bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 2, 2024
Abstract
Colorectal
cancer
(CRC)
is
the
third
most
diagnosed
and
second
leading
cause
of
cancer-related
deaths
globally,
often
due
to
late
detection
limited
treatment
options.
Recent
studies
have
linked
alterations
in
gut
microbiota
CRC,
particularly
emphasizing
role
short-chain
fatty
acids
(SCFAs)
like
acetate,
propionate,
butyrate
shaping
tumor
microenvironment
(TME).
SCFAs
contribute
CRC
pathogenesis
by
inducing
lysosomal
membrane
permeabilization,
cell
cycle
arrest,
apoptosis
cells.
Extracellular
vesicles
(EVs)
are
membrane-bound
that
facilitate
intercellular
communication
gained
attention
as
promising
non-invasive
biomarkers
for
diagnosis
monitoring.
EVs
participate
cellular
response
mechanisms
external
stimuli
transferring
proteins,
lipids,
nucleic
between
cells,
thus
modulating
target
behavior
promoting
coordinated
responses
stress
environmental
challenges.
This
process
essential
adaptation
plays
a
significant
pathophysiological
processes,
including
progression
immune
modulation,
making
highly
relevant
clinical
research.
study
examined
impact
on
EV
production
phenotype
The
results
indicated
notable
increase
EV-sized
particles
following
SCFA
colorectal
lines,
SW480
line.
For
while
co-precipitated
protein
levels
remained
stable,
there
was
slight
decrease
DNA
an
EV-associated
DNA.
KRAS-mutant
cells
exhibited
pronounced
response,
their
heightened
sensitivity
SCFA.
Notably,
microsatellite
instability
-
key
biomarker
immunotherapy
detected
both
small
large
populations
from
BRAF-mutant
RKO
after
treatment,
even
at
low
concentrations.
These
findings
underscore
potential
molecular
markers,
paving
way
further
exploration
precision
oncology.
Figure
Graphical
Abstract.
Effects
characteristics
Treatment
with
led
number
particles,
corresponding
EV-DNA.
also
identified
MSI
s-EV
L-EV,
Created
using
BioRender.
Naturally
occurring
extracellular
vesicles
(EVs)
and
synthetic
nanoparticles
like
liposomes
have
revolutionized
precision
diagnostics
medicine.
EVs
excel
in
biocompatibility
cell
targeting,
while
offer
enhanced
drug
loading
capacity
scalability.
The
clinical
translation
of
is
hindered
by
challenges
including
low
yield
heterogeneity,
whereas
face
rapid
immune
clearance
limited
targeting
efficiency.
To
bridge
these
gaps,
biomimetic
(SVs)
emerged
as
innovative
platforms,
combining
the
advantageous
properties
liposomes.
This
review
emphasizes
critical
aspects
EV
biology,
such
mechanisms
EV-cell
interaction
source-dependent
functionalities
modulation,
tissue
regeneration,
informing
SV
engineering.
We
reviewed
a
broad
array
SVs,
with
focus
on
lipid
bilayered
functionalized
proteins.
These
include
cell-derived
nanovesicles,
protein-functionalized
liposomes,
hybrid
vesicles.
By
addressing
current
highlighting
opportunities,
this
aims
to
advance
SVs
for
transformative
biomedical
applications.
Extracellular
vesicles
(EVs)
are
critical
mediators
of
intercellular
communication,
carrying
bioactive
cargo
and
displaying
diverse
surface
components
that
reflect
their
cellular
origins
functions.
The
EV
surface,
composed
proteins,
lipids,
glycocalyx
elements,
plays
a
pivotal
role
in
targeting
recipient
cells,
mediating
biological
interactions,
enabling
selective
delivery.
This
review
comprehensively
examined
the
molecular
architecture
surfaces,
linking
biogenesis
to
functional
diversity,
highlights
therapeutic
diagnostic
potential
diseases
such
as
cancer
cardiovascular
disorders.
Additionally,
we
explore
emerging
applications
EVs,
including
machine-learning-assisted
analysis,
chemical
integration,
cross-system
combinations.
also
discusses
some
key
challenges
clinical
translation
EV-related
technologies.
Pleural
Mesothelioma
(PM)
is
a
highly
aggressive
cancer,
for
which
effective
early
detection
remains
challenge
due
to
limited
screening
options
and
low
sensitivity
of
biomarkers
discovered
so
far.
While
extracellular
vesicles
(EVs)
have
emerged
as
promising
candidates
blood-based
biomarkers,
their
role
in
PM
has
not
been
studied
yet.
In
this
study,
we
characterized
the
transcriptomic
profile
EVs
secreted
by
primary
cells
explored
potential
biomarker
source
detection.
We
collected
cell
culture
supernatant
from
early-passage
cultures
derived
pleural
effusion
4
patients.
were
isolated
using
Qiagen
exoEasy
Maxi
kit.
RNA
isolation
was
done
mirVana
PARIS
Finally,
single-end
sequencing
with
Illumina
Novaseq
6000.
identified
range
species
expressed
cells,
including
protein-coding
(80%),
long
non-coding
(13%),
pseudogenes
(4.5%),
short
(1.6%).
detected
subset
genes
associated
previously
epithelioid
(32
genes)
sarcomatoid
molecular
components
(36
PM-EVs.
To
investigate
whether
these
markers
could
serve
blood,
compared
content
PM-EVs
cargo
plasma
healthy
donors
(publicly
available
data).
Majority
upregulated
RNAs.
Interestingly,
25
them
marker
genes.
functional
analysis
revealed
that
PM-EV
Epithelial-Mesenchymal
transition,
glycolysis,
hypoxia.
This
first
study
characterize
cultures,
demonstrating
Further
investigation
will
provide
new
insights
into
disease
biology
therapeutic
avenues.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Март 11, 2025
Extracellular
vesicles
(EVs)
are
secreted
by
most
cell
types
and
play
a
central
role
in
cell-cell
communication.
These
naturally
occurring
nanoparticles
have
been
particularly
implicated
cancer,
but
EV
heterogeneity
lengthy
isolation
methods
with
low
yield
make
them
difficult
to
study.
To
circumvent
the
challenges
research,
we
aimed
develop
unique
synthetic
model
engineering
bioinspired
liposomes
study
properties
their
impact
on
cellular
uptake.
We
produced
EV-like
mimicking
physicochemical
as
cancer
EVs.
First,
using
panel
of
non-cancer
lines,
small
EVs
were
isolated
ultracentrifugation
characterized
dynamic
light
scattering
(DLS)
nanoparticle
tracking
analysis
(NTA).
Cancer
ranged
mean
size
from
107.9
161
nm
NTA,
hydrodynamic
diameter
152
355
DLS,
zeta
potential
ranging
−
25
-6
mV.
markers
TSG101
CD81
positive
all
Using
microfluidics
bottom-up
approach,
nanoprecipitation
method
adapted
micromixers
developed
our
group.
A
library
liposome
formulations
was
created
that
mimicked
ranges
(90–222
nm)
(anionic
[-47
mV]
neutral
[-1
mV])
at
production
throughput
up
41
mL/h
yielding
concentration
1
×
1012
particles
per
mL.
reproduced
controlling
flow
conditions
lipid
composition
set
statistical
based
response
surface
methodology.
The
fairly
accurate
an
R-squared
>
70%
for
both
parameters
between
targeted
obtained
liposomes.
Finally,
internalization
fluorescently
labeled
assessed
confocal
microscopy
cytometry,
correlated
decreasing
less
negative
potential,
providing
insights
into
effects
key
properties.
Our
data
demonstrated
can
be
used
powerful
By
cell-derived
properties,
individually
combination.
Taken
together,
present
novel
system
accelerate
research
models.
npj Precision Oncology,
Год журнала:
2025,
Номер
9(1)
Опубликована: Март 24, 2025
Circulating
tumor
DNA
(ctDNA)
has
emerged
as
a
dynamic
biomarker
in
cancer,
evidenced
by
its
increasing
integration
into
clinical
practice.
Carrying
specific
characteristics,
ctDNA
can
be
used
to
inform
treatment
selection,
monitor
response,
and
identify
drug
resistance.
In
this
review,
we
provide
comprehensive,
up-to-date
summary
of
monitoring
response
with
focus
on
lung,
colorectal,
breast
cancers,
discuss
current
challenges
future
directions.
R
loops
are
three-stranded
nucleic
acid
structures
that
form
naturally
in
cells
under
various
conditions,
mainly
as
intermediates
during
replication
or
by-products
transcription.
involved
the
regulation
of
many
important
cellular
processes,
including
replication,
transcription,
centromere
stabilization,
protection
chromosome
ends,
control
telomere
length.
Unscheduled
linked
to
diseases,
cancer,
neurodegenerative,
inflammatory
disorders.
The
list
cancer
diseases
excessive
loop
accumulation
is
growing
rapidly.
There
currently
much
debate
about
understanding
abnormal
formation
and
its
impact
on
genome
instability
development.
In
this
review,
we
briefly
describe
nature
loops,
their
physiological
pathological
proteins
loops.
addition,
emphasize
possible
role
human
ribonuclease
Dicer,
a
multi-tasking
protein
mostly
known
for
microRNA
biogenesis,
We
also
discuss
involvement
development
potential
use
diagnostic
biomarkers.
Knowledge
molecular
mechanisms
underlying
dysregulation
may
significantly
improve
our
biology
provide
new
directions
research.
Expert Review of Molecular Diagnostics,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 3, 2025
Extracellular
vesicles
are
membranous
particles
released
by
cells
in
physiological
and
pathological
conditions.
Their
cargo
is
heterogeneous
since
it
includes
different
biomolecules
such
as
nucleic
acids
proteins.
Oncogenic
alterations
affect
the
composition
of
extracellular
model
their
content
during
cancer
evolution.
This
review
provides
an
overview
studies
focused
on
source
biomarkers
hematological
malignancies.
A
special
insight
into
vesicles-derived
tools
for
evaluating
prognosis
malignancies
response
to
treatment
given.
a
valuable
However,
translation
from
bench
bedside
challenged
lack
standardization
preanalytical
variables
experimental
workflow.
The
release
standard
operating
procedures
validation
large
cohort
patients
will
help
exploiting
potential
clinical
setting.
Molecular Diagnosis & Therapy,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 16, 2025
Cell-free
DNA
(cfDNA)
is
changing
the
face
of
liquid
biopsy
as
a
minimally
invasive
tool
for
disease
detection
and
monitoring,
with
its
main
applications
in
oncology
prenatal
testing,
rising
roles
transplant
patient
monitoring.
However,
processes
cfDNA
biogenesis,
fragmentation,
clearance
are
complex
require
further
investigation.
Evidence
suggests
that
production
relates
to
mechanisms
cell
death
repair,
both
which
influence
fragment
size
applicability
biomarker.
An
emerging
domain,
fragmentomics
being
explored
advancing
field
diagnostics
using
non-mutational
signatures
such
ratios
methylation
patterns.
Thus,
this
review
examines
structural
diversity
various
sizes.
In
examining
these
subsets,
we
discuss
their
distinct
biological
origins
potential
clinical
utility.
Development
sequencing
methodologies
has
broadened
application
diagnosing
cancers
organ-specific
pathologies,
well
directing
personalized
therapies.
This
been
achieved
by
identifying
uncovering
different
subsets
biofluids
biofluids.
Different
provide
important
insights
regarding
genomic
epigenetic
features,
enhancing
understanding
gene
regulation,
tissue-specific
functions,
progression.
Advancement
key
areas
asserts
increasing
relevance
use
Continued
exploration
expected
drive
innovation
integration
into
routine
practice.