Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(16)
Опубликована: Фев. 16, 2024
Enzymes
are
considered
safe
and
effective
therapeutic
tools
for
various
diseases.
With
the
increasing
integration
of
biomedicine
nanotechnology,
artificial
nanozymes
offer
advanced
controllability
functionality
in
medical
design.
However,
several
notable
gaps,
such
as
catalytic
diversity,
specificity
biosafety,
still
exist
between
their
native
counterparts.
Here
we
report
a
non-metal
single-selenium
(Se)-atom
nanozyme
(SeSAE),
which
exhibits
potent
nicotinamide
adenine
dinucleotide
phosphate
(NADPH)
oxidase-mimetic
activity.
This
novel
single
atom
provides
alternative
to
conventional
metal-based
catalysts
effectively
cuts
off
cellular
energy
reduction
equivalents
through
its
distinctive
function
tumors.
In
this
study,
have
demonstrated
substantial
efficacy
SeSAE
an
antitumor
nanomedicine
across
diverse
mouse
models
without
discernible
systemic
adverse
effects.
The
mechanism
NADPH
oxidase-like
activity
was
rationalized
by
density
functional
theory
calculations.
Furthermore,
comprehensive
elucidation
biological
functions,
cell
death
pathways,
metabolic
remodeling
effects
conducted,
aiming
provide
valuable
insights
into
development
with
clinical
translation
potential.
Advanced Materials,
Год журнала:
2023,
Номер
35(28)
Опубликована: Апрель 29, 2023
Acute
respiratory
distress
syndrome
(ARDS)
represents
a
significant
burden
to
the
healthcare
system,
with
≈200
000
cases
diagnosed
annually
in
USA.
ARDS
patients
suffer
from
severe
refractory
hypoxemia,
alveolar-capillary
barrier
dysfunction,
impaired
surfactant
function,
and
abnormal
upregulation
of
inflammatory
pathways
that
lead
intensive
care
unit
admission,
prolonged
hospitalization,
increased
disability-adjusted
life
years.
Currently,
there
is
no
cure
or
FDA-approved
therapy
for
ARDS.
This
work
describes
implementation
engineered
extracellular
vesicle
(eEV)-based
nanocarriers
targeted
nonviral
delivery
anti-inflammatory
payloads
inflamed/injured
lung.
The
results
show
ability
protein
A
(SPA)-functionalized
IL-4-
IL-10-loaded
eEVs
promote
intrapulmonary
retention
reduce
inflammation,
both
vitro
vivo.
Significant
attenuation
observed
tissue
damage,
proinflammatory
cytokine
secretion,
macrophage
activation,
influx
protein-rich
fluid,
neutrophil
infiltration
into
alveolar
space
as
early
6
h
post-eEVs
treatment.
Additionally,
metabolomics
analyses
eEV
treatment
causes
changes
metabolic
profile
inflamed
lungs,
driving
secretion
key
metabolites.
Altogether,
these
establish
potential
derived
dermal
fibroblasts
prevalence/progression
injury
during
via
genes/transcripts.
Annals of the Rheumatic Diseases,
Год журнала:
2023,
Номер
83(1), С. 72 - 87
Опубликована: Сен. 29, 2023
Objectives
To
investigate
the
effect
of
L-arginine
metabolism
on
arthritis
and
inflammation-mediated
bone
loss.
Methods
was
applied
to
three
models
(collagen-induced
arthritis,
serum-induced
human
TNF
transgenic
mice).
Inflammation
assessed
clinically
histologically,
while
changes
were
quantified
by
μCT
histomorphometry.
In
vitro,
effects
osteoclast
differentiation
analysed
RNA-seq
mass
spectrometry
(MS).
Seahorse,
Single
Cell
ENergetIc
profilIng
Translation
inHibition
transmission
electron
microscopy
used
for
detecting
metabolic
in
osteoclasts.
Moreover,
arginine-associated
metabolites
measured
serum
rheumatoid
(RA)
pre-RA
patients.
Results
inhibited
loss
all
directly
blocked
TNFα-induced
murine
osteoclastogenesis.
MS
analyses
indicated
that
switched
glycolysis
oxidative
phosphorylation
inflammatory
osteoclasts
leading
increased
ATP
production,
purine
elevated
inosine
hypoxanthine
levels.
Adenosine
deaminase
inhibitors
blocking
production
abolished
inhibition
osteoclastogenesis
vitro
vivo.
Altered
arginine
levels
also
found
RA
Conclusion
Our
study
demonstrated
ameliorates
erosion
through
reprogramming
perturbation
npj Systems Biology and Applications,
Год журнала:
2023,
Номер
9(1)
Опубликована: Сен. 9, 2023
Recent
advancement
in
integrated
multi-omics
has
significantly
contributed
to
many
areas
of
the
biomedical
field.
Radiation
research
also
grasped
uprising
omics
technologies
biomarker
identification
aid
triage
management.
Herein,
we
have
used
a
combinatorial
approach
based
on
transcriptomics
together
with
metabolomics
and
lipidomics
blood
from
murine
exposed
1
Gy
(LD)
7.5
(HD)
total-body
irradiation
(TBI)
for
comprehensive
understanding
biological
processes
through
pathways
networking.
Both
displayed
demarcation
HD
group
controls
using
multivariate
analysis.
Dysregulated
amino
acids,
various
PC,
PE
carnitine
were
observed
along
dysregulated
genes
(Nos2,
Hmgcs2,
Oxct2a,
etc.).
Joint-Pathway
Analysis
STITCH
interaction
showed
radiation
exposure
resulted
changes
acid,
carbohydrate,
lipid,
nucleotide,
fatty
acid
metabolism.
Elicited
immune
response
was
by
Gene
Ontology.
BioPAN
predicted
Elovl5,
Elovl6
Fads2
pathways,
only
group.
Collectively,
combined
facilitated
better
uncovering
metabolic
pathways.
Presumably,
this
is
first
that
utilized
an
following
TBI
mice.
Our
work
integration
could
be
valuable
tool
comprehending
mechanism
as
well
molecular
interactions.
Developmental Cell,
Год журнала:
2023,
Номер
58(18), С. 1782 - 1800.e10
Опубликована: Июль 25, 2023
Despite
the
key
roles
of
perilipin-2
(PLIN2)
in
governing
lipid
droplet
(LD)
metabolism,
mechanisms
that
regulate
PLIN2
levels
remain
incompletely
understood.
Here,
we
leverage
a
set
genome-edited
human
reporter
cell
lines
series
CRISPR-Cas9
loss-of-function
screens,
identifying
genetic
modifiers
influence
expression
and
post-translational
stability
under
different
metabolic
conditions
types.
These
regulators
include
canonical
genes
control
metabolism
as
well
involved
ubiquitination,
transcription,
mitochondrial
function.
We
further
demonstrate
role
for
E3
ligase
MARCH6
regulating
triacylglycerol
biosynthesis,
thereby
influencing
LD
abundance
stability.
Finally,
our
CRISPR
screens
several
published
provide
foundation
CRISPRlipid
(http://crisprlipid.org),
an
online
data
commons
lipid-related
functional
genomics
data.
Our
study
identifies
regulation
provides
extensive
resource
exploration
biology
metabolism.
