Translational Psychiatry,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Jan. 10, 2024
Abstract
Antipsychotic
(AP)-naive
first-episode
psychosis
(FEP)
patients
display
early
dysglycemia,
including
insulin
resistance
and
prediabetes.
Metabolic
dysregulation
may
therefore
be
intrinsic
to
spectrum
disorders
(PSDs),
independent
of
the
metabolic
effects
APs.
However,
potential
biological
pathways
that
overlap
between
PSDs
dysglycemic
states
remain
identified.
Using
meta-analytic
approaches
transcriptomic
datasets,
we
investigated
whether
AP-naive
FEP
share
overlapping
gene
expression
signatures
with
non-psychiatrically
ill
dysglycemia
individuals.
We
meta-analyzed
peripheral
datasets
subjects
identify
common
signatures.
Common
underwent
pathway
enrichment
analysis
were
then
used
new
pharmacological
compounds
via
Integrative
Library
Integrated
Network-Based
Cellular
Signatures
(iLINCS).
Our
search
results
yielded
5
studies
4
which
met
inclusion
criteria.
discovered
exhibiting
shared
221
signatures,
enriched
for
related
endoplasmic
reticulum
stress
abnormal
brain
energetics.
Nine
FDA-approved
drugs
identified
as
drug
treatments,
antidiabetic
metformin,
first-line
treatment
type
2
diabetes,
has
evidence
attenuate
dysfunction
in
PSDs.
Taken
together,
our
findings
support
changes
associating
disorders.
These
data
suggest
pathobiology
overlaps
potentially
contributes
dysglycemia.
Finally,
find
metformin
a
Molecules,
Journal Year:
2023,
Volume and Issue:
28(3), P. 1486 - 1486
Published: Feb. 3, 2023
Alzheimer’s
disease
(AD)
is
an
age-related
chronic
progressive
neurodegenerative
disease,
which
the
main
cause
of
dementia
in
elderly.
Much
evidence
shows
that
onset
and
late
symptoms
AD
are
caused
by
multiple
factors.
Among
them,
aging
factor
pathogenesis
AD,
most
important
risk
for
neuroinflammation.
So
far,
there
no
cure
but
relationship
between
neuroinflammation
may
provide
a
new
strategy
treatment
AD.
We
herein
discussed
etiology
hypothesis
role
as
well
anti-inflammatory
natural
products
with
potential
to
prevent
alleviate
symptoms,
including
alkaloids,
steroids,
terpenoids,
flavonoids
polyphenols,
available
great
development
anti-AD
drugs.
ACS Chemical Neuroscience,
Journal Year:
2024,
Volume and Issue:
15(2), P. 258 - 267
Published: Jan. 5, 2024
Neuroinflammation
plays
an
important
role
in
the
pathogenesis
of
neurodegenerative
diseases,
and
interrupting
microglial-mediated
neuroinflammation
has
been
suggested
as
a
promising
strategy
to
delay
or
prevent
progression
neurodegeneration.
In
this
study,
we
investigated
effects
JE-133,
optically
active
isochroman-2H-chromene
conjugate
containing
1,3-disubstituted
isochroman
unit,
on
lipopolysaccharide
(LPS)-induced
microglial
underlying
mechanisms
both
vitro
vivo.
First,
JE-133
treatment
decreased
LPS-induced
overproduction
interleukin-1
beta
(IL-1β),
interleukin-6
(IL-6),
tumor
necrosis
factor-α
(TNF-α),
nitrite,
nitric
oxide
synthase
(iNOS)
BV2
cells.
Further
study
revealed
that
downregulated
phosphorylation
level
JAK/STAT
upregulated
protein
Nrf2/HO-1
LPS-stimulated
cells
verified
directly
bound
Keap1
by
pull-down
assay.
Next,
administration
also
inhibited
vivo,
indicated
reduced
CD11b
overexpressed
mRNA
pro-inflammatory
cytokine
TNF-α
hippocampus
LPS-injected
mice.
Moreover,
regulative
pathways
were
Taken
together,
our
for
first
time
reports
exhibits
inhibitory
against
which
might
be
associated
with
simultaneous
regulation
Nrf2
pathways.
Our
findings
may
provide
clues
discovery
effective
drug
leads/candidates
neuroinflammation-associated
iScience,
Journal Year:
2023,
Volume and Issue:
26(4), P. 106460 - 106460
Published: March 21, 2023
The
abundance
of
biomedical
knowledge
gained
from
biological
experiments
and
clinical
practices
is
an
invaluable
resource
for
biomedicine.
emerging
graphs
(BKGs)
provide
efficient
effective
way
to
manage
the
abundant
in
life
science.
In
this
study,
we
created
a
comprehensive
BKG
called
integrative
Biomedical
Knowledge
Hub
(iBKH)
by
harmonizing
integrating
information
diverse
resources.
To
make
iBKH
easily
accessible
research,
developed
web-based,
user-friendly
graphical
portal
that
allows
fast
interactive
retrieval.
Additionally,
also
implemented
scalable
graph
learning
pipeline
discovering
novel
iBKH.
As
proof
concept,
performed
our
iBKH-based
method
computational
in-silico
drug
repurposing
Alzheimer's
disease.
publicly
available.
Translational Psychiatry,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Jan. 10, 2024
Abstract
Antipsychotic
(AP)-naive
first-episode
psychosis
(FEP)
patients
display
early
dysglycemia,
including
insulin
resistance
and
prediabetes.
Metabolic
dysregulation
may
therefore
be
intrinsic
to
spectrum
disorders
(PSDs),
independent
of
the
metabolic
effects
APs.
However,
potential
biological
pathways
that
overlap
between
PSDs
dysglycemic
states
remain
identified.
Using
meta-analytic
approaches
transcriptomic
datasets,
we
investigated
whether
AP-naive
FEP
share
overlapping
gene
expression
signatures
with
non-psychiatrically
ill
dysglycemia
individuals.
We
meta-analyzed
peripheral
datasets
subjects
identify
common
signatures.
Common
underwent
pathway
enrichment
analysis
were
then
used
new
pharmacological
compounds
via
Integrative
Library
Integrated
Network-Based
Cellular
Signatures
(iLINCS).
Our
search
results
yielded
5
studies
4
which
met
inclusion
criteria.
discovered
exhibiting
shared
221
signatures,
enriched
for
related
endoplasmic
reticulum
stress
abnormal
brain
energetics.
Nine
FDA-approved
drugs
identified
as
drug
treatments,
antidiabetic
metformin,
first-line
treatment
type
2
diabetes,
has
evidence
attenuate
dysfunction
in
PSDs.
Taken
together,
our
findings
support
changes
associating
disorders.
These
data
suggest
pathobiology
overlaps
potentially
contributes
dysglycemia.
Finally,
find
metformin
a
