Medicine in Drug Discovery,
Год журнала:
2024,
Номер
24, С. 100197 - 100197
Опубликована: Авг. 23, 2024
GPCRs
are
a
class
of
membrane
proteins
that
essential
to
signal
transduction,
and
this
is
vital
process
in
many
different
physiologies.
The
significant
mortality
rate
widespread
occurrence
stroke
highlight
the
need
accelerate
research
develop
viable
treatment
agents.
A
promising
prospect
for
development
new
approaches
increasing
comprehension
pathophysiology
crucial
roles
played
by
GPCRs.
Because
blood
clot,
glial
cells'
vascular
supply
abruptly
cut
off,
which
sets
off
series
events
include
inflammation
neuronal
damage
ultimately
lead
cell
death.
Numerous
therapeutic
treatments,
including
thrombolytic
agents
like
tissue
plasminogen
activator
urokinase,
have
been
discovered
as
potential
neuroprotective
medicines;
however,
their
use
restricted
because
modest
window.
Accepting
pertinent
factors
ischemic
stroke,
we
explore
medicinal
promise
GPCR-targeted
treatments
shortcomings
ought
be
resolved
order
translate
these
discoveries
clinical
cases.
Frontiers in Neurology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 7, 2025
The
combined
index
(HALP)
of
hemoglobin,
albumin,
lymphocytes,
and
platelets
is
considered
a
novel
scoring
system
that
reflects
systemic
inflammation
nutritional
status.
This
study
aimed
to
investigate
the
relationship
between
HALP
scores
poor
outcomes
in
acute
ischemic
stroke
(AIS)
patients
with
type
2
diabetes
mellitus
(DM).
Patients
AIS
DM
were
screened
from
Third
China
National
Stroke
Registry
(CNSR-III)
divided
into
quartiles
based
on
their
at
admission.
Clinical
adverse
functional
(modified
Rankin
scale
[mRS]
score
3-6
or
2-6)
all-cause
mortality
3
months
1
year.
association
risk
outcome
analyzed
by
multivariable
logistic
regression
Cox
proportional
hazards
regression.
A
total
3,603
included
this
study.
After
adjusting
for
confounders,
it
was
found
highest
quartile
had
lower
mRS
2-6
(odds
ratio
[OR],
0.64;
95%
confidence
interval
[CI],
0.51-0.80)
(OR,
0.53;
CI,
0.51-0.82)
3-month
follow-up.
At
1-year
follow-up,
significant
correlation
observed
0.65;
95%CI,
0.57-0.81)
0.47-0.86).
Additionally,
associated
reduced
follow-up
(hazard
[HR],
0.35;
0.13-0.93).
Similar
results
(HR,
0.34;
0.18-0.63).
poorer
mortality.
Frontiers in Neuroscience,
Год журнала:
2025,
Номер
18
Опубликована: Янв. 14, 2025
Background
Programmed
cell
death
plays
an
important
role
in
neuronal
injury
and
after
ischemic
stroke
(IS),
leading
to
cellular
glucose
deficiency.
Glucose
deficiency
can
cause
abnormal
accumulation
of
cytotoxic
disulfides,
resulting
disulfidptosis.
Ferroptosis,
apoptosis,
necroptosis,
autophagy
inhibitors
cannot
inhibit
this
novel
programmed
mechanism.
Nevertheless,
the
potential
mechanisms
disulfidptosis
IS
remain
unclear.
Methods
The
GSE16561
dataset
was
used
screen
for
differentially
expressed
disulfidptosis-related
biomarkers
(DE-DRBs).
A
correlation
between
DE-DRBs
detected.
optimal
machine-learning
(ML)
model
predictor
molecules
were
determined.
GSE58294
verify
accuracy
ML
model.
DE-DRB
expression
detected
blood
patients
with
IS.
Based
on
models,
experimental
analyses
performed
DE-DRBs.
Results
Leucine-rich
pentatricopeptide
repeat-containing
(LRPPRC)
NADH
dehydrogenase
[ubiquinone]
1
alpha
subcomplex
subunit
11
(NDUFA11)
identified
as
NADH:
ubiquinone
oxidoreductase
core
S1
(NDUFS1)
interacted
NDUFA11
LRPPRC.
support
vector
machine
(SVM)
level
20.9%
compared
that
normal
controls.
downregulated
vitro/in
vivo
models
number
formed
complexes
NDUFS1
decreased
Conclusion
This
research
suggests
is
a
specific
DRB
demonstrates
alterations
protein
NDUFS1-NDUFA11.
ACS Chemical Neuroscience,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 29, 2025
PANoptosis
is
a
newly
identified
form
of
cell
death
that
encompasses
pyroptosis,
apoptosis,
and
necroptosis.
Numerous
studies
have
highlighted
the
significance
in
brain
ischemia-reperfusion
(I/R)
injury.
Calycosin,
natural
product
with
diverse
biological
activities,
has
demonstrated
significant
reduction
neuronal
caused
by
ischemic
injury
modulating
multiple
pathways.
In
order
to
investigate
potential
mechanisms
underlying
neuroprotective
role
calycosin
alleviating
PANoptosis-induced
damage
stroke
therapy,
we
used
mouse
hippocampal
line
HT22
stimulate
ischemia
vitro
through
Oxygen
Glucose
Deprivation/Reperfusion
(OGD/R)
established
molecular
docking
assess
binding
affinity
Calycosin
key
targets
dynamics
simulations
(MDS)
study
stability
ligand-protein
complex.
The
results
demonstrate
could
improve
growth
HT22,
leading
enhanced
viability,
reduced
lactate
dehydrogenase
leakage,
decreased
apoptosis
after
OGD/R.
It
also
regulated
expression
PANoptosis-related
genes
such
as
NLRP3,
GSDMD,
MLKL,
RIPK1
increased
Bcl-2/Bax
ratio,
effectively
reducing
cellular
providing
protection.
Molecular
MDS
strong
activity
between
targets.
Furthermore,
successfully
passed
drug
similarity
(DS)
evaluation
exhibited
favorable
absorption,
distribution,
metabolism,
excretion,
toxicity
(ADMET)
properties
activity.
conclusion,
alleviate
inhibiting
PANoptosis,
inflammation
improving
Thus,
it
serve
therapy
for
stroke.
Biochemical Pharmacology,
Год журнала:
2025,
Номер
unknown, С. 116907 - 116907
Опубликована: Март 1, 2025
Ischemic
stroke
is
a
debilitating
condition
characterized
by
high
morbidity,
disability,
recurrence,
and
mortality
rates
on
global
scale,
posing
significant
threat
to
public
health
economic
stability.
Extensive
research
has
thoroughly
explored
the
molecular
mechanisms
underlying
ischemic
stroke,
elucidating
strong
association
between
soluble
N-ethylmaleimide-sensitive
factor
(NSF)
attachment
protein
receptor
proteins
(SNAREs)
pathogenesis
of
this
condition.
SNAREs,
class
highly
conserved
involved
in
membrane
fusion,
play
crucial
role
modulating
neuronal
information
transmission
promoting
myelin
formation
central
nervous
system
(CNS).
Preventing
SNARE
complex
formation,
malfunctions
SNARE-dependent
exocytosis,
altered
regulation
SNARE-mediated
vesicle
fusion
are
linked
excitotoxicity,
endoplasmic
reticulum
(ER)
stress,
programmed
cell
death
(PCD)
stroke.
However,
its
remain
unclear.
This
study
conducts
comprehensive
review
existing
literature
proteins,
encompassing
structure,
classification,
expression
family,
as
well
assembly
-
disassembly
cycle
complexes
their
physiological
roles
CNS.
We
examine
which
SNAREs
contribute
pathological
progression
associated
risk
factors
(hypertension,
hyperglycemia,
dyslipidemia,
atherosclerosis).
Furthermore,
our
findings
highlight
promise
viable
target
for
pharmacological
interventions
treatment
