Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Май 20, 2025
Hepatocellular
carcinoma
(HCC)
is
a
leading
cause
of
cancer
death
worldwide,
with
high
incidence
and
mortality
rates,
the
number
cases
expected
to
increase
by
2030.
Understanding
molecular
mechanisms
HCC
identifying
new
therapeutic
targets
biomarkers
for
are
crucial.
In
this
study,
we
examined
adaptor-related
protein
complex
5
subunit
ζ1
(AP5Z1)
expression
in
liver
nearby
noncancerous
tissues
explore
its
effects
on
cell
growth,
death,
autophagy.
The
functional
AP5Z1
were
studied
using
clinical
sample
analysis,
Western
blot
(WB),
immunohistochemistry
(IHC),
quantitative
reverse-transcription
polymerase
chain
reaction
(qRT‒PCR),
coimmunoprecipitation
(Co-IP),
proliferation
assays,
flow
cytometry
(FCM),
autophagy
electron
microscopy,
mass
spectrometry
(MS),
transcriptome
animal
model
experiments.
was
notably
higher
than
normal
linked
poor
prognosis.
results
both
vitro
vivo
studies
revealed
that
promoted
growth
reduced
apoptosis.
addition,
regulates
cellular
ubiquitinating
phosphatase
tensin
homolog
(PTEN)
modulating
phosphoinositide
3-kinase
(PI3K)/protein
kinase
B
(Akt)/mammalian
target
rapamycin
(mTOR)
pathway.
influences
apoptosis
cells
interacting
PTEN
modulate
PI3K/Akt/mTOR
This
gene
might
promote
ubiquitination
degradation
recruiting
tripartite
motif-containing
21
(TRIM21),
making
it
potential
biomarker
diagnosing
predicting
outcome
as
well
treatment
strategies.
Clinical and Experimental Medicine,
Год журнала:
2025,
Номер
25(1)
Опубликована: Март 6, 2025
Graft-versus-host
disease
remains
one
of
the
most
formidable
barriers
to
complete
success
hematopoietic
stem
cell
transplantation
that
has
emerged
as
curative
approach
for
many
malignancies
because
it
affects
quality
life
and
overall
survival.
Macrophages
are
among
important
members
immune
system,
which
perform
dual
roles
in
GVHD
both
therapeutic
tools
targets.
This
review
epitomizes
multifunctional
role
macrophages
pathophysiology
acute
chronic
GVHD.
play
an
early
phase
their
recruitment
infiltration
into
target
organs.
Furthermore,
they
polarize
two
functionally
different
phenotypes,
including
M1
M2.
In
case
GVHD,
express
phenotype
characterized
by
production
pro-inflammatory
cytokines
contribute
tissue
damage.
contrast,
tend
toward
M2
associated
with
repair
tissues
fibrosis.
A
critical
balance
these
phenotypes
is
central
course
severity
Further
interactions
other
lymphocytes
such
T
cells,
B
fibroblast
further
determine
Macrophage
interaction
alloreactive
cells
promotes
inflammation.
therefore
inducing
injuries
during
Interaction
macrophages,
cell,
fibroblast,
CD4+
fibrosis
and,
hence,
subsequent
dysfunction
These
some
insights,
while
several
challenges
remain.
First,
impact
dominant
on
polarization
incompletely
sometimes
controversial.
Second,
development
targeted
therapies
able
modulate
macrophage
function
without
systemic
side
effects
area
ongoing
investigation.
Future
directions
involve
exploration
macrophage-targeted
therapies,
small
molecules,
antibodies,
nanotechnology,
behavior
improve
patient
outcomes.
underlines
fact
a
profound
understanding
essential
developing
new
more
effective
strategies.
Targeting
might
represent
avenue
decreasing
incidence
improving
safety
HSCT.
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Март 17, 2025
Abstract
Recent
breakthroughs
in
tumor
immunotherapy
have
confirmed
the
capacity
of
immune
system
to
fight
several
cancers.
The
effective
means
treating
cancer
involves
accelerating
death
cells
and
improving
patient
immunity.
Dynamic
changes
microenvironment
alter
actual
effects
anti-tumor
drug
production
may
trigger
favorable
or
unfavorable
responses
by
modulating
tumor-infiltrating
lymphocytes.
Notably,
CD8
+
T
are
one
primary
that
provide
response.
Tumor
stem
will
resist
evade
destruction
through
various
mechanisms
as
exert
their
function.
This
paper
reviews
research
on
regulation
development
prognosis
directly
indirectly
role
cells.
We
also
discuss
related
strategies.
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Апрель 10, 2025
Systems
biology
is
a
holistic
approach
to
biological
sciences
that
combines
experimental
and
computational
strategies,
aimed
at
integrating
information
from
different
scales
of
processes
unravel
pathophysiological
mechanisms
behaviours.
In
this
scenario,
high-throughput
technologies
have
been
playing
major
role
in
providing
huge
amounts
omics
data,
whose
integration
would
offer
unprecedented
possibilities
gaining
insights
on
diseases
identifying
potential
biomarkers.
the
present
review,
we
focus
strategies
applied
literature
integrate
genomics,
transcriptomics,
proteomics,
metabolomics
year
range
2018-2024.
Integration
approaches
were
divided
into
three
main
categories:
statistical-based
approaches,
multivariate
methods,
machine
learning/artificial
intelligence
techniques.
Among
them,
statistical
(mainly
based
correlation)
ones
with
slightly
higher
prevalence,
followed
by
learning
Integrating
multiple
layers
has
shown
great
uncovering
molecular
mechanisms,
putative
biomarkers,
aid
classification,
most
time
resulting
better
performances
when
compared
single
analyses.
However,
significant
challenges
remain.
The
nature
platforms
introduces
issues
such
as
variable
data
quality,
missing
values,
collinearity,
dimensionality.
These
further
increase
combining
datasets,
complexity
heterogeneity
integration.
We
report
found
cope
these
challenges,
but
some
open
still
remain
should
be
addressed
disclose
full
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Янв. 23, 2025
The
colon
and
rectum
are
highly
innervated,
with
neural
components
within
the
tumor
microenvironment
playing
a
significant
role
in
colorectal
cancer
(CRC)
progression.
While
perineural
invasion
(PNI)
is
associated
poor
prognosis
CRC,
impact
of
nerve
density
diameter
on
behavior
remains
unclear.
This
study
aims
to
evaluate
prognostic
value
characteristics
CRC
verify
nerves
growth.
Tissue
samples
from
129
patients
were
stained
immunofluorescent
markers
NF-L
S100B
detect
nerves.
Nerve
measured
normalized.
Kaplan-Meier
survival
analysis
Cox
regression
models
used
identify
factors.
Prognostic
established
using
receiver
operating
characteristic
(ROC)
curve
assess
predictive
A
murine
chemical
denervation
model
was
employed
disrupt
sympathetic
6-hydroxydopamine,
inhibit
muscarinic
receptor
3
darifenacin,
ablate
sensory
neurons
capsaicin.
total
0.72
±
0.59/mm²,
intratumoral
(0.42
0.40/mm²)
being
significantly
lower
than
extratumoral
regions
(1.00
0.75/mm²).
average
28.14
6.04
μm,
no
difference
between
(28.2
7.65
μm)
(27.86
6.72
μm).
PNI
observed
65
(50.4%).
high
normalized
(NND)
shorter
overall
disease-free
patients,
identified
as
an
independent
factor.
Patients
exhibit
higher
NND.
Incorporating
NND
into
ROC
improved
sensitivity
specificity
predictions.
In
model,
sympathetic,
parasympathetic,
reduced
rectal
volume.
critical
factors
influencing
patient
enhance
accuracy
prediction
models.
Moreover,
effectively
inhibits
growth
vivo,
highlighting
potential
targeting
therapeutic
strategy
CRC.
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Апрель 10, 2025
Ischemic
stroke
is
a
prevalent
form
of
cerebrovascular
accident,
with
its
pathogenesis
involving
the
intricate
interplay
between
neuroinflammation
and
energy
metabolism.
Cerebral
ischemia
disrupts
oxygen
supply,
triggering
metabolic
dysregulation
activating
neuroinflammatory
responses,
ultimately
resulting
in
cellular
damage.
This
review
provides
an
exhaustive
analysis
complex
mechanisms
ischemic
stroke,
particular
focus
on
interaction
The
interruption
supply
due
to
cerebral
initiates
activates
including
release
inflammatory
cytokines
activation
immune
cells,
contributing
damage
further
disturbances.
Studies
indicate
that
metabolism
significantly
impairs
neural
cell
function
interacts
neuroinflammation,
exacerbating
brain
injury.
Therapeutic
strategies
primarily
concentrate
modulating
suppressing
emphasizing
importance
in-depth
research
into
their
provide
theoretical
foundation
for
new
treatment
stroke.
Future
should
how
balance
anti-inflammatory
regulation
minimize
promote
recovery.
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Апрель 24, 2025
Metabolic
Associated
Steatotic
Liver
Disease
(MASLD),
encompassing
conditions
simple
liver
steatosis
(MAFL)
and
metabolic
associated
steatohepatitis
(MASH),
is
the
most
prevalent
chronic
disease.
Currently,
management
of
MASLD
impeded
by
lack
reliable
diagnostic
biomarkers
effective
therapeutic
strategies.
We
analyzed
eight
independent
clinical
datasets
from
GEO
database.
Differential
expression
weighted
gene
co-expression
network
analyses
(WGCNA)
were
used
to
identify
23
genes
related
inflammation.
Five
hub
selected
using
machine
learning
techniques
(SVM-RFE,
LASSO,
RandomForest)
combined
with
a
literature
review.
Nomograms
created
predict
incidence,
potential
was
evaluated
through
receiver
operating
characteristic
(ROC)
curves.
Additionally,
Protein-Protein
Interaction
(PPI)
networks,
functional
enrichment,
immune
infiltration
performed.
Potential
transcription
factors
agents
also
explored.
Finally,
biological
significance
these
validated
animal
model,
histological
examination
transcriptomic
profiles.
identified
five
genes-UBD/FAT10,
STMN2,
LYZ,
DUSP8,
GPR88-that
are
for
MASLD.
These
exhibited
strong
potential,
either
individually
or
in
combination.
This
study
highlights
key
as
promising
candidates
understanding
findings
offer
new
insights
into
disease's
pathophysiology
may
contribute
development
better
approaches.
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Янв. 16, 2025
Colorectal
cancer
(CRC)
remains
a
major
global
health
challenge,
with
high
rates
of
incidence
and
mortality.
This
study
investigates
the
role
protein
arginine
methyltransferase
6
(PRMT6)
as
an
oncogene
in
CRC
its
mechanistic
involvement
tumor
progression.
We
found
that
PRMT6
is
significantly
overexpressed
tissues
compared
to
adjacent
normal
associated
poorer
patient
survival.
Functional
assays
demonstrated
promotes
cell
proliferation,
migration,
invasion.
Mechanistically,
enhances
MYC
signaling
by
stabilizing
c-MYC
through
mono-methylation
at
371,
which
inhibits
poly-ubiquitination
subsequent
degradation.
post-translational
modification
crucial
for
PRMT6-induced
proliferation.
Xenograft
models
further
validated
knockdown
results
reduced
growth
decreased
levels.
Our
findings
highlight
key
regulator
stability
progression,
suggesting
targeting
or
effects
on
could
offer
promising
strategy
treatment.
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Фев. 4, 2025
Prostate
Tumor
Overexpressed
1
(PTOV1)
is
overexpressed
and
associated
with
malignant
phenotypes
in
various
types
of
tumors.
However,
the
detailed
roles
PTOV1
its
underlying
mechanism
CRC
remain
unclear.
The
clinical
significance
was
assessed
databases
samples.
effects
on
tumor-associated
were
detected
by
several
vitro
assays
vivo
mouse
models.
Immunoprecipitation
(IP)
combined
protein
mass
spectrometry
Co-Immunoprecipitation
(Co-IP)
used
to
identify
p53
interacting
PTOV1.
Immunofluorescence
assay,
western
blot
transmission
electron
microscopy
(TEM)
analysis
evaluated
autophagy.
Here,
we
revealed
that
highly
expressed
human
tissues,
especially
at
advanced
stages,
reduced
survival
time
among
patients.
upregulated
promoted
cell
proliferation,
migration,
invasion,
tumor
growth
metastasis
cells
vivo.
At
molecular
level,
destabilized
activating
autophagy
recruiting
for
cargo
receptor
SQSTM1
directed
autophagic
degradation.
There
a
negative
expression
correlation
between
tissues.
Moreover,
overexpression
or
knockdown
reversed
pro-tumor
CRC.
Our
study
unveils
oncogenic
role
progression,
which
achieved
promoting
degradation
p53.
These
findings
highlight
potential
targeting
PTOV1-SQSTM1-p53
axis
as
therapeutic
approach