Diabetology & Metabolic Syndrome,
Год журнала:
2024,
Номер
16(1)
Опубликована: Дек. 18, 2024
To
assess
the
association
between
thyroid
dysfunction
and
diabetic
retinopathy
(DR),
a
two-sample
bidirectional
Mendelian
randomization
(MR)
study
utilizing
Genome-wide
Association
Study
(GWAS)
database
was
conducted
to
investigate
causal
relationship
these
two
variables.
In
this
study,
GWAS
of
48,328,151
single
nucleotide
polymorphisms(SNP)
in
European
population
from
IEU
open
were
utilized
as
genetic
tools
for
investigating
dysfunction.
The
total
sample
size
on
hyperthyroidism
460,499
(case
group:
3557;
control
456,942).
hypothyroidism
410,141
30,155;
37,986).
addition,
data
DR
extracted
FinnGen
Biobank,
comprising
319,046
individuals
(10,413
cases
308,633
controls).
For
forward
MR
analysis,
considered
exposures
with
outcome.
Reverse
analysis
using
exposure
outcomes.
Methods:
main
analytical
approach
employed
inverse
variance
weighting(IVW),
supplemented
by
MR-Egger,
Weighted
mode
method,
weighted
median,
Simple
mode.
Cochran's
Q
test,
MR-PRESSO,
MR-Egger
leave-one-out
used
evaluate
sensitivity
pleiotropy.
Two-sample
revealed
significant
presence
an
increased
risk
(IVW:
OR
=
1.29,
95%
[CI]
1.12–1.49,
P
<
0.001;
1.17,
CI
1.10–1.25,
0.001).
reverse
found
be
associated
elevated
developing
1.56,
1.38–1.76,
1.41,
1.25–1.59,
Furthermore,
most
supplementary
methods
also
demonstrated
statistically
differences
exhibited
effect
sizes
consistent
those
obtained
IVW.
confirmed
relative
reliability
our
findings.
Our
findings
provide
evidence
supporting
function
DR.
Cardiovascular Diabetology,
Год журнала:
2025,
Номер
24(1)
Опубликована: Фев. 7, 2025
Cardiovascular
diseases
represent
the
principal
cause
of
death
and
comorbidity
among
people
with
diabetes.
Ferroptosis,
an
iron-dependent
non-apoptotic
regulated
cellular
characterized
by
lipid
peroxidation,
is
involved
in
pathogenesis
diabetic
cardiovascular
diseases.
The
susceptibility
to
ferroptosis
hearts
possibly
related
myocardial
iron
accumulation,
abnormal
metabolism
excess
oxidative
stress
under
hyperglycemia
conditions.
Accumulating
evidence
suggests
can
be
therapeutic
target
for
This
review
summarizes
ferroptosis-related
mechanisms
novel
choices
targeting
pathways.
Further
study
on
ferroptosis-mediated
cardiac
injury
enhance
our
understanding
pathophysiology
provide
more
potential
choices.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Июнь 27, 2024
Ferroptosis,
a
new
type
of
programmed
cell
death
proposed
in
recent
years,
is
characterized
mainly
by
reactive
oxygen
species
and
iron-mediated
lipid
peroxidation
differs
from
death,
such
as
apoptosis,
necrosis,
autophagy.
Ferroptosis
associated
with
variety
physiological
pathophysiological
processes.
Recent
studies
have
shown
that
ferroptosis
can
aggravate
or
reduce
the
occurrence
development
diseases
targeting
metabolic
pathways
signaling
tumors,
ischemic
organ
damage,
other
degenerative
related
to
peroxidation.
Increasing
evidence
suggests
closely
linked
onset
progression
various
ophthalmic
conditions,
including
corneal
injury,
glaucoma,
age-related
macular
degeneration,
diabetic
retinopathy,
retinal
detachment,
retinoblastoma.
Our
review
current
research
on
reveals
significant
advancements
our
understanding
pathogenesis,
aetiology,
treatment
these
conditions.
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
68(3), С. 3309 - 3323
Опубликована: Янв. 30, 2025
A
highly
selective
ferroptosis
inducer
with
drug-like
properties
can
significantly
advance
the
research
on
inducing
for
anticancer
treatment.
We
previously
reported
a
active
GPX4
inhibitor
26a,
but
its
activity
and
stability
need
further
improvement.
In
this
work,
novel
(R)-9i
more
potent
cytotoxicity
(IC50
=
0.0003
μM
against
HT1080)
selectivity
(selectivity
index
24933)
was
gained
via
electrophilic
warhead
screening
structure-based
optimization.
The
cellular
thermal
shift
assay
(CETSA)
indicated
that
could
stabilize
Tm
value
of
6.2
°C.
Furthermore,
showed
strong
binding
affinity
(KD
20.4
nM).
More
importantly,
has
favorable
pharmacokinetic
than
which
endowed
potential
in
antitumor
as
tool
drug
study
ferroptosis.
Associated
these,
treatment
inhibited
tumor
growth
xenograft
mouse
model
without
detectable
toxicity.
Nutrition and Diabetes,
Год журнала:
2025,
Номер
15(1)
Опубликована: Фев. 22, 2025
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD)
is
a
common
complication
of
type
2
diabetes
mellitus
(DM).
The
transcription
factor
zinc
fingers
and
homeoboxes
(ZHX2)
has
been
implicated
in
the
pathogenesis
chronic
diseases,
yet
its
precise
role
underlying
mechanism
DM-induced
hepatic
injury
remain
poorly
elucidated.
To
investigate
this,
we
used
high-fat
diet
(HFD)
streptozotocin
(STZ)
administration
to
create
DM
model
mice,
while
high
glucose
(HG)
exposure
was
simulate
vitro.
Through
various
experiments
such
as
luciferase
reporter
assay,
chromatin
immunoprecipitation,
RNA
rescue
experiments,
aimed
uncover
mechanisms
involving
ZHX2.
Our
findings
revealed
that
ZHX2
lower
YTHDF2
higher
livers
mice
HG-induced
Huh7
cells.
overexpression
rescued
injury.
also
reversed
ferroptosis
vivo
Mechanistically,
recognized
m6A-modified
mRNA
promoted
degradation.
In
turn,
inhibited
by
binding
promoter
region.
Knockdown
led
increased
cells
through
activating
YTHDF2-induced
GPX4
SLC7A11
These
highlight
involvement
ZHX2-YTHDF2-ferroptosis
pathway
suggest
targeting
this
may
hold
therapeutic
potential
for
improving
injuries.
Retinal
ganglion
cells
(RGCs)
are
the
visual
gateway
of
brain,
with
their
axons
converging
to
form
optic
nerve,
making
them
most
vulnerable
target
in
diseases
such
as
glaucoma
and
traumatic
neuropathy
(TON).
In
both
diseases,
disruption
blood-retinal
barrier(BRB)
is
considered
an
important
mechanism
that
accelerates
RGC
degeneration
hinders
axon
regeneration.
The
BRB
consists
inner
barrier
(iBRB)
outer
(oBRB),
which
maintained
by
endothelial
cells(ECs),
pericytes(PCs),
retinal
pigment
epithelial
(RPE),
respectively.
Their
functions
include
regulating
nutrient
exchange,
oxidative
stress,
immune
microenvironment.
However,
TON,
structural
functional
integrity
severely
damaged
due
mechanical
inflammatory
reactions,
metabolic
disorders.
Emerging
evidence
highlights
leads
heightened
vascular
permeability,
cell
infiltration,
sustained
chronic
inflammation,
creating
a
hostile
microenvironment
for
survival.
Furthermore,
dynamic
interplay
imbalance
among
ECs,
PCs,
glial
within
neurovascular
unit
(NVU)
pivotal
drivers
destruction,
exacerbating
apoptosis
limiting
nerve
intricate
molecular
cellular
mechanisms
underlying
these
processes
underscore
BRB's
critical
role
TON
pathophysiology
while
offering
compelling
foundation
therapeutic
strategies
targeting
repair
stabilization.
This
review
provides
crucial
insights
lays
robust
groundwork
advancing
research
on
neural
regeneration
innovative
protective
strategies.
