PLoS Pathogens,
Год журнала:
2024,
Номер
20(12), С. e1012314 - e1012314
Опубликована: Дек. 23, 2024
The
Hog1
stress-activated
protein
kinase
(SAPK)
is
a
key
mediator
of
stress
resistance
and
virulence
in
Candida
albicans
.
activation
via
phosphorylation
the
canonical
TGY
motif
mediated
by
Pbs2
MAPKK,
which
itself
activated
Ssk2
MAPKKK.
Although
this
three-tiered
SAPK
signalling
module
well
characterised,
it
unclear
how
regulated
response
to
different
stresses.
Functioning
upstream
MAPKKK
two-component
related
signal
transduction
system
comprising
three
sensor
histidine
kinases,
phosphotransfer
Ypd1,
regulator
Ssk1.
Here,
we
report
that
Ssk1
master
promotes
diverse
stresses,
except
high
osmotic
stress.
Notably,
find
regulates
independent
manner
functioning
promote
interactions
between
kinases.
We
propose
function
important
maintain
basal
level
necessary
for
oxidative
stress,
but
not
activation.
triggers
robust
drives
its
dissociation
from
Ssk2.
In
contrast,
robustly
phosphorylated
following
Ssk1-mediated
Ssk2-Pbs2
interaction
remains
intact.
Instead,
stress-stimulated
increases
dependent
on
inhibition
tyrosine
phosphatases
negatively
regulate
coupled
with
promotion
activity.
Furthermore,
linked
hydrogen
peroxide
induced
oxidation
these
negative
regulators
mechanism
partly
thioredoxin.
Taken
together
data
reveal
contingent
changes
pathway
architecture
regulation
uncover
novel
mode
action
regulation.
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Март 7, 2025
Redox
signaling
acts
as
a
critical
mediator
in
the
dynamic
interactions
between
organisms
and
their
external
environment,
profoundly
influencing
both
onset
progression
of
various
diseases.
Under
physiological
conditions,
oxidative
free
radicals
generated
by
mitochondrial
respiratory
chain,
endoplasmic
reticulum,
NADPH
oxidases
can
be
effectively
neutralized
NRF2-mediated
antioxidant
responses.
These
responses
elevate
synthesis
superoxide
dismutase
(SOD),
catalase,
well
key
molecules
like
nicotinamide
adenine
dinucleotide
phosphate
(NADPH)
glutathione
(GSH),
thereby
maintaining
cellular
redox
homeostasis.
Disruption
this
finely
tuned
equilibrium
is
closely
linked
to
pathogenesis
wide
range
Recent
advances
have
broadened
our
understanding
molecular
mechanisms
underpinning
dysregulation,
highlighting
pivotal
roles
genomic
instability,
epigenetic
modifications,
protein
degradation,
metabolic
reprogramming.
findings
provide
foundation
for
exploring
regulation
mechanistic
basis
improving
therapeutic
strategies.
While
antioxidant-based
therapies
shown
early
promise
conditions
where
stress
plays
primary
pathological
role,
efficacy
diseases
characterized
complex,
multifactorial
etiologies
remains
controversial.
A
deeper,
context-specific
signaling,
particularly
redox-sensitive
proteins,
designing
targeted
aimed
at
re-establishing
balance.
Emerging
small
molecule
inhibitors
that
target
specific
cysteine
residues
proteins
demonstrated
promising
preclinical
outcomes,
setting
stage
forthcoming
clinical
trials.
In
review,
we
summarize
current
intricate
relationship
disease
also
discuss
how
these
insights
leveraged
optimize
strategies
practice.
Materials Today Bio,
Год журнала:
2025,
Номер
31, С. 101467 - 101467
Опубликована: Янв. 8, 2025
Defective
diabetic
wound
healing
is
a
major
clinical
challenge,
where
hyperglycemia
at
the
site
induces
excessive
reactive
oxygen
species
(ROS)
which
activate
MAPK
pathway
(particularly
p38
MAPK),
resulting
in
sustained
release
of
inflammatory
factors
and
cellular
damage/apoptosis.
Polyphenols
are
efficient
ROS
scavengers
reduce
level
inflammation
promote
healing,
but
low
bioavailability
limits
their
biomedical
application.
This
study
developed
simple
highly
method
for
preparing
proanthocyanidin
(PC)
capsules
through
hydrogen
bonding
hydrophobic
interactions
among
PC
molecules.
can
continuously
scavenge
free
radicals
proanthocyanidins,
significantly
enhancing
bioavailability.
A
single
dose
accelerates
mice
by
regulating
signaling
cascade,
reducing
mediator
concentration,
inhibiting
cell
apoptosis,
remodeling
microenvironment.
research
makes
an
important
contribution
to
field
polyphenol
reveals
potential
modulating
treating
other
oxidative
stress-related
diseases.
Essays in Biochemistry,
Год журнала:
2024,
Номер
68(1), С. 27 - 39
Опубликована: Фев. 15, 2024
Thioredoxin,
glutaredoxin
and
peroxiredoxin
systems
play
central
roles
in
redox
regulation,
signaling
metabolism
cells.
In
these
systems,
reducing
equivalents
from
NAD(P)H
are
transferred
by
coupled
thiol-disulfide
exchange
reactions
to
redoxins
which
then
reduce
a
wide
array
of
targets.
However,
the
characterization
redoxin
activity
has
been
unclear,
with
regarded
as
enzymes
some
studies
metabolites
others.
Consequently,
activities
have
quantified
enzyme
kinetic
parameters
vitro,
potentials
or
ratios
within
By
analyzing
all
computational
models
showed
that
many
properties
attributed
were
due
system-level
effects.
Models
cellular
networks
also
used
estimate
intracellular
hydrogen
peroxide
levels,
analyze
couple
omic
data
understand
regulation
disease.
Computational
modeling
emerged
powerful
complementary
tool
traditional
assays
integrates
number
sources
into
single
quantitative
framework
accelerate
analysis
systems.
PLoS Biology,
Год журнала:
2025,
Номер
23(1), С. e3002969 - e3002969
Опубликована: Янв. 7, 2025
Fission
yeast
is
an
excellent
model
system
that
has
been
widely
used
to
study
the
mechanism
control
cell
cycle
progression.
However,
there
a
lack
of
tools
allow
measure
with
high
precision
duration
different
phases
in
individual
cells.
To
circumvent
this
problem,
we
have
developed
fluorescent
reporter
allows
quantification
at
single-cell
level
most
genetic
backgrounds.
prove
accuracy
reporter,
tested
strains
known
delay
G1/S
or
G2/M
transitions,
confirming
strength
and
versatility
system.
An
advantage
it
eliminates
need
for
culture
synchronization,
avoiding
stressing
Using
show
unperturbed
cells
lacking
Sty1
standard
length
distribution
extended
these
due
their
increased
growth
rate
but
not
alterations
Journal of Nanobiotechnology,
Год журнала:
2025,
Номер
23(1)
Опубликована: Апрель 24, 2025
The
effective
treatment
of
Alzheimer's
disease
(AD)
is
challenging
because
its
complex
and
controversial
pathological
mechanisms.
Moreover,
multiple
barriers,
such
as
the
blood-brain
barrier
(BBB),
reduce
drug
delivery
efficiency.
Microglia-related
neuroinflammation
has
recently
attracted
increasing
attention
a
possible
cause
AD
become
novel
therapeutic
target.
Therefore,
overcoming
BBB
targeted
anti-inflammatory
agents
to
microglia
seem
be
practical
strategies
for
treating
AD.
A
large
proportion
natural
active
extracts
possess
exceptional
immunomodulating
capabilities.
In
this
study,
cooperative
berberine
(Ber)
palmatine
(Pal)
by
transferrin-decorated
extracellular
vesicles
(Tf-hEVs-Ber/Pal),
which
can
cross
precisely
target
microglia,
was
performed.
This
nanosystem
effectively
cleared
amyloid
β-protein
(Aβ)
aggregates,
significantly
regulated
neuroinflammatory
environment
both
in
vitro
vivo
markedly
altered
behavior
improved
cognitive
learning
abilities
model
mice.
efficacy
microglia-targeting
combined
approach
demonstrated,
broadens
potential
application
Chinese
herbal
ingredients.
