Biomedicines,
Год журнала:
2022,
Номер
10(12), С. 3108 - 3108
Опубликована: Дек. 1, 2022
Humans
and
other
organisms
are
continuously
exposed
to
thousands
of
chemicals
through
the
atmosphere,
drinking
water,
food,
or
direct
contact.
A
large
proportion
such
present
in
very
low
concentrations
may
have
synergistic
effects,
even
at
their
no-observed-adverse-effect
level
(NOAEL).
Complex
mixtures
contaminants
difficult
assess
by
traditional
toxicological
methods.
There
is
increasing
attention
on
how
different
pollutants
induce
adverse
physiological
functions
human
body
effects
circadian
rhythm.
However,
it
screen
for
compounds
with
circadian-rhythm-disrupting
from
a
number
complex
mixtures.
We
established
stable
firefly
luciferase
reporter
gene
knock-in
U2-OS
cell
line
CRISPR/Cas9
pollutants.
The
was
inserted
downstream
core
clock
BMAL1
controlled
an
endogenous
promoter.
Compared
detection
systems
using
exogenous
promoters,
these
cells
enable
that
interfere
rhythm
system
mediated
expression.
showed
activity
had
parallel
changes
when
treated
inhibitor
activator.
Furthermore,
has
high
sensitivity
faster
more
cost-effective
than
classic
toxicology
can
be
used
high-throughput
efficient
screening
as
drugs
Communications Biology,
Год журнала:
2024,
Номер
7(1)
Опубликована: Июль 22, 2024
Abstract
Environmental
and
lifestyle
factors,
including
air
pollution,
impaired
diet,
low
physical
activity,
have
been
associated
with
cardiometabolic
risk
factors
in
childhood
adolescence.
However,
environmental
exposures
do
not
exert
their
physiological
effects
isolation.
This
study
investigated
associations
between
an
exposome
score
to
measure
the
impact
of
multiple
exposures,
sleep
duration,
socioeconomic
status,
serum
metabolites
measured
using
LC-MS
NMR,
compared
individual
components
score.
A
general
population
504
children
aged
6–9
years
at
baseline
was
followed
up
for
eight
years.
Data
were
analysed
linear
mixed-effects
models
R
software.
The
31
metabolites,
which
12
any
exposure
category.
These
findings
highlight
value
a
composite
predict
metabolic
changes
since
childhood.
Molecules,
Год журнала:
2023,
Номер
28(16), С. 5952 - 5952
Опубликована: Авг. 8, 2023
In
recent
years,
plastic
and
especially
microplastic
in
the
oceans
have
caused
huge
problems
to
marine
flora
fauna.
Recently,
such
particles
also
been
detected
blood,
breast
milk,
placenta,
underlining
their
ability
enter
human
body,
presumably
via
food
chain
other
yet-unknown
mechanisms.
addition,
contains
plasticizers,
antioxidants,
or
lubricants,
whose
impact
on
health
is
under
investigation.
At
cellular
level,
most
important
enzymes
involved
metabolism
of
xenobiotic
compounds
are
cytochrome
P450
monooxygenases
(CYPs).
Despite
extensive
characterization
maintenance
balance,
interactions
with
related
products
unexplored.
this
study,
possible
between
several
plastic-related
one
cytochromes,
CYP2C19,
were
analyzed.
By
applying
virtual
compound
screening
molecular
docking
more
than
1000
commercially
available
compounds,
we
identified
candidates
that
likely
interact
protein.
A
growth
inhibition
assay
confirmed
cytotoxic
activity
a
CYP2C19-transfected
hepatic
cell
line.
Subsequently,
studied
effect
selected
transcriptome-wide
gene
expression
level
by
conducting
RNA
sequencing.
Three
candidate
molecules
identified,
i.e.,
2,2′-methylene
bis(6-tert-butyl-4-methylphenol),
1,1-bis(3,5-di-tert-butyl-2-hydroxyphenyl)
ethane,
bis(6-cyclohexyl-4-methylphenol)),
which
bound
high
affinity
CYP2C19
silico.
They
exerted
profound
cytotoxicity
vitro
interacted
metabolic
pathways,
‘cholesterol
biosynthesis
process’
was
affected.
affected
pathways
mitosis,
DNA
replication,
inflammation,
suggesting
an
increase
hepatotoxicity.
These
results
indicate
could
damage
liver
affecting
pathways.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(11), С. 6181 - 6181
Опубликована: Июнь 4, 2024
Organochlorine
pesticides
(OCPs)
are
a
class
of
environmentally
persistent
and
bioaccumulative
pollutants.
Among
these,
β-hexachlorocyclohexane
(β-HCH)
is
byproduct
lindane
synthesis,
one
the
most
worldwide
widespread
pesticides.
β-HCH
cellular
mechanisms
inducing
chemical
carcinogenesis
correspond
to
many
those
chemoresistance,
in
particular,
by
activation
signal
transducer
activator
transcription
3
(STAT3)
signaling
pathways.
For
this
purpose,
four
cell
lines,
representative
breast,
lung,
prostate,
hepatocellular
cancers,
were
treated
with
β-HCH,
specific
tyrosine
kinase
inhibitors
(TKIs),
STAT3
inhibitor.
All
samples
analyzed
viability
assay,
immunoblotting
analysis,
wound-healing
colony
formation
assay.
The
results
show
that
reduces
efficacy
TKIs.
protein,
context,
plays
central
role.
In
fact,
inhibiting
its
activity,
anticancer
drug
restored.
Furthermore,
manuscript
aimed
draw
attention
scientific
socio-healthcare
community
issue
prolonged
exposure
contaminants
their
impact
on
efficacy.
Biomedicines,
Год журнала:
2024,
Номер
12(8), С. 1905 - 1905
Опубликована: Авг. 20, 2024
The
vast
majority
of
gastric
cancer
(GC)
cases
are
adenocarcinomas
including
intestinal
and
diffuse
GC.
incidence
GC,
often
associated
with
poor
overall
survival,
has
constantly
increased
in
Western
countries.
Epidemiological
studies
have
reported
mortality
from
GC
after
occupational
exposure
to
pro-carcinogens
that
metabolically
activated
by
cytochrome
P450
enzymes
through
aryl
hydrocarbon
receptor
(AhR).
However,
little
is
known
about
the
role
AhR
environmental
ligands
as
compared
patients.
In
a
cohort
29,
we
demonstrated
significant
increase
protein
mRNA
expression
levels
GCs
independently
their
subtypes
clinical
parameters.
