Microglia,
the
resident
immune
cells
of
central
nervous
system
(CNS),
play
a
crucial
role
in
maintaining
tissue
homeostasis
by
monitoring
and
responding
to
environmental
changes
through
processes
such
as
phagocytosis,
cytokine
production
or
synapse
remodeling.
Their
dynamic
nature
diverse
functions
are
supported
regulation
multiple
metabolic
pathways,
enabling
microglia
efficiently
adapt
fluctuating
signals.
A
key
aspect
this
occurs
at
mitochondria-associated
ER
membranes
(MAM),
specialized
contact
sites
between
mitochondria.
These
structures
facilitate
exchange
calcium,
lipids,
metabolites
serve
signaling
hubs.
This
review
synthesizes
current
research
on
how
MAM
influence
microglial
physiology,
with
an
emphasis
their
immunometabolism,
offering
new
insights
into
integration
CNS
its
impact
context
neurodegeneration.
The
innate
immune
system
serves
as
the
body's
first
line
of
defense,
utilizing
pattern
recognition
receptors
like
Toll-like
to
detect
pathogens
and
initiate
rapid
response
mechanisms.
Following
this
initial
response,
adaptive
immunity
provides
highly
specific
sustained
killing
via
B
cells,
T
antibodies.
Traditionally,
it
has
been
assumed
that
activates
immunity;
however,
recent
studies
have
revealed
more
complex
interactions.
This
review
a
detailed
dissection
composition
function
systems,
emphasizing
their
synergistic
roles
in
physiological
pathological
contexts,
providing
new
insights
into
link
between
these
two
forms
immunity.
Precise
regulation
both
systems
at
same
time
is
beneficial
fight
against
immune-related
diseases,
for
example,
cGAS-STING
pathway
found
play
an
important
role
infections
cancers.
In
addition,
paper
summarizes
challenges
future
directions
field
immunity,
including
latest
single-cell
sequencing
technologies,
CAR-T
cell
therapy,
checkpoint
inhibitors.
By
summarizing
developments,
aims
enhance
our
understanding
complexity
interactions
perspectives
system.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(22), С. 12017 - 12017
Опубликована: Ноя. 8, 2024
The
extracellular
matrix
(ECM)
plays
a
central
role
in
the
structural
integrity
and
functionality
of
cardiovascular
system.
Moreover,
ECM
is
involved
atherosclerotic
plaque
formation
stability.
In
fact,
remodeling
affects
stability,
cellular
migration,
inflammatory
responses.
Collagens,
fibronectin,
laminin,
elastin,
proteoglycans
are
crucial
proteins
during
atherosclerosis
development.
This
dynamic
driven
by
proteolytic
enzymes
such
as
metalloproteinases
(MMPs),
cathepsins,
serine
proteases.
Exploring
investigating
dynamics
an
important
step
to
designing
innovative
therapeutic
strategies
targeting
mechanisms,
thus
offering
significant
advantages
management
diseases.
review
illustrates
structure
vascular
ECM,
presenting
new
perspective
on
its
potential
target
treatments.
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
178, С. 117196 - 117196
Опубликована: Июль 24, 2024
Necroptosis
is
a
crucial
modality
of
programmed
cell
death
characterized
by
distinct
morphological
and
biochemical
hallmarks,
including
membrane
rupture,
organelle
swelling,
cytoplasmic
nuclear
disintegration,
cellular
contents
leakage,
release
damage-associated
molecular
patterns
(DAMPs),
accompanied
the
inflammatory
responses.
Studies
have
shown
that
necroptosis
involved
in
etiology
evolution
variety
pathologies
organ
damage,
inflammation
disorders,
cancer.
Despite
its
significance,
field
research
grapples
with
challenge
non-standardized
detection
methodologies.
In
this
review,
we
introduce
fundamental
concepts
mechanisms
critically
appraise
principles,
merits,
inherent
limitations
current
technologies.
This
endeavor
seeks
to
establish
methodological
framework
for
detection,
thereby
propelling
deeper
insights
into
necroptosis.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 8, 2025
Tumors
can
exert
a
far-reaching
influence
on
the
body,
triggering
systemic
responses
that
contribute
to
debilitating
conditions
like
cancer
cachexia.
To
characterize
mechanisms
underlying
tumor-host
interactions,
we
utilized
BioID-based
proximity
labeling
method
identify
proteins
secreted
by
Yki
act
adult
Drosophila
gut
tumors
into
bloodstream/hemolymph.
Among
major
identified
are
coagulation
and
immune-responsive
factors
wasting
phenotypes
associated
with
tumors.
The
effect
of
innate
immunity
is
mediated
NFκB
transcription
Relish,
dorsal,
Dif,
which
in
turn
upregulate
expression
cachectic
Pvf1,
Impl2,
Upd3.
In
addition,
secrete
Eiger,
TNF-alpha
homolog,
activates
JNK
signaling
pathway
neighboring
non-tumor
cells,
leading
cell
death.
release
damage-associated
molecular
patterns
(DAMPs)
from
these
dying
cells
presumably
amplifies
inflammatory
response,
exacerbating
wasting.
Targeting
pathway,
or
production
could
potentially
alleviate
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.
