High inherited risk predicts age-associated increases in fibrosis in patients with MASLD
Journal of Hepatology,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 1, 2025
Язык: Английский
Subtypes of MASLD confer distinct clinical trajectories
Journal of Hepatology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 1, 2025
Язык: Английский
Identification of Novel Therapeutic Targets for MAFLD Based on Bioinformatics Analysis Combined with Mendelian Randomization
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(7), С. 3166 - 3166
Опубликована: Март 29, 2025
Metabolic-associated
fatty
liver
disease
(MAFLD)
is
a
chronic
condition
with
limited
therapeutic
options.
To
identify
novel
drug
targets,
we
integrated
bioinformatics,
Mendelian
randomization
(MR),
and
colocalization
analyses.
Using
the
Gene
Expression
Omnibus
(GEO)
database,
identified
differentially
expressed
genes
constructed
protein–protein
interaction
(PPI)
networks,
pinpointing
10
hub
genes.
MR
analyses
revealed
that
Ubiquitin-like
PHD
ring
finger
domains
1
(UHRF1)
causally
associated
MAFLD
driven
by
same
causal
variant
locus,
suggesting
its
potential
as
target.
Molecular
docking
disogenin
candidate
small-molecule
targeting
UHRF1.
Drug
affinity
responsive
target
stability
(DARTS)
assays
confirmed
direct
binding
between
UHRF1
disogenin.
In
vitro,
significantly
reduced
mRNA
protein
levels
induced
free
acids
(FFA)
in
AML12
HepG2
cells,
accompanied
decreased
cellular
total
cholesterol
(TC)
triglyceride
(TG)
levels.
vivo,
administration
alleviated
hepatic
lipid
accumulation,
inflammation,
fibrosis
methionine/choline-deficient
(MCD)-diet-fed
mice.
This
study
identifies
promising
for
validates
agent,
providing
foundation
further
investigation.
Язык: Английский
MRI Provides New Insights Into the Pharmacologic Mechanism of Bisacodyl: A Blueprint for Understanding Intestinal Drug Mechanisms
Clinical Pharmacology & Therapeutics,
Год журнала:
2025,
Номер
117(5), С. 1159 - 1161
Опубликована: Апрель 12, 2025
Язык: Английский
Experimental Models to Investigate PNPLA3 in Liver Steatosis
Liver International,
Год журнала:
2025,
Номер
45(5)
Опубликована: Апрель 15, 2025
ABSTRACT
Patatin‐like
phospholipase
domain‐containing
3
(PNPLA3)
was
the
first
gene
identified
through
genome‐wide
association
studies
to
be
linked
hepatic
fat
accumulation.
A
missense
variant,
encoding
PNPLA3‐148M
allele,
has
since
been
shown
increase
risk
for
full
spectrum
of
steatotic
liver
disease
(SLD),
from
simple
steatosis
steatohepatitis,
cirrhosis,
and
hepatocellular
carcinoma.
Despite
extensive
validation
this
ongoing
research
into
its
pathogenic
role,
precise
mechanisms
by
which
contributes
progression
SLD
remain
poorly
understood.
In
review,
we
evaluate
preclinical
in
vitro
vivo
models
used
investigate
PNPLA3
involvement
SLD,
with
particular
emphasis
on
metabolic
dysfunction‐associated
disease.
We
assess
strengths
limitations
these
models,
as
well
challenges
arising
species
differences
expression
function
between
human
murine
systems.
Язык: Английский
Gene-based therapies for steatotic liver disease
Molecular Therapy,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 1, 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
Alternative splicing: hallmark and therapeutic opportunity in metabolic liver disease
Gastroenterology report,
Год журнала:
2025,
Номер
13
Опубликована: Янв. 1, 2025
Abstract
Metabolic
dysfunction-associated
fatty
liver
disease
(MAFLD)
has
become
the
leading
cause
of
chronic
worldwide,
with
fibrosis
recognized
as
main
prognostic
factor
and
therapeutic
target.
While
early-stage
is
reversible,
advanced
poses
a
significant
clinical
challenge
due
to
limited
treatment
options,
highlighting
need
for
innovative
management
strategies.
Recent
studies
have
shown
that
alternative
pre-mRNA
splicing,
critical
mechanism
regulating
gene
expression
protein
diversity,
plays
fundamental
role
in
pathogenesis
MAFLD
associated
fibrosis.
Understanding
complex
relationship
between
splicing
progression
could
pave
way
novel
approaches
improve
outcomes.
In
this
review,
we
describe
intricate
mechanisms
MAFLD.
Specifically,
explored
pivotal
factors,
RNA-binding
proteins,
their
interactions
metabolic
epigenetic
regulators.
Furthermore,
provide
an
overview
latest
advancements
splicing-based
strategies
biomarker
development.
Particular
emphasis
placed
on
potential
application
antisense
oligonucleotides
rectifying
anomalies,
thereby
laying
foundation
precision
medicine
MAFLD-associated
Язык: Английский