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:
2023,
Volume and Issue:
14
Published: Oct. 4, 2023
The
symptoms
of
Behçet’s
disease
(BD),
a
multisystemic
condition
with
autoimmune
and
inflammation
as
hallmarks,
include
arthritis,
recurring
oral
vaginal
ulcers,
skin
rashes
lesions,
involvement
the
nervous,
gastrointestinal,
vascular
systems.
Non-coding
RNAs
(ncRNAs),
including
microRNAs
(miRNAs),
long
non-coding
(lncRNAs),
circular
(circRNAs),
may
be
important
regulators
disease.
These
ncRNAs
are
essential
to
physiological
pathophysiological
course,
miRNA
in
particular
has
received
significant
attention
for
its
role
function
BD
potential
use
diagnostic
biomarker
recent
years.
Although
promising
therapeutic
targets,
miRNAs
must
studied
further
fully
comprehend
how
act
biologically.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(18), P. 13755 - 13755
Published: Sept. 6, 2023
Adenoid
cystic
carcinoma
(ACC)
has
a
worldwide
incidence
of
three
to
four
cases
per
million
population.
Although
more
occur
in
the
minor
and
major
salivary
glands,
it
is
most
common
lacrimal
gland
malignancy.
ACC
low-grade,
indolent
histological
appearance,
but
relentlessly
progressive
over
time
strong
proclivity
recur
and/or
metastasise.
Current
treatment
options
are
limited
complete
surgical
excision
adjuvant
radiotherapy.
Intra-arterial
systemic
therapy
recent
innovation.
Recurrent/metastatic
disease
due
perineural
invasion,
largely
untreatable
as
refractory
conventional
chemotherapeutic
agents.
Given
rarity
this
tumour,
molecular
mechanisms
that
govern
pathogenesis
poorly
understood.
There
an
unmet,
critical
need
develop
effective,
personalised
targeted
therapies
for
order
reduce
morbidity
mortality
associated
with
disease.
This
review
details
evidence
relating
underpinnings
gland,
including
MYB-NFIB
chromosomal
translocations,
Notch-signalling
pathway
aberrations,
DNA
damage
repair
gene
mutations
epigenetic
modifications.
Journal of Cellular Immunology,
Journal Year:
2023,
Volume and Issue:
5(6), P. 174 - 183
Published: Jan. 1, 2023
Background:
Sepsis
remains
a
critical
global
health
challenge
with
high
mortality.
This
review
summarizes
current
understanding
of
the
intricate
molecular
mechanisms
governing
sepsis
pathogenesis
and
highlights
emerging
therapeutic
approaches.
Main
body
abstract:
The
dysregulated
immune
response
in
sepsis,
involving
both
excessive
inflammation
immunosuppression,
is
mediated
through
cytokines,
pattern
recognition
receptors,
disturbances
cell
function.
Endothelial
dysfunction,
coagulation
abnormalities,
microbiome
dysbiosis,
metabolic/mitochondrial
alterations
also
critically
contribute
to
progression.
Preclinical
models
have
facilitated
detailed
study
these
pathways
identification
potential
targets,
including
immunomodulators,
microbiome-directed
therapies,
endothelial
modulators,
anticoagulants,
agents.
Combination
therapies
targeting
multiple
pathogenic
aspects
may
be
necessary.
However,
translating
preclinical
findings
clinical
applications
challenging.
Heterogeneity
among
patients
key
issue,
underscoring
need
for
precision
medicine
Potential
adverse
effects
optimal
treatment
regimens
must
rigorously
evaluated.
Short
conclusion:
Further
research
should
focus
on
validating
discoveries,
subtypes,
developing
predictive
biomarkers
innovative
artificial
intelligence-based
tools,
bridging
knowledge
gaps
enhanced
academia-industry
collaboration.
Comprehensive
efforts
spanning
from
unraveling
translation
hold
promise
improving
outcomes
this
deadly
syndrome.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: March 8, 2024
With
the
continuous
development
of
nuclear
technology,
radiation
exposure
caused
by
therapy
is
a
serious
health
hazard.
It
great
significance
to
further
develop
effective
countermeasures.
B
cells
easily
succumb
irradiation
along
with
immunosuppressive
response.
The
approach
ameliorate
radiation-induced
cell
damage
rarely
studied,
implying
that
underlying
mechanisms
after
are
eager
be
revealed.
Recent
studies
suggest
Notch
signaling
plays
an
important
role
in
cell-mediated
immune
critical
regulator
for
maintain
function.
Although
accumulating
reported
contributes
functionality
hematopoietic
stem
and
T
cells,
its
scarcely
appreciated.
Presently,
we
discussed
regulation
on
under
provide
scientific
basis
prevent
damage.
Biomolecules,
Journal Year:
2024,
Volume and Issue:
14(5), P. 563 - 563
Published: May 8, 2024
Inflammageing
is
a
condition
of
perpetual
low-grade
inflammation
induced
by
ageing.
may
be
predicted
the
C-reactive
protein
(CRP)
or
recently
described
biomarker
which
measures
N-glycosylated
side
chains
carbohydrate
component
several
acute-phase
proteins
known
as
GlycA.
The
objective
this
study
was
to
examine
in
depth
genetic
relationships
between
CRP
and
GlycA
well
each
them
other
selected
cytokines,
shed
light
on
mechanisms
inflammageing.
Using
Olink
96
Inflammation
panel,
data
inflammatory
mediators
for
1518
twins
from
TwinsUK
dataset
were
acquired.
Summary
statistics
genome-wide
association
studies
cytokines
collected
public
sources.
Extensive
correlation
analyses,
colocalization
enrichment
analyses
carried
out
detect
shared
architecture
CRP.
Mendelian
randomization
assess
potential
causal
relationships.
examined
with
magnitude
twice
great
that
significantly
genetically
correlated
(Rg
=
0.4397
±
0.0854,
p-value
2.60
×
10−7).
No
evidence
relationship
CRP,
these
two
biomarkers
assessed
obtained.
However,
aforementioned
explained
horizontal
pleiotropy.
Five
exonic
variants
annotated
five
genes
explain
observed
CRP:
IL6R,
GCKR,
MLXIPL,
SERPINA1,
MAP1A.
possess
architecture,
but
appears
modest,
imply
promotion
differing
pathways.
more
robust
predictor
compared
Archiv der Pharmazie,
Journal Year:
2023,
Volume and Issue:
356(11)
Published: Aug. 25, 2023
Methotrexate
(MTX)-induced
hepatotoxicity
is
a
serious
adverse
effect
that
may
limit
its
use.
Therefore,
eligible
drugs
to
ameliorate
MTX-induced
are
required.
l-Carnitine
(LC)
natural
molecule
with
beneficial
metabolic
effects
and
infliximab
(INF)
an
anti-inflammatory
monoclonal
antibody
against
tumor
necrosis
factor-alpha
(TNF-α).
Recently,
Notch1/Hes-1
signaling
was
found
play
key
role
in
the
pathogenesis
of
liver
injury.
However,
unclear.
This
study
aimed
evaluate
modulatory
LC
or
INF
on
explore
underlying
mechanism
emphasis
pathway.
Sixty
rats
were
randomized
into
six
groups
(n
=
10):
(1)
control
(saline);
(2)
MTX
(20
mg/kg
MTX,
intraperitoneal
[ip],
once);
(3)
group
(500
ip,
5
days);
(4)
(7
(5)
MTX+LC
once,
500
days,
respectively);
(6)
MTX+INF
7
respectively).
Oxidative
stress,
inflammatory
markers,
investigated.
induced
expression
Notch1
Hes-1
proteins
increased
levels
TNF-α,
interleukin
(IL)-6,
IL-1β
liver.
Cotreatment
showed
apparent
antioxidant
effects.
Interestingly,
downregulation
more
prominent
cotreatment
as
compared
INF.
In
conclusion,
attenuates
through
modulation
signaling.
The
ameliorative
significantly
better
than
present
safe
therapeutically
effective
therapy
alleviating
hepatotoxicity.
