Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: July 31, 2023
Abstract
Cellular
mechanotransduction,
a
critical
regulator
of
numerous
biological
processes,
is
the
conversion
from
mechanical
signals
to
biochemical
regarding
cell
activities
and
metabolism.
Typical
cues
in
organisms
include
hydrostatic
pressure,
fluid
shear
stress,
tensile
force,
extracellular
matrix
stiffness
or
tissue
elasticity,
viscosity.
Mechanotransduction
has
been
expected
trigger
multiple
such
as
embryonic
development,
repair
regeneration.
However,
prolonged
excessive
stimulation
can
result
pathological
multi-organ
fibrosis,
tumorigenesis,
cancer
immunotherapy
resistance.
Although
associations
between
normal
homeostasis
diseases
have
identified,
regulatory
mechanisms
among
different
are
not
yet
comprehensively
illustrated,
no
effective
therapies
currently
available
targeting
cue-related
signaling.
This
review
systematically
summarizes
characteristics
typical
conditions
with
updated
evidence.
The
key
effectors
responding
stimulations
listed,
Piezo
channels,
integrins,
Yes-associated
protein
(YAP)
/transcriptional
coactivator
PDZ-binding
motif
(TAZ),
transient
receptor
potential
vanilloid
4
(TRPV4).
We
also
reviewed
signaling
pathways,
therapeutic
targets
cutting-edge
clinical
applications
related
cues.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(4), P. 4004 - 4004
Published: Feb. 16, 2023
Most
chronic
inflammatory
illnesses
include
fibrosis
as
a
pathogenic
characteristic.
Extracellular
matrix
(ECM)
components
build
up
in
excess
to
cause
or
scarring.
The
fibrotic
process
finally
results
organ
malfunction
and
death
if
it
is
severely
progressive.
Fibrosis
affects
nearly
all
tissues
of
the
body.
associated
with
inflammation,
metabolic
homeostasis,
transforming
growth
factor-β1
(TGF-β1)
signaling,
where
balance
between
oxidant
antioxidant
systems
appears
be
key
modulator
managing
these
processes.
Virtually
every
system,
including
lungs,
heart,
kidney,
liver,
can
affected
by
fibrosis,
which
characterized
an
excessive
accumulation
connective
tissue
components.
Organ
frequently
caused
remodeling,
also
linked
high
morbidity
mortality.
Up
45%
fatalities
industrialized
world
are
damage
any
organ.
Long
believed
persistently
progressing
irreversible,
has
now
been
revealed
very
dynamic
preclinical
models
clinical
studies
variety
systems.
pathways
from
and/or
main
topics
this
review.
Furthermore,
different
organs
their
effects
was
discussed.
Finally,
we
highlight
many
principal
mechanisms
fibrosis.
These
could
considered
promising
targets
for
development
potential
therapies
important
human
diseases.
Medicinal Research Reviews,
Journal Year:
2021,
Volume and Issue:
41(4), P. 1999 - 2038
Published: Jan. 19, 2021
Abstract
Huang‐Qi
(Astragali
Radix)
is
an
herbal
tonic
widely
used
in
China
and
many
other
countries.
It
derived
from
the
roots
of
Astragalus
membranaceus
A.
var.
mongholicus
shows
potent
cardiovascular
protective
effects.
In
this
article,
we
comprehensively
reviewed
189
small
molecules
isolated
two
species
discussed
interspecies
chemical
differences.
Moreover,
summarized
pharmacological
activities
mechanisms
action
its
major
bioactive
compounds
for
treatment
diseases.
This
review
covers
171
references
published
between
February
1983
March
2020.
International Journal of Molecular Sciences,
Journal Year:
2022,
Volume and Issue:
23(5), P. 2617 - 2617
Published: Feb. 27, 2022
Fibrosis
is
defined
as
the
excessive
deposition
of
extracellular
matrix
(ECM)
proteins
in
interstitium.
It
an
essential
pathological
response
to
chronic
inflammation.
ECM
protein
initially
protective
and
critical
for
wound
healing
tissue
regeneration.
However,
cardiac
remodeling
continuous
damage
with
subsequent
results
a
distorted
organ
architecture
significantly
impacts
function.
In
this
review,
we
summarized
discussed
histologic
features
fibrosis
signaling
factors
that
control
it.
We
evaluated
origin
characteristic
markers
fibroblasts.
also
lymphatic
vessels,
which
have
become
more
important
recent
years
improve
fibrosis.
Frontiers in Immunology,
Journal Year:
2022,
Volume and Issue:
13
Published: Aug. 5, 2022
Diabetes
is
a
systemic
disease
in
which
patients
with
diabetes
may
develop
peripheral
neuropathy
of
the
lower
extremities
and
vascular
due
to
long-term
continuous
exposure
high
glucose.
Delayed
wound
healing
one
major
complications
diabetes.
Slow
diabetic
associated
glucose
toxicity.
When
condition
deteriorates,
patient
needs
be
amputated,
seriously
affects
quality
life
even
endangers
patient.
In
general,
delayed
lack
chemokines,
abnormal
inflammatory
response,
angiogenesis
epithelial
formation,
fibroblast
dysfunction.
The
incidence
several
chronic
debilitating
conditions
increasing
diabetes,
such
as
renal
insufficiency,
heart
failure,
hepatic
insufficiency.
Fibrosis
an
inappropriate
deposition
extracellular
matrix
(ECM)
proteins.
It
common
causing
organ
fibrotic
mechanism
fibroblasts
involve
direct
activation
permanent
fibroblasts.
also
degeneration
fibers
after
hyperglycemia
stimulates
immune
cells,
or
organ-specific
parenchymal
cells.
Numerous
studies
confirm
that
play
essential
role
treating
its
complications.
primary
function
construct
reshape
ECM.
Nowadays,
widespread
use
single-cell
RNA
sequencing
(scRNA-seq),
number
have
found
become
critical
sentinel
can
detect
not
only
regulation
response
but
molecular
pattern
related
injury.
By
exploring
heterogeneity
functional
changes
manuscript
discusses
used
immunomodulatory
factors
refractory
healing,
providing
new
ideas
for
treatment
healing.
Cardiovascular Research,
Journal Year:
2022,
Volume and Issue:
118(18), P. 3536 - 3555
Published: Aug. 24, 2022
Abstract
Many
patients
with
symptoms
and
signs
of
heart
failure
have
a
left
ventricular
ejection
fraction
≥50%,
termed
preserved
(HFpEF).
HFpEF
is
heterogeneous
syndrome
mainly
affecting
older
people
who
many
other
cardiac
non-cardiac
conditions
that
often
cast
doubt
on
the
origin
symptoms,
such
as
breathlessness,
or
signs,
peripheral
oedema,
rendering
them
neither
sensitive
nor
specific
to
diagnosis
HFpEF.
Currently,
management
directed
at
controlling
treating
comorbid
hypertension,
atrial
fibrillation,
anaemia,
coronary
artery
disease.
also
characterized
by
persistent
increase
in
inflammatory
biomarkers.
Inflammation
may
be
key
driver
development
progression
its
associated
comorbidities.
Detailed
characterization
pathways
provide
insights
into
pathophysiology
guide
future
management.
There
growing
interest
novel
therapies
specifically
designed
target
deregulated
inflammation
therapeutic
areas,
including
cardiovascular
However,
large-scale
clinical
trials
investigating
effectiveness
anti-inflammatory
treatments
are
still
lacking.
In
this
manuscript,
we
review
role
possible
implications
for
trials.
Theranostics,
Journal Year:
2023,
Volume and Issue:
13(2), P. 685 - 703
Published: Jan. 1, 2023
Rationale:
Clinical
application
of
mesenchymal
stem
cells
(MSCs)
and
MSC-derived
exosomes
(MSC-Exos)
to
alleviate
myocardial
ischemia/reperfusion
(I/R)
injury
is
compromised
by
the
low
cell
engraftment
rate
uncontrolled
exosomal
content.As
one
their
active
ingredients,
single-component
microRNA
therapy
may
have
more
inherent
advantages.We
sought
find
an
ideal
candidate
determine
whether
it
could
reproduce
cardioprotective
effects
MSCs
MSC-Exos.Methods:
Cardiac
function
remodeling
in
MSC,
MSC-Exo,
or
oligonucleotide-treated
mouse
hearts
were
investigated
after
I/R
injury.The
oligonucleotides
on
cardiac
(macrophages,
cardiomyocytes,
fibroblasts,
endothelial
cells)
downstream
mechanisms
confirmed.Large
animals
also
employed
investigate
safety
therapy.
Results:The
results
showed
that
microRNA-125a-5p
(miR-125a-5p)
enriched
MSC-Exos,
intramyocardial
delivery
modified
(agomir)
myocardium,
as
well
exerted
obvious
cardioprotection
increasing
limiting
adverse
remodeling.In
addition,
miR-125a-5p
agomir
treatment
increased
M2
macrophage
polarization,
promoted
angiogenesis,
attenuated
fibroblast
proliferation
activation,
which
subsequently
contributed
improvements
cardiomyocyte
apoptosis
inflammation.Mechanistically,
Klf13,
Tgfbr1,
Daam1
are
considered
targets
for
regulating
macrophages,
cells,
respectively.Similar
observed
following
a
porcine
model,
with
no
increase
risk
arrhythmia
hepatic,
renal,
toxicity.Conclusions:
This
targeted
presents
effective
safe
strategy
repair.
