International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(13), С. 10650 - 10650
Опубликована: Июнь 26, 2023
Myotonic
Dystrophy
type
1
(DM1)
is
a
neuromuscular
disease
associated
with
toxic
RNA
containing
expanded
CUG
repeats.
The
developing
therapeutic
approaches
to
DM1
target
mutant
or
correct
early
events
downstream
of
the
RNA.
We
have
previously
described
benefits
correction
GSK3β-CUGBP1
pathway
in
mice
(HSALR
model)
expressing
250
repeats
using
GSK3
inhibitor
tideglusib
(TG).
Here,
we
show
that
TG
treatments
corrected
expression
~17%
genes
misregulated
mice,
including
involved
cell
transport,
development
and
differentiation.
chloride
channel
(Clcn1),
key
trigger
myotonia
DM1,
was
also
by
TG.
found
long
(DMSXL
beneficial
not
only
at
prenatal
postnatal
stages,
but
during
adulthood.
Using
mouse
model
dysregulated
CUGBP1,
which
mimics
alterations
showed
CUGBP1
contributes
toxicity
changing
gene
causing
CNS
abnormalities.
These
data
critical
role
muscle
pathologies,
suggesting
inhibitors
patients
different
forms
DM1.
Biochemical Pharmacology,
Год журнала:
2022,
Номер
208, С. 115407 - 115407
Опубликована: Дек. 31, 2022
Chronic
kidney
disease
(CKD)
is
a
high-risk
chronic
catabolic
due
to
its
high
morbidity
and
mortality.
CKD
accompanied
by
many
complications,
leading
poor
quality
of
life,
serious
complications
may
even
threaten
the
life
patients.
Muscle
atrophy
common
complication
CKD.
sarcopenia
in
patients
have
complex
pathways
that
are
related
multiple
mechanisms
factors.
This
review
not
only
discusses
which
inflammation,
oxidative
stress,
mitochondrial
dysfunction
promote
CKD-induced
muscle
but
also
explores
other
CKD-related
such
as
metabolic
acidosis,
vitamin
D
deficiency,
anorexia,
excess
angiotensin
II,
well
factors
play
role
atrophy,
insulin
resistance,
hormones,
hemodialysis,
uremic
toxins,
intestinal
flora
imbalance,
miRNA.
We
highlight
potential
treatments
drugs
can
effectively
treat
terms
treatment,
nutritional
supplementation,
physical
exercise,
drug
intervention,
thereby
helping
improve
prognosis
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Июль 19, 2023
Abstract
Skeletal
muscle
fibers
express
distinct
gene
programs
during
development
and
maturation,
but
the
underlying
regulatory
networks
that
confer
stage-specific
myofiber
properties
remain
unknown.
To
decipher
these
distinctive
how
they
respond
to
neural
activity,
we
generated
a
combined
multi-omic
single-nucleus
RNA-seq
ATAC-seq
atlas
of
mouse
skeletal
at
multiple
stages
embryonic,
fetal,
postnatal
life.
We
found
Myogenin,
Klf5,
Tead4
form
transcriptional
complex
synergistically
activates
expression
genes
in
developing
myofibers.
During
transcription
factor
Maf
acts
as
switch
activate
mature
fast
program.
In
muscles
mutant
mice
lacking
voltage-gated
L-type
Ca
2+
channels
(Cav1.1),
maturation
are
impaired.
These
findings
provide
reveal
genetic
links
between
formation,
contraction.
npj Regenerative Medicine,
Год журнала:
2024,
Номер
9(1)
Опубликована: Март 1, 2024
Skeletal
muscle
function
crucially
depends
on
innervation
while
repair
of
skeletal
relies
resident
stem
cells
(MuSCs).
However,
it
is
poorly
understood
how
affects
MuSC
properties
and
thereby
regeneration
muscle.
Here,
we
report
that
loss
causes
precocious
activation
MuSCs
concomitant
with
the
expression
markers
myogenic
differentiation.
This
aberrant
after
accompanied
by
profound
alterations
mRNA
protein
level.
Combination
injury
results
in
impaired
including
shifts
populations
delayed
maturation
regenerating
myofibers.
We
further
demonstrate
leads
to
myofibers
their
secretome,
which
then
affect
behavior.
In
particular,
identify
an
increased
secretion
Osteopontin
transforming
growth
factor
beta
1
(Tgfb1)
isolated
from
mice
had
undergone
sciatic
nerve
transection.
The
altered
secretome
upregulation
early
activating
transcription
factors,
such
as
Junb,
target
genes
MuSCs.
combination
different
secreted
factors
required
cause
observed
innervation.
These
data
first
causing
underscoring
importance
proper
for
functionality
Frontiers in Bioengineering and Biotechnology,
Год журнала:
2022,
Номер
10
Опубликована: Окт. 18, 2022
Peripheral
nerve
injury
is
a
clinically
common
that
causes
sensory
dysfunction
and
locomotor
system
degeneration,
which
seriously
affects
the
quality
of
patients’
daily
life.
Long
gapped
defects
in
large
are
difficult
to
repair
via
surgery
limited
donor
source
autologous
greatly
challenges
successful
by
transplantation.
Significantly,
remarkable
progress
has
been
made
repairing
peripheral
using
artificial
grafts
variety
products
for
have
emerged
approved
globally
recent
years.
The
raw
materials
these
commercial
includes
natural/synthetic
polymers,
extracellular
matrix.
Despite
lot
effort,
desirable
functional
recovery
still
remains
great
long
defects.
Thus
this
review
discusses
development
tissue
engineering
design
bionic
improving
local
microenvironment
accelerating
regeneration
against
disorder,
may
provide
potential
strategies
gaps
or
thick
multifunctional
biomaterials.
Abstract
Alzheimer’s
disease
(AD)
develops
along
a
continuum
that
spans
years
prior
to
diagnosis.
Decreased
muscle
function
and
mitochondrial
respiration
occur
earlier
in
those
develop
AD;
however,
it
is
unknown
what
causes
these
peripheral
phenotypes
of
the
brain.
Exercise
promotes
muscle,
mitochondria,
cognitive
health
proposed
be
potential
therapeutic
for
AD,
but
no
study
has
investigated
how
skeletal
adapts
exercise
training
an
AD-like
context.
Utilizing
5xFAD
mice,
AD
model
ad-like
pathology
impairments
around
6
mo
age,
we
examined
vivo
neuromuscular
adapations
(mitochondrial
RNA
sequencing)
before
manifestation
overt
impairment.
We
found
mice
dysfunction
beginning
as
early
4
characterized
by
impaired
nerve-stimulated
torque
production
compound
nerve
action
sciatic
nerve.
Furthermore,
had
altered,
sex-dependent,
adaptive
responses
gene
expression)
absence
Changes
systems,
specifically
neural
communication
may
harbingers
have
implications
lifestyle
interventions,
like
exercise,
AD.
Translational Neurodegeneration,
Год журнала:
2023,
Номер
12(1)
Опубликована: Окт. 12, 2023
Amyotrophic
lateral
sclerosis
(ALS)
is
a
poorly
treated
multifactorial
neurodegenerative
disease
associated
with
multiple
cell
types
and
subcellular
organelles.
As
other
diseases,
it
likely
that
drugs
will
need
to
target
processes
be
effective.
We
review
here
the
role
of
Janus
kinase
(JAK)/Signal
transducer
activator
transcription
(STAT)
signalling
in
ALS,
confirm
association
this
fundamental
ALS
using
BenevolentAI
Knowledge
Graph,
demonstrate
inhibitors
pathway
could
reduce
pathophysiology
neurons,
glia,
muscle
fibres,
blood
cells.
Specifically,
we
suggest
inhibition
JAK
enzymes
by
approved
known
as
Jakinibs
STAT3
activation
modify
progress
disease.
Analysis
highlights
baricitinib
suitable
candidate
due
its
ability
penetrate
central
nervous
system
exert
beneficial
effects
on
immune
system.
Therefore,
recommend
drug
tested
appropriately
designed
clinical
trials
for
ALS.
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 21, 2025
Abstract
Denervated
muscle
atrophy,
a
common
outcome
of
nerve
injury,
often
results
in
irreversible
fibrosis
due
to
the
limited
effectiveness
current
therapeutic
interventions.
While
extracellular
vesicles
(EVs)
offer
promise
for
treating
their
potential
is
hindered
by
challenges
delivery
and
bioactivity
within
complex
microenvironment
injury
site.
To
address
this
issue,
an
injectable
hydrogel
developed
that
responsive
both
ultrasound
pH,
with
inherent
anti‐inflammatory
antioxidant
properties,
designed
improve
targeted
stem
cell‐derived
EVs.
This
system
allows
controlled
release
EVs
from
human
umbilical
cord
mesenchymal
cells
(HUC‐MSCs),
adapting
specific
conditions
environment.
In
vivo
studies
using
rat
model
demonstrated
EV‐loaded
(EVs@UR‐gel)
significantly
preserved
function.
Six
weeks
post‐nerve
reconstruction,
treated
rats
exhibited
strength,
circumference,
wet
weight
reaching
89.53
±
0.96%,
76.02
7.49%,
88.0
2.65%
healthy
controls,
respectively,
alongside
improvement
sciatic
index
(−0.11±0.09).
platform
presents
novel
approach
maintaining
EV
bioactivity,
enabling
tunable
based
on
disease
state,
facilitating
restoration
structure