Neural Regeneration Research,
Год журнала:
2022,
Номер
18(1), С. 141 - 141
Опубликована: Май 6, 2022
Neuroinflammation
and
the
NACHT,
LRR,
PYD
domains-containing
protein
3
inflammasome
play
crucial
roles
in
secondary
tissue
damage
following
an
initial
insult
patients
with
traumatic
brain
injury
(TBI).
Maraviroc,
a
C-C
chemokine
receptor
type
5
antagonist,
has
been
viewed
as
new
therapeutic
strategy
for
many
neuroinflammatory
diseases.
We
studied
effect
of
maraviroc
on
TBI-induced
neuroinflammation.
A
moderate-TBI
mouse
model
was
subjected
to
controlled
cortical
impact
device.
Maraviroc
or
vehicle
injected
intraperitoneally
1
hour
after
TBI
then
once
per
day
consecutive
days.
Western
blot,
immunohistochemistry,
TUNEL
(terminal
deoxynucleotidyl
transferase-mediated
dUTP
nick-end
labeling)
analyses
were
performed
evaluate
molecular
mechanisms
at
days
post-TBI.
Our
results
suggest
that
administration
reduced
activation,
modulated
microglial
polarization
from
M1
M2,
decreased
neutrophil
macrophage
infiltration,
inhibited
release
inflammatory
factors
TBI.
Moreover,
treatment
activation
neurotoxic
reactive
astrocytes,
which,
turn,
exacerbated
neuronal
cell
death.
Additionally,
we
confirmed
neuroprotective
using
modified
neurological
severity
score,
rotarod
test,
Morris
water
maze
lesion
volume
measurements.
In
summary,
our
findings
indicate
might
be
desirable
pharmacotherapeutic
TBI,
promising
target
improve
recovery
Signal Transduction and Targeted Therapy,
Год журнала:
2021,
Номер
6(1)
Опубликована: Март 29, 2021
Abstract
Currently,
pyroptosis
has
received
more
and
attention
because
of
its
association
with
innate
immunity
disease.
The
research
scope
expanded
the
discovery
gasdermin
family.
A
great
deal
evidence
shows
that
can
affect
development
tumors.
relationship
between
tumors
is
diverse
in
different
tissues
genetic
backgrounds.
In
this
review,
we
provide
basic
knowledge
pyroptosis,
explain
tumors,
focus
on
significance
tumor
treatment.
addition,
further
summarize
possibility
as
a
potential
treatment
strategy
describe
side
effects
radiotherapy
chemotherapy
caused
by
pyroptosis.
brief,
double-edged
sword
for
rational
use
dual
effect
will
help
us
explore
formation
ideas
patients
to
develop
new
drugs
based
Pharmacological Reviews,
Год журнала:
2021,
Номер
73(3), С. 924 - 967
Опубликована: Июнь 4, 2021
The
endothelium,
a
cellular
monolayer
lining
the
blood
vessel
wall,
plays
critical
role
in
maintaining
multiorgan
health
and
homeostasis.
Endothelial
functions
include
dynamic
maintenance
of
vascular
tone,
angiogenesis,
hemostasis,
provision
an
antioxidant,
anti-inflammatory,
antithrombotic
interface.
Dysfunction
endothelium
presents
with
impaired
endothelium-dependent
vasodilation,
heightened
oxidative
stress,
chronic
inflammation,
leukocyte
adhesion
hyperpermeability,
endothelial
cell
senescence.
Recent
studies
have
implicated
altered
metabolism
endothelial-to-mesenchymal
transition
as
new
features
dysfunction.
dysfunction
is
regarded
hallmark
many
diverse
human
panvascular
diseases,
including
atherosclerosis,
hypertension,
diabetes.
has
also
been
severe
coronavirus
disease
2019.
Many
clinically
used
pharmacotherapies,
ranging
from
traditional
lipid-lowering
drugs,
antihypertensive
antidiabetic
drugs
to
proprotein
convertase
subtilisin/kexin
type
9
inhibitors
interleukin
1β
monoclonal
antibodies,
counter
part
their
clinical
benefits.
regulation
by
noncoding
RNAs
provided
novel
insights
into
these
newly
described
regulators
dysfunction,
thus
yielding
potential
therapeutic
approaches.
Altogether,
better
understanding
versatile
(dys)functions
cells
will
not
only
deepen
our
comprehension
diseases
but
accelerate
effective
drug
discovery.
In
this
review,
we
provide
timely
overview
multiple
layers
function,
describe
consequences
mechanisms
identify
pathways
targeted
therapies.
Significance
Statement
was
initially
considered
be
semipermeable
biomechanical
barrier
gatekeeper
health.
recent
decades,
deepened
biological
led
its
recognition
ubiquitous
tissue
regulating
behavior,
innate
immunity,
cell-cell
interactions,
wall.
cardiovascular,
metabolic,
emerging
infectious
diseases.
Pharmacotherapies
targeting
for
treatment
cardiovascular
other
Theranostics,
Год журнала:
2021,
Номер
11(18), С. 8813 - 8835
Опубликована: Янв. 1, 2021
In
recent
decades,
chemotherapies
targeting
apoptosis
have
emerged
and
demonstrated
remarkable
achievements.
However,
emerging
evidence
has
shown
that
chemoresistance
is
mediated
by
impairing
or
bypassing
apoptotic
cell
death.
Several
novel
types
of
programmed
death,
such
as
ferroptosis,
necroptosis,
pyroptosis,
recently
been
reported
to
play
significant
roles
in
the
modulation
cancer
progression
are
considered
a
promising
strategy
for
treatment.
Thus,
switch
between
pyroptosis
also
discussed.
Cancer
immunotherapy
gained
increasing
attention
due
breakthroughs
immune
checkpoint
inhibitors;
moreover,
highly
correlated
with
immunity
tumor
microenvironment.
Compared
necroptosis
primary
mechanism
host
defense
crucial
bridging
innate
adaptive
immunity.
Furthermore,
exerts
benefits
on
immunotherapies,
including
inhibitors
(ICIs)
chimeric
antigen
receptor
T-cell
therapy
(CAR-T).
Hence,
this
review,
we
elucidate
role
We
summarize
potential
small
molecules
nanomaterials
target
pyroptotic
death
mechanisms
their
therapeutic
effects
cancer.
Molecular Medicine,
Год журнала:
2020,
Номер
26(1)
Опубликована: Май 7, 2020
Abstract
Background
The
2019
novel
coronavirus
disease
(COVID-19)
causes
for
unresolved
reasons
acute
respiratory
distress
syndrome
in
vulnerable
individuals.
There
is
a
need
to
identify
key
pathogenic
molecules
COVID-19-associated
inflammation
attainable
target
with
existing
therapeutic
compounds.
endogenous
damage-associated
molecular
pattern
(DAMP)
molecule
HMGB1
initiates
via
two
separate
pathways.
Disulfide-HMGB1
triggers
TLR4
receptors
generating
pro-inflammatory
cytokine
release.
Extracellular
HMGB1,
released
from
dying
cells
or
secreted
by
activated
innate
immunity
cells,
forms
complexes
extracellular
DNA,
RNA
and
other
DAMP
pathogen-associated
after
lytic
cell
death.
These
are
endocytosed
RAGE,
constitutively
expressed
at
high
levels
the
lungs
only,
transported
endolysosomal
system,
which
disrupted
concentrations.
Danger
thus
get
access
cytosolic
proinflammatory
instigating
inflammasome
activation.
It
conceivable
that
SARS-CoV-2
may
reach
cellular
cytosol
HMGB1-assisted
transfer
combined
lysosome
leakage.
generally
exists
vivo
bound
molecules,
including
PAMPs
DAMPs
.
plausible
these
specifically
removed
revealed
40%
reduction
of
plasma
arterial
versus
venous
blood.
Abundant
pulmonary
RAGE
expression
enables
endocytosis
danger
be
destroyed
lysosomes
physiological
levels,
but
causing
detrimental
activation
levels.
Stress
induces
apoptosis
endothelial
females
necrosis
males.
Conclusion
Based
on
observations
we
propose
considered
as
COVID-19.
Pharmacological Research,
Год журнала:
2021,
Номер
170, С. 105748 - 105748
Опубликована: Июль 1, 2021
Pyroptosis,
a
type
of
programmed
cell
death
(PCD),
is
characterized
by
swelling
with
bubbles,
and
the
release
inflammatory
cytokines.
Cucurbitacin
B
(CuB),
extracted
from
muskmelon
pedicel,
natural
bioactive
product
that
could
effectively
exert
anti-tumor
activities
in
lung
cancer.
However,
exact
molecular
mechanisms
direct
targets
CuB
non-small
cancer
(NSCLC)
remain
to
be
discovered.
Here,
we
firstly
found
exerted
an
effect
via
pyroptosis
NSCLC
cells
mice
models.
Next,
based
on
docking
cellular
thermal
shift
assay
(CETSA),
identified
directly
bound
Toll-like
receptor
4
(TLR4)
activate
NLRP3
inflammasome,
which
further
caused
separation
N-
C-terminals
Gasdermin
D
(GSDMD)
execute
pyroptosis.
Moreover,
enhanced
mitochondrial
reactive
oxygen
species
(ROS),
membrane
protein
Tom20
accumulation,
cytosolic
calcium
(Ca
Cardiovascular Research,
Год журнала:
2021,
Номер
118(2), С. 372 - 385
Опубликована: Янв. 16, 2021
Abstract
Nucleotide-binding
oligomerization
domain-like
receptor
family
pyrin
domain
containing
3
(NLRP3)
is
an
intracellular
innate
immune
that
recognizes
a
diverse
range
of
stimuli
derived
from
pathogens,
damaged
or
dead
cells,
and
irritants.
NLRP3
activation
causes
the
assembly
large
multiprotein
complex
termed
inflammasome,
leads
to
secretion
bioactive
interleukin
(IL)-1β
IL-18
as
well
induction
inflammatory
cell
death
pyroptosis.
Accumulating
evidence
indicates
inflammasome
plays
key
role
in
pathogenesis
sterile
diseases,
including
atherosclerosis
other
vascular
diseases.
Indeed,
results
Canakinumab
Anti-inflammatory
Thrombosis
Outcome
Study
trial
demonstrated
IL-1β-mediated
inflammation
important
atherothrombotic
events
suggested
driver
atherosclerosis.
In
this
review,
we
will
summarize
current
state
knowledge
regarding
particular
atherosclerosis,
injury,
aortic
aneurysm,
Kawasaki
disease
vasculitis,
discuss
therapeutic
target
for
these
disorders.
