Targeted Delivery of α‐ketoglutarate to Macrophages in Bone: A Novel Therapeutic Strategy for Improving Fracture Healing in Type 2 Diabetes
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 25, 2025
Abstract
Impaired
fracture
healing
is
a
common
complication
in
type
2
diabetes
mellitus
(T2DM),
with
limited
effective
treatments.
This
study
investigates
the
role
of
macrophages
bone
repair
and
introduces
novel
therapeutic
strategy.
Reduced
glutaminase
(GLS)
expression
glutaminolysis
are
found
from
T2DM
mice
monocytes
patients.
Specific
deletion
GLS
altered
their
phenotypes
delayed
mice.
Mechanistically,
deficiency
reduced
α‐ketoglutarate
(α‐KG)
levels
macrophages,
which
impairs
morphogenetic
protein
(BMP2)
production
by
increasing
cytosine
methylation
on
promoter,
ultimately
hindering
osteogenic
differentiation
marrow
mesenchymal
stem
cells.
Importantly,
while
systemic
α‐KG
supplementation
deteriorates
mice,
targeted
delivery
using
α‐[email protected]@ALN‐Liposome
to
markedly
improves
healing.
These
findings
underscore
critical
macrophage
propose
as
promising
intervention
for
improving
Язык: Английский
Melatonin Protects Against Cocaine‐Induced Blood−Brain Barrier Dysfunction and Cognitive Impairment by Regulating miR‐320a‐Dependent GLUT1 Expression
Journal of Pineal Research,
Год журнала:
2024,
Номер
76(8)
Опубликована: Ноя. 13, 2024
Cocaine
abuse
has
been
strongly
linked
to
blood-brain
barrier
(BBB)
dysfunction,
though
the
exact
mechanism
by
which
cocaine
disrupts
BBB
remains
unclear.
In
this
study,
we
found
that
treatment
reduces
expression
of
glucose
transporter
1
(GLUT1)
in
brain
microvascular
endothelial
cells,
a
key
factor
cocaine-induced
uptake,
leakage,
and
cognitive
impairment.
Mechanistically,
our
results
show
upregulates
miR-320a,
turn
suppresses
GLUT1
via
beta
2-adrenergic
receptor
(ADRB2).
Notably,
administration
adeno-associated
viruses
encoding
full-length
or
miR-320a
inhibitors
endothelium
significantly
mitigated
leakage
deficits.
Additionally,
discovered
melatonin,
well-known
neuroprotective
hormone,
alleviates
disruption
This
protective
effect
melatonin
was
mediated
through
upregulation
miR-320a-dependent
cells
MT
Язык: Английский