bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 11, 2024
Abstract
The
coronary
arteries
develop
under
substantial
mechanical
loads.
However,
the
role
of
mechanosensitive
ion
channels
has
barely
been
addressed
in
this
system.
Here
we
demonstrate
expression
channel
PIEZO2
specific
endothelial
cell
populations
during
a
crucial
phase
vascular
modeling.
Piezo2
positive
cells
display
distinct
transcriptional
profiles
and
have
mechanically
activated
ionic
currents.
Strikingly,
-/-
mouse
embryos
mice
with
human
pathogenic
variants
vessel
malformations
left
ventricular
hyperplasia.
We
conclude
that
an
optimal
balance
function
is
indispensable
for
formation,
integrity,
remodeling
likely
proper
cardiac
function.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 30, 2025
Abstract
For
several
decades,
many
attempts
have
been
made
to
characterise
the
mechanical
properties
of
grey
and
white
matter,
which
constitute
two
main
compartments
central
nervous
system
(CNS),
with
various
methods
contradictory
results.
In
particular,
ratio
grey-to-white-matter
elasticity
is
sometimes
larger
than
1
smaller;
reason
for
this
apparent
discrepancy
currently
unknown.
Here,
we
exploited
atomic
force
microscopy
(AFM)-based
indentation
measurements
systematically
investigate
how
measurement
force,
speed,
post-mortem
interval
temperature
affect
measured
spinal
cord
tissue,
in
particular
(
K
g
/K
w
).
Within
explored
parameter
space,
increasing
speed
increased
both
matter.
However,
declined
from
values
as
high
∼5
at
low
forces
speeds
∼1
speeds.
also
strongly
depended
on
anatomical
plane
were
conducted
was
considerably
higher
transverse
sections
compared
longitudinal
sections.
Furthermore,
impacted
absolute
tissue
.
Grey
matter
started
decreasing
∼3
hours
until
reaching
a
plateau
after
∼6
hours.
contrast,
declining
beginning
post-mortem,
when
it
levelled
off.
As
result,
before
stabilising.
Between
20°C
38°C,
decreased
similar
rate,
without
affecting
We
thus
identified
differences
response
varying
strains
strain
rates,
interval,
excluded
factor
These
differential
responses
likely
contribute
results
obtained
different
working
regimes.
Statement
significance
here
showed
that
CNS
an
applied
differentially
depends
parameters
such
magnitude
forces,
well
axis
along
are
conducted.
broaden
our
understanding
mechanics
pave
way
better
more
targeted
experimental
design
future
experiments.
Ultimately,
they
may
help
reconcile
seemingly
literature
concerning
elasticity.
Therapeutic Delivery,
Год журнала:
2025,
Номер
unknown, С. 1 - 14
Опубликована: Март 25, 2025
Brain
cancer
has
become
an
emerging
medical
disorder
that
poses
a
threat
to
human
life
due
the
uncontrolled
growth
of
cells
and
their
gradual
spread
other
organs.
The
most
aggressive
life-threatening
several
types
is
GBM.
Treating
GBM
difficult
considering
drugs
are
not
exposed
at
brain's
site
action
because
BBTB
BBB.
Only
few
cytotoxic
presently
used
treat
GBM,
including
temozolomide,
paclitaxel,
doxorubicin,
only
temozolomide
enough
BBB
penetration.
In
this
context,
engineered
nanoparticles
transport
chemotherapeutic
medications
reduce
notable
peripheral
toxicity
on
normal
cells;
for
necessary
drug
dosages.
They
investigated
as
carriers
address
problem
resistance
linked
traditional
chemotherapy
treatments.
Many
nanostructures,
such
polymeric,
lipid-based,
inorganic
nanoparticles,
have
been
developed
drug-delivery
methods
in
recent
decades.
To
be
therapeutically
successful
therapy,
ENP
formulations
must
diffuse
through
efficiently
deliver
target
cells.
Various
coatings
surface
modifications
nanostructures
can
tailored
with
different
targeting
moieties
facilitate
uptake
by
malignant
while
safeguarding
healthy
tissues
from
damage.
Microglia,
the
central
nervous
system
(CNS)
resident
immune
cells,
are
pivotal
in
regulating
neurodevelopment,
maintaining
neural
homeostasis,
and
mediating
neuroinflammatory
responses.
Recent
research
has
highlighted
importance
of
mechanotransduction,
process
by
which
cells
convert
mechanical
stimuli
into
biochemical
signals,
microglial
activity.
Among
various
mechanosensitive
channels,
Piezo1
emerged
as
a
key
player
microglia,
influencing
their
behavior
under
both
physiological
pathological
conditions.
This
review
focuses
on
expression
role
particularly
context
neuroinflammation
tumorigenesis.
We
explore
how
mediates
responses
to
changes
within
CNS,
such
alterations
tissue
stiffness
fluid
shear
stress,
common
conditions
like
multiple
sclerosis,
Alzheimer's
disease,
cerebral
ischemia,
gliomas.
The
also
discusses
potential
targeting
for
therapeutic
intervention,
given
its
involvement
modulation
activity
impact
disease
progression.
integrates
findings
from
recent
studies
provide
comprehensive
overview
Piezo1's
mechanistic
pathways
function.
These
insights
illuminate
new
possibilities
developing
targeted
therapies
addressing
CNS
disorders
with
mechanics.
Cell Reports,
Год журнала:
2023,
Номер
42(8), С. 112848 - 112848
Опубликована: Июль 28, 2023
Oligodendrocytes
are
specialized
cells
that
insulate
and
support
axons
with
their
myelin
membrane,
allowing
proper
brain
function.
Here,
we
identify
lamin
A/C
(LMNA/C)
as
essential
for
transcriptional
functional
stability
of
myelinating
oligodendrocytes.
We
show
LMNA/C
levels
increase
differentiation
progenitors
loss
Lmna
in
differentiated
oligodendrocytes
profoundly
alters
chromatin
accessibility
signature.
deletion
glia
is
compatible
normal
developmental
myelination.
However,
altered
detected
fully
together
increased
expression
progenitor
genes
decreased
lipid-related
transcription
factors
inner
mitochondrial
membrane
transcripts.
These
changes
accompanied
by
metabolism,
lower
myelin-related
lipids,
structure
oligodendrocytes,
thereby
resulting
thinning
the
development
a
progressively
worsening
motor
phenotype.
Overall,
our
data
maintaining
Cell Reports Medicine,
Год журнала:
2024,
Номер
5(8), С. 101658 - 101658
Опубликована: Июль 24, 2024
The
DNA
damage
response
(DDR)
and
the
blood-tumor
barrier
(BTB)
restrict
chemotherapeutic
success
for
primary
brain
tumors
like
glioblastomas
(GBMs).
Coherently,
GBMs
almost
invariably
relapse
with
fatal
outcomes.
Here,
we
show
that
interaction
of
GBM
myeloid
cells
simultaneously
induces
chemoresistance
on
genetic
vascular
levels
by
activating
GP130
receptor
signaling,
which
can
be
addressed
therapeutically.
We
provide
data
from
transcriptomic
immunohistochemical
screens
human
material
pharmacological
experiments
a
humanized
organotypic
model,
proteomics,
transcriptomics,
cell-based
assays
report
nanomolar
concentrations
signaling
peptide
humanin
promote
temozolomide
(TMZ)
resistance
through
DDR
activation.
mouse
models
recapitulating
intratumoral
release
accelerated
BTB
formation.
blockade
attenuates
both
activity
formation,
resulting
in
improved
preclinical
efficacy.
Altogether,
describe
an
overarching
mechanism
TMZ
outline
translatable
strategy
predictive
markers
to
improve
chemotherapy
GBMs.
