Antioxidants,
Journal Year:
2023,
Volume and Issue:
12(3), P. 651 - 651
Published: March 6, 2023
Aging
is
a
complex
biological
process
accompanied
by
progressive
decline
in
the
physical
function
of
organism
and
an
increased
risk
age-related
chronic
diseases
such
as
cardiovascular
diseases,
cancer,
neurodegenerative
diseases.
Studies
have
established
that
there
exist
nine
hallmarks
aging
process,
including
(i)
telomere
shortening,
(ii)
genomic
instability,
(iii)
epigenetic
modifications,
(iv)
mitochondrial
dysfunction,
(v)
loss
proteostasis,
(vi)
dysregulated
nutrient
sensing,
(vii)
stem
cell
exhaustion,
(viii)
cellular
senescence,
(ix)
altered
communication.
All
these
alterations
been
linked
to
sustained
systemic
inflammation,
mechanisms
contribute
timing
not
clearly
determined
yet.
Nevertheless,
dysfunction
one
most
important
contributing
process.
Mitochondria
primary
endogenous
source
reactive
oxygen
species
(ROS).
During
ATP
production
elevated
ROS
together
with
antioxidant
defense.
Elevated
levels
can
cause
oxidative
stress
severe
damage
cell,
organelle
membranes,
DNA,
lipids,
proteins.
This
contributes
phenotype.
In
this
review,
we
summarize
recent
advances
emphasis
on
production.
Signal Transduction and Targeted Therapy,
Journal Year:
2021,
Volume and Issue:
6(1)
Published: Nov. 15, 2021
Abstract
Cancer
is
the
leading
cause
of
death
worldwide,
and
its
treatment
outcomes
have
been
dramatically
revolutionised
by
targeted
therapies.
As
most
frequently
mutated
oncogene,
Kirsten
rat
sarcoma
viral
oncogene
homologue
(KRAS)
has
attracted
substantial
attention.
The
understanding
KRAS
constantly
being
updated
numerous
studies
on
in
initiation
progression
cancer
diseases.
However,
deemed
a
challenging
therapeutic
target,
even
“undruggable”,
after
drug-targeting
efforts
over
past
four
decades.
Recently,
there
surprising
advances
directly
drugs
for
KRAS,
especially
(G12C)
inhibitors,
such
as
AMG510
(sotorasib)
MRTX849
(adagrasib),
which
obtained
encouraging
results
clinical
trials.
Excitingly,
was
first
to
be
approved
use
this
year.
This
review
summarises
recent
fundamental
aspects
relationship
between
mutations
tumour
immune
evasion,
new
progress
targeting
particularly
(G12C).
Moreover,
possible
mechanisms
resistance
inhibitors
combination
therapies
are
summarised,
with
view
providing
best
regimen
individualised
achieving
truly
precise
treatment.
Nature Communications,
Journal Year:
2021,
Volume and Issue:
12(1)
Published: Jan. 12, 2021
Skeletal
muscle
is
the
protein
reservoir
of
our
body
and
an
important
regulator
glucose
lipid
homeostasis.
Consequently,
growth
or
loss
mass
can
influence
general
metabolism,
locomotion,
eating
respiration.
Therefore,
it
not
surprising
that
excessive
a
bad
prognostic
index
variety
diseases
ranging
from
cancer,
organ
failure,
infections
unhealthy
ageing.
Muscle
function
influenced
by
different
quality
systems
regulate
contractile
proteins
organelles.
These
are
controlled
transcriptional
dependent
programs
adapt
cells
to
environmental
nutritional
clues.
Mechanical,
oxidative,
energy
stresses,
as
well
factors
cytokines
modulate
signaling
pathways
that,
ultimately,
converge
on
organelle
turnover.
Novel
insights
control
orchestrate
such
complex
network
continuously
emerging
will
be
summarized
in
this
review.
Understanding
mechanisms
provide
therapeutic
targets
for
treatment
inherited
non-hereditary
improvement
life
during
Nature Communications,
Journal Year:
2021,
Volume and Issue:
12(1)
Published: March 11, 2021
Glutathione
peroxidase
4
(GPX4)
utilizes
glutathione
(GSH)
to
detoxify
lipid
peroxidation
and
plays
an
essential
role
in
inhibiting
ferroptosis.
As
a
selenoprotein,
GPX4
protein
synthesis
is
highly
inefficient
energetically
costly.
How
cells
coordinate
with
nutrient
availability
remains
unclear.
In
this
study,
we
perform
integrated
proteomic
functional
analyses
reveal
that
SLC7A11-mediated
cystine
uptake
promotes
not
only
GSH
synthesis,
but
also
synthesis.
Mechanistically,
find
cyst(e)ine
activates
mechanistic/mammalian
target
of
rapamycin
complex
1
(mTORC1)
at
least
partly
through
the
Rag-mTORC1-4EBP
signaling
axis.
We
show
pharmacologic
inhibition
mTORC1
decreases
levels,
sensitizes
cancer
ferroptosis,
synergizes
ferroptosis
inducers
suppress
patient-derived
xenograft
tumor
growth
vivo.
Together,
our
results
regulatory
mechanism
suggest
using
combinatorial
therapy
inhibitors
treatment.
