Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Июль 22, 2024
Abstract
Stroke
is
a
leading
cause
of
mortality
and
long-term
disability
globally,
with
acute
ischemic
stroke
(AIS)
being
the
most
common
subtype.
Despite
significant
advances
in
reperfusion
therapies,
their
limited
time
window
associated
risks
underscore
necessity
for
novel
treatment
strategies.
Stem
cell-derived
extracellular
vesicles
(EVs)
have
emerged
as
promising
therapeutic
approach
due
to
ability
modulate
post-stroke
microenvironment
facilitate
neuroprotection
neurorestoration.
This
review
synthesizes
current
research
on
potential
stem
EVs
AIS,
focusing
origin,
biogenesis,
mechanisms
action,
strategies
enhancing
targeting
capacity
efficacy.
Additionally,
we
explore
innovative
combination
therapies
discuss
both
challenges
prospects
EV-based
treatments.
Our
findings
reveal
that
exhibit
diverse
effects
such
promoting
neuronal
survival,
diminishing
neuroinflammation,
protecting
blood-brain
barrier,
angiogenesis
neurogenesis.
Various
strategies,
including
modifications
cargo
modifications,
been
developed
improve
efficacy
EVs.
Combining
other
treatments,
therapy,
cell
transplantation,
nanomedicine,
gut
microbiome
modulation,
holds
great
promise
improving
outcomes.
However,
heterogeneity
need
standardized
protocols
EV
production
quality
control
remain
be
addressed.
represent
avenue
offering
address
limitations
Further
needed
optimize
translate
benefits
clinical
practice,
an
emphasis
ensuring
safety,
overcoming
regulatory
hurdles,
specificity
delivery
target
tissues.
Graphical
Frontiers in Oncology,
Год журнала:
2023,
Номер
13
Опубликована: Янв. 31, 2023
Notch
signaling
is
involved
in
cell
fate
determination
and
deregulated
human
solid
tumors.
Hypoxia
an
important
feature
many
tumors,
which
activates
hypoxia-induced
factors
(HIFs)
their
downstream
targets
to
promote
tumorigenesis
cancer
development.
Recently,
HIFs
have
been
shown
trigger
the
pathway
a
variety
of
organisms
tissues.
In
this
review,
we
focus
on
pro-
anti-tumorigenic
functions
discuss
crosstalk
between
cellular
hypoxic
response
pathogenesis,
including
epithelia-mesenchymal
transition,
angiogenesis,
maintenance
stem
cells.
The
pharmacological
strategies
targeting
hypoxia
are
also
discussed
review.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Фев. 20, 2024
Notch
signaling
pathway
is
a
highly
conserved
system
of
cell-to-cell
communication
that
participates
in
various
biological
processes,
such
as
stem
cell
maintenance,
fate
decision,
proliferation
and
death
during
homeostasis
development.
Dysregulation
has
been
associated
with
many
aspects
cancer
biology,
maintenance
stem-like
cells
(CSCs),
metabolism,
angiogenesis
tumor
immunity.
Particularly,
can
regulate
antitumor
or
pro-tumor
immune
within
the
microenvironment
(TME).
Currently,
drawn
significant
attention
therapeutic
development
treatment.
In
this
review,
we
focus
on
role
remodeling
microenvironment.
We
describe
impact
efficacy
immunotherapies.
Furthermore,
summarize
results
relevant
preclinical
clinical
trials
Notch-targeted
therapeutics
discuss
challenges
their
application
therapy.
An
improved
understanding
involvement
immunity
will
open
door
to
new
options
immunotherapy
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Янв. 17, 2025
Laminins
(LMs)
are
a
family
of
heterotrimeric
glycoproteins
that
form
the
structural
foundation
basement
membranes
(BM).
By
acting
as
molecular
bridges
between
cells
and
extracellular
matrix
(ECM)
through
integrins
other
surface
receptors,
they
regulate
key
cellular
signals
influence
cell
behavior
tissue
architecture.
Despite
their
physiological
importance,
our
understanding
role
LMs
in
cancer
pathobiology
remains
fragmented.
In
this
article,
we
review
diverse
functions
promoting
proliferation,
adhesion,
migration-critical
steps
metastasis.
Beyond
direct
effects
on
tumor
cells,
stromal
interactions
modulate
microenvironment
dynamics,
affecting
processes
such
angiogenesis,
immune
infiltration,
cancer-associated
fibroblast
activation,
evasion.
Understanding
complex
roles
biology,
well
differential
expression
patterns
malignancies,
could
provide
new
diagnostic
tools
for
predicting
disease
outcomes
pave
way
innovative
therapeutic
strategies,
targeting
LM-receptor
or
modulating
ECM
dynamics
to
impede
growth
Mechanobiology in Medicine,
Год журнала:
2025,
Номер
3(1), С. 100114 - 100114
Опубликована: Фев. 1, 2025
Atherosclerosis
(AS)
is
a
disease
characterized
by
focal
cholesterol
accumulation
and
insoluble
inflammation
in
arterial
intima,
leading
to
the
formation
of
an
atherosclerotic
plaque
consisting
lipids,
cells,
fibrous
matrix.
The
presence
can
restrict
or
obstruct
blood
flow,
resulting
stenosis
local
mechanical
microenvironment
changes
including
flow
shear
stress,
vascular
matrix
stiffness,
structural
stress.
Neovascularization
within
plays
crucial
role
both
growth
destabilization,
potentially
rupture
fatal
embolism.
However,
exact
interactions
between
neovessels
remain
unclear.
In
this
review,
we
provide
comprehensive
analysis
origin
intraplaque
neovessels,
contributing
factors,
underlying
molecular
mechanisms,
associated
signaling
pathways.
We
specifically
emphasize
factors
angiogenesis
plaques.
Additionally,
summarize
imaging
techniques
therapeutic
strategies
for
enhance
our
understanding
field.
Molecules,
Год журнала:
2025,
Номер
30(5), С. 987 - 987
Опубликована: Фев. 20, 2025
Angiogenesis,
primarily
driven
by
the
vascular
endothelial
growth
factor
(VEGF)
and
its
receptor,
VEGFR,
plays
a
key
role
in
various
pathological
processes
such
as
cancer
progression.
Here,
we
investigated
anti-angiogenic
effects
of
Lucknolide
A
(LA),
marine
Streptomyces-derived
compound,
evaluated
potential
VEGFR2
inhibitor.
LA
selectively
inhibited
proliferation
human
cells
EA.hy926
HUVEC
while
exhibiting
minimal
on
normal
fibroblasts
tumor
cells.
induced
S-phase
cell
cycle
arrest
apoptosis
cells,
increasing
apoptotic
markers
p53,
Bax,
p21
decreasing
anti-apoptotic
protein
Bcl-2,
with
these
being
further
enhanced
under
VEGF
stimulation.
Additionally,
suppressed
phosphorylation
downstream
signaling
pathways,
including
Akt/mTOR/p70S6K,
MEK/ERK,
Src,
FAK,
p38
MAPK,
which
are
crucial
for
survival
angiogenesis.
Molecular
docking
studies
revealed
that
binds
to
both
inactive
(DFG-out,
PDB:
4ASD)
active
(DFG-in,
3B8R)
conformations,
significantly
stronger
affinity
state
(−107.96
kcal/mol)
than
(−33.56
kcal/mol),
suggesting
kinase
Functionally,
VEGF-induced
migration,
tube
formation,
microvessel
sprouting
vitro
ex
vivo
rat
aortic
ring
assays.
reduced
tumor-associated
formation
breast
(MDA-MB-231),
indicating
suppress
VEGF-dependent
These
findings
suggest
is
promising
selective
agent
therapeutic
applications
angiogenesis-related
diseases
cancer.
Abstract
The
formation
of
a
blood
vessel
network
is
crucial
for
organ
development
and
regeneration.
Over
the
past
three
decades,
central
molecular
mechanisms
governing
growth
have
been
extensively
studied.
Recent
evidence
indicates
that
vascular
endothelial
cells—the
specialized
cells
lining
inner
surface
vessels—exhibit
significant
heterogeneity
to
meet
specific
needs
different
organs.
This
review
focuses
on
current
understanding
cell
heterogeneity,
which
includes
both
intra-organ
inter-organ
heterogeneity.
Intra-organ
encompasses
arterio-venous
tip-stalk
specialization,
while
refers
organ-specific
transcriptomic
profiles
functions.
Advances
in
single-cell
RNA
sequencing
(scRNA-seq)
enabled
identification
new
subpopulations
comparison
gene
expression
patterns
across
subsets
cells.
Integrating
scRNA-seq
with
other
high-throughput
technologies
promises
deepen
our
at
epigenetic
level
spatially
resolved
context.
To
further
explore
human
organoids
offer
powerful
tools
studying
function
three-dimensional
culture
systems
investigating
endothelial-tissue
interactions
using
Developing
presents
unique
opportunities
unravel
its
implications
disease.
Emerging
technologies,
such
as
organoids,
are
poised
transform
pave
way
innovative
therapeutic
strategies
address
diseases.
Graphical
Journal of Clinical Investigation,
Год журнала:
2022,
Номер
132(17)
Опубликована: Июль 12, 2022
An
extreme
chronic
wound
tissue
microenvironment
causes
epigenetic
gene
silencing.
unbiased
whole-genome
methylome
was
studied
in
the
wound-edge
of
patients
with
wounds.
A
total
4,689
differentially
methylated
regions
(DMRs)
were
identified
skin
compared
unwounded
human
skin.
Hypermethylation
more
frequently
observed
(3,661
DMRs)
hypomethylation
(1,028
DMRs).
Twenty-six
hypermethylated
DMRs
involved
epithelial-mesenchymal
transition
(EMT).
Bisulfite
sequencing
validated
hypermethylation
a
predicted
specific
upstream
regulator
TP53.
RNA-Seq
analysis
performed
to
qualify
findings
from
analysis.
Analysis
downregulated
genes
TP53
signaling
pathway
as
being
significantly
silenced.
Direct
comparison
and
4
genes,
ADAM17,
NOTCH,
TWIST1,
SMURF1,
that
functionally
represent
EMT
pathway.
Single-cell
studies
revealed
these
effects
on
expression
limited
keratinocyte
cell
compartment.
Experimental
murine
established
ischemia
potently
induces
methylation
5'-azacytidine,
inhibitor
methylation,
improved
closure.
To
specifically
address
significance
keratinocyte-specific
editing
at
edge
achieved
by
nanotransfection-based
CRISPR/dCas9
approach.
This
work
reversal
methylation-dependent
silencing
represents
productive
therapeutic
strategy
improve
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(8), С. 7208 - 7208
Опубликована: Апрель 13, 2023
Breast
cancer
(BC)
is
the
first
worldwide
most
frequent
in
both
sexes
and
commonly
diagnosed
females.
Although
BC
mortality
has
been
thoroughly
declining
over
past
decades,
there
are
still
considerable
differences
between
women
with
early
when
metastatic
diagnosed.
treatment
choice
widely
dependent
on
precise
histological
molecular
characterization.
However,
recurrence
or
distant
metastasis
occurs
even
recent
efficient
therapies.
Thus,
a
better
understanding
of
different
factors
underlying
tumor
escape
mainly
mandatory.
Among
leading
candidates
continuous
interplay
cells
their
microenvironment,
where
extracellular
vesicles
play
significant
role.
vesicles,
smaller
ones,
also
called
exosomes,
can
carry
biomolecules,
such
as
lipids,
proteins,
nucleic
acids,
generate
signal
transmission
through
an
intercellular
transfer
content.
This
mechanism
allows
to
recruit
modify
adjacent
systemic
microenvironment
support
further
invasion
dissemination.
By
reciprocity,
stromal
use
exosomes
profoundly
cell
behavior.
review
intends
cover
literature
role
vesicle
production
normal
cancerous
breast
tissues.
Specific
attention
paid
for
diagnosis,
follow-up,
prognosis
because
actually
under
spotlight
researchers
high-potential
source
liquid
biopsies.
Extracellular
new
targets
therapy
nanovectors
drive
drug
delivery
summarized.
