Analytical Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 20, 2024
Hepatic
ischemia-reperfusion
injury
(HIRI)
and
induced
systemic
inflammation
is
a
time-dependent
multistage
process
which
poses
risk
of
causing
direct
hepatic
dysfunction
multiorgan
failure.
Real-time
in
situ
comprehensive
visualization
assessment
important
scarce
for
imaging-guided
therapeutic
interventions
timely
efficacy
evaluation.
Here,
logically
activatable
nanoreporter
(termed
QD@IR783-TK-FITC)
developed
time-phase
imaging
quantification
HIRI
inflammation.
The
nanoreporters
could
be
used
vivo
ratiometric
NIR-IIb
fluorescence
sensing
reactive
oxygen
species
(ROS),
can
depict
the
ROS
fluctuation
early
diagnosis
initial
3
h.
Meanwhile,
ROS-specific
reaction
releases
renal-clearable
fluorophore
fragments
from
monitoring
systematic
by
via
longitudinal
urinalysis.
In
addition,
functional
relationship
between
digitized
signal
outputs
(NIR-IIb
ratios,
urinary
fluorescence)
with
scores
has
been
established,
realizing
precise
prediction
severity
preassessment
efficacy.
Such
time-phased
modular
toolbox
dynamically
report
HIRI-induced
vivo,
providing
an
efficient
approach
treatment.
Neuroinflammation
is
a
critical
factor
in
the
progression
of
cerebral
ischemia-reperfusion
injury
(CIRI).
Pyroptosis,
which
an
inflammatory
form
programmed
cell
death,
greatly
amplifies
neuroinflammatory
processes.
It
does
so
by
promoting
release
various
contents
that
intensify
overall
response
within
central
nervous
system.
Therefore,
targeting
pyroptosis
represents
promising
therapeutic
strategy
for
treatment
CIRI.
Excessive
generation
reactive
oxygen
species
(ROS)
overactivated
microglia
considered
to
serve
as
signal
molecule
triggers
NLRP3
inflammasome-mediated
pyroptosis.
However,
current
inhibitors
solely
focus
on
eliminating
existing
ROS
or
inhibiting
inflammasome
are
not
optimal.
Here,
coating
nanothylakoids
(NTs)
coengineered
with
fibrin-binding
peptide
and
MG1
onto
dihydrotanshinone
I
(DT)-loaded
nanocarriers,
we
have
developed
cascade-type
inhibitor
(MDN-MC)
comprehensively
regulates
ROS/NLRP3/pyroptosis
axis.
The
incorporation
catalase
surface
MDN-MC,
along
DT,
facilitated
cascade
inhibition
scavenging
suppressing
expression
NLRP3.
In
rat
model
transient
middle
artery
occlusion,
enhanced
behavioral
recovery
neuronal
repair
were
achieved
through
at
lesion
site
implementation
interventions
inhibit
pyroptosis,
thereby
demonstrating
effects.
Overall,
this
work
emphasizes
importance
cascade-regulated
reducing
neuroinflammation,
offering
important
mechanistic
understanding
possible
approaches
Advanced Functional Materials,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 23, 2025
Abstract
Spinal
cord
injury
(SCI)
constitutes
a
critical
occurrence
that
results
in
the
disruption
of
both
motor
and
sensory
functions.
Oxidative
stress‐induced
apoptosis
pyroptosis
have
been
identified
as
contributors
to
neuronal
damage
during
secondary
phase
following
SCI.
Therefore,
this
study
focuses
on
development
self‐enhancing
drug
pair‐driven
selenium
(Se)
nanotherapeutics,
loading
with
2,3,5,6‐tetramethylpyrazine
(TMP)
Ginsenoside
Rg1
(Rg1),
enhance
treatment
The
engineered
LET/TMP/Rg1@Se
NPs
exhibits
remarkable
antioxidant
properties,
effectively
reducing
oxidative
by
minimizing
reactive
oxygen
species
(ROS)
accumulation
restoring
mitochondrial
function.
In
addition
their
effects,
nanotherapeutics
demonstrates
significant
anti‐pyroptotic
effects
BV2
microglial
cells
modulating
NLRP3/caspase‐1
pathway,
leading
decreased
release
pro‐inflammatory
cytokines
IL‐1β
IL‐18.
Moreover,
inhibition
inflammatory
cascade
response
diminishes
neuroinflammation‐induced
promotes
axonal
regeneration
neurons
vitro.
mouse
model
SCI,
improved
function
regeneration,
attributed
pyroptosis,
highlighting
scientific
basis
for
synergistic
effect
Se
an
innovative
strategy
effective
SCI
therapy.
Abstract
Mitochondrial
double-stranded
RNA
(mtdsRNA),
a
long-stranded
molecule
generated
by
bidirectional
transcription
of
the
circular
mitochondrial
genome,
can
trigger
type
1
interferon
response
activating
pattern
recognition
receptors
in
cytoplasm
during
dysfunction.
However,
its
regulatory
and
pathogenic
mechanisms
intervertebral
disc
degeneration
are
poorly
understood.
Here,
we
showed
that
mtdsRNA
was
abnormally
elevated
degenerative
nucleus
pulposus
tissues.
Furthermore,
found
leakage
into
could
cause
MAVS
oligomerization
binding
to
RLRs,
oligomerized
then
promote
cell
pyroptosis
NLRP3.
To
further
elucidate
upstream
mechanism
mtdsRNA,
performed
untargeted
metabolomics
analysis,
which
revealed
downregulation
taurine
under
external
stimuli
drive
an
imbalance
homeostasis.
RNA-seq
exogenous
supplementation
with
protected
cells
from
mtdsRNA-induced
increasing
mitophagy.
In
conclusion,
our
study
links
metabolism,
nucleic
acids
suggests
is
important
causative
potential
therapeutic
target
degeneration.
Pharmaceutics,
Год журнала:
2024,
Номер
16(8), С. 979 - 979
Опубликована: Июль 24, 2024
Intervertebral
disc
degeneration
(IVDD)
stands
as
the
foremost
contributor
to
low
back
pain
(LBP),
imposing
a
substantial
weight
on
world
economy.
Traditional
treatment
modalities
encompass
both
conservative
approaches
and
surgical
interventions;
however,
former
falls
short
in
halting
IVDD
progression,
while
latter
carries
inherent
risks.
Hence,
quest
for
an
efficacious
method
reverse
onset
is
paramount.
Biomaterial
delivery
systems,
exemplified
by
hydrogels,
microspheres,
microneedles,
renowned
their
exceptional
biocompatibility,
biodegradability,
biological
efficacy,
mechanical
attributes,
have
found
widespread
application
bone,
cartilage,
various
tissue
engineering
endeavors.
Consequently,
IVD
has
emerged
burgeoning
field
of
interest.
This
paper
succinctly
introduces
intervertebral
(IVD)
structure
pathophysiology
IVDD,
meticulously
classifies
biomaterials
repair,
reviews
recent
advances
field.
Particularly,
strengths
weaknesses
are
emphasized,
potential
avenues
future
research
suggested.
