Frontiers in Physiology,
Journal Year:
2023,
Volume and Issue:
14
Published: April 25, 2023
Mitochondria
play
a
key
role
in
both
health
and
disease.
Their
function
is
not
limited
to
energy
production
but
serves
multiple
mechanisms
varying
from
iron
calcium
homeostasis
the
of
hormones
neurotransmitters,
such
as
melatonin.
They
enable
influence
communication
at
all
physical
levels
through
interaction
with
other
organelles,
nucleus,
outside
environment.
The
literature
suggests
crosstalk
between
mitochondria
circadian
clocks,
gut
microbiota,
immune
system.
might
even
be
hub
supporting
integrating
activity
across
these
domains.
Hence,
they
(missing)
link
Mitochondrial
dysfunction
related
metabolic
syndrome,
neuronal
diseases,
cancer,
cardiovascular
infectious
inflammatory
disorders.
In
this
regard,
diseases
Alzheimer’s,
Parkinson’s,
amyotrophic
lateral
sclerosis
(ALS),
chronic
fatigue
syndrome
(CFS),
pain
are
discussed.
This
review
focuses
on
understanding
mitochondrial
action
that
allow
for
maintenance
pathways
toward
dysregulated
mechanisms.
Although
have
allowed
us
adapt
changes
over
course
evolution,
turn,
evolution
has
shaped
mitochondria.
Each
evolution-based
intervention
influences
its
own
way.
use
physiological
stress
triggers
tolerance
stressor,
achieving
adaptability
resistance.
describes
strategies
could
recover
functioning
providing
comprehensive,
root-cause-focused,
integrative
approach
recovering
treating
people
suffering
diseases.
Experimental & Molecular Medicine,
Journal Year:
2022,
Volume and Issue:
54(8), P. 1067 - 1075
Published: Aug. 17, 2022
Intervertebral
disc
degeneration
(IDD)
is
a
common
degenerative
musculoskeletal
disorder
and
recognized
as
major
contributor
to
discogenic
lower
back
pain.
However,
the
molecular
mechanisms
underlying
IDD
remain
unclear,
therapeutic
strategies
for
are
currently
limited.
Oxidative
stress
plays
pivotal
roles
in
pathogenesis
progression
of
many
age-related
diseases
humans,
including
IDD.
Nuclear
factor
E2-related
2
(Nrf2)
master
antioxidant
transcription
that
protects
cells
against
oxidative
damage.
Nrf2
negatively
modulated
by
Kelch-like
ECH-associated
protein
1
(Keap1)
exerts
important
effects
on
progression.
Accumulating
evidence
has
revealed
can
facilitate
downstream
genes
binding
response
elements
(AREs)
promoter
regions,
heme
oxygenase-1
(HO-1),
glutathione
(GSH),
superoxide
dismutase
(SOD),
catalase
(CAT),
NADPH
quinone
dehydrogenase
(NQO1).
The
defense
system
regulates
cell
apoptosis,
senescence,
extracellular
matrix
(ECM)
metabolism,
inflammatory
nucleus
pulposus
(NP),
calcification
cartilaginous
endplates
(EP)
In
this
review,
we
aim
discuss
current
knowledge
systematically.
CNS Neuroscience & Therapeutics,
Journal Year:
2022,
Volume and Issue:
28(12), P. 2268 - 2280
Published: Oct. 2, 2022
Abstract
Aims
Hypoxic–ischemic
brain
injury
(HIBI)
often
results
in
cognitive
impairments.
Herein,
we
investigated
the
roles
of
ferroptosis
HIBI
and
underlying
signaling
pathways.
Methods
Ferrostatin‐1
(Fer‐1)
or
resveratrol
(Res)
treatments
were
administered
intracerebroventricularly
30
min
before
7‐day‐old
rats.
Glutathione
peroxidase
4
(GPx4)
expression,
malondialdehyde
(MDA)
concentration,
iron
content,
mitochondrial
morphology,
expression
silent
information
regulator
factor
2‐related
enzyme
1
(SIRT1)
nuclear
erythroid‐2‐related
2
(Nrf2)
measured
after
HIBI.
Additionally,
weight
ratio
left/right
hemisphere,
Nissl
staining,
Morris
water
maze
test
conducted
to
estimate
damage.
Results
At
24‐h
post‐HIBI,
GPx4
was
decreased,
MDA
concentration
content
increased
hippocampus.
led
atrophy,
atrophy/damage,
resultant
learning
memory
impairments,
which
alleviated
by
Fer‐1‐mediated
inhibition
ferroptosis.
Furthermore,
Res‐mediated
SIRT1
upregulation
Nrf2
thereby
attenuating
ferroptosis,
reducing
improving
abilities.
Conclusion
The
demonstrated
that
during
HIBI,
occurs
via
SIRT1/Nrf2/GPx4
pathway,
suggesting
it
as
a
potential
therapeutic
target
for
inhibiting
ameliorating
HIBI‐induced
Cancers,
Journal Year:
2021,
Volume and Issue:
13(23), P. 6062 - 6062
Published: Dec. 1, 2021
Chronic
inflammation
and
oxidative
stress
are
the
interconnected
pathological
processes,
which
lead
to
cancer
initiation
progression.
The
growing
level
of
inflammatory
damage
was
shown
increase
severity
contribute
tumor
spread.
overproduction
reactive
oxygen
species
(ROS),
is
associated
with
reduced
capacity
endogenous
cell
defense
mechanisms
and/or
metabolic
imbalance,
main
contributor
stress.
An
abnormal
ROS
defined
as
a
predisposing
factor
for
transformation
that
could
trigger
pro-oncogenic
signaling
pathways,
induce
changes
in
gene
expression,
facilitate
accumulation
mutations,
DNA
damage,
genomic
instability.
Additionally,
activation
transcription
factors
caused
by
prolonged
stress,
including
NF-κB,
p53,
HIF1α,
etc.,
leads
expression
several
genes
responsible
inflammation.
resulting
hyperactivation
mediators,
TNFα,
TGF-β,
interleukins,
prostaglandins
can
development
neoplasia.
Pro-inflammatory
cytokines
were
adaptive
reactions
acquisition
resistance
cells
apoptosis,
while
promoting
proliferation,
invasion,
angiogenesis.
Moreover,
chronic
response
excessive
production
free
radicals,
further
aggravate
initiated
reactions.
This
review
summarizes
recent
data
progress
discovery
associate
onset
metastasis.
In
addition,
provides
insights
therapeutic
approaches
natural
substances
will
be
able
simultaneously
inhibit
key
oncological
inflammation-related
targets.
Cell Communication and Signaling,
Journal Year:
2024,
Volume and Issue:
22(1)
Published: May 2, 2024
Abstract
Anticancer
immune
surveillance
and
immunotherapies
trigger
activation
of
cytotoxic
cytokine
signaling,
including
tumor
necrosis
factor-α
(TNF-α)
TNF-related
apoptosis-inducing
ligand
(TRAIL)
pathways.
The
pro-inflammatory
TNF-α
may
be
secreted
by
stromal
cells,
tumor-associated
macrophages,
cancer
indicating
a
prominent
role
in
the
microenvironment
(TME).
However,
tumors
manage
to
adapt,
escape
surveillance,
ultimately
develop
resistance
effects
TNF-α.
mechanisms
which
cells
evade
host
immunity
is
central
topic
current
research.
Resistance
mediated
diverse
molecular
mechanisms,
such
as
mutation
or
downregulation
TNF/TRAIL
receptors,
well
anti-apoptotic
enzymes
transcription
factors.
signaling
also
sphingosine
kinases
(SphK1
SphK2),
are
responsible
for
synthesis
growth-stimulating
phospholipid,
sphingosine-1-phosphate
(S1P).
Multiple
studies
have
demonstrated
crucial
S1P
its
transmembrane
receptors
(S1PR)
both
regulation
inflammatory
responses
progression
cancer.
Considering
that
SphK/S1P/S1PR
axis
mediates
resistance,
this
sphingolipid
pathway
mechanistic
significance
when
considering
immunotherapy-resistant
malignancies.
exact
mechanism
sphingolipids
contribute
evasion
abrogation
TNF-α-induced
apoptosis
remains
largely
unclear.
This
study
reviews
TNF-α-resistance
with
emphasis
on
pro-survival
immunomodulatory
sphingolipids.
Inhibition
SphK/S1P-linked
branch
facilitate
reactivation
pro-apoptotic
TNF
superfamily
effects,
although
SphK/S1P
inhibitors
TME
lymphocyte
trafficking
should
thoroughly
assessed
future
studies.
Heliyon,
Journal Year:
2024,
Volume and Issue:
10(5), P. e27028 - e27028
Published: Feb. 28, 2024
The
therapeutic
mechanism
of
oleanolic
acid
(OA)
in
breast
cancer
has
been
widely
reported,
but
little
known
about
the
combined
effects
transcriptome
and
gut
microbiome.
In
this
study,
phenotypic
effect
on
mice
was
tested
at
end
administration
cycle,
RNA
sequencing
murine
tumor
tissue
16S-rRNA
intestinal
contents
were
conducted
to
analyze
gene
expression
profiles
microbial
diversity
between
control
group
OA
treated
using
4T1-induced
model.
As
a
result,
it
confirmed
that
would
play
significant
inhibitory
development
tumors
mice.
Based
integrative
analysis
transcriptomic
metagenomic
data,
found
abundance
Lactobacillus
flora
significantly
increased
group.
Moreover,
up-regulation
Il10
had
inhibiting
progression,
which
played
role
through
cytokine-cytokine
receptor
interaction
pathway.
