Advancing neurological disorders therapies: Organic nanoparticles as a key to blood-brain barrier penetration
International Journal of Pharmaceutics,
Год журнала:
2025,
Номер
670, С. 125186 - 125186
Опубликована: Янв. 8, 2025
The
blood-brain
barrier
(BBB)
plays
a
vital
role
in
protecting
the
central
nervous
system
(CNS)
by
preventing
entry
of
harmful
pathogens
from
bloodstream.
However,
this
also
presents
significant
obstacle
when
it
comes
to
delivering
drugs
for
treatment
neurodegenerative
diseases
and
brain
cancer.
Recent
breakthroughs
nanotechnology
have
paved
way
creation
wide
range
nanoparticles
(NPs)
that
can
serve
as
carriers
diagnosis
therapy.
Regarding
their
promising
properties,
organic
NPs
potential
be
used
effective
drug
delivery
across
BBB
based
on
recent
advancements.
These
remarkable
ability
penetrate
using
various
mechanisms.
This
review
offers
comprehensive
examination
intricate
structure
distinct
properties
BBB,
emphasizing
its
crucial
function
preserving
balance
regulating
transport
ions
molecules.
disruption
conditions
such
stroke,
Alzheimer's
disease,
Parkinson's
disease
highlights
importance
developing
creative
approaches
drugs.
Through
encapsulation
therapeutic
molecules
precise
targeting
processes
vasculature,
NP
formulations
present
hopeful
strategy
improve
BBB.
We
explore
changes
pathological
investigate
factors
affect
successful
into
brain.
In
addition,
we
most
systems
associated
with
shown
positive
results
treating
ischemic
disorders.
opens
up
new
possibilities
nanotechnology-based
therapies
cerebral
diseases.
Язык: Английский
Molecular heterogeneity in human stroke – What can we learn from the peripheral blood transcriptome?
Journal of Cerebral Blood Flow & Metabolism,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 13, 2025
Stroke
is
a
multifaceted
disease
with
genetic
and
environmental
components
like
diet
lifestyle.
The
central
nervous
immune
systems
display
complex
interactions,
the
peripheral
response
participating
in
brain
injury
repair
mechanisms
following
stroke.
bidirectional
communication
between
injured
blood
presents
an
opportunity
to
investigate
molecular
changes
latter.
There
substantial
heterogeneity
stroke
pathogenesis,
pathophysiology,
comorbidities,
treatment
outcome.
This
captured
underscored
by
transcriptome.
current
review
highlights
role
of
human
transcriptome
architecture
for
phenotyping
different
etiologies
identifying
underlying
correlates
clinically
important
variables
outcomes.
Specific
features
can
potentially
provide
targets
clinical
translation
prioritizing
genes
pathways
evaluation
experimental
models.
We
also
propose
approach
study
patient-specific
transcriptional
uncover
combinatorial
altered
patients
that
guide
search
prevention
targets.
Deciphering
tissue
be
easily
accessed
monitored,
such
as
blood,
may
improve
trial
success.
Язык: Английский
Interaction between post-tumor inflammation and vascular smooth muscle cell dysfunction in sepsis-induced cardiomyopathy
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 10, 2025
Sepsis-induced
cardiomyopathy
(SIC)
presents
a
critical
complication
in
cancer
patients,
contributing
notably
to
heart
failure
and
elevated
mortality
rates.
While
its
clinical
relevance
is
well-documented,
the
intricate
molecular
mechanisms
that
link
sepsis,
tumor-driven
inflammation,
cardiac
dysfunction
remain
inadequately
explored.
This
study
aims
elucidate
interaction
between
post-tumor
intratumor
heterogeneity,
of
VSMC
SIC,
as
well
evaluate
therapeutic
potential
exercise
training
specific
pharmacological
interventions.
Transcriptomic
data
from
NCBI
GEO
databases
were
analyzed
identify
differentially
expressed
genes
(DEGs)
associated
with
SIC.
Weighted
gene
co-expression
network
analysis
(WGCNA),
ontology
(GO),
KEGG
pathway
enrichment
analyses
utilized
biological
significance
these
genes.
Molecular
docking
dynamics
simulations
used
investigate
drug-target
interactions,
immune
infiltration
mutation
carried
out
by
means
platforms
like
TIMER
2.0
DepMap
comprehend
influence
DVL1
on
responsiveness.
Through
utilization
datasets,
we
discovered
core
exhibited
remarkable
up-regulated
expression
both
SIC
diverse
kinds
cancers,
which
poor
prognosis
inflammatory
responses.
revealed
Digoxin
could
bind
reduce
oxidative
stress
The
module
related
was
identified
WGCNA,
demonstrated
distinctive
cell
patterns
impact
immunotherapeutic
resistance.
regulator
other
cancers
and,
therefore,
can
serve
target.
present
suggests
targeted
therapies
enhance
response
regimens
may
be
novel
tool
during
particularly
patients.
drugs,
Digoxin,
require
further
vivo
studies
confirm
their
effects
efforts
improve
outcomes
immunotherapy-resistant
Язык: Английский
Microglia Morphological Response to Mesenchymal Stromal Cell Extracellular Vesicles Demonstrates EV Therapeutic Potential for Modulating Neuroinflammation
Kanupriya R. Daga,
Andrew M. Larey,
Maria G. Morfin
и другие.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 3, 2024
ABSTRACT
Background
Mesenchymal
stromal
cell
derived
extracellular
vesicles
(MSC-EVs)
are
a
promising
therapeutic
for
neuroinflammation.
MSC-EVs
can
interact
with
microglia,
the
resident
immune
cells
of
brain,
to
exert
their
immunomodulatory
effects.
In
response
inflammatory
cues,
such
as
cytokines,
microglia
undergo
phenotypic
changes
indicative
function
e.g.
morphology
and
secretion.
However,
these
in
not
well
understood.
Additionally,
no
disease-relevant
screening
tools
assess
MSC-EV
bioactivity
exist,
which
has
further
impeded
clinical
translation.
Here,
we
developed
quantitative,
high
throughput
morphological
profiling
approach
neuroinflammation-relevant
signals
whether
this
be
used
indicate
MSC-EVs.
Results
Using
an
immortalized
human
cell-line,
observed
increased
size
(perimeter,
major
axis
length)
complexity
(form
factor)
upon
stimulation
interferon-gamma
(IFN-γ)
tumor
necrosis
factor-alpha
(TNF-α).
Upon
treatment
MSC-EVs,
overall
score
(determined
using
principal
component
analysis)
shifted
towards
unstimulated
morphology,
indicating
that
bioactive
modulate
microglia.
The
effects
TNF-γ/IFN-α
stimulated
were
concomitant
reduced
secretion
14
chemokines/cytokines
(e.g.
CXCL6,
CXCL9)
12
CXCL8,
CXCL10).
Proteomic
analysis
lysates
revealed
significant
increases
192
proteins
HIBADH,
MEAK7,
LAMC1)
decreases
257
PTEN,
TOM1,
MFF)
treatment.
Of
note,
many
involved
regulation
migration.
Gene
Set
Variation
Analysis
upregulation
pathways
associated
response,
cytokine
production,
infiltration
T
cells,
NK
cells)
Semaphorin,
RHO/Rac
signaling).
mitochondrial
measured
suggesting
metabolism.
Conclusion
This
study
comprehensively
demonstrates
on
microglial
secretion,
cellular
proteome,
content.
Our
high-throughput,
rapid,
low-cost
enables
batches
manufacturing
conditions
enhance
EV
mitigate
functional
heterogeneity
disease
relevant
manner.
is
highly
generalizable
adapted
refined
based
selection
signal,
target
cell,
product.
Язык: Английский
Microglia morphological response to mesenchymal stromal cell extracellular vesicles demonstrates EV therapeutic potential for modulating neuroinflammation
Kanupriya R. Daga,
Andrew M. Larey,
Maria G. Morfin
и другие.
Journal of Biological Engineering,
Год журнала:
2024,
Номер
18(1)
Опубликована: Окт. 17, 2024
Mesenchymal
stromal
cell
derived
extracellular
vesicles
(MSC-EVs)
are
a
promising
therapeutic
for
neuroinflammation.
MSC-EVs
can
interact
with
microglia,
the
resident
immune
cells
of
brain,
to
exert
their
immunomodulatory
effects.
In
response
inflammatory
cues,
such
as
cytokines,
microglia
undergo
phenotypic
changes
indicative
function
e.g.
morphology
and
secretion.
However,
these
in
not
well
understood.
Additionally,
no
disease-relevant
screening
tools
assess
MSC-EV
bioactivity
exist,
which
has
further
impeded
clinical
translation.
Here,
we
developed
quantitative,
high
throughput
morphological
profiling
approach
neuroinflammation-
relevant
signals
whether
this
be
used
indicate
MSC-EVs.
Язык: Английский