PLoS ONE,
Journal Year:
2025,
Volume and Issue:
20(2), P. e0316389 - e0316389
Published: Feb. 28, 2025
Depression
poses
a
significant
global
health
challenge,
affecting
an
estimated
300
million
people
worldwide.
While
amitriptyline
(Ami)
remains
one
of
the
most
effective
antidepressants,
its
numerous
side-effects
contribute
to
high
dropout
rate
among
patients.
Addressing
this
issue
requires
exploring
methods
enhance
bioavailability
and
reduce
dosage.
In
study,
we
describe
technique
for
producing
nanoparticles
(Ami-NPs)
improve
drug’s
efficiency.
The
effectiveness
was
assessed
by
comparing
dose-response
curves
Ami-NPs
non-encapsulated
Ami
in
male
female
Wistar
rats
subjected
forced
swimming
test
(FST).
were
fabricated
using
nanoprecipitation,
with
copolymer
poly
(methyl
vinyl
ether/maleic
acid)
as
encapsulant,
3%
solution
poloxamer
F-127
surfactant
stabilizer.
A
Box-Behnken
design
used
optimize
production
Ami-NPs,
resulting
following
optimal
characteristics:
size
198.6
±
38.1
nm,
polydispersity
index
0.005
0.03
zeta
potential
-32
6
mV,
encapsulation
efficiency
79.1
7.4%.
showed
higher
potency
efficacy
reducing
immobility
during
FST
(ED
50
=
7.06
mg/kg,
E
max
41.1%),
compared
(Ami-S)
11.89
33.2%).
occurred
at
12
while
Ami-S
peaked
15.8
mg/kg.
open
field
test,
only
treatment
(12
mg/kg)
empty
increased
immobility.
elevated
plus-maze,
significantly
reduced
closed-arm
entries
(2.1
0.6),
control
(9.5
1.8),
(8
1.0)
(11.5
2).
marble
burying
buried
marbles
(2.4
0.4)
(8.7
1.2).
These
findings
suggest
that
could
be
promising
approach
bioavailability,
thereby
increasing
antidepressant
efficacy,
improving
anxiolytic-like
effects.
Computational and Structural Biotechnology Journal,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 1, 2025
Tumor
necrosis
factor
(TNF)
receptor
1
(TNFR1)
plays
a
central
role
in
signal
transduction
mediating
inflammation
and
cell
death
associated
with
autoimmune
neurodegenerative
disorders.
Inhibition
of
TNFR1
signaling
is
highly
sought-after
strategy
to
target
these
diseases.
forms
pre-ligand
dimers
held
together
by
the
assembly
domain
(PLAD),
which
essential
for
signaling.
form
crucial
points
interaction
entire
complex
connecting
TNF
ligand
bound
trimeric
receptors.
While
previous
studies
have
shown
feasibility
disrupting
dimeric
interactions
through
competitive
mechanism
that
targets
PLAD,
our
recent
demonstrated
small
molecules
could
also
bind
PLAD
modulate
an
allosteric
mechanism.
Importantly,
modulators
alter
dynamics
propagate
long-range
conformational
perturbation
involves
reshuffling
receptors
cytosolic
domains
without
receptor-receptor
or
receptor-ligand
interactions.
In
this
study,
we
perform
molecular
docking
previously
reported
on
extracellular
understand
their
binding
sites
interacting
residues.
We
identify
inter-monomeric
space
between
as
novel
pocket
modulators.
further
conduct
pharmacological
analyses
bioactivity
compounds
residues
properties.
then
provide
insights
into
structure-activity
relationship
targeting
dynamics.
This
paves
way
developing
new
therapeutic
strategies
designing
chemical
scaffolds
International Journal of Nanomedicine,
Journal Year:
2025,
Volume and Issue:
Volume 20, P. 5893 - 5905
Published: May 1, 2025
The
blood-brain
barrier
(BBB)
is
a
critical
protective
that
regulates
the
exchange
of
substances
between
circulatory
system
and
brain,
restricting
access
drugs
to
brain
tissues.
Developing
novel
delivery
strategies
across
BBB
challenging
but
crucial.
Multifunctional
nanogels
are
promising
drug
carriers
for
delivering
therapeutic
agents
their
intended
target
areas
in
tissue.
This
study
introduced
carboxylic
acid-
amine-modified
Pluronic
F127
(ADF127
EDF127)-based
thermoresponsive
nanogel
systems
as
nanocarriers
release
profiles
3-butylidenephthalide
(BP)
from
were
investigated
vitro
phosphate-buffered
saline
(pH
7.4)
at
37
°C
48
h.
Additionally,
accumulation
DiR-labeled
vital
organs
was
observed
using
fluorescence
imaging.
A
relatively
sustained
BP
(27%)
ADF127,
followed
by
rapid
(39%)
within
first
4
h
observed.
In
vivo
studies
C57BL/6JNarl
mouse
model
showed
intravenously
administered
BP-loaded
copolymeric
exhibited
distribution
liver,
spleen,
heart,
kidney.
DiR
intensity
increased
order
<
ADF127
EDF127
nanogels.
Although
tissue
lower
than
those
other
organs,
approximately
10-fold
higher
intensity.
Positively
charged
carrier
nanomaterials
demonstrate
propensity
transfer
through
BBB,
significantly
expanding
applicability
positively
treatment
Therefore,
owing
permeability
(EDF127
ADF127)
will
also
offer
approach
Nanomaterials,
Journal Year:
2025,
Volume and Issue:
15(10), P. 704 - 704
Published: May 8, 2025
Intrinsically
disordered
proteins
(IDPs),
such
as
tau,
beta-amyloid
(Aβ),
and
alpha-synuclein
(αSyn),
are
prone
to
misfolding,
resulting
in
pathological
aggregation
propagation
that
drive
neurodegenerative
diseases,
including
Alzheimer’s
disease
(AD),
frontotemporal
dementia
(FTD),
Parkinson’s
(PD).
Misfolded
IDPs
aggregate
into
oligomers
fibrils,
exacerbating
progression
by
disrupting
cellular
functions
the
central
nervous
system,
triggering
neuroinflammation
neurodegeneration.
Furthermore,
aggregated
exhibit
prion-like
behavior,
acting
seeds
released
extracellular
space,
taken
up
neighboring
cells,
have
a
propagating
pathology
across
different
regions
of
brain.
Conventional
inhibitors,
small
molecules,
peptides,
antibodies,
face
challenges
stability
blood–brain
barrier
penetration,
limiting
their
efficacy.
In
recent
years,
nanotechnology-based
strategies,
multifunctional
nanoplatforms
or
nanoparticles,
emerged
promising
tools
address
these
challenges.
These
leverage
tailored
designs
prevent
remodel
reduce
associated
neurotoxicity.
This
review
discusses
advances
designed
target
Aβ,
αSyn
aggregation,
with
focus
on
roles
reducing
We
examine
critical
aspects
nanoplatform
design,
choice
material
backbone
targeting
moieties,
which
influence
interactions
IDPs.
also
highlight
key
mechanisms
interaction
between
inhibit
redirect
cascade
towards
nontoxic,
off-pathway
species,
disrupt
fibrillar
structures
soluble
forms.
further
outline
future
directions
for
enhancing
IDP
clearance,
achieving
spatiotemporal
control,
improving
cell-specific
targeting.
nanomedicine
strategies
offer
compelling
paths
forward
developing
more
effective
targeted
therapies
diseases.
Biomedicine,
Journal Year:
2024,
Volume and Issue:
14(4)
Published: Dec. 1, 2024
Introduction:
Our
previous
research
demonstrated
that
a
large
language
model
(LLM)
based
on
the
transformer
architecture,
specifically
MegaMolBART
encoder
with
an
XGBoost
classifier,
effectively
predicts
blood-brain
barrier
(BBB)
permeability
of
compounds.
However,
coefficients
compounds
can
traverse
this
remain
unclear.
Additionally,
absorption,
distribution,
metabolism,
and
excretion
(ADME)
characteristics
substances
obtained
from
Natural
Product
Research
Laboratory
(NPRL)
at
China
Medical
University
Hospital
(CMUH)
have
not
yet
been
determined.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(23), P. 12883 - 12883
Published: Nov. 29, 2024
MicroRNAs
(miRNAs)
maintain
cellular
homeostasis
by
blocking
mRNAs
binding
with
them
to
fine-tune
the
expression
of
genes
across
numerous
biological
pathways.
The
2024
Nobel
Prize
in
Medicine
and
Physiology
for
discovering
miRNAs
was
long
overdue.
We
anticipate
a
deluge
research
work
involving
repeat
history
prizes
awarded
on
other
RNAs.
Although
miRNA
therapies
are
included
several
complex
diseases,
realization
that
regulate
their
roles
addressing
hundreds
diseases
expected;
but
advancement
drug
discovery
tools,
we
even
faster
entry
new
drugs.
To
promote
this,
provide
details
current
science,
logic,
intellectual
property,
formulations,
regulatory
process
anticipation
many
more
researchers
will
introduce
novel
based
discussion
advice
provided
this
paper.
