Cisplatin
is
a
widely
used
chemotherapy
drug
but
it
induces
both
acute
and
chronic
kidney
diseases
(CKD)
in
cancer
patients.
The
pathogenesis
of
cisplatin-induced
CKD
unclear
effective
renoprotective
approaches
are
not
available.
Here,
we
report
that
repeated
low-dose
cisplatin
(RLDC)
treatment
C57BL/6
mice
induced
cellular
senescence
tubules,
accompanied
with
tubular
degeneration
pro-fibrotic
phenotype
transformation
culminated
maladaptive
repair
renal
fibrosis.
Suppression
by
senolytic
drugs
ABT-263
Fisetin
attenuated
fibrosis
improved
as
indicated
restoration
regeneration
function.
In
vitro,
RLDC
also
mouse
proximal
BUMPT
cells.
eliminated
senescent
cells
following
treatment,
reversed
the
increased
their
clonogenic
activity.
Moreover,
alleviated
paracrine
effect
RLDC-treated
on
fibroblasts
for
Consistently,
knockdown
p16
suppressed
post-RLDC
fibrotic
changes
cells,
effects
fibroblast
proliferation.
These
results
indicate
persistent
induction
plays
an
important
role
promoting
CKD.
Targeting
may
be
efficient
to
improve
prevention
FEBS Journal,
Год журнала:
2020,
Номер
288(1), С. 56 - 80
Опубликована: Сен. 22, 2020
Cellular
senescence
is
a
physiological
mechanism
whereby
proliferating
cell
undergoes
stable
cycle
arrest
upon
damage
or
stress
and
elicits
secretory
phenotype.
This
highly
dynamic
regulated
cellular
state
plays
beneficial
roles
in
physiology,
such
as
during
embryonic
development
wound
healing,
but
it
can
also
result
antagonistic
effects
age-related
pathologies,
degenerative
disorders,
ageing
cancer.
In
an
effort
to
better
identify
this
complex
state,
given
that
universal
marker
has
yet
be
identified,
general
set
of
hallmarks
describing
been
established.
However,
the
senescent
programme
becomes
more
defined,
further
complexities,
including
phenotype
heterogeneity,
have
emerged.
significantly
complicates
recognition
evaluation
senescence,
especially
within
tissues
living
organisms.
To
address
these
challenges,
substantial
efforts
are
currently
being
made
towards
discovery
novel
specific
biomarkers,
optimized
combinatorial
strategies
emerging
detection
techniques.
Here,
we
compile
advances
present
multifactorial
guide
assess
cultures,
The
reliable
assessment
identification
not
only
crucial
for
understanding
its
underlying
biology,
imperative
diagnostic
therapeutic
aimed
at
targeting
clinic.
Journal of Clinical Investigation,
Год журнала:
2022,
Номер
132(15)
Опубликована: Июль 31, 2022
Cellular
senescence
is
a
hallmark
of
aging
defined
by
stable
exit
from
the
cell
cycle
in
response
to
cellular
damage
and
stress.
Senescent
cells
(SnCs)
can
develop
characteristic
pathogenic
senescence-associated
secretory
phenotype
(SASP)
that
drives
secondary
disrupts
tissue
homeostasis,
resulting
loss
repair
regeneration.
The
use
transgenic
mouse
models
which
SnCs
be
genetically
ablated
has
established
key
role
for
driving
age-related
disease.
Importantly,
senotherapeutics
have
been
developed
pharmacologically
eliminate
SnCs,
termed
senolytics,
or
suppress
SASP
other
markers
senescence,
senomorphics.
Based
on
extensive
preclinical
studies
as
well
small
clinical
trials
demonstrating
benefits
senotherapeutics,
multiple
are
under
way.
This
Review
discusses
diseases,
strategies
target
approaches
discover
advances
senolytics.
Biology of Sex Differences,
Год журнала:
2020,
Номер
11(1)
Опубликована: Апрель 15, 2020
We
now
know
that
cancer
is
many
different
diseases,
with
great
variation
even
within
a
single
histological
subtype.
With
the
current
emphasis
on
developing
personalized
approaches
to
treatment,
it
astonishing
we
have
not
yet
systematically
incorporated
biology
of
sex
differences
into
our
paradigms
for
laboratory
and
clinical
research.
While
some
in
arise
through
actions
circulating
hormones,
other
are
independent
estrogen,
testosterone,
or
progesterone
levels.
Instead,
these
result
sexual
differentiation,
process
involves
genetic
epigenetic
mechanisms,
addition
acute
hormone
actions.
Sexual
differentiation
begins
fertilization
continues
beyond
menopause.
It
affects
virtually
every
body
system,
resulting
marked
such
areas
as
growth,
lifespan,
metabolism,
immunity,
all
which
can
impact
progression,
treatment
response,
survival.
These
organismal
level
correlates
at
cellular
level,
thus,
males
females
fundamentally
differ
their
protections
vulnerabilities
cancer,
from
transformation
stages
spread,
response
treatment.
Our
goal
this
review
cover
robust
exist
core
pathways
make
case
inclusion
biological
variable
finish
discussion
lab-
clinic-based
experimental
design
should
be
used
when
testing
whether
matters
appropriate
statistical
models
apply
data
analysis
rigorous
evaluations
potential
effects.
facilitate
evaluation
order
improve
outcomes
patients.
EMBO Molecular Medicine,
Год журнала:
2019,
Номер
11(12)
Опубликована: Ноя. 19, 2019
Organismal
ageing
is
a
complex
process
driving
progressive
impairment
of
functionality
and
regenerative
potential
tissues.
Cellular
senescence
state
stable
cell
cycle
arrest
occurring
in
response
to
damage
stress
considered
hallmark
ageing.
Senescent
cells
accumulate
multiple
organs
during
ageing,
contribute
tissue
dysfunction
give
rise
pathological
manifestations.
Senescence
therefore
defining
feature
variety
human
age-related
disorders,
including
cancer,
targeted
elimination
these
has
recently
emerged
as
promising
therapeutic
approach
ameliorate
promote
repair
regeneration.
In
addition,
vivo
identification
senescent
significant
for
early
diagnosis
pathologies.
Here,
we
review
existing
senolytics,
small
molecules
drug
delivery
tools
used
preclinical
strategies
involving
cellular
senescence,
well
probes
trace
cells.
We
also
the
clinical
research
landscape
discuss
how
identifying
targeting
might
positively
affect
processes.
Abstract
Pharmacologically
active
compounds
with
preferential
cytotoxic
activity
for
senescent
cells,
known
as
senolytics,
can
ameliorate
or
even
revert
pathological
manifestations
of
senescence
in
numerous
preclinical
mouse
disease
models,
including
cancer
models.
However,
translation
senolytic
therapies
to
human
is
hampered
by
their
suboptimal
specificity
cells
and
important
toxicities
that
narrow
therapeutic
windows.
We
have
previously
shown
the
high
levels
senescence‐associated
lysosomal
β‐galactosidase
(SA‐β‐gal)
found
within
be
exploited
specifically
release
tracers
cargoes
from
galactose‐encapsulated
nanoparticles
these
cells.
Here,
we
show
galacto‐conjugation
BCL‐2
family
inhibitor
Navitoclax
results
a
potent
prodrug
(Nav‐Gal),
preferentially
activated
SA‐β‐gal
wide
range
cell
types.
Nav‐Gal
selectively
induces
apoptosis
has
higher
index
than
(through
reduced
activation
nonsenescent
cells).
enhances
cytotoxicity
standard
senescence‐inducing
chemotherapy
(cisplatin)
A549
lung
Concomitant
treatment
cisplatin
vivo
eradication
significantly
reduces
tumour
growth.
Importantly,
Navitoclax‐induced
platelet
murine
blood
samples
treated
ex
vivo,
thrombocytopenia
at
therapeutically
effective
concentrations
Taken
together,
provide
potentially
versatile
strategy
generating
prodrugs
toxicities.
Pharmaceuticals,
Год журнала:
2023,
Номер
16(7), С. 1020 - 1020
Опубликована: Июль 18, 2023
Quercetin,
a
flavonoid
found
in
fruits
and
vegetables,
has
been
part
of
human
diets
for
centuries.
Its
numerous
health
benefits,
including
antioxidant,
antimicrobial,
anti-inflammatory,
antiviral,
anticancer
properties,
have
extensively
studied.
strong
antioxidant
properties
enable
it
to
scavenge
free
radicals,
reduce
oxidative
stress,
protect
against
cellular
damage.
Quercetin’s
anti-inflammatory
involve
inhibiting
the
production
inflammatory
cytokines
enzymes,
making
potential
therapeutic
agent
various
conditions.
It
also
exhibits
effects
by
cancer
cell
proliferation
inducing
apoptosis.
Finally,
quercetin
cardiovascular
benefits
such
as
lowering
blood
pressure,
reducing
cholesterol
levels,
improving
endothelial
function,
promising
candidate
preventing
treating
diseases.
This
review
provides
an
overview
chemical
structure,
biological
activities,
bioavailability
quercetin,
well
different
delivery
systems
available
quercetin.
Incorporating
quercetin-rich
foods
into
diet
or
taking
supplements
may
be
beneficial
maintaining
good
chronic
As
research
progresses,
future
perspectives
appear
promising,
with
applications
nutraceuticals,
pharmaceuticals,
functional
promote
overall
well-being
disease
prevention.
However,
further
studies
are
needed
elucidate
its
mechanisms
action,
optimize
bioavailability,
assess
long-term
safety
widespread
utilization.
