PLoS ONE,
Год журнала:
2020,
Номер
15(10), С. e0240149 - e0240149
Опубликована: Окт. 2, 2020
From
January
2020,
COVID-19
is
spreading
around
the
world
producing
serious
respiratory
symptoms
in
infected
patients
that
some
cases
can
be
complicated
by
severe
acute
syndrome,
sepsis
and
septic
shock,
multiorgan
failure,
including
kidney
injury
cardiac
injury.
Cost
time
efficient
approaches
to
reduce
burthen
of
disease
are
needed.
To
find
potential
treatments
among
whole
arsenal
existing
drugs,
we
combined
system
biology
artificial
intelligence-based
approaches.
The
drug
combination
pirfenidone
melatonin
has
been
identified
as
a
candidate
treatment
may
contribute
virus
infection.
Starting
from
different
targets
effect
drugs
converges
on
human
proteins
with
known
role
SARS-CoV-2
infection
cycle.
Simultaneously,
GUILDify
v2.0
web
server
used
an
alternative
method
corroborate
against
SARS-CoV-2.
We
have
also
predicted
therapeutic
over
associated
pathology,
thus
tackling
at
same
two
important
issues
COVID-19.
These
evidences,
together
fact
medical
point
view
both
considered
safe
current
standard
care
for
makes
this
very
attractive
treating
stage
II,
non-severe
symptomatic
presence
those
who
risk
developing
pulmonary
complications.
Cells,
Год журнала:
2021,
Номер
10(7), С. 1639 - 1639
Опубликована: Июнь 30, 2021
Ischemic
stroke
is
the
second
cause
of
mortality
and
first
long-term
disability
constituting
a
serious
socioeconomic
burden
worldwide.
Approved
treatments
include
thrombectomy
rtPA
intravenous
administration,
which,
despite
their
efficacy
in
some
cases,
are
not
suitable
for
great
proportion
patients.
Glial
cell-related
therapies
progressively
overcoming
inefficient
neuron-centered
approaches
preclinical
phase.
Exploiting
ability
microglia
to
naturally
switch
between
detrimental
protective
phenotypes
represents
promising
therapeutic
treatment,
similar
way
what
happens
with
astrocytes.
However,
duality
present
many
roles
these
cells
upon
ischemia
poses
notorious
difficulty
disentangling
precise
pathways
target.
Still,
promoting
M2/A2
microglia/astrocyte
inhibiting
M1/A1
neurotoxic
profiles
globally
rendering
results
different
vivo
models
stroke.
On
other
hand,
described
oligodendrogenesis
after
brain
seems
be
strictly
beneficial,
although
less
studied
players
paradigm
negative
effects
could
oligodendrocytes
next
years.
Here,
we
review
recent
advances
understanding
role
mentioned
glial
cell
types
main
pathological
events
ischemic
stroke,
including
inflammation,
blood
barrier
integrity,
excitotoxicity,
reactive
oxygen
species
management,
metabolic
support,
neurogenesis,
among
others,
special
attention
tested
approaches.
Frontiers in Neurology,
Год журнала:
2021,
Номер
12
Опубликована: Июль 1, 2021
Stroke
is
one
of
the
most
common
causes
death
worldwide.
The
subsequent
development
neuroinflammation
and
brain
edema
dramatically
increases
risks
associated
with
stroke,
leading
to
a
substantial
increase
in
mortality.
Although
considerable
progress
has
been
made
improving
cerebral
perfusion
acute
phase
effective
treatment
options
for
subacute
chronic
phases
infarction
are
limited.
Microglia,
innate
immune
cells
central
nervous
system
(CNS),
can
be
activated
polarized
take
on
different
phenotypes
response
stimulations
including
pro-inflammatory
anti-inflammatory
phenotypes,
which
affect
prognosis
stroke.
Therefore,
investigation
activation
polarizing
mechanisms
microglia
plays
critical
role
treating
aim
this
article
was
investigate
significance
microglial
phenotype
regulation
stroke
by
summarizing
activation,
mechanisms,
general
characteristics.
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(15), С. 8296 - 8296
Опубликована: Авг. 2, 2021
Melatonin
interacts
in
multiple
ways
with
microglia,
both
directly
and,
via
routes
of
crosstalk
astrocytes
and
neurons,
indirectly.
These
effects
melatonin
are
relevance
terms
antioxidative
protection,
not
only
concerning
free-radical
detoxification,
but
also
prevention
processes
that
cause,
promote,
or
propagate
oxidative
stress
neurodegeneration,
such
as
overexcitation,
toxicological
insults,
viral
bacterial
infections,
sterile
inflammation
different
grades.
The
immunological
interplay
the
CNS,
microglia
playing
a
central
role,
is
high
complexity
includes
signaling
toward
endothelial
cells
other
leukocytes
by
cytokines,
chemokines,
nitric
oxide,
eikosanoids.
interferes
these
steps.
In
addition
to
canonical
signal
transduction
MT1
MT2
receptors,
secondary
tertiary
has
be
considered,
e.g.,
upregulation
sirtuins
modulation
pro-
anti-inflammatory
microRNAs.
Many
details
macrophage
functionality
obviously
applicable
microglial
cells.
Of
particular
interest
polarization
M2
subtypes
instead
M1,
i.e.,
favor
being
at
expense
proinflammatory
activities,
which
well-documented
macrophages
applies
microglia.
ASN NEURO,
Год журнала:
2021,
Номер
13, С. 175909142110181 - 175909142110181
Опубликована: Янв. 1, 2021
Cerebrovascular
diseases
are
pathological
conditions
involving
impaired
blood
flow
in
the
brain,
primarily
including
ischaemic
stroke,
intracranial
haemorrhage,
and
subarachnoid
haemorrhage.
The
nucleotide-binding
oligomerisation
(NOD)
domain-like
receptor
(NLR)
family
pyrin
domain
(PYD)-containing
3
(NLRP3)
inflammasome
is
a
protein
complex
vital
component
of
immune
system.
Emerging
evidence
has
indicated
that
NLRP3
plays
an
important
role
cerebrovascular
diseases.
function
pathogenesis
remains
interesting
field
research.
In
this
review,
we
first
summarised
mechanism
aggravating
atherosclerosis
Second,
outlined
signalling
pathways
through
which
participates
or
mitigating
Reactive
oxygen
species
(ROS)/nuclear
factor
kappa-light-chain-enhancer
activated
B
cells
(NF-κB),
ROS/thioredoxin-interacting
(TXNIP)
purinergic
receptor-7
(P2X7R)
can
activate
inflammasome;
activation
aggravate
by
mediating
apoptosis
pyroptosis.
Autophagy/mitochondrial
autophagy,
nuclear
E2-related
factor-2
(Nrf2),
interferon
(IFN)-β,
sirtuin
(SIRT),
phosphoinositide
3-kinase
(PI3K)/protein
kinase
(AKT)
reportedly
alleviate
inhibiting
activation.
Finally,
explored
specific
inhibitors
based
on
two-step
inflammasome,
be
developed
as
new
drugs
to
treat
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(2), С. 907 - 907
Опубликована: Янв. 14, 2022
Cerebral
circulation
delivers
the
blood
flow
to
brain
through
a
dedicated
network
of
sanguine
vessels.
A
healthy
human
can
regulate
cerebral
(CBF)
according
any
physiological
or
pathological
challenges.
The
is
protected
by
its
self-regulatory
mechanisms,
which
are
dependent
on
neuronal
and
support
cellular
populations,
including
endothelial
ones,
as
well
metabolic,
even
myogenic
factors.Accumulating
data
suggest
that
"non-pharmacological"
approaches
might
provide
new
opportunities
for
stroke
therapy,
such
electro-/acupuncture,
hyperbaric
oxygen
hypothermia/cooling,
photobiomodulation,
therapeutic
gases,
transcranial
direct
current
stimulations,
magnetic
stimulations.
We
reviewed
recent
mechanisms
clinical
implications
these
non-pharmaceutical
treatments.To
present
state-of-the-art
currently
available
non-invasive,
non-pharmacological-related
interventions
in
acute
ischemic
stroke,
we
accomplished
this
synthetic
systematic
literature
review
based
Preferred
Reporting
Items
Systematic
Principles
Reviews
Meta-Analyses
(PRISMA).The
initial
number
obtained
articles
was
313.
After
fulfilling
five
steps
filtering/selection
methodology,
54
fully
eligible
papers
were
selected
review.
enhanced
our
documentation
with
other
bibliographic
resources
connected
subject,
identified
within
non-standardized
search,
fill
knowledge
gaps.
Fifteen
trials
also
identified.Non-invasive,
non-pharmacological
therapeutic/rehabilitative
mainly
holistic
therapies.
Therefore,
most
them
not
yet
routinely
used
practice,
despite
some
possible
beneficial
effects,
have
be
supplementarily
proven
more
related
studies.
Moreover,
few
already
completed
do
final
results.This
synthesizes
findings
interventions,
described
non-invasive
non-pharmacological.
Antioxidants and Redox Signaling,
Год журнала:
2022,
Номер
37(10-12), С. 704 - 725
Опубликована: Янв. 12, 2022
Melatonin
has
not
only
to
be
seen
as
a
regulator
of
circadian
clocks.
In
addition
its
chronobiotic
functions,
it
displays
other
actions,
especially
in
cell
protection.
This
includes
antioxidant,
anti-inflammatory,
and
mitochondria-protecting
effects.
Although
protection
is
also
modulated
by
the
system,
respective
actions
melatonin
can
distinguished
differ
with
regard
dose
requirements
therapeutic
settings.
It
aim
this
article
outline
these
differences
terms
function,
signaling,
dosage.
Focus
been
placed
on
both
nexus
dissecting
properties
between
noncircadian
mechanisms.
consider
details
beyond
classic
view
melatonin's
role,
such
widespread
synthesis
extrapineal
tissues,
formation
mitochondria,
effects
mitochondrial
permeability
transition
pore,
secondary
for
example,
via
upregulation
sirtuins
regulating
noncoding
RNAs,
microRNAs.
The
relevance
findings,
connections
functions
shed
light
regulation
inflammation,
including
macrophage/microglia
polarization,
damage-associated
molecular
patterns,
avoidance
cytokine
storms,
numerous
consequences
antioxidative
protection,
that
is,
aspects
high
actuality
deadly
viral
bacterial
diseases.
Antioxid.
Redox
Signal.
37,
704–725.
Pharmacological Research,
Год журнала:
2023,
Номер
190, С. 106714 - 106714
Опубликована: Фев. 28, 2023
Ischemic
stroke
is
closely
associated
with
gut
microbiota
dysbiosis
and
intestinal
barrier
dysfunction.
Prebiotic
intervention
could
modulate
the
microbiota,
thus
considered
a
practical
strategy
for
neurological
disorders.
Puerariae
Lobatae
Radix-resistant
starch
(PLR-RS)
potential
novel
prebiotic;
however,
its
role
in
ischemic
remains
unknown.
This
study
aimed
to
clarify
effects
underlying
mechanisms
of
PLR-RS
stroke.
Middle
cerebral
artery
occlusion
surgery
was
performed
establish
model
rats.
After
gavage
14
days,
attenuated
stroke-induced
brain
impairment
Moreover,
rescued
enriched
Akkermansia
Bifidobacterium.
We
transplanted
fecal
from
PLR-RS-treated
rats
into
found
that
colon
damage
were
also
ameliorated.
Notably,
we
promoted
produce
higher
level
melatonin.
Intriguingly,
exogenous
melatonin
injury.
In
particular,
via
positive
co-occurrence
pattern
microecology.
Specific
beneficial
bacteria
served
as
leaders
or
keystone
species
homeostasis,
such
Enterobacter,
Bacteroidales_S24–7_group,
Prevotella_9,
Ruminococcaceae
Lachnospiraceae.
Thus,
this
new
mechanism
explain
therapeutic
efficacy
on
at
least
partly
attributed
microbiota-derived
summary,
improving
microecology
by
prebiotic
supplementation
be
effective
therapies
Current Neuropharmacology,
Год журнала:
2023,
Номер
21(12), С. 2465 - 2480
Опубликована: Июль 19, 2023
Abstract:
Ischemic
stroke
is
the
predominant
cause
of
severe
morbidity
and
mortality
worldwide.
Post-stroke
neuroinflammation
has
recently
received
increasing
attention
with
aim
providing
a
new
effective
treatment
strategy
for
ischemic
stroke.
Microglia
astrocytes
are
major
components
innate
immune
system
central
nervous
system.
They
can
be
involved
in
all
phases
stroke,
from
early
stage,
contributing
to
first
wave
neuronal
cell
death,
late
stage
involving
phagocytosis
repair.
In
vicious
cycle
exists
between
activation
microglia
(through
astrocytic
connexin
43
hemichannels),
aggravating
neuroinflammatory
injury
post-stroke.
However,
repeatedly
activated
induce
formation
glial
scars
by
triggering
reactive
astrogliosis
peri-infarct
regions,
which
may
limit
movement
reverse
restrict
diffusion
inflammation
healthy
brain
tissues,
alleviating
poststroke.
this
review,
we
elucidated
various
roles
summarized
their
relationship
neuroinflammation.
We
also
examined
how
influence
each
other
at
different
stages
Several
potential
therapeutic
approaches
targeting
have
been
reviewed.
Understanding
details
astrocytemicroglia
interaction
processes
will
contribute
better
understanding
mechanisms
underlying
identification
interventions.