Cytokine,
Journal Year:
2023,
Volume and Issue:
171, P. 156370 - 156370
Published: Sept. 16, 2023
Chemotherapy-induced
peripheral
neuropathy
(CIPN)
is
a
common
side
effect
of
several
antitumor
agents
resulting
in
progressive
and
often
irreversible
damage
nerves.
In
addition
to
their
known
anticancer
effects,
taxanes,
including
paclitaxel,
can
also
induce
by
activating
microglia
astrocytes,
which
release
pro-inflammatory
cytokines
such
as
tumor
necrosis
factor-alpha
(TNF-α),
interleukin
1-beta
(IL-1β),
chemokine
(C-C
motif)
ligand
2
(CCL-2).
All
these
events
contribute
the
maintenance
neuropathic
or
inflammatory
response.
Complement
component
5a
(C5a)/C5a
receptor
1
(C5aR1)
signaling
was
very
recently
shown
play
crucial
role
paclitaxel-induced
neuropathy.
Our
recent
findings
highlighted
that
taxanes
have
previously
unreported
property
binding
C5aR1,
C5aR1
inhibition
DF3966A
effective
preventing
(PIPN)
animal
models.
Here,
we
investigated
if
maintains
efficacy
reducing
PIPN
therapeutic
setting.
Furthermore,
characterized
activation
paclitaxel
CIPN-associated
nod-like
(NLR)
family
pyrin
domain
containing
3
(NLRP3)
inflammasome.
results
clearly
show
administration
inhibitor
strongly
reduced
cold
mechanical
allodynia
mice
when
given
both
during
onset
well
established.
found
be
key
event
induction
factors
spinal
cord,
TNF-α,
ionized
calcium-binding
adapter
molecule
(Iba-1),
glial
fibrillary
acidic
protein
(GFAP).
addition,
significantly
mitigated
inflammation
inflammasome
IL-1β
NLRP3
expression
at
sciatic
dorsal
root
ganglia
level,
confirming
involvement
PIPN.
Moreover,
upregulation
treatment
central
nervous
system.
Lastly,
antinociceptive
confirmed
an
vitro
model
sensory
neurons
focused
on
channels
usually
activated
upon
conclusion,
proposed
option
with
potential
exert
long-term
protective
PIPN-associated
pain
inflammation.
ACS Chemical Neuroscience,
Journal Year:
2023,
Volume and Issue:
15(1), P. 56 - 70
Published: Dec. 18, 2023
The
majority
of
research
on
the
long-term
effects
spinal
cord
injury
(SCI)
has
primarily
focused
neuropathic
pain
(NP),
psychological
issues,
and
sensorimotor
impairments.
Among
SCI
patients,
mood
disorders,
such
as
anxiety
depression,
have
been
extensively
studied.
It
found
that
chronic
stress
NP
negative
consequences
reduce
quality
life
for
individuals
living
with
SCI.
Our
review
examined
both
human
experimental
evidence
to
explore
connection
between
changes
following
inflammatory
pathways,
a
specific
focus
NLRP3
inflammasome
signaling.
We
observed
increased
proinflammatory
factors
in
blood,
well
brain
tissues
models.
plays
crucial
role
various
diseases
by
controlling
release
molecules
like
interleukin
1β
(IL-1β)
IL-18.
Dysregulation
key
regions
associated
processing,
prefrontal
cortex
hippocampus,
contributes
development
disorders
In
this
review,
we
summarized
recent
expression
regulation
components
related
signaling
Finally,
discussed
potential
therapeutic
approaches
target
regulate
cytokines
way
treat
Advanced Science,
Journal Year:
2024,
Volume and Issue:
11(17)
Published: March 2, 2024
Abstract
Peripheral
nerve
injury
(PNI)
remains
a
challenging
area
in
regenerative
medicine.
Nerve
guide
conduit
(NGC)
transplantation
is
common
treatment
for
PNI,
but
the
prognosis
of
NGC
unsatisfactory
due
to
1)
neuromechanical
unmatching
and
2)
intra‐conduit
inflammatory
microenvironment
(IME)
resulting
from
Schwann
cell
pyroptosis
inflammatory‐polarized
macrophages.
A
neuromechanically
matched
composed
regenerated
silk
fibroin
(RSF)
loaded
with
poly(3,4‐ethylenedioxythiophene):
poly(styrene
sulfonate)
(P:P)
dimethyl
fumarate
(DMF)
are
designed,
which
exhibits
elastic
modulus
(25.1
±
3.5
MPa)
peripheral
highest
80%
elongation
at
break,
better
than
most
protein‐based
conduits.
Moreover,
can
gradually
regulate
IME
by
releasing
DMF
monitoring
sciatic
movements
via
piezoresistive
sensing.
The
combination
electrical
stimulation
modulates
support
PNI
regeneration
synergistically
inhibiting
reducing
factor
release,
shifting
macrophage
polarization
M1
phenotype
tissue
M2
functional
recovery
neurons.
In
rat
crush
model,
promoted
remyelination
structural
regeneration.
Generally,
DMF/RSF/P:P
provides
new
potential
therapeutic
approach
promote
repair
future
clinical
treatments.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(6), P. 1256 - 1256
Published: June 5, 2024
Nerve
injury
is
a
common
condition
that
occurs
as
result
of
trauma,
iatrogenic
injury,
or
long-lasting
stimulation.
Unlike
the
central
nervous
system
(CNS),
peripheral
(PNS)
has
strong
capacity
for
self-repair
and
regeneration.
Peripheral
nerve
results
in
degeneration
distal
axons
myelin
sheaths.
Macrophages
Schwann
cells
(SCs)
can
phagocytose
damaged
cells.
Wallerian
(WD)
makes
whole
axon
structure
degenerate,
creating
favorable
regenerative
environment
new
axons.
After
macrophages,
neutrophils
other
are
mobilized
recruited
to
site
necrotic
debris.
Pro-inflammatory
anti-inflammatory
factors
involved
inflammatory
response
provide
microenvironment
regeneration
regulate
effects
inflammation
on
body
through
relevant
signaling
pathways.
Previously,
was
thought
be
detrimental
body,
but
further
research
shown
appropriate
promotes
regeneration,
formation.
On
contrary,
excessive
cause
tissue
damage
pathological
changes,
even
lead
neurological
diseases.
Therefore,
after
various
interact
with
cytokines
chemokines
promote
repair
by
inhibiting
negative
harnessing
positive
specific
ways
at
times.
Understanding
interaction
between
neuroinflammation
provides
several
therapeutic
ideas
improve
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(2), P. 1186 - 1186
Published: Jan. 18, 2024
Major
depressive
disorder
(MDD)
is
a
common
complication
of
diabetes
and
often
observed
alongside
diabetic
neuropathic
pain
(DNP)
as
comorbidity
in
patients.
Long
non-coding
RNA
(lncRNA)
plays
an
important
role
various
pathophysiological
processes.
The
P2X7
receptor
responsible
for
triggering
inflammatory
responses,
such
pyroptosis,
linked
to
depression.
aim
this
study
was
investigate
the
effect
lncRNA
MSTRG.81401
on
hippocampal
pyroptosis
induced
by
rats
with
DNP
combined
MDD
(DNP
+
MDD).
Our
results
showed
that
expression
significantly
elevated
hippocampus
compared
control
group.
Following
administration
shRNA
targeting
MSTRG.81401,
notable
elevation
mechanical
thermal
thresholds
comorbid
MDD.
Additionally,
significant
improvements
depression-like
behaviors
were
evident
open-field
test
(OFT),
sucrose
preference
(SPT),
forced
swim
(FST).
In
rats,
levels
mRNA
protein
observed,
along
increased
co-expression
astrocytic
marker
glial
fibrillary
acidic
(GFAP).
Meanwhile,
heightened
NOD-like
3
(NLRP3),
apoptosis-associated
speck-like
(ASC),
pyroptosis-related
Gasdermin
D
(GSDMD),
caspase-1,
IL-1β,
IL-18,
TNF-α
detected,
addition
serum
IL-18
TNF-α.
After
treatment
above
abnormal
changes
indicators
inflammation
improved.
Therefore,
our
demonstrates
can
alleviate
associated
inhibiting
receptor-mediated
pathway
pro-inflammatory
responses.
This
suggests
P2X7R/NLRP3/caspase-1
implicated
scenario
may
serve
potential
target
management
diabetes.
Abstract
Aims
This
study
aimed
to
investigate
the
potential
therapeutic
applications
of
stigmasterol
for
treating
neuropathic
pain.
Methods
Related
mechanisms
were
investigated
by
DRG
single‐cell
sequencing
analysis
and
use
specific
inhibitors
in
cellular
experiments.
In
animal
experiments,
32
male
Sprague–Dawley
rats
randomly
divided
into
sham
operation
group,
CCI
ibuprofen
group.
We
performed
behavioral
tests,
ELISA,
H&E
staining
immunohistochemistry,
western
blotting.
Results
Cell
communication
reveals
that
after
peripheral
nerve
injury,
Schwann
cells
secrete
IL‐34
act
on
CSF1R
macrophages.
After
mRNA
expression
levels
pathway
NLRP3
inflammasome
macrophages
increased
DRG.
vitro
studies
demonstrated
can
reduce
secretion
LPS‐induced
RSC96
cells;
treatment
cell‐conditioned
medium
(L‐S‐CM)
does
not
induce
proliferation
migration
RAW264.7
macrophages;
L‐S‐CM
reduces
signaling
(CSF1R,
P38MAPK,
NFκB)
activation,
ROS
production.
vivo
experiments
have
verified
thermal
cold
hyperalgesia
rat
chronic
compressive
injury
(CCI)
model;
IL‐1β,
IL‐6,
TNF‐α,
CCL2,
SP,
PGE2
serum
rats;
immunohistochemistry
blot
confirmed
IL‐34/CSF1R
rats.
Conclusion
Stigmasterol
alleviates
pain
reducing
cell‐macrophage
cascade
modulating
axis.
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: May 25, 2023
Postherpetic
neuralgia
(PHN)
is
a
debilitating
complication
of
herpes
zoster,
characterized
by
persistent
neuropathic
pain
that
significantly
impairs
patients'
quality
life.
Identifying
factors
determine
PHN
susceptibility
crucial
for
its
management.
Interleukin-18
(IL-18),
pro-inflammatory
cytokine
implicated
in
chronic
pain,
may
play
critical
role
development.In
this
study,
we
conducted
bidirectional
two-sample
Mendelian
randomization
(MR)
analyses
to
assess
genetic
relationships
and
potential
causal
associations
between
IL-18
protein
levels
increasing
risk,
utilizing
genome-wide
association
study
(GWAS)
datasets
on
these
traits.
Two
obtained
from
the
EMBL's
European
Bioinformatics
Institute
database
which
contained
21,758
individuals
with
13,102,515
SNPs
Complete
GWAS
summary
data
3,394
5,270,646
SNPs.
The
dataset
FinnGen
biobank
had
195,191
16,380,406
SNPs.Our
findings
two
different
suggest
correlation
genetically
predicted
elevations
an
increased
PHN.(IVW,
OR
95%
CI:
2.26,
1.07
4.78;
p
=
0.03
2.15,
1.10
4.19;
=0.03,
respectively),
potentially
indicating
effect
risk.
However,
did
not
detect
any
liability
risk
levels.These
new
insights
into
identifying
at
developing
aid
development
novel
prevention
treatment
approaches
PHN.
Cell Biology International,
Journal Year:
2024,
Volume and Issue:
48(6), P. 872 - 882
Published: March 13, 2024
Abstract
Oxaliplatin
(OXA)
has
shown
high
effectiveness
in
the
treatment
of
cancers,
but
its
anticancer
clinical
effects
often
induce
neurotoxicity
leading
to
neuropathic
pain.
Oxidative
damage
and
NLRP3
inflammasome
play
important
roles
pain
development.
Here,
mouse
model
was
constructed
by
continuous
intraperitoneal
injection
OXA.
OXA
administration
induced
mechanical
pain,
spontaneous
thermal
hyperalgesia
motor
disability
mice.
The
spinal
cord
tissues
mice
exhibited
suppressed
antioxidative
response,
activated
mediated
inflammatory
responses,
increased
GSK‐3β
activity.
Next,
we
injected
curcumin
(CUR)
intraperitoneally
for
seven
consecutive
days.
CUR‐treated
showed
thresholds,
reduced
number
flinches,
paw
withdrawal
latency,
restored
latency
fall.
While
cord,
CUR
inhibited
Nrf2/GPX4‐mediated
antioxidant
decreased
mitochondrial
oxidative
generation.
Additionally,
combined
with
through
four
covalent
bonds
In
conclusion,
our
findings
suggest
that
inhibits
activation,
increases
Nrf2
reaction,
alleviates
OXA‐induced
Journal of Inflammation Research,
Journal Year:
2024,
Volume and Issue:
Volume 17, P. 3839 - 3864
Published: June 1, 2024
Pyroptosis
is
a
pro-inflammatory
form
of
cell
death
resulting
from
the
activation
gasdermins
(GSDMs)
pore-forming
proteins
and
release
several
factors.
However,
inflammasomes
are
intracellular
protein
complexes
that
cleave
gasdermin
D
(GSDMD),
leading
to
formation
robust
membrane
pores
initiation
pyroptosis.
Inflammasome
gasdermin-mediated
pore
important
intrinsic
processes
in
classical
pyroptotic
signaling
pathway.
Overactivation
NOD-like
receptor
thermal
domain
associated
3
(NLRP3)
inflammasome
triggers
pyroptosis
amplifies
inflammation.
Current
evidence
suggests
overactivation
may
further
induce
progression
cancers,
nerve
injury,
inflammatory
disorders
metabolic
dysfunctions.
also
indicates
pyroptosis-dependent
accelerates
diabetes
its
frequent
consequences
including
diabetic
peripheral
neuropathy
(DPN).
Pyroptosis-mediated
reaction
exacerbates
DPN-mediated
CNS
injury.
Accumulating
shows
molecular
mechanisms
trigger
insulin-producing
cells,
development
DPN.
Numerous
studies
have
suggested
certain
natural
compounds
or
drugs
possess
promising
pharmacological
properties
by
modulating
pyroptosis,
thereby
offering
potential
preventive
practical
therapeutic
approaches
for
treatment
management
This
review
elaborates
on
underlying
explores
possible
strategies
regulating
pyroptosis-regulated