Notch
signalling
activity
regulates
hematopoiesis
in
Drosophila
and
vertebrates
alike.
Parasitoid
wasp
infestation
of
larvae,
however,
requires
a
timely
downregulation
to
allow
the
formation
encapsulation-active
blood
cells.
Here
we
show
that
CSL
transcription
factor
Suppressor
Hairless
[Su(H)]
is
phosphorylated
at
Serine
269
response
parasitoid
infestation.
As
this
phosphorylation
interferes
with
DNA-binding
Su(H),
it
reversibly
precludes
its
activity.
Accordingly,
phospho-deficient
Su(H)
S269A
mutants
are
immune
compromised.
A
screen
for
kinases
involved
identified
Pkc53E,
required
normal
as
well
response.
Genetic
molecular
interactions
support
specificity
Su(H)-Pkc53E
relationship.
Moreover,
phorbol
ester
treatment
inhibits
vivo
human
cell
culture.
We
conclude
Pkc53E
targets
during
parasitic
infestation,
thereby
remodeling
population
egg
encapsulation.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: Feb. 20, 2024
Notch
signaling
pathway
is
a
highly
conserved
system
of
cell-to-cell
communication
that
participates
in
various
biological
processes,
such
as
stem
cell
maintenance,
fate
decision,
proliferation
and
death
during
homeostasis
development.
Dysregulation
has
been
associated
with
many
aspects
cancer
biology,
maintenance
stem-like
cells
(CSCs),
metabolism,
angiogenesis
tumor
immunity.
Particularly,
can
regulate
antitumor
or
pro-tumor
immune
within
the
microenvironment
(TME).
Currently,
drawn
significant
attention
therapeutic
development
treatment.
In
this
review,
we
focus
on
role
remodeling
microenvironment.
We
describe
impact
efficacy
immunotherapies.
Furthermore,
summarize
results
relevant
preclinical
clinical
trials
Notch-targeted
therapeutics
discuss
challenges
their
application
therapy.
An
improved
understanding
involvement
immunity
will
open
door
to
new
options
immunotherapy
Frontiers in Bioscience-Landmark,
Journal Year:
2024,
Volume and Issue:
29(2)
Published: Feb. 21, 2024
Human
umbilical
cord
mesenchymal
stem
cells
(hUCMSCs)
exhibit
potent
self-renewal
and
multilineage
differentiation
characteristics.
They
have
garnered
substantial
attention
within
the
domain
of
regenerative
medicine
owing
to
their
therapeutic
potential,
such
as
in
tissue
repair,
regeneration,
immunomodulation,
anti-inflammation,
angiogenesis,
wound
healing,
neuroprotection,
neuroregeneration.
The
process
fate
determination
is
initiated
by
multiple
signaling
molecules.
During
development
homeostasis,
Notch
pathway
assumes
a
pivotal
function
cell
renewal
cells.
A
growing
body
research
has
revealed
that
plays
role
hUCMSC
proliferation
differentiation.
latest
progress
concerning
crucial
functions
maintaining
homeostasis
determining
hUCMSCs
summarized.
Furthermore,
authors
also
summarized
mediators
related
differentiation,
well
alterations
mechanisms
involved
therapy.
Frontiers in Pharmacology,
Journal Year:
2025,
Volume and Issue:
15
Published: Jan. 6, 2025
Vascular
calcification
(VC)
commonly
occurs
in
diabetes
and
is
associated
with
cardiovascular
disease
incidence
mortality.
Currently,
there
no
drug
treatment
for
VC.
The
Danlian-Tongmai
formula
(DLTM)
a
traditional
Chinese
medicine
(TCM)
prescription
used
diabetic
VC
(DVC),
but
its
mechanisms
of
action
remain
unclear.
This
study
aims
to
elucidate
the
effects
DLTM
on
DVC
explore
underlying
action.
Ultra-high-performance
liquid
chromatography-mass
spectrometry
(UHPLC-MS)
was
identify
metabolites
DLTM.
A
rat
model
established
using
streptozotocin
(STZ)
combined
vitamin
D3
(VitD3).
were
evaluated
through
alizarin
red
staining,
calcium
deposition,
changes
osteogenic
contractile
markers.
specific
molecular
mechanism
treating
comprehensively
analyzed
by
transcriptomics,
docking
vivo
experimental
verification.
We
identified
108
major
In
vivo,
high-dose
significantly
alleviated
rats.
Transcriptomic
analysis
showed
that
markedly
altered
transcriptomic
profile
aortas,
which
regulating
CCN3/NOTCH
signaling
pathway,
promoting
vascular
smooth
muscle
contraction,
inhibiting
inflammatory
responses.
Molecular
dynamics
simulation
demonstrated
strong
binding
interactions
between
key
molecules
within
including
NOTCH1,
DLL1,
DLL4,
hes1,
hey1.
experiments
confirmed
could
upregulate
CCN3,
inhibit
activation
NOTCH
ligands
DLL1
downstream
transcription
factors
hes1
hey1,
reduce
release
cytokines
IL6,
IL1β,
TNFα.
alleviates
axis
Our
research
provides
basis
clinical
transformation
Journal of Inflammation Research,
Journal Year:
2025,
Volume and Issue:
Volume 18, P. 1787 - 1813
Published: Feb. 1, 2025
Abstract:
Reversion
inducing
cysteine
rich
protein
with
kazal
motifs
(RECK),
a
Kazal
motif-containing
protein,
regulates
pro-inflammatory
cytokines
production,
migration
of
inflammatory
cells,
vascular
endothelial
growth
factor
(VEGF)
and
Wnt
pathways
plays
critical
roles
in
septic
storms
dysfunction.
Recently,
RECK
has
been
defined
as
the
negative
regulator
adisintegrin
metalloproteinases
(ADAMs)
matrix
(MMPs),
which
are
both
membrane
"molecular
scissors"
aggravate
poor
prognosis
sepsis.
To
better
understand
related
mechanisms,
we
make
here
systematic
in-depth
review
RECK.
We
first
summarize
findings
on
structural
characteristics
regulation
at
transcription,
post-transcription,
or
level
Then,
discuss
inflammation,
infection,
injury
by
focusing
function
ADAMs
MMPs,
well
VEGF,
WNT,
angiopoietin,
notch
signaling.
In
conclusion,
participation
guardian
development
sepsis
provides
insight
into
strategies
precisely
intervening
dysregulationfor
treatment
Keywords:
RECK,
sepsis,
regulation,
inflammation
Frontiers in Microbiomes,
Journal Year:
2025,
Volume and Issue:
4
Published: Feb. 18, 2025
Enteric
microbiota
plays
a
crucial
role
in
the
health
and
productivity
of
poultry,
including
influences
on
nutrient
absorption,
immune
function,
pathogen
resistance.
In
this
study,
we
conducted
genome-wide
association
study
(GWAS)
to
identify
host
genetic
variants
associated
with
selected
bacterial
genera
found
chickens.
We
used
high-density
600K
SNP
Affymetrix
DNA
arrays
for
genotyping,
alongside
16S
rRNA
gene
sequencing
profile
caecal
from
same
individual
A
commercial
broiler
line
(Cobb400,
n
=
300)
an
indigenous
(Kadaknath,
chicken
breed
India
were
investigated,
allowing
comprehensive
cross-ecotype
analysis.
Our
analysis
identified
several
host-genetic
markers
candidate
genes
presence
abundance
specific
known
pathogenic
or
commensal
roles,
Enterotypes.
Whole-genome
data
then
further
investigate
regions
around
significantly
array.
Of
note,
nearby
coding
classical
complement
activation
component
C1q,
ephrin
receptors,
other
immunity
inflammatory
responses
as
well
products
vitamin
co-factor
metabolism.
The
results
underscore
impact
that
genetics
has
regulation
gut
highlights
potential
pathways
through
which
variation
host-bacterial
crosstalk
potentially
modulates
microbial
community
structure.
These
findings
contribute
growing
understanding
basis
host-microbiota
interactions
offer
new
avenues
improving
poultry
selective
breeding
strategies
targeting
microbiome.
Cell Biology and Toxicology,
Journal Year:
2025,
Volume and Issue:
41(1)
Published: March 7, 2025
Andrographolide
(AP)
has
been
shown
to
possess
anti-inflammatory
activities.
In
this
study,
the
impact
of
AP
in
sepsis-induced
acute
liver
injury
(ALI)
and
molecules
involved
were
dissected.
FKBP1A
was
predicted
be
sole
target
protein
that
also
differentially
expressed
GSE166868
dataset.
induced
expression
suppressed
NOTCH1
a
dose-dependent
manner.
ameliorated
ALI
mice
by
D-galactosamine
LPS
inhibited
LPS-induced
parenchymal
cell
vitro.
By
contrast,
protective
effect
significantly
lost
after
knockdown
FKBP1A.
As
positive
control,
therapeutic
dexamethasone
on
may
related
NOTCH1,
which
not
promoted
AK2
transcription
cells,
endoplasmic
reticulum
(ER)
stress
impairing
NOTCH1/AK2
signaling.
Restoration
reversed
hepatoprotective
activating
ER
pathway.
Therefore,
AP-promoted
inhibits
progression
blocking
NOTCH1/AK2-mediated
