Research Square (Research Square),
Год журнала:
2023,
Номер
unknown
Опубликована: Авг. 10, 2023
Abstract
Osteoarthritis
(OA)
is
increasing
in
prevalence
and
has
a
severe
impact
on
patients’
lives.
However,
our
understanding
of
biomarkers
driving
OA
risk
remains
limited.
We
developed
model
predicting
the
five-year
OA,
integrating
clinical,
lifestyle
biomarker
data
from
UK
Biobank
(19,120
patients
with
ROC-AUC:0.72
95%CI
(0.71
–
0.73)).
Higher
age,
BMI,
prescription
non-steroidal
anti-inflammatory
drugs
contributed
most
to
increased
prediction.
14
sub-groups
profiles
were
identified,
validated
an
independent
set
evaluating
11-year
risk,
88%
uniquely
assigned
one
sub-groups.
Individual
characterised
by
personalised
biomarkers.
Omics
integration
demonstrated
predictive
importance
key
genes
pathways
(e.g.
GDF5
TGF-β
signalling)
identified
OA-specific
CRTAC1
COL9A1).
In
summary,
this
work
opportunities
for
prevention
insights
into
its
underlying
pathogenesis.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Апрель 1, 2024
Abstract
Osteoarthritis
(OA)
is
increasing
in
prevalence
and
has
a
severe
impact
on
patients’
lives.
However,
our
understanding
of
biomarkers
driving
OA
risk
remains
limited.
We
developed
model
predicting
the
five-year
diagnosis,
integrating
retrospective
clinical,
lifestyle
biomarker
data
from
UK
Biobank
(19,120
patients
with
OA,
ROC-AUC:
0.72,
95%CI
(0.71–0.73)).
Higher
age,
BMI
prescription
non-steroidal
anti-inflammatory
drugs
contributed
most
to
increased
prediction
ahead
diagnosis.
identified
14
subgroups
profiles.
These
were
validated
an
independent
set
evaluating
11-year
risk,
88%
being
uniquely
assigned
one
subgroups.
Individual
profiles
characterised
by
personalised
biomarkers.
Omics
integration
demonstrated
predictive
importance
key
genes
pathways
(e.g.,
GDF5
TGF-β
signalling)
OA-specific
CRTAC1
COL9A1).
In
summary,
this
work
identifies
opportunities
for
prevention
insights
into
its
underlying
pathogenesis.
Abstract
Osteoarthritis
(OA)
poses
a
significant
challenge
in
orthopedics.
Inflammatory
pathways
are
regarded
as
central
mechanisms
the
onset
and
progression
of
OA.
Growing
evidence
suggests
that
senescence
acts
mediator
inflammation-induced
Given
lack
effective
treatments
for
OA,
there
is
an
urgent
need
clearer
understanding
its
pathogenesis.
In
this
review,
we
systematically
summarize
cross-talk
between
cellular
inflammation
We
begin
by
focusing
on
hallmarks
senescence,
summarizing
supports
relationship
inflammation.
then
discuss
interaction
inflammation,
including
senescence-associated
secretory
phenotypes
(SASP)
effects
pro-
anti-inflammatory
interventions
senescence.
Additionally,
focus
various
types
cartilage,
subchondral
bone,
synovium,
infrapatellar
fat
pad,
stem
cells,
immune
elucidating
their
impacts
Finally,
highlight
potential
therapies
targeting
senescent
cells
OA
strategy
promoting
cartilage
regeneration.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Май 23, 2024
Abstract
Comprehensive
single-cell
metabolic
profiling
is
critical
for
revealing
phenotypic
heterogeneity
and
elucidating
the
molecular
mechanisms
underlying
biological
processes.
However,
metabolomics
remains
challenging
because
of
limited
metabolite
coverage
inability
to
discriminate
isomers.
Herein,
we
establish
a
platform
in-depth
organic
mass
cytometry.
Extended
analysis
time
guarantees
sufficient
MS/MS
acquisition
identification
isomers
discrimination
while
online
sampling
ensures
high-throughput
method.
The
largest
number
identified
metabolites
(approximately
600)
are
achieved
in
single
cells
fine
subtyping
MCF-7
first
demonstrated
by
an
investigation
on
differential
levels
3-hydroxybutanoic
acid
among
clusters.
Single-cell
transcriptome
reveals
differences
expression
downstream
antioxidative
stress
genes,
such
as
metallothionein
2
(MT2A),
fluorescence-activated
cell
sorting
assay
confirms
positive
relationship
between
target
proteins;
these
results
suggest
that
provides
cancer
with
different
ability
resist
surrounding
oxidative
stress.
Our
method
paves
way
deep
metabolome
investigations
physiological
pathological
processes
occur
during
cancer.
Frontiers in Cell and Developmental Biology,
Год журнала:
2025,
Номер
13
Опубликована: Фев. 14, 2025
Introduction
Recent
research
indicated
a
strong
link
between
the
gut
microbiota
and
osteoarthritis.
However,
complex
interplay
microbiota,
serum
metabolites,
progression
of
osteoarthritis
in
affected
individuals
remains
largely
unexplored.
This
study
aimed
to
investigate
characteristics
metabolites
patients
with
Methods
Participants
either
healthy
knees
or
were
enrolled
categorized
into
control
(HC)
(OA)
groups.
Fecal
blood
samples
collected
for
16S
rRNA
gene
sequencing,
metabolomic
analysis
via
liquid
chromatography–mass
spectrometry
(LC-MS),
integrated
evaluation.
Results
The
results
showed
no
significant
variation
richness
diversity
two
abundance
Bacteroides
plebeius
Faecalibacterium
prausnitzii
was
reduced
OA
group,
both
which
are
known
their
potential
as
next-generation
probiotics
human
health.
Metabolomic
that
including
pyrogallol
3-hydroxybutyrate
(3HB),
significantly
lower
group.
These
positively
impact
other
diseases
demonstrated
good
diagnostic
performance
distinguishing
from
controls.
Correlation
revealed
positive
correlation
3HB.
Discussion
highlighted
specific
metabolite
profiles
patients,
suggesting
changes
bacteria
derived
closely
tied
progression.
underscores
modifiable
elements
therapeutic
targets
prevention.
D-β-hydroxybutyrate,
BHB,
has
been
previously
proposed
as
an
anti-senescent
agent
in
vitro
and
vivo
several
tissues
including
vascular
smooth
muscle.
Moreover,
BHB
derivatives
ketone
esters
alleviate
heart
failure.
Here,
we
provide
evidence
of
the
potential
therapeutic
effect
on
Hutchinson-Gilford
progeria
syndrome
(HGPS),
a
rare
condition
characterized
by
premature
aging
failure,
caused
presence
progerin,
aberrant
protein
derived
from
LMNA/C
gene
c.1824C
>
T
mutation.
We
have
assessed
hallmarks
HGPS-senescent
phenotype
vitro,
such
progerin
levels,
nuclear
morphometric
aberrations,
nucleolar
expansion,
cellular
senescent
morphology,
SA-βGal-positive
cells,
H3K9me3
heterochromatin,
γH2AX
foci,
Lamin
B1,
p21Waf1/Cip1
p16CDKN2A
abundance,
autophagy.
Strikingly,
improved
morphometrics,
diminished
senescence-phenotype,
unstuck
autophagy
HGPS
observed
enhanced
degradation
cargo
receptor
SQSTM1/p62,
suggesting
stimulation
autophagic
flux.
Additionally,
decrease
cause
senescence
HGPS.
Furthermore,
compound
C,
inhibitor
AMPK,
SBI-0206965,
ULK1/2
which
prevent
activation,
reversed
BHB-induced
decline
well
its
AMPK-mTORC1
dependent
manner.
Altogether,
these
results
suggest
that
anti-senescence
involves
clearance
activation
supporting
for
therapeutics
further
preclinical
trials.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Март 5, 2025
As
a
complex
joint
disease,
osteoarthritis
(OA)
increasingly
affects
the
elderly.
Currently,
existing
drugs
cannot
cure
OA.
There
is
an
urgent
need
for
new
targets.
Lactylation
closely
related
to
inflammation
and
emerging
target
in
treatment.
However,
potential
of
lactylation-related
genes
(LRGs)
OA
poorly
understood.
This
study
identified
differentially
expressed
(DELRGs)
through
bioinformatics
analysis,
constructed
model
combination
various
machine
learning
methods,
performed
immune
infiltration
single-cell
analysis
molecular
docking
predict
drugs.
Mendelian
randomization
was
used
causal
relationships
between
eQTLs
three
types
osteoarthritis.
Finally,
we
RT-qPCR
CCK-8
assays
validate
results
analysis.
We
generated
with
good
diagnostic
efficacy
seven
hub
genes,
which
revealed
that
associated
cells
such
as
dendritic
macrophages,
well
cell
communication
fibroblasts
macrophages.
Azacitidine,
significant
results,
obtained
genes.
The
verified
expression
LRGs
assay
indicated
azacitidine
can
significantly
inhibit
proliferation
cells.
Overall,
established
lactylation-based
novel
biomarkers,
are
expected
lead
development
strategies
diagnosis
treatment
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Май 16, 2025
Rheumatic
disease
is
a
chronic
inflammatory
that
imposes
significant
societal
and
economic
burdens.
Accumulating
evidence
has
demonstrated
cellular
senescence
plays
an
important
role
in
inflammation-induced
rheumatic
diseases.
Due
to
the
lack
of
effective
therapies,
there
urgent
need
for
deeper
understanding
etiopathogenesis
In
this
review,
we
systematically
summarized
We
first
focused
on
mechanisms
hallmarks
senescence,
then
can
induce
or
aggravate
as
well
related
signaling
pathways.
Next,
discussed
interaction
between
Additionally,
elucidated
impacts
chondrocyte
mesenchymal
stem
cell
(MSC)
osteoarthritis
(OA)
systemic
lupus
erythematosus
(SLE),
respectively.
Finally,
highlighted
potential
therapies
targeting
senescent
cells
diseases
strategy,
especially
multi-target
effect
traditional
Chinese
medicine.
