Biomolecules,
Год журнала:
2024,
Номер
14(7), С. 785 - 785
Опубликована: Июнь 30, 2024
Chemical
proteomics
using
biotin
probes
of
natural
products
have
significantly
advanced
our
understanding
molecular
targets
and
therapeutic
potential.
This
review
highlights
recent
progress
in
the
application
homoisoflavonoids
for
identifying
binding
proteins
elucidating
mechanisms
action.
Notably,
exhibit
antiangiogenic,
anti-inflammatory,
antidiabetic
effects.
A
combination
probes,
pull-down
assays,
mass
spectrometry,
modeling
has
revealed
how
their
derivatives
interact
with
several
such
as
ferrochelatase
(FECH),
soluble
epoxide
hydrolase
(sEH),
inosine
monophosphate
dehydrogenase
2
(IMPDH2),
phosphodiesterase
4
(PDE4),
deoxyhypusine
hydroxylase
(DOHH).
These
target
identification
approaches
pave
way
new
avenues,
especially
fields
oncology
ophthalmology.
Future
research
aimed
at
expanding
repertoire
promises
to
further
elucidate
complex
develop
drug
candidates.
Cerebral
ischemia
is
a
neurological
disorder
associated
with
complex
pathological
mechanisms,
including
autophagic
degradation
of
neuronal
mitochondria,
or
termed
mitophagy,
following
ischemic
events.
Despite
being
well-documented,
the
cellular
and
molecular
mechanisms
underlying
regulation
mitophagy
remain
unknown.
So
far,
evidence
suggests
autophagy
are
separately
regulated
in
neurons,
latter
more
likely
activated
by
reperfusional
injury.
Specifically,
given
polarized
morphology
different
compartments,
axonal
mitochondria
degraded
cell
body
ischemia-reperfusion
insult.
A
variety
molecules
have
been
adaptation
to
ischemia,
PTEN-induced
kinase
1,
Parkin,
BCL2
adenovirus
E1B
19-kDa-interacting
protein
3
(Bnip3),
Bnip3-like
(Bnip3l)
FUN14
domain-containing
1.
Moreover,
it
still
controversial
whether
protects
against
instead
aggravates
brain
Here,
we
review
recent
studies
on
this
topic
provide
an
updated
overview
role
during
Abstract
Background
Stroke
is
a
leading
cause
of
mortality
and
disability
with
ischemic
stroke
being
the
most
common
type
stroke.
Salvianolic
acid
C
(SalC),
polyphenolic
compound
found
in
Salviae
Miltiorrhizae
Radix
et
Rhizoma,
has
demonstrated
therapeutic
potential
recovery
phase
However,
its
pharmacological
effects
underlying
mechanisms
during
early
stages
remain
unclear.
This
study
aimed
to
examine
mechanism
action
SalC
using
network
pharmacology
strategies
RNA
sequencing
analysis.
Methods
on
infarct
volume,
neurological
deficits,
histopathological
changes
were
assessed
mouse
model
transient
middle
cerebral
artery
occlusion
(tMCAO).
By
integrating
data
vascular
disease
(CVD)-related
gene
database,
(CID)
containing
dysregulated
genes
from
tMCAO
was
constructed.
Network
analysis
algorithms
applied
evaluate
key
nodes
within
CID
network.
In
vivo
vitro
validation
crucial
targets
identified
pathways
conducted.
Results
treatment
significantly
reduced
improved
reversed
pathological
model.
The
integration
revealed
an
80%
reversion
rate
induced
by
Among
reverted
genes,
53.1%
exhibited
rates
exceeding
50%,
emphasizing
comprehensive
rebalancing
effect
Neuroinflammatory-related
regulated
SalC,
including
toll-like-receptor
4
(TLR4)-
triggering
receptor
expressed
myeloid
cells
1
(TREM1)-nuclear
factor
kappa
B
(NF-κB)
pathway,
identified.
Further
experiments
confirmed
that
TLR4-TREM1-NF-κB
pathway
down-regulated
microglia,
which
essential
for
anti-inflammatory
Conclusions
attenuated
injury
inhibiting
neuroinflammation
mediated
primarily
through
pathway.
These
findings
provide
valuable
insights
into
benefits
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(19), С. 10714 - 10714
Опубликована: Окт. 5, 2024
Breakthrough
symptoms
are
thought
to
occur
in
roughly
half
of
all
gastroesophageal
reflux
disease
(GERD)
patients
despite
maximal
acid
suppression
(proton
pump
inhibitor,
PPI)
therapy.
Topical
alginates
have
recently
been
shown
enhance
mucosal
defense
against
acid-pepsin
insult
during
GERD.
We
aimed
examine
potential
alginate
protection
transcriptomic
changes
a
cell
culture
model
PPI-recalcitrant
Immortalized
normal-derived
human
esophageal
epithelial
cells
underwent
pretreatment
with
commercial
alginate-based
anti-reflux
medications
(Gaviscon
Advance
or
Gaviscon
Double
Action),
matched-viscosity
placebo
control,
pH
7.4
buffer
(sham)
alone
for
1
min,
followed
by
exposure
6.0
+
pepsin
3
min.
RNA
sequencing
was
conducted,
and
Ingenuity
Pathway
Analysis
performed
false
discovery
rate
≤0.01
absolute
fold-change
≥1.3.
Pepsin-acid
disrupted
gene
expressions
associated
barrier
function,
chromatin
structure,
carcinogenesis,
inflammation.
Alginate
formulations
demonstrated
mitigating
these
promoting
extracellular
matrix
repair,
downregulating
proto-oncogenes,
enhancing
tumor
suppressor
expression.
These
data
suggest
molecular
mechanisms
which
provide
topical
injury
weakly
acidic
support
role
the
prevention
GERD-related
carcinogenesis.
Laboratory Animal Research,
Год журнала:
2025,
Номер
41(1)
Опубликована: Янв. 2, 2025
Abstract
Ischemic
stroke
(IS)
is
the
most
recorded
case
of
that
caused
by
decreased
blood
flow
to
brain.
Nowadays,
therapeutical
agents
for
IS
are
limited
and
they
have
not
shown
maximum
clinical
results.
Therefore,
exploration
new
candidates
treatment
continues
be
done.
Zebrafish
as
one
animal
models
has
its
advantages
currently
being
developed
incorporated
into
drug
discovery
pipeline
IS.
This
review
explores
latest
applications
zebrafish
model
in
screening
potential
therapeutic
Key
factors
related
experimental
design
such
developmental
stage
strain,
routes
administration,
induction
methods,
parameters
also
elaborated.
Finally,
this
offers
future
recommendations
use
pre-clinical
study
beneficial
a
reference
establishing
protocols
using
model.
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 25, 2025
Abstract
Meisoindigo
(Mei)
has
been
clinically
utilized
for
the
treatment
of
chronic
myeloid
leukemia
(CML),
yet
precise
molecular
targets
by
which
it
exerts
effects
remain
unclear.
Through
activity‐based
protein
profiling
(ABPP),
kinase,
membrane‐associated
tyrosine/threonine
1
(PKMYT1)
is
identified
as
a
direct
target
Mei.
Specifically,
Mei
forms
selective
and
reversible
covalent
bond
with
Cys301
residue
PKMYT1,
triggering
its
K48‐linked
polyubiquitination
accelerating
proteasomal
degradation,
mediated
E3
ligase
TRIM25.
The
study
reveals
that
acts
glue,
enhancing
interaction
between
PKMYT1
TRIM25
approximately
30‐fold,
thereby
facilitating
efficient
degradation.
Further
investigations
reveal
pivotal
role
in
cell
growth.
Knockdown
K562
cells
induces
G2/M
phase
arrest,
enhances
early
apoptosis,
inhibits
proliferation.
In
an
orthotopic
xenograft
model,
knockdown
delays
progression
reduces
lymph
node
metastasis,
reinforcing
CML
metastasis.
These
findings
provide
rationale
clinical
efficacy
highlight
promising
therapeutic
CML.
Additionally,
offers
valuable
scaffold
inspiration
development
novel
glue‐based
degraders.
