Circadian Control of Hepatic Ischemia/Reperfusion Injury via HSD17B13-Mediated Autophagy in Hepatocytes
Journal of Hepatology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 1, 2025
Язык: Английский
Rodent model of metabolic dysfunction‐associated fatty liver disease: a systematic review
Journal of Gastroenterology and Hepatology,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 25, 2024
Abstract
Although
significant
progress
has
been
made
in
developing
preclinical
models
for
metabolic
dysfunction‐associated
steatotic
liver
disease
(MASLD),
few
have
encapsulated
the
essential
biological
and
clinical
outcome
elements
reflective
of
human
condition.
We
conducted
a
comprehensive
literature
review
English‐language
original
research
articles
published
from
1990
to
2023,
sourced
PubMed,
Embase,
Web
Science,
aiming
collate
studies
that
provided
comparative
analysis
physiological,
metabolic,
hepatic
histological
characteristics
between
MASLD
control
groups.
The
establishment
robust
rodent
model
hinges
on
various
factors,
including
animal
species
strains,
sex,
induction
agents
methodologies,
duration
induction.
Through
this
review,
we
aim
guide
researchers
selecting
suitable
methods
constructing
aligned
with
their
specific
objectives
laboratory
conditions.
Future
should
strive
develop
simple,
reliable,
reproducible
models,
considering
model's
sensitivity
factors
such
as
light–dark
cycles,
housing
conditions,
environmental
temperature.
Additionally,
potential
diverse
vitro
3D
organ
technology,
warrants
further
exploration
valuable
tools
unraveling
cellular
mechanisms
underlying
fatty
disease.
Язык: Английский
Liver-specific inactivation of Cideb improves metabolic profiles and ameliorates steatohepatitis and fibrosis in animal models for MASH
Pharmacological Research,
Год журнала:
2025,
Номер
unknown, С. 107664 - 107664
Опубликована: Фев. 1, 2025
Germline
mutations
of
CIDEB,
a
lipid
droplets
(LDs)-associated
protein,
confer
protection
against
various
liver
diseases
in
humans.
It
remains
to
be
determined
whether
liver-specific
inhibition
CIDEB
will
bring
clinical
benefits.
We
aim
establish
pharmacological
proof
concept
by
testing
GalNAc-conjugated
Cideb
surrogate
siRNAs
respective
animal
models
obesity
and
MASH
develop
siRNA
drug
candidates
for
investigations.
Surrogate
targeting
mouse
were
designed
evaluated
via
panel
assays.
Concurrently,
humanized
knock-in
mice
generated
as
research
tool
facilitate
human
therapeutic
discovery.
In
vivo
administration
the
was
conducted
diet-induced
(DIO)
model
CDAA-HFD
MASH.
DIO
model,
knockdown
led
significant
reductions
serum
total
cholesterol
(TC)
triglyceride
(TG)
levels,
decrease
hepatic
macro-steatosis
notable
weight
loss.
treatment
significantly
reduced
TC
TG
levels.
Furthermore,
remarkable
steatosis
composite
NAS
score
observed
with
concomitant
amelioration
fibrosis.
Transcriptome
analyses
revealed
that
integrin
pathways
may
contribute
major
activities
upon
inactivation
beyond
metabolism.
exhibits
potential
target
Liver-targeting
are
under
development
hypothesis
Язык: Английский
Reversed role of CD36 deficiency in high-fat diet or methionine/choline-deficient diet-induced hepatic steatosis and steatohepatitis
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Март 5, 2025
Cluster
of
differentiation
36
(CD36)
is
highly
expressed
in
the
liver
patients
with
metabolic
dysfunction-associated
fatty
disease
(MAFLD)
or
steatohepatitis
(MASH).
However,
precise
role
CD36
MAFLD/MASH
controversial.
In
current
study,
we
aimed
to
uncover
early
stage
induced
by
high-fat
diet
(HFD)
and
methionine/choline-deficient
(MCD)
diet.
CD36-/-
mice
littermate
control
were
fed
a
normal
food
(NCD);
HFD
MCD
for
6
weeks.
We
determined
that
deficiency
attenuated
HFD-induced
hepatic
steatosis
while
exacerbating
diet-induced
steatohepatitis.
Mechanistically,
reduced
expression
acid
synthase
(FASN),
sterol
regulatory
element
binding
protein
1c
(SREBP1c),
acetyl-CoA
carboxylase
alpha
(ACC1),
thereby
inhibiting
de
novo
synthesis.
The
superoxide
dismutase
genes
involving
oxidation
was
inhibited
oxidation,
had
no
effect
on
these
mice.
Meanwhile,
diet-reduced
further
deficiency.
Thus,
MCD-induced
ROS
inflammation
enhanced
By
lipidomic
analysis,
found
levels
triglyceride
(TG),
diacylglycerols
(DG),
acylcarnitine
(AcCA),
ceramide
(Cer)
LPC
increased,
phosphatidylcholine/phosphatidylethanolamine
(PC/PE)
decreased
diet-treated
compared
wild
type
Indeed,
serine
palmitoyltransferase
2
(SPTLC2),
key
rate-limiting
enzyme
synthesis,
higher
improves
MAFLD
accelerating
MASH
via
promoting
Cer,
LPC,
TG
DG
accumulation
accelerate
inflammation.
complex
needs
more
investigation
discover
effective
strategy
when
targeting
CD36.
Язык: Английский
Gelsolin's Protective Role in MASH through F‐Actin Regulation and P53 Degradation
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 20, 2025
Abstract
Hepatic
steatosis,
inflammation,
and
fibrosis
are
the
hallmarks
of
metabolic‐associated
steatohepatitis
(MASH),
a
serious
health
risk.
This
study
emphasizes
how
important
gelsolin
(GSN)
is
to
pathophysiology
MASH.
The
results
show
that
GSN
significantly
overexpressed
in
both
MASH
patients
animal
models.
Under
models,
Gsn
knockout
(KO)
(
−/−
)
mice
demonstrate
exacerbated
hepatic
fibrosis,
underscoring
GSN's
protective
function.
Remarkably,
adeno‐associated
virus
(AAV)‐mediated
restoration
substantially
alleviates
these
pathological
features,
indicating
its
therapeutic
potential.
Mechanistically,
absence
leads
increased
F‐actin
polymerization
heightened
activation
Yes‐associated
protein
(YAP),
thereby
intensifying
inflammatory
response.
Subsequently,
experimental
data
identify
co‐expression
relationship
between
MDM2,
found
facilitate
ubiquitination
subsequent
degradation
P53
via
crucial
process
for
liver
protection.
These
findings
imply
essential
controlling
molecular
pathways
by
encouraging
P53's
MDM2‐mediated
degradation,
which
lessens
severity
steatosis.
research
offers
new
understandings
mechanisms
suggests
as
viable
target
reduce
damage
preserve
homeostasis.
Язык: Английский
Hepatocyte nuclear factor 4-Alpha: a key regulator in liver carcinogenesis
Hayam Hamdy,
Chang Shen,
Jiashun Xu
и другие.
Cellular Oncology,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 20, 2025
Язык: Английский
Polygenic Risk Score for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis: A Narrative Review
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(11), С. 5164 - 5164
Опубликована: Май 28, 2025
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD)
and
metabolic
steatohepatitis
(MASH)
are
spreading
worldwide
as
the
most
critical
causes
of
cirrhosis
hepatocellular
carcinoma
(HCC).
Thus,
improving
screening
managing
strategies
for
patients
with
MASLD
or
MASH
is
necessary.
A
traditional
non-systemic
review
provided
this
narrative.
Genetic
variations
associated
development
MASH,
such
PNPLA3,
TM6SF2,
GCKR,
MBOAT7,
MERTK,
HSD17B13,
were
initially
reviewed.
PNPLA3
genetic
variants
appeared
to
be
strongly
increased
pathogenesis
MASLD,
cirrhosis,
HCC.
We
also
reviewed
useful
polygenic
risk
score
(PRS)
their
related
occurrence
PRSs
better
predictors
HCC
in
than
any
single-nucleotide
polymorphisms.
RNA
interference
antisense
nucleotides
against
HSD17B13
being
developed.
Multidisciplinary
collaboration
cooperation
involving
hepatologists,
geneticists,
pharmacologists,
pathologists
should
resolve
complicated
problems
MASH.
This
narrative
highlights
importance
susceptibility
PRS
predictive
markers
personalized
medicine
future.
Язык: Английский
Role of PNPLA3 in Hepatic Stellate Cells and Hepatic Cellular Crosstalk
Liver International,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 12, 2024
ABSTRACT
Aims
Since
its
discovery,
the
patatin‐like
phospholipase
domain
containing
3
(PNPLA3)
(rs738409
C>G
p.I148M)
variant
has
been
studied
extensively
to
unravel
molecular
function.
Although
several
studies
proved
a
causal
relationship
between
PNPLA3
I148M
and
MASLD
development
particularly
fibrosis,
pathological
mechanisms
promoting
this
phenotype
have
not
yet
fully
clarified.
Methods
We
summarise
latest
data
regarding
in
hepatic
stellate
cells
(HSCs)
activation
macrophage
biology
or
path
inflammation‐induced
fibrosis.
Results
Elegant
but
contradictory
ascribed
hydrolase
an
acyltransferase
The
results
lipid
accumulation,
which
predisposes
hepatocyte
lipotoxicity
lipo‐apoptosis,
producing
DAMPs,
cytokines
chemokines
leading
recruitment
of
macrophages
HSCs,
propagating
Recent
showed
that
alters
HSCs
via
attenuation
PPARγ,
AP‐1,
LXRα
TGFβ
activity
signalling.
Conclusions
advent
refined
techniques
isolating
made
PNPLA3's
direct
role
for
liver
fibrosis
more
apparent.
However,
many
other
still
need
detailed
investigations.
Язык: Английский
Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances
Pharmaceuticals,
Год журнала:
2024,
Номер
17(12), С. 1724 - 1724
Опубликована: Дек. 20, 2024
Liver
fibrosis
is
a
progressive
scarring
process
primarily
caused
by
chronic
inflammation
and
injury,
often
closely
associated
with
viral
hepatitis,
alcoholic
liver
disease,
metabolic
dysfunction-associated
steatotic
disease
(MASLD),
drug-induced
autoimmune
(AILD).
Currently,
there
are
very
few
clinical
antifibrotic
drugs
available,
effective
targeted
therapy
lacking.
Recently,
emerging
immunomodulators
have
shown
promising
results
in
animal
studies,
some
entered
research
phases.
This
review
aims
to
systematically
the
molecular
mechanisms
underlying
fibrosis,
focusing
on
advancements
drug
treatments
for
hepatic
fibrosis.
Furthermore,
since
progression
or
endpoint
of
many
diseases,
it
crucial
address
etiological
treatment
secondary
prevention
We
will
also
pharmacological
available
common
hepatitis
leading
Язык: Английский
Novel Therapies for Nonalcoholic Steatohepatitis (NASH) and Cardiovascular Risk Reduction
Cardiovascular & Haematological Disorders - Drug Targets,
Год журнала:
2024,
Номер
24(4), С. 211 - 217
Опубликована: Ноя. 20, 2024
Nonalcoholic
steatohepatitis
(NASH)
is
a
type
of
nonalcoholic
fatty
liver
disease
(NAFLD)
characterized
by
hepatocyte
injury
and
inflammation,
in
addition
to
only
the
presence
steatosis
NAFLD.
We
review
existing
data
on
available
novel
therapies
for
NASH
NAFLD
also
discuss
several
development.
assessed
searching
databases
PubMed,
EMBASE,
Web
Science
(SCI)
from
their
inception
dates
until
September
15,
2024.
Search
terms
used
were:
disease,
steatohepatitis,
inflammation
injury.Until
very
recently,
therapeutic
lifestyle
change
was
primary
modality
treatment
NASH,
including
modification
diet
physical
activity.
The
FDA
recently
approved
resmetirom
using
its
expedited
approval
mechanism
NASH.
There
are
pharmacotherapies
development
which
aim
at
weight
loss,
insulin
sensitization
improvement
lipid
levels,
although
some
drugs
may
have
multiple
effects
discussed.
availability
offers
patients
with
an
effective
adjunctive
therapy
changes.
Several
other
currently
being
tested
will
add
our
armamentarium.
Язык: Английский