Cell Death and Disease,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Jan. 24, 2024
Abstract
Skin
fibrosis
is
characterized
by
the
excessive
accumulation
of
extracellular
matrix
(ECM)
caused
fibrotic
disorders
skin.
In
recent
years,
ECM
stiffness
has
emerged
as
a
prominent
mechanical
cue
that
precedes
skin
and
drives
its
progression
promoting
fibroblasts
activation.
However,
how
influences
activation
for
remains
unknown.
Here,
we
report
positive
feedback
loop
mediated
mechanosensitive
ion
channel
Piezo1
aberrant
tissue
mechanics
in
driving
fibrosis.
upregulated
both
humans
mice.
knockdown
dermal
lose
their
fibroproliferative
phenotypes
despite
being
grown
on
stiffer
substrate.
We
show
acts
through
Wnt2/Wnt11
pathway
to
mechanically
induce
secretion
C-C
motif
chemokine
ligand
24
(CCL24,
also
known
eotaxin-2),
potent
cytokine
associated
with
disorders.
Importantly,
adeno-associated
virus
(AAV)-mediated
ameliorated
Overall,
increased
promotes
inflammatory
Piezo1-Wnt2/Wnt11-CCL24
pathway.
turn,
microenvironment
increases
expression
exacerbate
aggression.
Therefore,
targeting
represents
strategy
break
between
mechanotransduction
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: June 11, 2024
Abstract
Microgravity
is
associated
with
immunological
dysfunction,
though
the
mechanisms
are
poorly
understood.
Here,
using
single-cell
analysis
of
human
peripheral
blood
mononuclear
cells
(PBMCs)
exposed
to
short
term
(25
hours)
simulated
microgravity,
we
characterize
altered
genes
and
pathways
at
basal
stimulated
states
a
Toll-like
Receptor-7/8
agonist.
We
validate
by
RNA
sequencing
super-resolution
microscopy,
against
data
from
Inspiration-4
(I4)
mission,
JAXA
(Cell-Free
Epigenome)
Twins
study,
spleens
mice
on
International
Space
Station.
Overall,
microgravity
alters
specific
for
optimal
immunity,
including
cytoskeleton,
interferon
signaling,
pyroptosis,
temperature-shock,
innate
inflammation
(e.g.,
Coronavirus
pathogenesis
pathway
IL-6
signaling),
nuclear
receptors,
sirtuin
signaling.
directs
monocyte
inflammatory
parameters,
impairs
T
cell
NK
functionality.
Using
machine
learning,
identify
numerous
compounds
linking
immune
transcription,
demonstrate
that
flavonol,
quercetin,
can
reverse
most
abnormal
pathways.
These
results
define
alterations
in
provide
opportunities
countermeasures
maintain
normal
immunity
space.
Bone Research,
Journal Year:
2024,
Volume and Issue:
12(1)
Published: Aug. 5, 2024
Abstract
Ageing
as
a
natural
irreversible
process
inherently
results
in
the
functional
deterioration
of
numerous
organ
systems
and
tissues,
including
skeletal
immune
systems.
Recent
studies
have
elucidated
intricate
bidirectional
interactions
between
these
two
In
this
review,
we
provide
comprehensive
synthesis
molecular
mechanisms
cell
ageing.
We
further
discuss
how
age-related
changes
influence
system
consequent
impact
alterations
on
system.
Finally,
highlight
clinical
implications
findings
propose
potential
strategies
to
promote
healthy
ageing
reduce
pathologic
both
European Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
273, P. 116502 - 116502
Published: May 14, 2024
The
cation
channel
Piezo1,
a
crucial
mechanotransducer
found
in
various
organs
and
tissues,
has
gained
considerable
attention
as
therapeutic
target
recent
years.
Following
this
trend,
several
Piezo1
inhibitors
have
been
discovered
studied
for
potential
pharmacological
properties.
This
review
provides
an
overview
of
the
structural
functional
importance
well
discussing
biological
activities
based
on
their
mechanism
action.
compounds
addressed
include
toxin
GsMTx4,
Aβ
peptides,
certain
fatty
acids,
ruthenium
red
gadolinium,
Dooku1,
natural
products
tubeimoside
I,
salvianolic
acid
B,
jatrorrhzine,
escin.
findings
revealed
that
misexpression
can
be
associated
with
number
chronic
diseases,
including
hypertension,
cancer,
hemolytic
anemia.
Consequently,
inhibiting
subsequent
calcium
influx
beneficial
effects
pathological
processes,
shown
by
many
vitro
vivo
studies.
However,
development
is
still
its
beginnings,
opportunities
challenges
remaining
to
explored.
Cell Death and Disease,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Jan. 24, 2024
Abstract
Skin
fibrosis
is
characterized
by
the
excessive
accumulation
of
extracellular
matrix
(ECM)
caused
fibrotic
disorders
skin.
In
recent
years,
ECM
stiffness
has
emerged
as
a
prominent
mechanical
cue
that
precedes
skin
and
drives
its
progression
promoting
fibroblasts
activation.
However,
how
influences
activation
for
remains
unknown.
Here,
we
report
positive
feedback
loop
mediated
mechanosensitive
ion
channel
Piezo1
aberrant
tissue
mechanics
in
driving
fibrosis.
upregulated
both
humans
mice.
knockdown
dermal
lose
their
fibroproliferative
phenotypes
despite
being
grown
on
stiffer
substrate.
We
show
acts
through
Wnt2/Wnt11
pathway
to
mechanically
induce
secretion
C-C
motif
chemokine
ligand
24
(CCL24,
also
known
eotaxin-2),
potent
cytokine
associated
with
disorders.
Importantly,
adeno-associated
virus
(AAV)-mediated
ameliorated
Overall,
increased
promotes
inflammatory
Piezo1-Wnt2/Wnt11-CCL24
pathway.
turn,
microenvironment
increases
expression
exacerbate
aggression.
Therefore,
targeting
represents
strategy
break
between
mechanotransduction
