Parasites & Vectors,
Год журнала:
2024,
Номер
17(1)
Опубликована: Фев. 10, 2024
Abstract
Background
Toxoplasma
gondii
is
an
important
protozoan
pathogen
with
medical
and
veterinary
importance
worldwide.
Drugs
currently
used
for
treatment
of
toxoplasmosis
are
less
effective
sometimes
cause
serious
side
effects.
There
urgent
need
the
development
more
drugs
relatively
low
toxicity.
Methods
The
effect
tylosin
on
viability
host
cells
was
measured
using
CCK8
assays.
To
assess
inhibition
T.
proliferation,
a
real-time
PCR
targeting
B1
gene
developed
detection
quantification.
Total
RNA
extracted
from
parasites
treated
then
subjected
to
transcriptome
analysis
by
sequencing
(RNA-seq).
Finally,
murine
infection
models
were
evaluate
protective
efficacy
against
virulent
RH
strain
or
avirulent
ME49
strain.
Results
We
found
that
displayed
toxicity,
its
50%
inhibitory
concentration
175.3
μM.
Tylsoin
also
inhibited
intracellular
tachyzoite
9.759
Transcriptome
showed
remarkably
perturbed
expression
,
genes
involved
in
“ribosome
biogenesis
(GO:0042254)”
(GO:0005840)”
significantly
dys-regulated.
In
model,
alone
(100
mg/kg,
i.p.)
combination
sulfadiazine
sodium
(200
i.g.)
prolonged
survival
time
raised
rate
animals
infected
Meanwhile,
decreased
parasite
burdens
multiple
organs
spleen
index
mice
acute
toxoplasmosis.
Conclusions
Our
findings
suggest
exhibited
potency
both
vitro
vivo,
which
offers
promise
human
Graphical
Cell,
Год журнала:
2024,
Номер
187(19), С. 5267 - 5281.e13
Опубликована: Авг. 9, 2024
The
nuclear
pore
complex
(NPC)
is
the
sole
mediator
of
nucleocytoplasmic
transport.
Despite
great
advances
in
understanding
its
conserved
core
architecture,
peripheral
regions
can
exhibit
considerable
variation
within
and
between
species.
One
such
structure
cage-like
basket.
crucial
roles
mRNA
surveillance
chromatin
organization,
an
architectural
has
remained
elusive.
Using
in-cell
cryo-electron
tomography
subtomogram
analysis,
we
explored
NPC's
structural
variations
basket
across
fungi
(yeast;
S.
cerevisiae),
mammals
(mouse;
M.
musculus),
protozoa
(T.
gondii).
integrative
modeling,
computed
a
model
yeast
that
revealed
how
hub
nucleoporins
(Nups)
ring
binds
to
basket-forming
Mlp/Tpr
proteins:
coiled-coil
domains
form
struts
basket,
while
their
unstructured
termini
constitute
distal
densities,
which
potentially
serve
as
docking
site
for
preprocessing
before
Pathogens,
Год журнала:
2021,
Номер
10(11), С. 1351 - 1351
Опубликована: Окт. 20, 2021
Toxoplasma
gondii
(T.
gondii)
is
a
prevalent
protozoan
parasite
of
medical
and
veterinary
significance.
It
the
etiologic
agent
toxoplasmosis,
neglected
disease
in
which
incidence
symptoms
differ
between
patients
regions.
In
immunocompetent
patients,
toxoplasmosis
manifests
as
acute
chronic
forms.
Acute
presents
mild
or
asymptomatic
that
evolves,
under
host
immune
response,
into
persistent
healthy
individuals.
Chronic
establishes
latent
tissue
cysts
brain
skeletal
muscles.
immunocompromised
may
reactivate,
leading
to
potentially
life-threatening
condition.
Recently,
association
various
diseases
has
been
shown.
These
span
primary
neuropathies,
behavioral
psychiatric
disorders,
different
types
cancer.
Currently,
direct
pre-clinical
clinical
molecular
connotation
most
its
associated
remains
poorly
understood.
this
review,
we
provide
comprehensive
overview
on
Toxoplasma-induced
with
focus
available
knowledge
players
dictating
these
associations.
We
will
also
abridge
existing
therapeutic
options
highlight
current
gaps
explore
implications
advance
treatment
modalities.
Neuroscience & Biobehavioral Reviews,
Год журнала:
2022,
Номер
142, С. 104894 - 104894
Опубликована: Сен. 28, 2022
Schizophrenia
has
been
an
evolutionary
paradox:
it
high
heritability,
but
is
associated
with
decreased
reproductive
success.
The
causal
genetic
variants
underlying
schizophrenia
are
thought
to
be
under
weak
negative
selection.
To
unravel
this
paradox,
many
explanations
have
suggested
for
schizophrenia.
We
critically
discuss
the
constellation
of
hypotheses
schizophrenia,
highlighting
lack
empirical
support
most
existing
hypotheses—with
exception
relatively
well
supported
mismatch
hypothesis.
It
posits
that
evolutionarily
novel
features
contemporary
environments,
such
as
chronic
stress,
low-grade
systemic
inflammation,
and
gut
dysbiosis,
increase
susceptibility
Environmental
factors
microbial
infections
(e.g.,
Toxoplasma
gondii)
can
better
predict
onset
than
polygenic
risk
scores.
However,
researchers
not
able
explain
why
only
a
small
minority
infected
people
develop
new
etiological
synthesis
indicates
interaction
between
host
genotype,
microbe
infection,
stress
causes
neuroinflammation
dysbiosis
mediating
pathway.
Instead
just
alleviating
symptoms
drugs,
parasite
x
genotype
model
emphasizes
treatment
should
focus
on
detecting
treating
possible
infection(s),
neuroinflammation,
stress.
PLoS Biology,
Год журнала:
2023,
Номер
21(7), С. e3002202 - e3002202
Опубликована: Июль 17, 2023
Toxoplasma
gondii
secretes
protein
effectors
to
subvert
the
human
immune
system
sufficiently
establish
a
chronic
infection.
Relative
murine
infections,
little
is
known
about
which
parasite
disarm
responses.
Here,
we
used
targeted
CRISPR
screening
identify
secreted
required
for
survival
in
IFNγ-activated
cells.
Independent
screens
were
carried
out
using
2
strains
that
differ
virulence
mice,
leading
identification
of
We
GRA57
and
other
proteins,
GRA70
GRA71,
together
form
complex
enhances
ability
parasites
persist
foreskin
fibroblasts
(HFFs).
Components
machinery
export
proteins
into
host
cell
also
found
be
important
resistance
IFNγ
cells,
but
these
components
function
independently
identified
complex.
Host-mediated
ubiquitination
vacuole
has
previously
been
associated
with
increased
clearance
from
find
vacuoles
GRA57,
GRA70,
GRA71
knockout
are
surprisingly
less
ubiquitinated
by
cell.
hypothesise
this
likely
secondary
consequence
deletion
complex,
unlinked
mediated
effectors.
Health Science Reports,
Год журнала:
2023,
Номер
6(6)
Опубликована: Июнь 1, 2023
Toxoplasmosis
is
the
most
widespread
zoonotic
disease
that
affects
one-third
of
world's
population,
and
imposes
a
major
public
health
problem
worldwide.
This
study
aimed
to
assess
prevalence
toxoplasmosis
among
patients
with
neuropsychiatric
patients.
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Фев. 6, 2023
The
efficacious
detection
of
pathogens
and
prompt
induction
innate
immune
signaling
serve
as
a
crucial
component
defense
against
infectious
pathogens.
Over
the
past
decade,
DNA-sensing
receptor
cyclic
GMP-AMP
synthase
(cGAS)
its
downstream
adaptor
stimulator
interferon
genes
(STING)
have
emerged
key
mediators
type
I
(IFN)
nuclear
factor-κB
(NF-κB)
responses
in
health
infection
diseases.
Moreover,
both
cGAS-STING
pathway
developed
delicate
strategies
to
resist
each
other
for
their
survival.
mechanistic
functional
comprehension
interplay
between
is
opening
way
development
application
pharmacological
agonists
antagonists
treatment
Here,
we
briefly
review
current
knowledge
DNA
sensing
through
pathway,
emphatically
highlight
potent
undertaking
host
pathogenic
organisms.
PLoS Pathogens,
Год журнала:
2023,
Номер
19(2), С. e1011140 - e1011140
Опубликована: Фев. 23, 2023
Extracellular
vesicles
(EVs)
provide
a
central
mechanism
of
cell–cell
communication.
While
EVs
are
found
in
most
organisms,
their
pathogenesis-promoting
roles
parasites
particular
interest
given
the
potential
for
medical
insight
and
consequential
therapeutic
intervention.
Yet,
key
feature
human
parasitic
protozoa
remains
elusive:
mechanisms
biogenesis.
Here,
we
survey
current
knowledge
on
biogenesis
pathways
secreted
by
four
main
clades
protozoa:
apicomplexans,
trypanosomatids,
flagellates,
amoebae.
In
particular,
shine
light
findings
pertaining
to
Endosomal
Sorting
Complex
Required
Transport
(ESCRT)
machinery,
as
mammals
it
plays
important
EV
This
review
highlights
diversity
protozoa,
well
related
involvement
ESCRT
system
these
unique
organisms.
Abstract
Despite
recent
major
advances
in
developing
effective
vaccines
against
toxoplasmosis,
finding
new
protective
vaccination
strategies
remains
a
challenging
and
elusive
goal
as
it
is
critical
to
prevent
the
disease.
Over
past
few
years,
various
experimental
approaches
have
shown
that
an
vaccine
T.
gondii
achievable.
However,
more
unknown
due
its
complicated
life
cycle,
difficulties
clinical
translation,
lack
of
standardized
platform.
This
minireview
summarizes
development
main
obstacles
safe,
durable
vaccine.
The
successes
failures
testing
candidates
for
are
also
discussed,
which
may
facilitate
future
vaccines.
Foods,
Год журнала:
2022,
Номер
11(16), С. 2542 - 2542
Опубликована: Авг. 22, 2022
Toxoplasma
gondii
is
an
obligate
intracellular
parasite
that
causes
toxoplasmosis,
with
approximately
one
third
of
the
population
around
world
seropositive.
The
consumption
contaminated
food
main
source
infection.
These
include
meat
products
T.
tissue
cysts,
and
dairy
tachyzoites.
Recently,
contamination
has
been
detected
in
fresh
oocysts
marine
products.
Despite
great
health
problems
are
caused
by
gondii,
currently
there
no
standardized
methods
for
its
detection
industry.
In
this
review,
we
analyze
current
methods,
prevalence
different
products,
control
measures.
bioassays,
cell
culture,
molecular
microscopic
techniques,
serological
but
some
these
do
not
have
applicability
As
a
result,
emerging
techniques
being
developed
aimed
at
multiple
parasites
simultaneously
would
make
their
application
more
efficient
Since
high
many
(meat
milk,
vegetables),
it
necessary
to
standardize
as
well
implement