Biomedicine & Pharmacotherapy,
Год журнала:
2022,
Номер
158, С. 114160 - 114160
Опубликована: Дек. 24, 2022
Nonalcoholic
steatohepatitis
(NASH)
is
among
the
most
common
liver
diseases
in
world.
Flavonoids
from
Scutellaria
amoena
(SAF)
are
used
treatment
of
hepatopathy
China.
However,
effect
and
mechanism
against
NASH
remain
unclear.
We
investigated
alleviating
SAF
on
via
regulating
mitochondrial
dysfunction
oxidative
stress.
The
effects
were
evaluated
using
vitro
vivo
methods.
L02
cells
induced
by
fat
emulsion
to
establish
an
adipocytes
model,
followed
with
for
24
h.
rat
models
established
administration
a
high-fat
diet
12
weeks
administered
six
weeks.
Changes
body
weight,
organ
indexes,
lipid
levels,
inflammatory
cytokines,
indicators,
fatty
acid
metabolism
investigated.
significantly
improved
injury,
infiltration
rats.
notably
regulated
interleukin-6,
tumor
necrotic
factor-alpha,
superoxide
dismutase
(SOD),
glutathione
(GSH),
malondialdehyde
(MDA),
kelch-like
ECH-associated
protein
1
(Keap1),
nuclear
factor-erythroid
factor
2-related
2
(Nrf2),
heme
oxygenase-1
(HO-1).
Additionally,
dysfunction,
increased
levels
GSH,
SOD,
ATP
synthase,
complex
I
II,
decreased
level
MDA
mitochondria.
expression
β-oxidation
genes,
including
peroxisome
proliferator-activated
receptor
-gamma
coactivator-1alpha
(PGC-1α),
carnitine
palmitoyltransferase-1
(CPT1)
A,
CPT1B,
medium-chain
acyl-CoA
dehydrogenase,
long-chain
very
PPARα.
can
alleviate
function
stress
Keap1/Nrf2/HO-1
axis.
Antioxidants,
Год журнала:
2023,
Номер
12(5), С. 1065 - 1065
Опубликована: Май 8, 2023
Together
with
the
global
rise
in
obesity
and
metabolic
syndrome,
prevalence
of
individuals
who
suffer
from
nonalcoholic
fatty
liver
disease
(NAFLD)
has
risen
dramatically.
NAFLD
is
currently
most
common
chronic
includes
a
continuum
disorders
initial
fat
accumulation
to
steatohepatitis
(NASH),
considered
more
severe
forms,
which
can
evolve
in,
cirrhosis,
hepatocellular
carcinoma.
Common
features
altered
lipid
metabolism
mainly
linked
mitochondrial
dysfunction,
which,
as
vicious
cycle,
aggravates
oxidative
stress
promotes
inflammation
and,
consequence,
progressive
death
hepatocytes
form
NAFLD.
A
ketogenic
diet
(KD),
i.e.,
very
low
carbohydrates
(<30
g/die)
that
induces
“physiological
ketosis”,
been
demonstrated
alleviate
restore
function.
Based
on
this,
aim
present
review
analyze
body
evidence
regarding
potential
therapeutic
role
KD
NAFLD,
focusing
interplay
between
mitochondria
liver,
effects
ketosis
pathways,
impact
Journal of Hepatology,
Год журнала:
2024,
Номер
80(6), С. 941 - 956
Опубликована: Фев. 15, 2024
Background
and
aims
The
PNPLA3
rs738409
C>G
(encoding
for
I148M)
variant
is
a
risk
locus
the
fibrogenic
progression
of
chronic
liver
diseases,
process
driven
by
hepatic
stellate
cells
(HSCs).
We
investigated
how
I148M
affects
HSCs
biology
using
transcriptomic
data
validated
findings
in
3D-culture
models.
Methods
RNA
sequencing
was
performed
on
2D-cultured
primary
human
biopsies
obese
individuals,
genotyped
variant.
Data
were
wild
type
(WT)
or
carrying
I148M-PNPLA3
cultured
3D
extracellular
matrix
(ECM)
scaffolds
from
healthy
cirrhotic
with/without
TGFB1
Cytosporone-B
(Csn-B)
treatment.
Results
Comparison
between
analysis
highlighted
shared
I148M-driven
dysregulated
pathways
related
to
mitochondrial
function,
antioxidant
response,
ECM
remodelling
signalling.
Analogous
WT/I148M-PNPLA3
scaffolds.
Mitochondrial
dysfunction
linked
respiratory
chain
complex
IV
insufficiency.
Antioxidant
capacity
lower
HSCs,
while
ROS
secretion
increased
higher
bioengineered
versus
signalling
pathway
followed
same
trend.
In
cells,
TGFB1-endogenous
inhibitor
NR4A1
expression
activation
decreased:
treatment
with
Csn-B
agonist
total
but
not
regulation
TGFB1/Csn-B
Akt
WT-PNPLA3
Erk
HSCs.
Conclusion
have
impaired
dampening
antifibrotic
activity.
These
features
are
exacerbated
ECM,
highlighting
dual
impact
fibrotic
microenvironment
progressive
diseases.
Impact
implications
Hepatic
(HSCs)
play
key
role
associated
disease.
genetic
mutation
has
been
fibrogenesis,
its
needs
further
investigation.
Here,
comparative
novel
vitro
model,
we
demonstrate
cell
behaviour,
show
that
it
cell's
function
as
well
gene
NR4A1.
Our
publicly
available
data,
platform
our
could
facilitate
discovery
targets
develop
more
effective
treatments
Analytical Chemistry,
Год журнала:
2024,
Номер
96(23), С. 9408 - 9415
Опубликована: Май 28, 2024
Reactive
oxygen
species
play
a
pivotal
role
in
liver
disease,
contributing
to
severe
damage
and
chronic
inflammation.
In
injury
driven
by
inflammation,
adenosine-5′-triphosphate
(ATP)
hypochlorite
ion
(ClO–)
emerge
as
novel
biomarkers,
reflecting
mitochondrial
dysfunction
amplified
oxidative
stress,
respectively.
However,
the
dynamic
fluctuations
of
ATP
ClO–
hepatocytes
mouse
livers
remain
unclear,
multidetection
techniques
for
these
biomarkers
are
yet
be
developed.
This
study
presents
RATP-NClO,
dual-channel
fluorescent
bioprobe
capable
synchronously
detecting
ions.
RATP-NClO
exhibits
excellent
selectivity
sensitivity
ions,
demonstrating
fluorescence
response
murine
hepatocyte
cell
line.
Upon
intravenous
administration,
reveals
synchronized
depletion
amplification
mice
with
experimental
metabolic
dysfunction-associated
steatohepatitis
(MASH).
Through
comprehensive
analysis
principal
mechanism
developed
verification
its
reliable
detection
ability
both
vitro
vivo
settings,
we
propose
it
unique
tool
monitoring
changes
intracellular
level.
These
findings
underscore
potential
practical
image-based
functional
phenotyping
MASH
pathogenesis.
Chemical Research in Toxicology,
Год журнала:
2024,
Номер
37(8), С. 1290 - 1305
Опубликована: Июль 9, 2024
Drug-induced
liver
injury
(DILI)
has
been
a
significant
challenge
in
drug
discovery,
often
leading
to
clinical
trial
failures
and
necessitating
withdrawals.
Over
the
last
decade,
existing
suite
of
Biomedicines,
Год журнала:
2023,
Номер
11(4), С. 1166 - 1166
Опубликована: Апрель 13, 2023
The
pathogenesis
of
hepatocellular
carcinoma
(HCC)
is
a
multifactorial
process
that
has
not
yet
been
fully
investigated.
Autophagy
and
apoptosis
are
two
important
cellular
pathways
critical
for
cell
survival
or
death.
balance
between
autophagy
regulates
liver
turnover
maintains
intracellular
homeostasis.
However,
the
often
dysregulated
in
many
cancers,
including
HCC.
may
be
either
independent
parallel
one
influence
other.
inhibit
promote
apoptosis,
thus
regulating
fate
cancer
cells.
In
this
review,
concise
overview
HCC
presented,
with
emphasis
on
new
developments,
role
endoplasmic
reticulum
stress,
implication
microRNAs
gut
microbiota.
characteristics
associated
specific
disease
also
described
brief
description
provided.
initiation,
progress
metastatic
potential
reviewed
experimental
evidence
indicating
an
interplay
extensively
analyzed.
ferroptosis,
recently
pathway
regulated
death,
presented.
Finally,
therapeutic
implications
drug
resistance
examined.
Antioxidants,
Год журнала:
2023,
Номер
12(11), С. 1928 - 1928
Опубликована: Окт. 29, 2023
Chronic
liver
disease
(CLD)
affects
a
significant
portion
of
the
global
population,
leading
to
substantial
number
deaths
each
year.
Distinct
forms
like
non-alcoholic
fatty
(NAFLD)
and
alcoholic
(ALD),
though
they
have
different
etiologies,
highlight
shared
pathologies
rooted
in
oxidative
stress.
Central
metabolism,
mitochondria
are
essential
for
ATP
production,
gluconeogenesis,
acid
oxidation,
heme
synthesis.
However,
diseases
NAFLD,
ALD,
fibrosis,
mitochondrial
function
is
compromised
by
inflammatory
cytokines,
hepatotoxins,
metabolic
irregularities.
This
dysfunction,
especially
electron
leakage,
exacerbates
production
reactive
oxygen
species
(ROS),
augmenting
damage.
Amidst
this,
nuclear
factor
erythroid
2-related
2
(NRF2)
emerges
as
cellular
protector.
It
not
only
counters
stress
regulating
antioxidant
genes
but
also
maintains
health
overseeing
autophagy
biogenesis.
The
synergy
between
NRF2
modulation
introduces
new
therapeutic
potentials
CLD,
focusing
on
preserving
integrity
against
threats.
review
delves
into
intricate
role
shedding
light
innovative
strategies
its
prevention
treatment,
through
pathways.
PeerJ,
Год журнала:
2023,
Номер
11, С. e14797 - e14797
Опубликована: Фев. 1, 2023
Liver
cancer
is
a
common
malignancy
with
high
morbidity
and
mortality
rates.
Changes
in
liver
metabolism
are
key
factors
the
development
of
primary
hepatic
carcinoma,
mitochondrial
dysfunction
closely
related
to
occurrence
tumours.
Accordingly,
study
metabolic
mechanism
mitochondria
carcinomas
has
gained
increasing
attention.
A
growing
body
research
suggests
that
defects
respiration
not
generally
responsible
for
aerobic
glycolysis,
nor
they
typically
selected
during
tumour
evolution.
Conversely,
oxidative
phosphorylation
(OXPHOS)
may
promote
proliferation,
metastasis,
invasion
carcinoma.
This
review
presents
current
paradigm
roles
glycolysis
OXPHOS
hepatocellular
carcinoma
(HCC).
Mitochondrial
cytoplasmic
cooperate
maintain
energy
balance
HCC
cells.
Our
provides
evidence
targeting
as
potential
therapy
HCC.