Vaccarin Ameliorates Renal Fibrosis by Inhibiting Ferroptosis via Nrf2/SLC7A11/GPX4 Signaling Pathway
Mengjiao Cui,
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Qiming Xu,
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Lianxiang Duan
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et al.
Drug Design Development and Therapy,
Journal Year:
2025,
Volume and Issue:
Volume 19, P. 1609 - 1626
Published: March 1, 2025
Purpose:
Vaccarin
is
a
natural
flavonoid
glycoside
with
anti-inflammatory,
antioxidant
and
nephroprotective
effects.
However,
the
effects
of
vaccarin
on
renal
fibrosis
(RF)
its
molecular
mechanisms
remain
unclear.
This
study
aimed
to
investigate
RF
mechanisms.
Methods:
Network
pharmacology
was
used
analyze
effect
RF,
docking
dynamics
simulations
were
performed
assess
binding
nuclear
factor
erythroid
2-related
2
(Nrf2)
vaccarin.
A
mouse
model
unilateral
ureteral
obstruction
(UUO)
established
in
vivo,
human
tubular
epithelial
(HK2)
cells
induced
transforming
growth
factor-β
(TGF-β)
RSL3,
respectively,
as
an
vitro
model.
The
anti-fibrotic
observed
by
histopathological
staining
determination
fibrous
markers.
Changes
oxidative
stress
ferroptosis-related
markers
detected
kits,
Western
blot
(WB),
qRT-PCR
immunofluorescence
(IF).
Finally,
Nrf2
inhibitors
added
observe
ferroptosis.
Results:
cross
genes
are
enriched
for
stress.
binds
stably
Both
vivo
experiments
showed
that
treatment
reduced
expression
markers,
decreased
levels
reactive
oxygen
species
(ROS),
malondialdehyde
(MDA),
lipid
peroxidation
(LPO)
Fe
2+
,
increased
glutathione
(GSH)
secretion.
In
addition,
down-regulated
Long-chain
acyl-CoA
synthetase
4
(ACSL4),
prostaglandin-endoperoxide
synthase
(PTGS2)
NADPH
oxidase
1
(NOX1),
up-regulated
downstream
solute
transport
family
7
member
11
(SLC7A11)
peroxidase
(GPX4)
expression.
Mechanistic
studies
indicated
activated
Nrf2/SLC7A11/GPX4
pathway
inhibit
ferroptosis,
this
inhibition
effectively
reversed
inhibitor.
Conclusion:
ameliorates
inhibiting
ferroptosis
via
pathway.
Keywords:
vaccarin,
fibrosis,
pathway,
stress,
network
Language: Английский
Targeted Analysis of Serum and Urinary Metabolites for Early Chronic Kidney Disease
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(7), P. 2862 - 2862
Published: March 21, 2025
Chronic
kidney
disease
(CKD)
has
become
one
of
the
most
rapidly
advancing
diseases
century,
contributing
significantly
to
increased
mortality
and
morbidity.
Metabolomics
presents
a
promising
approach
understanding
CKD
pathogenesis
identifying
novel
biomarkers
for
early
diagnosis.
This
study
evaluated
serum
urine
metabolomic
profiles
in
patients
with
declining
glomerular
filtration
rates
(eGFR).
Using
targeted
metabolomics,
we
quantified
seven
potential
metabolites
blood
samples
from
20
healthy
individuals
99
staged
by
eGFR
according
KDIGO
guidelines.
The
analysis
was
conducted
using
ultra-high
performance
liquid
chromatography
combined
electrospray
ionization
quadrupole
time-of-flight
mass
spectrometry.
investigated
included
L-phenylalanine,
L-methionine,
arginine,
indoxyl
sulfate,
kynurenic
acid,
L-acetylcarnitine.
Quantitative
assessments
were
performed
pure
standards
validated
through
methods
such
as
limit
detection
(LOD)
quantification
(LOQ).
findings
identified
diagnosis:
serum,
while
L-acetylcarnitine
significant
urine.
These
could
provide
valuable
insights
into
progression
support
developing
more
effective
diagnostic
tools
intervention.
Language: Английский
Telitacicept monotherapy for refractory idiopathic membranous nephropathy: a case report and literature review
Frontiers in Medicine,
Journal Year:
2025,
Volume and Issue:
12
Published: April 8, 2025
Background
Patients
with
refractory
membranous
nephropathy
(MN)
face
risks
of
progressive
renal
decline
and
end-stage
disease
(ESRD),
limited
treatment
efficacy.
Telitacicept,
a
novel
humanized
recombinant
fusion
protein
effective
in
lupus
nephritis
immunoglobulin
A
(IgAN),
has
few
reports
on
its
use
MN.
Case
presentation
In
May
2023,
an
82-year-old
man
was
admitted
to
Shaoxing
Second
Hospital
bilateral
lower
extremity
edema.
biopsy
confirmed
idiopathic
(IMN).
Standard
therapies,
including
glucocorticoids
(GC),
cyclophosphamide
(CYC),
tacrolimus
(TAC),
rituximab
(RTX),
were
ineffective.
He
developed
steroid-induced
diabetes
acute
failure
during
treatment.
Complete
proteinuria
remission
achieved
telitacicept
monotherapy.
The
patient
is
under
ongoing
clinical
follow-up.
Conclusion
Telitacicept
holds
promise
as
potential
second-line
therapy
for
MN
when
conventional
treatments
prove
However,
due
the
current
lack
robust
evidence
supporting
IMN,
further
research
warranted
establish
efficacy
safety.
Language: Английский
Short Chain Chlorinated Paraffins Impaired Spermatogenesis Process in Mice via Inhibiting α-KG/TET Enzyme Activity
Ruiyang Meng,
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Xingde Du,
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Yu Fu
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et al.
Environmental Science & Technology,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 19, 2024
Short
chain
chlorinated
paraffins
(SCCPs)
are
widely
found
in
various
environmental
media
and
potentially
threaten
human
health.
However,
the
toxicity
mechanisms
of
SCCPs
to
male
reproductive
system
remain
unclear.
In
this
study,
BALB/c
mice
GC-1
cells
were
used
investigate
their
molecular
mechanisms.
decreased
content
tricarboxylic
acid
cycle
intermediate
α-KG
testicular
cells,
thus
inhibiting
activity
DNA
demethylase
TET
enzyme
resulting
an
increase
overall
methylation
level
genome.
Correspondingly,
promoter
demethylation
expression
spermatogenesis-related
genes
Language: Английский