CNS Neuroscience & Therapeutics,
Год журнала:
2023,
Номер
29(7), С. 1981 - 1998
Опубликована: Март 7, 2023
Abstract
Aims
Beyond
digestion,
bile
acids
have
been
recognized
as
signaling
molecules
with
broad
paracrine
and
endocrine
functions
by
activating
plasma
membrane
receptor
(Takeda
G
protein‐coupled
5,
TGR5)
the
nuclear
farnesoid
X
(FXR).
The
present
study
investigated
role
of
in
alleviating
neuropathic
pain
TGR5
FXR.
Method
Neuropathic
was
induced
spared
nerve
injury
(SNI)
sciatic
nerve.
or
FXR
agonist
injected
intrathecally.
Pain
hypersensitivity
measured
Von
Frey
test.
amount
detected
using
a
acid
assay
kit.
Western
blotting
immunohistochemistry
were
used
to
assess
molecular
changes.
Results
We
found
that
downregulated,
whereas
expression
cytochrome
P450
cholesterol
7ahydroxylase
(CYP7A1),
rate‐limiting
enzyme
for
synthesis,
upregulated
exclusively
microglia
spinal
dorsal
horn
after
SNI.
Furthermore,
receptors
increased
glial
cells
GABAergic
neurons
on
day
7
Intrathecal
injection
either
SNI
alleviated
established
mechanical
allodynia
mice,
effects
blocked
antagonist.
Bile
agonists
inhibited
activation
ERK
pathway
horn.
All
above
allodynia,
cells,
abolished
intrathecal
GABA
A
antagonist
bicuculline.
Conclusion
These
results
suggest
counteracts
allodynia.
effect
mediated
potentiating
function
receptors,
which
then
neuronal
sensitization
Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology,
Год журнала:
2022,
Номер
13(1)
Опубликована: Июнь 8, 2022
Tauroursodeoxycholic
acid
(TUDCA),
a
hydrophilic
bile
acid,
is
the
main
medicinal
component
of
bear
and
commonly
used
to
treat
variety
hepatobiliary
diseases.
Meanwhile,
TUDCA
has
been
shown
modulate
intestinal
barrier
function
alleviate
DSS-induced
colitis
in
mice.
However,
effect
on
weaned
piglets
remains
largely
unclear.The
porcine
IPEC-J2
epithelial
cells
were
investigate
effects
explore
possible
underlying
mechanisms.
In
vivo,
72
healthy
randomly
allocated
into
2
groups
according
their
gender
body
weight,
fed
basal
diet
with
0
(control,
CON)
200
mg/kg
for
30
d,
respectively.
Three
female
three
male
reflecting
average
bodyweight
slaughtered
each
group
samples
collected.
vitro,
subjected
100
μmol/L
mechanisms.Our
results
demonstrated
that
dietary
supplementation
significantly
reduced
diarrhea
incidence
piglets,
possibly
attributing
TUDCA-enhanced
immunity.
addition,
altered
serum
metabolites
relative
abundance
certain
gut
bacteria,
which
might
contribute
improved
function.
Furthermore,
in-vitro
showed
E.
coli-induced
impairment
increased
Takeda
G-coupled
protein
receptor
5
(TGR5)
expression.
knockdown
TGR5
inhibition
myosin
light
chain
kinase
(MLCK)
pathway
abolished
TUDCA-improved
coli-treated
cells,
indicating
involvement
TGR5-MLCK
this
process.These
findings
associated
alteration
bacteria
suggesting
potential
application
improving
health
piglet
production.
Cell Metabolism,
Год журнала:
2022,
Номер
34(10), С. 1594 - 1610.e4
Опубликована: Сен. 12, 2022
Bile
acids
(BAs)
are
complex
and
incompletely
understood
enterohepatic-derived
hormones
that
control
whole-body
metabolism.
Here,
we
profiled
postprandial
BAs
in
the
liver,
feces,
plasma
of
360
chow-
or
high-fat-diet-fed
BXD
male
mice
demonstrated
both
genetics
diet
strongly
influence
BA
abundance,
composition,
correlation
with
metabolic
traits.
Through
an
integrated
systems
approach,
mapped
hundreds
quantitative
trait
loci
modulate
identified
known
unknown
regulators
homeostasis.
In
particular,
discovered
carboxylesterase
1c
(Ces1c)
as
a
genetic
determinant
tauroursodeoxycholic
acid
(TUDCA),
species
established
disease-preventing
actions.
The
association
between
Ces1c
TUDCA
was
validated
using
data
from
independent
mouse
cohorts
knockout
model.
Collectively,
our
unique
resource
to
dissect
physiological
importance
determinants
traits,
underscored
by
identification
CES1C
master
regulator
levels.
Pharmaceutics,
Год журнала:
2021,
Номер
13(7), С. 1041 - 1041
Опубликована: Июль 8, 2021
Aging
is
considered
a
contributing
factor
to
many
diseases
such
as
cardiovascular
disease,
Alzheimer’s
and
hearing
loss.
Age-related
loss,
also
termed
presbycusis,
one
of
the
most
common
sensory
impairments
worldwide,
affecting
in
five
people
over
50
years
age,
this
prevalence
growing
annually.
Associations
have
emerged
between
presbycusis
detrimental
health
outcomes,
including
social
isolation
mental
health.
It
remains
largely
untreatable
apart
from
aids,
with
no
globally
established
prevention
strategies
clinical
setting.
Hence,
review
aims
explore
pathophysiology
potential
therapies,
based
on
recent
advancement
bile
acid-based
bio-nanotechnologies.
A
comprehensive
online
search
was
carried
out
using
following
keywords:
drugs,
acids,
nanotechnology,
more
than
150
publications
were
directly
relevant.
Evidence
multifaceted
oxidative
stress
chronic
inflammation
involvement
cellular
damage
apoptosis
that
associated
loss
hair
cells,
damaged
inflamed
stria
vascularis,
neuronal
signalling
continues
emerge.
New
robust
effective
therapies
require
drug
delivery
deeper
into
various
layers
cochlea.
Bile
nanotechnology
has
gained
wide
interest
its
permeation-enhancing
ability
for
numerous
applications
treating
presbycusis.
Annals of Clinical and Translational Neurology,
Год журнала:
2022,
Номер
9(10), С. 1551 - 1564
Опубликована: Сен. 9, 2022
Abstract
Objective
ALS
is
a
rapidly
progressive,
fatal
disorder
caused
by
motor
neuron
degeneration,
for
which
there
great
unmet
therapeutic
need.
AMX0035,
combination
of
sodium
phenylbutyrate
(PB)
and
taurursodiol
(TUDCA,
TURSO),
has
shown
promising
results
in
early
clinical
trials,
but
its
mechanisms
action
remain
to
be
elucidated.
Therefore,
our
goal
was
obtain
an
unbiased
landscape
the
molecular
effects
AMX0035
patient‐derived
cells.
Methods
We
investigated
transcriptomic
metabolomic
profiles
primary
skin
fibroblasts
from
sporadic
patients
healthy
controls
(
n
=
12/group)
treated
with
PB,
TUDCA,
or
PB–TUDCA
(Combo).
Data
were
evaluated
multiple
approaches
including
differential
gene
expression
metabolite
abundance,
Gene
Ontology
metabolic
pathway
analysis,
weighted
co‐expression
correlation
analysis
(WGCNA),
combined
multiomics
integrated
analysis.
Results
Combo
changed
many
more
genes
metabolites
than
either
PB
TUDCA
individually.
Most
changes
unique
affected
involved
nucleocytoplasmic
transport,
unfolded
protein
response,
mitochondrial
function,
RNA
metabolism,
innate
immunity.
WGCNA
showed
significant
correlations
between
modules
parameters
that
abolished
treatment.
Interpretation
This
study
first
explore
It
shows
greater
distinct
impact
compared
individual
compounds
provides
clues
drug
targets
action,
may
underlie
benefits
this
investigational
combination.
CNS Neuroscience & Therapeutics,
Год журнала:
2023,
Номер
29(7), С. 1981 - 1998
Опубликована: Март 7, 2023
Abstract
Aims
Beyond
digestion,
bile
acids
have
been
recognized
as
signaling
molecules
with
broad
paracrine
and
endocrine
functions
by
activating
plasma
membrane
receptor
(Takeda
G
protein‐coupled
5,
TGR5)
the
nuclear
farnesoid
X
(FXR).
The
present
study
investigated
role
of
in
alleviating
neuropathic
pain
TGR5
FXR.
Method
Neuropathic
was
induced
spared
nerve
injury
(SNI)
sciatic
nerve.
or
FXR
agonist
injected
intrathecally.
Pain
hypersensitivity
measured
Von
Frey
test.
amount
detected
using
a
acid
assay
kit.
Western
blotting
immunohistochemistry
were
used
to
assess
molecular
changes.
Results
We
found
that
downregulated,
whereas
expression
cytochrome
P450
cholesterol
7ahydroxylase
(CYP7A1),
rate‐limiting
enzyme
for
synthesis,
upregulated
exclusively
microglia
spinal
dorsal
horn
after
SNI.
Furthermore,
receptors
increased
glial
cells
GABAergic
neurons
on
day
7
Intrathecal
injection
either
SNI
alleviated
established
mechanical
allodynia
mice,
effects
blocked
antagonist.
Bile
agonists
inhibited
activation
ERK
pathway
horn.
All
above
allodynia,
cells,
abolished
intrathecal
GABA
A
antagonist
bicuculline.
Conclusion
These
results
suggest
counteracts
allodynia.
effect
mediated
potentiating
function
receptors,
which
then
neuronal
sensitization
