Aging,
Journal Year:
2023,
Volume and Issue:
unknown
Published: Dec. 18, 2023
Sepsis
is
defined
as
a
life-threatening
organ
dysfunction
caused
by
dysregulated
host
response
to
infection.
It
characterized
high
morbidity
and
mortality
one
of
the
major
diseases
that
seriously
hang
over
global
human
health.
Autophagy
crucial
regulator
in
complicated
pathophysiological
processes
sepsis.
The
activation
autophagy
known
be
great
significance
for
protecting
sepsis
induced
dysfunction.
Recent
research
has
demonstrated
N6-methyladenosine
(m6A)
methylation
well-known
post-transcriptional
RNA
modification
controls
epigenetic
gene
expression
well
number
biological
In
addition,
m6A
affects
stability,
export,
splicing
translation
transcripts
involved
autophagic
process.
Although
it
been
suggested
regulates
metabolic
more
frequently
seen
progression
pathogenesis,
underlying
molecular
mechanisms
m6A-modified
have
not
thoroughly
elucidated.
present
article
fills
this
gap
providing
an
review
its
potential
role
development
novel
therapeutics.
Molecular Medicine,
Journal Year:
2023,
Volume and Issue:
29(1)
Published: Dec. 8, 2023
Abstract
N
6-methyladenosine
(m6A)
modification
is
a
kind
of
RNA
in
which
methylation
occurs
at
the
sixth
position
adenosine
RNA,
can
occur
various
RNAs
such
as
mRNAs,
lncRNAs
and
miRNAs.
This
one
most
prominent
frequent
posttranscriptional
modifications
within
organisms
has
been
shown
to
function
dynamically
reversibly
variety
ways,
including
splicing,
export,
attenuation
translation
initiation
efficiency
regulate
expression.
There
are
three
main
enzymes
associated
with
m6A
modification:
writers,
readers
erasers.
Increasing
evidence
that
onset
development
kidney
disease.
In
this
article,
we
address
important
physiological
pathological
roles
diseases
(uremia,
ischemia–reperfusion
injury,
drug-induced
diabetic
nephropathy)
its
molecular
mechanisms
provide
reference
for
diagnosis
clinical
management
diseases.
Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 10, 2024
Abstract
Inflammatory
responses,
apoptosis,
and
oxidative
stress,
are
key
factors
that
contribute
to
hepatic
ischemia/reperfusion
(I/R)
injury,
which
may
lead
the
failure
of
liver
surgeries,
such
as
hepatectomy
transplantation.
The
N6-methyladenosine
(m6A)
modification
has
been
implicated
in
multiple
biological
processes,
its
specific
role
mechanism
I/R
injury
require
further
investigation.
This
study
focused
on
RNA
methylase
METTL3
ischemia-reperfusion
injury.
Dot
blotting
analysis
was
used
profile
m6A
levels
tissues
at
different
reperfusion
time
points
mouse
models.
Hepatocyte-specific
knockdown
(HKD)
mice
were
determine
function
during
I/R.
sequencing
western
performed
assess
potential
signaling
pathways
involved
with
deficiency
METTL3.
Finally,
AAV8-TBG-METTL3
injected
through
tail
vein
elucidate
We
found
expression
upregulated
livers
led
an
exacerbated
inflammatory
response
increased
cell
death
I/R,
whereas
overexpression
reduced
extent
Bioinformatic
revealed
MAPK
pathway
significantly
enriched
METTL3-deficient
mice.
protected
from
possibly
by
inhibiting
phosphorylation
JNK
ERK,
but
not
P38.
Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: April 17, 2024
Abstract
N6-Methyladenosine
(m6A)
methylation
is
involved
in
various
pathological
processes.
Our
previous
study
found
abnormal
expression
of
the
methyltransferases
enzyme
METTL3
aging
kidney
tissues,
resulting
renal
fibrosis
and
aging.
In
this
study,
we
aim
to
elucidate
its
regulatory
mechanisms
diabetic
disease
(DKD)
by
establishing
a
conditional
knockout
model.
We
observed
elevated
m6A
levels
mice
with
type
I
diabetes
cultured
mouse
podocytes
exposed
advanced
glycation
end-products
(AGEs),
which
could
be
attributed
increased
expression.
Podocyte-specific
knockdown
significantly
mitigated
podocyte
injury
streptozotocin
(STZ)-induced
mice,
leading
reduced
urine
albuminuria
pathology.
Mechanistically,
induced
modification
MDM2,
triggering
subsequent
degradation
an
IGF2BP2
dependent
manner.
Consequently,
regulation
induces
MDM2
expression,
activates
Notch
signaling
pathway,
cell
cycle
re-entry
under
conditions,
releases
inflammatory
factors,
dedifferentiation
podocytes.
Thus,
METTL3-mediated
aberrant
plays
pivotal
role
conditions.
Targeting
via
potentially
effective
strategy
for
DKD
treatment.
International Journal of Medical Sciences,
Journal Year:
2024,
Volume and Issue:
21(6), P. 1037 - 1048
Published: Jan. 1, 2024
Background:
Inflammatory
responses,
apoptosis,
and
oxidative
stress,
are
key
factors
that
contribute
to
hepatic
ischemia/reperfusion
(I/R)
injury,
which
may
lead
the
failure
of
liver
surgeries,
such
as
hepatectomy
transplantation.The
N6-methyladenosine
(m
6
A)
modification
has
been
implicated
in
multiple
biological
processes,
its
specific
role
mechanism
I/R
injury
require
further
investigation.Methods:
Dot
blotting
analysis
was
used
profile
m
A
levels
tissues
at
different
reperfusion
time
points
mouse
models.Hepatocyte-specific
METTL3
knockdown
(HKD)
mice
were
determine
function
during
I/R.RNA
sequencing
western
performed
assess
potential
signaling
pathways
involved
with
deficiency
METTL3.Finally,
AAV8-TBG-METTL3
injected
through
tail
vein
elucidate
injury.Results:
The
expression
upregulated
livers
injury.METTL3
led
an
exacerbated
inflammatory
response
increased
cell
death
I/R,
whereas
overexpression
reduced
extent
injury.Bioinformatic
revealed
MAPK
pathway
significantly
enriched
METTL3-deficient
mice.METTL3
protected
from
possibly
by
inhibiting
phosphorylation
JNK
ERK,
but
not
P38.Conclusions:
aggravates
activating
pathway.METTL3
be
a
therapeutic
target
injury.
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: Aug. 13, 2024
Background
Methyltransferase-like
3
(METTL3),
a
component
of
the
N6-methyladenosine
(m6A)
methyltransferase
family,
exhibits
significant
expression
in
HEI-OC1
cells
and
cochlear
explants.
Aminoglycoside
antibiotics,
known
for
their
ototoxic
potential,
frequently
induce
irreversible
auditory
damage
hair
cells,
predominantly
through
oxidative
stress
mechanisms.
However,
specific
role
METTL3
kanamycin-induced
cell
loss
remains
unclear.
Objective
This
study
aims
to
elucidate
mechanisms
by
which
contributes
ototoxicity.
Methods
Results
In
vivo
experiments
demonstrated
notable
reduction
within
explants
following
kanamycin
administration,
concomitant
with
formation
granules
(SGs).
Similarly,
24-hour
treatment
led
decreased
induced
SG
both
neonatal
explants,
corroborating
observations.
Lentivirus-mediated
transfection
was
employed
overexpress
knockdown
cells.
Knockdown
resulted
increased
reactive
oxygen
species
(ROS)
levels
apoptosis
kanamycin,
while
concurrently
reducing
formation.
Conversely,
overexpression
attenuated
ROS
generation,
rates,
promoted
kanamycin.
Therefore,
METTL3-mediated
presents
promising
target
mitigating
generation
rate
apoptosis.
Conclusion
finding
indicates
that
holds
potential
impairments
rates.
MedComm,
Journal Year:
2024,
Volume and Issue:
5(11)
Published: Oct. 23, 2024
Abstract
N6‐methyladenosine
(m6A)
is
the
most
abundant
RNA
modification
in
eukaryotic
cells.
Previous
studies
have
shown
that
m6A
plays
a
critical
role
under
both
normal
physiological
and
pathological
conditions.
Hematopoiesis
differentiation
are
highly
regulated
processes,
recent
on
mRNA
methylation
revealed
how
this
controls
cell
fate
malignant
hematopoietic
states.
However,
despite
these
insights,
comprehensive
understanding
of
its
complex
roles
between
development
diseases
remains
elusive.
This
review
first
provides
an
overview
components
biological
functions
regulators.
Additionally,
it
highlights
origin,
process,
characteristics,
regulatory
mechanisms
stem
cells,
as
well
features,
immune
properties,
self‐renewal
pathways
leukemia
Last,
article
systematically
reviews
latest
research
advancements
factors
hematopoiesis
related
diseases.
More
importantly,
explores
targeting
regulators
various
signaling
could
effectively
intervene
leukemia,
providing
new
insights
potential
therapeutic
targets.
Targeting
may
hold
promise
for
achieving
more
precise
effective
treatments.
Human Genomics,
Journal Year:
2024,
Volume and Issue:
18(1)
Published: Nov. 14, 2024
Kidney
disease
is
marked
by
complex
pathological
mechanisms
and
significant
therapeutic
hurdles,
resulting
in
high
morbidity
mortality
rates
globally.
A
deeper
understanding
of
the
fundamental
processes
involved
can
aid
identifying
novel
targets
improving
treatment
efficacy.
Current
comprehensive
data
analyses
indicate
involvement
methyltransferase-like
3
(METTL3)
its
role
RNA
N6-methyladenosine
methylation
various
renal
pathologies,
including
acute
kidney
injury,
fibrosis,
chronic
disease.
However,
there
a
paucity
thorough
reviews
that
clarify
functional
METTL3
evaluate
importance
enhancing
outcomes.
This
review
seeks
to
systematically
examine
roles,
mechanisms,
potential
clinical
applications
diseases.
The
findings
presented
suggest
implicated
etiology
exacerbation
disorders,
affecting
their
onset,
progression,
malignancy,
responsiveness
chemotherapeutic
agents
through
regulation
specific
genetic
pathways.
In
conclusion,
this
underscores
detrimental
correlation
between
diseases,
highlighting
promise
targeting
METTL3.
Additionally,
it
offers
critical
insights
for
researchers
concerning
diagnosis,
prognosis,
strategies
conditions.
