Cell Death and Disease,
Год журнала:
2024,
Номер
15(12)
Опубликована: Дек. 19, 2024
Abstract
Cell
death
and
related
signaling
pathways
are
essential
during
development
in
various
physiological
pathological
conditions.
Post-translational
modifications
such
as
ubiquitination
phosphorylation
play
an
important
role
these
pathways.
The
involvement
of
kinases
-
enzymes
that
catalyze
protein
cell
has
been
extensively
studied.
On
the
other
hand,
not
many
studies
have
devoted
to
analyzing
phosphatases,
involved
removal
phosphorylated
residues
added
proteins
by
kinases.
Obviously,
two
opposite
reactions,
dephosphorylation,
equally
regulation
functions
subsequently
execution
program.
Here,
we
summarized
recent
work
on
serine-threonine
PP2C
phosphatases
pathways,
senescence
autophagy,
focusing
particular
most
studied
phosphatase
PPM1D
(PP2Cδ)
example
regulatory
PP2Cs
death.
review
should
help
draw
attention
importance
family
checkpoints
discover
new
targets
for
drug
development.
Journal of Hematology & Oncology,
Год журнала:
2025,
Номер
18(1)
Опубликована: Янв. 13, 2025
The
tumor
microenvironment
(TME)
is
integral
to
cancer
progression,
impacting
metastasis
and
treatment
response.
It
consists
of
diverse
cell
types,
extracellular
matrix
components,
signaling
molecules
that
interact
promote
growth
therapeutic
resistance.
Elucidating
the
intricate
interactions
between
cells
TME
crucial
in
understanding
progression
challenges.
A
critical
process
induced
by
epithelial-mesenchymal
transition
(EMT),
wherein
epithelial
acquire
mesenchymal
traits,
which
enhance
their
motility
invasiveness
progression.
By
targeting
various
components
TME,
novel
investigational
strategies
aim
disrupt
TME's
contribution
EMT,
thereby
improving
efficacy,
addressing
resistance,
offering
a
nuanced
approach
therapy.
This
review
scrutinizes
key
players
emphasizing
avenues
therapeutically
components.
Moreover,
article
discusses
implications
for
resistance
mechanisms
highlights
current
toward
modulation
along
with
potential
caveats.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(9), С. 5044 - 5044
Опубликована: Май 6, 2024
Vitamin
B12
(cobalamin)
is
an
essential
nutrient
for
humans
and
animals.
Metabolically
active
forms
of
B12-methylcobalamin
5-deoxyadenosylcobalamin
are
cofactors
the
enzymes
methionine
synthase
mitochondrial
methylmalonyl-CoA
mutase.
Malfunction
these
due
to
a
scarcity
vitamin
leads
disturbance
one-carbon
metabolism
impaired
function.
A
significant
fraction
population
(up
20%)
deficient
in
B12,
with
higher
rate
deficiency
among
elderly
people.
associated
numerous
hallmarks
aging
at
cellular
organismal
levels.
Cellular
senescence
characterized
by
high
levels
DNA
damage
metabolic
abnormalities,
increased
dysfunction,
epigenetic
regulation.
could
be
responsible
or
play
crucial
part
disorders.
In
this
review,
we
focus
on
comprehensive
analysis
molecular
mechanisms
through
which
influences
aging.
We
review
new
data
about
how
may
accelerate
Despite
indications
that
has
important
role
health
healthy
aging,
knowledge
influence
still
limited
requires
further
research.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(13), С. 7163 - 7163
Опубликована: Июнь 28, 2024
The
combination
of
a
polyphenol,
quercetin,
with
dasatinib
initiated
clinical
trials
to
evaluate
the
safety
and
efficacy
senolytics
in
idiopathic
pulmonary
fibrosis,
lung
disease
associated
presence
senescent
cells.
Another
approach
senotherapeutics
consists
controlling
inflammation
related
cellular
senescence
or
“inflammaging”,
which
participates,
among
other
processes,
establishing
fibrosis.
We
whether
polyphenols
such
as
caffeic
acid,
chlorogenic
epicatechin,
gallic
resveratrol
combined
different
metformin
rapamycin,
antifibrotic
drugs
nintedanib
pirfenidone,
could
present
beneficial
actions
an
vitro
model
MRC-5
fibroblasts.
A
senescent-associated
secretory
phenotype
(SASP)
was
evaluated
by
measurement
interleukin
(IL)-6,
IL-8,
IL-1β.
β-galactosidase
(SA-β-gal)
activity
proliferation
were
assessed.
Fibrosis
using
Picrosirius
red
assay
gene
expression
fibrosis-related
genes.
Epithelial-mesenchymal
transition
(EMT)
assayed
A549
cell
line
exposed
Transforming
Growth
Factor
(TGF)-β
vitro.
that
demonstrated
best
results
inhibiting
IL-6
IL-8
Metformin
acid
also
restore
reduce
SA-β-gal
during
induction.
collagen
production
cells
inhibited
epicatechin
alone
drugs.
Epicatechin
able
control
EMT
In
conclusion,
can
potentially
increase
effectiveness
senotherapeutic
diseases
whose
pathophysiological
component
is
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
Cellular
senescence,
a
stable
state
of
cell
cycle
arrest
induced
by
various
stressors
or
genomic
damage,
is
recognized
as
hallmark
cancer.
It
exerts
context-dependent
dual
role
in
cancer
initiation
and
progression,
functioning
tumor
suppressor
promoter.
The
complexity
senescence
arises
from
its
mechanistic
diversity,
potential
reversibility,
heterogeneity.
A
key
mediator
these
effects
the
senescence-associated
secretory
phenotype
(SASP),
repertoire
bioactive
molecules
that
influence
microenvironment
(TME)
remodeling,
modulate
behavior,
contribute
to
therapeutic
resistance.
Given
intricate
biology,
presents
both
challenges
opportunities
for
intervention.
Strategies
targeting
pathways,
including
senescence-inducing
therapies
senolytic
approaches,
offer
promising
avenues
treatment.
This
review
provides
comprehensive
analysis
regulatory
mechanisms
governing
cellular
tumors.
We
also
discuss
emerging
strategies
highlighting
novel
opportunities.
deeper
understanding
processes
essential
developing
precision
improving
clinical
outcomes.
Биохимия,
Год журнала:
2024,
Номер
89(5), С. 818 - 832
Опубликована: Ноя. 14, 2024
Tumor-associated
macrophages
(TAMs)
are
an
important
component
of
the
tumor
microenvironment
(TME)
and
most
abundant
population
immune
cells
infiltrating
a
tumor.
TAMs
can
largely
determine
direction
anti-tumor
response.
promote
it
or,
conversely,
contribute
to
formation
immunosuppressive
TME
that
allows
tumors
evade
control.
Through
interactions
with
or
other
in
microenvironment,
as
result
action
anti-cancer
therapy,
enter
senescence.
In
this
review,
we
have
attempted
summarize
information
available
literature
on
role
senescent
tumors.
With
recent
development
senolytic
therapeutic
strategies
aimed
at
removing
from
organism.
It
seems
discuss
functions
potential
drugs
reprogramming
enhance
response
improve
efficacy
cancer
treatment.
