Authorea (Authorea),
Год журнала:
2023,
Номер
unknown
Опубликована: Апрель 7, 2023
The
epigenetic
factor
bromodomain
and
extra-terminal
domain
(BET)
proteins
have
multiple
functions
in
regulating
cell
proliferation,
differentiation
inflammation
via
binding
to
acetylated
lysines
on
histones.
JQ1
I-BET726,
new
inhibitors
of
BET
proteins,
potential
therapeutic
benefit
for
autoimmune
diseases
(AD).
In
this
study,
we
explored
the
effects
I-BET726
innate
adaptive
immunity
experimental
encephalomyelitis
(EAE)
model
investigate
mechanism
AD.
LPS-induced
were
investigated
immune
cells
dendritic
(DCs),
macrophages,
DC-dependent
T
cells.
Different
pro-inflammatory
cytokines
assessed
real-time
PCR,
flow
cytometry,
Elispot.
Moreover,
EAE
animals
further
investigated,
including
alleviating
clinical
symptoms
inhibiting
demyelination
spinal
cords
PCR
immunohistochemical
staining.
efficiently
inhibited
LPS-increased
TNF-α
IL-6
expression
bone
marrow-derived
DC
macrophage
Raw264.7
They
also
suppressed
by
down-regulating
CD80/CD86
IL-12/GM-CSF
expressions,
priming.
they
effectively
involved
inflammatory
changes
model,
infiltration
demyelination.
Most
importantly,
attenuated
deterioration
mice.
Our
results
indicate
that
possess
benefits
adjusting
response,
indicating
might
be
molecular
targets
disease
therapy.
Basic & Clinical Pharmacology & Toxicology,
Год журнала:
2024,
Номер
134(5), С. 574 - 601
Опубликована: Март 13, 2024
Abstract
Studies
have
demonstrated
the
neuroprotective
effect
of
cannabidiol
(CBD)
and
other
Cannabis
sativa
L.
derivatives
on
diseases
central
nervous
system
caused
by
their
direct
or
indirect
interaction
with
endocannabinoid
system‐related
receptors
molecular
targets,
such
as
5‐HT
1A
receptor,
which
is
a
potential
pharmacological
target
CBD.
Interestingly,
CBD
binding
receptor
may
be
suitable
for
treatment
epilepsies,
parkinsonian
syndromes
amyotrophic
lateral
sclerosis,
in
serotonergic
plays
key
role.
The
aim
this
review
was
to
provide
an
overview
cannabinoid
effects
neurological
disorders,
epilepsy,
multiple
sclerosis
Parkinson's
diseases,
discuss
possible
mechanism
action,
highlighting
interactions
targets
phytocannabinoids.
has
been
shown
significant
therapeutic
epilepsy
disease,
while
nabiximols
contribute
reduction
spasticity
are
frequent
option
sclerosis.
Although
there
theories
cannabinoids
substantially
greater
progress
search
strong
scientific
evidence
effectiveness
needed.
Frontiers in Genetics,
Год журнала:
2023,
Номер
14
Опубликована: Янв. 30, 2023
From
the
perspective
of
precision
medicine,
challenge
for
future
is
to
improve
accuracy
diagnosis,
prognosis,
and
prediction
therapeutic
responses
through
identification
biomarkers.
In
this
framework,
omics
sciences
(genomics,
transcriptomics,
proteomics,
metabolomics)
their
combined
use
represent
innovative
approaches
exploration
complexity
heterogeneity
multiple
sclerosis
(MS).
This
review
examines
evidence
currently
available
on
application
MS,
analyses
methods,
limitations,
samples
used,
characteristics,
with
a
particular
focus
biomarkers
associated
disease
state,
exposure
disease-modifying
treatments
(DMTs),
drug
efficacies
safety
profiles.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(16), С. 8921 - 8921
Опубликована: Авг. 16, 2024
According
to
various
research,
the
risk
of
multiple
sclerosis
(MS)
is
strongly
influenced
by
genetic
variations.
Population,
familial,
and
molecular
studies
provide
strong
empirical
support
for
a
polygenic
pattern
inheritance,
mainly
due
relatively
common
allelic
variants
in
general
population.
The
strongest
MS
susceptibility
locus,
which
was
unmistakably
identified
tested
populations,
major
histocompatibility
complex
on
chromosome
6p21.3.
However,
effect
given
predisposing
variant
remains
modest,
so
there
possibility
that
gene-gene
and/or
gene-environment
interactions
could
significantly
increase
contribution
specific
overall
risk.
Furthermore,
as
known,
genes
can
be
subject
epigenetic
modifications,
greatly
complexity
heritability.
Investigating
environmental
factors
new
opportunities
basis
MS,
shows
complicated
pathogenesis.
Although
changes
only
began
last
decade,
growing
body
literature
suggests
these
may
involved
development
MS.
Here,
we
summarize
recent
regarding
related
initiation
progression.
discuss
how
current
address
important
clinical
questions
future
used
practice.
Multiple Sclerosis and Related Disorders,
Год журнала:
2023,
Номер
79, С. 104991 - 104991
Опубликована: Сен. 9, 2023
A
compelling
body
of
evidence
implicates
cigarette
smoking
and
lung
inflammation
in
Multiple
Sclerosis
(MS)
susceptibility
progression.
Previous
studies
have
reported
epigenetic
age
(DNAm
age)
acceleration
blood
immune
cells
glial
people
with
MS
(pwMS)
compared
to
healthy
controls
(HC).We
aimed
examine
biological
ageing
the
context
smoking.We
analyzed
residuals
bronchoalveolar
lavage
(BAL)
cells,
constituted
mainly
alveolar
macrophages,
from
17
pwMS
22
HC
relation
using
eight
DNA
methylation-based
clocks,
namely
AltumAge,
Horvath,
GrimAge,
PhenoAge,
Zhang,
SkinBlood,
Hannum,
Monocyte
clock
as
well
two
RNA-based
which
capture
different
aspects
ageing.After
adjustment
for
covariates,
five
clocks
showed
significant
differences
between
groups.
Four
them,
Horvath
(Padj
=
0.028),
GrimAge
4.28
×
10-7),
SkinBlood
0.001)
Zhang
0.02),
uncovered
sole
effect
on
estimates,
irrespective
clinical
group.
The
a
negative
impact
while
detected
smoking-associated
BAL
cells.
On
contrary,
AltumAge
revealed
indicated
that,
absence
smoking,
were
epigenetically
5.4
years
older
0.028).
Smoking
further
affected
specifically
non-smoking
exhibited
10.2-year
smokers
0.0049).
Of
note,
blood-derived
monocytes
did
not
show
any
MS-specific
or
smoking-related
differences.
difference
non-smokers
was
attributable
differential
methylation
114
AltumAge-CpGs
<
0.05)
affecting
genes
involved
innate
processes
such
cytokine
production,
defense
response
cell
motility.
These
changes
functionally
translated
into
transcriptional
non-smokers.BAL
display
inflammation-related
smoking-dependent
associated
captured
by
clock.
Future
examining
potential
confounders,
distribution
distinct
myeloid
types
control
individuals
may
clarify
varying
performance
DNAm
estimations
among
clocks.
Frontiers in Neurology,
Год журнала:
2023,
Номер
13
Опубликована: Янв. 9, 2023
Multiple
sclerosis
(MS)
is
a
chronic
inflammatory
disease
of
the
central
nervous
system
(CNS)
with
profound
neurodegenerative
component
early
in
pathogenesis.
Age
factor
well-described
effect
on
primary
phenotype,
namely,
relapsing-remitting
vs.
progressive
disease.
Moreover,
aging
prominent
contributing
to
transition
from
MS
(RRMS)
secondary
However,
sex
also
seems
to,
at
least
part,
dictate
phenotype
and
evolution,
as
evidenced
humans
animal
models
Sex-specific
gene
expression
profiles
have
recently
elucidated
an
association
differential
immunological
signatures
context
experimental
This
review
aims
summarize
current
knowledge
stemming
autoimmune
encephalomyelitis
(EAE)
regarding
effects
sex,
either
independently
or
combined
aging,
relevance
immune
CNS.
