ACS Biomaterials Science & Engineering,
Journal Year:
2024,
Volume and Issue:
10(8), P. 4823 - 4838
Published: July 26, 2024
Itaconic
acid
and
its
derivative
4-octyl
itaconate
(OI)
represent
a
novel
anti-inflammatory
medication
that
has
demonstrated
efficacy
in
multiple
inflammation
models
because
of
minimal
side
effects.
Recently,
natural
polymers
conjugated
with
small
molecule
drugs,
known
as
polymer-drug
conjugates
(PDCs),
have
emerged
promising
approach
to
sustained
drug
release.
In
this
work,
we
reported
an
prepare
PDC
containing
OI
make
it
into
injectable
hydrogel.
Chitosan
(CS)
was
selected
for
synthesis
abundant
free
amino
groups
can
be
molecules
carboxyl
by
carbodiimide
chemistry.
We
used
ethanol/water
cosolvent
system
synthesize
CS-OI
conjugate
via
EDC/NHS
catalysis.
The
had
improved
water
solubility
unique
activity
did
not
show
compromised
antibacterial
compared
unmodified
CS.
Beta-glycerophosphate
(β-GP)
cross-linked
hydrogel
exhibited
good
injectability
sustainable
release
effectively
modulated
inflammatory
response
rat
model.
Therefore,
study
provides
valuable
insights
the
design
hydrogels
modulatory
properties.
Communications Biology,
Journal Year:
2022,
Volume and Issue:
5(1)
Published: June 29, 2022
Osteoarthritis
(OA)
is
a
highly
prevalent
and
chronic
disorder
that
associated
with
substantial
social
economic
burden.
Itaconate,
as
an
important
regulator
of
cellular
inflammation,
metabolite
synthesised
by
enzyme
encoded
immune-responsive
gene
1.
However,
there
are
few
studys
regarding
the
effects
itaconate
on
OA.
Here,
we
show
effect
cell-permeable
derivative
4-octyl
(OI)
OI
attenuates
chondrocyte
apoptosis
induced
interleukin
1β
(IL-1β)
in
vitro,
indicating
protect
chondrocytes
against
apoptosis.
Moreover,
ameliorates
autophagy
inhibition
IL-1β
via
PI3K/AKT/mTOR
signalling
pathway.
Finally,
enhances
reduces
cartilage
degradation
rat
model
OA
established
destabilization
medial
meniscus
(DMM).
In
summary,
our
findings
reveal
involved
regulating
progression
The
above
results
shed
light
treatment
Theranostics,
Journal Year:
2022,
Volume and Issue:
12(7), P. 3251 - 3272
Published: Jan. 1, 2022
Rationale:
Inflammatory
macrophages
and
osteoclasts
(OCs)
play
critical
roles
in
joint
inflammation,
which
feature
the
excessive
production
of
reactive
oxygen
species
(ROS),
resulting
synovial
inflammation
bone
erosion.Scavenging
ROS,
especially
by
modulating
mitochondrial
metabolic
activity,
could
be
a
desirable
strategy
for
management
inflammatory
joints.This
study
aimed
to
develop
mitochondria-targeted
supramolecular
drug
delivery
system
with
exogenous
endogenous
ROS-scavenging
activities
treatment
inflammation.Methods:
In
this
study,
we
utilized
zinc-based
metal-organic
supercontainer
(MOSC)
as
proton
sponge
electron
reservoir
outstanding
binding
capacity,
extracellular
ability,
biocompatibility
establish
an
efficient
nanocarrier
endo/lysosomal
escape
targeting.4-Octyl
itaconate
(4-OI),
derivative,
served
loaded
guest
construction
synergistic
therapeutic
OCs.Results:
After
effective
encapsulation
4-OI,
4-OI@Zn-NH-pyr
not
only
exhibited
potent
but
also
reduced
ROS
mediating
respiration
macrophages.Regarding
its
anti-inflammatory
efficacy,
ameliorated
reaction
activating
nuclear
factor
erythroid
2-related
2
(Nrf2),
thus
increasing
antioxidants,
apart
from
inhibition
NF-κB
pathways.Additionally,
receptor
activator
factor-κB
ligand
(RANKL)-induced
osteoclast
differentiation
function
was
remarkably
suppressed
[email protected]
vitro
observations,
efficiently
inhibited
subchondral
destruction
acute
arthritis
model.Conclusion:
By
using
MOSCs
that
are
highly
drug-loaded
matrices
first
time,
provides
avenue
severe
designing
drug-delivery
systems
subcellular
targeting
capacity.
Journal of Cellular and Molecular Medicine,
Journal Year:
2022,
Volume and Issue:
26(5), P. 1515 - 1529
Published: Jan. 23, 2022
Abstract
Small
molecule
drug
intervention
for
chondrocytes
is
a
valuable
method
the
treatment
of
osteoarthritis
(OA).
The
4‐octyl
itaconate
(OI)
cellular
derivative
with
sound
cell
permeability
and
transformation
rate.
We
attempted
to
confirm
protective
role
OI
in
its
regulatory
mechanism.
used
lipopolysaccharide
(LPS)
induce
chondrocyte
inflammation
injury.
After
treatment,
secretion
mRNA
expression
Il
‐
6
,
10
Mcp
1
Tnf
α
were
detected
by
ELISA
qPCR.
effect
on
articular
cartilage
was
further
verified
surgical
destabilization
medial
meniscus
model
OA.
Cell
death
apoptosis
evaluated
based
CCK8,
LDH,
Typan
blue
staining,
Annexin
V
TUNEL
analyses.
small
interfering
RNAs
knockout
Nrf2
gene
verify
OI‐mediated
signalling
pathway.
results
revealed
that
protects
cells
from
LPS‐induced
inflammatory
injury
attenuates
induced
LPS.
Similar
effects
also
observed
mice.
activated
pathway
promoted
stable
translocation
into
nucleus.
When
blocked,
significantly
counteracted
mouse
arthritis
model.
Both
(i.e.,
OI)
showed
important
medical
Antioxidants and Redox Signaling,
Journal Year:
2023,
Volume and Issue:
39(1-3), P. 141 - 161
Published: May 22, 2023
Significance:
The
lack
of
disease-modifying
treatments
for
Alzheimer’s
disease
(AD)
that
substantially
alter
the
course
highlights
need
new
biological
models
progression
and
neurodegeneration.
Oxidation
macromolecules
within
brain,
including
lipids,
proteins,
DNA,
is
believed
to
contribute
AD
pathophysiology,
concomitant
with
dysregulation
redox-active
metals,
such
as
iron.
Creating
a
unified
model
pathogenesis
underpinned
by
iron
redox
in
could
lead
therapeutic
targets
potential.
Recent
Advances:
Ferroptosis,
which
was
named
2012,
necrotic
form
regulated
cell
death
depends
on
both
lipid
peroxidation.
While
it
distinct
from
other
types
death,
ferroptosis
regarded
being
mechanistically
synonymous
oxytosis.
paradigm
has
great
explanatory
potential
describing
how
neurons
degenerate
die
AD.
At
molecular
level,
executed
lethal
accumulation
phospholipid
hydroperoxides
generated
iron-dependent
peroxidation
polyunsaturated
fatty
acids,
while
major
defensive
protein
against
selenoenzyme,
glutathione
peroxidase
4
(GPX4).
An
expanding
network
protective
proteins
pathways
have
also
been
identified
complement
GPX4
protection
cells
ferroptosis,
central
role
emerging
nuclear
factor
erythroid
2-related
2
(NRF2).
Critical
Issues:
In
this
review,
we
provide
critical
overview
utility
NRF2
dysfunction
understanding
iron-
peroxide-associated
neurodegeneration
Future
Directions:
Finally,
discuss
providing
spectrum
targets.
Antioxid.
Redox
Signal.
39,
141–161.
ACS Biomaterials Science & Engineering,
Journal Year:
2024,
Volume and Issue:
10(8), P. 4823 - 4838
Published: July 26, 2024
Itaconic
acid
and
its
derivative
4-octyl
itaconate
(OI)
represent
a
novel
anti-inflammatory
medication
that
has
demonstrated
efficacy
in
multiple
inflammation
models
because
of
minimal
side
effects.
Recently,
natural
polymers
conjugated
with
small
molecule
drugs,
known
as
polymer-drug
conjugates
(PDCs),
have
emerged
promising
approach
to
sustained
drug
release.
In
this
work,
we
reported
an
prepare
PDC
containing
OI
make
it
into
injectable
hydrogel.
Chitosan
(CS)
was
selected
for
synthesis
abundant
free
amino
groups
can
be
molecules
carboxyl
by
carbodiimide
chemistry.
We
used
ethanol/water
cosolvent
system
synthesize
CS-OI
conjugate
via
EDC/NHS
catalysis.
The
had
improved
water
solubility
unique
activity
did
not
show
compromised
antibacterial
compared
unmodified
CS.
Beta-glycerophosphate
(β-GP)
cross-linked
hydrogel
exhibited
good
injectability
sustainable
release
effectively
modulated
inflammatory
response
rat
model.
Therefore,
study
provides
valuable
insights
the
design
hydrogels
modulatory
properties.
