Biochemical Pharmacology,
Journal Year:
2024,
Volume and Issue:
228, P. 116249 - 116249
Published: April 30, 2024
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD)
is
common
worldwide.
Genes
and
proteins
contributing
to
drug
disposition
may
show
altered
expression
as
MASLD
progresses.
To
assess
this
further,
we
undertook
transcriptomic
proteomic
analysis
of
137
pharmacogenes
in
biopsies
from
a
large
cohort.
We
performed
sequencing
on
RNA
216
(206
10
controls).
Untargeted
mass
spectrometry
proteomics
was
103
biopsy
subgroup.
Selected
signals
were
replicated
with
an
additional
187
biopsies.
Comparison
advanced
(fibrosis
score
3/4)
milder
0-2)
by
showed
significant
alterations
certain
phase
I,
II
ABC
transporters.
For
cytochromes
P450,
CYP2C19
the
most
decreased
(30
%
that
mild
disease)
but
other
CYPs
(including
CYP2C8
CYP2E1)
also
occurred.
decrease
comparing
inflammatory
form
(MASH)
non-MASH
Findings
for
confirmed
replication
Proteomics
original
discovery
cohort
levels
several
greatest
where
fell
40
control.
This
result
activity
could
be
problematic
prescription
drugs
activated
or
metabolized
advances.
More
limited
decreases
P450s
suggest
fewer
issues
non-CYP2C19
substrates.
Negative
correlations
at
level
between
cytokine
genes
provided
initial
insights
into
mechanism
underlying
expression.
International Journal of Biological Macromolecules,
Journal Year:
2024,
Volume and Issue:
271, P. 132452 - 132452
Published: May 20, 2024
Non-alcoholic
fatty
liver
disease
(NAFLD)
is
the
most
common
form
of
chronic
disease.
Little
known
about
how
gene
expression
and
chromatin
structure
are
regulated
in
NAFLD
due
to
lack
suitable
model.
Ducks
naturally
develop
similar
serious
human
non-alcoholic
(NAFL)
without
adipose
inflammation
fibrosis,
thus
serves
as
a
good
model
for
investigating
molecular
mechanisms
metabolism
anti-inflammation.
Here,
we
constructed
fibrosis
ducks.
By
performing
dynamic
pathological
transcriptomic
analyses,
identified
critical
genes
involving
regulation
NF-κB
MHCII
signaling,
which
usually
lead
fibrosis.
We
further
generated
three-dimensional
maps
during
formation
recovery.
This
showed
that
ducks
enlarged
hepatocyte
cell
nuclei
reduce
inter-chromosomal
interaction,
decompress
structure,
alter
strength
intra-TAD
loop
interactions
formation.
These
changes
partially
contributed
tight
control
signaling.
Our
analysis
uncovers
duck
reorganization
might
be
advantageous
maintain
regenerative
capacity
inflammation.
findings
shed
light
on
new
strategies
control.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: Dec. 11, 2024
There
is
increasing
evidence
that
the
intestinal
microbiota
plays
an
integral
role
in
disease
pathogenesis
and
treatment.
Specifically,
significantly
influences
pharmacokinetics
pharmacodynamics
of
orally
administered
drugs
through
direct
involvement
drug
metabolism
and,
consequently,
bioavailability.
However,
gut
also
exerts
immunoregulatory
effects
on
liver-the
organ
primarily
responsible
for
metabolism-thereby
indirectly
impacting
body's
capacity
to
metabolise
process
drugs.
Individual
differences
this
pathway
substantially
contribute
variability
clinical
treatment
outcomes
observed
between
patients.
This
review
examines
impact
liver
immune
responses,
as
triggered
by
microbiota,
activity
drug-metabolising
enzymes
discusses
implications
precision
medicine.
European Journal of Lipid Science and Technology,
Journal Year:
2024,
Volume and Issue:
126(5)
Published: March 13, 2024
Abstract
This
study
aimed
to
investigate
the
effect
of
a
virgin
flaxseed
oil
(FO)
rich
in
n
−
3
polyunsaturated
fatty
acid,
supplemented
or
not
with
bioactive
supplement
(BS)
containing
tocopherols
and
phytosterols
on
prevention
nonalcoholic
liver
disease
high‐fat
(HF)
animal
model.
Male
Wistar
rats
were
fed
60
days
recommended
(SO7,
soybean
7%)
an
HF
diet
(fat,
30%)
(SO30),
corn
(CO30),
FO
(FO30)
same
oils
1%
BS
(SO30BS,
CO30BS,
FO30BS,
respectively).
Hepatic
dietary
FA
composition,
triacylglycerides
(TAGs)
content
serum
liver,
nutritional
parameters,
vivo
TAG‐secretion
rate,
histology,
mRNA
levels
β‐oxidation‐related
genes,
carnitine
palmitoyl
transferase‐1a
(CPT‐1a)
enzyme
activity
determined.
At
levels,
FO30
FO30BS
groups
showed
highest
total
PUFA
diets
associated
lower
weight
gain,
TAG
content,
microsteatosis
degree.
The
CPT‐1a
was
enhanced
showing
differences
only
by
type
oil.
supplementation
induced
increase
gene
expression.
Virgin
prevented
steatosis
hepatomegaly
diets.
reduced
body
fat
accumulation
expression
β‐oxidation
related
without
affecting
hepatic
content.
Practical
Applications
:
Scientific
knowledge
functional
lipids
high
oxidative
stability
biological
has
great
practical
application
reducing
non‐communicable
chronic
diseases.
provides
evidence
potential
synergic
complementary
effects
FO,
TP,
PS
be
used
for
metabolic
disorders
involved
during
evolution
different
steps
NAFLD.
Specifically,
based
mechanisms,
this
stable
combination
could
prevent
development
exacerbated
but
also
hepatocellular
injury
seen
at
stages
from
steatohepatitis.
Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 14, 2024
AbstractBackground:
The
intricate
interplay
between
host
genes
and
intrahepatic
microbes
is
vital
in
shaping
the
hepatic
microenvironment
contributes
significantly
to
our
understanding
of
nonalcoholic
fatty
liver
disease
(NAFLD).
However,
underlying
mechanisms
progression
mediated
by
these
interactions
remain
largely
elusive.
Methods:
We
conducted
a
comprehensive
analysis
570
biopsy
transcriptomes
from
five
cohorts,
including
72
control,
124
(NAFL),
143
borderline
231
steatohepatitis
(NASH)
samples.
Least
Absolute
Shrinkage
Selection
Operator
penalized
regression
Sparse
Canonical
Correlation
Analysis
were
utilized
identify
host-microbiota
their
function.
Results:
observed
significant
upregulations
key
involved
mitochondrial
organization
across
all
stages,
while
related
antigen
processing
showed
abnormal
activations
advanced
stages
like
NASH.
Additionally,
abundances
Methyloversatilis
sp.
RAC08Ralstonia
insidiosadecreased
NAFLD
stages.
identified
5537,
1937,
1485,
2933
NAFL,
borderline,
NASH
samples,
respectively.
Notably,
interaction
strength
decreasing
trend,
especially
during
transition
stage
In
NAFL
bacteria
Bacillales,
insidiosa,
Micromonosporaceae
played
pivotal
roles
enhancing
mitophagy
interacting
with
SQSTM1,
OPTN,
BNIP3L.
such
functional
clusters
absent
Conclusion:
Disturbed
affecting
process
can
lead
pro-inflammatory
through
activation
immune
reactions,
potentially
driving
Discover Oncology,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Dec. 19, 2024
The
onset
of
metabolic
dysfunction-associated
steatotic
liver
disease-associated
hepatocellular
carcinoma
(MASLD-HCC)
is
insidious
and
exhibits
sex-specific
variations.
Effective
methods
for
monitoring
MASLD-HCC
progression
in
females
have
not
yet
been
developed.
Transcriptomic
data
female
tissue
samples
were
obtained
from
multiple
public
databases.
Differentially
expressed
genes
(DEGs)
identified
using
differential
expression
robust
rank
aggregation
analyses.
Diagnostic
prediction
models
MASLD
(DP.MASLD)
HCC
(DP.HCC)
developed
validated
elastic
net
analysis,
diagnostic
performance
was
evaluated
receiver
operating
characteristic
(ROC)
curve
analysis.
Bioinformatics
used
to
assess
the
pathogenesis
MASLD-HCC.
Seven
overlapping
DEGs
patients
with
HCC:
AKR1B10,
CLEC1B,
CYP2C19,
FREM2,
MT1H,
NRG1,
THBS1).
area
under
ROC
(AUC)
values
training
validation
groups
DP.MASLD
model
0.864
0.782,
0.932
1.000,
0.920
0.969
when
differentiating
between
steatosis
normal
liver,
steatohepatitis
steatosis,
groups,
respectively.
AUCs
DP.HCC
0.980
0.997
oncogenesis
associated
molecular
pathways,
including
cytochrome
P450-associated
drug
metabolism,
tyrosine
fatty
acid
degradation,
focal
adhesion,
extracellular
matrix
receptor
interactions,
protein
digestion
absorption.
A
novel
effective
method
quantitatively
risk
developed,
this
will
aid
generation
precise
diagnostic,
preventive,
therapeutic
strategies.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Dec. 30, 2024
Cell
type
deconvolution
methods
can
impute
cell
proportions
from
bulk
transcriptomics
data,
revealing
changes
in
disease
progression
or
organ
development.
But
benchmarking
studies
often
use
simulated
data
the
same
source
as
reference,
which
limits
its
application
scenarios.
This
study
examines
batch
effects
and
introduces
SCCAF-D,
a
computational
workflow
that
ensures
Pearson
Correlation
Coefficient
above
0.75
across
real
for
various
tissue
types.
Applied
to
non-alcoholic
fatty
liver
disease,
SCCAF-D
unveils
meaningful
insights
into
during
progression.
