International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(11), С. 5601 - 5601
Опубликована: Май 21, 2024
This
review
addresses
the
role
of
tight
junction
proteins
at
blood-brain
barrier
(BBB).
Their
expression
is
described,
and
their
in
physiological
pathological
processes
BBB
discussed.
Based
on
this,
new
approaches
are
depicted
for
paracellular
drug
delivery
diagnostics
treatment
cerebral
diseases.
Recent
data
provide
convincing
evidence
that,
addition
to
its
impairment
course
diseases,
could
be
involved
aetiology
CNS
disorders.
Further
progress
will
expected
based
insights
protein
structure
involvement
signalling
pathways.
Ischemic
stroke
(IS)
is
a
prominent
type
of
cerebrovascular
disease
leading
to
death
and
disability
in
an
aging
society
closely
related
oxidative
stress.
Gene
expression
profiling
(GSE222551)
was
derived
from
Expression
Omnibus
(GEO),
1934
stress
(OS)
genes
were
obtained
the
GeneCards
database.
Subsequently,
we
identified
149
differentially
expressed
OS
(DEOSGs).
Finally,
PTGS2,
FOS,
RYR1
as
diagnostic
markers
IS.
Moreover,
GSE16561
used
validate
DEOSGs.
Two
(PTGS2
FOS)
significantly
highly
expressed,
while
lowly
IS
group.
Remarkably,
immune
infiltration
characteristics
these
three
analyzed,
found
that
mainly
correlated
with
Mast
cells
activated,
Neutrophils,
Plasma
cells,
respectively.
Next,
intersected
DEOSGs
ferroptosis
gene
set,
findings
revealed
only
PTGS2
ferroptosis.
High
levels
infarcted
cortex
middle
cerebral
artery
occlusion
(MCAO)
rats
confirmed
by
immunofluorescence
(IF),
western
blotting
(WB),
Immunohistochemistry
(IHC).
Inhibition
clearly
improved
neurological
outcome
decreasing
infarct
volume,
problems,
modified
severity
scores
following
compared
controls.
The
protective
effect
silencing
may
be
anti-oxidative
In
conclusion,
this
work
provide
new
perspective
for
research
IS,
further
based
on
breakthrough.
AJP Cell Physiology,
Год журнала:
2024,
Номер
327(1), С. C65 - C73
Опубликована: Май 20, 2024
The
blood-brain
barrier
(BBB)
plays
a
critical
role
in
the
development
and
outcome
of
subarachnoid
hemorrhage
(SAH).
This
study
focuses
on
potential
mechanism
by
which
G-protein-coupled
estrogen
receptor
30
(GPR30)
affects
BBB
after
SAH.
A
rat
SAH
model
was
established
using
an
intravascular
perforation
approach.
G1
(GPR30
agonist)
administered
to
investigate
damage
Brain
water
content,
Western
blotting,
Evans
blue
leakage,
immunofluorescence
staining
were
performed.
microvascular
endothelial
cells
induced
hemin
establish
vitro.
By
adding
LY294002
[a
phosphatidylinositol
3-kinase
(PI3K)
blocker]
zinc
protoporphyrin
IX
(ZnPP
IX)
heme
oxygenase
1
(HO-1)
antagonist],
improving
integrity
through
activation
GPR30
studied.
In
vivo,
improved
disruption,
as
evidenced
decreased
cerebral
edema,
downregulated
albumin
expression,
reduced
extravasation
IgG
administration
rats.
Moreover,
levels
tight
junction
(TJ)
proteins,
whereas
treatment
with
reversed
effect
protective
vitro
consistent
that
reducing
impact
transendothelial
electrical
resistance
(TEER)
value,
dextran
diffusivity,
TJ
protein
brain
cells.
addition,
activated
PI3K/
kinase
B
(Akt)
nuclear
factor
erythroid
2-related
2
(Nrf2)/HO-1
pathways
both
vivo
Furthermore,
ZnPP
partially
hemin-stimulated
We
demonstrated
GPR30,
at
least
partly
PI3K/Akt
Nrf2/HO-1
pathways,
alleviated
introduced
novel
therapeutic
approach
for
protecting
SAH.NEW
&
NOTEWORTHY
might
be
mechanisms
protected
models.
Therefore,
activator
promising
strategy.
Fluids and Barriers of the CNS,
Год журнала:
2024,
Номер
21(1)
Опубликована: Ноя. 21, 2024
The
Blood-Brain
Barrier
(BBB)
is
a
complex
and
dynamic
interface
that
regulates
the
exchange
of
molecules
cells
between
blood
central
nervous
system.
It
undergoes
structural
functional
throughout
oxidative
stress
inflammation,
which
may
compromise
its
integrity
contribute
to
pathogenesis
neurodegenerative
diseases.
Maintaining
BBB
utmost
importance
in
preventing
wide
range
neurological
disorders.
NRF2
main
transcription
factor
cellular
redox
balance
inflammation-related
gene
expression.
has
also
demonstrated
potential
role
regulating
tight
junction
contributing
inhibition
ECM
remodeling,
by
reducing
expression
several
metalloprotease
family
members
involved
maintaining
function.
Overall,
we
review
current
insights
on
addressing
protection
against
effects
dysfunction,
discuss
involvement
maintenance
different
neuropathological
diseases,
as
well
as,
some
activators
have
been
used
vitro
vivo
animal
models
for
barrier
dysfunction.
Thus,
emerging
evidence
suggests
upregulation
target
genes
could
suppress
stress,
neuroinflammation,
restore
integrity,
increase
protection.
Journal of Biochemical and Molecular Toxicology,
Год журнала:
2023,
Номер
38(1)
Опубликована: Дек. 9, 2023
COVID-19
is
caused
by
a
novel
SARS-CoV-2
leading
to
pulmonary
and
extra-pulmonary
manifestations
due
oxidative
stress
(OS)
development
hyperinflammation.
primarily
asymptomatic
though
it
may
cause
acute
lung
injury
(ALI),
respiratory
distress
syndrome
(ARDS),
systemic
inflammation,
thrombotic
events
in
severe
cases.
SARS-CoV-2-induced
OS
triggers
the
activation
of
different
signaling
pathways,
which
counterbalances
this
complication.
One
these
pathways
nuclear
factor
erythroid
2-related
2
(Nrf2),
induces
series
cellular
interactions
mitigate
SARS-CoV-2-mediated
viral
toxicity
OS-induced
injury.
Nrf2
pathway
inhibits
expression
pro-inflammatory
cytokines
cytokine
storm
COVID-19.
Therefore,
activators
play
an
essential
role
reducing
infection-induced
inflammation
suppressing
NLRP3
inflammasome
Furthermore,
can
attenuate
endothelial
dysfunction
(ED),
renin-angiotensin
system
(RAS)
dysregulation,
immune
thrombosis,
coagulopathy.
Thus
mini-review
tries
clarify
possible
management
could
be
effective
therapeutic
strategy
Covid-19.
Preclinical
clinical
studies
are
recommended
regard.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(5), С. 2322 - 2322
Опубликована: Март 5, 2025
Triple-negative
breast
cancer
(TNBC)
presents
limited
therapeutic
options
and
is
characterized
by
a
poor
prognosis.
Although
Kinsenoside
(KIN)
possesses
wide
range
of
pharmacological
activities,
its
effect
mechanism
in
TNBC
remain
unclear.
The
objective
this
research
was
to
explore
the
effectiveness
molecular
mechanisms
KIN
on
TNBC.
Xenograft
experiment
carried
out
assess
impact
vivo.
vitro
evaluated
through
analysis
cell
cytotoxicity
colony
formation
assays.
Oil
Red
O
staining
BODIPY
493/503
fluorescence
were
employed
detect
lipid
droplet
(LD)
formation.
Transcriptomics
inhibitor-rescue
experiments
conducted
investigate
role
Mechanistic
experiments,
including
quantitative
real-time
polymerase
chain
reaction
(RT-qPCR),
Western
blotting,
diacylglycerol
acyltransferase
1
(DGAT1)
overexpression
assay,
flow
cytometric
uncover
regulatory
inhibited
tumor
growth
without
causing
obvious
toxicity
liver
kidneys.
In
demonstrated
that
significantly
viability
proliferation
cells,
accompanied
decreased
LD
content.
Polyunsaturated
fatty
acids
(PUFAs)
levels
increased
KIN.
Furthermore,
transcriptomics
revealed
induced
ferroptosis
cells.
could
regulate
ferroptosis-related
proteins.
Lipid
peroxidation,
iron
accumulation,
GSH
depletion
also
confirmed
this.
inducer
mitigated
KIN-induced
DGAT1
attenuated
effects
proliferation.
trigger
Our
findings
suppressing
DGAT1-mediated
formation,
thereby
demonstrating
promising
Pharmacological Research,
Год журнала:
2025,
Номер
unknown, С. 107734 - 107734
Опубликована: Апрель 1, 2025
Drug
discovery
before
the
20th
century
often
focused
on
single
genes,
molecules,
cells,
or
organs,
failing
to
capture
complexity
of
biological
systems.
The
emergence
protein-protein
interaction
network
studies
in
2001
marked
a
turning
point
and
promoted
holistic
approach
that
considers
human
body
as
an
interconnected
system.
This
is
particularly
evident
study
bidirectional
interactions
between
central
nervous
system
(CNS)
peripheral
which
are
critical
for
understanding
health
disease.
Understanding
these
complex
requires
integrating
multi-scale,
heterogeneous
data
from
molecular
organ
levels,
encompassing
both
omics
(e.g.,
genomics,
proteomics,
microbiomics)
non-omics
imaging,
clinical
phenotypes).
Artificial
intelligence
(AI),
multi-modal
models,
has
demonstrated
significant
potential
analyzing
CNS-peripheral
by
processing
vast,
datasets.
Specifically,
AI
facilitates
identification
biomarkers,
prediction
therapeutic
targets,
simulation
drug
effects
multi-organ
systems,
thereby
paving
way
novel
strategies.
review
highlights
AI's
transformative
role
research,
focusing
its
applications
unraveling
disease
mechanisms,
discovering
optimizing
trials
through
patient
stratification
adaptive
trial
design.
