Epigenomics,
Год журнала:
2023,
Номер
15(16), С. 819 - 833
Опубликована: Авг. 1, 2023
N6-methyladenosine
(m6A)
methylation,
the
most
prevalent
post-transcriptional
modification
in
eukaryotes,
represents
a
highly
dynamic
and
reversible
process
that
is
regulated
by
m6A
methyltransferases,
demethylases
RNA-binding
proteins
during
RNA
metabolism,
which
affects
function.
Notably,
significantly
enriched
brain
exerts
regulatory
roles
neurogenesis
neurodevelopment
through
various
mechanisms,
further
influencing
occurrence
progression
of
neurological
disorders.
This
study
systematically
summarizes
discusses
latest
findings
on
common
regulators,
examining
their
expression,
function
mechanisms
diseases.
Additionally,
we
explore
potential
diagnosing
treating
disorders,
aiming
to
provide
new
insights
into
molecular
therapeutic
strategies
for
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
162, С. 114583 - 114583
Опубликована: Март 28, 2023
N6-methyladenosine
(m6A)
is
a
ubiquitous
mRNA
modification
in
eukaryotes.
m6A
occurs
through
the
action
of
methyltransferases,
demethylases,
and
methylation-binding
proteins.
methylation
RNA
associated
with
various
neurological
disorders,
including
Alzheimer's
disease
(AD),
Parkinson's
(PD),
depression,
cerebral
apoplexy,
brain
injury,
epilepsy,
arteriovenous
malformations,
glioma.
Furthermore,
recent
studies
report
that
m6A-related
drugs
have
attracted
considerable
concerns
therapeutic
areas
disorders.
Here,
we
mainly
summarized
role
diseases
potential
drugs.
The
aim
this
review
expected
to
be
useful
systematically
assess
as
new
biomarker
develop
innovative
modulators
for
amelioration
treatment
International Journal of Surgery,
Год журнала:
2024,
Номер
110(9), С. 5396 - 5408
Опубликована: Июнь 14, 2024
Background
Traumatic
brain
injury
(TBI)
is
a
common
complication
of
acute
and
severe
neurosurgery.
Remodeling
N6-methyladenosine
(m6A)
stabilization
may
be
an
attractive
treatment
option
for
neurological
dysfunction
after
TBI.
In
the
present
study,
authors
explored
epigenetic
methylation
RNA-mediated
NLRP3
inflammasome
activation
Methods
Neurological
dysfunction,
histopathology,
associated
molecules
were
examined
in
conditional
knockout
(CKO)
WTAP
[flox/flox,
Camk2a-cre]
,
flox/flox
pAAV-U6-shRNA-YTHDF1-transfected
mice.
Primary
neurons
used
vitro
to
further
explore
molecular
mechanisms
action
WTAP/YTHDF1
following
neural
damage.
Results
The
found
that
m6A
levels
upregulated
at
early
stage
TBI,
deletion
did
not
affect
function
but
promoted
functional
recovery
Conditional
suppressed
neuroinflammation
TBI
phase:
could
directly
act
on
mRNA,
regulate
mRNA
level,
promote
expression
neuronal
injury.
Further
investigation
YTH
domain
YTHDF1
bind
protein
expression.
mutation
or
silencing
improved
injury,
inhibited
Caspase-1
activation,
decreased
IL-1β
levels.
This
effect
was
mediated
via
suppression
translation,
which
also
reversed
stimulative
overexpression
inflammation.
Conclusions
Our
results
indicate
participates
damage
by
translation
m6A-YTHDF1-dependent
manner
WTAP/m6A/YTHDF1
downregulation
therapeutics
viable
promising
approach
preserving
can
provide
support
targeted
drug
development.
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Фев. 11, 2024
The
role
of
m6A
modification
in
the
regulation
immune
microenvironment
(IME)
ischemic
stroke
(IS)
is
barely
known.
Thus,
we
aim
to
investigate
impact
on
IME
IS
and
its
diagnostic
value
IS.
We
comprehensively
assessed
patterns,
relationship
between
these
patterns
characteristics
IME.
individual
sample
were
quantified
by
m6Ascore.
performance
phenotype-related
genes
as
potential
biomarkers
was
evaluated
area
under
receiver
operating
characteristic
curve.
Experimental
validation
also
performed
qRT-PCR.
Six
dysregulated
regulators
identified
a
classification
model
consisting
four
key
(METLL3,
RBMX,
RBM15B,
YTDHF3)
could
distinguish
healthy
control
samples
well.
METTL3
YTHDF3
are
closely
related
circulating
neutrophil
abundance.
Two
distinct
determined
which
differed
immunocyte
six
(APOBEC3A,
PTMA,
FCGR3A,
LOC440926,
LOC649946,
FTH1L11),
further
explored
their
biological
function.
Among
them,
APOBEC3A,
FTH1L11
positively
associated
with
APOBEC3A
FCGR3A
stable
m6A-associated
both
discovery
cohorts.
This
study
reveals
that
plays
non-negligible
formation
diversified
complex
be
Journal of Integrative Neuroscience,
Год журнала:
2023,
Номер
22(6)
Опубликована: Окт. 23, 2023
Background:
Cerebral
stroke
is
a
leading
cause
of
death
and
disability
worldwide.
Ligusticum
Chuanxiong
Hort.
(LCH),
well-known
Chinese
herb,
widely
used
for
the
treatment
cerebral
stroke.
This
study
aimed
to
investigate
underlying
mechanisms
LCH
in
develop
diagnostic
model.
Methods:
We
employed
network
pharmacology
analyses
identify
active
compounds,
targets,
treating
Molecular
docking
was
performed
visualize
binding
site
between
core
compounds
hub
targets.
Furthermore,
model
constructed
based
on
transcriptomic
analysis.
Results:
Our
findings
revealed
that
contains
multiple
ingredients,
including
oleic
acid
caffeic
acid.
Protein-protein
interaction
analysis
identified
IL1B,
CCL2,
MAPK3,
PTGS2,
JUN,
MMP9,
TLR4,
HIF1A,
PPARA,
FOS,
PTEN,
NFE2L2,
TLR2,
TIMP1,
SOD2
as
top
15
genes.
Kyoto
Encyclopedia
Genes
Genomes
pathway
highlighted
enrichment
TNF
IL-17
signaling
pathways.
demonstrated
sites
acid,
PPARP,
TIMP1.
The
indicated
TLR2
serve
blood
biomarkers
Conclusions:
demonstrates
alleviates
symptoms
following
through
interactions
with
contribute
better
understanding
therapeutic
offer
insights
into
development
Heliyon,
Год журнала:
2024,
Номер
10(3), С. e25192 - e25192
Опубликована: Янв. 23, 2024
N6-methyladenosine
(m6A)
modification
is
the
most
frequently
occurring
internal
in
eukaryotic
RNAs.
By
modulating
various
aspects
of
RNA
life
cycle,
it
has
been
implicated
a
wide
range
pathological
and
physiological
processes
associated
with
human
diseases.
Ischemic
stroke
major
cause
death
disability
worldwide
few
treatment
options
narrow
therapeutic
window,
accumulating
evidence
indicated
involvement
m6A
modifications
development
progression
this
type
stroke.
In
review,
which
provides
insights
for
prevention
clinical
stroke,
we
present
an
overview
roles
played
by
ischemic
from
three
main
perspectives:
(1)
association
established
risk
factors
including
hypertension,
diabetes
mellitus,
hyperlipidemia,
obesity,
heart
disease;
(2)
regulators
their
functional
regulation
pathophysiological
injury
mechanisms
namely
oxidative
stress,
mitochondrial
dysfunction,
endothelial
neuroinflammation,
cell
processes;
(3)
diagnostic
potential
