Advanced Science,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 16, 2024
Abstract
Ischemia‐reperfusion
injury
(IRI)
is
the
leading
cause
of
hepatic
graft
dysfunction,
resulting
from
hepatocyte
damage.
Nevertheless,
given
few
specialized
therapeutics
available
in
IRI,
additional
mechanistic
insights
into
damage
are
required.
Here,
protein
solute
carrier
family
39
member
14
(SLC39A14)
identified
as
a
pro‐ferroptosis
target
hepatocytes
human
liver
allografts
through
single‐cell
RNA
sequencing
analysis.
SLC39A14
knockdown
significantly
mitigated
IRI
by
preventing
ferroptosis
vivo
and
vitro.
Mechanistically,
inhibition
suppressed
non‐transferrin‐bound
iron
(NTBI)
uptake
hepatocytes,
thereby
reducing
overload
cell
ferroptosis.
Moreover,
bone
marrow‐derived
mesenchymal
stem
cells
(hBMSCs)
found
to
exhibit
notable
therapeutic
effect
on
downregulating
expression.
Exosomes
derived
hBMSCs
delivered
abundant
miR‐16‐5p
which
post‐transcriptionally
expression
reduced
induced
IRI.
In
conclusion,
triggers
mediating
NTBI
inducing
hBMSC‐based
therapy
promising
reverse
this
progression
JHEP Reports,
Journal Year:
2023,
Volume and Issue:
6(1), P. 100960 - 100960
Published: Nov. 16, 2023
The
process
of
dead
cell
clearance
by
phagocytic
cells,
called
efferocytosis,
prevents
inflammatory
necrosis
and
promotes
resolution
repair.
Defective
efferocytosis
contributes
to
the
progression
numerous
diseases
in
which
death
prominent,
including
liver
disease.
Many
gaps
remain
our
understanding
how
macrophages
carry
out
this
goes
awry
various
types
diseases.
Studies
thus
far
have
suggested
that,
upon
injury,
resident
Kupffer
cells
(KCs)
infiltrating
monocyte-derived
(MoMϕs)
clear
limit
inflammation,
and,
through
macrophage
reprogramming,
repair
damage.
However,
unusual
settings,
can
promote
In
review,
we
will
focus
on
acute
chronic
diseases,
metabolic
dysfunction-associated
steatohepatitis.
Understanding
mechanisms
consequences
has
potential
shed
new
light
disease
pathophysiology
suggest
treatment
strategies
prevent
progression.
IUBMB Life,
Journal Year:
2024,
Volume and Issue:
76(8), P. 534 - 547
Published: Feb. 21, 2024
Baicalin
is
an
active
compound
extracted
from
Scutellaria
baicalensis
with
antioxidant
and
anti-inflammatory
properties.
Bone
mesenchymal
stem
cells
(BMSCs)-derived
exosomes
have
shown
promise
for
the
treatment
of
hepatic
ischemia-reperfusion
(I/R)
injury.
This
study
aims
to
investigate
role
Baicalin-pretreated
BMSCs-derived
in
I/R
injury
its
mechanisms.
BMSCs
were
pretreated
or
without
Baicalin,
their
(Ba-Exo
Exo)
collected
characterized.
These
administered
mice
via
tail
vein
injection.
Treatment
Exo
Ba-Exo
significantly
suppressed
elevation
ALT
AST
induced
by
Additionally,
both
treatments
resulted
a
reduction
liver
weight-to-body
weight
ratio.
RT-PCR
results
revealed
significant
downregulation
pro-inflammatory
cytokines
treatment.
Both
improved
Th17/Treg
cell
imbalance
reduced
cocultured
normal
cells,
expression
fibroblast
growth
factor
21
(FGF21)
was
elevated
through
After
treatment,
JAK2/STAT3
pathway
inhibited,
FOXO1
upregulated.
Finally,
recombinant
FGF21
injected
into
mouse
veins
assess
effects.
Recombinant
injection
further
inhibited
pathway,
increased
expression,
imbalance.
In
conclusion,
this
confirms
protective
effects
against
mitigates
injury,
achieved
inducing
inhibiting
activating
expression.
Therefore,
baicalin
pretreatment
emerges
as
promising
strategy
enhance
therapeutic
capability
I/R.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(3), P. 559 - 559
Published: March 1, 2024
Cell
death
is
crucial
for
maintaining
tissue
balance
and
responding
to
diseases.
However,
under
pathological
conditions,
the
surge
in
dying
cells
results
an
overwhelming
presence
of
cell
debris
release
danger
signals.
In
liver,
this
gives
rise
hepatic
inflammation
hepatocellular
death,
which
are
key
factors
various
liver
diseases
caused
by
viruses,
toxins,
metabolic
issues,
or
autoimmune
factors.
Both
clinical
vivo
studies
strongly
affirm
that
hepatocyte
serves
as
a
catalyst
progression
disease.
This
advancement
characterized
successive
stages
inflammation,
fibrosis,
cirrhosis,
culminating
higher
risk
tumor
development.
review,
we
explore
pivotal
forms
including
apoptosis,
pyroptosis,
necroptosis,
examining
their
roles
both
acute
chronic
cancer.
Furthermore,
discuss
significance
surgery
ischemia-reperfusion
injury.
Our
objective
illuminate
molecular
mechanisms
governing
diseases,
understanding
identifying
therapeutic
opportunities
aimed
at
modulating
pathways.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(4), P. 918 - 918
Published: April 20, 2024
Cysteine
dioxygenase
type
1
(Cdo1)
is
a
tumor
suppressor
gene.
It
regulates
the
metabolism
of
cysteine,
thereby
influencing
cellular
antioxidative
capacity.
This
function
puts
Cdo1
in
prominent
position
to
promote
ferroptosis
and
apoptosis.
promotes
mainly
by
decreasing
amounts
antioxidants,
leading
autoperoxidation
cell
membrane
through
Fenton
reaction.
apoptosis
product
cysteine
metabolism,
taurine,
low
level
antioxidants.
Many
cancers
exhibit
altered
Cdo1,
underscoring
its
crucial
role
cancer
survival.
Genetic
epigenetic
alterations
have
been
found,
with
methylation
promoter
as
most
common
mutation.
The
fact
that
no
was
found
be
caused
alone
indicates
mild.
By
compiling
current
knowledge
about
apoptosis,
ferroptosis,
this
review
suggests
possibilities
for
how
mild
anticancer
could
harnessed
new
therapies.
Here,
developing
drugs
targeting
considered
meaningful
neoadjuvant
therapies,
example,
helping
against
development
anti-cancer
drug
resistance
cells.
Cell Death Discovery,
Journal Year:
2025,
Volume and Issue:
11(1)
Published: April 1, 2025
Abstract
Hepatic
steatosis
significantly
elevates
the
vulnerability
of
graft
to
ischemia-reperfusion
(I/R)
injury
during
liver
transplantation
(LT).
We
investigated
protective
role
insulin-induced
gene
2
(Insig2)
in
steatotic
liver’s
I/R
and
underlying
mechanisms.
Employing
mouse
model
with
Insig2
knock-out
or
hepatocyte-specific
overexpression
high-fat
diets
induce
steatosis,
we
subjected
these
mice
hepatic
injury.
The
primary
hepatocytes
isolated
from
were
used
vitro
hypoxia/reoxygenation
(H/R)
experiment.
Our
integrated
vivo
approach
uncovered
that
deficiency
exacerbated
damage
following
injury,
whereas
its
offers
protection.
Mechanically,
integrative
analysis
transcriptome,
proteome,
metabolome
found
disturbed
lipid
metabolism
oxidative
stress
homeostasis,
particularly
inhibiting
GPX4
expression
ferroptosis.
Furthermore,
chemical
inhibition
ferroptosis
reversed
deleterious
effect
deficiency;
influence
was
negated
by
target
GPX4,
leading
an
exacerbation
damage.
These
insights
underscored
potential
Insig2-GPX4
axis
as
a
therapeutic
target,
presenting
novel
avenue
for
enhancing
resilience
grafts
against
Acta Biochimica et Biophysica Sinica,
Journal Year:
2023,
Volume and Issue:
55(9), P. 1337 - 1347
Published: June 16, 2023
Ferroptosis,
an
iron-dependent
form
of
regulated
cell
death,
results
in
lipid
peroxidation
polyunsaturated
fatty
acids
the
membrane,
which
is
catalyzed
by
iron
ions
and
accumulated
to
lethal
levels.
It
mechanistically
distinct
from
other
forms
such
as
apoptosis,
pyroptosis,
necroptosis,
so
it
may
address
problem
cancer
resistance
apoptosis
provide
new
therapeutic
strategies
for
treatment,
has
been
intensively
studied
over
past
few
years.
Notably,
considerable
advances
have
made
antitumor
research
natural
products
due
their
multitargets
side
effects.
According
research,
can
also
induce
ferroptosis
therapies.
In
this
review
we
summarize
molecular
mechanisms
ferroptosis,
introduce
key
regulatory
genes
discuss
progress
product
field
theoretical
guidance
on
product-induced
tumors.
Biomeditsinskaya Khimiya,
Journal Year:
2023,
Volume and Issue:
69(6), P. 333 - 352
Published: Jan. 1, 2023
The
review
considers
modern
data
on
the
mechanisms
of
activation
and
redox
regulation
NLRP3
inflammasome
gasdermins,
as
well
role
selenium
in
these
processes.
Activation
pyroptosis
represent
an
evolutionarily
conserved
mechanism
defense
against
pathogens,
described
for
various
types
cells
tissues
(macrophages
monocytes,
microglial
astrocytes,
podocytes
parenchymal
kidneys,
periodontal
tissues,
osteoclasts
osteoblasts,
digestive
urogenital
systems,
etc.).
Depending
characteristics
regulation,
participants
inflammation
can
be
subdivided
into
2
groups.
Members
first
group
block
mitochondrial
electron
transport
chain,
promote
formation
reactive
oxygen
species
development
oxidative
stress.
This
includes
granzymes,
antiviral
signaling
protein
MAVS,
others.
second
thioredoxin
interacting
(TXNIP),
erythroid-derived
nuclear
factor-2
(NRF2),
Kelch-like
ECH-associated
1
(Keap1),
ninjurin
(Ninj1),
scramblase
(TMEM16),
regulatory
kinase
(NEK7),
caspase-1,
gasdermins
GSDM
B,
D
They
have
redox-sensitive
domains
and/or
cysteine
residues
subjected
to
glutathionylation/deglutathionylation
or
other
regulation.
Suppression
stress
depends
activity
antioxidant
enzymes
glutathione
peroxidase
(GPX)
reductase
(TRXR),
containing
a
selenocysteine
residue
Sec
active
site.
expression
GPX
TRXR
is
regulated
by
NRF2
concentration
blood.
Selenium
deficiency
causes
ineffective
translation
UGA
codon,
termination,
and,
consequently,
synthesis
inactive
selenoproteins,
which
cause
programmed
cell
death:
apoptosis
nerve
sperm,
necroptosis
erythrocyte
precursors,
infected
myeloid
cells,
ferroptosis
T-
B-lymphocytes,
kidney
pancreatic
cells.
In
addition,
suboptimal
concentrations
blood
(0.86
μM
68
μg/l
less)
significant
impact
more
than
two
hundred
fifty
genes
compared
optimal
(1.43
113
μg/l).
Based
above,
we
propose
consider
important
parameter
homeostasis
cell.
Suboptimal
(or
states)
should
used
assessment
risk
developing
inflammatory
