Molecular Therapy — Nucleic Acids,
Год журнала:
2022,
Номер
30, С. 535 - 546
Опубликована: Ноя. 7, 2022
Autism
spectrum
disorder
(ASD)-a
congenital
mental
accompanied
by
social
dysfunction
and
stereotyped
behaviors-has
attracted
a
great
deal
of
attention
worldwide.
A
combination
genetic
environmental
factors
may
determine
the
pathogenesis
ASD.
Recent
research
multiple
ASD
models
indicates
that
microRNAs
(miRNAs)
play
central
role
at
onset
progression
repressing
translation
key
mRNAs
in
neural
development
functions.
As
such,
miRNAs
show
potential
to
serve
as
biomarkers
for
diagnosis
or
prognosis
therapeutic
targets
treatment
In
this
review,
we
discuss
regulatory
mechanisms
which
influence
phenotypes
through
various
vivo
vitro
models,
including
necropsy
specimens,
animal
cellular
and,
particular,
induced
pluripotent
stem
cells
derived
from
patients
with
We
then
miRNA-based
strategies
currently
being
evaluated
preclinical
studies.
Nucleic Acids Research,
Год журнала:
2025,
Номер
53(2)
Опубликована: Янв. 11, 2025
Abstract
We
present
a
robust
‘splice-at-will’
CRISPR
RNA
(crRNA)
engineering
mechanism
that
overcomes
the
limitations
of
clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)/Cas
system
in
directly
detecting
ultrashort
RNAs.
In
this
strategy,
an
intact
Cas12a
crRNA
can
be
split
from
almost
any
site
spacer
region
to
obtain
truncated
(tcrRNA)
cannot
activate
even
after
binding
auxiliary
DNA
activator.
While
splicing
tcrRNAs
with
moiety
RNA,
formed
combination
work
together
efficiently,
enabling
engineering.
Importantly,
exhibits
same
trans-cleavage
activation
efficiency
as
conventional
crRNA.
Therefore,
by
rationally
designing
activator
conserved
tcrRNA-complementary
sequence
and
arbitrary
RNA-of-interest
recognition
domain,
general
sensing
is
established
utilizes
traditional
DNA-activated
detect
This
strategy
could
faithfully
sequences
6–8
nt,
which
achieved
Cas13a
systems.
Additionally,
through
flexible
design,
our
method
precisely
distinguish
single-base
differences
microRNA
other
sequences.
has
significantly
expanded
Cas12a-based
diagnostic
toolbox
opened
new
avenues
for
detection.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Фев. 27, 2025
Mesenchymal
stem
cell
(MSC)
therapy
holds
promise
in
biomedical
applications
but
faces
challenges
efficient
transfection
without
compromising
viability.
Here,
we
show
a
serum-tolerant
MSC
nanotool,
APOs@BP,
composed
of
an
apolipoprotein
(APO)
corona
and
boronated
polyethyleneimine
(BP)
core.
The
APOs
corona's
serum-protein
resistance
cytomembrane
affinity
enable
APOs@BP
to
achieve
10.4-fold
higher
efficiency
improved
cytocompatibility
serum-containing
medium
compared
high-molecular-weight
polycationic
transfectants.
For
neural
differentiation,
miRNA-124
all-trans
retinoic
acid
derivative
(atRAN)
are
further
loaded
into
forming
polymeric
complex
for
sequential
drug
release
triggered
by
lysosomal
cytosolic
reactive
oxygen
species
post-transplantation.
Transcriptomic
analysis
confirms
that
this
system
enhances
differentiation
through
activation
atRAN-induced
potential
miRNA-124-directed
neurogenesis
via
cGMP-PKG,
MAPK,
PI3K-Akt
pathways.
Transplantation
engineered
MSCs
reconstructs
circuits
alleviates
cognitive
impairment
Alzheimer's
disease
model
mice.
Collectively,
provides
robust
convenient
method
MSC-based
regenerative
medicine.
Stem
therapies
have
huge
face
challenges.
the
authors
report
on
assembly
with
corona,
carry
stem-cell
differentiation.
Frontiers in Molecular Neuroscience,
Год журнала:
2023,
Номер
16
Опубликована: Июль 31, 2023
Astrocytes
are
specialized
non-neuronal
glial
cells
of
the
central
nervous
system,
contributing
to
neuronal
excitability
and
synaptic
transmission
(gliotransmission).
play
a
key
roles
in
epileptogenesis
seizure
generation.
Epilepsy,
as
chronic
disorder
characterized
by
hyperexcitation
hypersynchronization,
is
accompanied
substantial
disturbances
impairment
astrocytic
functions
signaling.
Anti-seizure
drugs
that
provide
symptomatic
control
seizures
primarily
target
neural
activity.
In
epileptic
patients
with
inadequate
available
anti-seizure
drugs,
novel
therapeutic
candidates
needed.
These
should
treat
epilepsy
anti-epileptogenic
disease-modifying
effects.
Evidence
from
human
animal
studies
shows
astrocytes
have
value
for
developing
new
drugs.
this
review,
we
present
hyperexcitability
activity
following
an
etiology-based
approach.
We
analyze
role
both
development
(epileptogenesis)
generation
(ictogenesis).
Several
promising
strategies
attempted
modify
astroglial
treating
being
developed:
(1)
selective
targeting
glia-related
molecular
mechanisms
glutamate
transport;
(2)
modulation
tonic
GABA
release
astrocytes;
(3)
gliotransmission;
(4)
Kir4.1-BDNF
system;
(5)
Na+/K+/ATPase
activity;
(6)
DNA
hypo-
or
hypermethylation
candidate
genes
(7)
gap
junction
regulators;
(8)
adenosine
kinase
(the
major
adenosine-metabolizing
enzyme);
(9)
microglia-astrocyte
communication
inflammatory
pathways.
Novel
now
been
developed,
such
astroglia-targeted
gene
therapy
broad
spectrum
genetic
constructs
cells.
Molecules and Cells,
Год журнала:
2023,
Номер
46(1), С. 21 - 32
Опубликована: Янв. 1, 2023
MicroRNAs
(miRNAs)
play
cardinal
roles
in
regulating
biological
pathways
and
processes,
resulting
significant
physiological
effects.To
understand
the
complex
regulatory
network
of
miRNAs,
previous
studies
have
utilized
massivescale
datasets
miRNA
targeting
attempted
to
computationally
predict
functional
targets
miRNAs.Many
target
prediction
tools
been
developed
are
widely
used
by
scientists
from
various
fields
biology
medicine.Most
these
consider
seed
pairing
between
miRNAs
their
mRNA
additionally
other
determinants
improve
accuracy.However,
exhibit
limited
accuracy
high
false
positive
rates.The
utilization
additional
determinants,
such
as
RNA
modifications
RNA-binding
protein
binding
sites,
may
further
prediction.In
this
review,
we
discuss
that
currently
potentially
predictive
but
unappreciated
accuracy.
Biomedicines,
Год журнала:
2025,
Номер
13(1), С. 167 - 167
Опубликована: Янв. 12, 2025
Background/Objectives:
The
dual
forces
of
structured
inquiry
and
serendipitous
discovery
have
long
shaped
neuropsychiatric
research,
with
groundbreaking
treatments
such
as
lithium
ketamine
resulting
from
unexpected
discoveries.
However,
relying
on
chance
is
becoming
increasingly
insufficient
to
address
the
rising
prevalence
mental
health
disorders
like
depression
schizophrenia,
which
necessitate
precise,
innovative
approaches.
Emerging
technologies
artificial
intelligence,
induced
pluripotent
stem
cells,
multi-omics
potential
transform
this
field
by
allowing
for
predictive,
patient-specific
interventions.
Despite
these
advancements,
traditional
methodologies
animal
models
single-variable
analyses
continue
be
used,
frequently
failing
capture
complexities
human
conditions.
Summary:
This
review
critically
evaluates
transition
serendipity
precision-based
in
research.
It
focuses
key
innovations
dynamic
systems
modeling
network-based
approaches
that
use
genetic,
molecular,
environmental
data
identify
new
therapeutic
targets.
Furthermore,
it
emphasizes
importance
interdisciplinary
collaboration
human-specific
overcoming
limitations
Conclusions:
We
highlight
precision
psychiatry’s
transformative
revolutionizing
care.
paradigm
shift,
combines
cutting-edge
systematic
frameworks,
promises
increased
diagnostic
accuracy,
reproducibility,
efficiency,
paving
way
tailored
better
patient
outcomes
