Metabolic consequences of erastin-induced ferroptosis in human ovarian cancer cells: an untargeted metabolomics study
Frontiers in Molecular Biosciences,
Год журнала:
2025,
Номер
11
Опубликована: Янв. 20, 2025
Introduction
Ovarian
cancer
has
been
difficult
to
cure
due
acquired
or
intrinsic
resistance
and
therefore,
newer
more
effective
drugs/approaches
are
needed
for
a
successful
treatment
in
the
clinic.
Erastin
(ER),
ferroptosis
inducer,
kills
tumor
cells
by
generating
accumulating
reactive
oxygen
species
(ROS)
within
cell,
resulting
an
iron-dependent
oxidative
damage-mediated
ferroptotic
cell
death.
Methods
We
have
utilized
human
ovarian
lines,
OVCAR-8
its
adriamycin-selected,
multi-drug
protein
(MDR1)-expressing
NCI/ADR-RES,
both
equally
sensitive
ER,
identify
metabolic
biomarkers
of
ferroptosis.
Results
Our
studies
showed
that
ER
rapidly
depleted
cellular
glutathione
cysteine
enhanced
formation
ophthalamate
(OPH)
cells.
Opthalalmate
proposed
be
biomarker
stress
study
also
found
significant
decreases
taurine,
natural
antioxidant
Additionally,
we
decreased
levels
NAD+/NADP+,
carnitines
glutamine/glutamate
cells,
suggesting
stress,
decrease
energy
production,
mitochondrial
disfunctions,
leading
Conclusion
identified
several
potential
ER-induced
including
OPH,
NAD+,
NADP+
glutamate
Identifying
specific
predictive
whether
is
susceptible
will
help
us
devise
modalities.
Язык: Английский
Metabolomics insights into the protective molecular mechanism of Vaccinium myrtillus against oxidative stress in intestinal cells
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Март 13, 2025
Abstract
Blueberry
(
Vaccinium
myrtillus
L.
)
is
a
rich
source
of
secondary
metabolites
known
for
their
potent
antioxidant,
anti-inflammatory,
and
cytoprotective
properties.
These
compounds
are
essential
in
neutralizing
reactive
oxygen
species
(ROS),
which
implicated
oxidative
stress-related
diseases.
In
this
study,
we
induced
stress
IEC-6
small
intestine
cells
using
hydrogen
peroxide
(H
2
O
),
creating
cellular
model
to
investigate
the
biochemical
response.
The
obtained
results
showed
that
blueberry
extract
(BLUBE)
significantly
exhibited
strong
antioxidant
capacity,
as
evidenced
by
DPPH,
FRAP
ABTS
vitro
tests.
Additionally,
BLUBE
effectively
inhibited
release
enhanced
response,
indicated
improved
wound
healing
clonogenic
potential
reduction
fibers
rearrangement
apoptosis.
Metabolomic
analysis,
specifically
High-Resolution
Mass
Spectrometry
(HR-MS),
was
employed
elucidate
metabolic
alterations
associated
with
protective
activity
against
cells.
Chemometric
approaches
were
applied
preprocess
data,
explore
variability,
identify
systematic
biases,
ensuring
removal
batch
effects
other
experimental
artifacts.
A
Partial
Least
Squares
Discriminant
Analysis
classification
confirmed
clear
group
stratifications
high
accuracy
(98.75
±
2.31%),
sensitivity,
specificity,
aiding
identification
significant
pathway
enrichment
analysis.
Key
pathways,
including
sphingolipid
metabolism,
taurine
hypotaurine
glycerophospholipid
cysteine
methionine
modulated,
supporting
basis
BLUBE’s
effects.
fact,
able
partially
reverse
downregulation
these
reducing
promoting
cell
survival.
This
study
highlights
power
HR-MS-based
metabolomics
uncovering
mechanisms
nutraceuticals
emphasizes
agent
It
also
underscores
growing
significance
food
pharmaceutical
industries.
Язык: Английский
Metabolic changes during cardiac regeneration in the axolotl
Developmental Dynamics,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 22, 2025
Abstract
Background
The
axolotl
is
a
prominent
model
organism
of
heart
regeneration
due
to
its
ability
anatomically
and
functionally
repair
the
after
an
injury
that
mimics
human
myocardial
infarction.
In
humans,
such
leads
permanent
scarring.
Cardiac
has
been
linked
metabolism
oxygenation
state,
but
so
far,
these
factors
remain
be
detailed
in
model.
this
descriptive
study,
we
have
investigated
metabolic
changes
occurred
during
cardiac
axolotl.
Results
We
describe
systemic
local
involving
early
upregulation
glucose
uptake
nucleotide
biosynthesis
followed
by
later
increase
acetate
uptake.
detect
several
promising
metabolites
for
future
studies
show
that,
unlike
other
popular
animal
models
capable
intrinsic
regeneration,
maintains
regenerative
under
hyperoxic
conditions.
Conclusions
Axolotls
undergo
dynamic
process
display
robust
reparative
response
cryo‐injury,
which
unaffected
hyperoxia.
Язык: Английский
Differences in the Fecal Metabolome of Autoimmune Pancreatitis Patients
United European Gastroenterology Journal,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 17, 2025
ABSTRACT
Background
Chronic
pancreatitis
is
a
risk
factor
for
pancreatic
cancer.
Autoimmune
unique
form
of
chronic
that
primarily
characterized
by
its
immune
mediate
etiology,
clinically
resembling
cancer,
yet
uniquely
responsive
to
steroid
treatment.
Objective
Early
and
accurate
diagnosis
autoimmune
vital
effective
treatment
patient
prognosis,
which
new
diagnostic
tools
are
urgently
required.
Gut
microbiota
dysbiosis
has
been
identified
correlate
with
the
development
diseases,
provides
opportunities
discovery
disease
biomarkers.
Methods
We
utilized
mass
spectrometric
global
metabolomics
investigation
fecal
samples,
investigating
microbiome,
dietary
human
metabolism.
Results
discovered
series
newly
metabolic
signatures
between
both
groups
including
enterolactone,
4‐guanidinobutanoic
acid,
methylthioadenosine
sulfoxide.
Additionally,
analysis
revealed
significant
differences
in
several
pathways
such
as
fatty
acids,
alkaloids,
amino
acids
peptides.
Conclusion
Our
observations
provide
novel
insights
into
important
microbiome‐derived
metabolites
distinguish
from
pancreatitis.
These
findings
reveal
systemic
responses
may
be
developed
potential
biomarkers
future
Язык: Английский
Multi-Omics Integration With Machine Learning Identified Early Diabetic Retinopathy, Diabetic Macula Edema and Anti-VEGF Treatment Response
Translational Vision Science & Technology,
Год журнала:
2024,
Номер
13(12), С. 23 - 23
Опубликована: Дек. 13, 2024
Purpose:
Identify
optimal
metabolic
features
and
pathways
across
diabetic
retinopathy
(DR)
stages,
develop
risk
models
to
differentiate
macular
edema
(DME),
predict
anti-vascular
endothelial
growth
factor
(anti-VEGF)
therapy
response.
Methods:
We
analyzed
108
aqueous
humor
samples
from
78
type
2
diabetes
mellitus
patients
30
healthy
controls.
Ultra-high-performance
liquid
chromatography–high-resolution-mass-spectrometry
detected
lipidomics
metabolomics
profiles.
DME
received
≥3
anti-VEGF
treatments,
categorized
into
strong
weak
response
groups.
Machine
learning
(ML)
screened
prospective
features,
developing
prediction
models.
Results:
Key
identified
in
the
datasets
included
n-acetyl
isoleucine
(odds
ratio
[OR]
=
1.635),
cis-aconitic
acid
(OR
3.296),
ophthalmic
0.836)
for
DR.
For
early-DR,
1.791)
decaethylene
glycol
(PEG-10)
0.170)
were
as
key
markers.
L-kynurenine
0.875),
niacinamide
0.843),
linoleoyl
ethanolamine
0.941)
significant
indicators
DME.
Trigonelline
1.441)
4-methylcatechol-2-sulfate
1.121)
emerged
predictors
anti-VEGF.
Predictive
achieved
R²
values
of
99.9%,
97.7%,
93.9%,
98.4%
DR,
DME,
groups
calibration
set,
respectively,
validated
well
with
96.3%,
96.8%,
79.9%,
96.3%.
Conclusions:
This
research
used
ML
identify
differential
DR
patients.
It
implies
that
can
effectively
early
disease
progression
potential
responders
eyes.
Translational
Relevance:
The
may
aid
predicting
optimizing
therapeutic
strategies
Язык: Английский
Ophthalmic acid is a bloodborne metabolite that contributes to age-induced cardiomyocyte hypertrophy
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 9, 2024
Cardiac
aging
involves
the
development
of
left
ventricular
hypertrophy
alongside
a
decline
in
functional
capacity.
Here,
we
use
neutral
blood
exchange
to
demonstrate
that
acute
removal
age-accumulated
factors
significantly
regresses
cardiac
aged
mice.
The
reversal
was
not
attributed
age-associated
hemodynamic
effects,
implicating
role
blood-derived
factors.
In
addition,
overarching
paradigm
systemic
maintains
age-related
overabundance
plasma
proteins
are
largely
responsible
for
causing
pathological
phenotypes
tissues.
Our
results
suggest
metabolites,
proteins,
drive
instead.
Upon
analyzing
serum
metabolomics
data
sets,
identified
ophthalmic
acid
as
circulating
metabolite
whose
levels
increase
with
advanced
age.
Treatment
adult
mouse
and
neonatal
rat
cardiomyocytes
culture
increased
their
relative
surface
areas.
This
study
uncovers
non-protein
may
contribute
cardiomyocyte
during
aging.
Identifying
method
counteract
acid's
hypertrophic
effects
reveal
novel
therapeutic
opportunities
rejuvenation.
Язык: Английский
Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 29, 2024
Abstract
Coordination
of
adaptive
metabolism
through
cellular
signaling
networks
and
metabolic
response
is
essential
for
balanced
flow
energy
homeostasis.
Post-translational
modifications
such
as
phosphorylation
offer
a
rapid,
efficient,
dynamic
mechanism
to
regulate
networks.
Although
numerous
sites
have
been
identified
on
enzymes,
much
remains
unknown
about
their
contribution
enzyme
function
systemic
metabolism.
In
this
study,
we
stratify
enzymes
based
location
with
respect
functional
dimerization
domains.
Our
analysis
reveals
that
the
majority
published
phosphosites
are
oxidoreductases,
particular
enrichment
phosphotyrosine
(pY)
in
proximity
binding
domains
substrates,
cofactors,
active
sites,
or
dimer
interfaces.
We
identify
altered
obesity
using
high
fat
diet
(HFD)
induced
model
coupled
multiomics,
interrogate
impact
pY
hepatic
HFD
dysregulation
redox
homeostasis
reductive
at
phosphoproteome
metabolome
level
sex-specific
manner,
which
was
reversed
by
supplementing
antioxidant
butylated
hydroxyanisole
(BHA).
Partial
least
squares
regression
(PLSR)
predict
BHA
changes
metabolites.
characterize
predictive
glutathione
S-transferase
pi
1
(GSTP1),
isocitrate
dehydrogenase
(IDH1),
uridine
monophosphate
synthase
(UMPS)
CRISPRi-rescue
stable
isotope
tracing.
revealed
GSTP1
UMPS
inhibit
activity
while
site
IDH1
induces
promote
carboxylation.
Overall,
our
approach
provides
insight
into
convergence
points
where
fine-tunes
Summary
Statement
By
employing
multi-disciplinary
structural
features
map
systems
obesity,
key
pathways
sex
specific
phosphoproteomic
responses,
validate
role
select
enzymes.
Язык: Английский
Metabolic abnormalities and reprogramming in cats with naturally occurring hypertrophic cardiomyopathy
ESC Heart Failure,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 5, 2024
Abstract
Background
and
aims
The
heart
is
a
metabolic
organ
rich
in
mitochondria.
failing
reprograms
to
utilize
different
energy
substrates,
which
increase
its
oxygen
consumption.
These
adaptive
changes
contribute
increased
oxidative
stress.
Hypertrophic
cardiomyopathy
(HCM)
common
condition,
affecting
approximately
15%
of
the
general
cat
population.
Feline
HCM
shares
phenotypical
genotypical
similarities
with
human
HCM,
but
disease
mechanisms
for
both
species
are
incompletely
understood.
Our
goal
was
characterize
global
metabolome
between
healthy
control
cats
stages
HCM.
Methods
Serum
samples
from
83
cats,
majority
(70/83)
were
domestic
shorthair
included
23
31
12
preclinical
American
College
Veterinary
Internal
Medicine
(ACVIM)
B1
B2,
respectively,
17
history
clinical
failure
or
arterial
thromboembolism
(ACVIM
stage
C),
collected
untargeted
metabolomic
analysis.
Multiple
linear
regression
adjusted
age,
sex
body
weight
applied
compare
across
groups.
Results
study
identified
1253
metabolites,
983
metabolites
had
known
identities.
Statistical
analysis
167
that
significantly
among
groups
(adjusted
P
<
0.1).
About
half
differentially
lipids,
including
glycerophospholipids,
sphingolipids
cholesterol.
concentrations
free
fatty
acids,
3‐hydroxy
acids
acylcarnitines
compared
group.
levels
creatine
phosphate
multiple
Krebs
cycle
intermediates,
succinate,
aconitate
α‐ketoglutarate,
also
accumulated
circulation
cats.
In
addition,
serum
nicotinamide
tryptophan,
precursors
de
novo
NAD+
biosynthesis,
reduced
versus
Glutathione
metabolism
altered.
cystine,
oxidized
form
cysteine
cysteine‐glutathione
disulfide,
elevated
groups,
indicative
heightened
Further,
level
ophthalmate,
an
endogenous
glutathione
analog
competitive
inhibitor,
by
more
than
twofold
Finally,
several
uremic
toxins,
guanidino
compounds
protein
bound
putrescine,
Conclusions
provided
evidence
deranged
metabolism,
altered
homeostasis
impaired
renal
toxin
excretion.
Altered
lipid
suggested
perturbed
structure
function
cardiac
sarcolemma
membrane
signalling.
Язык: Английский
Metabolomics analysis of rat blood in atherosclerosis modelling
Hygiene and Sanitation,
Год журнала:
2024,
Номер
103(11), С. 1392 - 1397
Опубликована: Дек. 16, 2024
Introduction.
Atherosclerotic
changes
in
blood
vessels
are
one
of
the
main
causes
death
from
cardiovascular
diseases
worldwide.
The
use
modern
approaches
to
study
disease
giving
a
more
detailed
description
its
pathophysiology
may
open
up
additional
opportunities
for
prevention,
diagnosis,
and
treatment.
Metabolomics
is
such
allows
obtaining
information
on
large
number
compounds,
combination
which
reflects
ongoing
metabolic
changes.
data
presented
this
article
supplement
our
previously
published
results.
aimed
find
relationship
between
thickness
wall
thoracic
aorta
animals
hyperlipidemic
diet
content
metabolites
blood.
Materials
methods.
involved
thirty
male
albino
Wistar
rats.
Atherosclerosis
was
modelled
using
consisting
standard
feed,
simple
sugars
fats
with
addition
vitamin
D3
Thiamazole.
Liquid
chromatography
tandem
mass
spectrometry
used
metabolomics
test.
Histological
sections
rat
aortas
were
stained
hematoxylin
eosin
analysis.
Results.
Histopathological
examination
fed
atherogenic
revealed
morphological
signs
atherosclerosis
severe
calcification
vascular
wall.
cases
(2.61
±
0.05
µm)
statistically
thicker
than
controls
(1.82
0.01
(p
<
0.001).
Correlation
analysis
significant
negative
relationships
aortic
arginine,
indole
three
derivatives,
ketodeoxycholic
acid,
positive
glutamate,
ophthalmic
adenosine
diphosphate,
two
long-chain
acylcarnitines,
glycocholic
oxidized
fatty
six
lysoglycerophospholipids.
Limitations.
included
only
rats
limited
rodents
per
group.
Conclusion.
metabolomic
alterations
indicates
restructuring
typical
atherosclerosis,
resulting
oxidative
stress,
an
inflammatory
response,
lipid
metabolism
disorders
characterized
by
calcification,
endothelial
dysfunction,
increased
thrombosis.
Язык: Английский