The Journal of Steroid Biochemistry and Molecular Biology,
Journal Year:
2024,
Volume and Issue:
241, P. 106520 - 106520
Published: April 13, 2024
Gonadal
hormone
deprivation
(GHD)
and
decline
such
as
menopause
bilateral
oophorectomy
are
associated
with
an
increased
risk
of
neurodegeneration.
Yet,
therapies
(HTs)
show
varying
efficacy,
influenced
by
factors
sex,
drug
type,
timing
treatment
relative
to
decline.
We
hypothesize
that
the
molecular
environment
brain
undergoes
a
transition
following
GHD,
impacting
effectiveness
HTs.
Using
GHD
model
in
mice
treated
Tibolone,
we
conducted
proteomic
analysis
identified
reprogrammed
response
compound
stimulates
estrogenic,
progestogenic,
androgenic
pathways.
Through
comprehensive
network
pharmacological
workflow,
particularly
within
"Pathways
Neurodegeneration",
well
interconnected
pathways
including
"cellular
respiration",
"carbon
metabolism",
homeostasis".
Analysis
revealed
23
proteins
whose
Tibolone
depended
on
and/or
implicating
critical
processes
like
oxidative
phosphorylation
calcium
signalling.
Our
findings
suggest
therapeutic
efficacy
HTs
may
depend
these
variables,
suggesting
need
for
greater
precision
medicine
considerations
whilst
highlighting
uncover
underlying
mechanisms.
Antioxidants,
Journal Year:
2023,
Volume and Issue:
12(2), P. 377 - 377
Published: Feb. 4, 2023
CHIR99021
is
an
aminopyrimidine
derivative,
which
can
efficiently
inhibit
the
activity
of
glycogen
synthesis
kinase
3α
(GSK-3α)
and
GSK-3β.
As
essential
component
stem
cell
culture
medium,
it
plays
important
role
in
maintaining
stemness.
However,
mechanism
its
not
fully
understood.
In
present
study,
we
first
found
that
removal
from
embryonic
medium
reduced
iron
storage
mouse
cells
(mESCs).
CHIR99021-treated
Neuro-2a
led
to
upregulation
ferritin
expression
increase
intracellular
levels,
along
with
GSK3β
inhibition
Wnt/GSK-3β/β-catenin
pathway
activation.
addition,
treatment
activated
classical
Wnt
by
affecting
β-catenin
cells.
Our
data
link
maintenance
stemness
via
signaling
pathway,
identify
intermediate
molecules,
including
Steap1,
Bola2,
Kdm6bos,
may
mediate
CHIR99021.
These
findings
reveal
novel
mechanisms
differentiation
provide
a
theoretical
basis
for
development
new
strategies
disease.
Mucosal Immunology,
Journal Year:
2024,
Volume and Issue:
17(4), P. 752 - 767
Published: June 12, 2024
Serving
as
a
part
of
intestinal
innate
immunity,
Paneth
cells
play
an
important
role
in
homeostasis
maintenance
via
their
multiple
functions.
However,
the
regulation
has
been
proven
to
be
complex
and
diverse.
Here,
we
identified
nuclear
receptor
Nur77
novel
regulator
cell
differentiation
function.
deficiency
led
loss
murine
ileal
crypts.
Intestinal
tissues
or
organoids
with
exhibited
impaired
stem
niche
failed
enhance
antimicrobial
peptide
expression
after
degranulation.
The
defects
peptides
Nur7−/−
mice
microbiota
disorders.
rendered
postnatal
susceptible
necrotizing
enterocolitis.
Mechanistically,
transcriptionally
inhibited
Dact1
activate
Wnt
signaling
activity,
thus
promoting
Taken
together,
our
data
suggest
regulatory
function
reveal
Dact1-mediated
inhibition
mechanism
development.
The Journal of Steroid Biochemistry and Molecular Biology,
Journal Year:
2024,
Volume and Issue:
241, P. 106520 - 106520
Published: April 13, 2024
Gonadal
hormone
deprivation
(GHD)
and
decline
such
as
menopause
bilateral
oophorectomy
are
associated
with
an
increased
risk
of
neurodegeneration.
Yet,
therapies
(HTs)
show
varying
efficacy,
influenced
by
factors
sex,
drug
type,
timing
treatment
relative
to
decline.
We
hypothesize
that
the
molecular
environment
brain
undergoes
a
transition
following
GHD,
impacting
effectiveness
HTs.
Using
GHD
model
in
mice
treated
Tibolone,
we
conducted
proteomic
analysis
identified
reprogrammed
response
compound
stimulates
estrogenic,
progestogenic,
androgenic
pathways.
Through
comprehensive
network
pharmacological
workflow,
particularly
within
"Pathways
Neurodegeneration",
well
interconnected
pathways
including
"cellular
respiration",
"carbon
metabolism",
homeostasis".
Analysis
revealed
23
proteins
whose
Tibolone
depended
on
and/or
implicating
critical
processes
like
oxidative
phosphorylation
calcium
signalling.
Our
findings
suggest
therapeutic
efficacy
HTs
may
depend
these
variables,
suggesting
need
for
greater
precision
medicine
considerations
whilst
highlighting
uncover
underlying
mechanisms.
