Biomolecules,
Год журнала:
2021,
Номер
11(9), С. 1292 - 1292
Опубликована: Авг. 31, 2021
Manganese
(Mn)
is
an
essential
metal,
which
at
high
exposures
causes
neurotoxic
effects
and
neurodegeneration.
The
of
Mn
are
mediated
by
neuroinflammation,
oxidative
endoplasmic
reticulum
stress,
mitochondrial
dysfunction,
other
mechanisms.
Recent
findings
have
demonstrated
the
potential
impact
overexposure
on
gut
microbiota
dysbiosis,
known
to
contribute
neurodegeneration
via
secretion
neuroactive
proinflammatory
metabolites.
Therefore,
in
this
review,
we
discuss
existing
data
exposure
biodiversity,
bacterial
metabolite
production,
wall
permeability
regulating
systemic
levels.
that
may
affect
biodiversity
altering
abundance
Shiegella,
Ruminococcus,
Dorea,
Fusicatenibacter,
Roseburia,
Parabacteroides,
Bacteroidetes,
Firmicutes,
Ruminococcaceae,
Streptococcaceae,
phyla.
A
Mn-induced
increase
Bacteroidetes
a
reduced
Firmicutes/Bacteroidetes
ratio
lipopolysaccharide
Moreover,
addition
increased
(LPS)
levels,
capable
potentiating
LPS
neurotoxicity.
Due
metabolic
activity
intestinal
microflora,
perturbations
result
significant
alteration
metabolome
has
least
partially
mediate
biological
overexposure.
At
same
time,
recent
study
healthy
microbiome
transplantation
alleviates
neurotoxicity,
indicative
role
microflora
cascade
Mn-mediated
High
doses
cause
enterocyte
toxicity
integrity
through
disruption
tight
junctions.
resulting
further
promotes
translocation
metabolites
blood
flow,
ultimately
gaining
access
brain
leading
neuroinflammation
neurotransmitter
imbalance.
lead
us
hypothesize
should
be
considered
as
target
toxicity,
although
more
detailed
studies
required
characterize
interplay
between
gut,
well
its
pathogenesis
diseases.
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Дек. 29, 2022
Sirtuins
(SIRTs)
are
nicotine
adenine
dinucleotide(+)-dependent
histone
deacetylases
regulating
critical
signaling
pathways
in
prokaryotes
and
eukaryotes,
involved
numerous
biological
processes.
Currently,
seven
mammalian
homologs
of
yeast
Sir2
named
SIRT1
to
SIRT7
have
been
identified.
Increasing
evidence
has
suggested
the
vital
roles
members
SIRT
family
health
disease
conditions.
Notably,
this
protein
plays
a
variety
important
cellular
biology
such
as
inflammation,
metabolism,
oxidative
stress,
apoptosis,
etc.,
thus,
it
is
considered
potential
therapeutic
target
for
different
kinds
pathologies
including
cancer,
cardiovascular
disease,
respiratory
other
Moreover,
identification
modulators
exploring
functions
these
prompted
increased
efforts
discover
new
small
molecules,
which
can
modify
activity.
Furthermore,
several
randomized
controlled
trials
indicated
that
interventions
might
affect
expression
human
samples,
supplementation
diverse
impact
on
physiological
function
participants.
In
review,
we
introduce
history
structure
family,
discuss
molecular
mechanisms
elaborate
regulatory
SIRTs
summarize
inhibitors
activators,
review
related
clinical
studies.
Journal of Cellular and Molecular Medicine,
Год журнала:
2022,
Номер
26(15), С. 4216 - 4229
Опубликована: Июль 5, 2022
Myocardial
ischemia/reperfusion
injury
(MI/RI)
is
the
main
cause
of
deaths
in
worldwide,
leading
to
severe
cardiac
dysfunction.
Resveratrol
(RSV)
a
polyphenol
plant-derived
compound.
Our
study
aimed
elucidate
underlying
molecular
mechanism
preconditioning
RSV
protecting
against
MI/RI.
Mice
were
ligated
and
re-perfused
by
left
anterior
descending
branch
with
or
without
(30
mg/kg·ip)
for
7
days.
Firstly,
we
found
that
pretreatment
significantly
alleviated
myocardial
infarct
size,
improved
function
decreased
oxidative
stress.
Furthermore,
activated
p-AMPK
SIRT1,
ameliorated
inflammation
including
level
TNF-α
IL-1β,
promoting
autophagy
level.
Moreover,
neonatal
rat
ventricular
myocytes
(NRVMs)
H9c2
cells
knockdown
expression
AMPK,
SIRT1
FOXO1
used
uncover
cardio-protection
RSV.
In
NRVMs,
increased
cellular
viability,
LDH
release
reduced
Importantly,
Compound
C(CpC)
EX527
reversed
effect
MI/RI
vivo
vitro
counteracted
induced
Together,
our
indicated
could
alleviate
stress
cardiomyocytes
through
activating
AMPK/SIRT1-FOXO1
signallingpathway
enhanced
level,
thus
presenting
high
potential
protection
on
The American Journal of Chinese Medicine,
Год журнала:
2022,
Номер
50(08), С. 2103 - 2123
Опубликована: Янв. 1, 2022
Doxorubicin
(DOX)
is
a
most
common
anthracycline
chemotherapeutic
agent;
however,
its
clinical
efficacy
limited
due
to
severe
and
irreversible
cardiotoxicity.
Ferroptosis,
characterized
by
iron
overload
lipid
peroxidation,
plays
pivotal
role
in
DOX-induced
Resveratrol
(RSV)
displays
cardioprotective
anticancer
effects,
owing
antioxidative
anti-inflammatory
properties.
However,
the
mechanism
of
RSV
DOX-mediated
ferroptosis
cardiomyocytes
unclear.
This
study
showed
that
DOX
decreased
cell
viability,
increased
accumulation
peroxidation
H9c2
cells;
these
effects
were
reversed
inhibitor
ferrostatin-1
(Fer-1)
pre-treatment.
Additionally,
significantly
viability
cells
treated
with
inducers
Erastin
(Era)
RSL3.
Mechanistically,
inhibited
mitochondrial
reactive
oxygen
species
(mtROS)
overproduction
upregulated
p62-NRF2/HO-1
pathway.
RSV-induced
NRF2
activation
was
partially
dependent
on
p62,
selective
inhibition
p62
(using
p62-siRNA
interference)
or
specific
inhibitor,
ML385)
abolished
anti-ferroptosis
function
RSV.
Furthermore,
treatment
protected
mice
against
cardiotoxicity,
including
improving
left
ventricular
function,
ameliorating
myocardial
fibrosis
suppressing
ferroptosis.
Consistent
vitro
results,
also
expression,
which
DOX,
myocardium.
Notably,
protective
effect
similar
Fer-1
vivo.
Thus,
p62-NRF2
axis
critical
regulating
cardiomyocytes.
as
potent
activator
has
potential
therapeutic
target
preventing
cardiotoxicity
via
modulation.
Theranostics,
Год журнала:
2023,
Номер
13(2), С. 810 - 832
Опубликована: Янв. 1, 2023
Background:
Caloric
restriction
mimetics
(CRMs)
mimic
the
favourable
effects
of
caloric
(CR)
and
have
been
shown
to
therapeutic
in
neuroinflammatory
disease.
However,
whether
CRMs
improve
functional
recovery
from
spinal
cord
injury
(SCI)
underlying
mechanism
action
remain
unclear.
In
this
study,
we
used
3,4-dimethoxychalcone
(3,4-DC)
evaluate
value
for
SCI.
Methods:
HE,
Masson
Nissl
staining;
footprint
analysis;
Basso
mouse
scale
were
determine
SCI
after
3,4-DC
treatment.
RNA
sequencing
was
identify
mechanisms
Western
blotting,
qPCR
immunofluorescence
detect
levels
pyroptosis,
necroptosis,
autophagy
AMPK-TRPML1-calcineurin
signalling
pathway.
We
employed
a
dual-luciferase
reporter
assay
vitro
applied
AAV
vectors
inhibit
TFEB
vivo
explore
3,4-DC.
Results:
reduced
glial
scar
area
motor
neuron
death
improved
RNA-sequencing
results
indicated
that
oxidative
stress,
may
be
involved
ability
recovery.
Furthermore,
inhibited
pyroptosis
necroptosis
by
enhancing
autophagy.
also
found
enhances
promoting
activity.
A
decrease
level
abolished
protective
effect
addition,
partially
regulated
activity
through
Conclusions:
promotes
upregulating
TFEB-mediated
inhibiting
SCI,
which
potential
clinical
application
value.
Ecotoxicology and Environmental Safety,
Год журнала:
2023,
Номер
256, С. 114872 - 114872
Опубликована: Апрель 5, 2023
Manganese
(Mn),
as
one
of
the
environmental
risk
factors
for
Parkinson's
disease
(PD),
has
been
widely
studied.
Though
autophagy
dysfunction
and
neuroinflammation
mainly
are
responsible
causative
issue
Mn
neurotoxicity,
molecular
mechanism
parkinsonism
caused
by
not
explored
clearly.
The
results
in
vivo
vitro
experiments
showed
that
overexposure
to
impairment
dysfunction,
accompanied
increase
IL-1β,
IL-6,
TNF-α
mRNA
expression,
nerve
cell
apoptosis,
microglia
activation,
NF-κB
poor
neurobehavior
performance.
This
is
due
Mn-induced
downregulation
SIRT1.
Upregulation
SIRT1
could
alleviate
neuroinflammation,
yet
these
beneficial
effects
were
abolished
following
3-MA
administration.
Furthermore,
we
found
interfered
with
acetylation
FOXO3
BV2
cells,
leading
a
decrease
nuclear
translocation
FOXO3,
its
binding
LC3B
promoter
transcription
activity.
be
antagonized
upregulation
Finally,
it
proved
SIRT1/FOXO3-LC3B
signaling
involves
impairment.
Frontiers in Nutrition,
Год журнала:
2023,
Номер
9
Опубликована: Янв. 18, 2023
Scope
Insulin
resistance
(IR)
has
a
close
relationship
with
the
main
clinical
manifestations
of
patients
PCOS;
hence,
research
and
development
new
drugs
to
treat
PCOS
by
improving
IR
is
desiderate
task
at
present.
Resveratrol
(RES)
possesses
variety
beneficial
pharmacological
functions,
such
as
antioxidation,
anti-inflammatory,
regulating
glucose,
lipid
metabolism.
However,
whether
RES
could
improve
underlying
mechanisms
remained
unclear
in
PCOS.
Methods
results
SD
rats
received
high-fat
diet
letrozole
for
30
days
establish
model
then
intervened
days.
The
demonstrated
that
played
protective
role
on
rats,
which
significantly
decreased
levels
blood
glucose
serum
insulin,
up
regulated
expression
IGF1R,
down
IGF1.
In
vitro
,
KGN
cells
were
treated
RES,
AGK2,
respectively.
We
found
high
dose
insulin
(4μg/mL)
inhibited
cell
viability,
level
lactic
acid,
increased
pyruvate,
while
(25μM)
attenuated
growth-inhibitory
effect,
well
acid
pyruvate
after
treatment.
Simultaneously,
crucial
rate-limiting
enzymes
relating
glycolytic
pathways,
LDHA,
HK2,
PKM2.
Furthermore,
AGK2
remarkably
SIRT2,
was
similar
same
negative
effects
processed
insulin.
Meanwhile,
overtly
repaired
glycolysis
process
reversing
together
PKM2,
Conclusion
effectively
restore
pathway
may
contribute
attenuating
ovarian
damage
provide
potential
treatment
