Applied Sciences,
Год журнала:
2024,
Номер
14(23), С. 11376 - 11376
Опубликована: Дек. 6, 2024
Rat
dental
pulp
stem
cells
(DPSCs)
can
be
used
to
elucidate
mesenchymal
cell
(MSC)
applications
in
regenerative
medicine.
However,
information
on
rat
DPSCs
during
long-term
passage,
which
could
lead
replicative
senescence,
is
limited.
In
this
study,
we
investigated
the
phenotypic
changes
after
3–26
passages
(3P–26P).
The
results
show
that
morphology
and
nuclear
size
increase
proportionally
with
passage
number.
phosphorylated
histone
H2A.X
(γ-H2A.X)
positive
(indicating
DNA
damage)
increased
significantly
earlier
than
4-Hydroxynonenal
(4-HNE)
stained
an
abundance
of
intracellular
reactive
oxygen
species).
Compared
subjected
3P
5P,
15P
showed
reduced
proliferation
despite
being
for
Ki67.
Furthermore,
growth
was
completely
arrested
26P.
senescence
markers,
senescence-associated
β-galactosidase
(SA-β-gal)
p16,
exhibited
similar
expression
patterns
were
not
correlated
those
p21
urokinase-type
plasminogen
activator
receptor
(uPAR).
Nearly
all
expressed
SA-β-gal
p16
26P,
whereas
only
half
uPAR.
These
will
contribute
understanding
characteristics
toward
are
applicable
mechanisms
related
medicine
aging.
Journal of Neuroinflammation,
Год журнала:
2025,
Номер
22(1)
Опубликована: Фев. 7, 2025
Mitochondrial
dysfunction
is
a
pivotal
instigator
of
neuroinflammation,
with
mitochondrial
DNA
(mtDNA)
leakage
as
critical
intermediary.
This
review
delineates
the
intricate
pathways
leading
to
mtDNA
release,
which
include
membrane
permeabilization,
vesicular
trafficking,
disruption
homeostatic
regulation,
and
abnormalities
in
dynamics.
The
escaped
activates
cytosolic
sensors,
especially
cyclic
gmp-amp
synthase
(cGAS)
signalling
inflammasome,
initiating
neuroinflammatory
cascades
via
pathways,
exacerbating
spectrum
neurological
pathologies.
therapeutic
promise
targeting
discussed
detail,
underscoring
necessity
for
multifaceted
strategy
that
encompasses
preservation
homeostasis,
prevention
leakage,
reestablishment
dynamics,
inhibition
activation
sensors.
Advancing
our
understanding
complex
interplay
between
neuroinflammation
imperative
developing
precision
interventions
disorders.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Апрель 7, 2025
The
activation
of
microglia
and
the
resulting
neuroinflammation
play
crucial
regulatory
roles
in
pathogenesis
progression
neurological
diseases,
although
specific
mechanisms
remain
incompletely
understood.
Cytidine
monophosphate
kinase
2
(CMPK2)
is
a
key
mitochondrial
nucleotide
involved
cellular
energy
metabolism
synthesis.
Recent
studies
suggest
that
CMPK2
plays
role
microglial-mediated
neuroinflammation;
however,
its
impact
on
microglial
remains
unclear.
In
this
study,
we
hypothesize
promotes
by
activating
cGAS-STING
signaling
pathway.
To
investigate
mechanism,
employed
lipopolysaccharide
(LPS)-treated
cells
to
detailed
which
regulates
neuroinflammation.
Our
experimental
results
indicate
BV2
mouse
primary
model,
both
protein
transcript
levels
were
significantly
elevated,
accompanied
phenotypes
such
as
increased
cell
size,
shortened
processes,
transformation
round
or
rod-like
shapes,
elevated
CD40
expression.
Concurrently,
there
was
an
increase
pro-inflammatory
cytokine
decrease
anti-inflammatory
levels.
Further
investigation
revealed
microglial,
expression
cGAS
STING
along
with
oxidative
products
inflammatory
responses.
CMA
stimulation
further
intensified
these
changes,
while
knockdown
mitigated
them.
Finally,
demonstrated
inhibited
stress,
activation-related
neuroinflammatory
responses
induced
overexpression
model.
Molecular
docking
experiments
showed
stably
binds
at
level.
These
findings
pathway
mediates
CMPK2-induced
activation.
summary,
our
study
demonstrates
LPS-induced
overactivity
through
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 13, 2025
Abstract
The
scarcity
of
effective
neuroprotective
agents
and
the
presence
blood‐brain
barrier
(BBB)‐mediated
extremely
inefficient
intracerebral
drug
delivery
are
predominant
obstacles
to
treatment
cerebral
ischemic
stroke
(CIS).
Herein,
ROS‐responsive
borneol‐based
amphiphilic
polymeric
NPs
constructed
by
using
traditional
Chinese
medicine
borneol
as
functional
blocks
that
served
surface
brain‐targeting
ligand,
inner
hydrophobic
core
for
efficient
loading
membrane‐permeable
calcium
chelator
BAPTA‐AM,
structural
component.
In
MCAO
mice,
nanoformulation
(polymer:
3.2
mg·kg
−1
,
BAPTA‐AM:
400
µg·kg
)
reversibly
opened
BBB
achieved
high
brain
biodistribution
up
12.7%ID/g
total
administered
dose
after
3
h
post
single
injection,
effectively
restoring
intracellular
Ca
2+
redox
homeostasis,
improving
histopathology,
inhibiting
mitochondrial
PI3K/Akt/Bcl‐2/Bax/Cyto‐C/Caspase‐3,9
apoptosis
pathway
rescuing
dying
neurons
(reduced
cell
from
59.5%
7.9%).
It
also
remodeled
inflammatory
microenvironment
in
penumbra
astrocyte
over‐activation,
reprogramming
microglia
polarization
toward
an
anti‐inflammatory
phenotype,
blocking
NF‐κB/TNF‐
α
/IL‐6
signaling
pathways.
These
interventions
eventually
reduced
infarction
area
96.3%,
significantly
improved
neurological
function,
restored
blood
flow
reperfusion
66.2%
≈100%,
all
while
facilitating
repair
avoiding
edema.
This
provides
a
potentially
multiple‐stage
sequential
strategy
clinical
CIS.
Cellular and Molecular Immunology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 13, 2025
Abstract
Neuroinflammation
plays
an
important
role
in
the
pathogenesis
of
various
central
nervous
system
(CNS)
diseases.
The
NLRP3
inflammasome
is
intracellular
multiprotein
complex
composed
innate
immune
receptor
NLRP3,
adaptor
protein
ASC,
and
protease
caspase-1.
activation
can
induce
pyroptosis
release
proinflammatory
cytokines
IL-1β
IL-18,
thus
playing
a
inflammatory
responses.
Recent
studies
have
revealed
that
activated
brain
to
neuroinflammation,
leading
further
neuronal
damage
functional
impairment,
contributes
pathological
process
neurological
diseases,
such
as
multiple
sclerosis,
Parkinson’s
disease,
Alzheimer’s
stroke.
In
this
review,
we
summarize
neuroinflammation
course
CNS
diseases
discuss
potential
approaches
target
for
treatment
