Drug Design Development and Therapy,
Год журнала:
2025,
Номер
Volume 19, С. 1595 - 1608
Опубликована: Март 1, 2025
Specnuezhenide
(SPN)
is
an
iridoid
glycoside
isolated
from
Fructus
Ligustri
Lucidi,
herb
prescribed
for
the
treatment
of
senile
osteoporosis.
However,
direct
role
SPN
on
bone
metabolism
remains
unclear.
In
this
study,
effects
d-galactose
(d-gal)-induced
mice,
marrow
mesenchymal
stem
cells
(BMSCs),
and
nuclear
factor-κB
ligand-induced
osteoclasts
were
examined.
Micro-computed
tomography
was
used
to
observe
microstructure.
Osteogenesis
examined
using
Western
blotting
alkaline
phosphatase
staining.
Osteoclastogenesis
F-actin
ring
Senescence-associated
β-galactosidase
detect
cell
senescence.
addition,
expression
Takeda
G
protein-coupled
receptor
5
(TGR5)/farnesoid
X
(FXR)
signaling
pathway-related
genes
proteins
determined
through
quantitative
real-time
polymerase
chain
reaction
immunofluorescence.
Oral
administration
improved
microstructure
in
d-gal-induced
mice
increased
mineral
density,
volume,
trabecular
thickness,
number.
also
upregulated
osteogenesis
markers
osteocalcin,
morphogenetic
protein
2,
runt-related
transcription
factor
2
downregulated
osteoclasis
tartrate-resistant
acid
phosphatase,
factor-κB,
activated
T-cells
bone.
Furthermore,
staining,
inhibited
formation,
reduced
activity
senescence-associated
vitro.
Mechanistically,
TGR5/FXR
pathway
BMSCs
osteoclasts.
The
protective
abolished
after
addition
TGR5
inhibitor
SBI-115
or
FXR
DY268.
Moreover,
could
elevate
mRNA
levels
TGR5,
FXR,
downstream
small
heterodimer
partner
alleviated
osteoporosis
senescence
by
activating
pathway.
Acta Biomaterialia,
Год журнала:
2024,
Номер
186, С. 424 - 438
Опубликована: Авг. 8, 2024
Mitophagy
influences
the
progression
and
prognosis
of
ischemic
stroke
(IS).
However,
whether
DNA
methylation
in
brain
is
associated
with
altered
mitophagy
hypoxia-injured
neurons
remains
unclear.
Here,
miR-138–5p
was
found
to
be
highly
expressed
exosomes
secreted
by
astrocytes
stimulated
oxygen
glucose
deprivation/re-oxygenation
(OGD/R),
which
could
influence
recovery
OGD/R-injured
through
autophagy.
Mechanistically,
promotes
stable
expression
Ras
homolog
enriched
like
1(Rhebl1)
DNA-methyltransferase-3a
(DNMT3A),
thereby
enhancing
ubiquitin-dependent
maintain
mitochondrial
homeostasis.
Furthermore,
we
employed
glycosylation
engineering
bioorthogonal
click
reactions
load
mirna
onto
surface
microglia
deliver
them
injured
region
utilising
inflammatory
chemotactic
properties
achieve
drug-targeted
delivery
central
nervous
system
(CNS).
Our
findings
demonstrate
improves
function
miR-138–5p/DNMT3A/Rhebl1
axis.
Additionally,
our
engineered
cell
vector-targeted
promising
for
treating
IS.
In
this
study,
demonstrated
that
under
hypoxia
plays
a
critical
role
treatment
neurons.
And
find
new
target
miR-138–5p,
DNMT3A,
affects
neuronal
thus
exerts
protective
effect
regulating
Rbebl1.
have
developed
carrier
combining
membrane
utilized
via
intravenous
injection.
This
groundbreaking
study
not
only
provides
novel
therapeutic
approach
ischemia-reperfusion
but
also
establishes
solid
theoretical
foundation
further
research
on
targeted
drug
diseases
clinical
applications.
Drug Design Development and Therapy,
Год журнала:
2025,
Номер
Volume 19, С. 1595 - 1608
Опубликована: Март 1, 2025
Specnuezhenide
(SPN)
is
an
iridoid
glycoside
isolated
from
Fructus
Ligustri
Lucidi,
herb
prescribed
for
the
treatment
of
senile
osteoporosis.
However,
direct
role
SPN
on
bone
metabolism
remains
unclear.
In
this
study,
effects
d-galactose
(d-gal)-induced
mice,
marrow
mesenchymal
stem
cells
(BMSCs),
and
nuclear
factor-κB
ligand-induced
osteoclasts
were
examined.
Micro-computed
tomography
was
used
to
observe
microstructure.
Osteogenesis
examined
using
Western
blotting
alkaline
phosphatase
staining.
Osteoclastogenesis
F-actin
ring
Senescence-associated
β-galactosidase
detect
cell
senescence.
addition,
expression
Takeda
G
protein-coupled
receptor
5
(TGR5)/farnesoid
X
(FXR)
signaling
pathway-related
genes
proteins
determined
through
quantitative
real-time
polymerase
chain
reaction
immunofluorescence.
Oral
administration
improved
microstructure
in
d-gal-induced
mice
increased
mineral
density,
volume,
trabecular
thickness,
number.
also
upregulated
osteogenesis
markers
osteocalcin,
morphogenetic
protein
2,
runt-related
transcription
factor
2
downregulated
osteoclasis
tartrate-resistant
acid
phosphatase,
factor-κB,
activated
T-cells
bone.
Furthermore,
staining,
inhibited
formation,
reduced
activity
senescence-associated
vitro.
Mechanistically,
TGR5/FXR
pathway
BMSCs
osteoclasts.
The
protective
abolished
after
addition
TGR5
inhibitor
SBI-115
or
FXR
DY268.
Moreover,
could
elevate
mRNA
levels
TGR5,
FXR,
downstream
small
heterodimer
partner
alleviated
osteoporosis
senescence
by
activating
pathway.
