 109858 - 109858
Опубликована: Окт. 1, 2021
Cell
death
provides
host
defense
and
maintains
homeostasis.
Zα-containing
molecules
are
essential
for
these
processes.
Z-DNA
binding
protein
1
(ZBP1)
activates
inflammatory
cell
death,
PANoptosis,
whereas
adenosine
deaminase
acting
on
RNA
(ADAR1)
serves
as
an
editor
to
maintain
Here,
we
identify
characterize
ADAR1's
interaction
with
ZBP1,
defining
its
role
in
regulation
tumorigenesis.
Combining
interferons
(IFNs)
nuclear
export
inhibitors
(NEIs)
ZBP1-dependent
PANoptosis.
ADAR1
suppresses
this
PANoptosis
by
interacting
the
Zα2
domain
of
ZBP1
limit
RIPK3
interactions.
Adar1
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Март 30, 2022
The
demise
of
cells
in
various
ways
enables
the
body
to
clear
unwanted
cells.
Studies
over
years
revealed
distinctive
molecular
mechanisms
and
functional
consequences
several
key
cell
death
pathways.
Currently,
most
intensively
investigated
programmed
(PCD)
includes
apoptosis,
necroptosis,
pyroptosis,
ferroptosis,
PANoptosis,
autophagy,
which
has
been
discovered
play
crucial
roles
modulating
immunosuppressive
tumor
microenvironment
(TME)
determining
clinical
outcomes
cancer
therapeutic
approaches.
PCD
can
dual
roles,
either
pro-tumor
or
anti-tumor,
partly
depending
on
intracellular
contents
released
during
process.
also
regulates
enrichment
effector
regulatory
immune
cells,
thus
participating
fine-tuning
anti-tumor
immunity
TME.
In
this
review,
we
focused
primarily
discussed
messengers
regulating
their
intricate
crosstalk
with
response
TME,
explored
immunological
consequence
its
implications
future
therapy
developments.
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Фев. 28, 2022
Metabolic
enzymes
have
an
indispensable
role
in
metabolic
reprogramming,
and
their
aberrant
expression
or
activity
has
been
associated
with
chemosensitivity.
Hence,
targeting
remains
attractive
approach
for
treating
tumors.
However,
the
influence
regulation
of
cysteine
desulfurase
(NFS1),
a
rate-limiting
enzyme
iron-sulfur
(Fe-S)
cluster
biogenesis,
colorectal
cancer
(CRC)
remain
elusive.
Here,
using
vivo
gene-based
clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)-Cas9
library
screen,
we
revealed
that
loss
NFS1
significantly
enhanced
sensitivity
CRC
cells
to
oxaliplatin.
In
vitro
results
showed
deficiency
synergizing
oxaliplatin
triggered
PANoptosis
(apoptosis,
necroptosis,
pyroptosis,
ferroptosis)
by
increasing
intracellular
levels
reactive
oxygen
species
(ROS).
Furthermore,
oxaliplatin-based
oxidative
stress
phosphorylation
level
serine
residues
NFS1,
which
prevented
S293
phosphorylation-dependent
manner
during
treatment.
addition,
high
transcriptionally
regulated
MYC,
was
found
tumor
tissues
poor
survival
hyposensitivity
chemotherapy
patients
CRC.
Overall,
findings
this
study
provided
insights
into
underlying
mechanisms
identified
inhibition
as
promising
strategy
improving
outcome
platinum-based
treatment
Science Immunology,
Год журнала:
2022,
Номер
7(74)
Опубликована: Май 19, 2022
Severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2),
the
virus
responsible
for
disease
2019
(COVID-19),
continues
to
cause
substantial
morbidity
and
mortality
in
ongoing
global
pandemic.
Understanding
fundamental
mechanisms
that
govern
innate
immune
inflammatory
responses
during
SARS-CoV-2
infection
is
critical
developing
effective
therapeutic
strategies.
Whereas
interferon
(IFN)–based
therapies
are
generally
expected
be
beneficial
viral
infection,
clinical
trials
COVID-19
have
shown
limited
efficacy
potential
detrimental
effects
of
IFN
treatment
infection.
However,
underlying
this
failure
remain
unknown.
In
study,
we
found
induced
Z-DNA-binding
protein
1
(ZBP1)–mediated
cell
death,
PANoptosis,
human
murine
macrophages
lungs
mice
infected
with
β-coronaviruses,
including
mouse
hepatitis
(MHV).
patients
COVID-19,
expression
sensor
ZBP1
was
increased
cells
from
those
who
succumbed
compared
recovered,
further
suggesting
a
link
between
pathology.
mice,
IFN-β
after
β-coronavirus
lethality,
genetic
deletion
Zbp1
or
its
Zα
domain
suppressed
death
protected
IFN-mediated
lethality
Overall,
our
results
identify
limits
therapy
by
driving
lethality.
Therefore,
inhibiting
activity
may
improve
therapy,
paving
way
development
new
critically
needed
therapeutics
as
well
other
infections
conditions
where
pathology
occur.
Cells,
Год журнала:
2022,
Номер
11(12), С. 1885 - 1885
Опубликована: Июнь 10, 2022
Alzheimer’s
disease
(AD)
is
a
neurodegenerative
disorder
molecularly
characterized
by
the
formation
of
amyloid
β
(Aβ)
plaques
and
type
2
microtubule-associated
protein
(Tau)
abnormalities.
Multiple
studies
have
shown
that
many
brain’s
immunological
cells,
specifically
microglia
astrocytes,
are
involved
in
AD
pathogenesis.
Cells
innate
immune
system
play
an
essential
role
eliminating
pathogens
but
also
regulate
brain
homeostasis
AD.
When
activated,
cells
can
cause
programmed
cell
death
through
multiple
pathways,
including
pyroptosis,
apoptosis,
necroptosis,
PANoptosis.
The
often
results
release
proinflammatory
cytokines
propagate
response
eliminate
Aβ
aggregated
Tau
proteins.
However,
chronic
neuroinflammation,
which
result
from
death,
has
been
linked
to
diseases
worsen
Therefore,
must
be
tightly
balanced
appropriately
clear
these
AD-related
structural
abnormalities
without
inducing
neuroinflammation.
In
this
review,
we
discuss
responses,
inflammatory
cytokine
secretion
as
they
relate
Therapeutic
strategies
targeting
mechanisms
will
critical
consider
for
future
preventive
or
palliative
treatments
The Journal of Immunology,
Год журнала:
2022,
Номер
209(9), С. 1625 - 1633
Опубликована: Окт. 20, 2022
Abstract
Innate
immunity
is
the
first
response
to
protect
against
pathogens
and
cellular
insults.
Pattern
recognition
receptors
sense
pathogen-
damage-associated
molecular
patterns
induce
an
innate
immune
characterized
by
inflammation
programmed
cell
death
(PCD).
In-depth
characterization
of
PCD
pathways
has
highlighted
significant
cross-talk.
Recent
advances
led
identification
a
unique
inflammatory
modality
called
PANoptosis,
which
regulated
multifaceted
PANoptosome
complexes
that
are
assembled
integrating
components
from
other
pathways.
The
totality
biological
effects
observed
in
PANoptosis
cannot
be
accounted
for
any
pathway
alone.
In
this
review,
we
briefly
describe
mechanisms
death,
including
activation
regulation.
We
also
highlight
PANoptosomes
identified
date
provide
overview
implications
disease
therapeutic
targeting.
Improved
understanding
immune-mediated
critical
inform
next
generation
treatment
strategies.
