ACS Chemical Biology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 17, 2025
Chronic
kidney
fibrosis
poses
a
significant
global
health
challenge
with
effective
therapeutic
strategies
remaining
elusive.
While
cell–extracellular
matrix
(ECM)
interactions
are
known
to
drive
progression,
the
specific
role
of
focal
adhesions
(FAs)
in
is
not
fully
understood.
In
this
study,
we
investigated
FAs
tubular
epithelial
cell
by
employing
precise
nanogold
patterning
modulate
integrin
distribution.
We
demonstrate
that
increasing
ligand
spacing
disrupts
clustering,
thereby
inhibiting
FA
formation
and
attenuating
fibrosis.
Importantly,
enhanced
activity
associated
both
human
disease
specimens
murine
models.
Mechanistically,
regulate
through
mechanotransduction
pathways,
our
vivo
experiments
show
suppressing
significantly
mitigates
mice.
These
findings
highlight
potential
targeting
as
strategy,
offering
new
insights
into
clinical
intervention
Chemical Engineering Journal,
Journal Year:
2024,
Volume and Issue:
488, P. 150631 - 150631
Published: March 26, 2024
The
skeletal
system
is
essential
for
preserving
body
structure
and
facilitating
mobility;
however,
bone
diseases
frequently
result
in
significant
disabilities,
necessitating
the
investigation
into
biomaterials
restoration.
Nevertheless,
these
may
elicit
immune
reactions
that
obstruct
healing
process.
Macrophages
assume
a
pivotal
role
modulating
inflammation
sustaining
homeostasis
regeneration.
A
comprehensive
understanding
of
molecular
interactions
between
macrophages
imperative
development
sophisticated
designed
to
regulate
environment
promote
remodeling.
This
review
delves
generation,
polarization,
interaction
with
principal
cell
types
implicated
osteogenesis,
detailing
mechanisms
by
which
influence
repair
their
response
biomaterials.
Additionally,
it
discusses
strategies
precise
modulation
macrophage
functionality
via
intelligent
mechanisms,
outlines
challenges
constraints
designing
integrate
functions.
By
elucidating
challenges,
lays
groundwork
creation
advanced
endowed
smart
immunomodulatory
capabilities,
heralding
novel
approaches
treatment
defects
advancement
regeneration
therapies.
Signal Transduction and Targeted Therapy,
Journal Year:
2025,
Volume and Issue:
10(1)
Published: March 7, 2025
Redox
signaling
acts
as
a
critical
mediator
in
the
dynamic
interactions
between
organisms
and
their
external
environment,
profoundly
influencing
both
onset
progression
of
various
diseases.
Under
physiological
conditions,
oxidative
free
radicals
generated
by
mitochondrial
respiratory
chain,
endoplasmic
reticulum,
NADPH
oxidases
can
be
effectively
neutralized
NRF2-mediated
antioxidant
responses.
These
responses
elevate
synthesis
superoxide
dismutase
(SOD),
catalase,
well
key
molecules
like
nicotinamide
adenine
dinucleotide
phosphate
(NADPH)
glutathione
(GSH),
thereby
maintaining
cellular
redox
homeostasis.
Disruption
this
finely
tuned
equilibrium
is
closely
linked
to
pathogenesis
wide
range
Recent
advances
have
broadened
our
understanding
molecular
mechanisms
underpinning
dysregulation,
highlighting
pivotal
roles
genomic
instability,
epigenetic
modifications,
protein
degradation,
metabolic
reprogramming.
findings
provide
foundation
for
exploring
regulation
mechanistic
basis
improving
therapeutic
strategies.
While
antioxidant-based
therapies
shown
early
promise
conditions
where
stress
plays
primary
pathological
role,
efficacy
diseases
characterized
complex,
multifactorial
etiologies
remains
controversial.
A
deeper,
context-specific
signaling,
particularly
redox-sensitive
proteins,
designing
targeted
aimed
at
re-establishing
balance.
Emerging
small
molecule
inhibitors
that
target
specific
cysteine
residues
proteins
demonstrated
promising
preclinical
outcomes,
setting
stage
forthcoming
clinical
trials.
In
review,
we
summarize
current
intricate
relationship
disease
also
discuss
how
these
insights
leveraged
optimize
strategies
practice.
European Journal of Clinical Investigation,
Journal Year:
2024,
Volume and Issue:
54(9)
Published: April 17, 2024
Intervertebral
disc
degeneration
(IVDD)
is
a
common
chronic
orthopaedic
disease
in
orthopaedics
that
imposes
heavy
economic
burden
on
people
and
society.
Although
it
well
established
IVDD
associated
with
genetic
susceptibility,
ageing
obesity,
its
pathogenesis
remains
incompletely
understood.
Previously,
was
thought
to
occur
because
of
excessive
mechanical
loading
leading
destruction
nucleus
pulposus
cells
(NPCs),
but
studies
have
shown
much
more
complex
process
inflammation,
metabolic
factors
NPCs
death
can
involve
all
parts
the
disc,
characterized
by
causing
extracellular
matrix
(ECM)
degradation.
The
damage
pattern
like
some
programmed
cell
death,
suggesting
death.
apoptosis
pyroptosis
been
studied
IVDD,
intervertebral
still
not
be
fully
elucidated
using
only
traditional
modalities.
With
increasing
research,
new
modes
PANoptosis,
ferroptosis
senescence
found
closely
related
degeneration.
Among
these,
PANoptosis
combines
essential
elements
pyroptosis,
necroptosis
form
highly
coordinated
dynamically
balanced
inflammatory
process.
Furthermore,
we
believe
may
also
crosstalk
senescence.
Therefore,
review
progress
research
multiple
deaths
provide
guidance
for
clinical
treatment.
Journal of Advanced Research,
Journal Year:
2023,
Volume and Issue:
62, P. 105 - 117
Published: Sept. 26, 2023
Osteoarthritis
(OA)
is
a
devastating
whole-joint
disease
affecting
large
population
worldwide
with
no
cure;
its
mechanism
remains
poorly
defined.
Abnormal
mechanical
stress
the
main
pathological
factor
of
OA.
To
investigate
effects
Piezo1
activation
on
osteoarthritis
development
and
progression
to
explore
Piezo1-targeting
OA
treatment.
The
expression
levels
were
determined
in
human
cartilage
experimental
mice.
Mice
genetic
deletion
chondrocytes
or
intra-articular
injection
activator
Yoda1
utilized
determine
DMM-induced
progression.
Effects
artemisinin
(ART),
potent
antimalarial
drug,
activation,
chondrocyte
metabolism
lesions
determined.
was
elevated
articular
mouse
cartilage.
largely
attenuates
OA-like
phenotypes.
In
contrast,
aggravates
knee
joint
PIEZO1
increases,
while
siRNA
knockdown
decreases,
RUNX2
catabolic
enzymes
MMP13
ADAMTS5
primary
PI3K-AKT
dependent
manner.
We
have
provided
strong
evidence
supporting
that
ART
novel
inhibitor
OA-HACs
all
cell
lines
examined,
including
endothelial
HUVEC
cells,
ATDC5
chondrocyte-like
cells
MLO-Y4
osteocytes-like
cells.
Results
from
vitro
experiments
confirmed
decreases
Yoda1-induced
increases
OA-related
genes
p-PI3K
p-AKT
proteins
alleviates
establish
critical
role
promoting
define
as
potential
Nanomaterials,
Journal Year:
2024,
Volume and Issue:
14(5), P. 429 - 429
Published: Feb. 27, 2024
Microplastics
are
considered
an
emerging
environmental
pollutant
due
to
their
ubiquitous
presence
in
the
environment.
However,
potential
impact
of
microplastics
on
human
health
warrants
further
research.
Recent
studies
have
reported
neurobehavioral
and
neurotoxic
effects
marine
rodent
models;
however,
underlying
cellular
physiology
mammals
remains
unclear.
Herein,
we
exposed
neural
stem
cells
cell-derived
astrocytes,
oligodendrocytes,
neurons
various
sizes
concentrations
polystyrene
nano-
microplastics.
We
investigated
uptake,
cytotoxicity,
alteration
gene
expression
through
transcriptome
profiling.
The
cell
type
most
affected
by
decreased
viability
were
astrocytes
after
7
days
repeated
exposure.
Transcriptional
analysis
showed
that
1274
genes
differentially
expressed
500
nm
microplastics,
but
only
531
altered
50
nanoplastics.
Both
canonical
pathway
Kyoto
Encyclopedia
Genes
Genomes
upregulated
pathways
involved
neuroinflammation,
innate
adaptive
immunity,
migration,
proliferation,
extracellular
matrix
remodeling,
cytoskeleton
structures.
downregulated
lipid
metabolism,
specifically
fatty
acid
oxidation
cholesterol
metabolism.
Our
results
show
repeatedly
for
undergo
changes
hallmarks
astrogliosis.
Advanced Science,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 25, 2024
Osteoporotic
fractures
are
characterized
by
abnormal
inflammation,
deterioration
of
the
bone
microenvironment,
weakened
mechanical
properties,
and
difficulties
in
osteogenic
differentiation.
The
chronic
inflammatory
state
aging
macrophages
leads
to
delayed
or
non-healing
fracture
even
formation
defects.
current
bottleneck
clinical
treatment
is
achieve
strong
fixation
comminuted
fragments
effective
regulation
complex
microenvironment
macrophages.
Inspired
cement
gravel
concrete
infrastructure,
a
biomimetic
glue
with
poly(lactic-co-glycolic
acid)
microspheres
developed
levodopa/oxidized
chitosan
hydrogel
stabilized
on
an
organic-inorganic
framework
nanohydroxyapatite,
named
DOPM.
DOPM
via
morphological
characterization
techniques,
vitro
experiments
marrow
mesenchymal
stromal
cells,
vivo
aged
SD
rat
model
exhibiting
osteoporotic
exhibited
excellent
adhesion
good
biocompatibility,
significant
Transcriptomic
analysis
revealed
that
improved
inhibiting
NF-κB
signaling
pathway
promoting
macrophage
polarization
toward
M2
macrophages,
thus
significantly
accelerating
defect
repair
regeneration.
This
glue,
which
enhances
osteointegration
reestablishes
homeostasis
has
potential
applications
RMD Open,
Journal Year:
2024,
Volume and Issue:
10(1), P. e003901 - e003901
Published: Jan. 1, 2024
Objective
Gastrointestinal
(GI)
involvements
were
scarcely
reported
in
adult
anti-nuclear
matrix
protein
2
(NXP2)
dermatomyositis
(NXP2
+
DM).
In
this
study,
we
investigated
the
clinical,
pathological
and
molecular
features
as
well
treatment
options
of
rare
yet
life-threatening
disease.
Methods
We
retrospectively
collected
data
cohort
NXP2
DM
from
2012
to
2022
our
hospital.
RNA
sequencing
was
performed
intestinal
samples
perforated
patients
compared
with
healthy
controls
set.
Results
A
total
56
including
10
cases
GI
involvements.
Abdominal
pain
melena
initial
manifestations
for
a
median
10-month
time
lag
after
diagnosis
when
myositis
largely
subsided.
Within
weeks,
perforation
occurred
8
patients,
while
five
underwent
eight
surgical
interventions
subsequently.
The
short-term
mortality
observed
four
patients.
presented
more
extramuscular
systemic
such
interstitial
lung
disease
subcutaneous
calcinosis.
encompassed
vasculitis/vasculopathy
high
MxA
expression,
smooth
muscle
necrosis
serosal
Gene
expression
profile
validated
type-I
interferon
activation
revealed
that
epithelial
mesenchymal
transition
focal
adhesion
pathway
may
also
contribute.
Finally,
vedolizumab,
an
anti-α4β7-integrin
monoclonal
antibody,
exhibited
promising
therapeutic
signals
which
should
be
further
investigated.
Conclusions
involvement
is
unique
complication
NXP2+DM.
Timely
recognition
targeted
therapy
turn
out
lifesaving.
