Frontiers in Physiology,
Год журнала:
2024,
Номер
15
Опубликована: Ноя. 25, 2024
Contrast-induced
acute
kidney
injury
(CI-AKI)
has
emerged
as
a
global
public
health
concern,
ranking
the
third
most
prevalent
cause
of
hospital-acquired
injury,
which
is
related
to
adverse
outcomes.
However,
its
precise
pathogenesis
remains
elusive.
Consequently,
researchers
are
dedicated
uncovering
CI-AKI's
pathophysiology
and
signaling
pathways,
including
inflammation,
oxidative
stress,
apoptosis,
ferroptosis,
improve
prevention
treatment.
This
review
thoroughly
analyzes
pathways
their
interactions
associated
with
CI-AKI,
assesses
impact
various
research
models
on
pathway
analysis,
explores
more
targeted
treatment
approaches.
Aims
furnish
robust
theoretical
foundation
for
molecular
mechanisms
underpinning
clinical
treatments.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(9), С. 8162 - 8162
Опубликована: Май 3, 2023
We
are
witnessing
the
globalization
of
a
specific
type
arteriosclerosis
with
rising
prevalence,
incidence
and
an
overall
cardiovascular
disease
burden.
Currently,
atherosclerosis
increasingly
affects
younger
generation
as
compared
to
previous
decades.
While
early
preventive
medicine
has
seen
improvements,
research
advances
in
laboratory
clinical
investigation
promise
provide
us
novel
diagnosis
tools.
Given
physio-pathological
complexity
epigenetic
patterns
discovery
new
molecules
involved,
therapeutic
field
room
for
substantial
growth.
Thus,
scientific
community
is
currently
investigating
role
nucleotide-binding
oligomerization
domain-like
receptor
family
pyrin
domain-containing
3
(NLRP3)
inflammasome,
crucial
component
innate
immune
system
different
inflammatory
disorders.
NLRP3
activated
by
distinct
factors
numerous
cellular
molecular
events
which
trigger
inflammasome
assembly
subsequent
cleavage
pro-interleukin
(IL)-1β
pro-IL-18
pathways
via
caspase-1
activation,
eliciting
endothelial
dysfunction,
promotion
oxidative
stress
inflammation
process
atherosclerosis.
In
this
review,
we
introduce
basic
mechanisms
activation
its
also
emphasize
promising
pharmaceutical
potential.
Tetramethylpyrazine
(TMP)
has
been
confirmed
to
suppress
inflammation
in
endometriosis
(EMs).
Herein,
this
study
investigated
whether
and
how
TMP
affected
NLRP3
inflammasomes
oxidative
stress
EMs.
After
establishment
of
an
EMs
rat
model,
rats
were
treated
with
different
concentrations
TMP.
The
size
endometriotic
lesions
the
latency
frequency
torsion
recorded,
followed
by
measurement
relevant
indicators
(TNF-α,
IL-6,
IL-2,
IL-10,
MDA,
SOD,
GSH,
CAT,
ROS,
NLRP3,
ASC,
GSDMD,
caspase-1,
Nrf2,
HO-1).
experimentally
determined
that
treatment
markedly
decreased
improved
levels
inflammatory
proteins,
markers,
inflammasome,
pyroptotic
proteins
elevated
EMs,
all
which
reversed
upon
treatment.
Additionally,
activities
CAT
lowered
partly
abrogated
Furthermore,
downregulation
Nrf2
HO-1
was
counteracted
To
sum
up,
represses
excessive
stress,
inflammasome
activation,
pyroptosis
may
activate
Nrf2/HO-1
pathway.
Diabetology & Metabolic Syndrome,
Год журнала:
2023,
Номер
15(1)
Опубликована: Июль 19, 2023
Diabetic
cardiomyopathy
(DC)
is
a
serious
heart
disease
caused
by
diabetes.
It
unrelated
to
hypertension
and
coronary
artery
can
lead
insufficiency,
failure
even
death.
Currently,
the
pathogenesis
of
DC
unclear,
clinical
intervention
mainly
symptomatic
therapy
lacks
effective
objectives.
Iron
overdose
mediated
cell
death,
also
known
as
ferroptosis,
widely
present
in
physiological
pathological
processes
diabetes
DC.
key
trace
element
human
body,
regulating
metabolism
glucose
lipids,
oxidative
stress
inflammation,
other
biological
processes.
Excessive
iron
accumulation
imbalance
antioxidant
system
activate
aggravate
such
excessive
autophagy
mitochondrial
dysfunction,
resulting
chain
reaction
accelerating
myocardial
microvascular
damage.
In-depth
understanding
mechanisms
ferroptosis
cardiovascular
vessels
help
improve
management.
Therefore,
this
review,
we
summarize
relationship
between
DC,
well
potential
targets,
discuss
analyze
limitations
future
development
prospects
these
targets.
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(23), С. 14570 - 14570
Опубликована: Ноя. 23, 2022
Doxorubicin
(DOX)
is
an
anticancer
antibiotic
which
has
various
effects
in
human
cancers.
It
one
of
the
commonly
known
causes
drug-induced
nephrotoxicity,
results
acute
renal
injury.
Adrenomedullin
(ADM),
a
vasodilator
peptide,
widely
distributed
many
tissues
and
potent
protective
effects.
Therefore,
current
study
aimed
to
examine
potential
mechanisms
ADM
against
DOX-induced
nephrotoxicity.
A
total
28
male
Wistar
rats
were
randomized
into
four
groups:
control
group,
doxorubicin
group
(15
mg/kg
single
intraperitoneal
injection
DOX),
adrenomedullin
+
(12
μg/kg/day
ADM)
3
days
prior
DOX
continuing
for
14
after
model
was
established,
group.
Kidney
function
biomarkers,
oxidative
stress
markers,
inflammatory
mediators
(TNF-α,
NLRP3,
IL-1β,
IL-18)
assessed.
The
expressions
gasdermin
D
ASC
assessed
by
real-time
PCR.
Furthermore,
abundances
caspase-1
(p20),
Bcl-2,
Bax
immunoreactivity
evaluated.
administration
improved
biochemical
parameters
significantly
reduced
damage
markers
mediators,
suppressed
both
apoptosis
pyroptosis.
These
confirmed
histopathological
findings
revealed
that
ADM's
antioxidant,
anti-inflammatory,
anti-apoptotic,
anti-pyroptotic
properties
may
have
prospective
applications
amelioration
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(19), С. 17833 - 17854
Опубликована: Сен. 20, 2024
The
NLRP3
inflammasome
plays
a
central
role
in
the
pathogenesis
of
various
intractable
human
diseases,
making
it
an
urgent
target
for
therapeutic
intervention.
Here,
we
report
development
SN3-1,
novel
orally
potent
inhibitor,
designed
through
lead
compound
strategy
centered
on
deep-learning-based
molecular
generative
models.
Our
enables
rapid
fragment
enumeration
and
takes
into
account
synthetic
accessibility
compounds,
thereby
significantly
enhancing
optimization
compounds
facilitating
discovery
inhibitors.
X-ray
crystallography
provided
insights
SN3-1
inhibitory
mechanism.
has
shown
favorable
safety
profile
both
acute
chronic
toxicity
assessments
exhibits
robust
pharmacokinetic
properties.
Furthermore,
demonstrated
significant
efficacy
disease
models
characterized
by
activation.
This
study
introduces
candidate
developing
inhibitors
expands
repertoire
tools
available
