Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: Jan. 22, 2025
N6-methylation
is
a
modification
in
which
methyl
group
added
to
the
adenine
base
of
nucleotide.
This
crucial
for
controlling
important
functions
that
are
vital
gene
expression,
including
mRNA
splicing,
stability,
and
translation.
Due
its
intricate
participation
both
normal
cellular
processes
course
disease,
as
well
critical
role
determining
cell
fate,
N6-methyladenosine
(m
6
A)
alteration
has
recently
attracted
lot
interest.
The
formation
progression
many
diseases,
especially
cancer,
can
be
attributed
dysregulated
m
A
alteration,
cause
disturbances
variety
functions,
such
immunological
responses,
proliferation,
differentiation.
In
this
study,
we
examine
how
dysregulation
affects
hepatocellular
carcinoma
(HCC),
with
particular
emphasis
on
it
contributes
evasion
carcinogenesis.
We
also
investigate
potential
novel
therapeutic
target,
providing
new
perspectives
approaches
meant
enhance
clinical
results
patients
HCC.
Redox Biology,
Journal Year:
2024,
Volume and Issue:
69, P. 103026 - 103026
Published: Jan. 4, 2024
Dementia,
with
homocysteine
(Hcy)
as
an
important
risk
factor,
is
a
severe
public
health
problem
in
the
aging
society.
Betaine
serves
methyl
donor
and
plays
role
reducing
Hcy.
However,
effects
mechanisms
of
betaine
on
Hcy-induced
cognitive
impairment
remain
unclear.
Firstly,
SD
rats
were
injected
Hcy
(400
μg/kg)
through
vena
caudalis,
(2.5
%
w/v)
was
supplemented
via
drinking
water
for
14
days.
supplementation
could
attenuate
Y
maze
novel
object
recognition
tests
by
repairing
brain
injury.
Meanwhile,
microglial
activation
observed
to
be
inhibited
using
immunofluorescence
sholl
analysis.
Secondly,
HMC3
cells
treated
betaine,
which
found
decrease
ROS
level,
ameliorate
cell
membrane
rupture,
reduce
release
LDH,
IL-18
IL-1β,
damage
microglia
neurons.
Mechanistically,
alleviates
inhibiting
pyroptosis
expressions
NLRP3,
ASC,
pro-caspase-1,
cleaved-caspase-1,
GSDMD,
GSDMD-N,
IL-1β.
treatment
can
increase
SAM/SAH
ratio,
confirming
its
enhancement
methylation
capacity.
Furthermore,
enhance
N6-methyladenosine
(m6A)
modification
NLRP3
mRNA,
reduced
mRNA
stability
increasing
expression
m6A
reader
YTH
RNA
binding
protein
2
(YTHDF2).
Finally,
silencing
YTHDF2
reverse
inhibitory
effect
pyroptosis.
Our
data
demonstrated
that
attenuated
suppressing
NLRP3/caspase-1/GSDMD
pathway
m6A-YTHDF2-dependent
manner.
International Journal of Surgery,
Journal Year:
2024,
Volume and Issue:
110(9), P. 5396 - 5408
Published: June 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.
Proceedings of the National Academy of Sciences,
Journal Year:
2024,
Volume and Issue:
121(6)
Published: Jan. 29, 2024
The
N6-methyladenosine
(m
6
A)
modification
of
RNA
is
an
emerging
epigenetic
regulatory
mechanism
that
has
been
shown
to
participate
in
various
pathophysiological
processes.
However,
its
involvement
modulating
neuropathic
pain
still
poorly
understood.
In
this
study,
we
elucidate
a
functional
role
the
m
A
demethylase
alkylation
repair
homolog
5
(ALKBH5)
trigeminal-mediated
pain.
Peripheral
nerve
injury
selectively
upregulated
expression
level
ALKBH5
injured
trigeminal
ganglion
(TG)
rats.
Blocking
upregulation
TGs
alleviated
pain,
while
mimicking
intact
TG
neurons
sufficiently
induced
pain-related
behaviors.
Mechanistically,
histone
deacetylase
11
downregulation
by
increases
H3
lysine
27
acetylation
(H3K27ac),
facilitating
binding
transcription
factor
forkhead
box
protein
D3
(FOXD3)
Alkbh5
promoter
and
promoting
transcription.
increased
erases
sites
Htr3a
messenger
(mRNA),
resulting
inability
YT521-B
homology
domain
2
(YTHDF2)
bind
mRNA,
thus
causing
increase
5-HT3A
5-HT3
channel
currents.
Conversely,
blocking
destabilizes
injury–induced
reverses
mechanical
allodynia,
effect
can
be
blocked
knockdown.
Together,
FOXD3-mediated
transactivation
promotes
through
A-dependent
stabilization
mRNA
neurons.
This
mechanistic
understanding
may
advance
discovery
new
therapeutic
targets
for
management.
Archives of Physiology and Biochemistry,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 11
Published: March 2, 2025
Objective:
This
study
explores
the
mechanism
of
methyltransferase
like
3
(METTL3)
on
sepsis-associated
encephalopathy
(SAE)-induced
hippocampal
neuronal
injury.
