Biomolecules,
Год журнала:
2025,
Номер
15(1), С. 71 - 71
Опубликована: Янв. 6, 2025
The
tumor
microenvironment
(TME)
plays
a
pivotal
role
in
neoplastic
initiation
and
progression.
Epigenetic
machinery,
governing
the
expression
of
core
oncogenes
suppressor
genes
transformed
cells,
significantly
contributes
to
development
at
both
primary
distant
sites.
Recent
studies
have
illuminated
how
epigenetic
mechanisms
integrate
external
cues
downstream
signals,
altering
phenotype
stromal
cells
immune
cells.
This
remolds
area
surrounding
ultimately
fostering
an
immunosuppressive
microenvironment.
Therefore,
correcting
TME
by
targeting
modifications
holds
substantial
promise
for
cancer
treatment.
review
synthesizes
recent
research
that
elucidates
impact
specific
regulations-ranging
from
DNA
methylation
histone
chromatin
remodeling-on
within
TME.
Notably,
we
highlight
their
functional
roles
either
promoting
or
restricting
We
also
discuss
potential
applications
agents
treatment,
envisaging
ability
normalize
ecosystem.
aims
assist
researchers
understanding
dynamic
interplay
between
epigenetics
TME,
paving
way
better
therapy.
Cancer Research,
Год журнала:
2024,
Номер
84(10), С. 1597 - 1612
Опубликована: Апрель 8, 2024
Resistance
to
immune
checkpoint
blockade
(ICB)
therapy
represents
a
formidable
clinical
challenge
limiting
the
efficacy
of
immunotherapy.
In
particular,
prostate
cancer
poses
for
ICB
due
its
immunosuppressive
features.
A
ketogenic
diet
(KD)
has
been
reported
enhance
response
in
some
other
models.
However,
adverse
effects
associated
with
continuous
KD
were
also
observed,
demanding
better
mechanistic
understanding
and
optimized
regimens
using
as
an
immunotherapy
sensitizer.
this
study,
we
established
series
ICB-resistant
cell
lines
developed
highly
effective
strategy
combining
anti-PD1
anti-CTLA4
antibodies
histone
deacetylase
inhibitor
(HDACi)
vorinostat,
cyclic
(CKD),
or
dietary
supplementation
ketone
body
β-hydroxybutyrate
(BHB),
which
is
endogenous
HDACi.
CKD
BHB
each
delayed
tumor
growth
monotherapy,
both
adaptive
immunity
required
antitumor
activity
CKD.
Single-cell
transcriptomic
proteomic
profiling
revealed
that
HDACi
ketogenesis
enhanced
through
cell-intrinsic
mechanisms,
including
upregulation
MHC
class
I
molecules,
-extrinsic
such
CD8+
T-cell
chemoattraction,
M1/M2
macrophage
rebalancing,
monocyte
differentiation
toward
antigen-presenting
cells,
diminished
neutrophil
infiltration.
Overall,
these
findings
illuminate
potential
path
cancer.
AJP Cell Physiology,
Год журнала:
2024,
Номер
326(2), С. C551 - C566
Опубликована: Янв. 9, 2024
β-Hydroxybutyrate
(βOHB)
is
the
major
ketone
in
body,
and
it
recognized
as
a
metabolic
energy
source
an
important
signaling
molecule.
While
oxidation
essential
brain
during
prolonged
fasting/starvation,
other
organs
such
skeletal
muscle
heart
also
use
ketones
substrates.
Additionally,
βOHB-mediated
molecular
events
occur
cells,
via
metabolism
and/or
signaling,
may
contribute
to
optimal
health
cardiac
function.
Of
importance,
when
of
for
ATP
production
molecules
becomes
disturbed
presence
underlying
obesity,
type
2
diabetes,
cardiovascular
diseases,
these
changes
cardiometabolic
disease.
As
result
disturbances
disease,
multiple
approaches
have
been
used
elevate
circulating
with
goal
optimizing
either
or
ketone-mediated
signaling.
These
produced
significant
improvements
disease
wide
range
benefits
that
include
improved
metabolism,
weight
loss,
better
glycemic
control,
vascular
function,
well
reduced
inflammation
oxidative
stress.
Herein,
we
present
evidence
indicates
therapy
could
be
approach
help
treat
diseases
by
targeting
muscles.
The Journal of Experimental Medicine,
Год журнала:
2024,
Номер
221(9)
Опубликована: Июль 4, 2024
Coordination
of
cellular
metabolism
is
essential
for
optimal
T
cell
responses.
Here,
we
identify
cytosolic
acetyl-CoA
production
as
an
metabolic
node
CD8
function
in
vivo.
We
show
that
responses
to
infection
depend
on
derived
from
citrate
via
the
enzyme
ATP
lyase
(ACLY).
However,
ablation
ACLY
triggers
alternative,
acetate-dependent
pathway
mediated
by
acyl-CoA
synthetase
short-chain
family
member
2
(ACSS2).
Mechanistically,
acetate
fuels
both
TCA
cycle
and
production,
impacting
effector
responses,
histone
acetylation,
chromatin
accessibility
at
gene
loci.
When
functional,
ACSS2
not
required,
suggesting
obligate
substrate
function.
loss
renders
cells
dependent
(via
ACSS2)
maintain
Together,
coordinate
Ketogenesis
is
a
dynamic
metabolic
conduit
supporting
hepatic
fat
oxidation
particularly
when
carbohydrates
are
in
short
supply.
Ketone
bodies
may
be
recycled
into
anabolic
substrates,
but
physiological
role
for
this
process
has
not
been
identified.
Here,
we
use
mass
spectrometry–based
13
C-isotope
tracing
and
shotgun
lipidomics
to
establish
link
between
ketogenesis
lipid
anabolism.
Unexpectedly,
mouse
liver
primary
hepatocytes
consumed
ketone
support
fatty
acid
biosynthesis
via
both
de
novo
lipogenesis
(DNL)
polyunsaturated
(PUFA)
elongation.
While
an
acetoacetate
intermediate
was
absolutely
required
source
DNL,
PUFA
elongation
activation
of
by
cytosolic
acetoacetyl–coenzyme
A
synthetase
(AACS).
Moreover,
AACS
deficiency
diminished
free
esterified
PUFAs
hepatocytes,
while
ketogenic
insufficiency
depleted
increased
triacylglycerols.
These
findings
suggest
that
influences
metabolism,
representing
molecular
mechanism
through
which
could
influence
systemic
physiology
chronic
diseases.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Янв. 19, 2024
Mycobacterium
tuberculosis
(
M.tb
)
effectively
manipulates
the
host
processes
to
establish
deadly
respiratory
disease,
Tuberculosis
(TB).
has
developed
key
mechanisms
disrupt
cell
health
combat
immune
responses
and
replicate
efficaciously.
antigens
such
as
ESAT-6,
19kDa
lipoprotein,
Hip1,
Hsp70
destroy
integrity
of
organelles
(Mitochondria,
Endoplasmic
Reticulum,
Nucleus,
Phagosomes)
or
delay
innate/adaptive
responses.
This
is
followed
by
induction
cellular
stress
in
host.
Such
cells
can
either
undergo
various
death
apoptosis
necrosis,
mount
effective
clear
invading
pathogen.
Further,
infection
progression,
secretes
extracellular
vesicles
exosomes
initiate
signaling.
The
contain
well
cell-derived
peptides
that
act
a
double-edged
sword
signaling
event.
host-symbiont
microbiota
produces
metabolites
are
beneficial
for
maintaining
healthy
tissue
microenvironment.
In
juxtaposition
above-mentioned
mechanisms,
dysregulates
gut
microbiome
support
its
replication
dissemination
process.
interconnected
Immunometabolism,
Cellular
stress,
Host
Microbiome,
Extracellular
less
explored
realm
exploration
novel
Host-directed
therapies
TB.
Therefore,
this
review
highlights
intertwined
control
survival
showcases
important
factors
be
targeted
designing
efficacious
therapy.
Abstract
Osteoarthritis
(OA)
is
widely
recognized
as
the
prevailing
joint
disease
associated
with
aging.
The
ketogenic
diet
(KD)
has
been
postulated
to
impede
advancement
of
various
inflammatory
ailments.
β‐Hydroxybutyrate
(βOHB),
a
prominent
constituent
ketone
bodies,
recently
proposed
possess
crucial
signaling
capabilities.
In
this
study,
we
propose
explore
role
and
mechanism
βOHB
in
OA.
Tissue
staining
factor
assay
were
employed
evaluate
impacts
KD
on
OA
rats.
oxidative
stress
conditions
chondrocytes
induced
using
tert‐butyl
hydroperoxide
(TBHP).
mechanisms
determined
siRNA
hydroxycarboxylic
acid
receptor
2
(HCAR2),
antagonist
adenosine
monophosphate‐activated
protein
kinase
(AMPK),
inhibitor
mitophagy.
administration
demonstrated
reduction
pathological
damage
cartilage,
well
decrease
plasma
levels
factors.
Furthermore,
it
resulted
an
increase
concentration
blood
synovial
fluid.
vitro
experiments
showed
that
facilitated
mitophagy
triphosphate
production.
Besides,
mitigated
chondrocyte
senescence,
factors
secretion,
extracellular
matrix
degradation,
apoptosis
by
TBHP.
Subsequent
investigations
indicated
protective
effects
no
longer
observed
following
knockdown
HCAR2,
AMPK,
or
Moreover,
vivo
studies
suggested
played
targeting
HCAR2‐AMPK‐PINK1
axis.
conclusion,
enhanced
through
HCAR2/AMPK/PINK1/Parkin
pathway,
offering
potential
therapeutic
approach
for
treatment
Cell chemical biology,
Год журнала:
2024,
Номер
31(5), С. 862 - 883
Опубликована: Фев. 29, 2024
The
immune
system
shapes
tumor
development
and
progression.
Although
immunotherapy
has
transformed
cancer
treatment,
its
overall
efficacy
remains
limited,
underscoring
the
need
to
uncover
mechanisms
improve
therapeutic
effects.
Metabolism-associated
processes,
including
intracellular
metabolic
reprogramming
intercellular
crosstalk,
are
emerging
as
instructive
signals
for
anti-tumor
immunity.
Here,
we
first
summarize
roles
of
pathways
in
controlling
cell
function
microenvironment.
How
communication
regulates
immunity,
impact
metabolites
or
nutrients
on
signaling
events,
also
discussed.
We
then
describe
how
targeting
cells
intratumoral
via
nutrient-based
interventions
may
boost
immunotherapies.
Finally,
conclude
with
discussions
profiling
functional
perturbation
methods
activity
cells,
perspectives
future
directions.
Uncovering
rewiring
microenvironment
enable
novel
