Age-related
kidney
impairment,
characterized
by
tubular
epithelial
cell
senescence
and
renal
fibrosis,
poses
a
significant
global
public
health
threat.
Although
N6-methyladenosine
(m6A)
methylation
is
implicated
in
various
pathological
processes,
its
regulatory
mechanism
aging
remains
unclear.
An
m6A-mRNA
epitranscriptomic
microarray
was
performed
to
identify
genes
with
abnormal
m6A
modifications
aged
human
tissues.
Histological,
immunohistochemical,
immunofluorescent
staining,
western
blot,
RT-qPCR
were
employed
examine
the
biological
functions
of
targeted
methyltransferases
both
vivo
vitro.
RNA
immunoprecipitation,
chromatin
ribosomal
luciferase
reporter
assays
used
investigate
specific
interactions
between
methyltransferases,
genes,
their
downstream
signals.
Significantly
lower
modification
levels
observed
GLIS1,
identified
as
"metabolic
remodeling
factor,"
showed
significantly
reduced
protein
modifications.
The
downregulation
GLIS1
induced
fibrosis
shifting
metabolic
from
fatty
acid
oxidation
(FAO)
glycolysis.
Additionally,
methylated
mRNA
regulated
expression
METTL3
YTHDF1.
Silencing
METTL3/YTHDF1
weakened
translation
disrupted
balance
FAO
Our
findings
suggest
that
activated
YTHDF1-dependent
manner,
leads
regulating
shift
This
provides
promising
therapeutic
target
for
aging.
Abstract
Renal
fibrosis
is
a
common
pathological
process
in
various
chronic
kidney
diseases.
The
accumulation
of
senescent
renal
tubular
epithelial
cells
(TECs)
tissues
plays
an
important
role
the
development
fibrosis.
Eliminating
TECs
has
been
proven
to
effectively
reduce
Procyanidin
C1
(PCC1)
senolytic
by
specifically
eliminating
and
extending
its
overall
lifespan.
However,
whether
PCC1
can
alleviate
unilateral
ureteral
obstruction
(UUO)‐induced
associated
therapeutic
mechanisms
remains
unclear.
Here,
we
observed
marked
increase
within
obstructed
human
tissue
demonstrated
positive
correlation
between
UUO‐induced
mice.
We
found
that
reduced
number
TECs,
restored
regenerative
phenotype
kidneys
with
fibrosis,
improved
repair
after
injury.
In
vitro,
cleared
HK2
inducing
apoptosis
via
ANGPTL4/NOX4
signaling.
Incubation
culture
medium
from
promoted
fibroblast
activation,
whereas
impeded
profibrotic
effects
downregulating
senescence‐associated
secretory
(SASP)
factors
cells.
Therefore,
alleviated
interstitial
not
only
clearing
improving
but
also
indirectly
attenuating
myofibroblast
activation
reducing
level
SASP.
summary,
may
be
novel
agent
for
treating
Age-related
alveolar
bone
resorption
poses
a
major
dental
health
challenge,
yet
its
mechanisms
and
treatments
are
poorly
understood.
This
study
investigates
the
impact
of
dasatinib
quercetin
(D
+
Q)
treatment
on
senescent
cells
(SnCs),
senescence-associated
secretory
phenotype
(SASP),
neutrophil
infiltration
in
aged
bone,
aiming
to
develop
new
strategies
for
combating
age-related
resorption.
C57BL/6
mice
(2
18
months)
were
used
examine
resorption,
inflammaging,
infiltration.
Aged
received
D
Q
assess
therapeutic
effects.
Key
measurements
included
cementoenamel
junction
crest
(CEJ-ABC)
distance,
periodontal
ligament
(PDL)
thickness,
osteometabolism
markers,
SnCs
accumulation,
SASP
expression,
showed
increased
CEJ-ABC
atrophied
ligament,
unbalanced
osteometabolism,
along
with
elevated
SnCs,
SASP,
neutrophils
compared
young
controls.
improved
these
conditions
by
reducing
enhancing
health,
boosting
metabolism.
It
also
lowered
expression
markers.
effectively
mitigates
aging
clearing
lowering
levels,
aggregation,
presenting
novel
approach
Animal Cells and Systems,
Год журнала:
2025,
Номер
29(1), С. 19 - 29
Опубликована: Март 12, 2025
Human
periodontal
ligament
stem
cells
(hPDLSCs)
are
candidate
seed
for
tissue
regeneration.
Enhancing
the
stemness
maintenance
and
osteogenic
differentiation
potential
of
hPDLSCs
is
conducive
to
their
role
in
The
combination
dasatinib
quercetin,
a
type
senolytic,
has
been
reported
affect
cell
senescence.
However,
whether
it
can
regulate
hPDLSCs,
related
mechanisms,
remain
unknown.
present
study
analyzed
optimal
concentrations
quercetin
found
that
enhanced
promoted
expression
stemness-related
markers
hPDLSCs.
levels
TAZ
YAP
were
improved
when
incubated
with
quercetin.
osteogenesis-promoting
effects
plus
partly
attenuated
was
knocked
down,
on
suppressed
inhibited.
Taken
together,
promotes
YAP/TAZ
may
be
involved
this
process.
This
hold
promise
improving
function
Archives of Toxicology,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 11, 2025
Abstract
Kidney
diseases
are
among
the
fastest
worldwide
growing
pathologies.
This
growth
together
with
their
high
mortality
rate
emphasizes
importance
of
generating
vital
information
about
mechanism
involved
in
pathophysiology
to
determine
possible
therapeutic
targets.
Recently,
mitochondrial
damage
and
implication
reactive
oxygen
spices
(ROS)
signaling
redox
homeostasis
have
emerged
as
a
hub
point
pathologic
renal
ROS
low
levels
necessary
maintain
cell
processes
well
mitochondria
its
association
other
organelles,
especially
endoplasmic
reticulum
(ER).
However,
how
interacts
interferes
cellular
has
not
been
fully
integrated.
Furthermore,
higher
concentrations,
these
promotes
pathways
linked
disease
progression
like,
biogenesis
reduction,
ER
stress,
calcium
overload,
inflammation,
death
fibrosis.
Therefore,
aim
this
review
is
describe
molecular
mechanisms
influence
on
homeostasis,
focusing
lipid
metabolism
ß-oxidation,
biogenesis,
inflammations,
stress
effects
alteration
genesis
development
disease,
emphasis
acute
kidney
injury
(AKI)
chronic
(CKD).
BMC Complementary Medicine and Therapies,
Год журнала:
2025,
Номер
25(1)
Опубликована: Апрель 23, 2025
Berberine
is
an
isoquinoline
alkaloid
isolated
from
Chinese
herb
coptis
chinensis
and
other
berberis
plants
which
can
be
used
to
treat
a
wide
range
of
chronic
diseases.
However,
the
current
research
evidence
on
therapeutic
effects
berberine
has
not
been
summarized.
We
aimed
synthesize
systematic
review
(SRs)
for
treatment
diverse
conditions.
A
comprehensive
search
Cochrane
Library,
PubMed,
EMBASE,
Web
Science,
CNKI,
Wanfang,
VIP,
SinoMed
was
performed
database
inception
April
11,
2024.
SRs
were
included
evaluated.
The
methodological
quality
reporting
each
SR
assessed
using
AMSTAR-2
tool
PRISMA
checklist,
respectively.
appraised
based
GRADE.
Fifty-four
analyzed.
Overall,
associations
found
between
70
health
outcomes
concerned
with
9
improved
most
these
diseases:
78%
(25/32)
cardiovascular
disease
outcomes,
92.59%
(25/27)
type
2
diabetes
mellitus
94.74%
(18/19)
gastrointestinal
disorders
72.22%
(13/18)
polycystic
ovary
syndrome
(PCOS)
86.67%
(13/15)
non-alcoholic
fatty
liver
(NAFLD)
92.31%
(12/13)
schizophrenia
90.91%
(10/11)
metabolic
57.14%
(4/7)
obesity
100.00%
(6/6)
dyslipidemia
outcomes.
There
high
overlap
primary
studies
(CCA
>
15%)
in
PCOS,
NAFLD,
obesity,
schizophrenia.
Only
one
rated
as
while
eight
low
forty-five
very
according
AMSTAR-2.
Regarding
quality,
Item
14,
15,
21,
22
poorly
reported
terms
PRSMA
assessment.
For
GRADE,
evidence,
twenty-two
moderate
110
quality.
Current
suggests
that
beneficial
people
Specifically,
significantly
improves
diabetes,
disorders,
schizophrenia,
syndrome,
caution
needed
considering
shortcomings
relevant
system
reviews
included.
Pharmaceuticals,
Год журнала:
2025,
Номер
18(6), С. 822 - 822
Опубликована: Май 30, 2025
Background/Objectives:
Acute
kidney
injury
(AKI)
remains
an
unsolved
medical
problem
due
to
the
lack
of
effective
treatments,
high
mortality,
and
increased
susceptibility
progression
chronic
disease
(CKD),
especially
in
elderly.
Cellular
senescence
has
been
described
AKI,
CKD,
aging
proposed
as
a
promising
therapeutic
target.
The
senolytic
drug
combination
dasatinib
plus
quercetin
(D&Q)
is
beneficial
some
pathological
conditions,
including
experimental
but
there
are
no
data
for
AKI.
Methods:
effect
D&Q
was
tested
folic
acid-induced
nephrotoxicity
(FAN-AKI),
murine
AKI
model.
Results:
pretreatment
did
not
prevent
renal
dysfunction
acute
phase
FAN-AKI,
determined
by
serum
creatinine
BUN
levels
at
48
h.
Moreover,
gene
expression
damage
biomarkers
Lcn2
Havcr1,
Cdkn1a
gene,
which
encodes
p21,
genes
encoding
components
senescent
cell
secretome
were
significantly
response
treatment.
number
p21-positive
cells
injured
kidneys
similar
untreated
or
D&Q-treated
FAN
mice.
In
addition,
downregulation
antiaging
factor
Klotho
damaged
kidneys.
Conclusions:
treatment
protective
exacerbating
deleterious
responses.
These
results
suggest
caution
when
exploring
clinical
translation
activity.