Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 26, 2024
Abstract
Primary
biliary
cholangitis
(PBC)
is
challenging
to
diagnose
and
treat
due
its
insidious
onset.
This
study
aimed
identify
effective
diagnostic
biomarkers
for
PBC
by
focusing
on
secreted
proteins
through
bioinformatics
approaches.
Two
PBC-related
bulk
datasets,
GSE119600
GSE61260,
were
retrieved
from
the
GEO
database
analysis
validation,
respectively.
Gene
sets
related
sourced
THPA
database.
The
of
included
differential
expression
analysis,
WGCNA,
immune
infiltration
enrichment
analyses.
By
intersecting
differentially
expressed
genes
(DEGs),
WGCNA
hub
module
genes,
proteins,
18
candidate
identified.
Machine
learning
techniques—LASSO,
random
forest,
GMM,
SVM-RFE—narrowed
these
four
genes:
CSF1R,
PLCH2,
SLC38A1,
CST7.
performance
was
assessed
using
LDA,
QDA,
Bayesian
test,
Nomogram
methods,
with
internal
external
validation
AUC
values
0.867
0.722,
Experimental
in
model
mice
confirmed
that
significantly
altered.
These
findings
suggest
CST7
could
serve
as
novel
early
detection
provide
insights
into
underlying
mechanisms.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(17), С. 9463 - 9463
Опубликована: Авг. 30, 2024
Colorectal
cancer
(CRC)
represents
a
significant
global
health
burden,
with
high
incidence
and
mortality
rates
worldwide.
Recent
progress
in
research
highlights
the
distinct
clinical
molecular
characteristics
of
colon
versus
rectal
cancers,
underscoring
tumor
location's
importance
treatment
approaches.
This
article
provides
comprehensive
review
our
current
understanding
CRC
epidemiology,
risk
factors,
pathogenesis,
management
strategies.
We
also
present
intricate
cellular
architecture
colonic
crypts
their
roles
intestinal
homeostasis.
carcinogenesis
multistep
processes
are
described,
covering
conventional
adenoma-carcinoma
sequence,
alternative
serrated
pathways,
influential
Vogelstein
model,
which
proposes
sequential
npj Parkinson s Disease,
Год журнала:
2024,
Номер
10(1)
Опубликована: Май 18, 2024
Abstract
Parkinson’s
disease
(PD)
is
the
second
most
prevalent
neurodegenerative
disease.
Primary
symptoms
of
PD
arise
with
loss
dopaminergic
(DA)
neurons
in
Substantia
Nigra
Pars
Compacta,
but
also
affects
hippocampus
and
cortex,
usually
its
later
stage.
Approximately
15%
cases
are
familial
a
genetic
mutation.
Two
associated
genes
autosomal
recessive
(AR)
early-onset
PINK1
PRKN
.
In
vitro
studies
these
mutations
needed
to
understand
neurophysiological
changes
patients’
that
may
contribute
neurodegeneration.
this
work,
we
generated
differentiated
DA
hippocampal
from
human
induced
pluripotent
stem
cells
(hiPSCs)
derived
two
patients
double
mutation
their
(one
homozygous
one
heterozygous)
assessed
neurophysiology
compared
healthy
controls.
We
showed
synaptic
activity
impaired
neurons.
Mutant
had
enhanced
excitatory
post-synaptic
activity.
addition,
exhibited
more
pronounced
electrophysiological
differences
control
Signaling
network
analysis
RNA
sequencing
results
revealed
Focal
adhesion
ECM
receptor
pathway
were
top
upregulated
pathways
mutant
Our
findings
reveal
phenotypes
linked
differ
those
other
mutations,
suggesting
unique
interplay
between
drives
different
mechanisms.
Molecular Biomedicine,
Год журнала:
2024,
Номер
5(1)
Опубликована: Ноя. 29, 2024
Abstract
Tumor
energy
metabolism
plays
a
crucial
role
in
the
occurrence,
progression,
and
drug
resistance
of
tumors.
The
study
tumor
has
gradually
become
an
emerging
field
treatment.
Recent
studies
have
shown
that
epigenetic
regulation
is
closely
linked
to
metabolism,
influencing
metabolic
remodeling
biological
traits
cells.
This
review
focuses
on
primary
pathways
explores
therapeutic
strategies
target
these
pathways.
It
covers
key
areas
such
as
glycolysis,
Warburg
effect,
mitochondrial
function,
oxidative
phosphorylation,
adaptability
Additionally,
this
article
examines
regulator
SWI/SNF
complex
specifically
its
interactions
with
glucose,
lipids,
amino
acids.
Summarizing
aimed
at
pathways,
including
inhibitors
mitochondrial-targeted
drugs,
exploitation
vulnerabilities,
recent
developments
related
complexes
potential
targets.
clinical
significance,
challenges,
future
directions
research
are
discussed,
overcome
resistance,
combination
therapy,
application
new
technologies.
Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Янв. 24, 2024
Abstract
Acute
myeloid
leukemia
(AML),
a
prevalent
form
of
in
adults,
is
often
characterized
by
low
response
rates
to
chemotherapy,
high
recurrence
rates,
and
unfavorable
prognosis.
A
critical
barrier
managing
refractory
or
recurrent
AML
the
resistance
chemotherapy.
Increasing
evidence
indicates
that
tumor
cell
metabolism
plays
crucial
role
progression,
survival,
metastasis,
treatment
resistance.
Autophagy,
an
essential
regulator
cellular
energy
metabolism,
increasingly
recognized
for
its
metabolic
reprogramming
AML.
Autophagy
sustains
cells
during
chemotherapy
not
only
providing
but
also
facilitating
rapid
proliferation
through
supply
components
such
as
amino
acids
nucleotides.
Conversely,
state
can
influence
activity
autophagy.
Their
mutual
coordination
helps
maintain
intrinsic
homeostasis,
which
significant
contributor
cells.
This
review
explores
recent
advancements
understanding
interaction
between
autophagy
cells,
emphasizing
their
roles
survival
drug
comprehensive
interplay
shed
light
on
strategies,
particularly
under
adverse
conditions
insight
may
pave
way
innovative
targeted
strategies.
Frontiers in Oncology,
Год журнала:
2025,
Номер
14
Опубликована: Янв. 20, 2025
Acute
myeloid
leukemia
(AML)
is
an
aggressive
hematological
malignancy;
it
the
most
common
acute
in
adults.
AML
prognosis
often
poor,
and
relapse
occurs
after
initial
remission.
Recurrent
genetic
abnormalities
underlying
this
disease
presence
of
leukemic
stem
cells
complicate
treatment.
However,
complex
metabolic
reprogramming
that
enables
unrestrained
cell
growth
seen
these
may
also
be
their
Achilles’
heel.
In
cells,
mitophagy
operates
as
a
double-edged
sword.
On
one
hand,
provides
source
building
blocks
for
further
division
serves
method
removing
damaged
organelles,
promoting
survival.
profound
changes
to
mitochondria
render
organelles
more
sensitive
damage
place
them
precariously
close
excess
mitophagic
activation.
This
review
discusses
dual
role
plays
survival,
importance
targeting
treat
AML,
current
progress
area.
The
discovery
mechanism
action
multiple
compounds
were
used
inhibit
or
stimulate
effects
on
survival
are
described.
Further,
we
explore
combination
strategy
mitophagy-targeting
with
existing
and/or
novel
chemotherapeutics
eradicate
discuss
strategies
uncover
new
drug
targets
mitochondria-targeting
drugs.
Cancer
immunotherapy
has
achieved
unprecedented
success
in
the
field
of
cancer
therapy.
However,
its
potential
is
constrained
by
a
low
therapeutic
response
rate.
Tertiary
lymphoid
structure
(TLS)
plays
crucial
role
antitumor
immunity
and
associated
with
good
prognosis.
Metabolic
reprogramming,
as
hallmark
tumor
microenvironment,
can
influence
promote
formation
follicular
helper
T
cells
germinal
centers.
many
current
studies
focus
on
correlation
between
metabolism
TLS
factors,
there
insufficient
direct
evidence
to
suggest
that
drives
formation.
This
review
provided
comprehensive
summary
relationship
formation,
highlighting
glucose
metabolism,
lipid
amino
acid
vitamin
metabolism.
In
future,
an
in-depth
exploration
how
affects
cell
interactions
microorganisms
will
significantly
advance
our
understanding
metabolism-enhanced
immunity.
ABSTRACT
Background
Acute
myeloid
leukemia
(AML)
is
an
aggressive
hematologic
malignancy
with
a
poor
prognosis,
particularly
in
older
patients.
AML
highly
heterogeneous,
influenced
by
various
chromosomal,
genetic,
and
epigenetic
alterations.
Methods
This
study
investigated
the
metabolic
profiles
of
primary
cells
from
46
patients,
focusing
on
mitochondrial
respiration
glycolysis.
We
hypothesized
that
would
reflect
distinct
disease
characteristics.
Using
Seahorse
technology,
we
measured
oxygen
consumption
rate
(OCR)
for
extracellular
acidification
(ECAR)
Results
Our
results
showed
significant
variability
activity,
some
samples
relying
more
glycolysis
than
respiration.
Mature
(FAB
M4/M5,
CD34
negative)
exhibited
increased
rates
both
glycolysis,
indicating
adaptations.
Higher
glycolytic
activity
was
observed
patients
adverse
cytogenetic
abnormalities.
However,
no
clear
associations
were
found
between
mutations
FLT3
or
NPM1
.
Conclusion
These
findings
highlight
role
suggest
targeting
specific
pathways
could
offer
therapeutic
opportunities,
subgroups
like
FAB
M4/M5
unique
features.
Further
studies
are
needed
to
refine
these
strategies
clinical
application.
