Abstract
Background
Low
back
pain
(LBP)
is
predominantly
caused
by
degeneration
of
the
intervertebral
disc
(IVD)
and
central
nucleus
pulposus
(NP)
region.
Conservative
treatments
fail
to
restore
function,
motivating
exploration
nucleic
acid
therapies,
such
as
use
microRNAs
(miRNAs).
miRNAs
have
potential
modulate
expression
discogenic
factors,
while
silencing
catabolic
cascade
associated
with
degeneration.
To
deliver
these
miRNAs,
nonviral
cell
penetrating
peptides
(CPPs)
are
gaining
favor
given
their
low
immunogenicity
strong
targeting
ability.
Single
miRNA
therapies
been
investigated
for
IVD
repair,
however
dual
delivery
strategies
not
commonly
examined
may
augment
regeneration.
Materials
methods
Transfection
four
pro‐discogenic
(miRNA
mimics:140‐5p;
149‐5p
inhibitors:
141‐3p;
221‐3p)
six
pairings
was
performed
using
two
CPPs,
RALA
GET
peptide
(FLR),
in
primary
rat
NP
monolayer
culture,
an
ex
vivo
organ
culture
model
caudal
discs.
Protein
(aggrecan,
collagen
type
II,
SOX9)
markers
(ADAMTS5
MMP13)
were
assessed.
Results
Monolayer
investigations
signified
enhanced
marker
following
delivery,
signifying
a
synergistic
effect
when
compared
single
transfection.
Utilization
appropriate
emphasized
our
experiment,
revealing
establishment
regenerative
microenvironment
characterized
reduced
enzyme
activity
matrix
deposition,
particularly
concurrent
FLR‐miRNA‐149‐5p
mimic
miRNA‐221‐3p
inhibitor.
Bioinformatics
analysis
miRNA‐149‐5p
inhibitor
identified
distinct
targets,
pathways,
interactions,
suggesting
mode
action
this
amplified
response.
Conclusion
Our
findings
suggest
+
create
anti‐catabolic
niche
within
foster
regeneration
moderate
cases
degeneration,
which
could
be
utilized
further
studies
overarching
aim
developing
LBP.
Bioactive Materials,
Год журнала:
2024,
Номер
37, С. 51 - 71
Опубликована: Март 15, 2024
Intervertebral
disc
degeneration
(IVDD)
can
be
caused
by
aging,
injury,
and
genetic
factors.
The
pathological
changes
associated
with
IVDD
include
the
excessive
accumulation
of
reactive
oxygen
species
(ROS),
cellular
pyroptosis,
extracellular
matrix
(ECM)
degradation.
There
are
currently
no
approved
specific
molecular
therapies
for
IVDD.
In
this
study,
we
developed
a
multifunctional
microenvironment-responsive
metal-phenolic
network
release
platform,
termed
TMP@Alg-PBA/PVA,
which
could
treat
(IL-1β)-induced
(TA-Mn-PVP,
TMP)
released
from
platform
targeted
mitochondria
to
efficiently
scavenge
ROS
reduce
ECM
Pyroptosis
was
suppressed
through
inhibition
IL-17/ERK
signaling
pathway.
These
findings
demonstrate
versatility
platform.
And
in
rat
model
IVDD,
TMP@Alg-PBA/PVA
exhibited
excellent
therapeutic
effects
reducing
progression
disease.
therefore,
presents
clinical
potential
treatment
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
176, С. 116863 - 116863
Опубликована: Июнь 7, 2024
Pyroptosis
is
a
lytic
and
pro-inflammatory
form
of
regulated
cell
death
characterized
by
the
formation
membrane
pores
mediated
gasdermin
protein
family.
Two
main
activation
pathways
have
been
documented:
caspase-1-dependent
canonical
pathway
caspase-4/5/11-dependent
noncanonical
pathway.
leads
to
swelling,
lysis,
subsequent
release
inflammatory
mediators,
including
interleukin-1β
(IL-1β)
interleukin-18
(IL-18).
Chronic
inflammation
well-established
foundation
driver
for
development
metabolic
diseases.
Conversely,
dysregulation
can
also
induce
cellular
pyroptosis.
Recent
studies
highlighted
significant
role
pyroptosis
modulation
in
various
diseases,
type
2
diabetes
mellitus,
obesity,
(dysfunction)
associated
fatty
liver
disease.
These
findings
suggest
that
may
serve
as
promising
novel
therapeutic
target
This
paper
reviews
an
in-depth
study
current
advancements
understanding
progression
ABSTRACT
Background
The
molecular
of
intervertebral
disc
degeneration
(IVDD)
is
still
unclear.
When
it
comes
to
treating
decoction,
traditional
Chinese
medicine
effective.
In
particular,
the
Duhuo
(Radix
Angelicae
Biseratae)
may
be
particularly
helpful.
Purpose
To
identify
nucleus
pulposus
cells
(NPCs)
subpopulations
and
immune
clarify
mechanism
IVDD
therapy,
offering
recommendations
for
diagnosis
treatment.
Methods
targets
from
Genecards
microarray
data
biological
databases.
find
key
genes
pathways
underlying
IVDD,
multiple
machine
learning
techniques
were
used.
associated
with
NPCs
as
revealed
by
single‐cell
analysis,
immunological
infiltration
was
identified
Immune
Cell
AI.
validate
which
activity
affects
network
pharmacology
docking
employed.
Results
process
linked
like
TP53,
JUN,
PTEN,
IL1B,
ERBB2,
MAPK8,
CASP9,
PTK2,
etc.
main
mechanisms
involved
in
this
are
responses,
inflammatory
factors
expression,
cellular
responses
mechanical
stimuli,
NPC
apoptosis.
AI
discovered
a
correlation
between
CD4
naïve,
B
cell,
monocyte,
NK,
macrophage
development
IVDD.
subtypes
namely
fibroNPCs,
adhesion
NPCs,
regulatory
homeostatic
hypertrophic
chondrocyte‐like
(HT‐CL
NPCs),
subject
mapping.
We
also
found
that
Osthole,
Columbianadin,
Bergapten,
principal
blood
entry
components
Dohuo,
have
role
modulating
PTGS1,
PARP1,
Conclusion
exist
HT‐CL
NPCs.
Furthermore,
variety
cell
infiltrates,
monocyte
macrophage,
significant
impact
on
advancement
Duhuo,
absorb
via
controlling
death
Abstract
Intervertebral
disc
(IVD)
herniation
is
a
prevalent
spinal
disorder,
often
necessitating
surgical
intervention
such
as
microdiscectomy
for
symptomatic
relief
and
nerve
decompression.
IVDs
comprise
gel‐like
nucleus
pulposus
(NP)
encased
by
an
annulus
fibrosus
(AF),
their
avascular
nature
renders
them
immune‐privileged.
Microdiscectomy
exposes
the
residual
NP
to
immune
system,
precipitating
cell
infiltration
attack
that
exacerbates
IVD
degeneration.
While
many
efforts
in
tissue
engineering
field
are
directed
toward
regeneration,
inherently
limited
regenerative
capacity
due
low‐cellularity
of
challenging
mechanical
environment
spine
impedes
success.
This
study,
aiming
prevent
degeneration
post‐microdiscectomy,
utilizes
mucin‐derived
gels
(Muc‐gels)
form
gel
at
site,
inspired
natural
mucin
coating
on
living
organisms
evade
reorganization.
It
shown
type
I
macrophages
present
severely
degenerated
human
discs.
Encapsulating
within
Muc‐gels
prevents
fibrous
encapsulation
macrophage
mouse
subcutaneous
model.
The
injection
rat
tail
model
up
24
weeks
post‐operation.
Mechanistic
investigations
indicate
attenuate
into
NPs,
offering
durable
protection
against
post‐microdiscectomy.
Heliyon,
Год журнала:
2023,
Номер
9(9), С. e19951 - e19951
Опубликована: Сен. 1, 2023
Intervertebral
disc
degeneration
(IDD)
has
been
widely
recognized
as
the
primary
cause
of
low
back
pain
and
is
one
major
chronic
diseases
imposing
a
severe
socioeconomic
burden
worldwide.
IDD
degenerative
process
characterized
by
inflammatory
responses,
its
underlying
pathological
mechanisms
remain
complex.
Genetic,
developmental,
biochemical,
biomechanical
factors
contribute
to
development
IDD.
There
pressing
need
for
an
effective
non-surgical
treatment,
mainly
due
lack
comprehensive
understanding
specific
involved
therapeutic
targets
Recently,
interleukin
(IL)-1β
essential
factor
key
mediator
in
Current
studies
have
found
that
IL-1β
affecting
metabolism
extracellular
matrix
regulating
cell
death
(RCD),
such
apoptosis,
pyroptosis,
ferroptosis
(a
new
form
RCD).
Although
analysis
clinical
samples
from
different
laboratories
confirmed
how
induced
IDD,
signal
transduction
pathway,
role
mediated
remains
unclear.
This
review
describes
molecules
IL-1β-mediated
their
roles
resolving
Understanding
signaling
pathways
may
lead
class
promote
remission
patients.
aims
provide
framework
treatment
analyzing
mechanism
function
related
IL-1β,
especially
terms
inflammation,
metabolism,
regulation.
