PXR Activation Relieves Deoxynivalenol‐Induced Liver Oxidative Stress Via Malat1 LncRNA m6A Demethylation
Advanced Science,
Год журнала:
2024,
Номер
11(25)
Опубликована: Апрель 24, 2024
Abstract
Deoxynivalenol
(DON)
is
a
prevalent
toxin
causing
severe
liver
damage
through
hepatocellular
oxidative
stress.
However,
the
underlying
mechanisms
and
effective
therapeutic
approaches
remain
unknown.
Here,
unique
role
of
xenobiotic
metabolism
factor
pregnane
X
receptor
(PXR)
in
mediating
DON‐induced
stress
investigated.
Treatment
with
PXR
agonist
3‐indole‐propionic
acid
(IPA)
alleviates
injury
both
vitro
vivo.
Mechanistically,
it
discovered
for
first
time
that
IPA
directly
transactivates
m
6
A
demethylase
FTO
expression,
leading
to
site‐specific
demethylation
decreased
abundance
YTHDC1‐bound
Malat1
lncRNA
at
single‐nucleotide
resolution.
The
diminished
modification
reduces
its
stability
augments
antioxidant
pathways
governed
by
NRF2,
consequently
mitigating
injury.
Furthermore,
knockout
mice
exhibit
injury,
emphasizing
Collectively,
findings
establish
PXR‐mediated
A‐dependent
expression
determines
hepatocyte
via
FTO,
providing
valuable
insights
into
potential
offers
strategies
treatment.
Язык: Английский
Lithocholic acid attenuates DON-induced inflammatory responses via epigenetic regulation of DUSP5 and TRAF5 in porcine intestinal epithelial cells
Frontiers in Veterinary Science,
Год журнала:
2025,
Номер
12
Опубликована: Фев. 28, 2025
Deoxynivalenol
(DON)
is
the
most
common
mycotoxin
that
frequently
contaminates
human
food
and
animal
feed,
resulting
in
intestinal
diseases
systemic
immunosuppression.
Lithocholic
acid
(LCA)
exhibits
various
pharmacological
activities.
RNA-seq
ChIP-qPCR
analysis
were
used
current
study
to
investigate
protective
mechanism
of
LCA
for
DON-induced
inflammatory
Responses
via
Epigenetic
Regulation
DUSP5
TRAF5
porcine
ileal
epithelial
cell
lines
(IPI-2I)
cells.
The
IPI-2I
cells
treated
with
vehicle
group,
250
ng/mL
DON,
20
μmol/L
LCA,
DON+
24
h
could
induce
By
analyzing
transcriptional
profiles
DON
LCA-treated
IPI-2I,
we
observed
significant
changes
Further
up-and
down-regulated
differential
genes
revealed
enrichment
pathways
closely
related
inflammation
apoptosis,
such
as
MAPK
signaling
pathway,
IL17
Wnt
pathway.
An
upregulated
(
p
<
0.05)
relative
mRNA
expression
level
RAP1B,
GDNF,
FGF2,
IL1R1,
RAPGEF2,
DUSP5,
TGFB3,
CACNA1G,
TEK
RPS6KA2
noted
exposed
DON.
DON-exposed
dramatically
enhanced
histone
marks
associated
activation,
H3K9ac,
H3K18ac,
H3K27ac,
H3K4me1,
H3K9bhb,
H3K18bhb
Pol-II
Ser5
at
enhancers
TRAF5.
Overall,
our
findings
provide
a
theoretical
basis
understanding
action
attenuating
injury
better
potential
treatment
or
prevention
mycotoxin-associated
swine
production.
Язык: Английский
Magnesium-based implants accelerate femoral fracture healing through promoting histone lactylation-mediated osteoclastogenesis inhibition
Life Sciences,
Год журнала:
2025,
Номер
372, С. 123639 - 123639
Опубликована: Апрель 17, 2025
To
investigate
the
molecular
mechanisms
by
which
magnesium
(Mg)-based
implants,
specifically
Mg-containing
intramedullary
nails
(Mg-IMNs),
promote
femoral
fracture
healing.
Rats
with
fractures
were
treated
Mg-IMNs.
In
vitro
experiments
conducted
to
assess
impact
of
Mg2+
on
osteoclastogenesis
and
histone
lactylation.
Histological
analysis,
Western
blotting,
qRT-PCR
employed
evaluate
osteoclast
maturation
pathways
involved.
vivo,
lactate
was
administered
replicate
Mg-IMN
effects,
production
inhibited
observe
potential
reversal
effects.
Mg-IMNs
significantly
enhanced
healing
inhibiting
osteoclastogenesis.
promoted
intracellular
production,
leading
lactylation,
suppressed
downregulating
NFATc1.
The
P300/H3K18LA/HDAC1
pathway
identified
as
a
key
mediator
in
this
process.
Additionally,
administration
mimicked
effects
Mg-IMNs,
while
blocking
reversed
these
This
study
uncovers
novel
mechanism
promotes
through
lactylation-mediated
inhibition
These
findings
offer
new
therapeutic
strategies
for
enhancing
repair
via
epigenetic
regulation.
Язык: Английский
The regulatory role of protein lactylation in various diseases: Special focus on the regulatory role of non-histone lactylation
Gene,
Год журнала:
2025,
Номер
unknown, С. 149595 - 149595
Опубликована: Май 1, 2025
Язык: Английский
Early Weaning Inhibits Intestinal Stem Cell Expansion to Disrupt the Intestinal Integrity of Duroc Piglets via Regulating the Keap1/Nrf2 Signaling
Antioxidants,
Год журнала:
2024,
Номер
13(10), С. 1188 - 1188
Опубликована: Сен. 30, 2024
There
are
different
stress
resistance
among
breeds
of
pigs.
Changes
in
intestinal
stem
cells
(ISCs)
still
unclear
various
piglets
after
early
weaning.
In
the
current
study,
Taoyuan
Black
and
Duroc
were
slaughtered
at
21
days
age
(early
weaning
day)
24
(3
weaning)
for
10
each
group.
The
results
showed
that
rate
ISC-driven
epithelial
renewal
local
pigs
hardly
changed
3
days.
However,
significantly
reduced
weight
duodenum
jejunum
piglets.
Meanwhile,
jejunal
villus
height,
tight
junction-related
proteins
(ZO-1,
Occludin,
Claudin1),
as
well
trans-epithelial
electrical
(TEER)
values,
down-regulated
Moreover,
compared
with
Unweaned
piglets,
numbers
Olfm4
Язык: Английский