Biomolecules & Therapeutics,
Journal Year:
2024,
Volume and Issue:
32(5), P. 531 - 539
Published: Aug. 21, 2024
Sleep
is
one
of
the
most
essential
physiological
phenomena
for
maintaining
health.Sleep
disturbances,
such
as
insomnia,
are
often
accompanied
by
psychiatric
or
physical
conditions
impaired
attention,
anxiety,
and
stress.Medication
used
to
treat
insomnia
have
concerns
about
potential
side
effects
with
long-term
use,
so
interest
in
use
alternative
medicine
increasing.In
this
study,
we
investigated
hypnotic
β-lapachone
(β-Lap),
a
natural
naphthoquinone
compound,
using
pentobarbital-induced
sleep
test,
immunohistochemistry,
real-time
PCR,
western
blot
mice.Our
results
indicated
that
β-Lap
exerts
significant
effect
showing
decrease
onset
latency
an
increase
total
time
model.The
c-Fos
immunostaining
showed
decreased
neuronal
activity
basal
forebrain
lateral
hypothalamus,
which
wakefulness-promoting
brain
regions,
while
increasing
ventrolateral
preoptic
nucleus,
sleep-promoting
region;
all
these
were
significantly
abolished
8-cyclopentyl-1,3-dipropylxanthine
(DPCPX),
adenosine
A1
receptor
(A1R)
antagonist.Western
analysis
increased
extracellular
signalregulated
kinase
phosphorylation
nuclear
factor-kappa
B
translocation
from
cytoplasm
nucleus;
inhibited
DPCPX.Additionally,
mRNA
levels
A1R.Taken
together,
suggest
effects,
potentially
through
A1R.
ACS Nano,
Journal Year:
2024,
Volume and Issue:
18(2), P. 1582 - 1598
Published: Jan. 3, 2024
Heterogeneity
of
the
tumor
microenvironment
(TME)
is
primarily
responsible
for
ineffective
treatment
and
uncontrolled
progression.
Pyroptosis-based
immunogenic
cell
death
(ICD)
therapy
an
ideal
strategy
to
overcome
TME
heterogeneity
obtain
a
satisfactory
antitumor
effect.
However,
efficiency
current
pyroptosis
therapeutics,
which
mainly
depends
on
single
endogenous
or
exogenous
stimulus,
limited
by
intrinsic
pathological
features
malignant
cells.
Thus,
it
necessary
develop
synergistic
with
high
specificity
modulability.
Herein,
nanoplatform
constructed
combining
neutrophil
camouflaging
shell
self-synergistic
reactive
oxygen
species
(ROS)
supplier-loaded
polymer.
The
covered
membranes
endow
stealthy
properties
facilitate
sufficient
accumulation.
Under
laser
irradiation,
photosensitizer
(indocyanine
green)
exogenously
triggers
ROS
generation
converts
irradiation
into
heat
upregulate
NAD(P)H:quinone
oxidoreductase
1,
further
catalyzes
β-Lapachone
self-produce
ROS,
resulting
in
amplified
ICD
outcomes.
results
confirm
that
continuously
production
not
only
eliminates
primary
but
also
concurrently
enhances
gasdermin
E-mediated
pyroptosis,
initiates
cascade,
re-educates
heterogeneous
TME,
promotes
systemic
immune
response
suppress
distant
tumors.
Overall,
this
provides
efficient
durable
method
redesigning
system
targeted
inhibition.
Cells,
Journal Year:
2024,
Volume and Issue:
13(15), P. 1272 - 1272
Published: July 29, 2024
Human
NAD(P)H-quinone
oxidoreductase1
(HNQO1)
is
a
two-electron
reductase
antioxidant
enzyme
whose
expression
driven
by
the
NRF2
transcription
factor
highly
active
in
prooxidant
milieu
found
human
malignancies.
The
resulting
abundance
of
NQO1
(up
to
200-fold)
cancers
and
barely
detectable
body
tissues
makes
it
selective
marker
neoplasms.
can
catalyze
repeated
futile
redox
cycling
certain
natural
synthetic
quinones
their
hydroxyquinones,
consuming
NADPH
generating
rapid
bursts
cytotoxic
reactive
oxygen
species
(ROS)
H2O2.
A
greater
level
this
quinone
bioactivation
due
elevated
content
has
been
recognized
as
tumor-specific
therapeutic
strategy,
which,
however,
not
clinically
exploited.
We
review
here
new
activated
NQO1,
catalytic
inhibitors,
ensuing
cell
death
mechanisms.
Further,
cancer-selective
opened
excellent
opportunities
for
distinguishing
cancer
cells/tissues
from
normal
counterparts.
Given
diagnostic,
prognostic,
importance,
we
others
have
engineered
large
number
specific
turn-on
small
molecule
probes
that
remain
latent
but
release
intense
fluorescence
groups
at
near-infrared
other
wavelengths,
following
enzymatic
cleavage
cells
tumor
masses.
This
sensitive
visualization/quantitation
powerful
imaging
technology
based
on
offers
promise
guided
surgery,
reagents
suggest
theranostic
potential
NQO1-targeted
chemotherapy.
Biomedicine & Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
174, P. 116439 - 116439
Published: March 21, 2024
Triple-negative
breast
cancer
(TNBC)
is
characterised
by
its
aggressiveness
and
resistance
to
chemotherapy,
demanding
the
development
of
effective
strategies
against
unique
characteristics.
Derived
from
lapacho
tree
bark,
β-lapachone
(β-LP)
selectively
targets
cells
with
elevated
levels
detoxifying
enzyme
NQO1.
Hydroxytyrosol
(HT)
a
phenolic
compound
derived
olive
trees
important
anticancer
properties
that
include
inhibition
stem
(CSCs)
metastatic
features
in
TNBC,
as
well
relevant
antioxidant
activities
mechanisms
such
induction
We
aimed
study
whether
these
compounds
could
have
synergistic
activity
TNBC
possible
role
For
this
pourpose,
we
assessed
impact
β-LP
(0.5
or
1.5
μM)
HT
(50
100
on
five
cell
lines.
demonstrated
combination
exhibits
anti-proliferative,
pro-apoptotic,
cycle
arrest
effects
several
cells,
including
docetaxel-resistant
cells.
Additionally,
it
effectively
inhibits
self-renewal
clonogenicity
CSCs,
modifying
their
aggressive
phenotype.
However,
notable
β-LP-HT
does
not
appear
be
solely
associated
NQO1
protein
ROS.
RNA-Seq
analysis
revealed
combination's
linked
strong
endoplasmic
reticulum
stress
apoptosis
through
unfolded
response.
In
conclusion,
study,
how
offer
an
affordable,
safe,
approach
TNBC.
Advanced Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 27, 2025
Abstract
Immune
evasion
and
metastasis
are
the
leading
causes
of
poor
prognosis
in
triple‐negative
breast
cancer
treatment.
Since
current
standard
immunotherapies
have
limited
efficacy
due
to
immunologically
cold
microenvironment,
it
is
crucial
explore
new
strategies
sensitize
anticancer
immune
response.
In
this
study,
found
that
incorporating
β
‐lapachone‐based
oxidation
therapy
with
CUDC101‐initiated
epigenetic
regulation
results
synergistic
antitumor
effects
potent
activation.
To
co‐deliver
these
two
hydrophobic
drugs,
IR783
cyanine
structure
serves
as
stabilizer
form
a
nanoformulation
based
on
small
molecule
self‐assembly.
Such
IR783‐stabilized
nanodrugs
can
not
only
lead
cell
apoptosis
through
HDAC
inhibition‐enhanced
but
also
cooperatively
induce
immunogenic
death
promote
pro‐inflammatory
cytokine
gene
expression
reshape
immunosuppressive
microenvironment.
Besides,
inhibit
both
primary
distant
tumor
growth
effectively
by
elevating
systemic
immunity.
This
study
provides
promising
approach
synergize
modulation
for
safe
efficient
immunotherapy.
International Journal for Parasitology Drugs and Drug Resistance,
Journal Year:
2025,
Volume and Issue:
27, P. 100583 - 100583
Published: Jan. 23, 2025
Giardia
duodenalis
is
a
widespread
intestinal
protozoan
that
affects
mammals,
including
humans.
Symptoms
can
range
from
being
subclinical
to
causing
severe
abdominal
pain
and
diarrhoea.
Giardiasis
often
requires
repeated
treatment
with
synthetic
drugs
like
metronidazole.
In
recent
years,
failures
in
clinical
cases
involving
nitroimidazoles
have
been
increasingly
reported.
Consequently,
identifying
therapeutic
alternatives
necessary.
Medicinal
plants
traditionally
used
as
antiparasitic
compounds,
but
systematic
evaluation
under
controlled
experimental
conditions
lacking.
Here,
we
evaluated
the
vitro
efficacy
of
Tabebuia
avellanedae
dry
hydroalcoholic
extracts,
well
one
its
active
β-lapachone,
potential
against
G.
infection.
We
observed
effective
antigiardial
activity
for
all
tested
β-lapachone
exhibiting
lower
IC50
values
than
Cytotoxic
effects
limit
concentration
windows
opportunity,
choosing
an
informative
model
assess
them
not
straightforward.
present
case,
only
T.
extract
showed
no
cytotoxicity
on
tumoral
human
Caco-2
cell
line,
trend
inhibition
when
canine
epithelial
kidney
MDCK
cells.
To
introduce
more
physiological
test
system,
infection
experiments
trans-well
set-up
using
organoid
derived
monolayers
(ODM)
at
same
time
drug
parasite
safety
primary
epithelia,
likely
surrogate
vivo
conditions.
Our
studies
this
point
towards
opportunity
non-systemic
applications
extracts
relevant
ingredient
these,
β-lapachone.
The
data
suggest
ODM
co-cultures
are
suitable
testing
providing
before
progressing
tests.
ACS Applied Materials & Interfaces,
Journal Year:
2024,
Volume and Issue:
16(30), P. 39021 - 39034
Published: July 21, 2024
Chemodynamic
therapy
(CDT),
employing
metal
ions
to
transform
endogenous
H2O2
into
lethal
hydroxyl
radicals
(•OH),
has
emerged
as
an
effective
approach
for
tumor
treatment.
Yet,
its
efficacy
is
diminished
by
glutathione
(GSH),
commonly
overexpressed
in
tumors.
Herein,
a
breakthrough
strategy
involving
extracellular
vesicle
(EV)
mimetic
nanovesicles
(NVs)
encapsulating
iron
oxide
nanoparticles
(IONPs)
and
β-Lapachone
(Lapa)
was
developed
amplify
intracellular
oxidative
stress.
The
combination,
NV-IONP-Lapa,
created
through
serial
extrusion
from
ovarian
epithelial
cells
showed
excellent
biocompatibility
leveraged
magnetic
guidance
enhance
endocytosis
cancer
cells,
resulting
selective
generation
Lapa
catalysis
NADPH
quinone
oxidoreductase
1
(NQO1).
Meanwhile,
the
released
IONPs
ionization
under
acidic
conditions
triggered
conversion
of
•OH
Fenton
reaction.
Additionally,
process
eliminated
GSH
tumor,
further
amplifying
designed
NV-IONP-Lapa
demonstrated
exceptional
targeting,
facilitating
MR
imaging,
enhanced
suppression
without
significant
side
effects.
This
study
presents
promising
NV-based
drug
delivery
system
exploiting
CDT
against
NQO1-overexpressing
tumors
augmenting
intratumoral
