ALTEX,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 1, 2024
Next
generation
risk
assessment
of
chemicals
revolves
around
the
use
mechanistic
information
without
animal
experimentation.
In
this
regard,
toxicogenomics
has
proven
to
be
a
useful
tool
elucidate
underlying
mechanisms
adverse
effects
xenobiotics.
present
study,
two
widely
used
human
in
vitro
hepatocyte
culture
systems,
namely
primary
hepatocytes
(PHH)
and
hepatoma
HepaRG
cells,
were
exposed
liver
toxicants
known
induce
cholestasis,
steatosis
or
necrosis.
Benchmark
concentration-response
modelling
was
applied
transcriptomics
gene
co-expression
networks
(modules)
derive
benchmark
concentrations
(BMCs)
gain
insight
into
hepatotoxic
effects.
BMCs
derived
by
modules
recapitulated
individual
genes.
Although
PHH
cells
showed
overlap
deregulated
genes
toxicants,
demonstrated
higher
responsiveness,
based
on
lower
co-regulated
modules.
Such
can
as
point
departure
(tPOD)
for
assessing
module-associated
cellular
(stress)
pathways/processes.
This
approach
identified
clear
tPODs
maximum
systemic
concentration
(Cmax)
levels
tested
drugs,
while
cosmetics
ingredients
10-100-fold
than
estimated
plasma
concentrations.
could
serve
next
practice
identify
early
responsive
at
low
BMCs,
that
linked
key
events
outcome
pathways.
turn,
assist
delineating
potential
hazards
new
test
using
systems
when
are
paired
with
chemical
exposure
assessment.
Plain
language
summaryRisk
traditionally
been
focused
experiments.
contrast,
uses
biological
obtained
from
experiments
cell
models
animals
hazards.
Since
is
main
target
organ
toxicity,
many
(hepatocyte)
have
developed
hazard
models,
HepaRG,
toxic
chemicals.
Biological
changes
expression
measured
range
which
response
perturbed
modelling.
Genes
belonging
same
process
joined
an
average
process.
animal-free
related
expected
Burns & Trauma,
Journal Year:
2025,
Volume and Issue:
13
Published: Jan. 1, 2025
Abstract
Effective
wound
management
and
treatment
are
crucial
in
clinical
practice,
yet
existing
strategies
often
fall
short
fully
addressing
the
complexities
of
skin
healing.
Recent
advancements
tissue
engineering
have
introduced
innovative
approaches,
particularly
through
use
nanobiomaterials,
to
enhance
healing
process.
In
this
context,
titanium
dioxide
nanoparticles
(TiO2
NPs)
garnered
attention
due
their
excellent
biological
properties,
including
antioxidant,
anti-inflammatory,
antimicrobial
properties.
Furthermore,
these
can
be
modified
therapeutic
benefits.
Scaffolds
dressings
containing
TiO2
NPs
demonstrated
promising
outcomes
accelerating
enhancing
regeneration.
This
review
paper
covers
process,
properties
that
make
them
suitable
for
promoting
healing,
methods
synthesizing
NPs,
scaffolds
application
potential
toxicity
NPs.
Environmental Research,
Journal Year:
2022,
Volume and Issue:
217, P. 114650 - 114650
Published: Oct. 26, 2022
While
human
regulatory
risk
assessment
(RA)
still
largely
relies
on
animal
studies,
new
approach
methodologies
(NAMs)
based
in
vitro,
silico
or
non-mammalian
alternative
models
are
increasingly
used
to
evaluate
chemical
hazards.
Moreover,
epidemiological
studies
with
biomarkers
of
effect
(BoE)
also
play
an
invaluable
role
identifying
health
effects
associated
exposures.
To
move
towards
the
next
generation
(NGRA),
it
is
therefore
crucial
establish
bridges
between
NAMs
and
standard
approaches,
processes
for
increasing
mechanistically-based
biological
plausibility
studies.
The
Adverse
Outcome
Pathway
(AOP)
framework
constitutes
important
tool
address
these
needs
but,
despite
a
significant
increase
knowledge
awareness,
use
AOPs
RA
remains
limited.
objective
this
paper
issues
related
using
context
from
various
perspectives
as
was
discussed
workshop
organized
within
European
Union
partnerships
HBM4EU
PARC
spring
2022.
presents
examples
where
AOP
has
been
proven
useful
process,
particularly
hazard
prioritization
characterization,
integrated
approaches
testing
(IATA),
identification
validation
BoE
Nevertheless,
several
limitations
were
identified
that
hinder
optimal
usability
acceptance
by
community
including
lack
quantitative
information
response-response
relationships
efficient
ways
map
data
(exposure
toxicity)
onto
AOPs.
summarizes
suggestions,
ongoing
initiatives
third-party
tools
may
help
overcome
obstacles
thus
assure
better
implementation
NGRA.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(5), P. 2912 - 2912
Published: March 2, 2024
This
study
aims
to
analyze
post-mortem
human
cardiac
specimens,
verify
and
evaluate
the
existence
or
extent
of
oxidative
stress
in
subjects
whose
cause
death
has
been
traced
sepsis,
through
immunohistological
oxidative/nitrosative
markers.
Indeed,
present
study,
i-NOS,
NOX2,
nitrotyrosine
markers
were
higher
expressed
septic
group
when
compared
control
group,
associated
with
also
a
significant
increase
8-OHdG,
highlighting
pivotal
role
etiopathogenesis.
In
particular,
70%
cardiomyocyte
nuclei
from
specimens
showed
positivity
for
8-OHdG.
Furthermore,
intense
massive
NOX2-positive
myocyte
immunoreaction
was
noticed
as
immunostaining
reaction
found
cells.
These
results
demonstrated
correlation
between
nitrosative
imbalance
pathophysiology
dysfunction
documented
cases
sepsis.
Therefore,
subsequent
studies
will
focus
on
expression
other
organs
tissues,
well
involvement
intracellular
pattern
apoptosis,
better
clarify
complex
pathogenesis
multi-organ
failure,
leading
support
rationale
including
therapies
targeting
redox
abnormalities
management
patients.
Chemosphere,
Journal Year:
2025,
Volume and Issue:
371, P. 144056 - 144056
Published: Jan. 4, 2025
For
decades,
studies
have
shown
how
exposure
to
non-essential
trace
metals
such
as
lead
(Pb)
and
cadmium
(Cd)
largely
impact
global
wildlife.
Ecoimmunotoxicology
has
emerged
in
the
past
two
decades
focuses
on
effects
of
pollutants
immune
system
free-ranging
organisms.
Adverse
outcome
pathways
(AOPs)
represent
a
conceptual
approach
explore
mechanistic
linkage
between
molecular
initiating
event
adverse
outcomes,
potentially
at
all
biological
levels
organisation.
The
present
paper
proposes
putative
AOPs
related
Cd,
Pb,
mixture
Cd-Pb,
mammals
address
future
questions
ecoimmunotoxicology.
Molecular
Initiating
Events
for
both
relate
entrance
cells
through
Ca2+
channels
or
bond
cell
surfaces.
Exposure
Pb
Cd-Pb
share
several
similar
Key
(KEs),
primarily
an
increase
oxidative
stress
(OS)
production
reactive
oxygen
species.
mixture,
OS
affects
mitochondrial
membranes,
induces
apoptosis,
ultimately
decreasing
number.
Both
affect
innate
nuclear
factor
kappa
B
(NF-κB)
mitogen-activated
protein
kinase
(MAPK)
inflammatory
signalling
pathways,
leading
upregulation
markers
mediators.
Adaptive
is
also
affected
by
though
decrease
CD4+/CD8+
ratio,
MHCII,
inactivation
TH1
TH2
response,
inhibition
humoral
response
mediated
various
Ig.
Mixture
are
less
documented
resulting
more
speculative
AOP,
but
potential
synergic
antagonistic
were
identified.
According
our
AOPs,
further
research
ecoimmunotoxicology
should
focus
KEs
NF-κB/MAPK
changes
ratio
MHCII
complexes,
AOs
auto-immune
disorders
effective
infection
rate,
particularly
case
metal
mixtures.
International Journal of Radiation Biology,
Journal Year:
2022,
Volume and Issue:
98(12), P. 1816 - 1831
Published: Aug. 17, 2022
Reproductive
effects
of
ionizing
radiation
in
organisms
have
been
observed
under
laboratory
and
field
conditions.
Such
assessments
often
rely
on
associations
between
exposure
effects,
thus
lacking
a
detailed
mechanistic
understanding
causality
occurring
at
different
levels
biological
organization.
The
Adverse
Outcome
Pathway
(AOP),
conceptual
knowledge
framework
to
capture,
organize,
evaluate
visualize
the
scientific
relevant
toxicological
has
potential
causal
relationships
molecular,
cellular,
individual,
population
effects.
This
paper
presents
first
development
set
consensus
AOPs
for
reproductive
wildlife.
work
was
performed
by
group
experts
formed
during
workshop
organized
jointly
Multidisciplinary
European
Low
Dose
Initiative
(MELODI)
Radioecology
Alliance
(ALLIANCE)
present
AOP
approach
tools.
series
taxon-specific
case
studies
that
were
used
identify
empirical
evidence,
common
components
propose
could
be
into
an
network
with
broader
taxonomic
applicability.Expert
consultation
led
identification
key
events
description
linkages
radiation,
impairment
reduction
fitness.
study
characterized
domain
AOPs,
identified
gaps
pertinent
reproductive-relevant
reflected
how
assist
applications
(radioecological)
research,
environmental
health
assessment,
radiological
protection.
Future
advancement
consolidation
is
planned
include
structured
weight
evidence
considerations,
formalized
review
critical
assessment
prior
formal
submission
OECD
sponsored
program.
Science Advances,
Journal Year:
2025,
Volume and Issue:
11(12)
Published: March 21, 2025
Lipid
metabolism
and
the
serine,
one-carbon,
glycine
(SOG)
methionine
pathways
are
independently
significantly
correlated
with
estrogen
receptor–negative
breast
cancer
(ERneg
BC).
Here,
we
propose
a
link
between
lipid
ERneg
BC
through
phosphoglycerate
dehydrogenase
(PHGDH),
rate-limiting
enzyme
in
de
novo
serine
pathway.
We
demonstrate
that
of
paradigmatic
medium-chain
fatty
acid
octanoic
leads
to
metabolic
shift
toward
SOG
pathways.
PHGDH
plays
role
both
forward
direction,
contributing
production
S-adenosylmethionine,
reverse
generating
oncometabolite
2-hydroxyglutarate,
leading
epigenomic
reprogramming
phenotypic
plasticity.
The
cycle
is
closely
linked
transsulfuration
Consequently,
observe
increases
antioxidant
glutathione,
which
mitigates
reactive
oxygen
species
(ROS),
enabling
survival
subset
cells
have
undergone
DNA
damage.
These
changes
contribute
several
hallmarks
cancer.
ALTEX,
Journal Year:
2023,
Volume and Issue:
unknown
Published: Jan. 1, 2023
The
adverse
outcome
pathways
(AOPs)
were
developed
to
accelerate
evidence-based
chemical
risk
assessment
by
leveraging
data
from
new
approach
methodologies.
Thanks
their
stressor-agnostic
approach,
AOPs
seen
as
instrumental
in
other
fields.
Here,
we
present
that
report
non-chemical
stressors
along
with
the
challenges
encountered
for
development.
Challenges
regarding
linked
nanomaterials
include
non-specific
molecular
initiating
events,
limited
understanding
of
nanomaterial
biodistribution,
and
needs
adaptations
silico
modeling
testing
systems.
Development
radiation
face
how
incorporate
ionizing
events
type,
dose
rate,
energy
deposition,
account
targeting
multiple
macromolecules.
COVID-19
required
inclusion
SARS-CoV-2-specific
replicative
steps
capture
essential
driving
disease.
Developing
evaluate
efficacy
toxicity
cell
therapies
necessitates
addressing
cellular
nature
therapeutic
function
stressor.
Finally,
emerging
biological
like
microbial
pesticides
can
learn
AOPs.
We
further
discuss
needed
expand
AOP
applicability
beyond
chemicals
are
mainly
at
levels
while
downstream
key
tissue
or
organ
level,
such
inflammation,
shared
many
initiated
various
stressors.
In
conclusion,
although
it
is
challenging
integrate
within
AOPs,
this
expands
opportunities
real-world
scenarios,
identify
vulnerable
individuals,
bridge
knowledge
on
mechanisms
adversity.
Plain
language
summaryThe
pathway
(AOP)
framework
was
help
predict
whether
have
toxic
effects
humans.
Structuring
available
information
an
accessible
database
reduce
animal
testing.
usually
path
interaction
a
stressor,
chemical,
human
body
outcome,
e.g.,
disease
symptom.
concept
has
now
been
expanded
nanomaterials,
radiation,
viruses,
cells
used
treat
patients,
microorganisms
employed
pesticides.
use
these
need
be
accommodated
point
out
share
inflammation
By
integrating
into
framework,
scenarios
where
people
may
exposed
different
stressor
types
considered,
individuals
identified,
compounded.
Frontiers in Public Health,
Journal Year:
2024,
Volume and Issue:
12
Published: April 8, 2024
Climate
change
is
accompanied
by
changes
in
the
exposome,
including
increased
heat,
ground-level
ozone,
and
other
air
pollutants,
infectious
agents,
pollens,
psychosocial
stress.
These
exposures
alter
internal
component
of
exposome
account
for
some
health
effects
climate
change.
The
adverse
outcome
pathways
describe
biological
events
leading
to
an
unfavorable
outcome.
In
this
perspective
study,
I
propose
use
toxicological
framework
better
steps
linking
a
stressor
associated
with
Such
also
allows
identification
possible
interactions
between
stressors
related
others,
such
as
chemical
pollution.
More
generally,
call
incorporation
part
improved
involved
its
effects.