High-concentrate
diet
induce
subacute
ruminal
acidosis
(SARA)
and
cause
liver
damage
in
ruminants.
It
has
been
reported
that
forkhead
box
protein
A2
(FOXA2)
can
enhance
mitochondrial
membrane
potential
but
its
function
dysfunction
induced
by
high
concentrate
diets
is
still
unknown.
Therefore,
the
aim
of
this
study
was
to
elucidate
effect
high-concentrate
(HC)
on
hepatic
FOXA2
expression,
unfolded
response
(UPRmt),
oxidative
stress.
A
total
12
healthy
mid-lactation
Holstein
cows
were
selected
randomized
into
2
groups:
low
(LC)
group
(concentrate:
forage
=
4:
6)
HC
6:
4).
The
trial
lasted
21
days.
rumen
fluid,
blood
tissue
collected
at
end
experiment.
results
showed
fluid
pH
level
reduced
lower
than
5.6
for
more
4
h/d,
indicating
feeding
successfully
SARA
dairy
cows.
Both
mRNA
abundance
significantly
compared
with
LC
group.
activity
antioxidant
enzymes
(CAT,
G6PDH,
T-SOD,
Cu/Zn
SOD,
Mn
SOD)
mtDNA
copy
number
decreased,
while
H2O2
increased,
increase
accompanied
a
decrease
phosphorylation
(OXPHOS).
balance
division
fusion
disrupted
group,
as
evidenced
decreased
OPA1,
MFN1,
MFN2
increased
Drp1,
Fis1,
MFF.
At
same
time,
downregulated
expression
SIRT1,
SIRT3,
PGC-1α,
TFAM,
Nrf1
inhibit
biogenesis.
UPRmt
upregulating
levels
CLPP,
LONP1,
CHOP,
Hsp10,
Hsp60.
In
addition,
could
Bax,
CytoC,
Caspase
3
Cleaved-Caspase
3,
Bcl-2
Bcl-2/Bax
ratio.
Overall,
our
suggests
may
be
related
UPRmt,
dysfunction,
stress,
apoptosis
fed
diet.
Communications Biology,
Год журнала:
2025,
Номер
8(1)
Опубликована: Март 25, 2025
Neuronal
hyperexcitation
affects
memory
and
neural
processing
across
the
Alzheimer's
disease
(AD)
cognitive
continuum.
Levetiracetam,
an
antiepileptic,
shows
promise
in
improving
impairment
by
restoring
excitation/inhibition
balance
AD
patients.
We
previously
identified
a
hyper-excitable
phenotype
cognitively
unimpaired
female
APOE-ε4
carriers
relative
to
male
counterparts
cross-sectionally.
This
sex
difference
lacks
longitudinal
validation;
however,
clarifying
vulnerability
of
ε4-carriers
could
better
inform
antiepileptic
treatment
efficacy.
Here,
we
investigated
this
sex-by-ε4
interaction
using
design.
used
resting-state
fMRI
diffusion
tensor
imaging
collected
longitudinally
from
106
participants
who
were
for
at
least
one
scan
event
but
may
have
been
assessed
clinical
dementia
ratings
corresponding
early
mild
over
time.
By
including
events
where
transitioned
impairment,
modeled
trajectory
whole-brain
excitation-inhibition
ratio
throughout
preclinical
healthy
continuum
extended
impairment.
A
linear
mixed
model
revealed
significant
three-way
among
sex,
ε4-status,
time,
with
showing
trajectory.
These
findings
suggest
possible
pathway
preventative
therapy
targeting
ε4-carriers.
Longitudinal
connectome
modeling
individuals
reveals
hyperexcitable
carriers.
Findings
anti-excitatory
therapies
mitigate
risk.
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 8, 2024
Abstract
Brain
inflammation
and
oxidative
stress
play
a
critical
role
in
the
neuronal
apoptosis
memory
dysfunction
Alzheimer’s
disease.
Crocin
is
natural
carotenoid
present
stigma
of
saffron
which
possesses
radical
scavenging,
anti-inflammatory,
anti-apoptotic
properties.
The
study
examined
protective
impact
crocin
on
apoptosis,
stress,
neuroinflammation
deficits
induced
by
lipopolysaccharide
(LPS)
rats.
Wistar
rats
received
at
dose
100
mg/kg
for
12
days.
Besides,
LPS
(1
mg/kg,
ip)
was
injected
days
8–12.
Spatial
evaluated
Morris
water
maze,
two
hours
after
injection
Gene
expression
nuclear
factor
(NF)-κB,
tumor
necrosis
factor-α
(TNF-α),
caspase
3
lipid
peroxidation
assessed
hippocampal
homogenates
end
behavioral
test.
Histopathological
changes
hippocampus
cerebral
cortex
using
H&E
staining.
According
to
results,
administration
caused
spatial
accompanied
upregulation
mRNA
NF-κB,
TNF-α
as
well
increased
tissue
damge
hippocampus.
Furthermore,
treatment
attenuated
impairments,
downregulated
decreased
also
ameliorated
LPS-induced
pathological
loss
cortex.
In
conclusion,
neuroprotective
effects
against
histopathological
behavioural
could
be
attributed
its
anti-apoptotic,
anti-inflammatory
radical-scavenging
activities
rat
brain.
Molecules,
Год журнала:
2024,
Номер
29(22), С. 5354 - 5354
Опубликована: Ноя. 14, 2024
Alzheimer's
disease
(AD)
is
a
neurodegenerative
disorder
associated
with
the
dysregulation
of
several
key
enzymes,
including
acetylcholinesterase
(AChE),
cyclooxygenase-2
(COX-2),
glycogen
synthase
kinase
3β
(GSK-3β),
β-site
amyloid
precursor
protein
cleaving
enzyme
1
(BACE-1),
and
caspase-3.
In
this
study,
machine
learning
algorithms
such
as
Random
Forest
(RF),
Gradient
Boost
(GB),
Extreme
(XGB)
were
employed
to
screen
US-FDA
approved
drugs
from
ZINC15
database
identify
potential
dual
inhibitors
COX-2
AChE.
The
models
trained
using
molecules
obtained
ChEMBL
database,
5039
for
AChE
3689
COX-2.
Specifically,
1248
3791
classified
active
inactive
AChE,
respectively,
while
858
2831
three
achieved
prediction
accuracies
ranging
92%
95%
both
Virtual
screening
identified
sertraline
(SETL)
inhibitor
Further
docking
studies
SETL
in
sites
COX-2,
well
BACE-1,
GSK-3β,
caspase-3,
revealed
strong
binding
affinities
all
five
proteins.
vivo
validation
was
conducted
lipopolysaccharide
(LPS)-induced
rat
model
pretreated
30
days.
results
demonstrated
significant
decrease
levels
(
Medicina,
Год журнала:
2023,
Номер
60(1), С. 46 - 46
Опубликована: Дек. 26, 2023
Background
and
Objectives:
Aripiprazole
(APZ),
an
atypical
antipsychotic,
is
mainly
prescribed
for
conditions
such
as
schizophrenia
bipolar
disorder,
while
ongoing
research
indicates
promising
neuroprotective
qualities.
APZ’s
mechanism
of
action,
involving
the
regulation
neurotransmitter
levels,
appears
to
contribute
its
potential
shield
neural
tissues
from
specific
forms
harm
degeneration.
Materials
Methods:
To
investigate
mechanisms,
groups
rats
were
orally
administered
APZ
at
1
or
2
mg/kg
once
daily
a
30-day
period.
In
addition,
neuronal
toxicity
was
induced
through
intraperitoneal
injection
four
doses
lipopolysaccharide
(LPS)
concentration
mg/kg.
evaluate
cognitive
function,
particularly,
short-term
recognition
memory,
procedure
implemented
novel
object
(NOR)
task.
Subsequently,
brain
gathered
examine
markers
linked
with
neuroinflammation,
oxidative
stress,
apoptosis.
Results:
The
administration
LPS
led
decline
in
memory
performance
during
NOR
tasks.
Simultaneously,
this
treatment
raised
inflammatory
like
cyclooxygenase
(COX)-2,
tumor
necrosis
factor
(TNF)-α,
nuclear
kappa
B
(NF-κB),
increased
malondialdehyde
(MDA),
triggered
apoptosis
Caspase-3
Bcl2
associated
X
protein
(Bax)
within
brain.
Furthermore,
it
decreased
levels
antioxidants
reduced
glutathione
(GSH)
catalase,
well
anti-apoptotic
marker
B-cell
lymphoma
(Bcl)-2
tissue.
use
resulted
enhanced
performance,
indicated
by
improved
exploration
discrimination
abilities
objects
Moreover,
lowered
vulnerability,
COX-2,
NF-κB,
MDA,
Caspase-3,
Bax.
Additionally,
protective
markers,
including
GSH,
Bcl-2
LPS-challenged
brains.
Conclusions:
summary,
findings
suggest
that
exhibits
properties
against
inflammation,
context
inflammatory-related
neurodegeneration.
Additional
in-depth
investigations
are
needed
further
explore
applications.
