Journal of the American Heart Association,
Journal Year:
2024,
Volume and Issue:
13(6)
Published: March 8, 2024
Pulmonary
arterial
hypertension
(PAH)
exhibits
phenotypic
heterogeneity
and
variable
response
to
therapy.
The
metabolome
has
been
implicated
in
the
pathogenesis
of
PAH,
but
previous
works
have
lacked
power
implicate
specific
metabolites.
Mendelian
randomization
(MR)
is
a
method
for
causal
inference
between
exposures
outcomes.
Journal of Inflammation Research,
Journal Year:
2025,
Volume and Issue:
Volume 18, P. 637 - 652
Published: Jan. 1, 2025
Immunometabolism
is
pivotal
in
rheumatoid
arthritis
(RA)
pathogenesis,
yet
the
intricacies
of
its
pathological
regulatory
mechanisms
remain
poorly
understood.
This
study
explores
complex
immunometabolic
landscape
RA
to
identify
potential
therapeutic
targets.
We
integrated
genome-wide
association
(GWAS)
data
involving
1,400
plasma
metabolites,
731
immune
cell
traits,
and
outcomes
from
over
58,000
participants.
Mendelian
randomization
(MR)
mediation
analyses
were
applied
evaluate
causal
relationships
among
cells,
RA.
further
analyzed
single-cell
bulk
transcriptomes
investigate
differential
gene
expression,
interactions,
relevant
biological
processes.
Machine
learning
models
identified
hub
genes,
which
validated
via
quantitative
real-time
PCR
(qRT-PCR).
Then,
small-molecule
drugs
screened
using
Connectivity
Map
(CMAP)
molecular
docking.
Finally,
a
phenome-wide
(PheWAS)
was
conducted
side
effects
targeting
genes.
Causalities
found
between
six
five
cells
genetically
determined
levels.
Notably,
DC
mediated
18%
protective
effect
PE
on
Autophagy-related
scores
elevated
both
subsets
PE-associated
Through
observation
functional
differences
cellular
interactions
clusters,
DCs
with
high
autophagy
may
process
such
as
necroptosis
activation
Jak-STAT
signaling
pathway
contributing
pathogenesis
Explainable
machine
learning,
PPI
network
analysis,
qPCR
jointly
four
genes
(PFN1,
SRP14,
S100A11,
SAP18).
CMAP,
docking,
PheWAS
analysis
highlighted
vismodegib
promising
candidate.
clarifies
key
RA,
pinpointing
paths
for
better
prevention,
diagnosis,
treatment.
Journal of Translational Medicine,
Journal Year:
2023,
Volume and Issue:
21(1)
Published: Nov. 17, 2023
Abstract
Background
Stroke
is
a
common
neurological
disorder
that
disproportionately
affects
middle-aged
and
elderly
individuals,
leading
to
significant
disability
mortality.
Recently,
human
blood
metabolites
have
been
discovered
be
useful
in
unraveling
the
underlying
biological
mechanisms
of
disorders.
Therefore,
we
aimed
evaluate
causal
relationship
between
susceptibility
stroke.
Methods
Summary
data
from
genome-wide
association
studies
(GWASs)
serum
stroke
its
subtypes
were
obtained
separately.
A
total
486
used
as
exposure.
Simultaneously,
11
different
phenotypes
set
outcomes,
including
any
(AS),
ischemic
(AIS),
large
artery
(LAS),
cardioembolic
(CES),
small
vessel
(SVS),
lacunar
(LS),
white
matter
hyperintensities
(WMH),
intracerebral
hemorrhage
(ICH),
subarachnoid
(SAH),
transient
attack
(TIA),
brain
microbleeds
(BMB).
two‐sample
Mendelian
randomization
(MR)
study
was
conducted
investigate
effects
on
subtypes.
The
inverse
variance-weighted
MR
analyses
estimates,
accompanied
by
series
sensitivity
robustness
results.
Furthermore,
reverse
analysis
assess
potential
for
causation.
Additionally,
metabolic
pathway
performed
using
web-based
MetOrigin
.
Results
After
correcting
false
discovery
rate
(FDR),
results
revealed
remarkable
causative
associations
with
25
metabolites.
Further
confirmed
only
four
involving
three
specific
passed
all
tests,
namely
ADpSGEGDFXAEGGGVR*
AS
(OR:
1.599,
95%
CI
1.283–1.993,
p
=
2.92
×
10
−5
)
AIS
1.776,
1.380–2.285,
8.05
−6
),
1-linoleoylglycerophosph-oethanolamine*
LAS
0.198,
0.091–0.428,
3.92
gamma-glutamylmethionine*
SAH
3.251,
1.876–5.635,
2.66
thereby
demonstrating
high
degree
stability.
Moreover,
eight
seven
other
both
tests
considered
robust.
result
one
metabolite
(glutamate
LAS)
non-robust.
As
remaining
metabolites,
speculate
they
may
potentially
possess
relationships.
Notably,
no
emerged
analysis.
after
FDR
correction,
identified
40
pathways
across
phenotypes.
Conclusions
their
associated
are
promising
circulating
biomarkers,
holding
application
screening
preventive
strategies
within
clinical
settings.
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: Dec. 21, 2023
Background
The
role
of
complement
component
1q
(C1Q)
related
genes
on
human
atherosclerotic
plaques
(HAP)
is
less
known.
Our
aim
to
establish
C1Q
associated
hub
using
single-cell
RNA
sequencing
(scRNA-seq)
and
bulk
analysis
diagnose
predict
HAP
patients
more
effectively
investigate
the
association
between
(ischemic
stroke)
bidirectional
Mendelian
randomization
(MR)
analysis.
Methods
scRNA-seq
bulk-RNA
data
were
download
from
Gene
Expression
Omnibus
(GEO)
database.
C1Q-related
was
screened
GBM,
LASSO
XGBoost
algorithms.
We
built
machine
learning
models
distinguish
types
atherosclerosis
generalized
linear
receiver
operating
characteristics
(ROC)
analyses.
Further,
we
scored
HALLMARK_COMPLEMENT
signaling
pathway
ssGSEA
confirmed
gene
expression
through
qRT-PCR
in
RAW264.7
macrophages
apoE-/-
mice.
Furthermore,
risk
assessed
MR
analysis,
with
as
exposure
ischemic
stroke
(IS,
large
artery
atherosclerosis)
outcomes.
Inverse
variance
weighting
(IVW)
used
main
method.
Results
utilized
dataset
(GSE159677)
identify
24
cell
clusters
12
types,
revealed
seven
DEGs
both
GEO
datasets.
then
select
C1QA
C1QC
DEGs.
findings
indicated
that
training
validation
cohorts
had
satisfactory
diagnostic
accuracy
for
identifying
HPAs.
Additionally,
SPI1
a
potential
TF
responsible
regulating
two
HAP.
further
correlated
activated
C1QC.
high
levels
C1QA,
ox-LDL-treated
mice
qPCR.
results
there
positive
genetic
IS,
evidenced
by
an
odds
ratio
(OR)
1.118
(95%CI:
1.013–1.234,
P
=
0.027).
Conclusion
authors
have
developed
validated
novel
signature
comprising
HAP,
while
has
provided
evidence
supporting
favorable
IS.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: April 15, 2024
Background
Extensive
evidence
suggests
a
link
between
alterations
in
serum
metabolite
composition
and
various
autoimmune
diseases
(ADs).
Nevertheless,
the
causal
relationship
underlying
these
correlations
their
potential
utility
as
dependable
biomarkers
for
early
AD
detection
remain
uncertain.
Objective
The
objective
of
this
study
was
to
employ
two-sample
Mendelian
randomization
(MR)
approach
ascertain
metabolites
ADs.
Additionally,
meta-analysis
incorporating
data
from
diverse
samples
conducted
enhance
validation
effect.
Materials
methods
A
MR
analysis
performed
investigate
association
486
human
six
prevalent
diseases:
systemic
lupus
erythematosus
(SLE),
rheumatoid
arthritis
(RA),
inflammatory
bowel
disease
(IBD),
dermatomyositis
(DM),
type
1
diabetes
(T1D),
celiac
(CeD).
inverse
variance
weighted
(IVW)
model
employed
primary
analytical
technique
analysis,
aiming
identify
blood
linked
with
diseases.
Independent
outcome
were
utilized
further
significant
metabolites.
Additional
sensitivity
analyses,
including
heterogeneity
test,
horizontal
pleiotropy
retention
rate
conducted.
results
analyses
subsequently
meta-integrated.
Finally,
metabolic
pathway
using
KEGG
Small
Molecule
Pathway
Databases
(SMPD).
Results
Following
discovery
replication
phases,
eight
identified
causally
associated
diseases,
encompassing
five
lipid
metabolism
types:
1-oleoylglycerophosphoethanolamine,
1-arachidonoylglycerophosphoethanolamine,
1-myristoylglycerophosphocholine,
arachidonate
(20:4
n6),
glycerol.
indicated
that
three
out
exhibited
protective
effect,
while
remaining
designated
pathogenic
factors.
robustness
associations
confirmed
through
analysis.
Moreover,
an
investigation
into
pathways
revealed
correlation
galactose
Conclusion
This
ADs,
providing
novel
insights
mechanism
development
mediated
by
possible
diagnosis.
BMC Pulmonary Medicine,
Journal Year:
2024,
Volume and Issue:
24(1)
Published: May 16, 2024
Abstract
Introduction
Lung
cancer
is
a
common
malignant
tumor,
and
different
types
of
immune
cells
may
have
effects
on
the
occurrence
development
lung
subtypes,
including
squamous
cell
carcinoma
(LUSC)
adenocarcinoma
(LUAD).
However,
causal
relationship
between
phenotype
still
unclear.
Methods
This
study
utilized
comprehensive
dataset
containing
731
phenotypes
from
European
Bioinformatics
Institute
(EBI)
to
evaluate
potential
LUSC
LUAD
using
inverse
variance
weighted
(IVW)
method
in
Mendelian
randomization
(MR).
Sensitivity
analyses,
MR-Egger
intercept,
Cochran
Q
test,
others,
were
conducted
for
robustness
results.
The
results
further
validated
through
meta-analysis
data
Transdisciplinary
Research
Into
Cancer
(TRICL)
data.
Additionally,
confounding
factors
excluded
ensure
findings.
Results
Among
final
selection
729
phenotypes,
three
exhibited
statistically
significant
with
LUSC.
CD28
expression
resting
CD4
regulatory
T
(OR
1.0980,
95%
CI:
1.0627–1.1344,
p
<
0.0001)
CD45RA
+
CD28-
CD8
%T
1.0011,
1.0007;
1.0015,
associated
increased
susceptibility
Conversely,
CCR2
monocytes
0.9399,
0.9177–0.9625,
was
correlated
decreased
risk
no
relationships
established
any
LUAD.
Conclusion
demonstrates
that
specific
are
but
not
While
these
findings
derived
solely
populations,
they
provide
clues
deeper
understanding
immunological
mechanisms
underlying
offer
new
directions
future
therapeutic
strategies
preventive
measures.
