Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 5, 2024
Abstract
The
medicinal
plant
Stephania
yunnanensis
is
rich
in
aporphine
alkaloids,
a
type
of
benzylisoquinoline
alkaloids
(BIAs),
with
being
the
representative
and
most
abundant
compound,
but
our
understanding
on
biosynthesis
BIA
this
have
been
relatively
limited.
Previous
research
has
reported
genome
S.
preliminarily
identified
upstream
gene
norcoclaurine
synthase
(NCS)
biosynthetic
pathways.
However,
key
genes
promoting
formation
skeleton
not
yet
reported.
In
study,
based
differences
content
crebanine
several
other
BIAs
different
tissues,
we
conducted
transcriptome
sequencing
roots,
stems,
leaves.
We
then
candidate
through
functional
annotation
sequence
alignment,
followed
by
transcriptomic
genomic
analyses.
Based
analysis,
three
CYP80
enzymes
(SyCYP80Q5-1,
SyCYP80Q5-3,
SyCYP80G6),
which
exhibited
activities
towards
(S)-
(R)-configured
substrates
yunnanensisand
demonstrated
strict
stereoselectivity
enroute
to
aporphine.
This
study
provides
metabolomic
information
offers
valuable
insights
into
elucidation
biosynthesis,
lays
foundation
for
complete
analysis
pathways
more
alkaloids.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(3), P. 501 - 501
Published: Feb. 23, 2024
Stroke
is
a
major
contributor
to
global
mortality
and
disability.
While
reperfusion
essential
for
preventing
neuronal
death
in
the
penumbra,
it
also
triggers
cerebral
ischemia-reperfusion
injury,
paradoxical
injury
primarily
caused
by
oxidative
stress,
inflammation,
blood–brain
barrier
disruption.
An
burst
inflicts
marked
cellular
damage,
ranging
from
alterations
mitochondrial
function
lipid
peroxidation
activation
of
intricate
signalling
pathways
that
can
even
lead
cell
death.
Thus,
given
pivotal
role
stress
mechanisms
reinforcement
antioxidant
defence
system
has
been
proposed
as
protective
approach.
Although
this
strategy
proven
be
successful
experimental
models,
its
translation
into
clinical
practice
yielded
inconsistent
results.
However,
should
considered
availability
numerous
molecules
with
wide
range
chemical
properties
affect
extent
injury;
several
groups
molecules,
including
polyphenols,
carotenoids,
vitamins,
among
other
compounds,
mitigate
damage
intervening
multiple
at
various
stages.
Multiple
trials
have
previously
conducted
evaluate
these
using
melatonin,
acetyl-L-carnitine,
chrysanthemum
extract,
edaravone
dexborneol,
saffron,
coenzyme
Q10,
oleoylethanolamide,
treatments.
Therefore,
multi-antioxidant
therapy
emerges
promising
novel
therapeutic
option
due
potential
synergistic
effect
provided
simultaneous
roles
individual
compounds.
Journal of Cellular and Molecular Medicine,
Journal Year:
2024,
Volume and Issue:
28(16)
Published: Aug. 1, 2024
The
onset
of
osteonecrosis
the
femoral
head
(ONFH)
is
intimately
associated
with
extensive
administration
glucocorticoids
(GCs).
Long-term
stimulation
GCs
can
induce
oxidative
stress
in
both
osteoclasts
(OCs)
and
osteoblasts
(OBs),
resulting
disturbance
bone
remodelling.
An
alkaloid
named
crebanine
(CN)
demonstrates
pharmacological
properties
including
anti-inflammation
reactive
oxygen
species
(ROS)
modulation.
Our
objective
to
assess
therapeutic
potential
CN
treating
ONFH
elucidate
underlying
mechanisms.
network
pharmacology
analysis
uncovered
that
played
a
role
regulating
ROS
metabolism.
In
vitro,
demonstrated
its
ability
reduce
dexamethasone
(DEX)-stimulated
generation
OCs
suppress
their
resorptive
function
by
downregulating
level
osteoclast
marker
genes.
Concurrently,
also
mitigated
DEX-induced
damage
OBs,
facilitating
restoration
osteoblast
gene
expression,
cellular
differentiation
function.
These
effects
were
achieved
augmenting
antioxidant
system
intracellular
levels.
Furthermore,
vitro
results
corroborated
micro-CT
histological
data,
which
showed
attenuated
MPS-induced
mice.
This
study
highlights
counteracting
GCs-induced
ONFH.
Molecules,
Journal Year:
2025,
Volume and Issue:
30(2), P. 259 - 259
Published: Jan. 10, 2025
The
medicinal
plant
Stephania
yunnanensis
is
rich
in
aporphine
alkaloids,
a
type
of
benzylisoquinoline
alkaloid
(BIA),
with
being
the
representative
and
most
abundant
compound,
but
our
understanding
biosynthesis
BIAs
this
has
been
relatively
limited.
Previous
research
reported
genome
S.
preliminarily
identified
norcoclaurine
synthase
(NCS),
which
involved
early
stages
BIA
biosynthetic
pathways.
However,
key
genes
promoting
formation
skeleton
have
not
yet
reported.
In
study,
based
on
differences
content
crebanine
several
other
different
tissues,
we
conducted
transcriptome
sequencing
roots,
stems,
leaves.
We
then
candidate
through
functional
annotation
sequence
alignment
further
analyzed
them
combination
genome.
Based
analysis,
three
CYP80
enzymes
(SyCYP80Q5-1,
SyCYP80Q5-3,
SyCYP80G6),
exhibited
activities
toward
(S)-
(R)-configured
substrates
demonstrated
strict
stereoselectivity
enroute
to
aporphine.
This
study
provides
metabolomic
transcriptomic
information
yunnanensis,
offers
valuable
insights
into
elucidation
biosynthesis,
lays
foundation
for
complete
analysis
pathways
more
alkaloids.
Journal of Anatomy and Histopathology,
Journal Year:
2025,
Volume and Issue:
13(4), P. 22 - 28
Published: Jan. 20, 2025
The
aim
was
to
observe
changes
in
NeuN
expression
the
cingulate
cortex
of
cerebral
hemispheres
mice
after
intraperitoneal
administration
various
doses
bacterial
lipopolysaccharide
(LPS).
Material
and
methods.
study
conducted
on
12
C57Bl/6
mice,
which
were
injected
intraperitoneally
at
same
time
for
4
days
with
saline
(control
group)
or
E.
coli
LPS
one
following
doses:
0.5
mg/kg/day
(1st
group),
1
(2nd
2
(3rd
group).
Brain
sampling
performed
animals
histological
preparations
a
5
µm
thickness
made
stained
antibodies
NeuN.
number
NeuN-expressing
cells
hemispheres,
Cg1
area/dorsal
anterior
cortex,
counted.
data
also
statistically
processed.
Results.
In
immunohistochemical
study,
neurons
expressing
1st
group
(LPS
dose
mg/kg/day)
8226.9±336.94
per
mm2,
2nd
–
7889.4±211.83
3rd
7039.7±580.42
control
9985.6±576.75
mm2.
Immunofluorescent
revealed
no
difference
between
samples.
Conclusion
.
When
is
administered
0.5–2
mg/kg/day,
NeuN,
marker
mature
neurons,
decreases.
obtained
can
be
used
create
model
age-related
neurodegeneration.
Antioxidants,
Journal Year:
2025,
Volume and Issue:
14(3), P. 363 - 363
Published: March 19, 2025
The
disruption
of
microglial
homeostasis
and
cytokine
release
are
critical
for
neuroinflammation
post-injury
strongly
implicated
in
retinal
neurodegenerative
diseases
like
glaucoma.
This
study
examines
responses
to
chemical
hypoxia
induced
by
cobalt
chloride
(CoCl2)
BV-2
murine
cells,
focusing
on
signaling
pathways
proteomic
alterations.
We
assessed
the
protective
effects
monoclonal
antibodies
against
TNFα
IL-1β.
CoCl2
exposure
led
decreased
cell
viability,
reduced
mitochondrial
membrane
potential,
increased
lactate
dehydrogenase
release,
elevated
reactive
oxygen
species
generation,
activation
inflammatory
pathways,
including
nitric
oxide
synthase
(iNOS),
STAT1,
NF-κB/NLRP3.
These
were
significantly
mitigated
treatment
with
anti-TNFα
anti-IL-1β,
suggesting
their
dual
role
reducing
damage
inhibiting
reactivity.
Additionally,
these
treatments
apoptosis
modulating
ATF4
p38
MAPK/caspase-3
pathways.
Label-free
quantitative
mass
spectrometry-based
proteomics
Gene
Ontology
revealed
that
upregulation
proteins
primarily
involved
endoplasmic
reticulum
catabolic
processes,
while
downregulated
associated
biosynthesis.
Anti-TNFα
anti-IL-1β
partially
restored
profile
toward
normalcy,
network
analysis
identifying
heat
shock
protein
family
A
member
8
(HSPA8)
as
a
central
mediator
recovery.
findings
offer
insights
into
pathogenesis
hypoxic
impairment
suggest
potential
therapeutic
targets.
Acta Physiologica,
Journal Year:
2025,
Volume and Issue:
241(6)
Published: May 19, 2025
ABSTRACT
Aim
Microglia
exhibit
innate
immune
memory,
altering
their
responses
to
subsequent
challenges.
Consumption
of
high‐fat
diet
(HFD)
triggers
responses,
but
the
characteristics
HFD‐induced
microglial
priming
remain
unclear.
We
aim
investigate
how
priming,
followed
by
a
lipopolysaccharide
(LPS)
challenge,
affects
brain
functions.
Methods
Male
Wistar
rats
were
divided
into
control,
unprimed,
and
primed
groups.
The
groups
received
either
single
LPS
injection
(0.5
mg/kg,
intraperitoneally)
or
HFD
consumption
for
4–8
weeks.
Following
phase,
all
(except
controls)
subjected
an
challenge
with
4‐
8‐week
interval.
After
24
h
cognition,
anxiety‐,
depressive‐like
behaviors
assessed.
hippocampus
collected
further
analysis.
Results
Both
LPS‐
4‐week
HFD‐primed
groups,
exhibited
increased
peripheral
oxidative
stress,
impaired
neurogenesis,
disrupted
neurotransmitter
balance,
altered
glycolysis
Krebs
cycle
substrates.
These
changes
also
caused
morphological
alterations,
elevated
C1q
levels,
synaptic
loss,
which
associated
anxiety‐
behaviors,
indicating
that
has
similar
ability
dose
injection.
Extending
8
weeks
exacerbated
inflammation,
behavioral
deficits.
Furthermore,
prolonging
interval
between
worsened
inflammation
cognitive
decline,
suggesting
persistent
effects
priming.
Conclusions
persistently
time‐dependently
primes
microglia
injection,
influencing
contributing
abnormalities.
