Advanced Science,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 16, 2024
Abstract
Acute
kidney
injury
(AKI)
is
a
prevalent
clinical
syndrome
with
high
morbidity
and
mortality.
Accumulating
studies
suggest
mitochondrial
dysfunction
as
the
typical
characteristics
key
process
of
AKI,
but
underlying
mechanism
remains
elusive.
The
YME1‐like
1
(YME1L1)
ATPase,
an
inner
membrane
protein,
screened
identified
to
be
downregulated
in
renal
tubular
epithelial
cells
various
mouse
models
patients
AKI.
Dramatically,
restoration
YME1L1
expression
significantly
alleviates
cisplatin‐induced
AKI
subsequent
chronic
disease
(CKD)
through
attenuating
via
maintaining
optic
atrophy
(OPA1)‐mediated
energy
metabolism
homeostasis.
Mechanistically,
upregulated
sterol
regulatory
element
binding
transcription
factor
1c
(SREBP1c)
demonstrated
responsible
for
cisplatin‐mediated
transcriptional
inhibition
directly
its
promoter
region.
Moreover,
methyltransferase‐like
3
(METTL3)‐mediated
m6A
modification
enhances
SREBP1c
mRNA
stability,
thereby
upregulating
expression.
Notably,
both
depletion
tubule‐specific
overexpression
markedly
ameliorate
transition
CKD.
Taken
together,
these
findings
that
METTL3‐mediated
upregulation
contributes
progression
CKD
disrupting
transcriptionally
suppressing
YME1L1.
Targeting
SREBP1c/YME1L1
signaling
may
serve
novel
therapeutic
strategy
against
Frontiers in Pharmacology,
Journal Year:
2025,
Volume and Issue:
16
Published: May 13, 2025
Aims
and
background
Autophagy
plays
an
increasingly
significant
role
in
diabetic
nephropathy
(DN),
but
the
mechanism
by
which
autophagy
participates
DN
injury
is
not
well
understood.
Our
previous
studies
have
shown
that
Astragalus
membranaceus
-
Cornus
officinalis
(AM-CO)
improves
lipid
metabolism
disorders,
however,
exact
of
also
defined.
The
aim
this
study
was
to
investigate
therapeutic
effects
AM-CO
on
action
using
lipidomic
techniques
network
pharmacological
approaches.
Experimental
methods
vivo
experiments
were
carried
out
KKAy
mice
model
with
intervention
AM-CO.
Analysis
kidney
serum
samples
from
treated
technology
obtain
biomarkers
for
treatment
identify
main
targets
associated
DN;
Analyse
potential
signalling
pathways
pharmacology
methods.
In
vitro
performed
PA-induced
HK-2
cells
results
verified
protein
blotting
immunofluorescence.
Results
Lipidomic
analysis
revealed
363
differential
metabolites
195
tissue,
compared
analysed
find
their
common
belonging
phosphatidylethanolamine
(PE)
classes,
respectively.
addition,
PE
a
vital
functiona
process
autophagy.
And
speculated
Calycosin
(Cal),
major
component
AM-CO,
could
ameliorate
regulating
through
modulating
PI3K-AKT
signaling
pathway.
showed
induce
autophagy,
increase
LC3II
expression
decrease
P62
expression.
Meanwhile,
Cal
inhibit
levels
p62,
PI3K,
P-AKT
AKT.
addition
PI3K
activator
resulted
reversal
Conclusion
conclusion,
can
pathway
its
regulation
key
Journal of Agricultural and Food Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 26, 2025
Studies
have
substantiated
that
dietary-fat-
and
fructose-overconsumption-caused
lipid
metabolism
disorders
can
trigger
renal
lipotoxicity
to
drive
the
progression
of
chronic
kidney
disease
(CKD).
This
study
was
conducted
evaluate
efficacy
morroniside,
a
natural
active
substance
extracted
from
fruit
Cornus
officinalis,
in
inhibiting
CKD
high-fat
high-fructose-fed
mice.
Our
results
showed
histological
changes
such
as
fatty
degeneration
tubular
cells,
dilatation,
glomerular
fibrosis,
abnormal
function
kidneys
high-fat-
mice,
which
significantly
improved
after
morroniside
treatment.
Mechanistically,
maintained
homeostasis
inhibited
NLRP3
inflammatory
vesicle
activation
by
activating
AMPKα
promote
TFEB
nuclear
translocation-mediated
lipophagy.
Consistent
were
observed
palmitic
acid-induced
HK-2
cells.
Notably,
silencing
or
both
reversed
effects
promoting
lipophagy
responses
vivo
vitro.
Therefore,
our
provides
compelling
evidence
delays
AMPK/TFEB-mediated
inflammasome
activation,
suggesting
dietary
supplementation
with
morroniside-rich
foods
(such
officinalis)
might
be
an
effective
strategy
for
prevention
CKD.
Frontiers in Medicine,
Journal Year:
2025,
Volume and Issue:
12
Published: May 9, 2025
Background
Diabetic
retinopathy
(DR),
one
of
the
most
common
complications
diabetes,
severely
impacts
patients’
quality
life.
The
combined
use
traditional
Chinese
medicines
Astragalus,
Fructus
ligustris,
and
Cornus
officinalis
has
yielded
considerable
therapeutic
effects
in
clinical
DR
treatment.
Methods
In
this
study,
a
multimodule
framework
(BNM)
encompassing
bioinformatics,
network
pharmacology,
machine
learning
(ML)
based
on
molecular
fingerprints
was
innovatively
developed
to
thoroughly
investigate
mechanisms
medicine
treating
DR.
Results
A
total
40
active
components
12
core
targets
were
identified.
Enrichment
analysis
identified
key
pathways
such
as
VEGF
signaling
pathway,
TNF
pathway
HIF-1
pathway.
Prediction
models
using
targets,
PPARG,
constructed
from
GEO
database
validated
via
immune
infiltration
docking,
revealing
that
PPARG
may
be
potential
target
for
Moreover,
component
medicine,
stigmasterol,
ML
model
fingerprints.
vivo
experiments
demonstrated
stigmasterol
can
regulate
glucose
lipid
metabolism,
improve
systemic
inflammatory
levels,
ameliorate
ocular
vascular
changes
by
modulating
expression
PPARG.
Conclusion
BNM
suggests
an
important
treatment
DR,
with
its
mechanism
potentially
related
VEGF/VEGFR
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: July 26, 2024
The
CBL
(Casitas
B-lineage
lymphoma)
family,
as
a
class
of
ubiquitin
ligases,
can
regulate
signal
transduction
and
activate
receptor
tyrosine
kinases
through
various
kinase-dependent
pathways.
There
are
three
members
the
family:
c-CBL,
CBL-b,
CBL-c.
Numerous
studies
have
demonstrated
important
role
in
cellular
pathways,
particularly
those
involved
occurrence
progression
cancer,
hematopoietic
development,
regulation
T
cell
receptors.
Therefore,
purpose
this
review
is
to
comprehensively
summarize
function
regulatory
family
proteins
different
human
tumors,
well
progress
drug
research
targeting
so
provide
broader
clinical
measurement
strategy
for
treatment
tumors.