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.
ACS Nano,
Год журнала:
2025,
Номер
19(5), С. 5460 - 5474
Опубликована: Янв. 30, 2025
Type-2-diabetes
is
a
metabolic
disorder
where
misfolding
and
oligomerization
of
islet
amyloid
polypeptide
(IAPP)
around
islet-β
cells
oligomerizes
participates
in
the
pathology.
The
oligomeric
stage
toxic
but
transitory
leads
to
formation
mature
fibrils.
pathological
specifics
fibrils
are
poorly
understood.
Here,
we
demonstrate
that
IAPP
amyloids
make
gel-like
transition,
increasing
viscosity
local
microenvironment
encasing
impeding
their
ability
sense
glucose
release
insulin.
Using
dual-targeted
gold
nanoparticles
(AuNPs)
capped
with
amyloid-fragments
βCasein
anti-IAPP
antibodies,
show
X-ray
irradiation
AuNPs
when
bound
results
therapeutic
remodelling
amyloids,
reduction
solution,
restoration
glucose/insulin
homeostasis.
This
study
establishes
can
participate
progressive
pathology
type-2-diabetes
by
suppressing
insulin
responsiveness
at
single
islet-cell
level.
It
also
identifies
model
reversal
using
AuNPs-mediated
therapy,
this
approach
be
rationally
expanded
other
pathologies,
such
as
Alzheimer's
Parkinson's
diseases.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(19), С. 14898 - 14898
Опубликована: Окт. 4, 2023
Neurological
diseases,
including
neurodegenerative
and
neurodevelopmental
disorders,
affect
nearly
one
in
six
of
the
world’s
population.
The
burden
resulting
deaths
disability
is
set
to
rise
during
next
few
decades
as
a
consequence
an
aging
To
address
this,
zebrafish
have
become
increasingly
prominent
model
for
studying
human
neurological
diseases
exploring
potential
therapies.
Zebrafish
offer
numerous
benefits,
such
genetic
homology
brain
similarities,
complementing
traditional
mammalian
models
serving
valuable
tool
screening
drug
discovery.
In
this
comprehensive
review,
we
highlight
various
delivery
techniques
systems
employed
therapeutic
interventions
zebrafish,
evaluate
their
suitability.
We
also
discuss
challenges
encountered
process
present
advancements
innovative
techniques.
The Science of The Total Environment,
Год журнала:
2024,
Номер
917, С. 170405 - 170405
Опубликована: Янв. 26, 2024
The
functional
conservation
of
important
selective
serotonin
reuptake
inhibitor
(SSRI)
targets
in
non-target
organisms
raises
concerns
about
their
potential
adverse
effects
on
the
ecosystems.
Although
environmental
levels
SSRIs
like
paroxetine
(PAR)
have
risen,
knowledge
regarding
long-term
exposure
to
PAR
is
limited.
This
study
investigated
impact
sub-chronic
(21
days)
two
sub-lethal
concentrations
(40
and
400
μg/L)
behaviour
adult
zebrafish
different
scenarios:
basal
activity
(under
dark
light
conditions),
stress
response
(evoked
by
sudden
transitions)
recovery.
A
new
framework
was
employed
for
integrative
fish's
swimming
performance
based
innate
ability
respond
shifts.
Several
swimming-associated
parameters
(e.g.,
total
distance,
time
inactivity,
angles)
thigmotaxis
were
monitored
an
integrated
analysis
each
scenario.
Data
revealed
reduced
activity,
impaired
behavioural
alterations
recovery
PAR-exposed
fish.
An
anxiolytic
effect
particularly
noticeable
fish
at
μg/L
(from
light)
dark)
exposed
40
μg/L.
detected
PAR-induced
modifications
suggest
a
disruption
brain
glucocorticoid
signalling
that
may
implications
individual
level
changing
responses
predators),
with
repercussions
population
community
levels.
Therefore,
applied
protocol
proved
sensitive
detecting
changes
induced
PAR.
Microsystems & Nanoengineering,
Год журнала:
2024,
Номер
10(1)
Опубликована: Янв. 29, 2024
This
paper
presents
the
design
of
a
vision-based
automated
robotic
microinjection
system
for
batch
injection
both
zebrafish
embryos
and
larvae.
A
novel
visual
recognition
algorithm
based
on
an
automatic
threshold
excessive
dilatation
is
introduced
to
accurately
identify
center
larval
yolks.
corresponding
software
developed
using
producer-consumer
model
as
framework
structure,
friendly
user
interface
designed
allow
operators
choose
from
range
desired
functions
according
their
different
needs.
In
addition,
microstructural
agarose
device
fabricated
simultaneously
immobilize
mixed
batches
Moreover,
prototype
by
integrating
hardware
devices
with
algorithms.
An
experimental
study
conducted
verify
performance
system.
The
results
show
that
reported
can
larvae
efficiently
complete
tasks
mixtures
success
rate
92.05%
in
13.88
s
per
sample.
Compared
manual
existing
systems,
proposed
demonstrates
merits
versatility,
excellent
efficiency,
high
rate,
survival
sufficient
stability.
Nanomaterials,
Год журнала:
2024,
Номер
14(4), С. 373 - 373
Опубликована: Фев. 17, 2024
Among
nanoparticles
(NPs),
titanium
dioxide
is
one
of
the
most
highly
manufactured
worldwide
and
widely
used
in
multiple
products
for
both
industrial
use
personal
care
products.
This
increases
probability
release
into
aquatic
environments,
potentially
affecting
these
ecosystems.
The
present
study
aimed
to
evaluate
TiO2
P25
NP
toxicity
zebrafish
embryos
eleutheroembryos
by
evaluating
LC50,
hatching
rate,
embryo
development,
chemical
analysis
concentration
accumulated
eleutheroembryo
tissues.
Zebrafish
~2
h
post-fertilization
(hpf)
were
exposed
75,
100,
150,
200,
250
mg/L
NPs
48
96
h.
A
total
40–60
placed
each
Petri
dish
respective
treatments.
Three
replicates
treatment
group.
Ti4+
concentrations
determined
inductively
coupled
plasma
optical
emission
spectrometry
(ICP-OES),
a
conversion
factor
was
calculate
highest
calculated
larvae
1.0199
after
1.2679
exposure.
toxicological
results
indicated
that
did
not
have
significant
effect
on
mortality
but
an
their
development.
LC20
LC30
experimentally,
LC50
LC80
estimated
using
four
different
methods.
Up
11%
also
presented
physical
malformations.
These
effects
can
be
detrimental
species
affect
Physical
malformations
observed
all
treatments,
indicating
teratogenic
effects.
Chemosphere,
Год журнала:
2023,
Номер
335, С. 139124 - 139124
Опубликована: Июнь 5, 2023
Selective
serotonin
reuptake
inhibitors
(SSRIs)
are
a
class
of
antidepressants
increasingly
prescribed
to
treat
patients
with
clinical
depression.
As
result
the
significant
negative
impact
COVID-19
pandemic
on
population's
mental
health,
its
consumption
is
expected
increase
even
more.
The
high
these
substances
leads
their
environmental
dissemination,
evidence
ability
compromise
molecular,
biochemical,
physiological,
and
behavioural
endpoints
in
non-target
organisms.
This
study
aimed
provide
critical
review
current
knowledge
regarding
effects
SSRI
fish
ecologically
relevant
behaviours
personality-dependent
traits.
A
literature
shows
limited
data
concerning
personality
responses
contaminants
how
such
could
be
influenced
by
SSRIs.
lack
information
may
attributable
widely
adopted
standardized
protocols
for
evaluating
fish.
existing
studies
examining
SSRIs
across
various
biological
levels
overlook
intra-specific
variations
behaviour
physiology
associated
different
patterns
or
coping
styles.
Consequently,
some
remain
undetected,
as
styles
capacity
handle
stressors.
oversight
potentially
long-term
ecological
implications.
Data
support
need
more
understand
traits
they
impair
fitness-related
behaviours.
Given
considerable
cross-species
similarity
dimensions,
collected
allow
new
insights
into
correlation
between
animal
fitness.
One
of
the
most
pressing
challenges
our
era
is
rising
occurrence
bacteria
that
are
resistant
to
antibiotics.
Staphylococci
prominent
pathogens
in
humans,
which
have
developed
multiple
strategies
evade
effects
Infections
caused
by
these
resulted
a
high
burden
on
health
care
system
and
significant
loss
lives.
In
this
study,
we
successfully
engineered
lytic
enzymes
exhibit
an
extraordinary
ability
eradicate
staphylococci.
Our
findings
substantiate
importance
meticulous
lead
candidate
selection
identify
therapeutically
promising
peptidoglycan
hydrolases
with
unprecedented
activity.
Hence,
they
offer
new
avenue
for
treating
staphylococcal
infections.
This
study
explores
the
potential
of
controlling
organismal
development
with
light
by
using
reversible
photomodulation
activity
in
bioactive
compounds.
Specifically,
our
research
focuses
on
plinabulin
1,
an
inhibitor
tubulin
dynamics
that
contains
a
photochromic
motif
called
hemipiperazine.
The
two
isomeric
forms,
Z-1
and
E-1,
can
partially
interconvert
light,
yet
show
remarkable
thermal
stability
darkness.
Z-isomer
exhibits
higher
cytotoxicity
due
to
stronger
binding
α-tubulin's
colchicine
site.
less
toxic
E-1
form,
considered
"pro-drug",
be
isolated
vitro
stored.
Upon
activation
blue
or
cyan
it
predominantly
generates
more
form.
Here
we
demonstrate
1
effectively
photomodulate
epiboly,
critical
microtubule-dependent
cell
movement
during
gastrulation
zebrafish
embryos.
highlights
for
precise
control
cellular
activities
development.