Immune-cell
reprogramming
driven
by
mitochondria-derived
reactive
electrophilic
immunometabolites
(mt-REMs—e.g.,
fumarate,
itaconate)
is
an
emerging
phenomenon
of
major
biomedical
importance.
Despite
their
localized
production,
mt-REMs
elicit
significantly-large
local
and
global
footprints
within
across
cells,
through
mechanisms
involving
electrophile
signaling.
Burgeoning
efforts
are
being
put
into
profiling
mt-REMs’
potential
protein-targets
phenotypic
mapping
multifaceted
inflammatory
behaviors.
Yet,
precision
indexing
first-responders
with
spatiotemporal
intelligence
locale-specific
function
assignments
remains
elusive.
Highlighting
the
latest
advances
overarching
challenges,
this
perspective
aims
to
stimulate
thoughts
spur
interdisciplinary
innovations
address
these
unmet
chemical-biotechnological
needs
at
therapeutic
immuno-signaling
frontiers.
Heliyon,
Год журнала:
2023,
Номер
9(7), С. e17909 - e17909
Опубликована: Июль 1, 2023
BackgroundPerforator
flaps
are
widely
used
in
hand
microsurgery
to
reconstruct
and
repair
soft
tissue
injuries.
However,
ischemia
subsequent
ischemia-reperfusion
injury
may
cause
distal
necrosis
of
the
flap.
Itaconic
acid
(IA)
is
a
modulator
macrophage
function,
which
exerts
anti-inflammatory
effects
activation.MethodsThe
necrotic
area
flap
was
detected
by
measuring
temperature
with
an
infrared
thermometer.
Flap
cell
apoptosis
TUNEL
staining
Western
blot
analysis
apoptosis-associated
proteins
Bcl-2
Bax.
HE
detect
angiogenesis
skin
flaps.
CD31
identify
positive
vascular
expression,
survival
choke
vessels
different
areas
assessed
arteriography.
In
addition,
performed
quantify
expressions
VEGF,
Nrf2,
LC3II,
SQSTM1,
CTSD.ResultsItaconic
raises
VEGF
protein
levels
number
CD31-positive
vessels.
The
IA
treatment
group
exhibited
higher
neovascularization
less
than
those
control
group.
results
revealed
that
attenuated
ischemic
combination
itaconic
Nrf2
inhibitor
ML385
reversed
this
beneficial
effect.
apoptosis,
enhanced
angiogenesis,
autophagy.ConclusionIn
summary,
our
findings
indicate
might
be
effective
reduce
necrosis.
Additionally,
study
identified
novel
mechanism
for
on
survival.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Июнь 11, 2024
Succinate,
traditionally
viewed
as
a
mere
intermediate
of
the
tricarboxylic
acid
(TCA)
cycle,
has
emerged
critical
mediator
in
inflammation.
Disruptions
within
TCA
cycle
lead
to
an
accumulation
succinate
mitochondrial
matrix.
This
excess
subsequently
diffuses
into
cytosol
and
is
released
extracellular
space.
Elevated
cytosolic
levels
stabilize
hypoxia-inducible
factor-1α
by
inhibiting
prolyl
hydroxylases,
which
enhances
inflammatory
responses.
Notably,
also
acts
extracellularly
signaling
molecule
engaging
receptor
1
on
immune
cells,
thus
modulating
their
pro-inflammatory
or
anti-inflammatory
activities.
Alterations
have
been
associated
with
various
disorders,
including
rheumatoid
arthritis,
bowel
disease,
obesity,
atherosclerosis.
These
associations
are
primarily
due
exaggerated
cell
Given
its
central
role
inflammation,
targeting
pathways
offers
promising
therapeutic
avenues
for
these
diseases.
paper
provides
extensive
review
succinate's
involvement
processes
highlights
potential
targets
future
research
possibilities
development.
Cancers,
Год журнала:
2024,
Номер
16(7), С. 1403 - 1403
Опубликована: Апрель 3, 2024
Metabolic
dysfunction
associated
with
obesity
leads
to
a
chronic
pro-inflammatory
state
systemic
effects,
including
the
alteration
of
macrophage
metabolism.
Tumor-associated
macrophages
have
been
linked
formation
cancer
through
production
metabolites
such
as
itaconate.
Itaconate
downregulates
peroxisome
proliferator-activated
receptor
gamma
tumor-suppressing
factor
and
upregulates
anti-inflammatory
cytokines
in
M2-like
macrophages.
Similarly,
leptin
adiponectin
also
influence
cytokine
expression
contribute
progression
colorectal
via
changes
gene
within
PI3K/AKT
pathway.
This
pathway
influences
cell
proliferation,
differentiation,
tumorigenesis.
work
provides
review
obesity-related
hormones
inflammatory
mechanisms
leading
development
early-onset
(EOCRC).
A
literature
search
was
performed
using
PubMed
Cochrane
databases
identify
studies
related
EOCRC,
keywords
'EOCRC',
'obesity',
'obesity-related
hormones',
'itaconate',
'adiponectin',
'leptin',
'M2a
macrophage',
'microbiome'.
With
this
concept
markers
contributing
increased
use
chemo-preventative
agents
aspirin
may
protective
effect.
Elucidating
association
between
obesity-related,
hormone/cytokine-driven
effects
EOCRC
help
lead
new
therapeutic
targets
preventing
treating
EOCRC.
Pharmaceutics,
Год журнала:
2024,
Номер
16(4), С. 444 - 444
Опубликована: Март 23, 2024
There
is
an
increasing
accumulation
of
data
on
the
exceptional
importance
mitochondria
in
occurrence
and
treatment
cancer,
all
lines
evidence
for
such
participation,
there
are
both
energetic
non-bioenergetic
functional
features
mitochondria.
This
analytical
review
examines
three
specific
adaptive
mitochondrial
changes
several
malignant
tumors.
The
first
feature
characteristic
solid
tumors,
whose
cells
forced
to
rebuild
their
energetics
due
absence
oxygen,
namely,
activate
fumarate
reductase
pathway
instead
traditional
succinate
oxidase
that
exists
aerobic
conditions.
For
a
restructuring,
presence
low-potential
quinone
necessary,
which
cannot
ensure
conventional
conversion
into
but
rather
enables
reverse
reaction,
is,
succinate.
In
this
scenario,
complex
I
becomes
only
generator
energy
second
increased
proliferation
aggressive
tumors
so-called
(peripheral)
benzodiazepine
receptor,
also
called
translocator
protein
(TSPO)
residing
outer
membrane,
function
oncogenic
transformation
stays
mysterious.
third
tumor
enhanced
retention
certain
molecules,
particular
mitochondrially
directed
cations
similar
rhodamine
123,
allows
selective
anticancer
drugs
These
can
be
targets
development
anti-cancer
strategy.
Journal of Neuroinflammation,
Год журнала:
2024,
Номер
21(1)
Опубликована: Авг. 20, 2024
Despite
advances
in
antimicrobial
and
anti-inflammatory
treatment,
inflammation
its
consequences
remain
a
major
challenge
the
field
of
medicine.
Inflammatory
reactions
can
lead
to
life-threatening
conditions
such
as
septic
shock,
while
chronic
has
potential
worsen
condition
body
tissues
ultimately
significant
impairment
their
functionality.
Although
central
nervous
system
long
been
considered
immune
privileged
peripheral
responses,
recent
research
shown
that
strong
responses
periphery
also
affect
brain,
leading
reactive
microglia,
which
belong
innate
reside
neuroinflammation.
The
inflammatory
response
is
primarily
protective
mechanism
defend
against
pathogens
tissue
damage.
However,
excessive
have
negative
effects
on
neuronal
structure
function.
Neuroinflammation
underlies
pathogenesis
many
neurological
neurodegenerative
diseases
accelerate
progression.
Consequently,
targeting
signaling
pathways
offers
therapeutic
strategies
for
various
neuropathological
conditions,
particularly
Parkinson's
Alzheimer's
disease,
by
curbing
inflammation.
Here
blood-brain
barrier
hurdle
strategies,
therefore
it
would
be
highly
advantageous
foster
utilize
brain
mechanisms.
tricarboxylic
acid
cycle-derived
metabolite
itaconate
upregulated
activated
macrophages
act
an
immunomodulator
with
functions.
Mesaconate,
isomer
itaconate,
similarly
reduces
macrophages.
Nevertheless,
most
studies
focused
esterified
forms
effects,
influence
CNS
remained
largely
unexplored.
Therefore,
this
study
investigated
immunomodulatory
endogenously
synthesized
mesaconate
lipopolysaccharide
(LPS)-induced
neuroinflammatory
processes.
Our
results
show
both
reduce
LPS-induced
neuroinflammation,
evidenced
lower
levels
mediators,
reduced
microglial
reactivity
rescue
synaptic
plasticity,
cellular
correlate
learning
memory
processes
brain.
Overall,
emphasizes
are
remarkable
importance
due
endogenous
origin
production,
usually
leads
high
tolerance.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Окт. 1, 2024
New
and
emerging
pathogens,
such
as
SARS-CoV2
have
highlighted
the
requirement
for
threat
agnostic
therapies.
Some
antibiotics
or
antivirals
can
demonstrate
broad-spectrum
activity
against
pathogens
in
same
family
genus
but
efficacy
quickly
reduce
due
to
their
specific
mechanism
of
action
ability
disease
causing
agent
evolve.
This
has
led
generation
antimicrobial
resistant
strains,
making
infectious
diseases
more
difficult
treat.
Alternative
approaches
therefore
need
be
considered,
which
include
exploring
utility
Host-Directed
Therapies
(HDTs).
is
a
growing
area
with
huge
potential
difficulties
arise
complexity
profiles.
For
example,
HDT
given
early
during
infection
may
not
appropriate
effective
when
become
chronic
patient
intensive
care.
With
understanding
immune
function,
new
treatment
could
allow
targeting
pathways
augment
diminish
host
response,
dependent
upon
profile,
bespoke
therapeutic
management
plans.
review
highlights
promising
approved
HDTs
that
manipulate
system
throughout
spectrum
disease,
particular
viral
bacterial
demonstrates
how
advantages
will
soon
outweigh
side
effects.
Digestive Diseases and Sciences,
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 4, 2024
In
inflammatory
bowel
diseases
(IBD),
the
most
promising
therapies
targeting
cytokines
or
immune
cell
trafficking
demonstrate
around
40%
efficacy.
As
IBD
is
a
multifactorial
inflammation
of
intestinal
tract,
single-target
approach
unlikely
to
solve
this
problem,
necessitating
an
alternative
strategy
that
addresses
its
variability.
One
often
overlooked
by
pharmaceutically
driven
therapeutic
options
address
impact
environmental
factors.
This
somewhat
surprising
considering
increasingly
viewed
as
condition
heavily
influenced
such
factors,
including
diet,
stress,
and
pollution-often
referred
"Western
lifestyle".
IBD,
responses
result
from
complex
interplay
among
genetic
background
patient,
molecules,
cells,
local
microenvironment
where
danger-
microbe-associated
molecular
patterns
(D/MAMPs)
provide
adjuvant-rich
environment.
Through
activating
DAMP
receptors,
array
pro-inflammatory
factors
can
stimulate,
for
example,
NLRP3
inflammasome-a
major
amplifier
response
in
various
cells
via
non-specific
bystander
activation
myeloid
(e.g.,
macrophages)
lymphocytes
tissue-resident
memory
T
cells).
Current
biological
treatment
approaches
dampen
response,
but
without
reducing
exposure
e.g.,
changing
diet
(reducing
ultra-processed
foods),
landscape
never
resolved
continues
drive
mucosal
dysregulation.
Thus,
are
not
enough
put
out
fire.
The
resultant
smoldering,
low-grade
diminishes
physiological
resilience
(micro)environment,
perpetuating
state
chronic
disease.
Therefore,
our
hypothesis
posits
successful
interventions
must
complexity
disease
simultaneously
all
modifiable
aspects:
innate
immunity
microbiota,
adaptive
cytokines,
relate
(micro)environment.
Thus
be
comprehensively
treated
across
nano-,
meso-,
microscales,
rather
than
with
focus
on
single
targets.
A
broader
perspective
also
includes
adapt
DAMPing
(micro)environment
warranted.
Communications Chemistry,
Год журнала:
2024,
Номер
7(1)
Опубликована: Сен. 2, 2024
Immune-cell
reprogramming
driven
by
mitochondria-derived
reactive
electrophilic
immunometabolites
(mt-REMs—e.g.,
fumarate,
itaconate)
is
an
emerging
phenomenon
of
major
biomedical
importance.
Despite
their
localized
production,
mt-REMs
elicit
significantly
large
local
and
global
footprints
within
across
cells,
through
mechanisms
involving
electrophile
signaling.
Burgeoning
efforts
are
being
put
into
profiling
mt-REMs'
potential
protein-targets
phenotypic
mapping
multifaceted
inflammatory
behaviors.
Yet,
precision
indexing
first-responders
with
spatiotemporal
intelligence
locale-specific
function
assignments
remain
elusive.
Highlighting
the
latest
advances
overarching
challenges,
this
perspective
aims
to
stimulate
thoughts
spur
interdisciplinary
innovations
address
these
unmet
chemical-biotechnological
needs
at
therapeutic
immuno-signaling
frontiers.
(mt-REMs)
Here,
authors
highlight
challenges
in
cellular
responses
assignments.
