medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Июль 10, 2022
ABSTRACT
Background
There
are
90
genetic
risk
variants
for
Parkinson’s
disease
(PD)
but
currently
only
five
nominated
loci
PD
progression.
The
biology
of
progression
is
likely
to
be
central
importance
in
defining
mechanisms
that
can
used
develop
new
treatments.
Methods
We
studied
6,766
patients,
over
15,340
visits
with
a
mean
follow-up
between
4.2
and
15.7
years
carried
out
genome
wide
survival
study
time
motor
endpoint,
defined
by
reaching
Hoehn
Yahr
stage
3
or
greater,
death
(mortality).
Findings
was
robust
effect
the
APOE
ε4
allele
on
mortality
PD.
identified
three
novel
progression,
genes
based
physical
proximity
and/or
expression
quantitative
trait
data.
One
locus
within
TBXAS1
gene
encoding
thromboxane
A
synthase
1
associated
(HR
=
2.04
[95%
CI
1.63
2.56],
p-value
7.71
x
10
-10
).
Another
near
SYT10
synaptotagmin
just
above
genome-wide
significance
(HR=1.36
1.21
1.51],
p-value=5.31×10
-8
also
report
4
independent
progression:
top
MORN1
(HR=2.76
1.97
3.87],
p-value=3.1×10
-9
),
second
most
significant
ASNS
,
third
PDE5A
fourth
XPO1
.
have
causal
position,
however
we
discuss
other
possible
loci,
colocalization
analysis,
tagging
rare
variants.
Only
non-Gaucher
causing
GBA1
variant
E326K,
known
variants,
Interpretation
six
mortality.
Further
work
needed
understand
links
these
genomic
underlying
biology.
However,
synthesis,
vesicular
peptidergic
neurotransmitter
release,
phosphodiesterase
inhibition
may
represent
candidates
modification
Funding
sources
UK,
Aligning
Science
Across
through
Michael
J
Fox
Foundation
Research,
Southern
Eastern
Norway
Regional
Health
Authority
Chinese Medical Journal - Pulmonary and Critical Care Medicine,
Год журнала:
2023,
Номер
1(2), С. 77 - 83
Опубликована: Янв. 23, 2023
The
pandemic
of
coronavirus
disease
2019
(COVID‑19),
caused
by
a
novel
severe
acute
respiratory
syndrome
(SARS)
2
(SARS-CoV-2),
has
an
enormous
impact
on
the
global
healthcare.
SARS-CoV-2
infection
primarily
targets
system.
Although
most
individuals
testing
positive
for
present
mild
or
no
upper
tract
symptoms,
patients
with
COVID-19
can
rapidly
progress
to
distress
(ARDS).
ARDS-related
pulmonary
fibrosis
is
recognized
sequelae
COVID-19.
Whether
post-COVID-19
lung
resolvable,
persistent,
even
becomes
progressive
as
seen
in
human
idiopathic
(IPF)
currently
not
known
and
remains
matter
debate.
With
emergence
effective
vaccines
treatments
against
COVID-19,
it
now
important
build
our
understanding
long-term
sequela
infection,
identify
survivors
who
are
at
risk
developing
chronic
fibrosis,
develop
anti-fibrotic
therapies.
current
review
aims
summarize
pathogenesis
system
highlights
potential
mechanisms.
It
envisions
fibrotic
complication
survivors,
particular
aged
population.
early
identification
development
therapies
discussed.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(15), С. 12490 - 12490
Опубликована: Авг. 6, 2023
Lung
fibrosis
is
a
progressive
fatal
disease
in
which
deregulated
wound
healing
of
lung
epithelial
cells
drives
fibrotic
changes.
Persistent
injury
due
to
oxidative
stress
and
chronic
inflammation
are
central
features
fibrosis.
Chronic
cigarette
smoking
causes
major
risk
factor
for
The
objective
this
manuscript
develop
an
adverse
outcome
pathway
(AOP)
that
serves
as
framework
investigation
the
mechanisms
caused
by
inhaled
toxicants,
including
smoke.
Based
on
weight
evidence,
proposed
molecular
initiating
event
(MIE)
leads
increased
secretion
proinflammatory
profibrotic
mediators
(key
1
(KE1)).
At
cellular
level,
these
signals
induce
recruitment
inflammatory
(KE2),
turn,
increase
fibroblast
proliferation
myofibroblast
differentiation
(KE3).
tissue
extracellular
matrix
deposition
(KE4)
subsequently
culminates
fibrosis,
outcome.
We
have
also
defined
new
KE
relationship
between
MIE
KE3.
This
AOP
provides
mechanistic
platform
understand
evaluate
how
persistent
from
may
into
International Journal of Environmental Research and Public Health,
Год журнала:
2024,
Номер
21(4), С. 473 - 473
Опубликована: Апрель 12, 2024
Introduction:
Long
COVID
(LC)
is
a
global
public
health
crisis
affecting
more
than
70
million
people.
There
emerging
evidence
of
different
pathophysiological
mechanisms
driving
the
wide
array
symptoms
in
LC.
Understanding
relationships
between
and
helps
guiding
clinical
management
identifying
potential
treatment
targets.
Methods:
This
was
mixed-methods
systematic
review
with
two
stages:
Stage
one
(Review
1)
included
only
existing
reviews
(meta-review)
2)
all
primary
studies.
The
search
strategy
involved
Medline,
Embase,
Emcare,
CINAHL
databases
to
identify
studies
that
described
statistical
analysis
and/or
discussion
plausible
causal
symptoms.
Only
control
arm
for
comparison
were
included.
Studies
assessed
quality
using
National
Heart,
Lung,
Blood
Institute
assessment
tools.
Results:
19
Review
1
46
2.
Overall,
reporting
across
this
second
moderate
poor.
strong
immune
system
dysregulation,
cerebral
hypoperfusion,
impaired
gas
transfer
lungs.
Other
weak
endothelial
damage
hypercoagulation,
mast
cell
activation,
auto-immunity
vascular
receptors.
Conclusions:
LC
complex
condition
multiple
organs
diverse
presentations
(or
traits)
underpinned
by
mechanisms.
A
‘treatable
trait’
approach
may
help
certain
groups
target
specific
interventions.
Future
research
must
include
understanding
response
intervention
based
on
these
mechanism-based
traits.
Biomedicines,
Год журнала:
2023,
Номер
11(5), С. 1302 - 1302
Опубликована: Апрель 27, 2023
Accumulating
evidence
implicates
obesity
as
a
risk
factor
for
increased
severity
of
disease
outcomes
in
patients
infected
with
severe
acute
respiratory
syndrome
coronavirus
type
2
(SARS-CoV-2).
Obesity
is
associated
adipose
tissue
dysfunction,
which
not
only
predisposes
individuals
to
metabolic
complications,
but
also
substantially
contributes
low-grade
systemic
inflammation,
altered
immune
cell
composition,
and
compromised
function.
This
seems
impact
the
susceptibility
outcome
diseases
caused
by
viruses,
obese
people
appear
more
vulnerable
developing
infections
they
recover
later
from
infectious
than
normal-weight
individuals.
Based
on
these
findings,
efforts
identify
suitable
diagnostic
prognostic
markers
Coronavirus
2019
(COVID-19)
predict
have
been
made.
includes
analysis
cytokines
secreted
tissues
(adipokines),
multiple
regulatory
functions
body;
instance,
modulating
insulin
sensitivity,
blood
pressure,
lipid
metabolism,
appetite,
fertility.
Most
relevant
context
viral
infections,
adipokines
influence
number,
consequences
overall
activity
Hence,
circulating
levels
diverse
SARS-CoV-2
considered
reveal
COVID-19
markers.
review
article
summarizes
findings
aimed
correlate
progression
COVID-19.
Several
studies
provided
insights
chemerin,
adiponectin,
leptin,
resistin,
galectin-3
SARS-CoV-2-infected
patients,
while
limited
information
yet
available
apelin
visfatin
Altogether,
current
points
at
resistin
being
value
disease.
Frontiers in Pharmacology,
Год журнала:
2023,
Номер
14
Опубликована: Авг. 3, 2023
As
the
outbreak
of
COVID-19
caused
by
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
first
broke
out
in
Hubei
Province,
China,
at
end
2019.
It
has
brought
great
challenges
and
harms
to
global
public
health.
SARS-CoV-2
mainly
affects
lungs
is
manifested
as
pulmonary
disease.
However,
one
biggest
crises
arises
from
emergence
COVID-19-induced
fibrosis.
At
present,
there
are
still
many
questions
about
how
induced
fibrosis
(PF)
occurs
treat
regulate
its
long-term
effects.
In
addition,
an
important
process
fibrosis,
effect
on
epithelial-mesenchymal
transition
(EMT)
may
be
factor
driving
PF.
This
review
summarizes
main
pathogenesis
treatment
mechanisms
related
Starting
with
basic
PF,
such
EMT,
transforming
growth
factor-β
(TGF-β),
fibroblasts
myofibroblasts,
inflammation,
macrophages,
innate
lymphoid
cells,
matrix
metalloproteinases
tissue
inhibitors
metalloproteinases,
hedgehog
pathway
well
Notch
signaling.
Further,
we
highlight
importance
EMT
PF
provide
overview
molecular
mechanisms,
which
will
facilitate
future
research
propose
new
clinical
therapeutic
solutions
for
Immunobiology,
Год журнала:
2024,
Номер
229(4), С. 152813 - 152813
Опубликована: Май 24, 2024
Post-COVID
symptoms
are
reported
in
10–35
%
of
patients
not
requiring
hospitalization,
and
up
to
80
hospitalized
with
severe
disease.
The
pathogenesis
post-COVID
syndrome
remains
largely
unknown.
Some
evidence
suggests
that
prolonged
inflammation
has
a
key
role
the
most
manifestations.
We
evaluated
panel
inflammatory
immune-mediated
cytokines
individuals
altered
HRCT
features
without
any
long-term
COVID
symptoms.
Blood
samples
89
adult
previously
COVID-19
were
collected
stratified
as
fibrotic
lung
alterations.
Serum
analyte
concentrations
IL-4,
IL-2,
CXCL10
(IP-10),
IL-1β,
TNF-α,
CCL2
(MCP-1),
IL-17A,
IL-6,
IL-10,
IFN-γ,
IL-12p70
TGF-β1
(free
active
form)
quantified
by
bead-based
multiplex
assay.
Clinical
functional
data
recorded
database.
With
use
machine
learning
approach,
IL-32,
IL-8,
IL-10
proved
be
associated
development
sequelae
at
follow-up.
Direct
comparison
cytokine
levels
two
groups
showed
increased
IL-32
decreased
IL-8
impairment.
After
further
stratification
severity
(severe
versus
mild/moderate)
during
emerged
only
showing
patients.
These
findings
contribute
better
understanding
immune
response
potential
prognostic
markers
after
COVID-19.
Frontiers in Pharmacology,
Год журнала:
2023,
Номер
14
Опубликована: Июнь 15, 2023
In
the
past
few
years,
COVID-19
became
leading
cause
of
morbidity
and
mortality
worldwide.
Although
World
Health
Organization
has
declared
an
end
to
as
a
public
health
emergency,
it
can
be
expected,
that
emerging
new
cases
at
top
previous
ones
will
result
in
increasing
number
patients
with
post-COVID-19
sequelae.
Despite
fact
majority
recover,
severe
acute
lung
tissue
injury
susceptible
individuals
progress
interstitial
pulmonary
involvement.
Our
goal
is
provide
overview
various
aspects
associated
Post-COVID-19
fibrosis
focus
on
its
potential
pharmacological
treatment
options.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Июль 20, 2023
SARS-CoV-2,
the
cause
of
COVID-19
pandemic,
possesses
eleven
accessory
proteins
encoded
in
its
genome.
Their
roles
during
infection
are
still
not
completely
understood.
In
this
study,
transcriptomics
analysis
revealed
that
both
WNT5A
and
IL11
were
significantly
up-regulated
A549
cells
expressing
individual
ORF6,
ORF8,
ORF9b
or
ORF9c
from
SARS-CoV-2
(Wuhan-Hu-1
isolate).
is
a
member
IL6
family
cytokines.
signaling-related
genes
also
differentially
expressed.
Bioinformatics
disclosed
involved
pulmonary
fibrosis
idiopathic
disease
functional
assays
confirmed
their
association
with
profibrotic
cell
responses.
Subsequently,
data
comparison
lung
lines
infected
biopsies
patients
COVID-19,
evidenced
altered
gene
expression
matched
those
obtained
study.
Our
results
show
involvement
inflammatory
Thus,
these
could
be
targeted
by
new
therapies
against
disease.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(5), С. 4928 - 4928
Опубликована: Март 3, 2023
The
coronavirus
disease
pandemic,
which
profoundly
reshaped
the
world
in
2019
(COVID-19),
and
is
currently
ongoing,
has
affected
over
200
countries,
caused
500
million
cumulative
cases,
claimed
lives
of
6.4
people
worldwide
as
August
2022.
causative
agent
severe
acute
respiratory
syndrome
2
(SARS-CoV-2).
Depicting
this
virus’
life
cycle
pathogenic
mechanisms,
well
cellular
host
factors
pathways
involved
during
infection,
great
relevance
for
development
therapeutic
strategies.
Autophagy
a
catabolic
process
that
sequesters
damaged
cell
organelles,
proteins,
external
invading
microbes,
delivers
them
to
lysosomes
degradation.
would
be
entry,
endo,
release,
transcription
translation,
viral
particles
cell.
Secretory
autophagy
also
developing
thrombotic
immune-inflammatory
seen
significant
number
COVID-19
patients
can
lead
illness
even
death.
This
review
aims
main
aspects
characterize
complex
not
yet
fully
elucidated
relationship
between
SARS-CoV-2
infection
autophagy.
It
briefly
describes
key
concepts
regarding
mentions
its
pro-
antiviral
roles,
while
noting
reciprocal
effect
autophagic
their
clinical
aspects.
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июль 3, 2023
A
prominent
theory
of
psychedelics
is
that
they
increase
brain
entropy.
Twelve
studies
have
evaluated
psychedelic
effects
on
fMRI
entropy
quantifications,
no
findings
been
replicated.
Here
we
these
metrics
in
an
independent
28-participant
healthy
cohort
with
121
pre-
and
post-psilocybin
scans.
We
assessed
relations
between
plasma
psilocin,
serotonin
2A
receptor
occupancy,
a
subjective
drug
intensity
rating
using
linear
mixed-effects
models.
observed
significant
positive
associations
for
Shannon
path-length,
instantaneous
correlation
distributions,
divergent
sample
at
varying
time-scales.
did
not
observe
8
13
metrics.
Brain
quantifications
showed
limited
inter-measure
correlations.
Our
observations
support
nuanced
acute
effect
entropy,
underscoring
the
need
replication
do
reflect
singular
construct.
highlight
candidate
may
mediate
clinical
psychedelics.