Intestine‐Decipher Engineered Capsules Protect Against Sepsis‐induced Intestinal Injury via Broad‐spectrum Anti‐inflammation and Parthanatos Inhibition
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 21, 2025
Abstract
Sepsis
is
a
severe
systemic
inflammatory
syndrome
characterized
by
dysregulated
immune
response
to
infection,
often
leading
high
mortality
rates.
The
intestine,
owing
its
distinct
structure
and
physiological
environment,
plays
pivotal
role
in
the
pathophysiology
of
sepsis.
It
functions
as
“central
organ”
or
“engine”
progression
sepsis,
with
intestinal
injury
exacerbating
condition.
Despite
availability
current
therapies
that
offer
partial
symptom
relief,
they
fall
short
adequately
protecting
barrier.
In
this
study,
an
advanced
nanodrug
formulation
(OLA@MΦ
NPs)
developed
coating
macrophage
membranes
onto
polymeric
organic
nanoparticles
encapsulating
olaparib.
When
loaded
into
pH‐responsive
capsules,
intestine‐decipher
engineered
capsule
(cp‐OLA@MΦ
successfully
formulated.
Upon
oral
administration
septic
mice,
these
capsules
withstand
gastric
acid
release
their
contents
specifically
targeting
injured
tissues.
released
OLA@MΦ
NPs
effectively
neutralize
pro‐inflammatory
cytokines
via
membrane
receptors,
while
olaparib
inhibits
epithelial
parthanatos
(a
form
programmed
cell
death)
suppressing
poly(ADP‐ribose)
polymerase
1
(PARP1)
activation.
This
strategy
significantly
reduces
bacterial
translocation,
slows
enhances
survival
thus
presenting
promising
therapeutic
approach
for
sepsis
clinical
applications.
Язык: Английский
Plasma EphA2 level is a superior biomarker to Del-1 for sepsis diagnosis and prognosis
Frontiers in Medicine,
Год журнала:
2025,
Номер
12
Опубликована: Янв. 24, 2025
Background
Sepsis,
characterized
by
a
dysregulated
host
response
to
infection,
often
leads
organ
dysfunction,
and
vascular
endothelial
dysfunction
plays
central
role.
The
erythropoietin-producing
hepatocellular
carcinoma
(Eph)A2
receptor
is
associated
with
increased
permeability;
however,
the
developmental
locus-1
(Del-1),
has
contrasting
effects
on
function.
Hence,
we
examined
their
potential
as
biomarkers
of
sepsis.
Methods
In
total,
117
participants,
including
20
healthy
controls,
21
patients
systemic
inflammatory
syndrome
(SIRS),
76
sepsis,
were
enrolled
in
this
study.
Sepsis
severity
was
assessed
using
Acute
Physiology
Chronic
Health
Evaluation
(APACHE)
II
Sequential
Organ
Failure
Assessment
(SOFA)
scores.
Results
Median
plasma
EphA2
levels
progressively
from
controls
SIRS
sepsis
cases
(154.29,
293.52,
554.24
pg/mL;
all
p
<
0.05).
median
Del-1
highest
lowest
SIRS,
intermediate
level
(101.27,
16.88,
36.9
0.001).
both
higher
28-day
non-survivors
than
survivors,
(EphA2:898.09
vs.
475.88
pg/mL,
0.001;
Del-1:46.09
32.68
=
0.193);
only
statistically
significant.
area
under
curve
for
0.74
receiver
operating
characteristic
analysis
predicting
mortality,
whereas
APACHE
II,
SOFA,
showed
values
0.762,
0.614,
0.595,
respectively.
Kaplan–Meier
these
cutoffs
revealed
that
survival
significantly
group
low
compared
high
markers
(
Conclusion
Plasma
consistently
severity,
suggesting
its
biomarker
value
diagnosis
prognosis.
contrast,
variable,
indicating
limited
prognostic
utility.
Язык: Английский
Protective role of olfactomedin-4 gene polymorphisms in preterm neonates with sepsis
Early Human Development,
Год журнала:
2025,
Номер
202, С. 106223 - 106223
Опубликована: Фев. 20, 2025
Язык: Английский
Sepsis: the evolution of molecular pathogenesis concepts and clinical management
MedComm,
Год журнала:
2025,
Номер
6(3)
Опубликована: Фев. 23, 2025
Abstract
The
mortality
rate
of
sepsis
is
approximately
22.5%,
accounting
for
19.7%
the
total
global
mortality.
Since
Lewis
Thomas
proposed
in
1972
that
“it
our
response
makes
disease
(sepsis)”
rather
than
invading
microorganisms,
numerous
drugs
have
been
developed
to
suppress
“overwhelming”
inflammatory
response,
but
none
them
has
achieved
desired
effect.
Continued
failure
led
investigators
question
whether
deaths
septic
patients
are
indeed
caused
by
uncontrolled
inflammation.
Here,
we
review
history
clinical
trials
based
on
evolving
concepts
pathogenesis
over
past
half
century,
summarize
factors
these
historical
and
prerequisites
success
future
drugs,
propose
basic
principles
preclinical
research
ensure
successful
translation.
strategy
targeting
like
attempting
eliminate
invaders
suppressing
host's
armed
forces,
which
logically
untenable.
Sepsis
may
not
be
complex;
rather,
result
a
fight
microbes
when
force
an
pathogen
overwhelms
defenses.
Thus,
strengthening
body's
defense
forces
instead
correct
overcome
sepsis.
Язык: Английский
Endothelial soluble guanylyl cyclase enzyme inhibitors as novel target for treatment of sepsis related hypotension
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 20, 2024
Abstract
Background
Sepsis-related
hypotension
is
a
life-threatening
condition
due
to
systemic
infection
leading
widespread
inflammation
and
blood
vessel
dilation.
This
can
cause
dramatic
drop
in
pressure,
impairing
flow
vital
organs
potentially
organ
failure
death.
NO
was
recognized
as
significant
factor
sepsis
1990
became
an
important
therapeutic
target.
plays
dual
role
sepsis,
exhibiting
both
beneficial
harmful
effects.
Inhibiting
sGC
may
help
reduce
the
excessive
vasodilation
associated
with
sepsis-induced
vasoplegia.
Methods
study
utilized
CADD
screen
over
320
naturally
occurring
compounds
from
PubChem
database
for
potential
inhibitors.
A
comprehensive
virtual
screening
process,
which
included
protein-ligand
docking,
binding
free
energy
calculations,
pharmacokinetic
profiling,
led
identification
of
promising
candidates
such
Hypericin
Hypocrellin
A2.
Results
These
demonstrated
superior
affinities
properties
compared
existing
achieved
docking
score
-14.232,
indicating
strong
interactions
receptor.
It
also
exhibited
favourable
characteristics,
including
tissue-binding
stability
within
pocket,
well
low
predicted
toxicity
substantial
safety
margin.
Conclusions
research
lays
groundwork
future
vitro
vivo
studies,
could
improve
Hypericin-based
effective
therapies
vasoplegia
hypotension.
Язык: Английский
The Need for Standardized Guidelines for the Use of Monocyte Distribution Width (MDW) in the Early Diagnosis of Sepsis
Journal of Personalized Medicine,
Год журнала:
2024,
Номер
15(1), С. 5 - 5
Опубликована: Дек. 27, 2024
Sepsis
is
a
complex
and
potentially
life-threatening
syndrome
characterized
by
an
abnormal
immune
response
to
infection,
which
can
lead
organ
dysfunction,
septic
shock,
death.
Early
diagnosis
crucial
improving
prognosis
reducing
hospital
management
costs.
This
narrative
review
aims
summarize
evaluate
the
current
literature
on
role
of
monocyte
distribution
width
(MDW)
as
diagnostic
biomarker
for
sepsis,
highlighting
its
advantages,
limitations,
potential
clinical
applications.
MDW
measures
volumetric
monocytes,
reflecting
monocytic
anisocytosis,
detected
using
advanced
hematological
analyzers.
In
2019,
it
was
approved
FDA
sepsis
due
ability
identify
systemic
inflammatory
at
early
stage.
Thirty-one
studies
analyzed
us
have
shown
that
increased
value
associated
with
higher
risk
combination
parameters
(such
qSOFA)
other
biomarkers
(CRP,
PCT)
enhance
sensitivity
stratification
capacity.
Despite
high
sensitivity,
has
lower
specificity
compared
more
established
such
procalcitonin,
thus
requiring
multimodal
integration
accurate
diagnosis.
The
use
in
emergency
intensive
care
settings
represents
opportunity
improve
critical
patient
management,
particularly
when
combined
markers
tools.
However,
further
are
needed
define
universal
cut-off
confirm
validity
different
contexts
pathological
scenarios.
Язык: Английский