Authorea (Authorea),
Год журнала:
2023,
Номер
unknown
Опубликована: Авг. 17, 2023
Cancer
cachexia
is
a
metabolic
and
wasting
disease
that
occurs
in
up
to
80%
of
cancer
patients.
Currently,
there
are
no
clear
diagnostic
criteria,
its
effects
irreversible,
it
cannot
be
treated.
Most
patients
progress
undetected
late
stages
cachexia,
stop
responding
traditional
treatment,
die
without
an
effective
intervention.
To
determine
the
effect
tumor
bearing
on
muscle
metabolism,
heart
gastrocnemius
tissues
from
15-week-old
male
Apc(min/+)
litter-matched
non-carrier
mice
(wildtype)
were
analyzed
by
untargeted
GC/MS
metabolomics.
The
mouse
spontaneously
forms
tumors
along
intestinal
tract
well-accepted
preclinical
model
colorectal
cancer.
In
heart,
pathways
related
taurine/hypotaurine
metabolism;
biosynthesis
unsaturated
fatty
acids;
alanine,
glutamate,
aspartate;
arginine
proline;
affected
bearing.
skeletal
muscle,
involving
biosynthesis;
aspartate,
proline
metabolism
cachexia.
Taken
together,
these
data
demonstrate
altered
hearts
cachectic
mice.
Interestingly,
cardiac
showed
non-preferential
fuel
switch
towards
less
energetically
favorable
glycolysis
(vs.
acid
metabolism)
coincided
with
dysfunction,
while
exhibited
glucose
dysregulation
possible
insulin
resistance.
These
shed
important
light
derangements
associated
lead
dysfunction
atrophy.
Such
may
provide
valuable
stepping
stone
understanding
consequence
assist
identification
therapeutic
targets.
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Июнь 24, 2024
Cardiovascular
diseases
(CVD)
remain
the
leading
cause
of
death
worldwide
and
represent
a
major
public
health
challenge.
YiyiFuzi
Powder
(YYFZ),
composed
Coicis
semen
Fuzi,
is
classical
traditional
Chinese
medicine
prescription
from
Synopsis
Golden
Chamber
dating
back
to
Han
Dynasty.
Historically,
YYFZ
has
been
used
treat
various
CVD,
rooted
in
therapeutic
principles.
Network
pharmacology
analysis
indicated
that
may
exhibit
direct
or
indirect
effects
on
mitochondria-endoplasmic
reticulum
(ER)
interactions.
This
review,
focusing
cardiovascular
protective
summarizes
potential
mechanisms
by
which
acts
mitochondria
ER.
The
underlying
are
associated
with
regulating
risk
factors
(such
as
blood
lipids
glucose),
impacting
mitochondrial
structure
function,
modulating
ER
stress,
inhibiting
oxidative
suppressing
inflammatory
responses,
cellular
apoptosis,
maintaining
calcium
ion
balance.
involved
pathways
include,
but
were
not
limited
to,
upregulating
IGF-1/PI3K/AKT,
cAMP/PKA,
eNOS/NO/cGMP/SIRT1,
SIRT1/PGC-1α,
Klotho/SIRT1,
OXPHOS/ATP,
PPARα/PGC-1α/SIRT3,
AMPK/JNK,
PTEN/PI3K/AKT,
β2-AR/PI3K/AKT,
modified
Q
cycle
signaling
pathways.
Meanwhile,
MCU,
NF-κB,
JAK/STAT
downregulated.
PERK/eIF2α/ATF4/CHOP,
PERK/SREBP-1c/FAS,
IRE1,
PINK1-dependent
mitophagy,
AMPK/mTOR
bidirectionally
regulated.
High-quality
experimental
studies
needed
further
elucidate
CVD
treatment.
Communications Biology,
Год журнала:
2024,
Номер
7(1)
Опубликована: Окт. 22, 2024
Chronic
heart
failure
(CHF)
is
closely
associated
with
inflammation
and
mitochondrial
dysfunction
in
cardiomyocytes.
This
study
attempts
to
investigate
the
effects
of
microRNA-21-3p
(miR-21-3p)
on
macrophage
polarization
mitophagy
CHF.
Here
we
found
miR-21-3p
was
upregulated
CHF
negatively
correlated
carnitine
palmitoyl
transferase
1A
(CPT1A).
L-palmitoyl
(L-PC)
exacerbated
isoproterenol
(ISO)-induced
myocardial
structural
disruption
fibrosis
rats,
which
by
miR-21-3p.
Mechanistically,
accelerated
M1
polarization.
Both
inhibitor
CPT1A
overexpression
suppressed
mitophagy.
The
inhibition
reversed
MiR-21-3p
targeted
mRNA
co-localized
protein
In
co-culture
system
macrophages
H9c2
cells,
mimics
cells
promoted
polarization,
whereas
reduced
phenotype.
cell
damage.
These
findings
support
potential
therapeutic
targeting
regulate
inducing
Binding
fatty
acid
metabolism-related
target
gene
affects
development
chronic
failure.
Abstract
Background
Heart
failure
(HF)
is
characterized
by
a
disorder
of
cardiomyocyte
energy
metabolism.
Xinbao
Pill
(XBW),
traditional
Chinese
medicine
formulation
integrating
“Liushen
Pill”
and
“Shenfu
Decoction,”
has
been
approved
China
Food
Drug
Administration
for
the
treatment
HF
many
years.
The
present
study
reveals
novel
mechanism
XBW
in
through
modulation
cardiac
Methods
In
vivo,
(60,
90,
120
mg/kg/d)
fenofibrate
(100
were
treated
six
weeks
Sprague–Dawley
rats
that
stimulated
isoproterenol
to
induce
HF.
Cardiac
function
parameters
measured
echocardiography,
pathological
changes
assessed
using
H&E,
Masson,
WGA
staining.
vitro,
primary
cultured
neonatal
rat
cardiomyocytes
(NRCMs)
induced
investigate
effects
on
myocardial
cell
damage,
mitochondrial
fatty
acid
involvement
SGLT1/AMPK/PPARα
signalling
axis
was
investigated.
Results
both
vitro
vivo
models
ISO-induced
HF,
significantly
ameliorated
hypertrophy
fibrosis,
improved
function.
Significantly,
metabolism
mitigated
damage.
Mechanistically,
effectively
suppressed
expression
SGLT1
protein
while
upregulating
phosphorylation
level
AMPK,
ultimately
facilitating
nuclear
translocation
PPARα
enhancing
its
transcriptional
activity.
Knockdown
further
enhanced
XBW,
overexpression
reversed
cardio-protective
effect
highlighting
probably
critical
target
regulation
Conclusions
improves
alleviate
via
axis.
Journal of Biobased Materials and Bioenergy,
Год журнала:
2024,
Номер
18(4), С. 721 - 747
Опубликована: Фев. 28, 2024
Jianxin
Granules,
a
Traditional
Chinese
Medicine
(TCM),
consisting
of
eight
flavors,
including
Huang
Qi
(astragalus),
Hong
Shen
(red
ginseng),
Pu
(pollen
typhae),
Dan
(salvia
miltiorrhiza),
Zhu
Ling
(polyporus),
Bai
(atractylodes
macrocephala),
Gui
Zhi
(cassia
twig),
Ting
Li
Zi
(semen
lepidii).
granules
has
multi-system,
multi-target,
and
multi-directional
comprehensive
regulatory
effect
on
inhibiting
ventricular
remodeling,
which
is
an
effective
formulation
for
the
prevention
treatment
heart
failure,
good
application
prospect.
However,
many
ingredients,
pharmacologically
active
in
remain
unclear.
Here,
we
attempted
to
develop
metabolomics
method
component
identification,
quantitation,
pattern
recognition,
cross-comparison
granules.
Chemical
analysis,
identification
quantification
analyse
were
conducted
with
combination
UHPLC-QTOF-MS/MS
bioinformatics.
Assessment
correlation
between
technical
bio-replicated
pharmacological
ingredients
was
implemented
by
Principal
Component
Analysis
(PCA),
addition
Partial
Least
Squares
Discriminant
(PLS-DA).
UHPLC-QTOFMS/
MS,
method,
developed
adapted
characterize
granules,
consisted
178
216
molecular
signatures.
The
quantitative
analysis
95
frequently
occurring
signatures
carried
out
single
exogenous
reference
internal
standard.
Of
these,
47
have
been
identified
using
diverse
databases,
2
glycosylglycerol
derivatives,
lipids,
spiro
compounds,
cyclohexanecarboxylic
acids,
glycosides,
5
terpenoids,
7
oligopeptides,
17
favonoids,
8
various
such
as
hydroxycoumarin,
chalcone,
benzofuran,
benzodioxole,
benzaldehyde,
aromatic
ketone,
alkyl
cafeate
ester.
established
demonstrates
robust
reliability
reproducibility,
making
it
suitable
applications
compositional
quantification,
quality
assessment
constituents
