Ionizing radiation-induced disruption of Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunction
Cell Communication and Signaling,
Год журнала:
2025,
Номер
23(1)
Опубликована: Янв. 31, 2025
Ionizing
radiation
(IR)
poses
a
significant
threat
to
male
fertility
by
inducing
substantial
changes
in
the
testis,
yet
mechanisms
underlying
IR-induced
spermatogenesis
disorders
remain
poorly
understood,
necessitating
development
of
more
effective
radioprotective
agents.
We
employed
Bulk
RNA-seq
and
single-cell
(scRNA-seq)
on
Balb/c
mice
testes
models
following
IR
exposure
assess
cellular
transcriptional
alterations.
Histological
examination,
sperm
concentration
motility
analysis,
Western
blotting
(WB),
reverse
transcription
quantitative
PCR
(RT-qPCR)
were
used
evaluate
testicular
injury.
The
therapeutic
potential
NF-κB
agonists
was
investigated
an
disorder
model.
A
6
Gy
dose
induced
suppressed
spliceosome
pathway,
predominantly
affecting
cell
abundance
spermatogonia
primary
spermatocytes.
Bioinformatics
analysis
revealed
that
splicing
differentiation-related
genes,
thereby
impairing
differentiation
ability
Mechanistically,
This
disruption
linked
inhibition
NF-κB/Rela
Bclaf1
activity.
Notably,
found
ameliorate
this
damage
via
upregulating
spliceosome-related
genes
expression,
normalizing
patterns
rescuing
disorders.
study
reveals
novel
IR-mediated
Rela-Bclaf1-spliceosome
regulatory
axis
spermatocytes
propose
Rela
as
drug
target
for
mitigating
not
only
provides
new
insights
further
research
into
spermatogenic
caused
other
factors,
but
also
offers
strategies
developing
agents
cancer
radiotherapy.
Язык: Английский
Sodium alginate microspheres loaded with Quercetin/Mg nanoparticles as novel drug delivery systems for osteoarthritis therapy
Journal of Orthopaedic Surgery and Research,
Год журнала:
2025,
Номер
20(1)
Опубликована: Март 20, 2025
Osteoarthritis
(OA)
is
the
most
prevalent
arthritic
disease
characterized
by
cartilage
degradation
and
low-grade
inflammation,
for
which
there
remains
a
lack
of
efficacious
therapeutic
interventions.
Notably,
mitigating
impact
oxidative
stress
(OS)
inflammatory
factors
could
help
alleviate
or
hinder
advancement
OA.
Given
benefits
both
quercetin
(Que)
Magnesium
ion
(Mg2+)
in
OA
treatment,
coupled
with
structural
properties
Que,
we
have
innovatively
developed
Que-Mg2+
nanoparticles
(NPs),
aiming
to
deliver
Que
Mg2+
simultaneously
achieve
enhanced
outcomes
Moreover,
avoid
adverse
reactions
linked
frequent
injections,
sodium
alginate
(SA)
microspheres
encapsulating
NPs
(Que-Mg@SA)
were
designed
treat
H2O2-induced
cell
model.
Que-Mg@SA
synthesized
using
ionotropic
gelation
technique,
calcium
chloride
acting
as
cross-linking
agent.
Comprehensive
characterization
was
conducted
through
transmission
electron
microscope
(TEM),
dynamic
light
scattering
(DLS),
optical
microscope,
scanning
(SEM),
provided
detailed
insights
into
their
size,
zeta
potential,
morphology,
micromorphology.
Additionally,
microsphere
swelling
rate
release
evaluated.
The
biocompatibility
microspheres,
along
on
chondrocyte
viability,
detected
CCK-8
assay
live/dead
staining.
Furthermore,
antioxidant
anti-inflammatory
evaluated
examining
ROS
scavenging
ability
pro-inflammatory
levels,
respectively.
Finally,
regulatory
influence
extracellular
matrix
(ECM)
metabolism
assessed
immunofluorescence
staining
Western
blot.
Characterization
results
revealed
that
Que-Mg
exhibit
nanoscale
diameter,
exceptional
stability,
good
dispersibility,
while
possesses
high
entrapment
efficiency
(EE%)
loading
(LE%),
pronounced
hygroscopic
properties,
sustained
drug-release
capabilities.
vitro
cellular
assays
biocompatible
significantly
restored
scavenged
excessive
ROS,
reduced
levels
cytokines,
upregulated
anabolic
gene
expression,
downregulated
catabolic
protease
maintained
metabolic
balance
tissue.
functionalized
our
study
hold
great
promise
drug
delivery
system
potentially
other
biomedical
applications.
Not
applicable.
Язык: Английский
Polygonum multiflorum Inhibits Pulmonary Inflammation and Fibrosis in PM2.5-Induced Dysfunction Through the Regulation of the TLR4/TGF-β1 Signaling Pathway in Mice
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(11), С. 5080 - 5080
Опубликована: Май 25, 2025
Industrial
development
has
improved
living
standards;
however,
mortality
associated
with
fine
particulate
matter
(PM2.5)
exposure
continues
to
rise.
Despite
increasing
awareness
of
its
health
risks,
effective
strategies
mitigate
PM2.5-induced
pulmonary
damage
remain
limited.
This
study
examines
the
protective
properties
an
ethanolic
extract
from
Polygonum
multiflorum
(EPM)
in
preventing
dysfunction
induced
by
PM2.5,
as
well
possible
use
a
dietary
intervention
improve
respiratory
health.
The
physiological
compounds
EPM
were
identified
using
ultra-performance
liquid
chromatography,
and
effects
evaluated
via
vitro
assays
A549
RPMI
2650
cells.
antioxidant
system
mitochondrial
function
further
analyzed
lung
tissues
PM2.5-exposed
BALB/c
mice,
molecular
mechanisms
elucidated
Western
blot
analysis.
main
bioactive
included
2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside.
modulated
Nrf2
signaling
pathway,
enhancing
defense
regulating
expression
antioxidant-related
proteins.
Furthermore,
exhibited
against
inflammation,
apoptosis,
fibrosis
through
TLR4/p-JNK
TGF-β1
pathways.
These
findings
suggest
that
exerts
oxidative
stress
inflammation
may
be
used
functional
food
ingredient
for
Язык: Английский
The Potential Therapeutic Prospect of PANoptosis in Heart Failure
Journal of Inflammation Research,
Год журнала:
2024,
Номер
Volume 17, С. 9147 - 9168
Опубликована: Ноя. 1, 2024
Heart
failure
(HF)
represents
a
serious
manifestation
or
advanced
stage
of
various
cardiac
diseases.
HF
continues
to
impose
significant
global
disease
burden,
characterized
by
high
rates
hospitalization
and
fatality.
Furthermore,
the
pathogenesis
pathophysiological
processes
underlying
remain
incompletely
understood,
complicating
its
prevention
treatment
strategies.
One
mechanism
associated
with
is
systemic
inflammatory
response.
PANoptosis,
novel
mode
cell
death,
has
been
extensively
studied
in
context
infectious
diseases,
neurodegenerative
disorders,
cancers,
other
conditions.
Recent
investigations
have
revealed
that
PANoptosis-related
genes
are
markedly
dysregulated
specimens.
Consequently,
PANoptosis-mediated
response
may
represent
potential
therapeutic
target
for
HF.
This
paper
conducts
comprehensive
analysis
molecular
pathways
drive
PANoptosis.
We
discuss
role
targets
HF,
thereby
providing
valuable
insights
clinical
development
therapies.
Язык: Английский