Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Март 19, 2025
Anti-programmed
death
1
(αPD1)
immune
checkpoint
blockade
is
used
in
combination
for
cancer
treatment
but
associated
with
cardiovascular
toxicity.
Leflunomide
(Lef)
can
suppress
the
growth
of
several
tumor
and
mitigate
cardiac
remodeling
mice.
However,
role
Lef
αPD1-induced
cardiotoxicity
remains
unclear.
Here,
we
report
that
inhibits
αPD1-related
without
compromising
efficacy
αPD1-mediated
immunotherapy.
changes
community
structure
gut
microbiota
αPD1-treated
melanoma-bearing
Moreover,
mice
receiving
transplants
from
Lef+αPD1-treated
have
better
function
compared
to
Mechanistically,
analyze
metabolomics
identify
indole-3-propionic
acid
(IPA),
which
protects
dysfunction
IPA
directly
bind
aryl
hydrocarbon
receptor
promote
phosphoinositide
3-kinase
expression,
thus
curtailing
cardiomyocyte
response
injury.
Our
findings
reveal
mitigates
toxicity
through
modulation
microbiota-IPA-heart
axis.
The
authors
show
leflunomide
microbiota-indole-3-propionic
acid-heart
Redox Biology,
Год журнала:
2025,
Номер
81, С. 103580 - 103580
Опубликована: Март 5, 2025
Despite
the
increasing
recognition
of
interplay
between
depression
and
cardiovascular
disease
(CVD),
precise
mechanisms
by
which
contributes
to
pathogenesis
remain
inadequately
understood.
The
involvement
gut
microbiota
their
metabolites
health
susceptibility
has
been
gaining
attention.
In
this
study,
it
was
found
that
exacerbated
cardiac
injury,
impaired
function
(EF%:
P
<
0.01;
FS%:
0.05),
hindered
long-term
survival
(P
0.01),
intensified
adverse
remodeling
(WGA:
MASSON:
0.0001)
after
myocardial
ischemia/reperfusion
(MI/R)
in
mice.
Then
we
mice
receiving
transplants
from
chronic
social
defeat
stress
(CSDS)
exhibited
worse
0.01)
than
those
non-CSDS
MI/R
injury.
Moreover,
tryptophan
metabolism
due
alterations
composition
structure
observed
CSDS
Mechanistically,
analyzed
metabolomics
fecal
serum
samples
identified
indole-3-propionic
acid
(IPA)
as
a
protective
agent
for
cardiomyocytes
against
ferroptosis
via
NRF2/System
xc-/GPX4
axis,
played
role
mediating
detrimental
influence
on
MI/R.
Our
findings
provide
new
insights
into
IPA
CVD,
forming
basis
intervention
strategies
aimed
at
mitigating
deterioration
following
patients
experiencing
depression.
Frontiers in Cellular and Infection Microbiology,
Год журнала:
2025,
Номер
15
Опубликована: Март 13, 2025
Heart
failure
with
preserved
left
ventricular
ejection
fraction
(HFpEF)
is
a
disease
that
affects
multiple
organs
throughout
the
body,
accounting
for
over
50%
of
heart
cases.
HFpEF
has
significant
impact
on
individuals’
life
expectancy
and
quality
life,
but
exact
pathogenesis
remains
unclear.
Emerging
evidence
implicates
low-grade
systemic
inflammation
as
crucial
role
in
onset
progression
HFpEF.
Gut
microbiota
dysregulation
associated
metabolites
alteration,
including
short-chain
fatty
acids,
trimethylamine
N-oxides,
amino
bile
acids
can
exacerbate
chronic
inflammatory
responses
potentially
contribute
to
In
light
these
findings,
we
propose
hypothesis
“gut
microbiota-inflammation-HFpEF
axis”,
positing
interplay
within
this
axis
could
be
factor
development
This
review
focuses
gut
dysregulation-induced
HFpEF’s
etiology.
It
explores
potential
mechanisms
linking
cardiac
dysfunction
evaluates
therapeutic
restoring
balance
mitigating
severity.
The
objective
offer
novel
insights
strategies
management
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Март 19, 2025
Anti-programmed
death
1
(αPD1)
immune
checkpoint
blockade
is
used
in
combination
for
cancer
treatment
but
associated
with
cardiovascular
toxicity.
Leflunomide
(Lef)
can
suppress
the
growth
of
several
tumor
and
mitigate
cardiac
remodeling
mice.
However,
role
Lef
αPD1-induced
cardiotoxicity
remains
unclear.
Here,
we
report
that
inhibits
αPD1-related
without
compromising
efficacy
αPD1-mediated
immunotherapy.
changes
community
structure
gut
microbiota
αPD1-treated
melanoma-bearing
Moreover,
mice
receiving
transplants
from
Lef+αPD1-treated
have
better
function
compared
to
Mechanistically,
analyze
metabolomics
identify
indole-3-propionic
acid
(IPA),
which
protects
dysfunction
IPA
directly
bind
aryl
hydrocarbon
receptor
promote
phosphoinositide
3-kinase
expression,
thus
curtailing
cardiomyocyte
response
injury.
Our
findings
reveal
mitigates
toxicity
through
modulation
microbiota-IPA-heart
axis.
The
authors
show
leflunomide
microbiota-indole-3-propionic
acid-heart
