Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Nov. 2, 2024
Fumarylacetoacetate
hydrolase
(FAH)
catalyzes
the
final
step
of
tyrosine
degradation
pathway.
In
this
study,
we
isolated
and
characterized
two
homologous
BnaFAH
genes
in
Brassica
napus
L.
variant
Westar,
then
used
CRISPR/Cas9-mediated
targeted
mutagenesis
to
generate
a
series
transgene-free
mutant
lines
either
with
single
or
double-null
bnafah
alleles.
Among
these
lines,
aacc
(bnafah)
line,
rather
than
aaCC
(bnaa06fah)
exhibited
programmed
cell
death
(PCD)
under
short
days
(SD).
Histochemical
staining
content
measurement
confirmed
that
accumulation
reactive
oxygen
species
(ROS)
was
significantly
higher
bnaa06fah.
To
further
elucidate
mechanism
PCD,
performed
transcriptomic
analyses
bnaa06fah
at
different
SD
stages.
A
heatmap
cluster
differentially
expressed
(DEGs)
revealed
PCD
may
be
related
various
redox
regulatory
involved
antioxidant
activity,
ROS-responsive
regulation
calcium
signaling.
Combined
results
previous
studies,
our
work
expression
levels
BnaC04CAT2,
BnaA09/C09SAL1,
BnaA08/C08ACO2,
BnaA07/C06ERO1,
BnaA08ACA1,
BnaC04BIK1,
BnaA09CRK36
BnaA03CPK4
were
might
candidate
hub
for
PCD.
Together,
underscore
ability
phenotypes
alter
orthologs
through
gene
editing
elucidated
molecular
mechanisms
oxidative
stress-induced
plants.
Gut Microbes,
Journal Year:
2025,
Volume and Issue:
17(1)
Published: Jan. 16, 2025
Enterococcus
faecalis-infected
macrophages
produce
4-hydroxynonenal
(4-HNE)
that
mediates
microbiota-induced
bystander
effect
(MIBE)
leading
to
colorectal
cancer
(CRC).
Glutathione
S-transferase
alpha
4
(Gsta4),
a
specific
detoxifying
enzyme
for
4-HNE,
is
overexpressed
in
human
CRC
and
E.
faecalis-induced
murine
CRC.
However,
the
roles
of
Gsta4
colitis
remain
unclear.
Herein,
we
demonstrate
essential
MIBE
by
protecting
from
ferroptosis.
faecalis
OG1RFSS
was
used
induce
Gsta4-/-
Il10-/-/Gsta4-/-
mice
orogastric
gavage.
Ferroptosis
assessed
Gsta4-deficient
macrophages.
We
found
that,
unlike
Il10-/-
mice,
colonized
with
failed
develop
or
Immunofluorescent
staining
showed
reduction
lamina
propria
faecalis-colonized
as
well
decreased
Gpx4
expression,
indicating
occurrence
further
confirmed
infected
faecalis.
Moreover,
inactivation
induced
upregulation
Hmox1
phosphorylated
c-Jun
while
blocked
Nos2
accumulation
intracellular
ferrous
iron,
lipid
peroxidation
and,
eventually,
Finally,
Mapk8,
ferroptosis
driver,
remarkably
elevated
These
results
suggest
blocks
eliminating
macrophages,
thereby
attenuates
Science Advances,
Journal Year:
2024,
Volume and Issue:
10(42)
Published: Oct. 16, 2024
A
major
therapeutic
barrier
in
melanoma
is
the
coexistence
of
diverse
cellular
states
marked
by
distinct
metabolic
traits.
Transitioning
from
a
proliferative
to
an
invasive
phenotype
coupled
with
increased
ferroptosis
vulnerability.
However,
regulatory
circuits
controlling
susceptibility
across
cell
are
unknown.
In
this
work,
we
identified
Apolipoprotein
E
(
APOE
)
as
top
lipid-metabolism
gene
segregating
MITF
high
/AXL
low
proliferative/ferroptosis-resistant
invasive/ferroptosis-sensitive
state.
Mechanistically,
ApoE
secreted
cells
protects
ferroptosis-inducing
agents
reducing
content
peroxidation-prone
polyunsaturated
fatty
acids
and
boosting
GPX4
levels
both
vitro
vivo.
Whole-exome
sequencing
indicates
that
expression
patients
associated
resistance
ferroptosis,
regardless
germline
status.
aggregate,
found
ferroptosis-resistance
mechanism
between
relying
on
potential
biomarker
for
poor
response
melanoma.
Cell Death and Disease,
Journal Year:
2023,
Volume and Issue:
14(8)
Published: Aug. 21, 2023
Acinar
cell
dedifferentiation
is
one
of
the
most
notable
features
acute
and
chronic
pancreatitis.
It
can
also
be
initial
step
that
facilitates
pancreatic
cancer
development.
In
present
study,
we
further
decipher
precise
mechanisms
regulation
using
primary
human
cells
murine
experimental
models.
Our
RNAseq
analysis
indicates
that,
in
both
species,
early
acinar
accompanied
by
multiple
pathways
related
to
survival
are
highly
enriched,
where
SLC7A11
(xCT)
transiently
upregulated.
xCT
specific
subunit
cystine/glutamate
antiporter
system
xC-.
To
its
role,
gene
silencing,
pharmacological
inhibition
a
knock-out
mouse
model
were
used.
with
depleted
or
reduced
function
show
an
increase
ferroptosis
relating
lipid
peroxidation.
Lower
glutathione
levels
more
ROS
accumulation
could
rescued
antioxidant
N-acetylcysteine
inhibitor
ferrostatin-1.
caerulein-induced
pancreatitis
mice,
prevents
peroxidation
cells.
conclusion,
during
stress,
fate
seems
poised
for
avoiding
several
forms
death.
specifically
fueling
pool
maintaining
balance.
The
data
suggest
offers
druggable
tipping
point
steer
stress
conditions.
Journal of Pancreatology,
Journal Year:
2023,
Volume and Issue:
7(1), P. 10 - 20
Published: Dec. 29, 2023
Acute
pancreatitis
is
a
severe
inflammatory
disorder
with
limited
treatment
options.
Improved
understanding
of
disease
mechanisms
has
led
to
new
and
potential
therapies.
Here
we
summarize
what
view
as
some
the
most
promising
therapies
for
treating
acute
pancreatitis,
emphasizing
rationale
specific
treatments
based
on
mechanisms.
Targeted
pharmacologic
interventions
are
highlighted.
We
explore
benefits
risks
concerning
reducing
injury,
minimizing
complications,
improving
long-term
outcomes.
Mechanisms
associated
initiation,
perpetuation,
reconstitution
highlighted,
along
therapeutic
targets
how
these
relate
treatments.
