Research Square (Research Square),
Год журнала:
2023,
Номер
unknown
Опубликована: Окт. 31, 2023
Abstract
Background:
Amyloid
β
(Aβ)
and
neuroinflammation
are
recognized
as
crucial
to
the
pathogenesis
of
Alzheimer's
disease
(AD).
Compound
(
E
)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one
D30
),
a
pyromeconic
acid
derivative,
inhibits
Aβ
aggregation
reverses
scopolamine-induced
cognitive
impairment.
However,
in
vivo
therapeutic
potential
was
not
known
for
Aβ-induced
neuropathology.
Thus,
we
investigated
effects
mechanisms
fibril
Aβ(fAβ)-induced
AD
mouse
model.
Methods:
We
established
an
model
by
intracerebroventricular
injection
fAβ
determine
whether
could
alleviate
fAβ-induced
Behavior
tests
(Open
Field,
New
Object
Recognition,
Morris
Water
Maze)
were
conducted
evaluate
function.
assessed
immunohistochemistry,
immunofluorescence
staining,
immunoblotting
cortex
hippocampus.
Glial
cell
morphology,
neuroinflammation,
neuronal
properties
staining
hippocampal
brain
slices.
Cortex
hippocampus
also
subjected
ELISA
assays.
The
on
primary
microglia
measured
immunoblotting,
immunofluorescence,
real-time
quantitative
PCR.
Results:
alleviated
promoted
removal
injected
from
suppressed
oxidative
stress
activation
astrocytes.
reversed
loss
dendritic
spines
synaptic
proteins.
demonstrated
first
time
that
exogenous
greatly
increased
Galectin-3
(Gal-3)
level
brain,
increase
Gal-3
blocked
.
In
addition,
activated
p62/Nrf2/HO-1
signaling
pathway
disposal
relief
neuroinflammation.
its
comprehensive
activities
disposal,
antioxidation,
anti-neuroinflammation,
protected
synapses
function,
with
strong
involvement
regulation,
thereby
exhibiting
novel
potential.
EMBO Molecular Medicine,
Год журнала:
2025,
Номер
17(2), С. 301 - 335
Опубликована: Янв. 6, 2025
Abstract
Current
studies
pictured
the
enteric
nervous
system
and
macrophages
as
modulators
of
neuroimmune
processes
in
inflamed
gut.
Expanding
this
view,
we
investigated
impact
neuron–macrophage
interactions
on
postoperative
trauma
subsequent
motility
disturbances,
i.e.,
ileus.
In
early
postsurgical
phase,
detected
strong
neuronal
activation,
followed
by
transcriptional
translational
signatures
indicating
death
synaptic
damage.
Simultaneously,
our
study
revealed
neurodegenerative
profiles
macrophage-specific
transcriptomes
after
trauma.
Validating
role
resident
monocyte-derived
macrophages,
depleted
CSF-1R-antibodies
used
CCR2
−/−
mice,
known
for
reduced
monocyte
infiltration,
POI
studies.
Only
CSF-1R-antibody-treated
animals
showed
decreased
lessened
decay,
emphasizing
significance
macrophages.
human
gut
samples
taken
late
during
abdominal
surgery,
substantiated
mouse
model
data
found
reactive
apoptotic
neurons
dysregulation
genes,
a
species’
overarching
mechanism.
Our
demonstrates
that
surgical
activates
induces
neurodegeneration,
mediated
introducing
neuroprotection
an
option
faster
recovery
surgery.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(12), С. 6591 - 6591
Опубликована: Июнь 15, 2024
Senescence
is
a
physiological
and
pathological
cellular
program
triggered
by
various
types
of
stress.
Senescent
cells
exhibit
multiple
characteristic
changes.
Among
them,
the
flattened
enlarged
morphology
exhibited
in
senescent
observed
regardless
stimuli
causing
senescence.
Several
studies
have
provided
important
insights
into
pro-adhesive
properties
senescence,
suggesting
that
cell
adhesion
to
extracellular
matrix
(ECM),
which
involved
morphological
changes,
may
play
pivotal
roles
Matricellular
proteins,
group
structurally
unrelated
ECM
molecules
are
secreted
environment,
unique
ability
control
binding
receptors,
including
integrins.
Recent
reports
certified
matricellular
proteins
closely
Through
this
biological
function,
thought
pathogenesis
age-related
diseases,
fibrosis,
osteoarthritis,
intervertebral
disc
degeneration,
atherosclerosis,
cancer.
This
review
outlines
recent
on
role
inducing
We
highlight
integrin-mediated
signaling
senescence
provide
new
therapeutic
options
for
diseases
targeting
Biomolecules,
Год журнала:
2025,
Номер
15(2), С. 158 - 158
Опубликована: Янв. 21, 2025
Multiple
sclerosis
(MS)
is
a
highly
disabling
chronic
neurological
condition
affecting
young
adults.
Inflammation,
demyelination,
and
axonal
damage
are
key
pathological
features
of
MS
its
animal
model,
experimental
autoimmune
encephalomyelitis
(EAE).
Our
previous
work
demonstrated
that
inhibiting
spermine
oxidase
(SMOX)
with
MDL72527,
selective
irreversible
pharmacological
inhibitor,
significantly
reduced
clinical
symptoms,
retinal
ganglion
cell
(RGC)
loss,
optic
nerve
inflammation
in
EAE
mice.
The
present
study
explored
the
broader
therapeutic
potential
SMOX
inhibition,
focusing
on
myelin
preservation,
integrity,
visual
function
model.
Electron
microscopy
cross-sections
showed
significant
preservation
thickness
integrity
due
to
inhibition.
quantitative
assessment
g-ratio
axon
count
metrics
were
improved
MDL72527-treated
mice
compared
their
vehicle-treated
counterparts.
Immunofluorescence
studies
confirmed
these
findings,
showing
increased
proteins
group.
Functional
(Electroretinography)
improvement
RGC
conduction
treated
MDL72527.
Furthermore,
inhibition
downregulated
expression
galectin3
(Gal3),
mediator
neuroinflammation,
indicating
Gal3’s
role
SMOX-mediated
neuroprotection.
This
provides
compelling
evidence
for
as
strategy
multiple
other
demyelinating
disorders.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Фев. 13, 2025
Introduction
Multiple
Sclerosis
(MS)
is
a
complex
neurodegenerative
disease
marked
by
recurring
inflammatory
episodes,
demyelination,
axonal
damage,
and
subsequent
loss
of
function.
MS
presents
wide
range
clinical
courses,
with
the
progressive
forms
leading
to
irreversible
neurological
disability.
Cortical
demyelinating
lesions
are
central
pathology
these
forms,
gaining
critical
importance
in
recent
decades
due
their
strong
correlation
physical
disability
cognitive
decline.
Despite
this,
underlying
mechanisms
driving
cortical
lesion
formation
remain
poorly
understood,
no
specific
treatments
currently
available.
A
significant
challenge
lies
lack
animal
models
that
accurately
mirror
key
characteristics
lesions.
Methods
We
developed
focal
model
replicates
many
features
lesions,
including
impairment.
This
study
focuses
on
conducting
proteomic
analyses
both
cerebrospinal
fluid
(CSF)
from
animals,
aiming
identify
proteins
biomarkers
could
be
validated
patients.
Results
Proteomic
differences
between
frontal
cortex
tissue
CSF
were
observed
when
comparing
experimental
animals
controls.
Among
identified
proteins,
some
have
been
previously
described
patients
models,
while
others
represent
novel
discoveries.
Notably,
we
two
S100A8
orosomucoid-1,
highly
expressed
regions.
Conclusions
These
findings
suggest
prognostic
molecules
this
facilitate
discovery
new
or
relevant
MS,
particularly
mainly
characterized
disease.
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 8, 2025
In
the
post-GPT
era,
Llama-Gram
represents
a
promising
advancement
in
AI-driven
chemical
drug
discovery,
grounded
principle
that
molecular
structure
determines
properties.
This
folding-based
end-to-end
framework
seeks
to
address
hallucination
issues
of
traditional
large
language
models
by
integrating
protein
folding
embeddings,
graph-based
representations,
and
uncertainty
estimation
better
capture
structural
complexities
protein–ligand
interactions.
By
leveraging
frozen-gradient
ESMFold
model
Graph
Transformer
variant,
aims
enhance
predictive
accuracy
reliability
through
grouped-query
attention
Gram
layer
inspired
support
points
theory.
incorporating
information,
demonstrates
competitive
performance
against
state-of-the-art
approaches
such
as
CPI
2.0
Graph-DTA,
offering
improvements
compound–target
interaction.
provides
scalable
innovative
theory
could
contribute
accelerating
discovery
process.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(7), С. 3064 - 3064
Опубликована: Март 27, 2025
The
SCORE
(Systematic
Coronary
Risk
Evaluation)
scale
is
useful
for
cardiovascular
disease
(CVD)
risk
stratification.
However,
there
a
new
biomarker,
namely,
galectin-3
(gal-3),
that
offers
additional
predictive
value.
This
cross-sectional
study
assessed
the
relationship
between
serum
gal-3
concentrations
and
CVD
based
on
in
Polish
cohort
from
PURE
study.
A
total
of
259
participants
with
complete
cholesterol,
blood
pressure
(BP),
smoking
data
were
included.
Individuals
myocardial
infarction,
stroke,
diabetes,
or
renal
failure
excluded.
Gal-3
measured
using
ELISA,
statistical
analyses
examined
associations
categories.
median
concentration
was
221.32(161.64-360.00)
ng/mL.
Higher
found
older
individuals,
smokers,
those
elevated
BP(p
<
0.05).
Positive
correlations
observed
values
(r
=
0.39)
systolic
BP
0.64).
Participants
≥5%
had
significantly
higher
concentrations.
ROC
analysis
showed
moderate
diagnostic
value
≥
10%
(sensitivity
0.618
specificity
0.810).
diastolic
are
independent
factors
increased
concentrations,
explaining
79.5%
variance
studied
group.
Serum
associated
estimated
by
SCORE,
supporting
its
potential
role
Journal of Proteome Research,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 30, 2025
This
study
aimed
to
gain
insights
into
the
dynamic
proteome
changes
and
underlying
molecular
mechanisms
of
de/remyelination
in
a
cuprizone
model,
widely
used
preclinical
model
multiple
sclerosis
(MS).
Longitudinal
sampling
control
or
cuprizone-treated
mouse
brains
was
executed
at
6
time
points
over
weeks.
Data
analysis
included
8489
quantified
proteins.
Differential
proteomic
GO
analyses
revealed
that
5.9%
altered,
including
reported
novel
de/remyelination-relevant
protein
pathways.
We
found
oligodendrocyte
proteins
(Fa2h
Ugt8)
were
significantly
changed
during
demyelination,
suggesting
dysregulated
sphingolipid
metabolism
MS
may
stem
from
pathology.
Importantly,
we
showed
cholesterol
biosynthesis
pathway
most
enriched
biological
process
subset
proteins,
where
myelination
highly
enriched.
further
validated
through
targeted
GC-MS
intermediate
sterols,
supporting
critical
role
de/remyelination.
Unexpectedly,
myelin-associated
Mbp
Plp1,
minimal,
while
Ermn
significant
reduction
tracking
with
indicating
some
myelin
are
more
sensitive
demyelination.
Together
list
altered
results
this
could
benefit
future
remyelination
research.