Genomics,
Год журнала:
2024,
Номер
117(1), С. 110977 - 110977
Опубликована: Дек. 9, 2024
Abnormal
programmed
cell
death
(PCD)
plays
a
central
role
in
spermatogenic
dysfunction.
However,
the
molecular
mechanisms
and
biomarkers
of
PCD
patients
with
nonobstructive
azoospermia
(NOA)
remain
unclear.
The
genetic
conditions
NOA
were
analysed
using
bulk
transcriptomic,
single-cell
single
nucleotide
polymorphism
(SNP),
clinical
data
from
multiple
centres.
A
total
675
machine
learning
methods
applied
to
construct
models
12
different
PCDs
screen
for
distinctive
genes.
new
PCDscore
system
was
created
measure
degree
patients.
Using
mouse
model,
TUNEL,
qRT-PCR,
Western
blotting,
immunohistochemistry
(IHC)
utilized
validate
status
testes
expression
levels
hub
PCD-related
genes
(PCDRGs).
Mouse
testicular
samples
used
sequencing
whole
transcriptome.
results
evaluate
correlation
between
scores
built
characteristic
PCDRGs
chosen
by
learning.
correlated
gene
interaction
immune
activity
changes.
Leydig,
Sertoli,
T
cells
prominent
interactions
testis
increased.
Among
PCDRGs,
BCL2L14,
GGA1,
GPX4,
PHKG2,
SLC39A8
strongly
linked
spermatogenesis.
PHKG2
statuses.
changes
these
may
be
due
effects
SNPs,
which
lead
male
reproductive
disorders.
Our
study
provides
insights
into
via
multiomics
proposes
reliable
diagnosis
use
biomarkers.
deeper
understanding
aid
treatment
NOA.
Immunity Inflammation and Disease,
Год журнала:
2025,
Номер
13(2)
Опубликована: Фев. 1, 2025
ABSTRACT
Background
The
precise
mechanisms
responsible
for
renal
injury
in
IgA
nephropathy
(IgAN)
are
not
fully
understood.
Our
study
employed
an
extensive
scRNA‐seq
analysis
of
kidney
biopsies
obtained
from
individuals
with
IgAN,
a
specific
emphasis
on
investigating
the
involvement
endothelial
cells.
Methods
We
data
Gene
Expression
Omnibus
database
and
conducted
bioinformatics
analysis,
which
included
enrichment
differentially
expressed
genes,
AUCell
high‐dimensional
weighted
gene
co‐expression
network
(hdWGCNA).
results
these
analyses
were
further
validated
using
human
glomerular
cells
(HRGECs).
Results
ScRNA‐seq
uncovered
notable
variations
expression
between
IgAN
control
tissues.
demonstrated
high
presence
adhesion
molecules
components
related
to
mitogen‐activated
protein
kinase
signaling
pathway
within
Furthermore,
through
hdWGCNA
it
was
discovered
that
interleukin
(IL)‐6,
Rac1,
cadherin
exhibited
associations
Stimulation
HRGECs
IL‐6/IL‐6
receptor
resulted
significant
reduction
VE‐cad
while
inhibiting
Rac1
led
substantial
decrease
Rac1‐GTP
levels
increase
expression.
Conclusion
This
presents
novel
findings
regarding
contribution
development
as
demonstrates
IL‐6
negatively
regulates
via
Rac1.
These
highlight
pathogenesis
IgAN.
Asian Journal of Andrology,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 14, 2025
Infertility,
defined
as
the
inability
to
conceive
after
1
year
of
regular
unprotected
intercourse,
impacts
10%-20%
couples
globally.
Both
male
and
female
factors
contribute
equally
this
condition.
Azoospermia,
particularly
nonobstructive
azoospermia
(NOA),
which
affects
10%-15%
infertile
men,
represents
a
significant
challenge
in
infertility.
The
advent
assisted
reproductive
technology
(ART),
specifically
microdissection
testicular
sperm
extraction
(micro-TESE)
followed
by
intracytoplasmic
injection
(ICSI),
offers
possibility
for
men
with
NOA
father
biological
children.
Recent
studies
have
focused
on
predictors
retrieval
patients,
such
age,
volume,
follicle-stimulating
hormone
(FSH)
level.
This
review
aims
explore
limited
data
anatomical
characteristics
patients
provide
surgical
considerations
micro-TESE,
thereby
enhancing
understanding
improving
outcomes
challenging
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 26, 2025
AbstractBackground:
Gouty
arthritis
is
a
common
inflammatory
disease
triggered
by
the
deposition
of
monosodium
urate
(MSU)crystals
in
joints,
leading
to
both
acute
and
chronic
inflammation.
While
macrophages
have
long
been
implicated
pathogenesis
gouty
arthritis,
exact
mechanisms,
differentiation
conditions,
key
molecules
involved
remain
unclear.
Methods:
Gene
Set
Enrichment
Analysis
(GSEA)
was
used
determine
primary
functions
macrophages.
High-dimensional
weighted
gene
co-expression
network
analysis
(hdWGCNA),
transcription
factor
activity
analysis,
pseudotemporal
trajectory
were
applied
identify
VAV3
as
regulating
macrophage
differentiation.
The
correlation
between
expression
relevant
biological
processes
further
validated
through
Variation
(GSVA)
examining
related
bulk
RNA
sequencing
datasets
from
GEO
database,
confirming
its
association
with
arthritis.
Results:
Our
indicates
that
are
crucial
cell
type
synovial
fluid
microenvironment
where
their
influenced
various
factors.
function,
positively
correlated
several
phenotypic
features
progression,
including
angiogenesis
differential
across
multiple
database.
Conclusion:
findings
underscore
critical
role
novel
biomarker
potential
therapeutic
target.
These
results
deepen
our
understanding
suggest
could
broader
implications
other
gout-related
such
nephropathy.
Frontiers in Endocrinology,
Год журнала:
2025,
Номер
16
Опубликована: Март 19, 2025
Non-obstructive
azoospermia
(NOA)
constitutes
one
of
the
most
severe
forms
male
infertility.
Recent
advancements
in
single-cell
sequencing
have
significantly
contributed
to
understanding
molecular
landscape
NOA
human
testicular
tissues,
elucidating
factors
that
underpin
spermatogenic
dysfunction.
This
technology
has
improved
our
condition
at
a
cellular
level.
Concurrently,
bioinformatics
developments
facilitated
re-analysis
publicly
available
datasets,
offering
novel
insights
into
disorder.
Nevertheless,
comprehensive
review
integrating
primary
and
studies
is
lacking.
systematically
evaluates
10
reporting
original
data
samples
22
secondary
re-analyzed
these
published
data.
We
explore
applications
germ
cells,
Sertoli
Leydig
overview
Our
highlights
findings
studies,
including
roles
transcriptional
regulators,
RNA
transcription,
endocrine
disruptors,
microtubular
cytoskeleton,
thereby
bridging
studies.
Additionally,
we
discussed
future
research
directions
challenges
translating
clinical
applications.
In
summary,
offers
high-resolution,
perspective
tissue,
paving
way
for
innovative
therapeutic
strategies
Current Alzheimer Research,
Год журнала:
2024,
Номер
21(2), С. 120 - 140
Опубликована: Фев. 1, 2024
Background:
Alzheimer's
disease
(AD)
is
a
recognized
complex
and
severe
neurodegenerative
disorder,
presenting
significant
challenge
to
global
health.
Its
hallmark
pathological
features
include
the
deposition
of
β-amyloid
plaques
formation
neurofibrillary
tangles.
Given
this
context,
it
becomes
imperative
develop
an
early
accurate
biomarker
model
for
AD
diagnosis,
employing
machine
learning
bioinformatics
analysis.
Methods:
In
study,
single-cell
data
analysis
was
employed
identify
cellular
subtypes
that
exhibited
differences
between
diseased
control
groups.
Following
identification
NK
cells,
hdWGCNA
communication
were
conducted
pinpoint
cell
subset
with
most
robust
effects.
Subsequently,
three
algorithms-LASSO,
Random
Forest,
SVM-RFE-were
jointly
screen
modular
genes
highly
associated
AD.
A
logistic
regression
diagnostic
then
designed
based
on
these
characterized
genes.
Additionally,
protein-protein
interaction
(PPI)
networks
established.
Furthermore,
unsupervised
cluster
classify
genes,
followed
by
immune
infiltration
in
different
subtypes.
Finally,
Spearman
correlation
coefficient
utilized
explore
as
well
inflammatory
factors.
Results:
We
have
successfully
identified
(RPLP2,
RPSA,
RPL18A)
exhibit
high
association
The
nomogram
provides
practical
assistance
diagnosing
predicting
patients'
outcomes.
interconnected
screened
through
PPI
are
intricately
linked
ribosome
metabolism
COVID-19
pathway.
Utilizing
expression
unveiled
distinct
Particularly
noteworthy
subtype
C3,
expression,
which
correlates
elevated
levels
Hence,
can
be
inferred
establishment
environment
patients
closely
intertwined
heightened
Conclusion:
This
study
has
not
only
established
valuable
but
also
delved
deeply
into
pivotal
role
shaping
individuals
These
findings
offer
crucial
insights
diagnosis
patient
management
strategies.
Current Opinion in Urology,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 28, 2024
Purpose
of
review
This
article
aims
to
describe
new
developments
in
the
field
nonobstructive
azoospermia
biology,
diagnostics,
biomarkers,
and
therapeutic
strategies.
Recent
findings
studies
have
investigated
molecular
underpinnings
cellular
dysfunction
that
is
contributing
spermatogenic
suggest
abnormalities
across
both
somatic
germ
cells.
Biomarkers
predict
chances
sperm
retrieval
are
being
explored
utilizing
cell
free
(cf)
DNA
RNA
from
various
body
fluids,
addition
a
full
range
transcripts
epigenetics
within
seminal
fluid.
Various
approaches
optimize
identification
surgical
specimens
including
microfluidic
machine
learning
approaches.
Finally,
regenerating
production
males
with
evolving
include
3-dimensional
culture
techniques
integration
computational
modeling.
Summary
The
landscape
underpinnings,
technological
more
reliably
identify
novel
regenerative
strategies
likely
transform
male
reproduction
years
come.