Clinical & Experimental Immunology,
Journal Year:
2023,
Volume and Issue:
215(3), P. 251 - 260
Published: Nov. 9, 2023
Abstract
MicroRNAs
(miRNAs)
are
small
non-coding
RNAs
that
post-transcriptionally
regulate
gene
expression
and
different
immune-related
pathways.
There
is
a
great
interest
in
identifying
miRNAs
involved
immune
cell
development
function
to
elucidate
the
biological
mechanisms
underlying
system,
its
regulation,
disease.
In
this
study,
we
aimed
investigate
association
of
circulating
with
blood
compositions
blood-based
markers.
Circulating
levels
2083
were
measured
by
RNA-sequencing
plasma
samples
1999
participants
from
population-based
Rotterdam
Study
collected
between
2002
2005.
Full
count
measurements
performed
for
absolute
granulocyte,
platelet,
lymphocyte,
monocyte,
white,
red
counts.
Multivariate
analyses
test
We
evaluated
overlap
predicted
target
genes
candidate
associated
markers
determining
response
First,
principal
component
regression
analysis
showed
significantly
cell,
lymphocyte
Second,
cross-sectional
identified
210
(P
<
2.82
×
10−5)
neutrophil-to-lymphocyte
ratio
(NLR),
platelet-to-lymphocyte
(PLR),
systemic
immune-inflammation
index.
Further
genetic
look-ups
seven
(miR-1233-3p,
miR-149-3p,
miR-150-5p,
miR-342-3p,
miR-34b-3p,
miR-4644,
miR-7106-5p)
also
previously
linked
NLR
PLR
Collectively,
our
study
suggests
several
innate
adaptive
systems,
providing
insight
into
pathogenesis
diseases
paving
way
future
clinical
applications.
Nutrients,
Journal Year:
2022,
Volume and Issue:
14(24), P. 5361 - 5361
Published: Dec. 16, 2022
It
is
widely
accepted
that
the
gut
microbiota
plays
a
significant
role
in
modulating
inflammatory
and
immune
responses
of
their
host.
In
recent
years,
host-microbiota
interface
has
gained
relevance
understanding
development
many
non-communicable
chronic
conditions,
including
cardiovascular
disease,
cancer,
autoimmunity
neurodegeneration.
Importantly,
dietary
fibre
(DF)
associated
compounds
digested
by
resulting
metabolites,
especially
short-chain
fatty
acids
(SCFA),
were
significantly
with
health
beneficial
effects,
such
as
via
proposed
anti-inflammatory
mechanisms.
However,
SCFA
metabolic
pathways
are
not
fully
understood.
Major
steps
include
production
microbiota,
uptake
colonic
epithelium,
first-pass
effects
at
liver,
followed
biodistribution
metabolism
host's
cellular
level.
As
patterns
do
affect
all
individuals
equally,
host
genetic
makeup
may
play
fate
these
addition
to
other
factors
might
influence
age,
birth
through
caesarean,
medication
intake,
alcohol
tobacco
consumption,
pathogen
exposure
physical
activity.
this
article,
we
review
DF,
from
intake
intracellular
fibre-derived
products,
identify
possible
sources
inter-individual
variability
related
variation.
Such
be
indicative
phenotypic
flexibility
response
diet,
predictive
long-term
adaptations
factors,
maladaptation
tissue
damage,
which
develop
into
disease
specific
predispositions,
thus
allowing
for
better
prediction
potential
following
personalized
intervention
DF.
The Journal of Experimental Medicine,
Journal Year:
2023,
Volume and Issue:
220(5)
Published: March 8, 2023
STAT6
(signal
transducer
and
activator
of
transcription
6)
is
a
factor
that
plays
central
role
in
the
pathophysiology
allergic
inflammation.
We
have
identified
16
patients
from
10
families
spanning
three
continents
with
profound
phenotype
early-life
onset
immune
dysregulation,
widespread
treatment-resistant
atopic
dermatitis,
hypereosinophilia
esosinophilic
gastrointestinal
disease,
asthma,
elevated
serum
IgE,
IgE-mediated
food
allergies,
anaphylaxis.
The
cases
were
either
sporadic
(seven
kindreds)
or
followed
an
autosomal
dominant
inheritance
pattern
(three
kindreds).
All
carried
monoallelic
rare
variants
functional
studies
established
their
gain-of-function
(GOF)
sustained
phosphorylation,
increased
target
gene
expression,
TH2
skewing.
Precision
treatment
anti–IL-4Rα
antibody,
dupilumab,
was
highly
effective
improving
both
clinical
manifestations
immunological
biomarkers.
This
study
identifies
heterozygous
GOF
as
novel
disorder.
anticipate
our
discovery
multiple
kindreds
germline
will
facilitate
recognition
more
affected
individuals
full
definition
this
new
primary
Nature Biotechnology,
Journal Year:
2022,
Volume and Issue:
40(11), P. 1644 - 1653
Published: June 6, 2022
Abstract
Genome-wide
association
studies
in
combination
with
single-cell
genomic
atlases
can
provide
insights
into
the
mechanisms
of
disease-causal
genetic
variation.
However,
identification
disease-relevant
or
trait-relevant
cell
types,
states
and
trajectories
is
often
hampered
by
sparsity
noise,
particularly
analysis
epigenomic
data.
To
overcome
these
challenges,
we
present
SCAVENGE,
a
computational
algorithm
that
uses
network
propagation
to
map
causal
variants
their
relevant
cellular
context
at
resolution.
We
demonstrate
how
SCAVENGE
help
identify
key
biological
underlying
human
variation,
applying
method
blood
traits
distinct
stages
hematopoiesis,
monocyte
subsets
increase
risk
for
severe
Coronavirus
Disease
2019
(COVID-19)
intermediate
lymphocyte
developmental
predispose
acute
leukemia.
Our
approach
not
only
provides
framework
enabling
variant-to-function
resolution
but
also
suggests
more
general
strategy
maximizing
inferences
be
made
using
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Feb. 24, 2023
Primary
sclerosing
cholangitis
(PSC)
is
a
rare
autoimmune
bile
duct
disease
that
strongly
associated
with
immune-mediated
disorders.
In
this
study,
we
implemented
multitrait
joint
analyses
to
genome-wide
association
summary
statistics
of
PSC
and
numerous
clinical
epidemiological
traits
estimate
the
genetic
contribution
each
trait
correlations
between
identify
new
lead
risk-associated
loci.
We
identified
seven
loci
have
not
been
previously
reported
one
independent
variant
in
locus.
Functional
annotation
fine-mapping
nominated
several
potential
susceptibility
genes
such
as
MANBA
IRF5.
Network-based
silico
drug
efficacy
screening
provided
candidate
agents
for
further
study
pharmacological
effect
PSC.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: April 14, 2023
Abstract
We
introduce
mvSuSiE,
a
multi-trait
fine-mapping
method
for
identifying
putative
causal
variants
from
genetic
association
data
(individual-level
or
summary
data).
mvSuSiE
learns
patterns
of
shared
effects
data,
and
exploits
these
to
improve
power
identify
SNPs.
Comparisons
on
simulated
show
that
is
competitive
in
speed,
precision
with
existing
methods,
uniformly
improves
single-trait
(SuSiE)
each
trait
separately.
applied
jointly
fine-map
16
blood
cell
traits
using
the
UK
Biobank.
By
analyzing
modeling
heterogeneous
effect
sharing
patterns,
we
discovered
much
larger
number
SNPs
(>3,000)
compared
fine-mapping,
narrower
credible
sets.
also
more
comprehensively
characterized
ways
which
affect
one
traits;
68%
showed
significant
than
type.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(19), P. 14857 - 14857
Published: Oct. 3, 2023
Fatty
acid
metabolism,
including
β-oxidation
(βOX),
plays
an
important
role
in
human
physiology
and
pathology.
βOX
is
essential
process
the
energy
metabolism
of
most
cells.
Moreover,
also
source
acetyl-CoA,
substrate
for
(a)
ketone
bodies
synthesis,
(b)
cholesterol
(c)
phase
II
detoxication,
(d)
protein
acetylation,
synthesis
many
other
compounds,
N-acetylglutamate—an
regulator
urea
synthesis.
This
review
describes
current
knowledge
on
importance
mitochondrial
peroxisomal
various
organs,
liver,
heart,
kidney,
lung,
gastrointestinal
tract,
peripheral
white
blood
cells,
In
addition,
diseases
associated
with
a
disturbance
fatty
oxidation
(FAO)
alimentary
organs
or
cells
are
presented.
Special
attention
was
paid
to
abnormalities
FAO
cancer
caused
by
mutations
gene-encoding
enzymes
involved
FAO.
Finally,
issues
related
α-
ω-
discussed.
Annals of the Rheumatic Diseases,
Journal Year:
2023,
Volume and Issue:
82(6), P. 837 - 847
Published: Feb. 16, 2023
Objectives
The
number
of
susceptibility
loci
currently
associated
with
vasculitis
is
lower
than
in
other
immune-mediated
diseases
due
part
to
small
cohort
sizes,
a
consequence
the
low
prevalence
vasculitides.
This
study
aimed
identify
new
genetic
risk
for
main
systemic
vasculitides
through
comprehensive
analysis
their
overlap.
Methods
Genome-wide
data
from
8467
patients
any
forms
and
29
795
healthy
controls
were
meta-analysed
using
ASSET.
Pleiotropic
variants
functionally
annotated
linked
target
genes.
Prioritised
genes
queried
DrugBank
potentially
repositionable
drugs
treatment
vasculitis.
Results
Sixteen
independently
two
or
more
vasculitides,
15
them
representing
shared
loci.
Two
these
pleiotropic
signals,
located
close
CTLA4
CPLX1
,
emerged
as
novel
Most
polymorphisms
appeared
affect
by
regulating
gene
expression.
In
this
regard,
some
common
potential
causal
prioritised
based
on
functional
annotation,
including
RNF145
IL12B
IL5
IRF1
IFNGR1
PTK2B
TRIM35
EGR2
ETS2
each
which
has
key
roles
inflammation.
addition,
drug
repositioning
showed
that
several
drugs,
abatacept
ustekinumab,
could
be
repurposed
management
analysed
Conclusions
We
identified
impact
pinpointed
genes,
represent
promising
targets
Frontiers in Oncology,
Journal Year:
2024,
Volume and Issue:
13
Published: Jan. 9, 2024
Acute
lymphoblastic
leukemia
(ALL)
is
the
most
common
cancer
in
children,
and
disproportionately
affects
children
of
Hispanic/Latino
ethnicity
United
States,
who
have
highest
incidence
disease
compared
with
other
racial/ethnic
groups.
Incidence
childhood
ALL
similarly
high
several
Latin
American
countries,
notably
Mexico,
concern
rising
some
populations
that
may
further
widen
this
disparity.
Prior
studies
implicated
germline
genetic
variants
increased
risk
among
children.
In
review,
we
describe
known
disparities
as
well
patient
outcomes
affect
across
Americas,
focus
on
role
variation
Indigenous
ancestry
etiology
these
disparities.
Finally,
discuss
future
avenues
research
to
our
understanding
causes
origin,
which
will
be
required
for
precision
prevention
efforts.
Cell Genomics,
Journal Year:
2024,
Volume and Issue:
4(6), P. 100562 - 100562
Published: May 14, 2024
The
phenotypic
impact
of
genetic
variation
repetitive
features
in
the
human
genome
is
currently
understudied.
One
such
feature
multi-copy
47S
ribosomal
DNA
(rDNA)
that
codes
for
rRNA
components
ribosome.
Here,
we
present
an
analysis
rDNA
copy
number
(CN)
UK
Biobank
(UKB).
From
first
release
UKB
whole-genome
sequencing
(WGS)
data,
a
discovery
White
British
individuals
reveals
CN
associates
with
altered
counts
specific
blood
cell
subtypes,
as
neutrophils,
and
estimated
glomerular
filtration
rate,
marker
kidney
function.
Similar
trends
are
observed
other
ancestries.
A
range
analyses
argue
against
reverse
causality
or
common
confounder
effects,
all
core
results
replicate
second
WGS
release.
Our
work
demonstrates
influence
on
trait
variance
humans.