Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Фев. 1, 2024
Background
It
is
well
established
that
females
are
more
susceptible
to
the
toxic
effects
of
alcohol,
although
exact
mechanisms
still
poorly
understood.
Previous
studies
noted
alcohol
reduces
expression
mitogen-activated
protein
kinase
phosphatase
1
(MKP1),
a
negative
regulator
kinases
(MAPK)
in
liver.
However,
role
hepatocyte-
specific
MKP1
pathogenesis
alcohol-associated
liver
disease
(ALD)
remains
uncharacterized.
This
study
aimed
evaluate
hepatocyte-specific
susceptibility
and
sexual
dimorphism
alcohol-induced
injury.
Methods
C57Bl/6
mice
were
used
an
intragastric
ethanol
feeding
model
steatohepatitis
(ASH).
Hepatocyte-specific
Mkp1
-/-
knockout
(
+/+
“f/f”
male
female
subjected
NIAAA
chronic
plus
binge
model.
Primary
mouse
hepatocytes
for
vitro
studies.
Liver
RNA
sequencing
was
performed
on
Illumina
NextSeq
500.
injury
evaluated
by
plasma
alanine
transaminase
(ALT),
hepatic
ER
stress
inflammation
markers.
Statistical
analysis
carried
out
using
ANOVA
unpaired
Student’s
t-test.
Results
ASH
associated
with
severe
accompanied
increased
endoplasmic
reticulum
(ER)
significant
downregulation
Dusp1
mRNA
expression.
In
,
treatment
resulted
time-dependent
decrease
primary
both
males
females;
however,
this
effect
significantly
pronounced
from
females.
vivo
developed
which
comparison,
not
changed
mice,
while
they
milder
alcohol.
deletion
led
induced
injury,
sexes.
Conclusion
Hepatocyte
plays
Alcohol
downregulates
sex
dependent
manner
could
play
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
25(1), С. 150 - 150
Опубликована: Дек. 21, 2023
Alcohol-related
liver
disease
(ALD)
encompasses
a
range
of
pathological
conditions
that
are
complex
to
study
at
the
clinical
and
preclinical
levels.
Despite
global
burden
ALD,
there
is
lack
effective
treatments,
mortality
high.
One
reasons
for
unsuccessful
development
novel
therapies
experimental
studies
hindered
by
challenge
recapitulating
this
multifactorial
disorder
in
vitro,
including
contributions
hepatotoxicity,
impaired
lipid
metabolism,
fibrosis
inflammatory
cytokine
storm,
which
critical
drivers
pathogenesis
ALD
patients
primary
targets
drug
development.
Here,
we
present
unique
characteristics
culture
human
precision-cut
slices
(PCLS)
replicate
key
processes
ALD.
PCLS
were
prepared
from
specimens
treated
with
ethanol
alone
or
combination
fatty
acids
lipopolysaccharide
(FA
+
LPS)
up
5
days
induce
hepatotoxic,
fibrotic
events
associated
Alcohol
insult
induced
hepatocyte
death
was
more
pronounced
addition
FA
LPS.
This
mixture
showed
significant
increase
cytokines
conventionally
prototypical
response
observed
severe
interestingly,
alcohol
exhibited
different
effect.
Profibrogenic
activation
also
investigated
context
slice
preparation.
These
results
support
versatility
organotypic
model
pathways
involved
alcohol-induced
damage
progression
highlight
applicability
discovery,
confirming
their
relevance
as
bridge
between
studies.
Journal of Food Biochemistry,
Год журнала:
2024,
Номер
2024, С. 1 - 13
Опубликована: Янв. 18, 2024
Since
chronic
alcoholic
liver
disease
(ALD)
is
a
significant
global
health
concern,
several
studies
have
shown
that
chitooligosaccharides
(COS)
exhibit
hepatoprotective
effects.
This
paper
examined
the
COS
protective
effect
on
ALD
mice.
Results
showed
improved
lipid
accumulation,
injury,
and
oxidative
stress
levels
in
mice
while
inhibiting
cytochrome
P450
protein
2E1
(CYP2E1)
expression
promoting
alcohol
dehydrogenase
(ADH)
acetaldehyde
(ALDH1)
expression,
indicating
could
ameliorate
metabolism.
Moreover,
intervention
also
enhanced
antioxidant
capacity
of
upregulated
peroxisome
proliferator-activated
receptor
gamma
coactivator
1α
(PGC-1),
silent
information
regulator
1
(SIRT1),
HO-1,
nuclear
factor-erythroid
2-related
factor
2
(NRF2)
levels.
In
addition,
increased
α
(PPARα),
acyl-CoA
oxidase
(ACOX),
synthetase
long-chain
family
member
(ACSL),
carnitine
palmitoyltransferase
1A
(CPT-1A),
(CPT2)
by
upregulating
fatty
acid
β
oxidation
pathway
restoring
mitochondrial
genesis.
From
liver-gut
axis
perspective,
intestinal
barrier
function
increasing
adhesion
junction
(AJ)
tight
(TJ)
expression.
Therefore,
displayed
ability
against
ALD.
The
results
provide
theoretical
basis
for
utilizing
supplemental
dietary
as
functional
food
alternative
treating
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Фев. 1, 2024
Background
It
is
well
established
that
females
are
more
susceptible
to
the
toxic
effects
of
alcohol,
although
exact
mechanisms
still
poorly
understood.
Previous
studies
noted
alcohol
reduces
expression
mitogen-activated
protein
kinase
phosphatase
1
(MKP1),
a
negative
regulator
kinases
(MAPK)
in
liver.
However,
role
hepatocyte-
specific
MKP1
pathogenesis
alcohol-associated
liver
disease
(ALD)
remains
uncharacterized.
This
study
aimed
evaluate
hepatocyte-specific
susceptibility
and
sexual
dimorphism
alcohol-induced
injury.
Methods
C57Bl/6
mice
were
used
an
intragastric
ethanol
feeding
model
steatohepatitis
(ASH).
Hepatocyte-specific
Mkp1
-/-
knockout
(
+/+
“f/f”
male
female
subjected
NIAAA
chronic
plus
binge
model.
Primary
mouse
hepatocytes
for
vitro
studies.
Liver
RNA
sequencing
was
performed
on
Illumina
NextSeq
500.
injury
evaluated
by
plasma
alanine
transaminase
(ALT),
hepatic
ER
stress
inflammation
markers.
Statistical
analysis
carried
out
using
ANOVA
unpaired
Student’s
t-test.
Results
ASH
associated
with
severe
accompanied
increased
endoplasmic
reticulum
(ER)
significant
downregulation
Dusp1
mRNA
expression.
In
,
treatment
resulted
time-dependent
decrease
primary
both
males
females;
however,
this
effect
significantly
pronounced
from
females.
vivo
developed
which
comparison,
not
changed
mice,
while
they
milder
alcohol.
deletion
led
induced
injury,
sexes.
Conclusion
Hepatocyte
plays
Alcohol
downregulates
sex
dependent
manner
could
play
