Dihydrolipoamide
dehydrogenase
(DLD)
deficiency
is
a
recessive
mitochondrial
disease
caused
by
variants
in
DLD,
the
E3
subunit
of
α-keto
acid
complexes.
DLD
symptoms
are
multi-systemic,
variably
manifesting
as
Leigh
syndrome,
neurodevelopmental
disability,
seizures,
cardiomyopathy,
liver
disease,
fatigue
and
lactic
acidemia.
While
most
attributed
to
dysfunction
pyruvate
complex,
understanding
effects
other
deficiencies
remain
unclear.
Current
therapies
for
ineffective,
with
no
vertebrate
animal
model
available
preclinical
study.
We
created
viable
Danio
rerio
(zebrafish)
KO
deficiency,
dldhcri3.
Detailed
phenotypic
characterization
revealed
shortened
larval
survival,
uninflated
swim
bladder,
hepatomegaly
fatty
liver,
reduced
activity.
These
animals
displayed
increased
lactate
levels,
severe
disruption
branched-chain
amino
catabolism
manifest
valine,
leucine,
isoleucine,
α-ketoisovalerate,
α-ketoglutarate
levels.
Evaluation
ultrastructure
gross
enlargement,
cristae
reduction
matrix
electron
density
intestines,
muscle.
Therapeutic
modeling
candidate
demonstrated
probucol
or
thiamine
improved
Overall,
this
characteristic
metabolic
alterations
offering
robust
platform
screen
characterize
therapies.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(4), С. 1444 - 1444
Опубликована: Фев. 8, 2025
The
aim
of
this
review
is
to
summarize
the
current
knowledge
on
use
coumarin-derived
compounds
in
zebrafish
(Danio
rerio)
model.
Coumarins,
a
class
naturally
occurring
with
diverse
biological
activities,
including
such
as
coumarin,
angelicin,
and
warfarin,
have
attracted
considerable
attention
study
potential
therapeutic
agents
for
cancer,
central
nervous
system
disorders,
infectious
diseases.
capabilities
coumarins
active
led
synthesizing
various
derivatives
their
own
properties.
While
variety
certainly
promising,
it
also
cumbersome
due
large
amount
research
needed
find
most
optimal
compounds.
model
offers
unique
advantages
studies,
high
genetic
physiological
homology
mammals,
optical
transparency
embryos,
rapid
developmental
processes,
facilitating
assessment
compound
toxicity
underlying
mechanisms
action.
This
provides
an
in-depth
analysis
chemical
properties
coumarins,
activity,
results
previous
studies
evaluating
efficacy
these
assays.
allows
holistic
coumarin
derivatives,
offering
valuable
insights
advancing
drug
discovery
development.
Toxicology Mechanisms and Methods,
Год журнала:
2025,
Номер
unknown, С. 1 - 19
Опубликована: Март 10, 2025
The
androgen
receptor
(AR)
activation
by
androgens
is
vital
for
tissue
development,
sexual
differentiation,
and
reproductive
attributes
in
zebrafish
(Danio
rerio).
However,
our
understanding
of
the
molecular
mechanisms
behind
their
remains
limited.
In
this
study,
we
employed
both
ab
initio
(AlphaFold)
homology
(SWISS-MODEL)
structure
models
ligand-binding
domain
(zAR-LBD)
to
explore
binding
specificity,
affinity,
interactions
endogenous
hormones
(testosterone
(T),
11-ketotestosterone
(11-KT),
dihydrotestosterone
(DHT))
a
computational
simulation.
Molecular
docking
analysis
showed
that
structures
formed
same
similar
patterns
energy
with
androgens.
Dynamics
(MD)
simulation
revealed
hydrogen
bond
occupancy
aligned
vitro
findings
related
androgenic
effect.
When
comparing
complexes
modeled
SWISS-MODEL
AlphaFold,
significant
differences
were
observed
root
mean
square
deviation
(RMSD)
fluctuations
(RMSF).
AlphaFold
also
exhibited
clear
separation
between
ligands
principal
component
analysis.
Further
correlation
silico
features
EC50
values
identified
MMPBSA
energies
as
most
contributors
ligand-specific
variance
(p
<
0.05).
Overall,
integrative
approach
offers
insights
into
underlying
AR
activity.
Life,
Год журнала:
2025,
Номер
15(4), С. 538 - 538
Опубликована: Март 25, 2025
The
use
of
different
commercial
products
that
involve
one
or
multiple
active
substances
with
specific
targeted-pests
control
has
become
a
widespread
practice.
Because
this,
severe
range
significant
consequences
been
often
reported.
Among
the
most
used
pesticides
worldwide
are
deltamethrin
(DM)
and
imidacloprid
(IMI).
With
significative
effect
on
insect’s
nervous
system,
DM
acts
voltage-gated
sodium
channels
in
nerve
cell
membranes,
while
IMI
mimics
acetylcholine
neurotransmitter
by
binding
irreversibly
to
nicotinic
receptors.
This
study
investigates
neurotoxic
effects
sub-chronic
exposure
formulations
(IMI)
adult
zebrafish,
both
individually
combination.
this
contain
additional
ingredients
commonly
found
pesticide
products,
which
may
contribute
overall
toxicity.
Fish
were
exposed
environmentally
relevant
concentrations
these
for
21
days,
Behavioral,
molecular,
histopathological
analyses
conducted
assess
impact
pesticides.
Zebrafish
exhibited
dose-dependent
behavioral
alterations,
particularly
combined
groups,
including
increased
erratic
swimming
anxiety-like
behavior.
Gene
expression
analysis
revealed
changes
neurotrophic
factors
(BDNF,
NGF,
ntf-3,
ntf-4/5,
ntf-6/7)
their
receptors
(ntrk1,
ntrk2a,
ntrk2b,
ntrk3a,
ntrk3b,
ngfra,
ngfrb),
indicating
potential
effects.
Histopathological
examination
confirmed
neuronal
degeneration,
gliosis,
vacuolization,
more
impairments
observed
mixture
treatments.
These
findings
highlight
aquatic
environments
emphasize
need
stricter
regulations
mixtures
further
research
interactions.
Our
combination
could
trigger
synergistic
maximizing
toxicity
each
compound.
Thus,
it
is
well-known
practice
pyrethroids
neonicotinoids
be
together
agriculture.
Even
so,
its
prevalence
agriculture
investigate
actual
human
health,
biodiversity,
ecosystem
mitigates
development
new
strategies
assessing
risk
and,
at
same
time,
enhancing
effectiveness.
Journal of Developmental Biology,
Год журнала:
2023,
Номер
11(1), С. 14 - 14
Опубликована: Март 18, 2023
Nephrons
are
the
functional
units
which
comprise
kidney.
Each
nephron
contains
a
number
of
physiologically
unique
populations
specialized
epithelial
cells
that
organized
into
discrete
domains
known
as
segments.
The
principles
segment
development
have
been
subject
many
studies
in
recent
years.
Understanding
mechanisms
nephrogenesis
has
enormous
potential
to
expand
our
knowledge
about
basis
congenital
anomalies
kidney
and
urinary
tract
(CAKUT),
contribute
ongoing
regenerative
medicine
efforts
aimed
at
identifying
renal
repair
generating
replacement
tissue.
study
zebrafish
embryonic
kidney,
or
pronephros,
provides
opportunities
identify
genes
signaling
pathways
control
development.
Here,
we
describe
advances
patterning
differentiation
zebrafish,
with
focus
on
distal
formation.
Toxics,
Год журнала:
2024,
Номер
12(2), С. 150 - 150
Опубликована: Фев. 15, 2024
Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)
(PEDOT:PSS)
is
a
conductive
polymer
commonly
used
in
various
technological
applications.
However,
its
impact
on
aquatic
ecosystems
remains
largely
unexplored.
In
this
study,
we
investigated
the
toxicity
effects
of
PEDOT:PSS
zebrafish.
We
first
determined
lethal
concentration
(LC50)
zebrafish
and
then
exposed
AB-type
embryos
to
different
concentrations
for
120
h.
Our
investigation
elucidated
development,
including
morphological
assessments,
heart
rate
measurements,
behavioral
analysis,
transcriptome
profiling,
histopathological
analysis.
discovered
that
exhibited
detrimental
early
developmental
stages
zebrafish,
exacerbating
oxidative
stress
level,
suppressing
activity,
impairing
cardiac
causing
intestinal
cell
damage.
This
study
adds
new
dimension
findings
contribute
our
understanding
ecological
repercussions
highlight
importance
responsible
development
application
novel
materials
rapidly
evolving
landscape.
Development Genes and Evolution,
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 30, 2024
Abstract
The
zebrafish
is
an
invaluable
model
organism
for
genetic,
developmental,
and
disease
research.
Although
its
high
conservation
with
humans
often
cited
as
justification
use,
the
harbors
oft-ignored
genetic
characteristics
that
may
provide
unique
insights
into
gene
structure
function.
Zebrafish,
along
other
teleost
fish,
underwent
additional
round
of
whole
genome
duplication
after
their
split
from
tetrapods—resulting
in
abundance
duplicated
genes
when
compared
to
vertebrates.
These
have
evolved
distinct
ways
over
ensuing
350
million
years.
Thus,
each
within
a
pair
has
nuanced
differences
create
identity.
By
investigating
both
members
together,
we
can
elucidate
mechanisms
underly
protein
function
drive
complex
interplay
biological
systems,
such
signal
transduction
cascades,
regulatory
networks,
evolution
tissue
organ
It
crucial
leverage
studies
explore
these
molecular
dynamics,
which
could
far-reaching
implications
basic
science
therapeutic
development.
Here,
will
review
role
duplications
existing
models
divergence
retention
following
events.
We
also
highlight
examples
where
comparing
yielded
key
structure,
function,
regulation.
