Functions of the Muscleblind-like protein family and their role in disease
Cell Communication and Signaling,
Год журнала:
2025,
Номер
23(1)
Опубликована: Фев. 18, 2025
Язык: Английский
Exploring the Impact of Microgravity on Gene Expression: Dysregulated Pathways and Candidate Repurposed Drugs
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(3), С. 1287 - 1287
Опубликована: Фев. 2, 2025
Space
exploration
has
progressed
from
contemporary
discoveries
to
current
endeavors,
such
as
space
tourism
and
Mars
missions.
As
human
activity
in
accelerates,
understanding
the
physiological
effects
of
microgravity
on
body
is
becoming
increasingly
critical.
This
study
analyzes
transcriptomic
data
cell
lines
exposed
microgravity,
investigates
its
gene
expression,
identifies
potential
therapeutic
interventions
for
health
challenges
posed
by
spaceflight.
Our
analysis
identified
five
under-expressed
genes
(DNPH1,
EXOSC5,
L3MBTL2,
LGALS3BP,
SPRYD4)
six
over-expressed
(CSGALNACT2,
CSNK2A2,
HIPK1,
MBNL2,
PHF21A,
RAP1A),
all
which
exhibited
distinct
expression
patterns
response
microgravity.
Enrichment
highlighted
significant
biological
functions
influenced
these
conditions,
while
silico
drug
repurposing
modulators
that
could
counteract
changes.
introduces
a
novel
approach
addressing
during
missions
existing
drugs
specific
pathways
biomarkers
health.
findings
represent
first
systematic
effort
repurpose
spaceflight,
establishing
foundation
development
targeted
therapies
astronauts.
Future
research
should
aim
validate
authentic
environments
explore
broader
impacts.
Язык: Английский
New insights into Smad3 in cardiac fibrosis
Gene,
Год журнала:
2025,
Номер
952, С. 149418 - 149418
Опубликована: Март 14, 2025
Язык: Английский
DsbA-L activates TGF-β1/SMAD3 signaling and M2 macrophage polarization by stimulating AKT1 and NLRP3 to promote pulmonary fibrosis
Molecular Medicine,
Год журнала:
2024,
Номер
30(1)
Опубликована: Ноя. 23, 2024
Abstract
Background
Pulmonary
fibrosis
(PF)
is
a
progressive
and
difficult-to-heal
lung
disease
that
poses
significant
threat
to
human
life
health.
This
study
aimed
investigate
the
potential
pathological
mechanisms
of
PF
identify
new
avenues
for
treatment
PF.
Methods
Clinical
samples
were
collected
assess
effect
disulfide-bond
A
oxidoreductase-like
protein
(DsbA-L)
on
TGF-β1-induced
MLE-12
cell
model
bleomycin
(BLM)-induced
mice
established.
Changes
in
physiological
morphology
observed
tissues.
The
degree
apoptosis
mitochondrial
function
was
analyzed.
expression
relative
cytokines
examined.
CD68
+
/CD206
ratio
determined
indicate
M2
macrophage
polarization.
Results
DsbA-L
upregulated
patients
with
PF-like
models.
In
vitro,
overexpression
exacerbated
deposition
extracellular
matrix
(ECM),
apoptosis,
inflammation,
damage,
whereas
silencing
exerted
opposite
effects.
inhibited
activation
AKT1,
NLRP3,
SMAD3
by
TGF-β1.
cells
limited
polarization
RAW264.7
towards
phenotype.
AKT1
agonist
or
NLRP3
reversed
role
inhibiting
TGF-β1/SMAD3
pathway
vivo,
knockout
protected
from
damage
caused
BLM.
Conclusion
exhibited
profibrotic
epithelial
mice,
which
increased
levels
activate
These
findings
could
shed
light
clues
comprehension
Язык: Английский
CheekAge, a next-generation epigenetic buccal clock, is predictive of mortality in human blood
Frontiers in Aging,
Год журнала:
2024,
Номер
5
Опубликована: Окт. 1, 2024
While
earlier
first-generation
epigenetic
aging
clocks
were
trained
to
estimate
chronological
age
as
accurately
possible,
more
recent
next-generation
incorporate
DNA
methylation
information
pertinent
health,
lifestyle,
and/or
outcomes.
Recently,
we
produced
a
non-invasive
clock
using
Infinium
MethylationEPIC
data
from
than
8,000
diverse
adult
buccal
samples.
this
correlated
with
various
and
disease
factors,
did
not
assess
its
ability
capture
mortality.
To
address
gap,
applied
CheekAge
the
longitudinal
Lothian
Birth
Cohorts
of
1921
1936.
Despite
missing
nearly
half
CpG
inputs,
was
significantly
associated
mortality
in
blood
dataset.
Specifically,
change
one
standard
deviation
corresponded
hazard
ratio
(HR)
1.21
(FDR
q
=
1.66e-6).
performed
better
all
tested
displayed
comparable
HR
next-generation,
blood-trained
DNAm
PhenoAge
(HR
1.23,
2.45e-9).
understand
relative
importance
each
input
blood,
iteratively
removed
re-calculated
overall
association.
The
most
significant
effect
came
omitting
cg14386193,
which
is
annotated
gene
ALPK2
.
Excluding
site
increased
FDR
value
by
threefold
(to
4.92e-06).
We
additionally
enrichment
analyses
top
CpGs
that
impact
their
biology.
Taken
together,
provide
important
validation
for
highlight
novel
underlie
newly
identified
Язык: Английский