EBioMedicine,
Journal Year:
2024,
Volume and Issue:
102, P. 105088 - 105088
Published: March 26, 2024
Metabolic
dysfunction-associated
steatohepatitis
(MASH)
is
characterised
by
cell
death
of
parenchymal
liver
cells
which
interact
with
their
microenvironment
to
drive
disease
activity
and
fibrosis.
The
identification
the
major
type
could
pave
way
towards
pharmacotherapy
for
MASH.
To
date,
increasing
evidence
suggest
a
regulated
death,
named
ferroptosis,
occurs
through
iron-catalysed
peroxidation
polyunsaturated
fatty
acids
(PUFA)
in
membrane
phospholipids.
Lipid
enjoys
renewed
interest
light
as
druggable
target
This
review
recapitulates
molecular
mechanisms
ferroptosis
physiology,
human
MASH
critically
appraises
results
targeting
preclinical
models.
Rewiring
redox,
iron
PUFA
metabolism
creates
proferroptotic
environment
involved
MASH-related
hepatocellular
carcinoma
(HCC)
development.
Ferroptosis
induction
might
be
promising
novel
approach
eradicate
HCC,
while
its
inhibition
ameliorate
progression.
Science,
Journal Year:
2021,
Volume and Issue:
373(6553)
Published: July 22, 2021
Intestinal
HDL
is
hepatoprotective
High-density
lipoprotein
(HDL)
important
for
cholesterol
metabolism
and
may
have
anti-inflammatory
antimicrobial
properties.
Although
mainly
produced
by
the
liver,
intestine
also
a
source.
Han
et
al.
show
in
mice
that
intestinal
not
routed
to
systemic
circulation.
Rather,
form
of
HDL3,
it
directly
transported
liver
through
hepatic
portal
vein.
There,
sequesters
bacterial
lipopolysaccharide
from
gut
can
trigger
inflammation
damage.
In
various
models
injury,
loss
enteric
exacerbated
pathology.
By
contrast,
drugs
elevating
improved
disease
outcomes.
HDL3
enriched
human
venous
blood,
suggesting
be
targetable
treatment
disease.
Science
,
abe6729,
this
issue
p.
eabe6729
International Journal of Molecular Sciences,
Journal Year:
2022,
Volume and Issue:
23(7), P. 3778 - 3778
Published: March 29, 2022
The
prevalence
of
liver
cancer
is
constantly
rising,
with
increasing
incidence
and
mortality
in
Europe
the
USA
recent
decades.
Among
different
subtypes
cancers,
hepatocellular
carcinoma
(HCC)
most
commonly
diagnosed
cancer.
Besides
advances
diagnosis
promising
results
pre-clinical
studies,
HCC
remains
a
highly
lethal
disease.
In
many
cases,
an
effect
chronic
inflammation,
which
leads
to
formation
complex
tumor
microenvironment
(TME)
composed
immune
stromal
cells.
TME
patients
challenge
for
therapies,
as
it
involved
metastasis
development
resistance.
However,
given
that
intricate
system
cells
interacting
cells,
new
immune-based
therapies
are
being
developed
target
HCC.
Therefore,
understanding
complexity
will
provide
possibilities
design
novel
more
effective
immunotherapeutics
combinatorial
overcome
resistance
treatment.
this
review,
we
describe
role
inflammation
during
progression
by
focusing
on
TME.
We
also
therapeutic
possible
treatment
options.
Cardiovascular Research,
Journal Year:
2022,
Volume and Issue:
119(3), P. 772 - 785
Published: Aug. 11, 2022
Abstract
Aims
Macrophages
have
a
critical
and
dual
role
in
post-ischaemic
cardiac
repair,
as
they
can
foster
both
tissue
healing
damage.
Multiple
subsets
of
resident
monocyte-derived
macrophages
coexist
the
infarcted
heart,
but
their
precise
identity,
temporal
dynamics,
mechanisms
regulating
acquisition
discrete
states
are
not
fully
understood.
To
address
this,
we
used
multi-modal
single-cell
immune
profiling,
combined
with
targeted
cell
depletion
macrophage
fate
mapping,
to
precisely
map
monocyte/macrophage
transitions
after
experimental
myocardial
infarction.
Methods
results
We
performed
transcriptomic
cell-surface
marker
profiling
circulating
cells
mice
challenged
acute
infarction,
integrated
transcriptomes
obtained
before
at
1,
3,
5,
7,
11
days
Using
complementary
strategies
CCR2+
monocyte
mapping
macrophages,
determined
origin
populations.
The
landscape
heart
was
dominated
by
comprising
two
pro-inflammatory
populations
defined
Isg15hi
MHCII+Il1b+,
alongside
non-inflammatory
Trem2hi
cells.
were
observed
ischaemic
area,
remote
viable
myocardium,
comprised
subpopulations
sequentially
populating
Trem2hiSpp1hi
monocyte-to-macrophage
intermediates,
differentiated
Trem2hiGdf15hi
macrophages.
Cardiac
showed
similarities
‘lipid-associated
macrophages’
found
mouse
models
metabolic
diseases
human
indicating
conserved
features
this
state
across
species.
Ischaemic
injury
induced
shift
Ly6Chi
monocytes
towards
Chil3hi
granulocyte-like
features,
signature
occurred
tissue.
In
vitro,
acquired
following
apoptotic-cell
efferocytosis.
Conclusion
Our
work
provides
comprehensive
constituting
valuable
resource
for
further
investigating
how
these
may
be
harnessed
modulated
promote
repair.
Molecular Aspects of Medicine,
Journal Year:
2023,
Volume and Issue:
95, P. 101231 - 101231
Published: Dec. 5, 2023
Liver
fibrosis,
as
an
excess
deposition
of
extracellular
matrix
(ECM)
components,
results
from
chronic
liver
injury
well
persistent
activation
inflammatory
response
and
fibrogenesis.
fibrosis
is
a
major
determinant
for
disease
(CLD)
progression
in
the
last
two
decades
our
understanding
on
molecular
cellular
mechanisms
underlying
fibrogenic
CLD
has
dramatically
improved,
boosting
pre-clinical
studies
clinical
trials
designed
to
find
novel
therapeutic
approaches.
From
these
several
critical
concepts
have
emerged,
starting
reveal
complexity
pro-fibrotic
microenvironment
which
involves
very
complex,
dynamic
interrelated
interactions
between
different
hepatic
extrahepatic
cell
populations.
This
review
will
offer
first
recapitulation
established
pathophysiological
basic
principles
by
intentionally
focus
attention
NAFLD/NASH,
metabolic-related
form
with
high
impact
general
population
emerging
leading
cause
worldwide.
NAFLD/NASH-related
pro-inflammatory
profibrogenic
be
analysed
information
cells,
mediators
signalling
pathways
taken
advantage
methodological
approaches
techniques
(single
genomics,
imaging
mass
cytometry,
vitro
two-
three-dimensional
models,
etc.).
We
next
overview
recent
advancement
diagnostic
prognostic
tools,
including
serum
biomarkers
polygenic
scores,
support
analysis
biopsies.
Finally,
this
provide
current
therapies
treatment
NAFLD/NASH
patients.
