PLoS ONE,
Journal Year:
2023,
Volume and Issue:
18(11), P. e0294432 - e0294432
Published: Nov. 29, 2023
Insulin-positive
(+)
cells
(IPCs),
detected
in
multiple
organs,
are
of
great
interest
as
a
probable
alternative
to
ameliorate
pancreatic
beta-cells
dysfunction
and
insulin
deficiency
diabetes.
Liver
is
potential
source
IPCs
due
it
common
embryological
origin
with
pancreas.
We
previously
demonstrated
the
presence
liver
healthy
diabetic
rats,
but
detailed
description
analysis
factors,
which
potentially
can
induced
ectopic
hepatic
expression
type
1
(T1D)
2
diabetes
(T2D),
were
not
performed.
In
present
study
we
evaluate
mass
rat
models
T1D
T2D
discuss
may
stimulate
generation:
glycaemia,
organ
injury,
involving
stem/progenitor
cell
compartment,
transcription
factors
inflammation.
Quantity
was
up
by
1.7-fold
rats
10-fold
compared
non-diabetic
(ND)
rats.
concluded
that
gene
activated
combined
action
number
inflammation
playing
decision
role.
Journal of Biomedical Science,
Journal Year:
2024,
Volume and Issue:
31(1)
Published: May 30, 2024
Abstract
Severe
infection
and
sepsis
are
medical
emergencies.
High
morbidity
mortality
linked
to
CNS
dysfunction,
excessive
inflammation,
immune
compromise,
coagulopathy
multiple
organ
dysfunction.
Males
appear
have
a
higher
risk
of
than
females.
Currently,
there
few
or
no
effective
drug
therapies
protect
the
brain,
maintain
blood
brain
barrier,
resolve
inflammation
reduce
secondary
injury
in
other
vital
organs.
We
propose
major
reason
for
lack
progress
is
consequence
treat-as-you-go,
single-nodal
target
approach,
rather
more
integrated,
systems-based
approach.
A
new
revolution
required
better
understand
how
body
responds
an
infection,
identify
markers
detect
its
progression
discover
system-acting
drugs
treat
it.
In
this
review,
we
present
brief
history
followed
by
pathophysiology
from
systems’
perspective
future
opportunities.
argue
that
targeting
body’s
early
immune-driven
CNS-response
may
improve
patient
outcomes.
If
barrage
PAMPs
DAMPs
can
be
reduced
early,
CNS-organ
circuits
(or
axes)
will
preserved
reduced.
been
developing
systems-based,
small-volume,
fluid
therapy
comprising
adenosine,
lidocaine
magnesium
(ALM)
endotoxemia.
Our
studies
indicate
ALM
shifts
sympathetic
parasympathetic
dominance,
maintains
cardiovascular-endothelial
glycocalyx
coupling,
reduces
corrects
coagulopathy,
tissue
O
2
supply.
Future
research
investigate
potential
translation
humans.
Metabolites,
Journal Year:
2025,
Volume and Issue:
15(5), P. 290 - 290
Published: April 25, 2025
Background:
Sepsis-induced
acute
lung
injury
(SALI)
is
a
critical
clinical
challenge
with
high
mortality.
Metabolic
dysregulation
drives
SALI
pathogenesis,
disrupting
function
and
energy
metabolism.
Despite
proven
benefits,
metabolic
restoration
underused
in
sepsis.
This
study
explores
chiglitazar’s
role
balancing
metabolism
to
protect
against
SALI.
Methods:
The
protective
effects
of
chiglitazar
CLP
rats
were
demonstrated
by
the
survival
curve,
histological
analysis,
immunohistochemical
analysis
tissue.
Metabolomic
lipidomic
analyses
tissue
samples
using
gas
chromatography–mass
spectrometry
(GC-MS)
liquid
(LC-MS)
performed
evaluate
shifts
induced
surgery
pretreatment.
mRNA
protein
levels
underlying
targets
directing
nicotinamide
adenine
dinucleotide
(NAD+)
triglyceride
synthesis
analyzed
qPCR
Western
blotting.
To
validate
mechanism
which
protected
SALI,
SIRT1
inhibitor
EX-527
was
applied
human
normal
epithelial
(BEAS-2B)
cells
another
batch
observe
its
reverse
effect
action.
Results:
Chiglitazar
pretreatment
significantly
restored
NAD+
improved
dysregulated
lipid
enhancing
triglycerides
(TGs)
suppressing
accumulated
fatty
acids
(FAs).
modulation
mediated
associated
upregulations
SIRT1/PGC-1α/PPARα/GPAT3
axis.
Co-treatment
LPS-stimulated
BEAS-2B
inhibited
on
aforementioned
signaling
pathways
worsened
injury,
respectively.
Conclusions:
alleviates
restoring
TG
synthesis,
highlighting
as
promising
therapeutic
strategy
management
Journal of Clinical Medicine,
Journal Year:
2025,
Volume and Issue:
14(10), P. 3313 - 3313
Published: May 9, 2025
Background:
The
pathophysiological
mechanisms
underlying
altered
plasma
glutamine
concentrations
in
sepsis
remain
poorly
understood.
Identifying
clinical,
immunological,
and
metabolic
correlates
of
fluctuations
is
crucial
to
advancing
precision
medicine,
developing
targeted
therapies,
improving
survival
outcomes
septic
patients.
Methods:
We
enrolled
469
patients
with
assessed
inflammatory
markers—including
body
temperature,
white
blood
cell
count,
C-reactive
protein
levels—upon
admission
the
internal
medicine
unit.
Lymphocyte
count
glutamine,
glutamic
acid,
5-oxoproline,
phenylalanine,
tyrosine,
leucine
were
measured
using
gas
chromatography–mass
spectrometry.
Patients
stratified
into
three
groups
based
on
levels.
Mortality
was
recorded
at
30
days
6
months.
Results:
Low,
intermediate,
high
levels
observed
46%
(n
=
217),
47%
218),
7%
34)
patients,
respectively.
hyperglutaminemia
exhibited
significantly
lower
lymphocyte
counts,
levels,
acid-to-5-oxoproline
ratio
(a
surrogate
marker
glutathione
availability),
along
elevated
phenylalanine
tyrosine-to-phenylalanine
(all
p
<
0.01).
Metabolic
disruption
mortality
increased
progressively
across
level
groups.
Kaplan–Meier
analysis
demonstrated
higher
both
(log-rank
0.03)
months
0.05).
Conclusions:
At
baseline,
increasing
are
associated
deeper
lymphopenia,
more
pronounced
derangement,
short-
long-term
sepsis.
AJP Gastrointestinal and Liver Physiology,
Journal Year:
2023,
Volume and Issue:
325(5), P. G471 - G491
Published: Sept. 12, 2023
The
liver
plays
a
significant
role
in
regulating
wide
range
of
metabolic,
homeostatic,
and
host-defense
functions.
However,
the
impact
injury
on
host's
ability
to
control
bacteremia
morbidity
sepsis
is
not
well
understood.
Leukocyte
recruitment
activation
lead
cytokine
chemokine
release,
which,
turn,
trigger
hepatocellular
elevate
nucleotide
levels
extracellular
milieu.
P2Y2
purinergic
receptors,
G
protein-coupled
activated
by
ATP/UTP,
are
expressed
at
cell
surface
hepatocytes
nonparenchymal
cells.
We
sought
determine
whether
receptor
function
necessary
for
maladaptive
host
response
bacterial
infection
endotoxin-mediated
inflammatory
mortality
mice.
report
that
knockout
mice
(P2Y2
