Network-Based Identification of Key Toxic Compounds in Airborne Chemical Exposome
Environmental Science & Technology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 14, 2025
Air
pollution
is
a
leading
contributor
to
the
global
disease
burden.
However,
complex
nature
of
chemicals
which
humans
are
exposed
through
inhalation
has
obscured
identification
key
compounds
responsible
for
diseases.
Here,
we
develop
network
topology-based
framework
identify
toxic
in
airborne
chemical
exposome.
Using
cardiovascular
diseases
(CVDs)
as
model
disease,
found
that
modules
various
closely
linked
CVDs.
The
proximity
compound
target
can
indicate
extent
toxicity
induced
by
compounds.
By
integrating
mass
spectrometry-based
external
exposure
concentrations
and
machine
learning-predicted
internal
concentrations,
established
comprehensive
linkage
connecting
disease-related
risk
These
findings
were
subsequently
validated
using
data
on
regional
scale.
This
work
provides
an
effective
strategy
identifying
within
environmental
exposomes
establishes
new
paradigm
understanding
pathogenicity
air
pollution.
Язык: Английский
New insights into the mechanism of triphenyl phosphate and its metabolite diphenyl phosphate in diabetic kidney disease
Ecotoxicology and Environmental Safety,
Год журнала:
2025,
Номер
291, С. 117877 - 117877
Опубликована: Фев. 1, 2025
Diabetic
kidney
disease
is
a
significant
complication
of
diabetes
mellitus,
and
exposure
to
certain
chemicals
may
play
role
in
its
development.
Triphenyl
phosphate
(TPHP)
commonly
used
plastics
flame
retardants.
This
study
aims
investigate
the
potential
impact
TPHP
metabolite
diphenyl
(DPHP)
on
diabetic
using
various
methods,
including
network
toxicology,
molecular
docking,
cell
experiments
like
CCK8
assay
real-time-PCR.
The
research
examined
relationship
between
urinary
DPHP
levels
function
American
adults
data
from
National
Health
Nutrition
Examination
Survey
(NHANES)
2017
March
2020.
Additionally,
explored
targets
action
for
toxicity
analysis,
conducted
protein
interaction
functional
aspects
through
Gene
Ontology
Kyoto
Encyclopedia
Genes
Genomes
enrichment
analysis.
Furthermore,
identified
key
proteins
involved
experimental
verification
by
treating
cells
with
DPHP.
Toxicity
analysis
showed
that
could
cause
dose-dependent
mouse
podocyte
clone
5
(MPC5)
mesangial
(MES13).
also
detected
mRNA
expression
core
molecularly
docked
results
indicated
statistically
regulation
most
MPC5,
MES13,
human
kidney-2
cells.
Язык: Английский
Triphenyl phosphate induces lipid metabolism disorder and promotes obesity through PI3K/AKT signaling pathway
Tianlan Li,
Yiwa Liu,
Jingyi Cao
и другие.
Environment International,
Год журнала:
2025,
Номер
198, С. 109428 - 109428
Опубликована: Апрель 1, 2025
Triphenyl
phosphate
(TPHP)
is
a
widely
used
organic
flame
retardant
that
has
been
reported
as
potential
environmental
obesogen.
However,
the
impact
and
mechanism
of
action
TPHP
on
adipose
tissue
are
still
unclear.
This
study
investigates
lipid
metabolism
disorders
through
in
vivo
vitro
experiments.
Male
female
BALB/c
mice
were
exposed
to
(0,
1,
10,
150
mg/kg/day)
for
60
days,
3T3-L1
preadipocytes
treated
with
concentrations
0.1,
10
μM)
during
differentiation.
The
results
showed
exposure
could
cause
gender
specific
dyslipidemia,
male
exhibiting
dose-dependent
increases
inguinal
coefficient,
adipocyte
hypertrophy,
upregulation
differentiation
adipogenesis-related
genes.
In
contrast,
did
not
show
significant
changes
morphology.
suggested
might
promote
occurrence
adiposity
by
disrupting
homeostasis
tissue.
During
maturation
process
preadipocytes,
led
increased
accumulation
disrupted
simultaneous
activation
adipogenesis
lipolysis.
Multiple
omics
data
peroxisome
proliferator-activated
receptor
γ
(PPARγ)
signaling
pathway
fatty
acid
was
core
induced
metabolic
dysfunction.
Further
research
activated
PI3K/AKT
pathway,
PI3K
inhibitor
(LY294002)
rescue
droplet
formation
normalize
expression
adipogenic
markers.
These
findings
confirm
obesogen
can
disrupt
white
PPARγ
pathways,
higher
susceptibility
males.
provides
compelling
evidence
obesogenic
effects
information
risk
assessment
organophosphorus
retardants.
Язык: Английский
Mechanisms underlying targeted mitochondrial therapy for programmed cardiac cell death
Frontiers in Physiology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 11, 2025
Heart
diseases
are
common
clinical
diseases,
such
as
cardiac
fibrosis,
heart
failure,
hypertension
and
arrhythmia.
Globally,
the
incidence
rate
mortality
of
increasing
by
years.
The
main
mechanism
disease
is
related
to
cellular
state.
Mitochondrion
organ
energy
supply,
participating
in
various
signal
transduction
pathways
playing
a
vital
role
occurrence
development
disease.
This
review
summarizes
cell
death
patterns
molecular
mechanisms
associated
with
mitochondrial
dysfunction.
Язык: Английский
Mechanism of Nano‐Microplastics Exposure‐Induced Myocardial Fibrosis: DKK3‐Mediated Mitophagy Dysfunction and Pyroptosis
Journal of Biochemical and Molecular Toxicology,
Год журнала:
2025,
Номер
39(5)
Опубликована: Апрель 22, 2025
ABSTRACT
Nano‐microplastics
(NMPs),
as
environmental
pollutants,
are
widely
present
in
nature
and
pose
potential
threats
to
biological
health.
This
study
aims
investigate
the
mechanisms
by
which
NMPs
inhibit
mitophagy
through
suppression
of
dickkopf‐related
protein
3
(DKK3)
expression,
leading
NOD‐like
receptor
family,
pyrin
domain
containing
(NLRP3)
inflammasome‐mediated
cardiomyocyte
pyroptosis
promoting
myocardial
fibrosis.
Healthy
adult
male
C57BL/6
mice
were
administered
NMP
solution
via
gavage,
their
cardiac
function
was
monitored.
The
results
showed
that
exposure
significantly
reduced
left
ventricular
ejection
fraction
(LVEF)
fractional
shortening
(LVFS)
increased
extent
Transcriptome
sequencing
identified
14
differentially
expressed
genes
(DEGs),
including
MYL7.
Using
random
forest
algorithm
functional
enrichment
analysis,
DKK3
a
key
gene.
In
Vitro
experiments
further
confirmed
downregulate
thereby
inhibiting
pyroptosis.
elucidates
molecular
induce
fibrosis
provides
new
theoretical
bases
targets
for
diagnosis
treatment
heart
diseases.
Язык: Английский
Adipogenic Effects of Cresyl Diphenyl Phosphate (Triphenyl Phosphate Alternative) through Peroxisome Proliferator-Activated Receptor Gamma Pathway: A Comprehensive Study Integrating In Vitro, In Vivo, and In Silico from Molecule to Health Risk
Environmental Science & Technology,
Год журнала:
2024,
Номер
58(42), С. 18631 - 18641
Опубликована: Окт. 9, 2024
Cresyl
diphenyl
phosphate
(CDP),
a
novel
organophosphate
ester
(OPE),
has
been
detected
in
various
environmental
and
human
samples.
However,
there
is
very
limited
knowledge
regarding
its
toxicity,
mechanisms
of
action,
potential
health
risks.
Using
new
alternative
methods
(NAMs),
across
the
molecular
interactions,
signaling
pathways,
cell
functions,
animal
effects,
population
risks,
we
investigated
adipogenic
effects
associated
risks
CDP
legacy
OPE
triphenyl
(TPHP)
by
acting
on
peroxisome
proliferator-activated
receptor
gamma
(PPARγ).
Among
19
screened
OPEs,
bound
to
PPARγ
with
highest
binding
potency,
followed
TPHP.
activated
through
fitting
into
pocket
strong
hydrophobicity
hydrogen
bond
interactions;
exhibited
higher
potency
compared
In
3T3-L1
cells,
enhanced
PPARγ-mediated
adipogenesis
activity,
exhibiting
greater
than
The
intracellular
concentration
receptor-bound
concentrations
(RBC)
were
also
those
TPHP
both
HEK293
cells
cells.
mice,
exposure
pathway,
leading
an
increased
white
adipose
tissue
weight
gain.
Overall,
could
bind
activate
PPARγ,
thereby
promoting
preadipocyte
differentiation
development
tissue.
Its
obesogenic
should
be
high
concern.
Язык: Английский
Cresyl diphenyl phosphate (a novel organophosphate ester) induces hepatic steatosis by directly binding to liver X receptor α: From molecule action to risk assessment
Environment International,
Год журнала:
2024,
Номер
194, С. 109168 - 109168
Опубликована: Ноя. 26, 2024
Язык: Английский